{"metadata": {"review_pmid": "39932103"}, "inputs": {"background": "Various approaches to physical rehabilitation to improve function and mobility are used after stroke. There is considerable controversy around the relative effectiveness of approaches, and little known about optimal delivery and dose. Some physiotherapists base their treatments on a single approach; others use components from several different approaches.", "objectives": "Primary objective: To determine whether physical rehabilitation is effective for recovery of function and mobility in people with stroke, and to assess if any one physical rehabilitation approach is more effective than any other approach.", "selection criteria": "Inclusion criteria: Randomised controlled trials (RCTs) of physical rehabilitation approaches aimed at promoting the recovery of function or mobility in adult participants with a clinical diagnosis of stroke."}, "context": [{"title": "Muscle strengthening and physical conditioning to reduce impairment and disability in chronic stroke survivors.", "abstract": "To evaluate the impact of a program of muscle strengthening and physical conditioning on impairment and disability in chronic stroke subjects.\n\nA randomized pretest and posttest control group, followed by a single-group pretest and posttest design.\n\nThirteen community-dwelling stroke survivors of at least 9 months.\n\nA 10-week (3 days/week) program consisting of a warm-up, aerobic exercises, lower extremity muscle strengthening, and a cool-down.\n\nPeak isokinetic torque of the major muscle groups of the affected lower limb, quadriceps and ankle plantarflexor spasticity, gait speed, rate of stair climbing, the Human Activity Profile (HAP), and the Nottingham Health Profile (NHP) were recorded twice for the treatment group and three times for the control group.\n\nSignificant improvements were found for all the selected outcome measures (HAP, NHP, and gait speed) for the treatment group (p < .001). In terms of overall training effects, the 13 subjects demonstrated increases in strength of the affected major muscle groups, in HAP and NHP profiles, and in gait speed and rate of stair climbing without concomitant increases in either quadriceps or ankle plantarflexor spasticity.\n\nThe 10-week combined program of muscle strengthening and physical conditioning resulted in gains in all measures of impairment and disability. These gains were not associated with measurable changes of spasticity in either quadriceps or ankle plantarflexors.", "PMID": "10527076"}, {"title": "Task-related circuit training improves performance of locomotor tasks in chronic stroke: a randomized, controlled pilot trial.", "abstract": "To evaluate the immediate and retention effects of a 4-week training program on the performance of locomotor-related tasks in chronic stroke.\n\nRandomized, controlled pilot study with 2-month follow-up.\n\nRehabilitation center.\n\nA convenience sample consisting of 12 chronic stroke subjects was used. Subjects were randomly assigned to the experimental or the control group. Three subjects withdrew from the study.\n\nBoth experimental and control groups participated in exercise classes three times a week for 4 weeks. The exercise class for the experimental group focused on strengthening the affected lower limb and practicing functional tasks involving the lower limbs, while the control group practiced upper-limb tasks.\n\nLower-limb function was evaluated by measuring walking speed and endurance, peak vertical ground reaction force through the affected foot during sit-to-stand, and the step test.\n\nThe experimental group demonstrated significant immediate and retained (2-month follow-up) improvement (p < or = .05) compared with the control group in walking speed and endurance, force production through the affected leg during sit-to-stand, and the number of repetitions of the step test.\n\nThe pilot study provides evidence for the efficacy of a task-related circuit class at improving locomotor function in chronic stroke.", "PMID": "10768528"}, {"title": "Bobath or motor relearning programme? A comparison of two different approaches of physiotherapy in stroke rehabilitation: a randomized controlled study.", "abstract": "To examine whether two different physiotherapy regimes caused any differences in outcome in rehabilitation after acute stroke.\n\nA double-blind study of patients with acute first-ever stroke. Sixty-one patients were consecutively included, block randomized into two groups, and stratified according to gender and hemiplegic site. Group 1 (33 patients) and group 2 (28 patients) had physiotherapy according to Motor Relearning Programme (MRP) and Bobath, respectively. The supplemental treatment did not differ in the two groups.\n\nThe Motor Assessment Scale (MAS), the S\u00f8dring Motor Evaluation Scale (SMES), the Barthel ADL Index and the Nottingham Health Profile (NHP) were used. The following parameters were also registered: length of stay in the hospital, use of assistive devices for mobility, and the patient's accommodation after discharge from the hospital.\n\nPatients treated according to MRP stayed fewer days in hospital than those treated according to Bobath (mean 21 days versus 34 days, p = 0.008). Both groups improved in MAS and SMES, but the improvement in motor function was significantly better in the MRP group. The two groups improved in Barthel ADL Index without significant differences between the groups. However, women treated by MRP improved more in ADL than women treated by Bobath. There were no differences between the groups in the life quality test (NHP), use of assistive devices or accommodation after discharge from the hospital.\n\nThe present study indicates that physiotherapy treatment using the MRP is preferable to that using the Bobath programme in the acute rehabilitation of stroke patients.", "PMID": "10945420"}, {"title": "Physiotherapy for patients with mobility problems more than 1 year after stroke: a randomised controlled trial.", "abstract": "Community physiotherapy is often prescribed for stroke patients with long-term mobility problems. We aimed to assess the effectiveness of this treatment in patients who had mobility problems 1 year after stroke.\n\nWe screened 359 patients older than 50 years for a single-masked, randomised controlled trial to assess the effects of community physiotherapy. Assessments were made at baseline, 3, 6, and 9 months in 170 eligible patients assigned treatment or no intervention. The primary outcome measure was mobility measured by the Rivermead mobility index. Secondary outcome measures were gait speed, number of falls, daily activity (Barthel index scores), social activity (Frenchay activities index), hospital anxiety and depression scale, and emotional stress of carers (general health questionnaire 28). Analyses were by intention to treat.\n\nFollow-up was available for 146 patients (86%). Changes in scores on the Rivermead mobility index (score range 0-15) differed significantly between treatment and control groups at 3 months (p=0.018), but only by a median of 1 point (95% CI 0-1), with an interpolated value of 0.55 (0.08-1.04). Gait speed was 2.6 m/min (0.30-4.95) higher in the treatment group at 3 months. Neither treatment effect persisted at 6-months' and 9-months' follow-up. Treatment had no effect on patients' daily activity, social activity, anxiety, depression, and number of falls, or on emotional stress of carers.\n\nCommunity physiotherapy treatment for patients with mobility problems 1 year after stroke leads to significant, but clinically small, improvements in mobility and gait speed that are not sustained after treatment ends.", "PMID": "11812553"}, {"title": "Effect of duration of upper- and lower-extremity rehabilitation sessions and walking speed on recovery of interlimb coordination in hemiplegic gait.", "abstract": "The effects of different durations of rehabilitation sessions for the upper extremities (UEs) and lower extremities (LEs) on the recovery of interlimb coordination in hemiplegic gait in patients who have had a stroke were investigated.\n\nFifty-three subjects who had strokes involving their middle cerebral arteries were assigned to rehabilitation programs with (1) an emphasis on the LEs, (2) an emphasis on the paretic UE, or (3) a condition in which the paretic arm (UE) and leg (LE) were immobilized with an inflatable pressure splint (control treatment). The 3 treatment regimens were applied for 30 minutes, 5 days a week, during the first 20 weeks after onset of stroke. All subjects also participated in a rehabilitation program 5 days a week that consisted of 15 minutes of UE exercises and 15 minutes of LE exercises in addition to a weekly 11/2-hour session of training in activities of daily living. A repeated-measures design was used. Differences among the 3 treatment regimens were evaluated in terms of comfortable and maximal walking speeds. In addition, mean continuous relative phase (CRP) between paretic arm and leg (PAL) movements and nonparetic arm and leg (NAL) movements and standard deviations of CRP of both limb pairs as a measurement of stability (variability) were evaluated.\n\nComfortable walking speed improved in the group that received interventions involving the LEs compared with the group that received interventions involving the UEs and the group that received the control treatment. No differences among the 3 treatment conditions were found for the mean CRP of NAL and PAL as well as the standard deviation of CRP of both limb pairs.\n\nWith the exception of an improved comfortable walking speed as a result of a longer duration of rehabilitation sessions, no differential effects of duration of rehabilitation sessions for the LEs and UEs on the variable we measured related to hemiplegic gait were found. Increasing walking speed, however, resulted in a larger mean CRP for both limb pairs, with increased stability and asymmetry of walking, indicating that walking speed influences interlimb coordination in hemiplegic gait.", "PMID": "11991797"}, {"title": "The effect of independent practice of motor tasks by stroke patients: a pilot randomized controlled trial.", "abstract": "To investigate the effect of independent practice of sitting balance as an addition to standard physiotherapy treatment for patients with stroke.\n\nRandomized controlled trial, using blocked randomization procedure with 2:1 ratio.\n\nInpatients with diagnosis of stroke, having achieved one minute of independent sitting balance but not yet achieved 10 independent steps, and with no known previous disabilities, pathology or neurological deficit affecting mobility prior to stroke.\n\nA four-week regime of independent practice aimed at improving aspects of balance, as an addition to standard physiotherapy treatment based on the Bobath Approach.\n\nProportion of patients achieving 'normal' symmetry of weight distribution during sitting, standing, rising to stand, sitting down, and reaching.\n\nNineteen subjects were randomized to the control group; nine to the intervention group. There were no clinically significant differences in measured outcome between the groups.\n\nThe regime of independent practice had no measured beneficial effect on the balance ability of patients with recently acquired stroke.", "PMID": "12194618"}, {"title": "Training symmetry of weight distribution after stroke: a randomized controlled pilot study comparing task-related reach, Bobath and feedback training approaches.", "abstract": "To determine (1) the most effective of three treatment approaches to retrain seated weight distribution long-term after stroke and (2) whether improvements could be generalized to weight distribution in standing.\n\nInpatient rehabilitation unit.\n\nForty asymmetrical acute stroke subjects were randomly allocated to one of four groups in this pilot study. Changes in weight distribution were compared between the 10 subjects of each of three treatment groups (task-specific reach, Bobath, or Balance Performance Monitor [BPM] feedback training) and a no specific treatment control group. One week of measurement only was followed by two weeks of daily training sessions with the treatment to which the subject was randomly allocated. Measurements were performed using the BPM daily before treatment sessions, two weeks after cessation of treatment and 12 weeks post study. Weight distribution was calculated in terms of mean balance (percentage of total body weight) or the mean of 300 balance points over a 30-s data run.\n\nIn the short term, the Bobath approach was the most effective treatment for retraining sitting symmetry after stroke (p = 0.004). Training with the BPM and no training were also significant (p = 0.038 and p = 0.035 respectively) and task-specific reach training failed to reach significance (p = 0.26). At 12 weeks post study 83% of the BPM training group, 38% of the task-specific reach group, 29% of the Bobath group and 0% of the untrained group were found to be distributing their weight to both sides. Some generalization of symmetry training in sitting to standing was noted in the BPM training group which appeared to persist long term.\n\nResults should be treated with caution due to the small group sizes. However, these preliminary findings suggest that it might be possible to restore postural symmetry in sitting in the early stages of rehabilitation with therapy that focuses on creating an awareness of body position.", "PMID": "12392332"}, {"title": "Sitting training early after stroke improves sitting ability and quality and carries over to standing up but not to walking: a randomised trial.", "abstract": "What is the effect of a sitting training protocol in people early after stroke on sitting ability and quality, and does it carry over to mobility?\n\nRandomised placebo-controlled trial with concealed allocation, assessor blinding and intention-to-treat analysis.\n\nTwelve individuals who had a stroke less than three months previously and were able to sit unsupported.\n\nThe experimental group completed a 2-week sitting training protocol that involved practising reaching tasks beyond arm's length. The control group completed a 2-week sham sitting training protocol that involved practising cognitive-manipulative tasks within arm's length.\n\nThe primary outcome was sitting ability (maximum reach distance). Secondary outcomes were sitting quality (reach movement time and peak vertical force through affected foot during reaching) and carry over to mobility (peak vertical force through affected foot during standing up and walking speed during 10 m Walk Test). Outcome measures were taken before and after training and six months later.\n\nAfter 2 weeks' training, the experimental group had increased their maximum reach distance by 0.17 m (95% CI 0.12 to 0.21), decreased their movement time by 0.5 s (95% CI -0.8 to -0.2), increased their peak vertical force through the affected foot during reaching by 13% of body weight (95% CI 6 to 20) and increased their peak vertical force through the affected foot during standing up by 21% of body weight (95% CI 14 to 28) compared with the control group. After 6 months, significant between-group differences were maintained for maximum reach distance and peak vertical force through the affected foot during standing up.\n\nThe sitting training protocol was both feasible and effective in improving sitting and standing up early after stroke and somewhat effective six months later.", "PMID": "17535145"}, {"title": "Additional exercises improve trunk performance after stroke: a pilot randomized controlled trial.", "abstract": "Sitting balance and the ability to perform selective trunk movements are important predictors of functional outcome after stroke. However, studies evaluating the effect of exercises aimed at improving trunk performance are sparse.\n\nTo examine the effect of additional trunk exercises on trunk performance after stroke.\n\nAn assessor-blinded randomized controlled trial was carried out at an inpatient stroke rehabilitation center. In total 33 participants were assigned to an experimental group (n = 17) or a control group (n = 16). In addition to conventional therapy, the experimental group received 10 hours of individual and supervised trunk exercises; 30 minutes, 4 times a week, for 5 weeks. Trunk performance was evaluated by the Trunk Impairment Scale (TIS) and its subscales of static and dynamic sitting balance and coordination. A general linear repeated measures model was used to analyze the results of our study.\n\nNo significant differences were found pretreatment between the 2 groups for the collected demographic variables, stroke-related parameters, clinical measures, number of therapy sessions received, and primary outcome measure used. Posttreatment, a significantly better improvement was noted in the experimental group compared to the control group for the dynamic sitting balance subscale only; measuring selective lateral flexion initiated from the upper and lower part of the trunk, (P = .002, post hoc power calculation = .90, effect size = 1.16).\n\nOur results suggest that, in addition to conventional therapy, trunk exercises aimed at improving sitting balance and selective trunk movements have a beneficial effect on the selective performance of lateral flexion of the trunk after stroke.", "PMID": "18955513"}, {"title": "Additional exercises improve trunk performance after stroke: a pilot randomized controlled trial.", "abstract": "Sitting balance and the ability to perform selective trunk movements are important predictors of functional outcome after stroke. However, studies evaluating the effect of exercises aimed at improving trunk performance are sparse.\n\nTo examine the effect of additional trunk exercises on trunk performance after stroke.\n\nAn assessor-blinded randomized controlled trial was carried out at an inpatient stroke rehabilitation center. In total 33 participants were assigned to an experimental group (n = 17) or a control group (n = 16). In addition to conventional therapy, the experimental group received 10 hours of individual and supervised trunk exercises; 30 minutes, 4 times a week, for 5 weeks. Trunk performance was evaluated by the Trunk Impairment Scale (TIS) and its subscales of static and dynamic sitting balance and coordination. A general linear repeated measures model was used to analyze the results of our study.\n\nNo significant differences were found pretreatment between the 2 groups for the collected demographic variables, stroke-related parameters, clinical measures, number of therapy sessions received, and primary outcome measure used. Posttreatment, a significantly better improvement was noted in the experimental group compared to the control group for the dynamic sitting balance subscale only; measuring selective lateral flexion initiated from the upper and lower part of the trunk, (P = .002, post hoc power calculation = .90, effect size = 1.16).\n\nOur results suggest that, in addition to conventional therapy, trunk exercises aimed at improving sitting balance and selective trunk movements have a beneficial effect on the selective performance of lateral flexion of the trunk after stroke.", "PMID": "18955513"}], "labels": [{"PMID": "10527076", "label": "included"}, {"PMID": "10768528", "label": "included"}, {"PMID": "10945420", "label": "included"}, {"PMID": "11812553", "label": "included"}, {"PMID": "11991797", "label": "included"}, {"PMID": "12194618", "label": "excluded"}, {"PMID": "12392332", "label": "excluded"}, {"PMID": "17535145", "label": "excluded"}, {"PMID": "18955513", "label": "excluded"}, {"PMID": "18955513", "label": "excluded"}]}
{"metadata": {"review_pmid": "39878158"}, "inputs": {"background": "Electronic cigarettes (ECs) are handheld electronic vaping devices that produce an aerosol by heating an e-liquid. People who smoke, healthcare providers, and regulators want to know if ECs can help people quit smoking, and if they are safe to use for this purpose. This is a review update conducted as part of a living systematic review.", "objectives": "To examine the safety, tolerability, and effectiveness of using EC to help people who smoke tobacco achieve long-term smoking abstinence, in comparison to non-nicotine EC, other smoking cessation treatments, and no treatment.", "selection criteria": "We included trials randomizing people who smoke to an EC or control condition. We included uncontrolled intervention studies in which all participants received an EC intervention. Studies had to report an eligible outcome."}, "context": [{"title": "Effect of an electronic nicotine delivery device (e-Cigarette) on smoking reduction and cessation: a prospective 6-month pilot study.", "abstract": "Cigarette smoking is a tough addiction to break. Therefore, improved approaches to smoking cessation are necessary. The electronic-cigarette (e-Cigarette), a battery-powered electronic nicotine delivery device (ENDD) resembling a cigarette, may help smokers to remain abstinent during their quit attempt or to reduce cigarette consumption. Efficacy and safety of these devices in long-term smoking cessation and/or smoking reduction studies have never been investigated.\n\nIn this prospective proof-of-concept study we monitored possible modifications in smoking habits of 40 regular smokers (unwilling to quit) experimenting the 'Categoria' e-Cigarette with a focus on smoking reduction and smoking abstinence. Study participants were invited to attend a total of five study visits: at baseline, week-4, week-8, week-12 and week-24. Product use, number of cigarettes smoked, and exhaled carbon monoxide (eCO) levels were measured at each visit. Smoking reduction and abstinence rates were calculated. Adverse events and product preferences were also reviewed.\n\nSustained 50% reduction in the number of cig/day at week-24 was shown in 13/40(32.5%) participants; their median of 25 cigs/day decreasing to 6 cigs/day (p < 0.001). Sustained 80% reduction was shown in 5/40(12.5%) participants; their median of 30 cigs/day decreasing to 3 cigs/day (p = 0.043). Sustained smoking abstinence at week-24 was observed in 9/40(22.5%) participants, with 6/9 still using the e-Cigarette by the end of the study. Combined sustained 50% reduction and smoking abstinence was shown in 22/40 (55%) participants, with an overall 88% fall in cigs/day. Mouth (20.6%) and throat (32.4%) irritation, and dry cough (32.4%) were common, but diminished substantially by week-24. Overall, 2 to 3 cartridges/day were used throughout the study. Participants' perception and acceptance of the product was good.\n\nThe use of e-Cigarette substantially decreased cigarette consumption without causing significant side effects in smokers not intending to quit (http://ClinicalTrials.gov number NCT01195597).", "PMID": "21989407"}, {"title": "Impact of an electronic cigarette on smoking reduction and cessation in schizophrenic smokers: a prospective 12-month pilot study.", "abstract": "Cigarette smoking is a tough addiction to break. This dependence is the most common dual diagnosis for individuals with schizophrenia. Currently three effective drugs are approved for smoking cessation: nicotine replacement therapy (NRT), varenicline and bupropion. However, some serious side effects of varenicline have been reported, including depression, suicidal thoughts, and suicide. The use of bupropion also has side effects. It should not be used by people who have epilepsy or any condition that lowers the seizure threshold, nor by people who take a specific class of drugs called monoamine oxidase inhibitors. Hence, there are pharmacodynamic reason to believe they could precipitate or exacerbate psychosis. For its capacity to deliver nicotine and provide a coping mechanism for conditioned smoking cues by replacing some of the rituals associated with smoking gestures, electronic-cigarettes may reduce nicotine withdrawal symptoms without serious side effects. Our recent work with ECs in healthy smokers not intending to quit consistently show surprisingly high success rates. We hypothesised that these positive findings could be replicated in difficult patients with schizophrenia This tool may help smokers with schizophrenia remain abstinent during their quitting attempts or to reduce cigarette consumption. Efficacy and safety of these devices in long-term smoking cessation and/or smoking reduction studies have never been investigated for this special population.\n\nIn this study we monitored possible modifications in smoking habits of 14 smokers (not intending to quit) with schizophrenia experimenting with the \"Categoria\" e-Cigarette with a focus on smoking reduction and smoking abstinence. Study participants were invited to attend six study visits: at baseline, week-4, week-8, week-12 week-24 and week 52. Product use, number of cigarettes smoked, carbon monoxide in exhaled breath (eCO) and positive and negative symptoms of schizophrenia levels were measured at each visit. Smoking reduction and abstinence rates were calculated. Adverse events were also reviewed.\n\nSustained 50% reduction in the number of cig/day at week-52 was shown in 7/14 (50%) participants; their median of 30 cig/day decreasing significantly to 15 cig/day (p = 0.018). Sustained smoking abstinence at week-52 was observed in 2/14 (14.3%) participants. Combined sustained 50% reduction and smoking abstinence was shown in 9/14 (64.3%) participants. Nausea was observed in 2/14 (14.4%) of participants, throat irritation in 2/14 (14.4%) of participants, headache in 2/14 (14.4%) of participants , and dry cough in 4/14 (28.6%) of participants. However, these adverse events diminished substantially by week-24. Overall, one to two cartridges/day were used throughout the study. Positive and negative symptoms of schizophrenia are not increased after smoking reduction/cessation in patients using e-cigarettes.\n\nWe have shown for the first time that the use of e-cigarette substantially decreased cigarette consumption without causing significant side effects in chronic schizophrenic patients who smoke not intending to quit. This was achieved without negative impacts on the symptoms of schizophrenia as assessed by SAPS and SANS symptoms scales.", "PMID": "23358230"}, {"title": "Study protocol for a randomised controlled trial of electronic cigarettes versus nicotine patch for smoking cessation.", "abstract": "Electronic cigarettes (e-cigarettes or electronic nicotine delivery systems [ENDS]) are electrically powered devices generally similar in appearance to a cigarette that deliver a propylene glycol and/or glycerol mist to the airway of users when drawing on the mouthpiece. Nicotine and other substances such as flavourings may be included in the fluid vaporised by the device. People report using e-cigarettes to help quit smoking and studies of their effects on tobacco withdrawal and craving suggest good potential as smoking cessation aids. However, to date there have been no adequately powered randomised trials investigating their cessation efficacy or safety. This paper outlines the protocol for this study.\n\nParallel group, 3-arm, randomised controlled trial.\n\nPeople aged \u226518 years resident in Auckland, New Zealand (NZ) who want to quit smoking.\n\nStratified blocked randomisation to allocate participants to either Elusion\u2122 e-cigarettes with nicotine cartridges (16 mg) or with placebo cartridges (i.e. no nicotine), or to nicotine patch (21 mg) alone. PARTICIPANTS randomised to the e-cigarette groups will be told to use them ad libitum for one week before and 12 weeks after quit day, while participants randomised to patches will be told to use them daily for the same period. All participants will be offered behavioural support to quit from the NZ Quitline.\n\nBiochemically verified (exhaled carbon monoxide) continuous abstinence at six months after quit day.\n\n657 people (292 in both the nicotine e-cigarette and nicotine patch groups and 73 in the placebo e-cigarettes group) will provide 80% power at p = 0.05 to detect an absolute difference of 10% in abstinence between the nicotine e-cigarette and nicotine patch groups, and 15% between the nicotine and placebo e-cigarette groups.\n\nThis trial will inform international debate and policy on the regulation and availability of e-cigarettes. If shown to be efficacious and safe, these devices could help many smokers as an alternative smoking cessation aid to standard nicotine products.\n\nAustralian NZ Clinical Trials Registry (ACTRN12610000866000).", "PMID": "23496861"}, {"title": "EffiCiency and Safety of an eLectronic cigAreTte (ECLAT) as tobacco cigarettes substitute: a prospective 12-month randomized control design study.", "abstract": "Electronic cigarettes (e-cigarettes) are becoming increasingly popular with smokers worldwide. Users report buying them to help quit smoking, to reduce cigarette consumption, to relieve tobacco withdrawal symptoms, and to continue having a 'smoking' experience, but with reduced health risks. Research on e-cigarettes is urgently needed in order to ensure that the decisions of regulators, healthcare providers and consumers are based on science. Methods ECLAT is a prospective 12-month randomized, controlled trial that evaluates smoking reduction/abstinence in 300 smokers not intending to quit experimenting two different nicotine strengths of a popular e-cigarette model ('Categoria'; Arbi Group Srl, Italy) compared to its non-nicotine choice. GroupA (n\u200a=\u200a100) received 7.2 mg nicotine cartridges for 12 weeks; GroupB (n\u200a=\u200a100), a 6-week 7.2 mg nicotine cartridges followed by a further 6-week 5.4 mg nicotine cartridges; GroupC (n\u200a=\u200a100) received no-nicotine cartridges for 12 weeks. The study consisted of nine visits during which cig/day use and exhaled carbon monoxide (eCO) levels were measured. Smoking reduction and abstinence rates were calculated. Adverse events and product preferences were also reviewed.\n\nDeclines in cig/day use and eCO levels were observed at each study visits in all three study groups (p<0.001 vs baseline), with no consistent differences among study groups. Smoking reduction was documented in 22.3% and 10.3% at week-12 and week-52 respectively. Complete abstinence from tobacco smoking was documented in 10.7% and 8.7% at week-12 and week-52 respectively. A substantial decrease in adverse events from baseline was observed and withdrawal symptoms were infrequently reported during the study. Participants' perception and acceptance of the product under investigation was satisfactory.\n\nIn smokers not intending to quit, the use of e-cigarettes, with or without nicotine, decreased cigarette consumption and elicited enduring tobacco abstinence without causing significant side effects.\n\nClinicalTrials.gov NCT01164072 NCT01164072.", "PMID": "23826093"}, {"title": "Effectiveness and tolerability of electronic cigarette in real-life: a 24-month prospective observational study.", "abstract": "Electronic cigarettes (e-Cigarette) are battery-operated devices designed to vaporise nicotine that may aid smokers to quit or reduce their cigarette consumption. Research on e-Cigarettes is urgently needed to ensure that the decisions of regulators, healthcare providers and consumers are evidence based. Here we assessed long-term effectiveness and tolerability of e-Cigarette used in a 'naturalistic' setting. This prospective observational study evaluated smoking reduction/abstinence in smokers not intending to quit using an e-Cigarette ('Categoria'; Arbi Group, Italy). After an intervention phase of 6 months, during which e-Cigarette use was provided on a regular basis, cigarettes per day (cig/day) and exhaled carbon monoxide (eCO) levels were followed up in an observation phase at 18 and 24 months. Efficacy measures included: (a) \u226550% reduction in the number of cig/day from baseline, defined as self-reported reduction in the number of cig/day (\u226550%) compared to baseline; (b) \u226580% reduction in the number of cig/day from baseline, defined as self-reported reduction in the number of cig/day (\u226580%) compared to baseline; (c) abstinence from smoking, defined as complete self-reported abstinence from tobacco smoking (together with an eCO concentration of \u226410 ppm). Smoking reduction and abstinence rates were computed, and adverse events reviewed. Of the 40 subjects, 17 were lost to follow-up at 24 months. A >50% reduction in the number of cig/day at 24 months was shown in 11/40 (27.5%) participants with a median of 24 cig/day use at baseline decreasing significantly to 4 cig/day (p = 0.003). Smoking abstinence was reported in 5/40 (12.5%) participants while combined >50% reduction and smoking abstinence was observed in 16/40 (40%) participants at 24 months. Five subjects stopped e-Cigarette use (and stayed quit), three relapsed back to tobacco smoking and four upgraded to more performing products by 24 months. Only some mouth irritation, throat irritation, and dry cough were reported. Withdrawal symptoms were uncommon. Long-term e-Cigarette use can substantially decrease cigarette consumption in smokers not willing to quit and is well tolerated. ( http://ClinicalTrials.govnumberNCT01195597 ).", "PMID": "23873169"}, {"title": "Electronic cigarettes for smoking cessation: a randomised controlled trial.", "abstract": "Electronic cigarettes (e-cigarettes) can deliver nicotine and mitigate tobacco withdrawal and are used by many smokers to assist quit attempts. We investigated whether e-cigarettes are more effective than nicotine patches at helping smokers to quit.\n\nWe did this pragmatic randomised-controlled superiority trial in Auckland, New Zealand, between Sept 6, 2011, and July 5, 2013. Adult (\u226518 years) smokers wanting to quit were randomised (with computerised block randomisation, block size nine, stratified by ethnicity [M\u0101ori; Pacific; or non-M\u0101ori, non-Pacific], sex [men or women], and level of nicotine dependence [>5 or \u22645 Fagerstr\u00f6m test for nicotine dependence]) in a 4:4:1 ratio to 16 mg nicotine e-cigarettes, nicotine patches (21 mg patch, one daily), or placebo e-cigarettes (no nicotine), from 1 week before until 12 weeks after quit day, with low intensity behavioural support via voluntary telephone counselling. The primary outcome was biochemically verified continuous abstinence at 6 months (exhaled breath carbon monoxide measurement <10 ppm). Primary analysis was by intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12610000866000.\n\n657 people were randomised (289 to nicotine e-cigarettes, 295 to patches, and 73 to placebo e-cigarettes) and were included in the intention-to-treat analysis. At 6 months, verified abstinence was 7\u00b73% (21 of 289) with nicotine e-cigarettes, 5\u00b78% (17 of 295) with patches, and 4\u00b71% (three of 73) with placebo e-cigarettes (risk difference for nicotine e-cigarette vs patches 1\u00b751 [95% CI -2\u00b749 to 5\u00b751]; for nicotine e-cigarettes vs placebo e-cigarettes 3\u00b716 [95% CI -2\u00b729 to 8\u00b761]). Achievement of abstinence was substantially lower than we anticipated for the power calculation, thus we had insufficient statistical power to conclude superiority of nicotine e-cigarettes to patches or to placebo e-cigarettes. We identified no significant differences in adverse events, with 137 events in the nicotine e-cigarettes group, 119 events in the patches group, and 36 events in the placebo e-cigarettes group. We noted no evidence of an association between adverse events and study product.\n\nE-cigarettes, with or without nicotine, were modestly effective at helping smokers to quit, with similar achievement of abstinence as with nicotine patches, and few adverse events. Uncertainty exists about the place of e-cigarettes in tobacco control, and more research is urgently needed to clearly establish their overall benefits and harms at both individual and population levels.\n\nHealth Research Council of New Zealand.", "PMID": "24029165"}, {"title": "Carboxyhaemoglobin levels, health and lifestyle perceptions in smokers converting from tobacco cigarettes to electronic cigarettes.", "abstract": "Chronic obstructive pulmonary disease and lung cancer are diseases associated with smoking tobacco cigarettes. Smokers find cessation difficult.\n\nTo determine whether smoking the Twisp electronic cigarette (e-cigarette), containing nicotine in a vegetable-based glycerine substance, would reduce carboxyhaemoglobin (COHb) levels in regular cigarette smokers by (i) comparing arterial and venous COHb levels before and after smoking the Twisp e-cigarette for 2 weeks; and (ii) evaluating changes in participants' perception of their health and lifestyle following the use of Twisp e-cigarettes.\n\nA single group within-subject design was used where tobacco cigarette smokers converted to Twisp e-cigarettes for 2 weeks. Prior to using the Twisp e-cigarette and after using this device for 2 weeks, arterial COHb, venous COHb and venous cotinine levels were determined. Additionally, the participants were asked to complete a questionnaire outlining their perceptions on health and lifestyle.\n\nThirteen participants of median age 38 years (range 23 - 46) with a smoking median of 20 cigarettes/day (range 12 - 30) completed the study. COHb levels (%) were significantly reduced after smoking Twisp e-cigarettes for 2 weeks (mean \u00b1 standard deviation (SD) arterial COHb before 4.66\u00b11.99 v. after 2.46\u00b11.35; p=0.014 and mean \u00b1SD venous COHb before 4.37\u00b12.1 v. after 2.50\u00b11.23; p=0.018). There was excellent agreement between arterial and venous COHb levels (intraclass correlation coefficient 0.916). A decrease in cotinine levels (p=0.001) and an increase in oxygen saturation (p=0.002) were also observed. The majority of participants perceived improvements in their health and lifestyle parameters.\n\nSmoking the Twisp e-cigarette may be a healthier and more acceptable alternative to smoking tobacco cigarettes.", "PMID": "24148175"}, {"title": "Electronic cigarettes and smoking cessation: a quandary? - Authors' reply.", "abstract": "", "PMID": "24485579"}, {"title": "e-Cigarette awareness, use, and harm perceptions in US adults.", "abstract": "We estimated e-cigarette (electronic nicotine delivery system) awareness, use, and harm perceptions among US adults.\n\nWe drew data from 2 surveys conducted in 2010: a national online study (n = 2649) and the Legacy Longitudinal Smoker Cohort (n = 3658). We used multivariable models to examine e-cigarette awareness, use, and harm perceptions.\n\nIn the online survey, 40.2% (95% confidence interval [CI]\u2009= 37.3, 43.1) had heard of e-cigarettes, with awareness highest among current smokers. Utilization was higher among current smokers (11.4%; 95% CI = 9.3, 14.0) than in the total population (3.4%; 95% CI = 2.6, 4.2), with 2.0% (95% CI = 1.0, 3.8) of former smokers and 0.8% (95% CI = 0.35, 1.7) of never-smokers ever using e-cigarettes. In both surveys, non-Hispanic Whites, current smokers, young adults, and those with at least a high-school diploma were most likely to perceive e-cigarettes as less harmful than regular cigarettes.\n\nAwareness of e-cigarettes is high, and use among current and former smokers is evident. We recommend product regulation and careful surveillance to monitor public health impact and emerging utilization patterns, and to ascertain why, how, and under what conditions e-cigarettes are being used.", "PMID": "22813087"}, {"title": "Electronic nicotine delivery systems: international tobacco control four-country survey.", "abstract": "Electronic nicotine delivery systems (ENDS) initially emerged in 2003 and have since become widely available globally, particularly over the Internet.\n\nData on ENDS usage patterns are limited. The current paper examines patterns of ENDS awareness, use, and product-associated beliefs among current and former smokers in four countries.\n\nData come from Wave 8 of the International Tobacco Control Four-Country Survey, collected July 2010 to June 2011 and analyzed through June 2012. Respondents included 5939 current and former smokers in Canada (n=1581); the U.S. (n=1520); the United Kingdom (UK; n=1325); and Australia (n=1513).\n\nOverall, 46.6% were aware of ENDS (U.S.: 73%, UK: 54%, Canada: 40%, Australia: 20%); 7.6% had tried ENDS (16% of those aware of ENDS); and 2.9% were current users (39% of triers). Awareness of ENDS was higher among younger, non-minority smokers with higher incomes who were heavier smokers. Prevalence of trying ENDS was higher among younger, nondaily smokers with a high income and among those who perceived ENDS as less harmful than traditional cigarettes. Current use was higher among both nondaily and heavy (\u226520 cigarettes per day) smokers. In all, 79.8% reported using ENDS because they were considered less harmful than traditional cigarettes; 75.4% stated that they used ENDS to help them reduce their smoking; and 85.1% reported using ENDS to help them quit smoking.\n\nAwareness of ENDS is high, especially in countries where they are legal (i.e., the U.S. and UK). Because trial was associated with nondaily smoking and a desire to quit smoking, ENDS may have the potential to serve as a cessation aid.", "PMID": "23415116"}], "labels": [{"PMID": "21989407", "label": "included"}, {"PMID": "23358230", "label": "included"}, {"PMID": "23496861", "label": "included"}, {"PMID": "23826093", "label": "included"}, {"PMID": "23873169", "label": "included"}, {"PMID": "24029165", "label": "included"}, {"PMID": "24148175", "label": "included"}, {"PMID": "24485579", "label": "included"}, {"PMID": "22813087", "label": "excluded"}, {"PMID": "23415116", "label": "excluded"}]}
{"metadata": {"review_pmid": "39804128"}, "inputs": {"background": "Cognitive stimulation (CS) is an intervention for people with dementia offering a range of enjoyable activities providing general stimulation for thinking, concentration and memory, usually in a social setting, such as a small group. CS is distinguished from other approaches such as cognitive training and cognitive rehabilitation by its broad focus and social elements, aiming to improve domains such as quality of life (QoL) and mood as well as cognitive function. Recommended in various guidelines and widely implemented internationally, questions remain regarding different modes of delivery and the clinical significance of any benefits. A systematic review of CS is important to clarify its effectiveness and place practice recommendations on a sound evidence base. This review was last updated in 2012.", "objectives": "To evaluate the evidence for the effectiveness of CS for people with dementia, including any negative effects, on cognition and other relevant outcomes, accounting where possible for differences in its implementation.", "selection criteria": "We included all randomised controlled trials (RCTs) of CS for dementia published in peer review journals in the English language incorporating a measure of cognitive change."}, "context": [{"title": "Efficacy of an evidence-based cognitive stimulation therapy programme for people with dementia: randomised controlled trial.", "abstract": "A recent Cochrane review of reality orientation therapy identified the need for large, well-designed, multi-centre trials.\n\nTo test the hypothesis that cognitive stimulation therapy (CST) for older people with dementia would benefit cognition and quality of life.\n\nA single-blind, multi-centre, randomised controlled trial recruited 201 older people with dementia. The main outcome measures were change in cognitive function and quality of life. An intention-to-treat analysis used analysis of covariance to control for potential variability in baseline measures.\n\nOne hundred and fifteen people were randomised within centres to the intervention group and 86 to the control group. At follow-up the intervention group had significantly improved relative to the control group on the Mini-Mental State Examination (P=0.044), the Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog) (P=0.014) and Quality of Life - Alzheimer's Disease scales (P=0.028). Using criteria of 4 points or more improvement on the ADAS-Cog the number needed to treat was 6 for the intervention group.\n\nThe results compare favourably with trials of drugs for dementia. CST groups may have worthwhile benefits for many people with dementia.", "PMID": "12948999"}, {"title": "The role of reality orientation therapy in restorative care of elderly patients with dementia plus stroke in the subacute nursing home setting.", "abstract": "", "PMID": "14764370"}, {"title": "Effects of cholinergic drugs and cognitive training on dementia.", "abstract": "A study was performed on patients with Alzheimer's disease (AD) in order to evaluate the efficacy of a combined treatment (donepezil plus cognitive training) in both cognitive processes and affective states. Eighty-six subjects, 25 men and 61 women, with an average age of 75.58 years, were studied. Almost all the subjects had a basic educational level. Donezepil was administered at a dose of 10 mg daily along with cognitive treatment involving images of everyday life and reminiscent music; the sessions took place on Monday to Friday and lasted three quarters of an hour. The study lasted 12 months. Subjects underwent test-retest with the following tests: Mini-Mental State Examination (MMSE), the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog); the Geriatric Depression Scale (GDS) and the overall deterioration scale (FAST). The results showed that subjects receiving the combined treatment had a better response than those who did not receive any cognitive training. These subjects' MMSE score decreased by 3.24 on average. The affective symptomatology of those receiving only drug treatment improved whereas the cognitive processes did not.", "PMID": "15084794"}, {"title": "Comparison of a reality orientation program for geriatric patients with and without music.", "abstract": "Reality orientation (RO) is a technique used with patients exhibiting confused or disoriented behavior. The purpose of RO is to reverse or halt confusion, social withdrawal, and apathy characteristic of elderly institutionalized patients. The purpose of this study was to compare the effects of a traditional versus music-based RO program. Eight residents of the Chateau de Notre Dame Nursing Home were randomly assigned to experimental and control groups. A pretest was administered to identify any significant differences in RO and behavior functioning between the two groups. The specific goals and objectives for the RO program were then formulated from information gathered on the pretest. The experimental group received two 30-minute music-based RO sessions a week for 8 weeks, while the control group received the same number of traditional RO sessions without music. Upon completion of the treatment, the posttest was administered to each subject. A two-way \"mixed effects\" analysis of variance was used to analyze the data. A significant interaction (p less than .05) was found between the groups and the treatment condition, with the control group remaining at the same level across trials and the group receiving the music-based RO showing marked improvement.", "PMID": "10245502"}, {"title": "Intervention effects on dementia caregiving interaction: a stress-adaptation modeling approach.", "abstract": "Our purpose was to evaluate the adequacy of a stress adaptation framework for guiding intervention research on caregivers and patients coping with Alzheimer's disease, and to test the effect of a cognitive stimulation intervention as an interactive outcome.\n\nUsing a repeated measures design, 87 caregiver-patient dyads were randomized to one of three conditions: active cognitive stimulation, passive stimulation, or control.  Assessments occurred at preintervention, postintervention (3 months), and 9 months.\n\nThe LISREL model was entirely satisfactory by the chi-square goodness-of-fit criteria.  However, the coefficients associated with the paths between the mediating concepts and the dyadic interaction differed significantly at 3 months and 9 months.  The intervention group caregivers were shown to be more satisfied with their interaction with the impaired member.\n\nThe improvement in caregiver satisfaction was attributed to an attenuation of the behavioral stressor effects through increased use of a problem-focused coping strategy, namely, positive reappraisal of the stressful situation.", "PMID": "10848143"}, {"title": "Coping with dementia: evaluation of four nonpharmacologic interventions.", "abstract": "To evaluate nonpharmacologic interventions, caregivers (65 women, 38 men) and their dementia-diagnosed spouses (patients) were randomized to one of four treatment programs (cognitive stimulation, dyadic counseling, dual supportive seminar, and early-stage day care) or to a wait-list control group. Assessments occurred initially and at postintervention (3 months). Patients were evaluated on memory, verbal fluency, and problem-solving ability, and caregivers were assessed on marital interaction, emotional status, and physical health, along with stress, coping, and social support. Caregivers also completed a program evaluation. Repeated measures procedures showed that patients in the cognitive stimulation group demonstrated more improvement over time in cognitive outcomes, and caregivers decreased in depressive symptoms. Early-stage day-care and dual supportive seminar group caregivers reported a decrease in hostility and a decrease in use of negative coping strategies, respectively. Although qualitatively derived benefits differed across groups, similarities in program content reduced the potential for quantitative differentiation among the groups.", "PMID": "10937544"}, {"title": "Cognitive intervention in Alzheimer disease: a randomized placebo-controlled study.", "abstract": "The efficacy of a cognitive intervention consisting of training in face-name associations, spaced retrieval, and cognitive stimulation was tested in a sample of 37 patients (16 men, 21 women) with probable Alzheimer disease (AD). Patients with AD were randomly assigned to receive either the cognitive intervention or a mock (placebo) intervention for 5 weeks. The placebo group then crossed over to receive the intervention. During the intervention, AD patients showed significant improvement in recall of personal information, face-name recall, and performance on the Verbal Series Attention Test. Improvement did not generalize to additional neuropsychologic measures of dementia severity, verbal memory, visual memory, word generation, or motor speed, or to caregiver-assessed patient quality of life. Results suggest that although face-name training, spaced retrieval, and cognitive stimulation may produce small gains in learning personal information and on a measure of attention, improvement does not generalize to overall neuropsychologic functioning or patient quality of life.", "PMID": "11236819"}, {"title": "Reality orientation, a therapy for psychogeriatric patient: a controlled study.", "abstract": "", "PMID": "1139081"}, {"title": "Who participates in psychosocial interventions for caregivers of patients with dementia?", "abstract": "The purpose of the present study is to evaluate if the participants in psychosocial interventions for dementia caregivers are representative of the whole population of dementia patients or if some socioeconomic groups are over- or underrepresented.\n\nThe demographic and socioeconomic characteristics of the 128 participants of a randomized controlled study on the effects of caregiver education were compared with those of all the elderly residents of the City of Zurich (n = 64,856, elderly group), of all demented patients entering a City of Zurich nursing home in a 6-month period (n = 218, NH entry group) and of all demented inhabitants evaluated during a 20-month follow-up at a community memory clinic (n = 187, memory group).\n\nData on income and wealth were derived from official tax records. The characteristics of the different groups were compared by chi2 or t tests.\n\nAs expected in a study on caregiver education, the demented patients were younger, more often male and married than all other study groups (p < 0.01). The participants in the psychosocial intervention had significantly (p < 0.01) higher education than all other groups; this effect is caused in part by the higher proportion of males. The NH entry group was less well educated than the elderly group (p < 0.05). The intervention group had a higher income and was wealthier than the three other groups (p < 0.01), but there was no significant difference with respect to the wealth of the memory group. The 25% poorest of the elderly group made up only about 10% of the participants in the intervention group. However, the 25% richest of the elderly group made up 42% of the intervention group. The method of recruitment for the psychosocial intervention (by media, referral of physicians and by a memory clinic) was not significantly related to any of the demographic or socioeconomic parameters.\n\nThe lower socioeconomic strata are clearly underrepresented in psychosocial interventions.", "PMID": "15087582"}, {"title": "Benefits of cognitive-motor intervention in MCI and mild to moderate Alzheimer disease.", "abstract": "To evaluate the efficacy of a cognitive-motor program in patients with early Alzheimer disease (AD) who are treated with a cholinesterase inhibitor (ChEI).\n\nPatients with mild cognitive impairment (MCI) (12), mild AD (48), and moderate AD (24) (Global Deterioration Scale stages 3, 4, and 5) were randomized to receive psychosocial support plus cognitive-motor intervention (experimental group) or psychosocial support alone (control group). Cognitive-motor intervention (CMI) consisted of a 1-year structured program of 103 sessions of cognitive exercises, plus social and psychomotor activities. The primary efficacy measure was the cognitive subscale of the AD Assessment Scale (ADAS-cog). Secondary efficacy measures were the Mini-Mental State Examination, the Functional Activities Questionnaire, and the Geriatric Depression Scale. Evaluations were conducted at 1, 3, 6, and 12 months by blinded evaluators.\n\nPatients in the CMI group maintained cognitive status at month 6, whereas patients in the control group had significantly declined at that time. Cognitive response was higher in the patients with fewer years of formal education. In addition, more patients in the experimental group maintained or improved their affective status at month 12 (experimental group, 75%; control group, 47%; p = 0.017).\n\nA long-term CMI in ChEI-treated early Alzheimer disease patients produced additional mood and cognitive benefits.", "PMID": "15623698"}], "labels": [{"PMID": "12948999", "label": "included"}, {"PMID": "14764370", "label": "included"}, {"PMID": "15084794", "label": "included"}, {"PMID": "10245502", "label": "excluded"}, {"PMID": "10848143", "label": "excluded"}, {"PMID": "10937544", "label": "excluded"}, {"PMID": "11236819", "label": "excluded"}, {"PMID": "1139081", "label": "excluded"}, {"PMID": "15087582", "label": "excluded"}, {"PMID": "15623698", "label": "excluded"}]}
{"metadata": {"review_pmid": "39679851"}, "inputs": {"background": "Sample collection is a key driver of accuracy in the diagnosis of SARS-CoV-2 infection. Viral load may vary at different anatomical sampling sites and accuracy may be compromised by difficulties obtaining specimens and the expertise of the person taking the sample. It is important to optimise sampling accuracy within cost, safety and accessibility constraints.", "objectives": "To compare the sensitivity of different sampling collection sites and methods for the detection of current SARS-CoV-2 infection with any molecular or antigen-based test.", "selection criteria": "We included studies of symptomatic or asymptomatic people with suspected SARS-CoV-2 infection undergoing testing. We included studies of any design that compared results from different sample types (anatomical location, operator, collection device) collected from the same participant within a 24-hour period."}, "context": [{"title": "Comparison of Copan ESwab and FLOQSwab for COVID-19 Diagnosis: Working around a Supply Shortage.", "abstract": "", "PMID": "32295895"}, {"title": "Nasal Swab Sampling for SARS-CoV-2: a Convenient Alternative in Times of Nasopharyngeal Swab Shortage.", "abstract": "", "PMID": "32295896"}, {"title": "Comparison of nasopharyngeal and oropharyngeal swabs for SARS-CoV-2 detection in 353 patients received tests with both specimens simultaneously.", "abstract": "Since the outbreak of coronavirus disease (COVID-19) in Wuhan in December 2019, by March 10, 2020, a total of 80,932 confirmed cases have been reported in China. Two consecutively negative RT-PCR test results in respiratory tract specimens is required for the evaluation of discharge from hospital, and oropharyngeal swabs were the most common sample. However, false negative results occurred in the late stage of hospitalization, and avoiding false negative result is critical essential.\n\nWe reviewed the medical record of 353 patients who received tests with both specimens simultaneously, and compared the performance between nasopharyngeal and oropharyngeal swabs.\n\nOf the 353 patients (outpatients, 192; inpatients, 161) studied, the median age was 54 years, and 177 (50.1%) were women. Higher positive rate (positive tests/total tests) was observed in nasopharyngeal swabs than oropharyngeal swabs, especially in inpatients. Nasopharyngeal swabs from inpatients showed higher positive rate than outpatients. Nasopharyngeal swabs from male showed higher positive rate than female, especially in outpatients. Detection with both specimens slightly increased the positive rate than nasopharyngeal swab only. Moreover, the consistency between from nasopharyngeal and oropharyngeal swabs were poor (Kappa=0.308).\n\nIn conclusion, our study suggests that nasopharyngeal swabs may be more suitable than oropharyngeal swab at this stage of COVID-19 outbreak.", "PMID": "32315809"}, {"title": "Saliva as a Noninvasive Specimen for Detection of SARS-CoV-2.", "abstract": "", "PMID": "32317257"}, {"title": "Self-collection: An appropriate alternative during the SARS-CoV-2 pandemic.", "abstract": "To evaluate the reliability of self-collection for SARS-CoV-2 and other respiratory viruses because swab collections for SARS-CoV-2 put health workers at risk of infection and require use of personal protective equipment (PPE).\n\nIn a prospective study, patients from two states in Australia attending dedicated COVID-19 collection clinics were offered the option to first self-collect (SC) nasal and throat swabs (SCNT) prior to health worker collect (HC) using throat and nasal swabs (Site 1) or throat and nasopharyngeal swabs (Site 2). Samples were analysed for SARS-CoV-2 as well as common respiratory viruses. Concordance of results between methods was assessed using Cohen's kappa (\u03ba) and Cycle threshold (Ct) values were recorded for all positive results as a surrogate measure for viral load.\n\nOf 236 patients sampled by HC and SC, 25 had SARS-CoV-2 (24 by HC and 25 by SC) and 63 had other respiratory viruses (56 by HC and 58 by SC). SC was highly concordant with HC (\u03ba\u202f=\u202f0.890) for all viruses including SARS-CoV-2 and more concordant than HC to positive results by any method (\u03ba\u202f=\u202f0.959 vs 0.933). Mean SARS-CoV-2 E-gene and N-gene, rhinovirus and parainfluenza Ct values did not differ between HC and SCNT.\n\nSelf-collection of nasal and throat swabs offers a reliable alternative to health worker collection for the diagnosis of SARS-CoV-2 and other respiratory viruses and provides patients with easier access to testing, reduces exposure of the community and health workers to those being tested and reduces requirement for PPE.", "PMID": "32403007"}, {"title": "Saliva as an Alternate Specimen Source for Detection of SARS-CoV-2 in Symptomatic Patients Using Cepheid Xpert Xpress SARS-CoV-2.", "abstract": "", "PMID": "32414838"}, {"title": "Saliva sample as a non-invasive specimen for the diagnosis of coronavirus disease 2019: a cross-sectional study.", "abstract": "Amid the increasing number of pandemic coronavirus disease 2019 (COVID-19) cases, there is a need for a quick and easy method to obtain a non-invasive sample for the detection of this novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2). We aimed to investigate the potential use of saliva samples as a non-invasive tool for the diagnosis of COVID-19.\n\nFrom 27 March to 4 April 2020, we prospectively collected saliva samples and a standard nasopharyngeal and throat swab in persons seeking care at an acute respiratory infection clinic in a university hospital during the outbreak of COVID-19. Real-time polymerase chain reaction (RT-PCR) was performed, and the results of the two specimens were compared.\n\nTwo-hundred pairs of samples were collected. Sixty-nine (34.5%) individuals were male, and the median (interquartile) age was 36 (28-48) years. Using nasopharyngeal and throat swab RT-PCR as the reference standard, the prevalence of COVID-19 diagnosed by nasopharyngeal and throat swab RT-PCR was 9.5%. The sensitivity and specificity of the saliva sample RT-PCR were 84.2% (95% CI 60.4%-96.6%), and 98.9% (95% CI 96.1%-99.9%), respectively. An analysis of the agreement between the two specimens demonstrated 97.5% observed agreement (\u03ba coefficient 0.851, 95% CI 0.723-0.979; p\u00a0<\u00a00.001).\n\nSaliva might be an alternative specimen for the diagnosis of COVID-19. The collection is non-invasive, and non-aerosol generating. This method could facilitate the diagnosis of the disease, given the simplicity of specimen collection and good diagnostic performance.", "PMID": "32422408"}, {"title": "Clinical Evaluation and Utilization of Multiple Molecular In Vitro Diagnostic Assays for the Detection of SARS-CoV-2.", "abstract": "To evaluate the clinical performance of 3 molecular assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).\n\nWe used 184 nasopharyngeal swab specimens to compare Abbott ID NOW COVID-19 (Abbott ID NOW), DiaSorin Molecular Simplexa COVID-19 Direct (DiaSorin Simplexa), and Roche cobas 6800 SARS-CoV-2 (Roche cobas) assays. In a separate analysis, 3 specimens (nasopharyngeal, oropharyngeal, and nasal) were collected from 182 unique patients presenting to the emergency department with suspicion of coronavirus disease 2019 and were tested utilizing Abbott ID NOW. To further characterize each assay, relative limits of detection were evaluated utilizing positive nasopharyngeal patient samples.\n\nThe positive percent agreement was 91% (95% confidence interval [CI], 0.76-0.97) for Abbott ID NOW and 100% (95% CI, 0.90-1.00) for DiaSorin Simplexa and Roche cobas. The negative percent agreement was 100% (95% CI, 0.98-1.00) for all 3 assays. All swab types tested with the Abbott assay produced concordant results. Polymerase chain reaction assays had approximately 10 to 100 times lower limits of detection than Abbott ID NOW.\n\nBased on these evaluations, a multiplatform testing approach is proposed, depending on patient population and assay sensitivity, to address testing needs during a public health emergency.", "PMID": "32462195"}, {"title": "Swabs Collected by Patients or Health Care Workers for SARS-CoV-2 Testing.", "abstract": "", "PMID": "32492294"}, {"title": "Swabs Collected by Patients or Health Care Workers for SARS-CoV-2 Testing.", "abstract": "", "PMID": "32492294"}], "labels": [{"PMID": "32295895", "label": "included"}, {"PMID": "32295896", "label": "included"}, {"PMID": "32315809", "label": "included"}, {"PMID": "32317257", "label": "included"}, {"PMID": "32403007", "label": "included"}, {"PMID": "32414838", "label": "included"}, {"PMID": "32422408", "label": "included"}, {"PMID": "32462195", "label": "included"}, {"PMID": "32492294", "label": "included"}, {"PMID": "32492294", "label": "included"}]}
{"metadata": {"review_pmid": "39651635"}, "inputs": {"background": "Multiple sclerosis (MS) is an immune-mediated, chronic, inflammatory demyelinating disease of the central nervous system, impacting around 2.8 million people worldwide. Characterised by recurrent relapses or progression, or both, it represents a substantial global health burden, affecting people, predominantly women, at a young age (the mean age of diagnosis is 32 years). Azathioprine is used to treat chronic inflammatory and autoimmune diseases, and it is used in clinical practice as an off-label intervention for MS, especially where access to on-label disease-modifying treatments (DMTs) for MS is limited. Given this, a review of azathioprine's benefits and harms would be timely and valuable to inform shared healthcare decisions.", "objectives": "To evaluate the benefits and harms of azathioprine (AZA) for relapsing and progressive multiple sclerosis (MS), compared to other disease-modifying treatments (DMTs), placebo or no treatment. Specifically, we will assess the following comparisons. AZA compared with other DMTs or placebo as first-choice treatment for relapsing forms of multiple sclerosis AZA compared with other DMTs or placebo for relapsing forms of MS when switching from another DMT AZA compared with other DMTs or placebo as first-choice treatment for progressive forms of MS AZA compared with other DMTs or placebo for progressive forms of MS when switching from another DMT", "selection criteria": "We included randomised controlled trials (RCTs) lasting 12 months or more that compared azathioprine versus DMTs, placebo or no intervention in adults with MS. We considered evidence from non-randomised studies of interventions (NRSIs) as these studies may provide additional evidence not available from RCTS. We excluded cluster-randomised trials, cross-over trials, interrupted time series, case reports and studies of within-group design with no control group."}, "context": [{"title": "Longitudinal MRI study: the effects of azathioprine in MS patients refractory to interferon beta-1b.", "abstract": "An open-label study was performed to assess the effectiveness of oral azathioprine (AZA) on augmenting the response to interferon beta-1b (IFNbeta-1b) in patients with treatment-refractory relapsing-remitting MS. Six IFNbeta-1b-treated MS patients with continued disease activity were studied on IFNbeta-1b and AZA therapy for a median period of 15 months. A 69% reduction in the number of contrast-enhancing lesions was observed during the combination therapy (p = 0.002).", "PMID": "12796549"}, {"title": "Serum immunologic markers in multiple sclerosis patients on continuous combined therapy with beta-interferon 1a, prednisone and azathioprine.", "abstract": "Break-through symptoms (BTS) in multiple sclerosis (MS) patients on beta-interferon (beta-IFN) monotherapy are most frequently treated with a brief administration of steroids. Here, we report the results of monitoring serum immunologic markers recorded at three-month intervals for 1.5 years in responders to beta-INF 1a (Avonex) monotherapy (n =21) and MS patients placed on Avonex with prednisone (n =83) and Avonex, prednisone and azathioprine (AZA) (n =21) because of BTS. Compared to 23 healthy controls, patients on Avonex monotherapy and Avonex with prednisone, in individuals on Avonex, prednisone and AZA, a significant decrease in serum concentration of soluble intercellular adhesion molecule-1 (sICAM-1) (P=0.001) was established. Combined therapy with Avonex, prednisone and AZA was associated with a significant increase in the serum level of interleukin (IL)10 (P <0.001). Compared to Avonex monotherapy, combined therapy suppressed the serum level of IL12p40, antagonized elevation in the serum concentration of soluble IL2 receptor (sIL2R) and inhibited an increase in the serum soluble CD95 (sCD95) molecule. In patients studied, no significant differences in the serum level of IL18 and tumor necrosis factor-alpha (TNF-alpha) were established. These findings are important in understanding some of the immunoregulatory mechanisms induced by combined therapy in MS.", "PMID": "17086913"}, {"title": "Treatment with azathioprine and cyclic methylprednisolone has little or no effect on bioactivity in anti-interferon beta antibody-positive patients with multiple sclerosis.", "abstract": "It is unknown whether immunosuppression of patients who have developed interferon-beta (IFN-beta) neutralizing antibodies (NAbs) hastens disappearance of NAbs in the blood.\n\nWe wanted to test whether immunosuppression with cyclic methylprednisolone (MP) in combination with azathioprine (AZA) for 6 months accelerates recovery of IFN-beta bioactivity in patients with multiple sclerosis (MS) with abolished in-vivo myxovirus resistance protein A (MxA) mRNA response to IFN-beta.\n\nWe included 13 patients with MS with NAbs and a low IFN-beta bioavailability detected by the MxA-mRNA response in a descriptive, non-randomized trial. Another 14 NAb-positive patients with a low MxA-mRNA response served as controls. The primary outcome was the fraction of patients who regained an MxA-mRNA response to IFN-beta. NAbs were measured by means of a clinically validated cytopathic effect assay and a new reporter gene assay. The in-vivo MxA-mRNA response was measured by real-time polymerase chain reaction.\n\nA total of 11 patients in the treatment group completed the trial. In all, two of these 11 patients regained an in-vivo MxA-mRNA response as compared to one of 14 patients in the control group.\n\nTreatment with AZA and cyclic MP for 6 months has little or no effect on IFN-beta bioactivity in NAb-positive patients with MS.", "PMID": "19028832"}, {"title": "Cyclosporine versus azathioprine in the treatment of multiple sclerosis: 12-month clinical and immunological evaluation.", "abstract": "The aim of this trial was to compare the efficacy and tolerance of cyclosporine A (CYA) and azathioprine (AZA) as long-term immunosuppressive treatment for patients with multiple sclerosis. 31 randomly assigned patients completed a 12-month treatment with either CYA (5 mg/kg/day) or AZA (2 mg/kg/day). Evaluation included serial quantitative clinical assessments and circulating T cell markers. The CYA treatment group improved in only one of three scoring systems (p less than 0.05), while no difference was observed in the AZA group. CYA and AZA did not influence CD4+/CD8+ ratio of circulating T cells but affected HNK-1+ cells. The overall frequency of abnormal laboratory values were comparable in both groups. We conclude that CYA given in a low dose is relatively well tolerated but its benefits appear to be of limited value.", "PMID": "2209678"}, {"title": "Azathioprine reduces intrathecal IgG synthesis in multiple sclerosis.", "abstract": "Intrathecal IgG synthesis and CSF oligoclonal bands were reexamined after 18-24 months in 66 patients with multiple sclerosis; 40 of them received azathioprine (AZA) 2.5 mg/Kg/die; all received a course of dexamethasone (DEXA) during clinical relapses. The IgG Index was significantly reduced in the group treated with AZA, especially in patients with short disease duration, low disability and high IgG index. Changes observed in CSF banding pattern were not significant. These results suggest an effect of AZA on IgG synthesis, as reported by in vitro studies.", "PMID": "3577680"}, {"title": "Therapeutic trial of Imuran (azathioprine) in multiple sclerosis.", "abstract": "", "PMID": "4105313"}, {"title": "Intensive immunosuppression in the treatment of multiple sclerosis.", "abstract": "", "PMID": "4139403"}, {"title": "Prolonged azathioprine treatment of non-remitting multiple sclerosis.", "abstract": "Two groups of 85 and 42 ambulatory patients with moderately advanced non-remitting multiple sclerosis were treated for six to 14 and three to six years with daily azathioprine. Less than 10% of these patients became confined to a wheelchair. This far exceeds any possible result in a group of non-remitting multiple sclerosis patients not so treated.", "PMID": "458481"}, {"title": "Double-blind, controlled trial of immunosuppression in treatment of multiple sclerosis.", "abstract": "30 multiple sclerosis patients in a double-blind, controlled trial were given immunosuppressive treatment consisting of antilymphocyte globulin, prednisolone, and azathioprine, or placebo. After 15 months of treatment the immunosuppressed group had a reduction in the number of relapses and some retardation of the clinical course of the disease (p < 0.06). The beneficial effect was seen only in females.", "PMID": "6107592"}, {"title": "Double-blind controlled trial of immunosuppression in the treatment of multiple sclerosis: final report.", "abstract": "In a double-blind controlled trial 43 patients with relapsing-remitting multiple sclerosis were treated either with anti-lymphocyte globulin, prednisolone, and azathioprine, or with placebo preparations. Treatment began with a combination of the three medicaments but after 1 month was continued for another 14 months with azathioprine (3 mg/kg dialy) only. There was a marginally beneficial effect of immunosuppression on the overall relapse rate and clinical progression. However, there were significant effects on in-vitro lymphocyte function and in the visual evoked potentials in favour of the group receiving suppressive treatment. Placebo-treated patients of the HLA A3 tissue type had significantly more relapses than placebo-treated patients who were not of type HLA A3. Nevertheless, HLA-A3-positive patients treated with immunosuppression had significantly fewer relapses than A3-positive placebo-treated patients.", "PMID": "6124759"}], "labels": [{"PMID": "12796549", "label": "excluded"}, {"PMID": "17086913", "label": "excluded"}, {"PMID": "19028832", "label": "excluded"}, {"PMID": "2209678", "label": "excluded"}, {"PMID": "3577680", "label": "excluded"}, {"PMID": "4105313", "label": "excluded"}, {"PMID": "4139403", "label": "excluded"}, {"PMID": "458481", "label": "excluded"}, {"PMID": "6107592", "label": "excluded"}, {"PMID": "6124759", "label": "excluded"}]}
{"metadata": {"review_pmid": "39625073"}, "inputs": {"background": "Pressure ulcers occur when people cannot reposition themselves to relieve pressure over bony prominences. They are difficult to heal, costly, and reduce quality of life. Dressings and topical agents (lotions, creams, and oils) for pressure ulcer prevention are widely used. However, their effectiveness is unclear. This is the third update of this review.", "objectives": "To evaluate the effects of dressings and topical agents on pressure ulcer prevention, in people of any age without existing pressure ulcers, but at risk of developing one, in any healthcare setting.", "selection criteria": "We included randomised controlled trials that enroled people at risk of developing a pressure ulcer."}, "context": [{"title": "The effectiveness of a hyperoxygenated fatty acid compound in preventing pressure ulcers.", "abstract": "To compare the effects of Mepentol, a hyperoxygenated fatty acid preparation, with a placebo treatment in preventing the development of pressure ulcers.\n\nThe research study consisted of a multicentre double-blind randomised clinical trial. The incidence of pressure ulcers, relative risk (RR), preventable fraction and number necessary to treat (NNT) were calculated. In addition, Kaplan-Meier survival curves, with log-rank test, and Cox's proportional hazards regression model were used to compare both groups.\n\nA total of 331 patients completed the study: 167 in the control group and 164 in the study group. Pressure-ulcer incidence during the study was 7.32% in the intervention group versus 17.37% in the placebo group (p 0.006). These results show that for each 10 patients treated with Mepentol one pressure ulcer was prevented (NNT = 9.95). Survival curves and the regression model showed a significant statistical difference for both groups (p < or = 0.001). The average cost of Mepentol during the study was 7.74 Euro.\n\nMepentol is an effective measure for pressure ulcer prevention. It was more effective than a greasy placebo product, and was found to be cost-effective.", "PMID": "15779642"}, {"title": "Evaluation of a new pressure ulcer preventive dressing containing ceramide 2 with low frictional outer layer.", "abstract": "This paper is a report of an evaluation of the effectiveness of a newly developed dressing for preventing persistent erythema and pressure ulcer development and improving the water-holding capacity without increasing the skin pH in bedridden older patients.\n\nShear forces and skin dryness play important roles in persistent erythema and pressure ulcer development. To eliminate these risks, we developed a dressing to reduce shear forces and improve the water-holding capacity. However, the effects of this dressing in clinical settings remain unknown.\n\nAn experimental bilateral comparison study was conducted at a hospital in Japan in 2004 with 37 bedridden older patients at risk of pressure ulcer development. The dressing was randomly applied to the right or left greater trochanter for 3 weeks. No dressing was applied to the opposite side as a control. The skin was monitored weekly during the 3-week application for persistent erythema and pressure ulcer development. Skin hydration and pH were also assessed during the intervention and for 1 week after dressing removal.\n\nThe incidence of persistent erythema was significantly lower in the intervention area than the control area [P = 0.007, RR 0.18 (95% CI: 0.05-0.73) and NNT 4.11 (2.50-11.63) ]. No pressure ulcers occurred in either the intervention or control area. Skin hydration increased significantly during dressing application and remained high after removal (P < 0.001) relative to the control area. Skin pH decreased significantly during the application (P < 0.001) but returned to control levels after removal (P = 0.38).\n\nThis safe and effective dressing can be used for patients with highly prominent bones and dry skin to prevent pressure ulcers.", "PMID": "17681081"}, {"title": "IPARZINE-SKR study: randomized, double-blind clinical trial of a new topical product versus placebo to prevent pressure ulcers.", "abstract": "This study compared the efficacy of a new topical agent (IPARZINE-4A-SKR) on preventing category I pressure ulcers (PUs) over a 2-week period, compared with a placebo. A double-blind, randomised, multi-centre, placebo-controlled clinical trial in two parallel groups was conducted. The primary objective was to compare PU incidence between groups. Hospital and socio-sanitary centre patients (n = 194) at risk of developing a PU (Braden scale) were randomised into two groups. The intervention group included 99 patients, and the placebo group comprised 95 patients. Patients were comparable in terms of age, sex and PU risk. In both groups, patients had a high risk of developing PUs. The product was applied on the sacrum, trochanters and heels. Six PUs (incidence = 6\u00b71%) were detected in the intervention group versus seven (incidence = 7\u00b74%) in the placebo group. Differences were not statistically significant (z = 0\u00b708; P = 0\u00b794), relative risk = 0\u00b782 (95% confidence interval = 0\u00b729\u20132\u00b736). The main limitation of the study was the sample size and, therefore, the main difficulty encountered was in determining whether the product is ineffective or simply has not been used with sufficient patients. In conclusion, it is not possible to confirm that there are any differences between the studied and the placebo treatments in the prevention of PUs. The results obtained were similar to those obtained in studies of PU prevention using products based on topical fatty acids.", "PMID": "23166914"}, {"title": "[Comparison of efficacy of heel ulcer prevention between classic padded bandage and polyurethane heel in a medium-stay hospital: randomized controlled trial].", "abstract": "The aim of the study is to determine the incidence of heel pressure ulcers (UPPT) and to compare the two systems for UPPT prevention: classic padded bandage and polyurethane heel.\n\nProspective intervention study in a medium-long hospital stay of all people admitted that had no UPPT but had a risk of UPPT according to the Braden Scale or clinical judgment. The patients were randomized to prevention with classic padded bandage or polyurethane heel. The outcome variable was the incidence of UPPT for each study group, which was recorded every 15 days or when there were clinical changes.\n\nOf the 940 patients evaluated, 409 with a mean age of 80.5 years and 59.1% women,were included in the study. Of these, 78% had Barthel score \u226430; 28.6% dementia; delirium 37.6%; 27.6% diabetes; and 19.6% other UPP. The overall incidence was 2.9% UPPT; 2.49% in the classic padded bandage and 3.37% in the polyurethane heel group (p=0.82).\n\nNo statistically significant differences were observed between the group with the classical dressing and the group with the polyurethane heel dressing. The use of multiple measures to prevent UPPT achieved a low incidence of these.", "PMID": "23199818"}, {"title": "A randomised controlled trial of the effectiveness of soft silicone multi-layered foam dressings in the prevention of sacral and heel pressure ulcers in trauma and critically ill patients: the border trial.", "abstract": "The prevention of hospital acquired pressure ulcers in critically ill patients remains a significant clinical challenge. The aim of this trial was to investigate the effectiveness of multi-layered soft silicone foam dressings in preventing intensive care unit (ICU) pressure ulcers when applied in the emergency department to 440 trauma and critically ill patients. Intervention group patients (n = 219) had Mepilex(\u00ae) Border Sacrum and Mepilex(\u00ae) Heel dressings applied in the emergency department and maintained throughout their ICU stay. Results revealed that there were significantly fewer patients with pressure ulcers in the intervention group compared to the control group (5 versus 20, P = 0\u00b7001). This represented a 10% difference in incidence between the groups (3\u00b71% versus 13\u00b71%) and a number needed to treat of ten patients to prevent one pressure ulcer. Overall there were fewer sacral (2 versus 8, P = 0\u00b705) and heel pressure ulcers (5 versus 19, P = 0\u00b7002) and pressure injuries overall (7 versus 27, P = 0\u00b7002) in interventions than in controls. The time to injury survival analysis indicated that intervention group patients had a hazard ratio of 0\u00b719 (P = 0\u00b7002) compared to control group patients. We conclude that multi-layered soft silicone foam dressings are effective in preventing pressure ulcers in critically ill patients when applied in the emergency department prior to ICU transfer. ", "PMID": "23711244"}, {"title": "The effectiveness of massage with and without dimethyl sulfoxide in preventing pressure ulcers: a randomized, double-blind cross-over trial in patients prone to pressure ulcers.", "abstract": "Although guidelines advise against massage, it is one of the methods widely regarded and used by nurses to prevent pressure ulcers (PU).\n\nThe purpose of this study was to examine the effectiveness of different variations of massage in preventing pressure ulcers.\n\nA randomized, double-blind cross-over design, in which patients of nursing homes who are prone to PU underwent two of the three possible interventions; 'position changes only', 'massaging with an indifferent cream' and 'massaging with a dimethyl sulfoxide (DMSO) cream'.\n\nThe results of three interventions did not differ significantly. DMSO did not fulfil the expectations raised by literature and a previous pilot-study.", "PMID": "17553503"}, {"title": "Preventing pressure sores of the nasal ala after nasotracheal tube intubation: from animal model to clinical application.", "abstract": "Nasal-ala pressure sores induced by nasotracheal intubation are common complications of oral and maxillofacial surgery, but are easily ignored. To determine whether such sores could be prevented, we studied the effects of a combination of cushioning material in an animal model, and then analyzed the efficacy of this combination clinically.\n\nFour pigs received nasotracheal intubation. Each pig received intubation for 4, 8, 12, or 16 hours. Outcomes from pigs undergoing 500-gram-weight compression on each nostril were compared: one nostril received an application of cushioning materials, and the contralateral nostril did not. After the required study period, clinical assessment and further evaluation were performed by measuring pressure-sore dimensions and performing incisional biopsies. Clinical applications of this protective technique were then undertaken. Eight patients who underwent intubation without Soft Liner (GC Co, Tokyo, Japan) and DuoDERM CGF (ConvaTec, Inc, Princeton, NJ) protection, and 10 patients with Soft Liner and DuoDERM protection, were evaluated.\n\nThe protective efficacy of the cushioning materials was significant in the animal model as well as in clinical practice. Pressure sores were avoided on the protected side, with severe tissue necrosis documented on the control side.\n\nWe found that the combined use of Soft Liner and DuoDERM reduced the size and severity of nasal-ala pressure sores attributable to nasotracheal intubation during oral and maxillofacial surgery.", "PMID": "19231778"}, {"title": "Preventing pressure ulcers on the heel: a Canadian cost study.", "abstract": "An adaptation of a clinical study of 130 patients at risk of developing a pressure ulcer on the heels was performed using Canadian costs. The aim of the study was to compare the cost effectiveness of a specially shaped hydrocellular dressing (Allevyn Heel) versus that of a protective heel bandage (Soffban and gauze) in pressure ulcer prevention over an 8-week period.", "PMID": "19873692"}, {"title": "Clinical and cost effectiveness evaluation of low friction and shear garments.", "abstract": "To determine the effectiveness of Parafricta low-friction garments in reducing the incidence and prevalence of pressure ulceration and to evaluate the curative aspects of these products on pre-existing skin breakdown within a hospital setting.\n\nPatients with a Waterlow score of >15 and who were unable to reposition independently were offered the low-friction undergarments and bootees. A total of 650 patient cases were initially reviewed. Of these, 204 met the criteria for use of the products in the 3 months prior to the start of the evaluation (cohort 1) and 165 patients met the criteria during the period when the garments were used (cohort 2). Data collected included pressure ulcer incidence, location, grading, and outcome of ulcer on discharge. Locally derived costs for length of stay, wound dressings, pressure-redistributing mattresses and additional cost of the low-friction garments were applied to build a cost-effectiveness model.\n\nIn patients at risk of skin breakdown there was a statistically significant reduction in the number of patients who developed pressure ulcers following use of the low-friction garments in cohort 2 when compared with cohort 1 (16% reduction; p = 0.0286). In addition, the number of patients who were ulcer free on admission but who developed ulcers and then improved or completely healed before discharge was also statistically significant (41% increase; p = 0.0065) when cohort 2 was compared with cohort 1. Fewer patients admitted with ulcers deteriorated when using the low-friction garments (21% reduction; p = 0.0012). The costs, which were calculated by comparing patient throughput for these patients, suggest that the savings associated with preventing skin breakdown outweighed the cost of the products used (base case model indicated a saving of over \u00a363,000 per 100 at risk patients).\n\nThe results support the conclusion that low-friction garment products have a role to play in the prevention of skin breakdown, and appear to be both clinically effective and cost effective.\n\nThe authors have no conflicts of interest to declare. APA Parafricta provided the products, as well as financial support for training of the ward staff who participated in the evaluation and for the data collection and analysis (which was performed by Xcelerate Health Outcomes Unit, NHS Innovations London).", "PMID": "21160445"}, {"title": "A major contributor. Evaluation of Comfeel Pressure Relieving Dressing.", "abstract": "", "PMID": "2217219"}], "labels": [{"PMID": "15779642", "label": "included"}, {"PMID": "17681081", "label": "included"}, {"PMID": "23166914", "label": "included"}, {"PMID": "23199818", "label": "included"}, {"PMID": "23711244", "label": "included"}, {"PMID": "17553503", "label": "excluded"}, {"PMID": "19231778", "label": "excluded"}, {"PMID": "19873692", "label": "excluded"}, {"PMID": "21160445", "label": "excluded"}, {"PMID": "2217219", "label": "excluded"}]}
{"metadata": {"review_pmid": "39601298"}, "inputs": {"background": "As the burden of cardiovascular disease grows, so does the number of cardiac surgeries. Surgery is increasingly performed on older people with comorbidities who are at higher risk of developing perioperative complications such as low cardiac output state (LCOS). Surgery-associated LCOS represents a serious pathology responsible for substantial morbidity and mortality. Prevention of LCOS is a critical and worthwhile aim to further improve the outcome and effectiveness of cardiac surgery. However, guidelines consistently report a lack of evidence for pharmacological LCOS prophylaxis.", "objectives": "To assess the benefits and harms of the prophylactic use of any inotropic agent to prevent low cardiac output and associated morbidity and mortality in adults undergoing cardiac surgery.", "selection criteria": "We included randomised controlled trials (RCTs) enrolling adults who underwent cardiac surgery and were prophylactically treated with one or multiple inotropic agent(s) in comparison to any type of control (i.e. standard cardiac care, placebo, other inotropic agents)."}, "context": [{"title": "The efficacy of preemptive Milrinone or Amrinone therapy in patients undergoing coronary artery bypass grafting.", "abstract": "Acute deterioration in ventricular function and oxygen transport is common after cardiac surgery. We hypothesized that milrinone or amrinone may reduce their occurrence and catecholamine requirements and increase cellular enzyme levels in patients undergoing coronary artery bypass. In 45 patients, we randomly administered milrinone 50 microg/kg plus 0.5 microg x kg(-1) x min(-1) infusion for 10 h, amrinone 1.5 mg/kg plus 10 microg x kg(-1) x min(-1) infusion for 10 h, or placebo at release of aortic cross-clamp. Hemodynamic variables, dopamine requirement, and laboratory values were recorded. At the postoperative nadir, stroke volume index was higher in the Milrinone and Amrinone groups (mean +/- SD, 27.8 +/- 4.0 and 26.1 +/- 3.2 vs. 20.4 +/- 5.1 mL x min (-1) x m(-2) per beat, P < 0.0001), and oxygen transport index was higher (354.7 +/- 57.8 and 353.7 +/- 91.2 vs 283.0 +/- 83.9 mL. min(-1) x m(-2), P = 0.009). The postoperative dopamine requirement was less (6.6 +/- 2.7 and 6.8 +/- 2.6 vs 10.4 +/- 2.0 mg/kg, P < 0.008), and postoperative serum lactate, alanine and aspartate aminotransferase, lactate dehydrogenase, creatinine kinase, C-reactive protein, and glucose levels were less (P < 0.01). The mean postoperative heart rate was faster in the Milrinone group than in the Amrinone and Placebo groups (96.8 +/- 10.3 vs. 86.9 +/- 9.5 and 87.8 +/- 10.8 bpm, P < 0.01). Milrinone and amrinone administered preemptively reduce postoperative deterioration in cardiac function and oxygen transport, dopamine requirement, and increases in serum lactate, glucose, and enzyme levels, although milrinone may increase heart rate.\n\nPreemptive milrinone or amrinone administration before separation from cardiopulmonary bypass in cardiac surgical patients not only ameliorates postoperative deterioration in cardiac function and oxygen transport, but also reduces dopamine requirement and increases serum lactate, glucose, and cellular enzyme levels, although milrinone may increase heart rate.", "PMID": "11772795"}, {"title": "Should we give prophylactic renal-dose dopamine after coronary artery bypass surgery?", "abstract": "A prospective double-blind randomized study undertaken to assess the effect of postoperative prophylactic \"renal-dose\" dopamine on post-coronary artery bypass grafting surgery's clinical outcome.\n\nEighty-five consecutive patients undergoing CABG operation were randomized to receive either 3-5 microg/kg/min dopamine (group D, n = 41) or saline as placebo (group P, n = 45) for 48 postoperative hours. Clinical outcome parameters were collected for four postoperative days.\n\nPreoperative and operative parameters were similar in both groups. Four patients from group P and none from group D reached an end-point of the study (oliguria, renal dysfunction) and received dopamine. Two patients from group P and none from group D needed an additional inotropic support. Mean arterial pressure values were similar during the first 24 hours after operation, but left atrial pressure values tended to be higher in group P (10 +/- 4 vs 7 +/- 3 mmH2O, p = 0.18). The mean pH was higher in group D at 8 hours after operation (7.38 +/- 0.2 vs 7.36 +/- 0.3, p = NS), due to higher bicarbonate levels (23 +/- 2 mmol/l vs 21 +/- 2, p = 0.49). The incidence of lung congestion in chest X-rays and CT scans was significantly higher in group P (50% vs 29%, p = 0.073 at 48 hours postoperatively). Room air blood O2 saturation and maximal expiratory volume tended to be higher in group D (at 72 hours after operation- 92 +/- 4 vs 90%+/- 5, p = 0.29 and 646 +/- 276 vs 485 ml +/- 206, p = 0.16, respectively). There was no statistical difference in urine output but the amount of furosemide given to patients in group P was significantly higher (during the first 8 hours 2.5 +/- 0.5 vs. 0.3 mg +/- 1.6, p = 0.07). Plasma creatinine levels were significantly lower in group D (at 24 hours 0.93 +/- 0.02 vs 1.05 mg/dL +/- 0.02, p = 0.02). Mobilization after surgery was faster in group D.\n\nProphylactic dopamine administration after coronary artery bypass grafting surgery improves patient hemodynamic and renal status, reduces the need for additional medical support (inotropes and furosemide) and thus, provides stable postoperative course.", "PMID": "15016048"}, {"title": "Preconditioning effects of levosimendan in coronary artery bypass grafting--a pilot study.", "abstract": "The calcium sensitizer levosimendan protects against myocardial ischaemia and reperfusion injury in animal models.\n\nThe present pilot study investigated whether a short infusion before coronary artery bypass grafting (CABG) would protect the myocardium and improve postoperative haemodynamics. Twenty-four patients with stable angina undergoing elective CABG surgery were randomized to receive either placebo or levosimendan (24 microg kg(-1)) infused i.v. over a 10 min period just before placing the patient on cardiopulmonary bypass.\n\nPerioperative haemodynamic variables, concentrations of cardiac troponin I over the 48 h postoperative period, and clinical outcomes were assessed. There were no adverse effects related to levosimendan. Compared with control patients, levosimendan-treated patients had lower postoperative troponin I concentrations (P<0.05) and a higher cardiac index (P<0.05).\n\nPatients receiving a short infusion of levosimendan before CABG showed evidence of less myocardial damage, suggestive of a preconditioning effect. Larger outcome studies are thus indicated to confirm benefit.", "PMID": "16595616"}, {"title": "The effects of levosimendan in cardiac surgery patients with poor left ventricular function.", "abstract": "Patients with poor left ventricular function often require inotropic drug support immediately after cardiopulmonary bypass. Levosimendan improves cardiac function by a novel mechanism of action compared to currently available drugs. We hypothesized that, in patients with severely compromised ventricular function, the use of levosimendan would be associated with better postoperative cardiac function than with inotropic drugs that increase myocardial oxygen consumption.\n\nThirty patients with a preoperative ejection fraction < or =30% scheduled for elective cardiac surgery with cardiopulmonary bypass were randomized to two different inotropic protocols: milrinone 0.5 microg [corrected] x kg(-1) x min(-1) or levosimendan 0.1 microg [corrected] x kg(-1) x min(-1), started immediately after the release of the aortic crossclamp. The treatment was masked to the observers. All patients received dobutamine 5 microg [corrected] x kg(-1) x min(-1).\n\nStroke volume was similar between groups initially after surgery, but it declined 12 h after surgery in the milrinone group but not in the levosimendan group (P < 0.05 between groups) despite similar filling pressures. Total dose, duration of inotropic drug administration and norepinephrine dose were lower in the levosimendan group than in the milrinone group (P < 0.05). The duration of tracheal intubation was shorter in the former group compared with the milrinone group (P = 0008). Three patients in the milrinone group but none in the levosimendan group died within 30 days of surgery.\n\nIn cardiac surgery patients with a low preoperative ejection fraction, stroke volume was better maintained with the combination of dobutamine with levosimendan than with the combination of dobutamine with milrinone.", "PMID": "17377079"}, {"title": "Levosimendan in aortic valve surgery: cardiac performance and recovery.", "abstract": "The aim of the present study was to test the hypothesis that levosimendan has beneficial effects on cardiac performance and that the need for other vasoactive medications during and after cardiac surgery would be reduced by levosimendan in patients with severe aortic stenosis (AS) and left ventricular (LV) hypertrophy.\n\nA prospective, randomized, double-blind, placebo-controlled clinical study.\n\nA university hospital.\n\nTwenty-four patients scheduled for aortic valve surgery with or without coronary artery bypass graft surgery were enrolled in the study.\n\nTwelve patients received a 24-hour levosimendan infusion (0.2 microg/kg/min) beginning after the induction of anesthesia, and 12 patients received a placebo infusion.\n\nLeft ventricular ejection fraction, measured before study drug infusion, was lower in the treatment group than in the control group (42% v 54%, p = 0.015). After sternum closure, the ejection fraction dropped in the control group but was maintained at the same level in the treatment group (45% v 48%, not significant). Mixed venous and central venous saturations were significantly lower in the treatment group than in the control group at the baseline, but after the beginning of the study drug infusion, the groups were similar throughout the rest of the follow-up period. The treatment group required more norepinephrine during the operation and less nitroprusside postoperatively.\n\nLow output is a result of myocardial stunning and is common after cardiopulmonary bypass. According to the present results, levosimendan may be useful in patients with severe AS and LV hypertrophy because it may prevent LV function from dropping to a critically low level postoperatively. Levosimendan causes vasodilation and thereby decreases mean arterial pressure, but this can be controlled with the use of norepinephrine.", "PMID": "18922425"}, {"title": "Levosimendan pre-treatment improves outcomes in patients undergoing coronary artery bypass graft surgery.", "abstract": "The calcium sensitizer levosimendan has anti-ischaemic effects mediated via the opening of sarcolemmal and mitochondrial ATP-sensitive potassium channels. These properties suggest potential application in clinical situations where cardioprotection would be beneficial, such as cardiac surgery. We thus decided to investigate whether pharmacological pre-treatment with levosimendan reduces intensive care unit (ICU) length of stay in patients undergoing elective myocardial revascularization under cardiopulmonary bypass.\n\nOne hundred and six patients undergoing elective coronary artery bypass grafting were randomly assigned in a double-blind manner to receive levosimendan or placebo. Levosimendan (24 microg kg(-1)) or placebo was administered as a slow i.v. bolus over a 10 min period before the initiation of bypass.\n\nTracheal intubation time and the length of ICU stay were significantly reduced in the levosimendan group (P<0.01). The number of patients needing inotropic support for >12 h was significantly higher in the control group (18.0% vs 3.8%; P=0.021). Compared with control patients, levosimendan-treated patients had lower postoperative troponin I concentrations (P<0.0001) and a higher cardiac power index (P<0.0001).\n\nPre-treatment with levosimendan in patients undergoing surgical myocardial revascularization resulted in less myocardial injury, a reduction in tracheal intubation time, less requirement for inotropic support, and a shorter length of ICU stay.", "PMID": "19151048"}, {"title": "Levosimendan facilitates weaning from cardiopulmonary bypass in patients undergoing coronary artery bypass grafting with impaired left ventricular function.", "abstract": "Levosimendan is a compound with vasodilatory and inotropic properties. Experimental data suggest effective reversal of stunning and cardioprotective properties.\n\nThis prospective, randomized, placebo-controlled, double-blind study included 60 patients with 3-vessel coronary disease and left ventricular ejection fraction (LVEF) of less than 0.50. Levosimendan administration (12 microg/kg bolus, followed by an infusion of 0.2 microg/kg/min) was started immediately after induction anesthesia. Predefined strict hemodynamic criteria were used to assess the success of weaning. If weaning was not successful, CPB was reinstituted and an epinephrine infusion was started. If the second weaning attempt failed, intraaortic balloon pumping (IABP) was instituted.\n\nThe groups had comparable demographics. The mean (standard deviation) preoperative LVEF was 0.36 (0.8) in both groups. The baseline cardiac index was 1.8 (0.3) L/min/m(2) in the levosimendan group and 1.9 (0.4) L/min/m(2) in the placebo group. The mean duration of CPB to primary weaning attempt was 104 (25) minutes in the levosimendan and 109 (22) minutes in the placebo group. Primary weaning was successful in 22 patients (73%) in the levosimendan group and in 10 (33%) in the placebo group (p = 0.002). The odds ratio for failure in primary weaning was 0.182 (95% confidence interval, 0.060 to 0.552). Four patients in the placebo group failed the second weaning and underwent IABP compared with none in the levosimendan group (p = 0.112).\n\nLevosimendan significantly enhanced primary weaning from CPB compared with placebo in patients undergoing 3-vessel on-pump coronary artery bypass grafting. The need for additional inotropic or mechanical therapy was decreased.", "PMID": "19161758"}, {"title": "Levosimendan enhances cardiac performance after cardiopulmonary bypass: a prospective, randomized placebo-controlled trial.", "abstract": "Levosimendan is a new myofilament calcium (Ca2+) sensitizer that increases myocardial contractility by stabilizing the Ca2+-bound conformation of troponin C. We tested the hypothesis that levosimendan enhances cardiac performance after cardiopulmonary bypass (CPB). Anesthesia was induced and maintained with midazolam, sufentanil, and vecuronium in 18 patients randomly assigned to receive levosimendan (18 or 36 microg/kg loading dose and 0.2 or 0.3 microg/kg/min infusion, respectively) or placebo 15 min before and continued for 6 h after CPB. Significant (p < 0.05) increases in heart rate (HR) and decreases in systemic vascular resistance (SVR) occurred 15 min after CPB in patients receiving placebo. Later increases in mean arterial pressure (MAP) and cardiac output (CO) and decreases in stroke volume (SV) and pulmonary vascular resistance also were observed. HR was greater in patients receiving high- but not low-dose levosimendan versus placebo immediately after CPB. MAP also was lower in patients treated with either dose of levosimendan compared with placebo after CPB. Levosimendan increased CO and decreased SVR (4.2 +/- 0.4 to 7.9 +/- 0.4 L/min and 1,150 +/- 99 to 512 +/- 42 dyn/s/cm5, respectively, 15 min after CPB; mean +/- SEM). CO and SV were higher and SVR was lower in patients receiving levosimendan versus placebo after CPB. No differences in arterial oxygenation and perioperative arrhythmias (Holter analysis) were observed between groups. The results indicate that levosimendan enhances cardiac performance after CPB in humans.", "PMID": "10445673"}, {"title": "Effects of single administration of a phosphodiesterase III inhibitor during cardiopulmonary bypass: comparison of milrinone and amrinone.", "abstract": "The effects of phosphodiesterase III (PDE III) inhibitors administered after aortic declamping during cardiopulmonary bypass (CPB) for open heart surgery were investigated. Ten patients (group M) were administered milrinone (50 microg/kg) after aortic declamping during CPB, 10 patients were administered amrinone (1 mg/kg) at the same time during their surgery (group A), and 10 patients served as controls with no drug administered (group C). Soon after bolus infusion of the PDE III inhibitor, perfusion pressure dropped significantly in groups M and A. However, after release of CPB and at the end of surgery, there was no difference in aortic pressure between the 3 groups. There were also no differences between the groups in heart rate, pulmonary artery pressure, and pulmonary capillary wedge pressure. After weaning from CPB, the cardiac index was high and systemic vascular resistance index was low in groups M and A. There were no significant differences in the need for additional catecholamines and time for rewarming between groups. No adverse reactions were observed. A single administration of a PDE III inhibitor during CPB was useful for post-CPB management of patients undergoing open heart surgery. Amrinone reduced perfusion pressures more than milrinone, but cardiac indices and aortic pressures after weaning from CPB showed no differences between group M and group A patients.", "PMID": "10478810"}, {"title": "Comparison of enoximone and piroximone in patients after mitral valve operation: a prospective and controlled clinical study.", "abstract": "Phosphodiesterase III (PDEII) inhibitors as so-called inodilators have previously proven a valuable alternative to positive inotropes in patients with cardiac insufficiency. In this study we compared patients receiving piroximone (P, n = 14, 0.5-mg/kg bolus in 30 min and then 3-6 micrograms/kg/min) with enoximone patients (E, n = 13, 1-mg/kg bolus and then 4-20 micrograms/kg/min) and with a third group (D, n = 14) receiving a combination of dopamine (4-10 micrograms/kg/min) and glyceroltrinitrate (0.5-5 micrograms/kg/min) for hemodynamic support. All three groups were comparable in terms of age, body surface area, and preoperative cardiac function [cardiac index (CI) less than or equal to 2.5 L/min/m2, LAP greater than 15 mm Hg]. Hemodynamic measurements (10) and Holter monitoring were performed until 18 h post MVR. In all groups, epinephrine was used for additional inotropic therapy if mean arterial pressure (MAP) was less than 60 mm Hg and/or CI was less than 2.5 L/min/m2. There was no early or late postoperative mortality in either group. Continuous support with epinephrine was necessary in 8 patients in group D, whereas initially 8 patients in group E and 6 patients in group P required epinephrine support. After PDE III inhibitor infusion, 2 patients in group E and 2 patients in group P remained epinephrine dependent (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)", "PMID": "1378106"}], "labels": [{"PMID": "11772795", "label": "included"}, {"PMID": "15016048", "label": "included"}, {"PMID": "16595616", "label": "included"}, {"PMID": "17377079", "label": "included"}, {"PMID": "18922425", "label": "included"}, {"PMID": "19151048", "label": "included"}, {"PMID": "19161758", "label": "included"}, {"PMID": "10445673", "label": "excluded"}, {"PMID": "10478810", "label": "excluded"}, {"PMID": "1378106", "label": "excluded"}]}
{"metadata": {"review_pmid": "39588800"}, "inputs": {"background": "Paediatric patients undergoing surgery for congenital heart disease (CHD) are at risk for postoperative low cardiac output syndrome (LCOS) and mortality. LCOS affects up to 25% of children after heart surgery. It consists of reduced myocardial function and increases postoperative morbidity, prolongs mechanical ventilation, and lengthens the duration of intensive care unit (ICU) stay. Pharmacological prophylaxis involves inotropes, including catecholamines, phosphodiesterase III inhibitors, or calcium sensitisers, to enhance myocardial contractility. It is unclear whether they are effective in preventing LCOS or death in this vulnerable population.", "objectives": "1. To evaluate the relative benefits and harms of inotropes for the prevention of LCOS and mortality in paediatric patients undergoing surgery for CHD. 2. To generate a clinically useful ranking of prophylactic inotropes for the prevention of LCOS and mortality in paediatric patients undergoing surgery for CHD according to benefits and harms.", "selection criteria": "We included randomised controlled trials comparing inotropes from one drug class (catecholamines, phosphodiesterase type III inhibitors, calcium sensitisers) to another (either alone or in combination) or placebo, in paediatric patients (birth to 18 years of age) undergoing surgery for CHD."}, "context": [{"title": "Prophylactic intravenous use of milrinone after cardiac operation in pediatrics (PRIMACORP) study. Prophylactic Intravenous Use of Milrinone After Cardiac Operation in Pediatrics.", "abstract": "Many pediatric patients undergoing cardiac surgery involving cardiopulmonary bypass have a predictable fall in the cardiac index 6 to 18 hours after surgery, the so-called low cardiac output syndrome (LCOS). Because patients who have LCOS require more monitoring and support and have a prolonged stay in the intensive care unit, the syndrome is associated with a costly morbidity. Milrinone, a phosphodiesterase III inhibitor, improves cardiac muscle contractile force and vascular muscle relaxation through positive inotropic and vasodilatory effects. The purpose of the Prophylactic Intravenous Use of Milrinone After Cardiac Operation in Pediatrics (PRIMACORP) study is to evaluate the safety and efficacy of the prophylactic use of milrinone in pediatric patients at high risk for development of LCOS after undergoing cardiac surgery.\n\nPatients in the multicenter, randomized, double-blind, placebo-controlled, parallel treatment study will be randomized to 1 of 3 treatment arms: (1) low-dose milrinone (25 microg/kg intravenous bolus over 60 minutes followed by a 0.25 microg/kg/min infusion for 35 hours), (2) high-dose milrinone (75 microg/kg intravenous bolus over 60 minutes followed by a 0.75 microg/kg/min infusion for 35 hours), or (3) placebo.\n\nThe primary end point for efficacy evaluation will be based on a composite variable consisting of death or development of LCOS requiring additional mechanical or pharmacologic support, up to 36 hours after randomization. A 2-sided test with a 0.025 type I error will be used for the primary end point analysis. The PRIMACORP study will enroll a total of 240 patients. Six additional secondary end points will be analyzed.\n\nThe PRIMACORP study will address several questions regarding the safety and efficacy of prophylactic milrinone use in pediatric patients at high risk for development of LCOS after cardiac surgery.", "PMID": "11773907"}, {"title": "Efficacy and safety of milrinone in preventing low cardiac output syndrome in infants and children after corrective surgery for congenital heart disease.", "abstract": "Low cardiac output syndrome (LCOS), affecting up to 25% of neonates and young children after cardiac surgery, contributes to postoperative morbidity and mortality. This study evaluated the efficacy and safety of prophylactic milrinone in pediatric patients at high risk for developing LCOS.\n\nThe study was a double-blind, placebo-controlled trial with 3 parallel groups (low dose, 25- microg/kg bolus over 60 minutes followed by a 0.25- microg/kg per min infusion for 35 hours; high dose, 75- microg/kg bolus followed by a 0.75- microg/kg per min infusion for 35 hours; or placebo). The composite end point of death or the development of LCOS was evaluated at 36 hours and up to 30 days after randomization. Among 238 treated patients, 25.9%, 17.5%, and 11.7% in the placebo, low-dose milrinone, and high-dose milrinone groups, respectively, developed LCOS in the first 36 hours after surgery. High-dose milrinone significantly reduced the risk the development of LCOS compared with placebo, with a relative risk reduction of 55% (P=0.023) in 238 treated patients and 64% (P=0.007) in 227 patients without major protocol violations. There were 2 deaths, both after infusion of study drug. The use of high-dose milrinone reduced the risk of the LCOS through the final visit by 48% (P=0.049).\n\nThe use of high-dose milrinone after pediatric congenital heart surgery reduces the risk of LCOS.", "PMID": "12600913"}, {"title": "Levosimendan in congenital cardiac surgery: a randomized, double-blind clinical trial.", "abstract": "In this study, the authors used a continuous infusion of either levosimendan or milrinone as inotropic support after corrective congenital cardiac surgery. The hemodynamic and biochemical parameters were compared.\n\nA prospective, randomized, double-blind clinical study.\n\nA university hospital.\n\nForty-one patients between 0 and 5 years old requiring inotropic support for corrective congenital heart surgery under cardiopulmonary bypass (CPB) were enrolled in this trial. Thirty-six patients completed the study.\n\nPatients were randomized in a double-blind fashion to a continuous infusion of either levosimendan at 0.05 \u03bcg/kg/min or milrinone at 0.4 \u03bcg/kg/min started at the onset of CPB. Epinephrine was started at 0.02 \u03bcg/kg/min after aortic cross-clamp release in both groups.\n\nThere was no significant difference between serum lactate levels of groups. The rate-pressure index (the product of heart rate and systolic blood pressure), which is an indicator of myocardial oxygen demand, was significantly lower at 24 hours and 48 hours postoperatively in the levosimendan group (p < 0.001) in comparison to the milrinone group. Although not significantly different, the troponin values in the levosimendan group were less at 1 hour (median [P(25)-P(75)]: 20.7 [15.3- 48.3] v 34.6 [23.8- 64.5] ng/mL and 4 hours postoperatively: 30.4 [17.3-59.9] v 33.3 [25.5-76.7] ng/mL).\n\nLevosimendan is at least as efficacious as milrinone after corrective congenital cardiac surgery in neonates and infants.", "PMID": "20829069"}, {"title": "Amrinone versus dopamine and nitroglycerin in neonates after arterial switch operation for transposition of the great arteries.", "abstract": "To compare the efficacy and safety of amrinone and a combination of dopamine and nitroglycerin in neonates after reconstructive surgery for transposition of the great arteries.\n\nA prospective, randomized, double-blind study.\n\nPediatric intensive care unit in a university hospital.\n\nThirty-five neonates with transposition of the great arteries.\n\nA loading dose of amrinone, 2 mg/kg, followed by a maintenance infusion of 7.5 microg/kg/min, were administered to 16 neonates before separation from cardiopulmonary bypass. The remaining 19 patients were administered a combination of dopamine, 5 microg/kg/min, and nitroglycerin, 1 microg/kg/min. An open-label epinephrine infusion was administered in both groups as required.\n\nThe circulatory state of the patients was evaluated from 4 to 18 hours after cardiopulmonary bypass. The systemic blood flow index, calculated using the Fick principle, was higher in the amrinone group (1.7+/-0.5 L/min/m2 [mean +/- SD]) compared with the dopamine-nitroglycerin group (1.4+/-0.4 L/min/m2; p < 0.04). The systemic vascular resistance in the amrinone group was lower (26+/-8 Wood units x m2) than in the dopamine-nitroglycerin group (35+/-12 Wood units x m2; p < 0.02). The oxygen extraction ratio was higher in the dopamine-nitroglycerin group (0.34+/-0.08) compared with the amrinone group (0.28+/-0.06; p < 0.02). Lower platelet counts were observed in the amrinone group, but no difference in hemorrhagic complications was seen between the groups.\n\nWith the dosage regimen used, supplemented with epinephrine, amrinone provides a higher cardiac output and more favorable oxygen dynamics than a combination of dopamine and nitroglycerin.", "PMID": "10230954"}, {"title": "Hemodynamic effects of dobutamine and dopexamine after cardiopulmonary bypass in pediatric cardiac surgery.", "abstract": "After surgical repair of congenital heart disease, inotropic support is sometimes necessary to wean from cardiopulmonary bypass. In pediatric cardiac surgery, dobutamine and dopamine are often used as inotropic support. Dopexamine is a synthetic catecholamine, which has positive inotropic and vasodilating properties. Because the hemodynamic effects of catecholamines are modified after cardiopulmonary bypass, the aim of this study was to investigate the effects of dobutamine and dopexamine on cardiac index and systemic vascular resistance index after cardiopulmonary bypass in pediatric cardiac surgery.\n\nThe study was performed in a prospective, randomized, and double-blinded cross-over design. The investigation included 11 children for elective, noncomplex congenital heart surgery. After weaning from cardiopulmonary bypass and a 20-min period of steady state, children received either 2.5 microg x kg(-1) x min(-1) dobutamine or 1 microg x kg(-1) x min(-1) dopexamine for 20 min. Cardiac index (transpulmonary thermodilution), mean arterial pressure, central venous pressure, stroke volume, systemic vascular resistance, and central venous oxygen saturation were determined. The primary outcome variable was cardiac index.\n\nNo difference in cardiac index was observed between the two groups (P = 0.594). Both drugs increased cardiac index, dopexamine from 3.9 +/- 0.6 to 4.7 +/- 0.8 l x min(-1) x m(-2) (P = 0.003) and dobutamine from 4.1 +/- 0.7 to 4.8 +/- 0.7 l x min(-1) x m(-2) (P = 0.004). During treatment with dobutamine, children presented with significantly higher mean arterial pressure (P = 0.003) and systemic vascular resistance index (P = 0.026).\n\nThis trial demonstrates that low-dose dobutamine and dopexamine both increase cardiac index during pediatric cardiac surgery but with different hemodynamic effects.", "PMID": "19650844"}, {"title": "Additive effect of phosphodiesterase inhibitors in control of pulmonary hypertension after congenital cardiac surgery in children.", "abstract": "Control of residual pulmonary arterial hypertension (PAH) after closure of left to right shunts in children is still a challenging issue. The purpose of this study was to compare the effect of two phosphodiesterase inhibitors in pediatric cardiac surgical patients.\n\nA total of 48 postoperative children were enrolled in the study between 2008 and 2010. Patients were stratified based upon choice of pulmonary vasodilator into three equal groups (n = 16); Milrinone group received intravenous milrinone (0.75 \u00b5/kg/min), Sildenafil group received oral sildenafil (0.3 mg/kg every 3 hours) and the Combination group received both medications.\n\nDemographic variables and types of congenital anomalies were not different among the 3 groups. Patients in the Combination group had higher preoperative pulmonary artery to aortic (PA/AO) pressure ratios compared to other two groups (P=0.001). Postoperatively, patients in Milrinone group incurred lower systolic PA and PA/AO pressures compared to Sildenafil group (P=0.014, 0.003), but it was the same in Sildenafil and Combination group (P=0.2; 0.330 respectively). Pulmonary hypertensive crisis was noted in 6 patients in Sildenafil group, and 3 patients in Combination group (P=0.02). Significant rise in PA pressure was noticed after discontinuation of drug in Milrinone group (P=0.001), which was not observed in the Combination group (P= 0.6). No mortality was noticed in any of the groups.\n\nIntravenous milrinone is more effective than oral sildenafil in control of postoperative PAH and elimination of pulmonary hypertensive crisis. Combination of two drugs reduces the risk of rebound pulmonary arterial hypertension after discontinuation of milrinone.", "PMID": "23550065"}, {"title": "The Effect of Milrinone on Splanchnic and Cerebral Perfusion in Infants With Congenital Heart Disease Prior to Surgery: An Observational Study.", "abstract": "Despite the advancement in the postoperative care of neonates with congenital heart disease (CHD), there is little information on preoperative management of systemic and regional hemodynamics, which may be related to outcomes. We aimed to determine the preoperative effect of milrinone, a phosphodiesterase III inhibitor, on cardiac output and splanchnic and cerebral perfusion in neonates with CHD. Neonates with CHD requiring cardiac surgery were enrolled in a prospective, single-blinded study once a clinical decision of starting milrinone (0.75 \u03bcg/kg per minute intravenously) using institutional criteria was made. Demographic and clinical variables and outcomes were recorded. Combined cardiac output and measures of splanchnic (superior mesenteric and celiac arteries) and cerebral (anterior and middle cerebral arteries) perfusion were determined by Doppler studies at 0, 6, 24, and 48 h after milrinone infusion. Investigators were unaware of intervention time points and patients in analyzing blood flow measurements. Seventeen term (39.2 \u00b1 1.3 weeks) neonates were included with hypoplastic left-sided heart syndrome (78.5%) as the most common diagnosis. Combined cardiac output increased by 28% within 48 h (613 \u00b1 154 vs. 479 \u00b1 147 mL/kg per minute at baseline, P < 0.05). Superior mesenteric artery mean velocity increased at 6 h and throughout 48 h of milrinone infusion (P < 0.05). Peak and mean velocities at cerebral arteries increased with milrinone infusion (P < 0.05~0.08), and the corresponding changes at celiac artery were modest. There were no significant changes in splanchnic and cerebral resistive and pulsatility indices during milrinone infusion. Milrinone increases cardiac output with concurrent effects on splanchnic and cerebral blood flows during the short-term preoperative use in neonates with CHD.", "PMID": "25895150"}, {"title": "Assessment of the effect of two regimens of milrinone infusion in pediatric patients undergoing fontan procedure: A randomized study.", "abstract": "The aim of the study was to compare the effect of two different regimens of milrinone on hemodynamics and oxygen saturation in pediatric patients undergoing Fontan procedure.\n\nThis was a randomized study.\n\nCardiac centers.\n\nThis study included 116 patients undergoing Fontan procedure.\n\nGroup E: Milrinone was started as infusion 0.5 \u03bcg/kg/min without a loading dose at the beginning of cardiopulmonary bypass (CPB) followed by infusion 0.5-0.75 \u03bcg/kg/min in the pediatric cardiac surgical intensive care unit (PSICU). Group L: Milrinone was started as a loading dose 50 \u03bcg/kg over 10 min before weaning from CPB followed by infusion 0.5-0.75 \u03bcg/kg/min in the PSICU.\n\nHeart rate, mean arterial blood pressure, central venous pressure, transpulmonary pressure, cardiac index, pharmacological support, lactate level, urine output, oxygen saturation, ICU, and hospital length of stay.\n\nThere were no changes in the heart rate and mean arterial blood pressure (P > 0.05). The increase in the postoperative central venous pressure, transpulmonary pressure and lactate level was lower in Group E than Group L (P < 0.05). The increase in the postoperative cardiac index, oxygen saturation, and urine output was higher in Group E than Group L (P < 0.05). The requirement for pharmacological support was lower in the Group E (P < 0.05). The ICU and hospital length of stay were shorter in the Group E than Group L (P < 0.05).\n\nEarly use of milrinone during Fontan procedure facilitated the weaning from CPB, decreased the elevation in the central venous pressure, transpulmonary gradient pressure, and the requirement for pharmacological support. Furthermore, it increased the cardiac index and arterial oxygen saturation.", "PMID": "29652273"}, {"title": "Levosimendan for Pediatric Anomalous Left Coronary Artery From the Pulmonary Artery Undergoing Repair: A Single-Center Experience.", "abstract": "", "PMID": "30155453"}, {"title": "Does Inhaled Milrinone Facilitate Weaning From Cardiopulmonary Bypass in Children with Congenital Heart Diseases Complicated with Pulmonary Arterial Hypertension?", "abstract": "The aim of the present study was to evaluate the efficacy of inhaled milrinone in controlling pulmonary arterial hypertension (PAH) in paediatric cardiac surgery and its effect on weaning from cardiopulmonary bypass (CPB).\n\nA total of 40 patients with congenital heart diseases complicated by PAH submitted to cardiac surgery requiring CPB were included in the present study and were randomly classified into the control group (n=20) who received intravenous milrinone 0.5 \u03bcg kg\n\nmPAP and HR were significantly lower, and MAP and MAP/mPAP ratio were significantly higher in the inhaled group than in the control group. Vasoactive drug requirements were significantly lesser, and the time needed to wean the patients was significantly shorter in the inhaled group than in the control group.\n\nMilrinone inhalation facilitated the weaning from CPB as it significantly reduced mPAP and maintained MAP with subsequently less needs for vasoactive drugs.", "PMID": "32259144"}], "labels": [{"PMID": "11773907", "label": "included"}, {"PMID": "12600913", "label": "included"}, {"PMID": "20829069", "label": "included"}, {"PMID": "10230954", "label": "excluded"}, {"PMID": "19650844", "label": "excluded"}, {"PMID": "23550065", "label": "excluded"}, {"PMID": "25895150", "label": "excluded"}, {"PMID": "29652273", "label": "excluded"}, {"PMID": "30155453", "label": "excluded"}, {"PMID": "32259144", "label": "excluded"}]}
{"metadata": {"review_pmid": "39474992"}, "inputs": {"background": "Peripheral arterial disease (PAD) of the lower limbs is caused by atherosclerotic occlusive disease in which narrowing of arteries reduces blood flow to the lower limbs. PAD is common; it is estimated to affect 236 million individuals worldwide. Advanced age, smoking, hypertension, diabetes and concomitant cardiovascular disease are common factors associated with increased risk of PAD. Complications of PAD can include claudication pain, rest pain, wounds, gangrene, amputation and increased cardiovascular morbidity and mortality. It is therefore clinically important to use diagnostic tests that accurately identify PAD. Accurate and timely detection of PAD allows clinicians to implement appropriate risk management strategies to prevent complications, slow progression or intervene when indicated. Toe-brachial index (TBI) and toe systolic blood pressure (TSBP) are amongst a suite of non-invasive bedside tests used to detect PAD. Both TBI and TSBP are commonly utilised by a variety of clinicians in different settings, therefore a systematic review and meta-analysis of their diagnostic accuracy is warranted and highly relevant to inform clinical practice.", "objectives": "To (1) estimate the accuracy of TSBP and TBI for the diagnosis of PAD in the lower extremities at different cut-off values for test positivity in populations at risk of PAD, and (2) compare the accuracy of TBI and TSBP for the diagnosis of PAD in the lower extremities. Secondary objectives were to investigate several possible sources of heterogeneity in test accuracy, including the following: patient group tested (people with type 1 or type 2 diabetes, people with renal disease and general population), type of equipment used, positivity threshold and type of reference standard.", "selection criteria": "We included diagnostic case-control, cross-sectional, prospective and retrospective studies in which all participants had either a TSBP or TBI measurement plus a validated method of vascular diagnostic imaging for PAD. We needed to be able to cross-tabulate (2 x 2 table) results of the index test and the reference standard to include a study. To be included, study populations had to be adults aged 18 years and over. We included studies of symptomatic and asymptomatic participants. Studies had to use TSBP and TBI (also called toe-brachial pressure index (TBPI)), either individually, or in addition to other non-invasive tests as index tests to diagnose PAD in individuals with suspected disease. We included data collected by photoplethysmography, laser Doppler, continuous wave Doppler, sphygmomanometers (both manual and aneroid) and manual or automated digital equipment."}, "context": [{"title": "An evaluation of the efficacy of methods used in screening for lower-limb arterial disease in diabetes.", "abstract": "Foot-related disease is the most common cause for hospital admission among the diabetic population. Lower-limb peripheral arterial occlusive disease (PAOD) is a major risk factor in diabetic foot disease. Screening for PAOD commonly includes foot pulses and the ankle-brachial pressure index (ABPI) and/or the toe-brachial pressure index (TBI), but concerns persist regarding their accuracy. We evaluated the efficacy of several commonly used screening methods in different subject populations.\n\nWe studied 130 limbs in 68 individuals with no critical ischemia over 8 months. Limbs were grouped on the basis of the presence or absence of diabetes, clinically detectable peripheral neuropathy, and PAOD identified on color duplex imaging. Comparative analyses of foot pulses, the ABPI, the TBI, and distal Doppler waveform analysis were performed.\n\nFoot pulses, the TBI, and qualitative waveform analyses were highly sensitive screening methods in individuals with and without diabetes. However, detectable peripheral neuropathy was associated with a reduced sensitivity and poor specificity of foot pulses, a reduction in sensitivity of the ABPI (71 to 38%), and a reduction in specificity of the TBI (81 to 61%) and qualitative waveform analysis (96 to 66%). Quantitative analysis failed to detect disease with severely damped and low-intensity signals.\n\nScreening tools that are effective in screening for lower-limb PAOD in the nondiabetic population are less efficacious in diabetes, particularly in the presence of detectable peripheral neuropathy. Qualitative waveform analysis and the TBI were demonstrated to be more effective screening methods than the ABPI and foot pulses particularly in high-risk limbs with detectable peripheral neuropathy.", "PMID": "16123491"}, {"title": "Peripheral arterial occlusive disease is more prevalent in patients with hemodialysis: comparison with the findings of multidetector-row computed tomography.", "abstract": "Peripheral arterial occlusive disease (PAOD) influences the mortality of patients on hemodialysis therapy. Although the ankle-brachial pressure index (ABI) is used widely to detect PAOD, it yields false-negative results because of calcifications of vascular walls. To more accurately assess the prevalence of PAOD, we investigated which noninvasive method, among ABI, toe-brachial pressure index, transcutaneous Po(2), and skin perfusion pressure (SPP), had superior sensitivity and specificity to the others.\n\nMultidetector-row computed tomography was performed in 36 hemodialysis patients. We then compared the 4 noninvasive methods with findings of multidetector-row computed tomography and calculated the sensitivity and specificity of each method by means of receiver operating characteristic analysis. Irrespective of symptoms, PAOD is defined as the presence of complete obstruction in the case of lesions below the knee or more than 75% stenosis for lesions above the knee.\n\nSeven of 36 patients (19.4%) had an ABI less than 0.9. Sensitivity of the ABI was only 29.9%, whereas an SPP set at 50 mm Hg was more accurate, with sensitivity of 84.9% and specificity of 76.9%. A total of 41.4% of patients had an SPP less than 50 mm Hg. For lesions located above the knee, toe-brachial pressure index provided sensitivity of 91.7% and specificity of 86.7%.\n\nSPP is the most useful tool for detecting PAOD in hemodialysis patients, with accuracy of 84.9%. There is a strong possibility that more patients than previously expected have early PAOD.", "PMID": "16860193"}, {"title": "Utility of Toe-brachial Index for Diagnosis of Peripheral Artery Disease.", "abstract": "The ankle brachial pressure index (ABI) is a simple, useful method for diagnosing peripheral artery disease (PAD). Although the ABI is an objective diagnostic method, it has limited reliability in certain scenarios. The aim of the present study was to determine the accuracy and reliability of the toe brachial index (TBI) as a diagnostic tool for detecting stenosis in PAD, associated with normal or low ABI values.\n\nABI and TBI values were measured in 15 patients with diabetic gangrene who were suspected of having lower extremity arterial insufficiency. The ABI and TBI values were measured using a device that allowed the simultaneous measurement of systolic blood pressure in the upper and lower extremities. In addition, the ABI and TBI values were compared pre- and post-angiography.\n\nPatients with an ABI of 0.9-1.3 showed almost no difference between the 2 measurements. The patients with TBI >0.6 had no arterial insufficiency. The patients with TBI <0.6 required vascular intervention with ballooning. After the angiography, the gangrenous wounds decreased in size more rapidly than they did prior to the intervention.\n\nOur findings suggest that TBI is the method of choice for evaluating lower limb perfusion disorders. This result requires further studies of TBI in a larger number of patients. Future long-term studies should therefore evaluate the utility of TBI as a means of screening for PAD and the present findings should be regarded as preliminary outcomes.", "PMID": "22783531"}, {"title": "Exercise-ankle brachial pressure index with one-minute treadmill walking in patients on maintenance hemodialysis.", "abstract": "The ankle-brachial pressure index (ABI) is widely used as a standard screening method for arterial occlusive lesion above the knee. However, the sensitivity of ABI is low in hemodialysis (HD) patients. Exercise stress (Ex-ABI) may reduce the false negative results.\n\nAfter measuring resting ABI and toe-brachial pressure index (TBI), ankle pressure and ABI immediately after walking (Post-AP, Post-ABI) were measured using one-minute treadmill walking in 52 lower limbs of 26 HD patients. The definition of peripheral arterial occlusive disease (PAD) required an ABI value of less than 0.90, TBI value of less than 0.60, and decrease of more than 15% of the Post-ABI value and 20 mmHg of Post-AP in Ex-ABI. Computed tomographic angiography (CTA) was performed in 32 lower limbs of 16 HD patients. PAD is defined as presence of stenosis of more than 75% in the case of lesions from an iliac artery to knee on CTA.\n\nThe accuracy of Ex-ABI (Sensitivity, 85.7%; Specificity, 77.7%) was higher than those of ABI (Sensitivity, 42.9%; Specificity, 83.3%) or TBI (Sensitivity, 78.6%; Specificity, 61.1%).\n\nEx-ABI with one-minute treadmill walking is the most useful tool for the screening of arterial occlusive lesions above the knee in maintenance HD patients.", "PMID": "23641284"}, {"title": "Non-invasive vascular assessment in the foot with diabetes: sensitivity and specificity of the ankle brachial index, toe brachial index and continuous wave Doppler for detecting peripheral arterial disease.", "abstract": "Non-invasive lower limb vascular assessment in people at risk of peripheral arterial disease (PAD) including those with diabetes is crucial. There is evidence that standard assessment techniques such as the ankle-brachial index (ABI) may be less effective in people with diabetes. However there is limited evidence for other frequently used tests including continuous wave Doppler (CWD), and the toe-brachial index (TBI). The aim of this study was to determine the sensitivity and specificity of, ABI, CWD and TBI in a population with, and without diabetes.\n\nParticipants with and without diabetes who met current guidelines for vascular screening were recruited, and CWD waveforms, an ABI and a TBI were obtained from the right lower limb. Diagnostic accuracy was determined using colour duplex ultrasound (CFDU). Receiver operating characteristic curves were calculated.\n\n117 participants were recruited, seventy-two with diabetes and forty-five without diabetes. CWD had the highest sensitivity in people with diabetes (74%) and without (84%). CWD also had the highest specificity in people with diabetes (74%) and without (84%) compared to both TBI and ABI. In participants with diabetes, the ABI was a poor test, area under the curve: 0.58 (p=0.27).\n\nCWD waveform is more likely to detect significant PAD compared to ABI and TBI in people with and without diabetes.", "PMID": "26281971"}, {"title": "Toe brachial index measured by automated device compared to duplex ultrasonography for detecting peripheral arterial disease in older people.", "abstract": "Introduction To investigate the diagnostic accuracy of an automated toe blood pressure device for detecting peripheral arterial disease in older people. Methods Ninety participants underwent toe and brachial blood pressure measurements and colour duplex ultrasonography of the right lower limb. Peripheral arterial disease was diagnosed if\u2009>\u200950% arterial obstruction was identified in any lower limb vessel using colour duplex ultrasonography. A receiver operating characteristic curve was analysed and the sensitivity and specificity of commonly used toe brachial index and toe blood pressure values were determined. Results The optimum toe brachial index threshold value for diagnosing peripheral arterial disease was 0.72 (sensitivity 76.2%, specificity 75%). The area under the curve was 0.829 (95% CI 0.743 to 0.915, p\u2009<\u20090.0001) suggesting fair diagnostic accuracy. A toe blood pressure of 70\u2009mmHg was found to have excellent specificity (97.92%) for detecting PAD but poor sensitivity (42.86%). Conclusions The accuracy of automated toe blood pressure and TBI measurements was determined to be good when using colour duplex ultrasound as the reference standard for the non-invasive diagnosis of peripheral arterial disease. Results should be interpreted in the context of all clinical signs and symptoms.", "PMID": "28423999"}, {"title": "Diagnostic accuracy of resting systolic toe pressure for diagnosis of peripheral arterial disease in people with and without diabetes: a cross-sectional\u00a0retrospective case-control study.", "abstract": "The resting systolic toe pressure (TP) is a measure of small arterial function in the periphery. TP is used in addition\u00a0to the\u00a0ankle-brachial index when screening for peripheral arterial disease (PAD) of the lower limb in those with diabetes, particularly in the presence of lower limb\u00a0medial arterial calcification. It may be used as an adjunct\u00a0assessment of lower limb vascular function and as a predictor of wound healing. The aim of this study was to determine the diagnostic accuracy of TP for detecting PAD in people with and without diabetes.\n\nThis was a retrospective case-control study. Two researchers extracted information from consecutive patient records, including TP measurements, colour Duplex ultrasound results, demographic information, and medical history. Measures of diagnostic accuracy were determined by receiver operating curve (ROC) analysis, and calculation of sensitivity, specificity, and positive and negative likelihood ratios.\n\nThree hundred and nintey-four\u00a0participants\u00a0with suspected PAD were included. In the diabetes group (\n\nOur findings indicate that TPs are useful to assist in diagnosing PAD in clinical practice, however, results should be interpreted with caution due to the small probability of PAD being present with a negative test.", "PMID": "29270232"}, {"title": "Clinical examination and non-invasive screening tests in the diagnosis of peripheral artery disease in people with diabetes-related foot ulceration.", "abstract": "Peripheral artery disease is common in people with diabetes-related foot ulceration and is a risk factor for amputation. The best method for the detection or exclusion of peripheral artery disease is unknown. This study investigated the utility of clinical examination and non-invasive bedside tests in screening for peripheral artery disease in diabetes-related foot ulceration.\n\nSome 60 people presenting with new-onset ulceration participated. Accuracy of pulses, ankle pressure, toe pressure, toe-brachial index (TBI), ankle-brachial pressure index (ABPI), pole test at ankle, transcutaneous oxygen pressure and distal tibial waveform on ultrasound were examined. The gold standard diagnostic test used was > 50% stenosis in any artery or monophasic flow distal to calcification in any ipsilateral vessel on duplex ultrasound.\n\nThe negative and positive likelihood ratios of pedal pulse assessment (0.75, 1.38) and the other clinical assessment tools were poor. The negative and positive likelihood ratios of ABPI (0.53, 1.69), transcutaneous oxygen pressure (1.10, 0.81) and ankle pressure (0.67, 2.25) were unsatisfactory. The lowest negative likelihood ratios were for tibial waveform assessment (0.15) and TBI (0.24). The highest positive likelihood ratios were for toe pressure (17.55) and pole test at the ankle (10.29) but the negative likelihood ratios were poor at 0.56 and 0.74.\n\nPulse assessment and ABPI have limited utility in the detection of peripheral artery disease in people with diabetes foot ulceration. TBI and distal tibial waveforms are useful for selecting those needing diagnostic testing.", "PMID": "29633431"}, {"title": "Critical analysis and limitations of resting ankle-brachial index in the diagnosis of symptomatic peripheral arterial disease patients and the role of diabetes mellitus and chronic kidney disease.", "abstract": "The ankle-brachial index (ABI) may underestimate the severity of peripheral arterial disease (PAD) in patients with noncompressible vessels. This study analyzed limitations of the ABI and toe-brachial index (TBI), if done alone, in patients with symptomatic PAD, diagnosed by duplex ultrasound (DUS) examination, particularly in patients with diabetes and chronic kidney disease (CKD).\n\nThis is a retrospective review of prospectively collected data. All patients underwent resting ABIs, TBI, and/or DUS. An ABIs of 0.90 or less in either leg was considered abnormal, and the term inconclusive ABIs (noncompressibility) was used if the ABI was 1.3 or greater. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy (OA) of ABIs in detecting 50% or greater stenosis of any arterial segment based on DUS were determined. A TBI of less than 0.7 was considered abnormal.\n\nWe included 2226 ABIs and 1383 DUS examinations: 46% of patients had diabetes, 16% had CKD, and 39% had coronary artery disease. Fifty-three percent of the ABIs were normal, 34% were abnormal, and 13% were inconclusive. For patients with limb-threatening ischemia, 40% had normal ABIs, 40% abnormal ABIs, and 20% were inconclusive. The sensitivity and OA for ABIs in detecting 50% or greater stenosis in the whole series were 57% (95% confidence interval [CI], 53.7-61.2) and 74% (95% CI, 71.9-76.6); for diabetics 51% (95% CI, 46.1-56.3) and 66% (95% CI, 62.3-69.8); nondiabetics 66% (95% CI, 59.9-70.9) and 81% (95% CI, 78.2-83.9). For patients with CKD, the sensitivity and OA for ABIs in detecting 50% or greater stenosis was 43% (95% CI, 34.3-52.7) and 67% (95% CI, 60.2-73.0) versus patients with no CKD 60% (95% CI, 56.3-64.6) and 76% (95% CI, 73.1-78.1). If patients with inconclusive ABIs were excluded, these values were 69% (95% CI, 65.2-72.9) and 80% (95% CI, 77.2-81.9) in the whole series; 67% (95% CI, 61.6-72.7) and 75% (95% CI, 70.5-78.4) for diabetics; and 63% (95% CI, 51.3-73.0) and 78% (95% CI, 70.6-83.9) for patients with CKD. Thirty-three percent of TBIs were normal and 67% were abnormal. The sensitivity and OA for abnormal TBI in detecting 50% or greater stenosis were 85% (95% CI, 78.9-90.0) and 75% (95% CI, 70.1-80.2) in the whole series; 84% (95% CI, 76.0-90.3) and 74% (95% CI, 67.1-80.2) for diabetics; and 77% (95% CI, 61.4-88.2) and 72% (95% CI, 59.9-82.3) for patients with CKD. For those with inconclusive ABIs, these values for TBI were 75% and 69%.\n\nOf symptomatic patients with PAD with 50% or greater stenosis on DUS examination, 43% had normal/inconclusive resting ABIs (49% in diabetics and 57% in CKD). TBI may help in patients with inconclusive ABIs. These patients should undergo further imaging to determine proper treatment.", "PMID": "31471230"}, {"title": "Non-invasive vascular assessment in people with type 2 diabetes: Diagnostic performance of Plethysmographic-and-Doppler derived ankle brachial index, toe brachial index, and pulse volume wave analysis for detection of peripheral arterial disease.", "abstract": "There is evidence that standard assessment techniques for detecting PAD might be of less diagnostic accuracy in people with type 2 diabetes. The aim of this study was to examine diagnostic performance of Plethysmographic-and-Doppler derived ankle brachial index, toe brachial index, and Pulse volume waveform analysis for detecting PAD in people with T2DM.\n\nIn this cross-sectional study 303 patients with T2DM were included in the study. The participants underwent ABI measurement, applying both Plethysmographic and Doppler derived devices, as well as TBI, PVW was also recorded for each patient. Diagnostic performance of each test for detecting PAD, applying ultrasound Doppler scan as the reference standard, was measured. Moreover, the best cut-off point for each method to detect PAD was determined.\n\nPVW showed the highest sensitivity (81.8%) for detecting PAD, followed by ABI\n\nWithin this population of patients with T2DM, TBI less than 0.38 provided the best sensitivity for detection of PAD followed by PVW, ABI", "PMID": "31624003"}], "labels": [{"PMID": "16123491", "label": "included"}, {"PMID": "16860193", "label": "included"}, {"PMID": "22783531", "label": "included"}, {"PMID": "23641284", "label": "included"}, {"PMID": "26281971", "label": "included"}, {"PMID": "28423999", "label": "included"}, {"PMID": "29270232", "label": "included"}, {"PMID": "29633431", "label": "included"}, {"PMID": "31471230", "label": "included"}, {"PMID": "31624003", "label": "included"}]}
{"metadata": {"review_pmid": "39470185"}, "inputs": {"background": "Adverse drug events, encompassing both adverse drug reactions and medication errors, pose a significant threat to health, leading to illness and, in severe cases, death. Timely and voluntary reporting of adverse drug events by healthcare professionals plays a crucial role in mitigating the morbidity and mortality linked to unexpected reactions and improper medication usage.", "objectives": "To assess the effectiveness of different interventions aimed at healthcare professionals to improve the reporting of adverse drug events.", "selection criteria": "We included randomised trials, non-randomised controlled studies, controlled before-after studies, interrupted time series studies (ITS) and repeated measures studies, assessing the effect of any intervention aimed at healthcare professionals and designed to increase adverse drug event reporting. Eligible comparators were healthcare professionals' usual reporting practice or a different intervention or interventions designed to improve adverse drug event reporting rate. We excluded studies of interventions targeted at adverse event reporting following immunisation. Our primary outcome measures were the total number of adverse drug event reports (including both adverse drug reaction reports and medication error reports) and the number of false adverse drug event reports (encompassing both adverse drug reaction reports and medication error reports) submitted by healthcare professionals. Secondary outcomes were the number of serious, high-causality, unexpected or previously unknown, and new drug-related adverse drug event reports submitted by healthcare professionals. We used GRADE to assess the certainty of evidence."}, "context": [{"title": "A novel scheme for the reporting of adverse drug reactions.", "abstract": "The safety of medicines used in children is of considerable public interest, yet available data to monitor the safety of medicines in children is limited.\n\nTo raise awareness and stimulate reporting of adverse drug reactions (ADRs) in children in the Trent region.\n\nA pilot Paediatric Regional Monitoring Centre (PRMC) has been established in the Trent region. The scheme operates as an extension of the UK's spontaneous reporting scheme, the Yellow Card Scheme run by the Medicines Control Agency and the Committee on Safety of Medicines. Proactive interventions including a monthly reminder letter and presentations to staff in the identified hospitals have been made.\n\nDuring the first year of the PRMC, 95 reports were received from the Trent region compared to 40 for the previous year. Twenty four of these reports were for medicines used \"off label\". The 95 reports involved 105 drugs and 171 suspected ADRs. Twenty six of the ADRs (15%) were considered medically significant.\n\nThe number of ADR reports from the Trent region has increased considerably in the first year of the scheme. The results show that intensive education and promotion of ADR reporting can result in a major increase in reporting. This initiative will increase our knowledge about the safety of medicines used to treat children and so help protect public health.", "PMID": "11259235"}, {"title": "Improving adverse-drug-reaction reporting in ambulatory care clinics at a Veterans Affairs hospital.", "abstract": "The detection of adverse drug reactions (ADRs) by a traditional passive reporting system and by a method involving patient and provider interviews was studied. The study sample consisted of randomly selected outpatients seen by their primary care provider during scheduled appointments in January and February 2001 at a Veterans Affairs medical center. After ambulatory care clinic sessions, patients and providers were asked (by telephone and in person, respectively) to identify potential ADRs. Also obtained were demographic data, information about drug regimens, and the severity and management of each ADR. A standardized ADR-assessment tool was used to determine the severity of each reported reaction and its causal relationship with the medication. A total of 198 patients were included. Of these, 51 (26%) had one or more ADRs. The patient and provider interviews identified a total of 83 ADRs, compared with 1 ADR identified by the passive reporting system. When providers were made aware of the ADRs they had not identified, changes were made to the patient's medication regimen in 34% of cases. The risk of an ADR was not associated with age, number of medications, or provider type. Direct patient and provider interviews yielded a significantly higher rate of ADR detection in an ambulatory care setting than did a passive ADR-reporting system.", "PMID": "12004462"}, {"title": "Spontaneous reporting of adverse drug reactions by nurses.", "abstract": "Spontaneous reporting of adverse drug reactions (ADRs) remains one of the most effective methods to detect new and serious drug reactions. However, it is well known that there is a high degree of under-reporting.\n\nThis study was carried out as an attempt to improve and increase the reporting of ADRs by investigating the utility of nurses reporting in addition to physicians, as usual.\n\nDuring a 12-month study period, nurses working at two departments of geriatric medicine in northern Sweden received special instruction regarding drugs and ADRs, ADR reporting and special aspects of ADRs in elderly people. The reports from the nurses were scrutinized concerning the seriousness of the reaction, reported drugs and type of reaction (type A or B). All nurses working at the two departments (117) were eligible to report but in practice only those attending the teaching sessions did so. A comparison with historical reporting and with reporting from other geriatric departments in Sweden was also carried out. At the end of the study all participating nurses received a questionnaire aimed at investigating their attitudes towards ADR reporting.\n\nAfter the 12-month study period 18 ADR reports involving 22 reactions had been received. Seven of these were assessed as serious reactions. All of the reactions were of type A. In comparison, during the corresponding time period from the study clinics during the preceding year, only two reports were registered. During the study period only 15 reports were registered from the other 50 geriatric departments in Sweden.\n\nEven though the total number of ADR reports was small, our data indicate a substantial increase in the reporting rate. This indicates that instructed and interested nurses could play an important role in detecting and reporting suspected ADRs.", "PMID": "12512239"}, {"title": "Impact of nurse case manager-pharmacist collaboration on adverse-drug-event reporting.", "abstract": "", "PMID": "15018225"}, {"title": "Electronic adverse-drug-reaction-reporting program.", "abstract": "", "PMID": "15259751"}, {"title": "A distance-learning programme in pharmacovigilance linked to educational credits is associated with improved reporting of suspected adverse drug reactions via the UK yellow card scheme.", "abstract": "The effect of a distance-learning package linked to educational credits on the rate and quality of spontaneous adverse drug reaction (ADR) reporting by general practitioners (GPs) and pharmacists in Wales was investigated.\n\nIn April 2000, 477 GPs and 261 pharmacists enrolled in the 12 month programme.\n\nThe number and quality of yellow card reports improved compared with those of a control region in England (Northern Region).\n\nWe conclude that an educational initiative in drug safety linked to incentives may be associated with a significant but perhaps short-lived improvement in the rate and quality of ADR reporting.", "PMID": "16042677"}, {"title": "A small economic inducement to stimulate increased reporting of adverse drug reactions--a way of dealing with an old problem?", "abstract": "To assess the effect of a small economic inducement on the rate of spontaneous reporting of adverse drug reactions (ADRs) and the attitudes of general practitioners and physicians towards reporting of ADRs.\n\nOne intervention and one control county were selected for the study. Written information about the main purpose of spontaneous reporting of ADRs was personally addressed to all physicians in the two counties. The information was identical, except for the addition that during a period of 6 months two lottery tickets would be given to the receivers in the intervention area with the standard personal feedback to the reporter of the ADR. After the 6-month study period, the actual number of reported ADRs and the seriousness of the reported ADRs were assessed. To investigate the attitude towards this stimulation of reporting, a questionnaire was addressed to all physicians within the intervention area (IA).\n\nFrom the IA a total number of 57 ADR reports were received containing 62 suspected ADRs, 40% of which were assessed as serious reactions. From the control area (CA), 49 reports containing 50 suspected ADRs were received, 32% of which were assessed as serious reactions. The increase of ADR reports from the IA compared to the same time period the previous year was 59% as compared to an unchanged reporting from the CA. Of those responding to the questionnaire, 80% did not believe that a small economic bonus would be a useful tool to improve the reporting rate.\n\nA small economic inducement is associated with an increase in the reporting of suspected ADRs.", "PMID": "16572320"}, {"title": "Development of a videotape on adverse drug reactions.", "abstract": "A pharmacy department's development and evaluation of a 20-minute videotape on adverse drug reaction (ADR) reporting is described. At the University of Mississippi Medical Center Hospital, a 545-bed hospital, it was determined that inadequate education of staff was a major contributing factor to the failure of ADR-reporting programs. Since no videotape educational program on ADRs was available, the pharmacy department developed its own at a cost of approximately $400. The videotape demonstrates a variety of ADRs that occur in adult inpatients and provides instructions on how to report ADRs. The description of each ADR includes manifestations of the reaction, drugs associated with the reaction, and implications for the patient. During a three-month evaluation period on four patient-care units, nine ADRs were reported by nurses who were shown the videotape, while no ADRs were reported by nurses who were provided with only an oral presentation on ADR reporting. The videotape is now used hospitalwide, primarily with nurses and new pharmacy personnel. The videotape developed by the pharmacy department proved to be an effective means for demonstrating clinical manifestations of ADRs and explaining procedures for voluntary reporting.", "PMID": "1695062"}, {"title": "Effects of a pharmacist-led pediatrics medication safety team on medication-error reporting.", "abstract": "The effects of a pharmacist-led pediatrics medication safety team (PMST) on the frequency and severity of medication errors reported were studied.\n\nThis study was conducted in a pediatric critical care center (PCCC) in three phases. Phase 1 consisted of retrospective collection of medication-error reports before any interventions were made. Phases 2 and 3 included prospective collection of medication-error reports after several interventions. Phase 2 introduced a pediatrics clinical pharmacist to the PCCC. A pediatrics clinical pharmacist-led PMST (including a pediatrics critical care nurse and pediatrics intensivist), a new reporting form, and educational forums were added during phase 3 of the study. In addition, education focus groups were held for all intensive care unit staff. Outcomes for all phases were measured by the number of medication-error reports processed, the number of incidents, error severity, and the specialty of the reporter.\n\nMedication-error reporting increased twofold, threefold, and sixfold between phases 1 and 2, phases 2 and 3, and phases 1 and 3, respectively. Error severity decreased over the three time periods. In phases 1, 2, and 3, 46%, 8%, and 0% of the errors were classified as category D or E, respectively. Conversely, the reporting of near-miss errors increased from 9% in phase 1 to 38% in phase 2 and to 51% in phase 3.\n\nAn increase in the number of medication errors reported and a decrease in the severity of errors reported were observed in a PCCC after implementation of a PMST, provision of education to health care providers, and addition of a clinical pharmacist.", "PMID": "17592009"}, {"title": "Efficacy of an adverse drug reaction electronic reporting system integrated into a hospital information system.", "abstract": "Adverse drug reaction (ADR) spontaneous reporting is the primary method of postmarketing drug surveillance; although it is an important part of postmarketing drug surveillance, it is underused. Before 2004, almost no ADRs were reported in our 400-bed hospital. As an electronic hospital information system was available in our hospital, we developed a tool (ADR-RS-IHIS) for ADR reporting integrated into the hospital information system to facilitate reporting through easy use, automatic input of certain information, increased accessibility, real-time review, and intervention.\n\nTo analyze the efficacy of the ADR-RS-IHIS in increasing ADR reporting to the national drug surveillance system, propose and implement improvements to increase ADR reporting, and evaluate the impact of these improvements.\n\nEvery ADR reported through the ADR-RS-IHIS was evaluated retrospectively. Two study phases for evaluating ADR-RS-IHIS efficacy were identified. Phase I took place April 2004-August 2006; in April 2006, an interim analysis was performed to propose improvements. Phase II took place September 2006-April 2007 for evaluation of the impact made by the proposed improvements. Efficacy in the phase I and improvement impact on phase II were measured as the number of ADRs reported to the national drug surveillance system.\n\nThe rate of ADRs reported per month to the national system increased from 0 before 2004 to 0.91 in phase I and 1.62 in phase II (2.25 if delayed reporting was considered). Improvement measures included: allowing nurses to report ADRs in the same way as physicians and pharmacists, automatic form filling of certain information from the electronic hospital information system, easier ADR report analysis, and automatic notification to the allergy department regarding suspected allergies.\n\nAn ADR reporting system integrated into the electronic hospital information system is effective for increasing the number of ADRs reported to the national drug surveillance system. Allowing nurses to report ADRs in a manner similar to that of physicians and pharmacists, as well as automatic entry of certain data into the form, contributes to the improvement of the system.", "PMID": "18780808"}], "labels": [{"PMID": "11259235", "label": "excluded"}, {"PMID": "12004462", "label": "excluded"}, {"PMID": "12512239", "label": "excluded"}, {"PMID": "15018225", "label": "excluded"}, {"PMID": "15259751", "label": "excluded"}, {"PMID": "16042677", "label": "excluded"}, {"PMID": "16572320", "label": "excluded"}, {"PMID": "1695062", "label": "excluded"}, {"PMID": "17592009", "label": "excluded"}, {"PMID": "18780808", "label": "excluded"}]}
{"metadata": {"review_pmid": "39324693"}, "inputs": {"background": "Malaria and HIV infection overlap geographically in sub-Saharan Africa and share risk factors. HIV infection increases malaria's severity, especially in pregnant women. The World Health Organization (WHO) recommends intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) for pregnant women living in areas of stable malaria transmission. However, HIV-positive women on daily cotrimoxazole prophylaxis (recommended for prevention of opportunistic infections in people with HIV) cannot receive SP due to adverse drug interactions, so malaria prevention in this vulnerable population currently relies on daily cotrimoxazole prophylaxis alone. This review is based on a new protocol and provides an update to the 2011 Cochrane Review that evaluated alternative drugs for IPTp to prevent malaria in HIV-positive women.", "objectives": "To compare the safety and efficacy of intermittent preventive treatment regimens for malaria prevention in HIV-positive pregnant women.", "selection criteria": "We included randomized controlled trials (RCTs) comparing any intermittent preventive treatment regimen for preventing malaria in HIV-positive pregnant women against daily cotrimoxazole prophylaxis alone, placebo, current or previous standard of care, or combinations of these options. By 'standard of care' we refer to the country's recommended drug regimen to prevent malaria in pregnancy among HIV-positive women, or the treatment that a trial's research team considered to be the standard of care."}, "context": [{"title": "Randomized trial of 2-dose versus monthly sulfadoxine-pyrimethamine intermittent preventive treatment for malaria in HIV-positive and HIV-negative pregnant women in Malawi.", "abstract": "Intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) decreases placental malaria parasitemia and associated maternal anemia, premature delivery, and low birth weight. However, the optimal regimen in the setting of a high prevalence of human immunodeficiency virus (HIV) infection remains unclear.\n\nIn Malawi, where the efficacy of SP for the treatment of malaria in children is decreasing, we conducted a randomized, nonblinded study to compare the efficacy of monthly SP IPTp with a 2-dose regimen for the prevention of placental parasitemia in HIV-positive and -negative primigravid and secundigravid women.\n\nOf HIV-positive women, 7.8% who received monthly SP had placental malaria, compared with 21.5% of those who received 2-dose SP (relative risk [RR], 0.36 [95% confidence interval {CI}, 0.17-0.79]). Of HIV-negative women, 2.3% who received monthly SP and 6.3% who received 2-dose SP had placental malaria (RR, 0.37 [95% CI, 0.11-1.19]). Less than 1% of women reported adverse drug reactions, with no increase in HIV-positive women or those who received monthly SP.\n\nIn HIV-positive pregnant women, monthly SP IPTp is more efficacious than a 2-dose regimen in preventing placental malaria. The study also demonstrates the continued efficacy of SP for the prevention of placental malaria, even in the face of its decreasing efficacy for the treatment of malaria in children. In areas with intense transmission of falciparum malaria and a high prevalence of HIV infection, monthly SP IPTp should be adopted.", "PMID": "16826475"}, {"title": "Two-dose versus monthly intermittent preventive treatment of malaria with sulfadoxine-pyrimethamine in HIV-seropositive pregnant Zambian women.", "abstract": "Intermittent preventive treatment of malaria during pregnancy (IPTp) reduces placental infection, maternal anemia, and low birth weight (LBW). However, the optimal dosing regimen in settings in which human immunodeficiency virus (HIV) is highly prevalent among pregnant women remains controversial.\n\nWe conducted a randomized, double-blind, placebo-controlled study of IPTp comparing the standard 2-dose sulfadoxine-pyrimethamine (SP) regimen with monthly IPTp among a cohort of HIV-positive pregnant Zambian women. Primary outcomes included placental malaria (by smear and histology) and maternal peripheral parasitemia at delivery.\n\nThere were no differences between monthly IPTp (n=224) and standard IPTp (n=232) in placental malaria by histopathology (26% vs. 29%; relative risk [RR], 0.90 [95% confidence interval {CI}, 0.64-1.26]) or placental parasitemia (2% vs. 4%; RR, 0.55 [95% CI, 0.17-1.79]). There also were no differences in maternal anemia, stillbirths, preterm delivery, LBW, or all-cause mortality of infants at 6 weeks.\n\nIn an area of mesoendemicity in Zambia, monthly SP IPTp was not more efficacious than the standard 2-dose regimen for the prevention of placental malaria or adverse birth outcomes. IPTp policy recommendations need to take into account local malaria transmission patterns and the prevalence of HIV.\n\nClinicalTrials.gov identifier: NCT00270530.", "PMID": "18008241"}, {"title": "A randomized placebo-controlled trial of intermittent preventive treatment in pregnant women in the context of insecticide treated nets delivered through the antenatal clinic.", "abstract": "Current recommendations to prevent malaria in African pregnant women rely on insecticide treated nets (ITNs) and intermittent preventive treatment (IPTp). However, there is no information on the safety and efficacy of their combined use.\n\n1030 pregnant Mozambican women of all gravidities received a long-lasting ITN during antenatal clinic (ANC) visits and, irrespective of HIV status, were enrolled in a randomised, double blind, placebo-controlled trial, to assess the safety and efficacy of 2-dose sulphadoxine-pyrimethamine (SP). The main outcome was the reduction in low birth weight.\n\nTwo-dose SP was safe and well tolerated, but was not associated with reductions in anaemia prevalence at delivery (RR, 0.92 [95% CI, 0.79-1.08]), low birth weight (RR, 0.99 [95% CI, 0.70-1.39]), or overall placental infection (p = 0.964). However, the SP group showed a 40% reduction (95% CI, 7.40-61.20]; p = 0.020) in the incidence of clinical malaria during pregnancy, and reductions in the prevalence of peripheral parasitaemia (7.10% vs 15.15%) (p<0.001), and of actively infected placentas (7.04% vs 13.60%) (p = 0.002). There was a reduction in severe anaemia at delivery of borderline statistical significance (p = 0.055). These effects were not modified by gravidity or HIV status. Reported ITN's use was more than 90% in both groups.\n\nTwo-dose SP was associated with a reduction in some indicators, but these were not translated to significant improvement in other maternal or birth outcomes. The use of ITNs during pregnancy may reduce the need to administer IPTp. ITNs should be part of the ANC package in sub-Saharan Africa.\n\nClinicalTrials.gov NCT00209781.", "PMID": "18398460"}, {"title": "Mother-to-child transmission of HIV-1: association with malaria prevention, anaemia and placental malaria.", "abstract": "Malaria infection may impact on mother-to-child transmission (MTCT) of HIV-1. Prevention of malaria in pregnancy could thus potentially affect MTCT of HIV. We studied the impact of intermittent preventive treatment during pregnancy (IPTp) on HIV-1 MTCT in southern Mozambique.\n\nA total of 207 HIV-positive Mozambican pregnant women were enrolled in the study as part of a randomized placebo-controlled trial of two-dose sulfadoxine-pyrimethamine (SP) IPTp in women receiving single-dose nevirapine to prevent MTCT of HIV. HIV RNA viral load, maternal anaemia and peripheral and placental malaria were assessed at delivery. Infant HIV status was determined by DNA polymerase chain reaction (PCR) at 1 month of age.\n\nThere were 19 transmissions of HIV in 153 mother-infant pairs. IPTp with SP did not have a significant impact on MTCT (11.8% in the SP group vs. 13.2% in the placebo group; P=0.784) or on maternal HIV RNA viral load [16 312 (interquartile range {IQR} 4076-69 296) HIV-1 RNA copies/mL in the SP group vs. 18 274 (IQR 5471-74 104) copies/mL in the placebo group; P=0.715]. In multivariate analysis, maternal HIV RNA viral load [adjusted odds ratio (AOR) 19.9; 95% confidence interval (CI) 2.3-172; P=0.006] and anaemia (haematocrit <33%; AOR 7.5; 95% CI 1.7-32.4; P=0.007) were independent risk factors for MTCT. Placental malaria was associated with a decrease in MTCT (AOR 0.23; 95% CI 0.06-0.89; P=0.034).\n\nIPTp with SP was not associated with a significant impact on MTCT of HIV. Maternal anaemia was an independent risk factor for MTCT.", "PMID": "18651857"}, {"title": "Cotrimoxazole prophylaxis versus mefloquine intermittent preventive treatment to prevent malaria in HIV-infected pregnant women: two randomized controlled trials.", "abstract": "Malaria during pregnancy has serious consequences that are worsened by HIV infection. Malaria preventive measures for HIV-infected pregnant women include cotrimoxazole (CTX) prophylaxis given to prevent HIV-related opportunistic infections and also protective against malaria, or intermittent preventive treatment (IPTp) with an antimalarial drug. Here, we present the first study evaluating CTX efficacy versus mefloquine (MQ)-IPTp, alone and in combination, in HIV-infected pregnant women.\n\nWe conducted 2 randomized, open-label, noninferiority trials in Benin. In the CTX-mandatory trial, HIV-infected women with CD4 counts of <350 per cubic millimeter received CTX either alone or with MQ-IPTp (N = 292). In the CTX-not-mandatory trial (CD4 count >350/mm), CTX was compared with MQ-IPTp (N = 140). In both the trials, the primary end point was microscopic placental parasitemia.\n\nAt delivery, 1 woman in each CTX-alone treatment group exhibited placental parasitemia, versus no women in the groups receiving MQ. CTX alone demonstrated noninferiority in the CTX-mandatory trial. However, polymerase chain reaction-detected placental parasitemia was markedly reduced in the CTX + MQ group compared with CTX alone (0/105 vs. 5/103, P = 0.03). Because of insufficient recruitment in the CTX-not-mandatory trial, noninferiority could not be conclusively assessed. Dizziness and vomiting of moderate intensity were reported by 34%-37% of women receiving MQ in both the trials, versus 0%-3% in CTX groups (P < 0.0001). No serious adverse events related to these drugs were found.\n\nCTX alone provided adequate protection against malaria in HIV-infected pregnant women, although MQ-IPTp showed higher efficacy against placental infection. Although more frequently associated with dizziness and vomiting, MQ-IPTp may be an effective alternative given concerns about parasite resistance to CTX.", "PMID": "24220287"}, {"title": "Cotrimoxazole prophylaxis versus mefloquine intermittent preventive treatment to prevent malaria in HIV-infected pregnant women: two randomized controlled trials.", "abstract": "Malaria during pregnancy has serious consequences that are worsened by HIV infection. Malaria preventive measures for HIV-infected pregnant women include cotrimoxazole (CTX) prophylaxis given to prevent HIV-related opportunistic infections and also protective against malaria, or intermittent preventive treatment (IPTp) with an antimalarial drug. Here, we present the first study evaluating CTX efficacy versus mefloquine (MQ)-IPTp, alone and in combination, in HIV-infected pregnant women.\n\nWe conducted 2 randomized, open-label, noninferiority trials in Benin. In the CTX-mandatory trial, HIV-infected women with CD4 counts of <350 per cubic millimeter received CTX either alone or with MQ-IPTp (N = 292). In the CTX-not-mandatory trial (CD4 count >350/mm), CTX was compared with MQ-IPTp (N = 140). In both the trials, the primary end point was microscopic placental parasitemia.\n\nAt delivery, 1 woman in each CTX-alone treatment group exhibited placental parasitemia, versus no women in the groups receiving MQ. CTX alone demonstrated noninferiority in the CTX-mandatory trial. However, polymerase chain reaction-detected placental parasitemia was markedly reduced in the CTX + MQ group compared with CTX alone (0/105 vs. 5/103, P = 0.03). Because of insufficient recruitment in the CTX-not-mandatory trial, noninferiority could not be conclusively assessed. Dizziness and vomiting of moderate intensity were reported by 34%-37% of women receiving MQ in both the trials, versus 0%-3% in CTX groups (P < 0.0001). No serious adverse events related to these drugs were found.\n\nCTX alone provided adequate protection against malaria in HIV-infected pregnant women, although MQ-IPTp showed higher efficacy against placental infection. Although more frequently associated with dizziness and vomiting, MQ-IPTp may be an effective alternative given concerns about parasite resistance to CTX.", "PMID": "24220287"}, {"title": "Inferiority of single-dose sulfadoxine-pyrimethamine intermittent preventive therapy for malaria during pregnancy among HIV-positive Zambian women.", "abstract": "The World Health Organization advocates 2-3 doses of sulfadoxine-pyrimethamine (SP) for intermittent preventive treatment of malaria (SP IPTp). The optimal number of doses and the consequences of single-dose therapy remain unclear.\n\nData were from a randomized, controlled study of human immunodeficiency virus-positive Zambian women comparing monthly versus 2-dose SP IPTp. We compared maternal and neonatal birth outcomes as a function of how many doses the mothers received (1 to > or =4 doses).\n\nOf 387 deliveries, 34 received 1 dose of SP. Single-dose SP was significantly associated with higher proportions of maternal anemia, peripheral and cord blood parasitemia, infant prematurity, and low birth weight. SP conferred dose-dependent benefits, particularly in the transition from 1 to 2 doses of SP. Women randomized to the standard 2-dose regimen were much more likely to receive only 1 dose than were women randomized to monthly IPT (relative risk, 16.4 [95% confidence interval, 4.0-68.3]).\n\nSingle-dose SP was a common result of trying to implement the standard 2-dose regimen and was inferior to all other dosing regimens. At a programmatic level, this implies that monthly SP IPTp may ultimately be more effective than the standard regimen by reducing the risk of inadvertently underdosing mothers.", "PMID": "18008240"}, {"title": "Effect of repeated treatment of pregnant women with sulfadoxine-pyrimethamine and azithromycin on preterm delivery in Malawi: a randomized controlled trial.", "abstract": "Preterm delivery, which is associated with infections during pregnancy, is common in sub-Saharan Africa. We enrolled 1,320 pregnant women into a randomized, controlled trial in Malawi to study whether preterm delivery and low birth weight (LBW) incidence can be reduced by intermittent preventive treatment of maternal malaria and reproductive tract infections. The participants received either sulfadoxine-pyrimethamine (SP) twice (controls), monthly SP, or monthly SP and two doses of azithromycin (AZI-SP). The incidence of preterm delivery was 17.9% in controls, 15.4% in the monthly SP group (P = 0.32), and 11.8% in AZI-SP group (risk ratio = 0.66, P = 0.01). Compared with controls, those in AZI-SP group had a risk ratio of 0.61 (P = 0.02) for LBW. Incidence of serious adverse events was low in all groups. In conclusion, the incidence of preterm delivery and LBW can in some conditions be reduced by treating pregnant women with monthly SP and two azithromycin doses.", "PMID": "21118924"}, {"title": "The effect of monthly sulfadoxine-pyrimethamine, alone or with azithromycin, on PCR-diagnosed malaria at delivery: a randomized controlled trial.", "abstract": "New regimens for intermittent preventive treatment in pregnancy (IPTp) against malaria are needed as the effectiveness of the standard two-dose sulfadoxine-pyrimethamine (SP) regimen is under threat. Previous trials have shown that IPTp with monthly SP benefits HIV-positive primi- and secundigravidae, but there is no conclusive evidence of the possible benefits of this regimen to HIV-negative women, or to a population comprising of both HIV-positive and -negative women of different gravidities.\n\nThis study analyzed 484 samples collected at delivery as part of a randomized, partially placebo controlled clinical trial, conducted in rural Malawi between 2003 and 2007. The study included pregnant women regardless of their gravidity or HIV-infection status. The participants received SP twice (controls), monthly SP, or monthly SP and two doses of azithromycin (AZI-SP). The main outcome was the prevalence of peripheral Plasmodium falciparum malaria at delivery diagnosed with a real-time polymerase chain reaction (PCR) assay.\n\nOverall prevalence of PCR-diagnosed peripheral P. falciparum malaria at delivery was 10.5%. Compared with the controls, participants in the monthly SP group had a risk ratio (95% CI) of 0.33 (0.17 to 0.64, P<0.001) and those in the AZI-SP group 0.23 (0.11 to 0.48, P<0.001) for malaria at delivery. When only HIV-negative participants were analyzed, the corresponding figures were 0.26 (0.12 to 0.57, P<0.001) for women in the monthly SP group, and 0.24 (0.11 to 0.53, P<0.001) for those in the AZI-SP group.\n\nOur results suggest that increasing the frequency of SP administration during pregnancy improves the efficacy against malaria at delivery among HIV-negative women, as well as a population consisting of both HIV-positive and -negative pregnant women of all gravidities, in a setting of relatively low but holoendemic malaria transmission, frequent use of bed nets and high SP resistance.", "PMID": "22829919"}, {"title": "Efficacy of sulfadoxine-pyrimethamine for prevention of placental malaria in an area of Kenya with a high prevalence of malaria and human immunodeficiency virus infection.", "abstract": "A fever case management (CM) approach using sulfadoxine-pyrimethamine (SP) was compared with two presumptive intertmittent SP treatment regimens in the second and third trimesters in pregnant primigravidae and secundigravidae in an area of intense Plasmodium falciparum malaria transmission in western Kenya. The investigation evaluated efficacy of the antimalarial regimens for prevention of placental malaria and examined the effect of human immunodeficiency virus (HIV) infection on antimalarial drug efficacy and adverse drug reactions. Twenty-seven percent (93 of 343) of pregnant women in the CM group had placental malaria compared with 12% (38 of 330; P < 0.001) of women who received two doses of SP and compared with 9% (28 of 316; P < 0.001) of women who received monthly SP. Fourteen percent (49 of 341) of women in the CM group delivered low birth weight (LBW) infants compared with 8% (27 of 325; P=0.118) of women who received two doses of SP and compared with 8% (26 of 331; P=0.078) of women who received monthly SP. Seven percent (7 of 99) of the HIV-negative women on the two-dose SP regimen had placental malaria compared with 25% (10 of 39; P=0.007) of HIV-positive women on the same regimen; the rate of placental malaria in HIV-positive women was reduced to 7% (2 of 28; P=-0.051) for women on the monthly SP regimen. Less than 2% of women reported adverse drug reactions, with no statistically significant differences between HIV-positive and HIV-negative women. Intermittent treatment with SP is safe and efficacious for the prevention of placental malaria in pregnant primigravidae and secundigravidae in sub-Saharan Africa. While a two-dose SP regimen may be effective in areas with low HIV seroprevalence, administration of SP monthly during the second and third trimesters of pregnancy should be considered in areas of high HIV seroprevalence to prevent the effects of maternal malaria on the newborn.", "PMID": "9840604"}], "labels": [{"PMID": "16826475", "label": "included"}, {"PMID": "18008241", "label": "included"}, {"PMID": "18398460", "label": "included"}, {"PMID": "18651857", "label": "included"}, {"PMID": "24220287", "label": "included"}, {"PMID": "24220287", "label": "included"}, {"PMID": "18008240", "label": "excluded"}, {"PMID": "21118924", "label": "excluded"}, {"PMID": "22829919", "label": "excluded"}, {"PMID": "9840604", "label": "excluded"}]}
{"metadata": {"review_pmid": "39319863"}, "inputs": {"background": "Dementia and mild cognitive impairment are significant contributors to disability and dependency in older adults. Current treatments for managing these conditions are limited. Exergaming, a novel technology-driven intervention combining physical exercise with cognitive tasks, is a potential therapeutic approach.", "objectives": "To assess the effects of exergaming interventions on physical and cognitive outcomes, and activities of daily living, in people with dementia and mild cognitive impairment.", "selection criteria": "We included randomised controlled trials (RCTs) that recruited individuals diagnosed with dementia or mild cognitive impairment (MCI). Exergaming interventions involved participants being engaged in physical activity of at least moderate intensity, and used immersive and non-immersive virtual reality (VR) technology and real-time interaction. We planned to classify comparators as inactive control group (e.g. no treatment, waiting list), active control group (e.g. standard treatment, non-specific active control), or alternative treatment (e.g. physical activity, computerised cognitive training). Outcomes were to be measured using validated instruments."}, "context": [{"title": "Interactive video gaming compared with health education in older adults with mild cognitive impairment: a feasibility study.", "abstract": "We evaluated the feasibility of a trial of Wii interactive video gaming, and its potential efficacy at improving cognitive functioning compared with health education, in a community sample of older adults with neuropsychologically defined mild cognitive impairment.\n\nTwenty older adults were equally randomized to either group-based interactive video gaming or health education for 90\u2009min each week for 24\u2009weeks. Although the primary outcomes were related to study feasibility, we also explored the effect of the intervention on neuropsychological performance and other secondary outcomes.\n\nAll 20 participants completed the intervention, and 18 attended at least 80% of the sessions. The majority (80%) of participants were \"very much\" satisfied with the intervention. Bowling was enjoyed by the most participants and was also rated the highest among the games for mental, social, and physical stimulation. We observed medium effect sizes for cognitive and physical functioning in favor of the interactive video gaming condition, but these effects were not statistically significant in this small sample.\n\nInteractive video gaming is feasible for older adults with mild cognitive impairment, and medium effect sizes in favor of the Wii group warrant a larger efficacy trial.", "PMID": "24452845"}, {"title": "Does cognition-specific computer training have better clinical outcomes than non-specific computer training? A single-blind, randomized controlled trial.", "abstract": "The purpose of this study was to investigate differences between non-specific computer training (NCT) and cognition-specific computer training (CCT).\n\nRandomized controlled experimental study.\n\nLocal community welfare center.\n\nA total of 78 subjects with mild cognitive impairment (MCI) were randomly assigned to the NCT ( n\u2009=\u200939) or CCT group ( n\u2009=\u200939).\n\nThe NCT group underwent NCT using Nintendo Wii for improving functional performance, while the CCT group underwent CCT using CoTras for improving function of the cognitive domain specifically. Subjects in both groups received 30-minute intervention three times a week for 10\u2009weeks.\n\nTo identify effects on cognitive function, the Wechsler Adult Intelligence Scale (WAIS) digit span subtests, Rey Auditory Verbal Learning Test (RAVLT), Trail Making Test-Part B (TMT-B), Rey-Osterrieth Complex Figure Test, and Modified Taylor Complex Figure (MTCF) were used. Health-related quality of life (HRQoL) was assessed using the Short-Form 36-item questionnaire.\n\nAfter 10\u2009weeks, the WAIS subtests (digit span forward: 0.48\u2009\u00b1\u20090.08 vs. 0.12\u2009\u00b1\u20090.04; digit span backward: 0.46\u2009\u00b1\u20090.09 vs. 0.11\u2009\u00b1\u20090.04) and HRQoL (vitality: 9.05\u2009\u00b1\u20091.17 vs. 2.69\u2009\u00b1\u20091.67; role-emotional: 8.31\u2009\u00b1\u20091.20 vs. 4.15\u2009\u00b1\u20090.71; mental health: 11.62\u2009\u00b1\u20091.63 vs. 6.95\u2009\u00b1\u20091.75; bodily pain: 4.21\u2009\u00b1\u20092.17 vs. 0.10\u2009\u00b1\u20090.38) were significantly higher in the NCT group ( P\u2009<\u20090.05).\n\nNCT was superior to CCT for improving cognitive function and HRQoL of elderly adults with MCI.", "PMID": "28726492"}, {"title": "The quest for synergy between physical exercise and cognitive stimulation via exergaming in people with dementia: a randomized controlled trial.", "abstract": "Exercise is often proposed as a non-pharmacological intervention to delay cognitive decline in people\u00a0with dementia, but evidence remains inconclusive. Previous studies suggest that combining physical exercise with cognitive stimulation may be more successful in this respect. Exergaming is a promising intervention in which physical exercise is combined with cognitively challenging tasks in a single session. The aim of this study was to investigate the effect of exergame training and aerobic training on cognitive functioning in older adults with dementia.\n\nA three-armed randomized controlled trial (RCT) compared exergame training, aerobic training and an active control intervention consisting of relaxation and flexibility exercises. Individuals with dementia were randomized and individually trained three times a week during 12\u2009weeks. Cognitive functioning was measured at baseline, after the 12-week intervention period and at 24-week follow-up by neuropsychological assessment. The domains of executive function, episodic memory, working memory and psychomotor speed were evaluated. Test scores were converted into standardized z-scores that were averaged per domain. Between-group differences were analysed with analysis of covariance.\n\nData from 115 people with dementia (mean (SD) age\u2009=\u200979.2 (6.9) years; mean (SD) MMSE score\u2009=\u200922.9 (3.4)) were analysed. There was a significant improvement in psychomotor speed in the aerobic and exergame groups compared to the active control group (mean difference domain score (95% CI) aerobic versus control 0.370 (0.103-0.637), p\u2009=\u20090.007; exergame versus control 0.326 (0.081-0.571), p\u2009=\u20090.009). The effect size was moderate (partial \u03b7\n\nTo our knowledge, this is the first RCT evaluating the effects of exergame training and aerobic training on cognitive functioning in people with dementia. We found that both exergame training and aerobic training improve psychomotor speed, compared to an active control group. This finding may be clinically relevant as psychomotor speed is an important predictor for functional decline. No effects were found on executive function, episodic memory and working memory.\n\nNetherlands Trial Register, NTR5581 . Registered on 7 October 2015.", "PMID": "30611286"}, {"title": "Exergaming as a Physical Exercise Strategy Reduces Frailty in People With Dementia: A Randomized Controlled Trial.", "abstract": "People with dementia are known to be physically frailer, more sedentary, and participate less in regular physical exercise compared to their healthy peers. Physical activity interventions have the potential to reduce the level of frailty in community-dwelling older adults. Exergaming combines physical exercise with cognitive stimulation in a virtual environment. It is an innovative and fun way of exercising, which may aid people with dementia to be more physically active. The primary aim of this study was to investigate the efficacy of a 12-week exergame training and equally long aerobic training, both compared to an active control group, on frailty in people with dementia.\n\nA 3-armed randomized controlled trial compared exergame training, aerobic training, and an active control intervention.\n\n115 people with dementia [mean (standard deviation [SD]) age\u00a0=\u00a079.2 (6.9) years; mean (SD) Mini-Mental State Examination score\u00a0=\u00a022.9 (3.4)].\n\nParticipants were randomized and individually trained 3 times a week during 12\u00a0weeks. The Evaluative Frailty Index for Physical activity (EFIP) was used to assess the level of frailty at baseline and after the 12-week intervention period. Between-group differences were analyzed with analysis of covariance.\n\nThe exergame group showed a trend toward higher adherence compared to the aerobic group (87.3% vs 81.1%, P\u00a0=\u00a0.05). A significant reduction on the EFIP was found in the exergame group (EG) compared to the active control group (CG) [mean difference (95% confidence interval) between EG and CG:\u00a0-0.034 [-0.062,\u00a0-0.007], P\u00a0=\u00a0.012], with a small-to-moderate effect size (partial \u03b7\n\nThis is the first study to show that a 12-week exergame intervention reduces the level of frailty in people with dementia. This is an important and promising result, because frailty is a powerful predictor for adverse health outcomes, and its reduction may have positive effects on health status. Moreover, exergaming resulted in high adherence rates of physical exercise, which makes it an effective strategy to engage people with dementia in physical activity.", "PMID": "31409559"}, {"title": "The Effectiveness of a Virtual Reality-Based Intervention on Cognitive Functions in Older Adults with Mild Cognitive Impairment: A Single-Blind, Randomized Controlled Trial.", "abstract": "", "PMID": "33058735"}, {"title": "The efficacy of exergaming in people with major neurocognitive disorder residing in long-term care facilities: a pilot randomized controlled trial.", "abstract": "It is currently unknown whether exergaming is efficacious in people with major neurocognitive disorder (MNCD) residing in long-term care facilities. This pilot randomized controlled trial (RCT) explored the efficacy of a stepping exergame program on gait speed, balance, mobility, reaction time, cognitive and neuropsychiatric outcomes, quality of life, and daily life functioning in people with MNCD residing in long-term care facilities.\n\nParticipants were randomly assigned to 8\u00a0weeks, three times weekly, 15\u2009min of exergaming versus watching preferred music videos. The exergame device consisted of a pressure-sensitive step training platform on which participants performed stepping movements to play the games. The device automatically adapted the training level to the participants' capabilities. The Short Physical Performance Battery (SPPB), step reaction time test (SRTT), Montr\u00e9al Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), Cornell Scale for Depression in Dementia (CSDD), Dementia Quality of Life (DQoL), and Katz Activities of Daily Living (Katz ADL) were assessed at baseline and post-intervention. A Quade's non-parametric ANCOVA controlling for baseline values with post hoc Bonferroni correction (p\u2009<\u20090.00625) was used to analyze pre- and post-differences between the groups. Partial eta-squared (\u03b7\n\nForty-five of 55 randomized inpatients with mild to moderate MNCD (Mini-Mental State Examination score\u2009=\u200917.2\u2009\u00b1\u20094.5; aged 70-91; 35 women) completed the study. The exergame group (n\u2009=\u200923) demonstrated improvements in gait speed (p\u2009<\u20090.001, \u03b7\n\nThe findings of this pilot RCT suggest that an individually adapted exergame training improves lower extremity functioning, cognitive functioning and step reaction time and symptoms of depression in inpatients with MNCD residing in long-term care facilities.\n\nClinicalTrials.gov, NCT04436302.", "PMID": "33785077"}, {"title": "Efficacy of serious exergames in improving neuropsychiatric symptoms in neurocognitive disorders: Results of the X-TORP cluster randomized trial.", "abstract": "The aim of this study was to evaluate the efficacy of a serious exergame in improving the neuropsychiatric symptoms of patients with neurocognitive disorders.\n\nX-Torp is a serious exergame combining motor and cognitive activities. Ninety-one subjects (mean age\u00a0=\u00a081.7 years, mean Mini-Mental State Examination\u00a0=\u00a018.3) were recruited in 16 centers. Centers were randomized into intervention and control centers. Subjects underwent assessment for cognitive and behavioral symptoms at baseline (BL), the end of the intervention (W12), and 12\u00a0weeks after the end of the intervention (W24).\n\nThe comparison of neuropsychiatric symptoms between BL and W12 and W24 showed that subjects of the intervention group improved in apathy between BL and W12. Mixed analysis (time BL, W12, W24 x group) indicated a significant increase in apathy and neuropsychiatric symptoms in the control subjects.\n\nThe use of X-Torp improved neuropsychiatric symptoms, particularly apathy. Future studies should more consistently use behavioral and neuropsychiatric symptoms as outcome measures.", "PMID": "34013018"}, {"title": "Exergaming and older adult cognition: a cluster randomized clinical trial.", "abstract": "Dementia cases may reach 100 million by 2050. Interventions are sought to curb or prevent cognitive decline. Exercise yields cognitive benefits, but few older adults exercise. Virtual reality-enhanced exercise or \"exergames\" may elicit greater participation.\n\nTo test the following hypotheses: (1) stationary cycling with virtual reality tours (\"cybercycle\") will enhance executive function and clinical status more than traditional exercise; (2) exercise effort will explain improvement; and (3) brain-derived neurotrophic growth factor (BDNF) will increase.\n\nMulti-site cluster randomized clinical trial (RCT) of the impact of 3 months of cybercycling versus traditional exercise, on cognitive function in older adults. Data were collected in 2008-2010; analyses were conducted in 2010-2011.\n\n102 older adults from eight retirement communities enrolled; 79 were randomized and 63 completed.\n\nA recumbent stationary ergometer was utilized; virtual reality tours and competitors were enabled on the cybercycle.\n\nExecutive function (Color Trails Difference, Stroop C, Digits Backward); clinical status (mild cognitive impairment; MCI); exercise effort/fitness; and plasma BDNF.\n\nIntent-to-treat analyses, controlling for age, education, and cluster randomization, revealed a significant group X time interaction for composite executive function (p=0.002). Cybercycling yielded a medium effect over traditional exercise (d=0.50). Cybercyclists had a 23% relative risk reduction in clinical progression to MCI. Exercise effort and fitness were comparable, suggesting another underlying mechanism. A significant group X time interaction for BDNF (p=0.05) indicated enhanced neuroplasticity among cybercyclists.\n\nCybercycling older adults achieved better cognitive function than traditional exercisers, for the same effort, suggesting that simultaneous cognitive and physical exercise has greater potential for preventing cognitive decline.\n\nThis study is registered at Clinicaltrials.gov NCT01167400.", "PMID": "22261206"}, {"title": "Wii-fit for improving gait and balance in an assisted living facility: a pilot study.", "abstract": "Objectives. To determine the effects on balance and gait of a Wii-Fit program compared to a walking program in subjects with mild Alzheimer's dementia (AD). Methods. A prospective randomized (1\u2009:\u20091) pilot study with two intervention arms was conducted in an assisted living facility with twenty-two mild AD subjects. In both groups the intervention occurred under supervision for 30 minutes daily, five times a week for eight weeks. Repeated measures ANOVA and paired t-tests were used to analyze changes. Results. Both groups showed improvement in Berg Balance Scale (BBS), Tinetti Test (TT) and Timed Up and Go (TUG) over 8 weeks. However, there was no statistically significant difference between the groups over time. Intragroup analysis in the Wii-Fit group showed significant improvement on BBS (P = 0.003), and TT (P = 0.013). The walking group showed a trend towards improvement on BBS (P = 0.06) and TUG (P = 0.07) and significant improvement in TT (P = 0.06). Conclusion. This pilot study demonstrates the safety and efficacy of Wii-Fit in an assisted living facility in subjects with mild AD. Use of Wii-Fit resulted in significant improvements in balance and gait comparable to those in the robust monitored walking program. These results need to be confirmed in a larger, methodologically sound study.", "PMID": "22745909"}, {"title": "V-TIME: a treadmill training program augmented by virtual reality to decrease fall risk in older adults: study design of a randomized controlled trial.", "abstract": "Recent work has demonstrated that fall risk can be attributed to cognitive as well as motor deficits. Indeed, everyday walking in complex environments utilizes executive function, dual tasking, planning and scanning, all while walking forward. Pilot studies suggest that a multi-modal intervention that combines treadmill training to target motor function and a virtual reality obstacle course to address the cognitive components of fall risk may be used to successfully address the motor-cognitive interactions that are fundamental for fall risk reduction. The proposed randomized controlled trial will evaluate the effects of treadmill training augmented with virtual reality on fall risk.\n\nThree hundred older adults with a history of falls will be recruited to participate in this study. This will include older adults (n=100), patients with mild cognitive impairment (n=100), and patients with Parkinson's disease (n=100). These three sub-groups will be recruited in order to evaluate the effects of the intervention in people with a range of motor and cognitive deficits. Subjects will be randomly assigned to the intervention group (treadmill training with virtual reality) or to the active-control group (treadmill training without virtual reality). Each person will participate in a training program set in an outpatient setting 3 times per week for 6 weeks. Assessments will take place before, after, and 1 month and 6 months after the completion of the training. A falls calendar will be kept by each participant for 6 months after completing the training to assess fall incidence (i.e., the number of falls, multiple falls and falls rate). In addition, we will measure gait under usual and dual task conditions, balance, community mobility, health related quality of life, user satisfaction and cognitive function.\n\nThis randomized controlled trial will demonstrate the extent to which an intervention that combines treadmill training augmented by virtual reality reduces fall risk, improves mobility and enhances cognitive function in a diverse group of older adults. In addition, the comparison to an active control group that undergoes treadmill training without virtual reality will provide evidence as to the added value of addressing motor cognitive interactions as an integrated unit.\n\n(NIH)-NCT01732653.", "PMID": "23388087"}], "labels": [{"PMID": "24452845", "label": "included"}, {"PMID": "28726492", "label": "included"}, {"PMID": "30611286", "label": "included"}, {"PMID": "31409559", "label": "included"}, {"PMID": "33058735", "label": "included"}, {"PMID": "33785077", "label": "included"}, {"PMID": "34013018", "label": "included"}, {"PMID": "22261206", "label": "excluded"}, {"PMID": "22745909", "label": "excluded"}, {"PMID": "23388087", "label": "excluded"}]}
{"metadata": {"review_pmid": "39254048"}, "inputs": {"background": "In recent years a broader range of immunomodulatory and immunosuppressive treatment options have emerged for people with progressive forms of multiple sclerosis (PMS). While consensus supports these options as reducing relapses, their relative benefit and safety profiles remain unclear due to a lack of direct comparison trials.", "objectives": "To compare through network meta-analysis the efficacy and safety of alemtuzumab, azathioprine, cladribine, cyclophosphamide, daclizumab, dimethylfumarate, diroximel fumarate, fingolimod, fludarabine, glatiramer acetate, immunoglobulins, interferon beta 1-a and beta 1-b, interferon beta-1b (Betaferon), interferon beta-1a (Avonex, Rebif), laquinimod, leflunomide, methotrexate, minocycline, mitoxantrone, mycophenolate mofetil, natalizumab, ocrelizumab, ofatumumab, ozanimod, pegylated interferon beta-1a, ponesimod, rituximab, siponimod, corticosteroids, and teriflunomide for PMS.", "selection criteria": "Randomised controlled trials (RCTs) that studied one or more treatments as monotherapy, compared to placebo or to another active agent, for use in adults with PMS."}, "context": [{"title": "Randomized controlled trial of interferon- beta-1a in secondary progressive MS: Clinical results.", "abstract": "The beneficial effect of interferon beta on exacerbations in relapsing-remitting MS has been demonstrated repeatedly, but results concerning disability vary.\n\nThis multicenter, randomized, parallel-group, placebo-controlled study tested two doses of interferon beta-1a in patients with secondary progressive MS, which may include relapses but is dominated by accumulating disability.\n\nA total of 618 patients received subcutaneous placebo or interferon beta-1a, 22 or 44 microg three times weekly for 3 years. Patients were assessed every 3 months.\n\nThe primary outcome, time to confirmed progression in disability, was not significantly affected by treatment (hazard ratio, 0.83; 95% CI, 0.65 to 1.07; p = 0.146 for 44 microg versus placebo). Relapse rate was reduced from 0.71 per year with placebo to 0.50 per year with treatment (p < 0.001 for both doses). Significant treatment effects were seen on other exacerbation-related outcomes and on a composite measure incorporating five separate clinical and MRI outcomes. The hazard ratio for time to progression for the combined interferon beta-1a groups compared with placebo was 0.74 among patients reporting relapses in the 2 years before study (p = 0.055), and 1.01 for those without prestudy relapses (p = 0.934). An unexpected treatment-by-sex interaction favored women. The drug was well tolerated.\n\nTreatment with interferon beta-1a did not significantly affect disability progression in this cohort, although significant treatment benefit was observed on exacerbation-related outcomes. Exploratory post hoc analyses suggested greater benefit in women and in patients who had reported at least one relapse in the 2 years before the study.", "PMID": "11402106"}, {"title": "Benefit of interferon beta-1a on MSFC progression in secondary progressive MS.", "abstract": "Interferon beta-1a (IFNbeta-1a, Avonex) is efficacious in relapsing forms of MS. Studies of other IFNbeta preparations in secondary progressive MS (SPMS) yielded conflicting results. This study was undertaken to determine whether IFNbeta-1a slowed disease progression in SP-MS.\n\nA total of 436 subjects with SPMS and Expanded Disability Status Scale (EDSS) score 3.5 to 6.5 were randomized to receive IFNbeta-1a (60 micro g) or placebo by weekly intramuscular injection for 2 years. The primary outcome measure, used for the first time in a large-scale MS trial, was baseline to month 24 change in the MS Functional Composite (MSFC), comprising quantitative tests of ambulation (Timed 25-Foot Walk), arm function (Nine-Hole Peg Test [9HPT]), and cognition (Paced Auditory Serial Addition Test [PASAT]).\n\nMedian MSFC Z-score change was reduced 40.4% in IFNbeta-1a subjects (-0.096 vs -0.161 in placebo subjects, p = 0.033), an effect driven mainly by the 9HPT and PASAT. There was no discernible benefit on the EDSS, which in this range principally reflects walking ability. IFNbeta-1a subjects had 33% fewer relapses (p = 0.008). There was significant benefit on eight of 11 MS Quality of Life Inventory subscales. New or enlarging T2-hyperintense brain MRI lesions and gadolinium-enhancing lesions were reduced at months 12 and 24 (both p < 0.001). IFNbeta-1a was well tolerated by the majority of subjects. Neutralizing antibodies developed in 3.3% of IFNbeta-1a-treated subjects.\n\nIFNbeta-1a demonstrated benefit on MSFC progression, relapses, quality of life, and MRI activity in SPMS.", "PMID": "12221157"}, {"title": "Interferon beta-1a in primary progressive MS: an exploratory, randomized, controlled trial.", "abstract": "Patients with primary progressive MS have atypical clinical and MRI characteristics and have been excluded from most therapeutic trials. The authors report a randomized, controlled trial restricted to primary progressive MS.\n\nFifty subjects were randomized to weekly IM interferon beta-1a 30 microg, 60 microg, or placebo for 2 years. The primary endpoint was time to sustained progression in disability. Secondary outcomes included the timed 10-meter walk, nine-hole peg test, and on MRI, T2 and T1 brain lesion loads and brain and spinal cord atrophy.\n\nThe 30- microg dose of interferon beta-1a was well tolerated, but the 60- microg dose caused severe flulike reactions and raised liver enzymes. No treatment effect was seen on the primary endpoint. Subjects on interferon beta-1a 30 microg had a lower rate of accumulation of T2 lesion load than controls (p = 0.025); subjects on 60 microg had a greater rate of ventricular enlargement than controls (p = 0.025).\n\nThis study has demonstrated that interferon beta-1a 30 microg was well tolerated, identified useful outcome measures, but showed no efficacy on the primary outcome measure or on most of the secondary outcome measures.", "PMID": "12525716"}, {"title": "Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial.", "abstract": "Treatment options for patients with secondary progressive multiple sclerosis are few. Encouraging results in open-label studies prompted this randomised trial of mitoxantrone in such patients.\n\n194 patients with worsening relapsing-remitting or secondary progressive multiple sclerosis were assigned placebo or mitoxantrone (5 mg/m(2) [exploratory group] or 12 mg/m(2) intravenously) every 3 months for 24 months. Clinical assessments were made every 3 months for 24 months. The primary endpoint was a multivariate analysis of five clinical measures. Analyses of mitoxantrone 12 mg/m(2) versus placebo were based on patients who received at least one dose and returned for at least one assessment of efficacy.\n\nOf 194 patients enrolled, 188 were able to be assessed at 24 months. There were no drug-related serious adverse events or evidence of clinically significant cardiac dysfunction. At 24 months, the mitoxantrone group experienced benefits compared with the placebo group for the primary outcome (difference 0.30 [95% CI 0.17-0.44]; p<0.0001) and the preplanned univariate analyses of those measures: change in expanded disability status scale (0.24 [0.04-0.44]; p=0.0194), change in ambulation index (0.21 [0.02-0.40]; p=0.0306), adjusted total number of treated relapses (0.38 [0.18-0.59]; p=0.0002), time to first treated relapse (0.44 [0.20-0.69]; p=0.0004), and change in standardised neurological status (0.23 [0.03-0.43]; p=0.0268).\n\nMitoxantrone 12 mg/m(2) was generally well tolerated and reduced progression of disability and clinical exacerbations. Further studies are needed to identify the patients with these forms of multiple sclerosis who are most likely to respond to therapy, the best treatment protocols, and the frequency of long-term drug-related side-effects.", "PMID": "12504397"}, {"title": "Multiple sclerosis. Trials of maintenance treatment with prednisolone and soluble aspirin.", "abstract": "", "PMID": "13770773"}, {"title": "The Canadian cooperative trial of cyclophosphamide and plasma exchange in progressive multiple sclerosis. The Canadian Cooperative Multiple Sclerosis Study Group.", "abstract": "To find out whether non-specific immunosuppression is beneficial in multiple sclerosis (MS) a randomised, placebo-controlled, single-masked trial was carried out in nine university centres. 168 patients with clinically or laboratory-supported definite MS in progressive phase (deterioration by at least 1.0 on the expanded disability status scale [EDSS] in the previous year) were randomised to receive intravenous cyclophosphamide and oral prednisone (n = 55); daily oral cyclophosphamide, alternate day prednisone (22 weeks), and weekly plasma exchange (20 weeks) (n = 57); or placebo medications and sham plasma exchange (n = 56). All patients were followed for at least 12 months (mean 30.4 months) by a monitoring neurologist, who was aware of treatment allocation, and an evaluating neurologist, who was not. The primary analysis was a comparison of rates of treatment failure (worsening of evaluating neurologist's assessment of EDSS by 1.0 or more on two consecutive 6-monthly assessments). There were no significant differences among the groups in this primary analysis (19 [35%] treatment failures with cyclophosphamide; 18 [32%] with plasma exchange; 16 [29%] with placebo). Nor were there any differences in the proportions improved, stabilised, or worsened at each 6 month assessment or in the mean change in the EDSS at the final assessment (0.81 cyclophosphamide; 0.69 plasma exchange; 0.69 placebo). A slight trend favouring the plasma exchange group at 12-24 months of follow-up was not sustained at the final assessment. This study fails to confirm previous reports that immunosuppressive treatments result in stabilisation or improvement in progressive MS.", "PMID": "1671468"}, {"title": "A 10-year follow-up of the European multicenter trial of interferon \u03b2-1b in secondary-progressive multiple sclerosis.", "abstract": "To explore long-term effects of treatment and prognostic relevance of variables assessed at baseline and during the European secondary progressive multiple sclerosis (SPMS) trial of interferon beta 1b (IFNB-1b).\n\nWe assessed 362 patients (60% female; median age 41 years; Expanded Disability Status Scale (EDSS): 5.5; 51% randomized to IFNB-1b) for their EDSS and treatment history after 10 years. Non-parametric analysis of covariance (ANCOVA) and multivariate linear regression models were applied.\n\nMedian EDSS was 6.0 at the end of the randomized controlled trial (RCT), in the IFNB-1b and placebo groups, and 7.0 in long-term follow-up patients (those receiving IFNB-1b in the RCT were 6.5 and those receiving placebo in the RCT were 7.0; p = 0.086). 24 patients (6.6%) were deceased. The EDSS at baseline and the EDSS change during the RCT were the most important predictors of the EDSS 10 years later (partial R(2): 0.47). The ability to predict changes in EDSS 10 years after the RCT was limited (R(2): 0.12). Magnetic resonance imaging (MRI) measures remained in the predictive models, but explained < 5% of the variability.\n\nThe results from this analysis did not provide convincing evidence to support a favorable long-term outcome in those patients allocated IFNB-1b during the RCT, in our SPMS cohort. The progressive stage of the disease remains largely unpredictable by clinical and conventional MRI measures, so better prognostic markers are needed.", "PMID": "26362898"}, {"title": "Double-masked trial of azathioprine in multiple sclerosis. British and Dutch Multiple Sclerosis Azathioprine Trial Group.", "abstract": "354 patients with multiple sclerosis were randomised to receive either azathioprine 2.5 mg/kg daily or placebo in a double-masked trial. During follow-up of at least 3 years only small differences emerged between the groups. After 3 years the mean deterioration in Kurtzke disability score was 0.62 in the azathioprine group and 0.80 in the placebo group, a difference of 0.18 (95% confidence intervals [CI] -0.15 to +0.52) and in the ambulation index it was 0.84 and 1.25, respectively, difference 0.41 (95% CI 0.03 to 0.80). After 3 years there had been slightly fewer relapses in the azathioprine group (average 2.2) than in the placebo group (average 2.5) but the difference of 0.3 (95% CI -0.2 to +0.9) was not significant. Although the results favour a small beneficial effect from azathioprine the benefit is so small that the use of azathioprine cannot be generally recommended for most patients with multiple sclerosis. Analysis of subgroups (by sex, age, severity, rate of progression, HLA status, relapsing or progressive course) has not revealed any that have shown clear clinical benefit.", "PMID": "2899660"}, {"title": "Evaluation of no evidence of progression or active disease (NEPAD) in patients with primary progressive multiple sclerosis in the ORATORIO trial.", "abstract": "No evidence of progression or active disease (NEPAD) is a novel combined endpoint defined by the absence of both progression and inflammatory disease activity in primary progressive multiple sclerosis (PPMS). In the placebo-controlled phase III ORATORIO study (NCT01194570), we investigated the effect of ocrelizumab on this comprehensive outcome and its components in a post-hoc analysis.\n\nThe proportion of patients with NEPAD (no evidence of progression [NEP; no 12-week confirmed progression of \u22651/\u22650.5 points on the Expanded Disability Status Scale if the baseline score was \u22645.5/>5.5 points, respectively; no 12-week confirmed progression of \u226520% on the Timed 25-Foot Walk test and 9-Hole Peg Test], no brain magnetic resonance imaging activity [no new/enlarging T2 lesions and no T1 gadolinium-enhancing lesions], and no protocol-defined relapse) from baseline to week 120 was determined in ocrelizumab- (600\u2009mg; n\u2009=\u2009465) and placebo-treated (n\u2009=\u2009234) patients.\n\nThe majority of ORATORIO study patients with PPMS experienced clinical progression or evidence of disease activity. From baseline to week 120, 29.9% and 42.7% ocrelizumab-treated compared to 9.4% and 29.1% placebo-treated patients maintained NEPAD (relative risk [95% confidence interval {CI}], 3.15 [2.07-4.79]; p\u2009<\u20090.001) and NEP (relative risk [95% CI], 1.47 [1.17-1.84]; p\u2009<\u20090.001), respectively. Effects on the individual components of both measures were consistent with the compound outcomes.\n\nCompared to placebo, ocrelizumab enhanced 3-fold the proportion of PPMS patients with no evidence of either progression or inflammatory disease activity. NEPAD may represent a sensitive and meaningful comprehensive measure of disease control in patients with PPMS. Ann Neurol 2018;84:527-536.", "PMID": "30155979"}, {"title": "Ocrelizumab reduces progression of upper extremity impairment in patients with primary progressive multiple sclerosis: Findings from the phase III randomized ORATORIO trial.", "abstract": "Upper extremity (UE) impairment is common with primary progressive multiple sclerosis (PPMS).\n\nThis exploratory analysis examined the effects of ocrelizumab on confirmed progression (CP) and confirmed improvement (CI) in UE impairment in patients from ORATORIO.\n\nPatients with PPMS received ocrelizumab 600\u2009mg or placebo every 24\u2009weeks for \u2a7e120\u2009weeks. The Nine-Hole Peg Test (9HPT) was administered at baseline (BL) and every 12\u2009weeks thereafter. Prespecified exploratory endpoints included change in 9HPT time and proportion of patients with CP of \u2a7e20% in 9HPT. Analysis populations included intention-to-treat (ITT) patients and subgroups stratified by BL 9HPT time and Expanded Disability Status Scale. Post hoc analyses included the proportion of patients achieving more severe thresholds of CP and the proportion achieving CI in 9HPT.\n\nAmong ITT patients, ocrelizumab significantly reduced the change in 9HPT time over 120\u2009weeks, the risk of CP of \u2a7e20% in 9HPT time for both hands and the risk of more severe 9HPT progression versus placebo. Numerical trends also favoured ocrelizumab versus placebo with respect to achieving CI. Consistent directional trends were observed in subgroup analyses.\n\nOcrelizumab reduces the risk of UE disability progression and may increase the possibility of improvement versus placebo in PPMS.", "PMID": "30415593"}], "labels": [{"PMID": "11402106", "label": "included"}, {"PMID": "12221157", "label": "included"}, {"PMID": "12525716", "label": "included"}, {"PMID": "12504397", "label": "excluded"}, {"PMID": "13770773", "label": "excluded"}, {"PMID": "1671468", "label": "excluded"}, {"PMID": "26362898", "label": "excluded"}, {"PMID": "2899660", "label": "excluded"}, {"PMID": "30155979", "label": "included"}, {"PMID": "30415593", "label": "included"}]}
{"metadata": {"review_pmid": "39189465"}, "inputs": {"background": "Healthcare workers sometimes develop their own informal solutions to deliver services. One such solution is to use their personal mobile phones or other mobile devices in ways that are unregulated by their workplace. This can help them carry out their work when their workplace lacks functional formal communication and information systems, but it can also lead to new challenges.", "objectives": "To explore the views, experiences, and practices of healthcare workers, managers and other professionals working in healthcare services regarding their informal, innovative uses of mobile devices to support their work.", "selection criteria": "We included qualitative studies and mixed-methods studies with a qualitative component. We included studies that explored healthcare workers' views, experiences, and practices regarding mobile phones and other mobile devices, and that included data about healthcare workers' informal use of these devices for work purposes."}, "context": [{"title": "Clinicians and their cameras: policy, ethics and practice in an Australian tertiary hospital.", "abstract": "Medical photography illustrates what people would prefer to keep private, is practiced when people are vulnerable, and has the power to freeze a moment in time. Given it is a sensitive area of health, lawful and ethical practice is paramount. This paper recognises and seeks to clarify the possibility of widespread clinician-taken medical photography in a tertiary hospital in northern Australia, examining the legal and ethical implications of this practice. A framework of Northern Territory law, state Department of Health policy and human rights theory were used to argue the thesis. Clinicians from 13 purposively chosen wards were asked to participate in an anonymous survey and confidential in-depth interviews. Questions were generated from the literature and local knowledge on the topics of 'occurrence', 'image use', 'quality of consent', 'cameras and technology', 'confidentiality', 'data storage and security', 'hospital policy and law' and 'cultural issues'. One hundred and seventy surveys and eights interviews were analysed using descriptive statistics and theme and content analysis, then triangulated for similarity, difference and unique responses. Forty-eight percent of clinicians surveyed take medical photographs, with the majority using hospital-owned cameras. However, one-fifth of clinicians reported photographing with personal mobile phones. Non-compliance with written consent requirements articulated in policy was endemic, with most clinicians surveyed obtaining only verbal consent. Labeling, storage, copyright and cultural issues were generally misunderstood, with a significant number of clinicians risking the security of patient information by storing images on personal devices. If this tertiary hospital does not develop a clinical photography action plan to address staff lack of knowledge, and noncompliance with policy and mobile phone use, patients' data is at risk of being distributed into the public domain where unauthorised publication may cause psychological harm and have legal ramifications for th hospital, its patients, and staff.", "PMID": "23777890"}, {"title": "Peer mentors, mobile phone and pills: collective monitoring and adherence in Kenyatta National Hospital's HIV treatment programme.", "abstract": "In 2006, the Kenyan state joined the international commitment to make antiretroviral treatment free in public health institutions to people infected with HIV. Less than a decade later, treatment has reached over 60% of those who need it in Kenya. This paper, which is based on an in-depth ethnographic case study of the HIV treatment programme at Kenyatta National Hospital, conducted intermittently between 2008 and 2014, examines how HIV-positive peer mentors encourage and track adherence to treatment regimens within and beyond the clinic walls using mobile phones and computer technology. This research into the everyday practices of patient monitoring demonstrates that both surveillance and adherence are collective activities. Peer mentors provide counselling services, follow up people who stray from treatment regimens, and perform a range of other tasks related to patient management and treatment adherence. Despite peer mentors' involvement in many tasks key to encouraging optimal adherence, their role is rarely acknowledged by co-workers, hospital administrators, or public health officials. Following a biomedical paradigm, adherence at Kenyatta and in Kenya is framed by programme administrators as something individual clients must do and for which they must be held accountable. This framing simultaneously conceals the sociality of adherence and undervalues the work of peer mentors in treatment programmes. ", "PMID": "25175291"}, {"title": "The use of smartphones on General Internal Medicine wards: a mixed methods study.", "abstract": "To describe the uses of institutional and personal smartphones on General Internal Medicine wards and highlight potential consequences from their use.\n\nA mixed methods study consisting of both quantitative and qualitative research methods was conducted in General Internal Medicine wards across four academic teaching hospitals in Toronto, Ontario. Participants included medical students, residents, attending physicians and allied health professionals. Data collection consisted of work shadowing observations, semi-structured interviews and surveys.\n\nPersonal smartphones were used for both clinical communication and non-work-related activities. Clinicians used their personal devices to communicate with their medical teams and with other medical specialties and healthcare professionals. Participants understood the risks associated with communicating confidential health information via their personal smartphones, but appear to favor efficiency over privacy issues. From survey responses, 9 of 23 residents (39%) reported using their personal cell phones to email or text patient information that may have contained patient identifiers. Although some residents were observed using their personal smartphones for non-work-related activities, personal use was infrequent and most residents did not engage in this activity.\n\nClinicians are using personal smartphones for work-related purposes on the wards. With the increasing popularity of smartphone devices, it is anticipated that an increasing number of clinicians will use their personal smartphones for clinical work. This trend poses risks to the secure transfer of confidential personal health information and may lead to increased distractions for clinicians.", "PMID": "25298819"}, {"title": "Nurses' experiences of using a smart mobile device application to assist home care for patients with chronic disease: a qualitative study.", "abstract": "To examine nurses' experiences regarding the benefits and obstacles of using a smart mobile device application in home care.\n\nThe popularity of mobile phones and Internet technology has established an opportunity for interaction between patients and health care professionals. Line is an application allowing instant communication that is available for free globally. However, the literature relating to use of Line in this area is limited.\n\nA qualitative study involving individual in-depth interviews.\n\nParticipants included community nurses (N\u00a0=\u00a017) from six home care facilities in southern Taiwan who had used Line for home care of chronically ill patients for at least six months. The study was conducted using semi-structured in-depth interviews, which were recorded and converted into transcripts for content analysis.\n\nSeven themes emerged from data analysis: reduction in medical care consumption and costs, reduction in workload and stress, facilitating improvement in the quality of care, promotion of the nurse-patient relationship, perceived risk, lack of organisational incentives and operating procedures and disturbance to personal life.\n\nNurses considered Line valuable for use in home care. While this application has diverse functions, its video transfer function could in particular help nursing staff make prompt decisions about patients' problems and promote nurse-patient relationships. However, there might be hidden risks including legal consequences, safety risks to patients, possible violations of professionalism and increased risk of nurse burnout. Increasing nursing staff awareness of using mobile messaging software applications is necessary.\n\nThis study provides relevant information about the benefits, disadvantages, risks and limitations of nurses' use of Line. The study also provides suggestions for software programmers and future organisational strategy and development.", "PMID": "27136280"}, {"title": "Calling in at work: Acute care nursing cell phone policies.", "abstract": "", "PMID": "27273025"}, {"title": "Who bears the cost of 'informal mhealth'? Health-workers' mobile phone practices and associated political-moral economies of care in Ghana and Malawi.", "abstract": "Africa's recent communications 'revolution' has generated optimism that using mobile phones for health (mhealth) can help bridge healthcare gaps, particularly for rural, hard-to-reach populations. However, while scale-up of mhealth pilots remains limited, health-workers across the continent possess mobile phones. This article draws on interviews from Ghana and Malawi to ask whether/how health-workers are using their phones informally and with what consequences. Health-workers were found to use personal mobile phones for a wide range of purposes: obtaining help in emergencies; communicating with patients/colleagues; facilitating community-based care, patient monitoring and medication adherence; obtaining clinical advice/information and managing logistics. However, the costs were being borne by the health-workers themselves, particularly by those at the lower echelons, in rural communities, often on minimal stipends/salaries, who are required to 'care' even at substantial personal cost. Although there is significant potential for 'informal mhealth' to improve (rural) healthcare, there is a risk that the associated moral and political economies of care will reinforce existing socioeconomic and geographic inequalities.", "PMID": "27476501"}, {"title": "Exploring the use of smartphones and tablets by medical House Officers in Korle-Bu Teaching Hospital.", "abstract": "Smartphones and tablets are being used widely in the Western World creating benefits in healthcare. The Ministry of Health in Ghana has an e-Health strategy, with the aim of integrating such resources into healthcare. Whilst there are numerous mHealth projects going on in Ghana, there is little evidence of doctors using such devices in their practice.\n\nA qualitative study was undertaken in Korle-Bu Teaching Hospital. Random sampling was used to identify House Officers, who engaged in semi-structured interviews. Interviews were recorded, transcribed and analysed using thematic content analysis. Consent was gained from all participants and the University of Leeds granted ethical approval.\n\nThe results demonstrate that current House Officers began using smartphones and tablets at various stages during medical school. Their use has increased since qualification. Although the overall use has increased, some staff remain resistant to the use of smartphones and tablets. In the future, the integration of smartphones and tablets into medical practice can be improved by integration with the medical curriculum and accepted practice.\n\nHouse Officers are routinely using smartphones and tablets to assist them in their daily practice. The use is informal and is peer led. Whilst they bring many benefits, there are issues, which need to be addressed. In Korle-Bu Teaching Hospital integrating smartphone and tablet use into practice is feasible and would prove beneficial.", "PMID": "27605725"}, {"title": "Sociotechnical analysis of nurses' use of personal mobile phones at work.", "abstract": "Nurses' use of personal mobiles phones at work is a growing trend in healthcare organizations. Although recent studies have explored the positive and negative implications of nurses using personal mobile phones at work, none has yet analyzed the interactions of sociotechnical components (users, technology and policy) on nurses' use of personal mobile phones at work.\n\nIdentify sociotechnical interactions by analyzing each sociotechnical component (users, technology and policy) that affects nurses' use of personal mobile phones at work.\n\nIn-depth interviews were conducted with 30 nurses employed in 13 hospitals in the Philippines. The respondents include staff nurses (n=23), charge nurses (n=4), and nurse managers (n=3). Staff nurses were asked on their use of personal mobile phones at work, while charge and nurse managers were asked on their observations regarding staff nurses' use of personal mobile phones at work. Responses were analyzed qualitatively using sociotechnical analysis.\n\nSociotechnical analysis indicated that staff nurses used their personal mobile phones at work in various ways because its use helped in their nursing work, but inevitably altered a few of their routines. Although most hospitals had policies that prohibit the use of mobile phones, staff nurses justified their use of personal mobile phones by using it for work purposes and for the benefit of their patients. Staff nurses highlighted the absence of hospital-provided mobile phones as a key reason for using personal mobile phones at work. Charge nurses and nurse managers also influenced staff nurses' use of personal mobile phones at work.\n\nNurses could use their personal mobile phones at work for work purposes to enhance their clinical performance and improve patient care. Hospital administrators can leverage on nurses' use of personal mobile phones at work by formulating policies that consider both the benefits and potential drawbacks of mobile phone usage. Recommendations are made for the formulation of hospital policies to optimize the use of personal mobile phones of nurses at work.", "PMID": "27697234"}, {"title": "Doctors' use of mobile devices in the clinical setting: a mixed methods study.", "abstract": "Mobile device use has become almost ubiquitous in daily life and therefore includes use by doctors in clinical settings. There has been little study as to the patterns of use and impact this has on doctors in the workplace and how negatively or positively it impacts at the point of care.\n\nTo explore how doctors use mobile devices in the clinical setting and understand drivers for use.\n\nA mixed methods study was used with doctors in a paediatric and adult teaching hospital in 2013. A paper-based survey examined mobile device usage data by doctors in the clinical setting. Focus groups explored doctors' reasons for using or refraining from using mobile devices in the clinical setting, and their attitudes about others' use.\n\nThe survey, completed by 109 doctors, showed that 91% owned a smartphone and 88% used their mobile devices frequently in the clinical setting. Trainees were more likely than consultants to use their mobile devices for learning and accessing information related to patient care, as well as for personal communication unrelated to work. Focus group data highlighted a range of factors that influenced doctors to use personal mobile devices in the clinical setting, including convenience for medical photography, and factors that limited use. Distraction in the clinical setting due to use of mobile devices was a key issue. Personal experience and confidence in using mobile devices affected their use, and was guided by role modelling and expectations within a medical team.\n\nDoctors use mobile devices to enhance efficiency in the workplace. In the current environment, doctors are making their own decisions based on balancing the risks and benefits of using mobile devices in the clinical setting. There is a need for guidelines around acceptable and ethical use that is patient-centred and that respects patient privacy.", "PMID": "27925381"}, {"title": "Nurses' use of mobile instant messaging applications: A uses and gratifications perspective.", "abstract": "To explore how and why mobile instant messaging applications are used by Filipino nurses as part of their work.\n\nGuided by the uses and gratifications theory, in-depth interviews with 20 staff nurses working in 9 hospitals (ie, 4 private and 5 public hospitals) in the Philippines were conducted in July 2015. Interview data were analysed through a phenomenological perspective to thematic analysis.\n\nResults show that mobile instant messaging applications such as Facebook Messenger and Viber were mostly used by staff nurses and these were accessed using their own smartphones. Thematic analysis indicates that they were used to meet staff nurses' need for information exchange, socialization, and catharsis. Moreover, user interactions vary depending on members within a chat group. For instance, communication via mobile instant messaging applications are much formal when superiors are included in a chat group.\n\nIn general, the results show that mobile instant messaging applications are routinely used by Filipino staff nurses not only for clinical purposes (ie, information exchange) but also for non-clinical purposes (ie, socialization and catharsis). This paper ends with several practical and theoretical implications including future research directions.", "PMID": "28752519"}], "labels": [{"PMID": "23777890", "label": "included"}, {"PMID": "25175291", "label": "included"}, {"PMID": "25298819", "label": "included"}, {"PMID": "27136280", "label": "included"}, {"PMID": "27273025", "label": "included"}, {"PMID": "27476501", "label": "included"}, {"PMID": "27605725", "label": "included"}, {"PMID": "27697234", "label": "included"}, {"PMID": "27925381", "label": "included"}, {"PMID": "28752519", "label": "included"}]}
{"metadata": {"review_pmid": "39132734"}, "inputs": {"background": "Atopic dermatitis (eczema), can have a significant impact on well-being and quality of life for affected people and their families. Standard treatment is avoidance of triggers or irritants and regular application of emollients and topical steroids or calcineurin inhibitors. Thorough physical and psychological assessment is central to good-quality treatment. Overcoming barriers to provision of holistic treatment in dermatological practice is dependent on evaluation of the efficacy and economics of both psychological and educational interventions in this participant group. This review is based on a previous Cochrane review published in 2014, and now includes adults as well as children.", "objectives": "To assess the clinical outcomes of educational and psychological interventions in children and adults with atopic dermatitis (eczema) and to summarise the availability and principal findings of relevant economic evaluations.", "selection criteria": "Randomised, cluster-randomised and cross-over RCTs that assess educational and psychological interventions for treating eczema in children and adults."}, "context": [{"title": "Evaluation of massage with essential oils on childhood atopic eczema.", "abstract": "Childhood atopic eczema is an increasingly common condition in young children. As well as being irritating to the child, it causes sleepless nights for both the child and the family and leads to difficulties in parental relationships and can have severe effects on employment. A group of eight children, born to professional working mothers were studied to test the hypothesis that massage with essential oils (aromatherapy) used as a complementary therapy in conjunction with normal medical treatment, would help to alleviate the symptoms of childhood atopic eczema. The children were randomly allocated to the massage with essential oils group and both counselled and massaged with a mixture of essential oils by the therapist once a week and the mother every day over a period of 8 weeks. The preferred essential oils, chosen by the mothers for their child, from 36 commonly used aromatherapy oils, were: sweet marjoram, frankinsence, German chamomile, myrrh, thyme, benzoin, spike lavender and Litsea cubeba. A control group of children received the counselling and massage without essential oils. The treatments were evaluated by means of daily day-time irritation scores and night time disturbance scores, determined by the mother before and during the treatment, both over an 8 week period; finally general improvement scores were allocated 2 weeks after the treatment by the therapist, the general practitioner and the mother. The study employed a single case experimental design across subjects, such that there were both a within-subject control and between-subjects control, through the interventions being introduced at different times. The results showed a significant improvement in the eczema in the two groups of children following therapy, but there was no significant difference in improvement shown between the aromatherapy massage and massage only group. Thus there is evidence that tactile contact between mother and child benefits the symptoms of atopic eczema but there is no proof that adding essential oils is more beneficial than massage alone. Further studies on the essential oil massage group showed a deterioration in the eczematous condition after two further 8 week periods of therapy, following a period of rest after the initial period of contact. This may have been due to a decline in the novelty of the treatment, or, it strongly suggests possible allergic contact dermatitis provoked by the essential oils themselves. The results of this study indicate the necessity of prolonged studies with novel plant extracts as short-term beneficial results could be overturned by adverse effects after repeated usage.", "PMID": "10960901"}, {"title": "A randomized controlled trial of nurse follow-up clinics: do they help patients and do they free up consultants' time?", "abstract": "Nurse follow-up clinics have become increasingly popular in recent years. Their impact on service delivery within dermatology may be useful in relation to chronic diseases, where education and treatment concordance are important factors in disease management.\n\nTo assess the impact of providing a nurse follow-up clinic in addition to the normal service provided by the dermatology outpatient department at Queen's Medical Centre, Nottingham, and to obtain pilot data with which to inform future study design.\n\nNewly referred patients aged >/= 14 years and with a diagnosis of either eczema or psoriasis were identified. In a randomized, parallel-group study with a follow-up period of 6 weeks, participants were randomized either to normal care, or to receive an additional session with a dermatology nurse specialist immediately after their consultation with the dermatologist. The primary outcome measure was change in quality of life at 6 weeks, as assessed by the Dermatology Life Quality Index (DLQI). Secondary outcomes comprised a comparison of patient knowledge at 6 weeks and the number of consultations (in secondary and primary care) that occurred during the 6-week follow-up period.\n\nBoth groups improved by approximately 3 points on the DLQI scale after 6 weeks. The between-group difference was 0.27 (95% confidence interval - 2.3 to 2.8, P = 0.83). Patients who had seen the nurse were more likely to know how long they should apply treatment (P = 0.05). There was also a marked difference in patients' understanding of how to obtain a repeat prescription (P = 0.01) and from whom they could receive further support (P < 0.001). Following the addition of this service, 33% of follow-up appointments with a doctor were cancelled in the nurse intervention group.\n\nDermatology nurses can add to a dermatology consultation and provide effective patient education and support in managing a skin condition. With this added service nurses could help to free up dermatologists' time, thus allowing them to see more new patients. Cost-effectiveness studies are now needed.", "PMID": "12207593"}, {"title": "Complementary psychocutaneous therapies in dermatology.", "abstract": "The skin and the nervous system develop side by side in the fetus and remain intimately interconnected and interactive throughout life. Because of the skin-nervous system interactions, there is a significant psychosomatic or behavioral component to many dermatologic conditions. This permits complementary nonpharmacologic psychotherapeutic interventions, such as acupuncture, aromatherapy, biofeedback, cognitive-behavioral therapy, hypnosis, placebo, and suggestion, to have positive impacts on many dermatologic diseases. Complementary pharmacologic psychotherapeutic interventions, such as herbs and supplements, also may help improve some dermatologic disorders.", "PMID": "16112450"}, {"title": "Classical conditioning and expectancy in placebo hypoalgesia: a randomized controlled study in patients with atopic dermatitis and persons with healthy skin.", "abstract": "The effectiveness of placebos is unchallenged. However, it is still not clear on which mechanisms the placebo effect is based. Besides expectancy theories, classical conditioning is discussed as a major explanatory model. In an experimental conditioning design we tested 96 participants, 48 with atopic dermatitis (24 male, 24 female) and 48 with healthy skin (24 male and 24 female). All of them received a neutral ointment with a different briefing (\"pain-reducing ointment\" versus \"neutral ointment\"). Electrical pain stimuli were subsequently applied, which selectively induce a painful sensation. In the case of the learning condition (classical conditioning) and unbeknown to the participants, the intensity of the pain stimulus was reduced by 50% after the ointment had been applied. The study addressed the question whether the pain experienced by the patients with atopic dermatitis could be reduced through a placebo effect and whether the placebo effect was achieved through expectancy or through a process of classical conditioning or both. The results indicate that a placebo effect is achieved via expectancy and classical conditioning. However, conditioning processes seem to be necessary for a longer lasting effect. The extent of this effect seemed to be greater in atopics than in healthy controls. Expectancy, achieved through verbal instruction, might also be seen as a conditioned stimulus that reactivates earlier stimulus associations.", "PMID": "17030095"}, {"title": "Web-based consultations for parents of children with atopic dermatitis: results of a randomized controlled trial.", "abstract": "To analyse how web-based consultations for parents of children with atopic dermatitis affect self-management behaviour, health outcome, health resource use and family costs.\n\nNinety-eight children with atopic dermatitis were randomly assigned to intervention and control groups. The intervention group received remote dermatology consultations through a secure web-based communication system. The control group was encouraged to seek treatment through traditional means such as general practitioner visits and hospital care. Both groups received an extensive individual educational session prior to the intervention.\n\nThirty-eight percent of the intervention group used web-based consultations 158 times ranging from 1 to 38 consultations per patient. We found no change in self-management behaviour, health outcome or costs. The intervention group tended to have fewer visits to practitioners offering complementary therapies than the control group, and we found a positive correlation between emergency visits at baseline and messages sent. Both groups, however, reduced the mean number of skin care treatments performed per week and had fewer total health care visits after the intervention.\n\nWe found no effect of supplementing traditional treatment for childhood dermatitis with web-based consultations. This study showed that web consultations is feasible, but more research is needed to determine its effect on self-management skills, health outcome and resource use.", "PMID": "18795905"}, {"title": "Effects of virtual reality immersion and audiovisual distraction techniques for patients with pruritus.", "abstract": "Virtual reality immersion (VRI), an advanced computer-generated technique, decreased subjective reports of pain in experimental and procedural medical therapies. Furthermore, VRI significantly reduced pain-related brain activity as measured by functional magnetic resonance imaging. Resemblance between anatomical and neuroendocrine pathways of pain and pruritus may prove VRI to be a suitable adjunct for basic and clinical studies of the complex aspects of pruritus.\n\nTo compare effects of VRI with audiovisual distraction (AVD) techniques for attenuation of pruritus in patients with atopic dermatitis and psoriasis vulgaris.\n\nTwenty-four patients suffering from chronic pruritus - 16 due to atopic dermatitis and eight due to psoriasis vulgaris - were randomly assigned to play an interactive computer game using a special visor or a computer screen. Pruritus intensity was self-rated before, during and 10 min after exposure using a visual analogue scale ranging from 0 to 10. The interviewer rated observed scratching on a three-point scale during each distraction program.\n\nStudent's t tests were significant for reduction of pruritus intensity before and during VRI and AVD (P=0.0002 and P=0.01, respectively) and were significant only between ratings before and after VRI (P=0.017). Scratching was mostly absent or mild during both programs.\n\nVRI and AVD techniques demonstrated the ability to diminish itching sensations temporarily. Further studies on the immediate and late effects of interactive computer distraction techniques to interrupt itching episodes will open potential paths for future pruritus research.", "PMID": "19714267"}, {"title": "A randomized controlled trial in children with eczema: nurse practitioner vs. dermatologist.", "abstract": "Background We hypothesized that a nurse practitioner would improve the quality of life of a child with eczema more than a dermatologist because of a structured intervention and more consultation time. Objectives To compare the level of care by nurse practitioners with that by dermatologists in children with eczema. Methods New referrals aged < or = 16 years with a diagnosis of eczema were recruited. In a randomized, parallel-group study with a follow-up period of 1 year, 160 participants were randomized either to conventional care from a dermatologist or to care from a nurse practitioner. The primary outcome measure was change in quality of life at 12 months, as assessed by the Infants' Dermatitis Quality of Life Index (IDQOL) for children aged < or = 4 years, and by the illustrated version of the Children's Dermatology Life Quality Index (CDLQI) for children aged 4-16 years. Secondary outcomes were changes in IDQOL and CDLQI at 4 and 8 months, family impact of childhood atopic dermatitis (Dermatitis Family Impact Questionnaire, DFI), eczema severity (objective SCORAD) and patient satisfaction (Client Satisfaction Questionnaire-8, CSQ-8) at 4, 8 and 12 months. Results The mean IDQOL in the dermatologist group improved significantly from 11.6 [SD 8.1; 95% confidence interval (CI) 9.0-14.2] at the baseline to 5.6 (SD 3.9; 95% CI 4.3-7.0) at 12 months with a mean change from the baseline of -6.5 (SD 6.6; 95% CI -14.2 to -8.9; P < 0.001). The mean IDQOL in the nurse practitioner group improved significantly from 10.7 (SD 4.9; 95% CI 9.1-12.3) at baseline to 5.7 (SD 5.4; 95% CI 4.0-7.5) at 12 months with a mean change from the baseline of -4.9 (SD 5.5; 95% CI -6.8 to -3.0; P < 0.001). The between-groups difference was (-)1.7 (95% CI -4.6 to 1.2; P = 0.26). The mean CDLQI in the dermatologist group improved significantly from 12.1 (SD 6.3; 95% CI 9.9-14.2) at baseline to 5.6 (SD 4.2; 95% CI 4.2-7.1) at 12 months with a mean change from the baseline of -5.9 (SD 6.0; 95% CI -8.0 to -3.9; P < 0.001). The mean CDLQI in the nurse practitioner group improved significantly from 10.0 (SD 4.4; 95% CI 8.5-11.4) at the baseline to 4.9 (SD 3.5; 95% CI 3.7-6.1) at 12 months with a mean change from the baseline of -5.2 (SD 4.0; 95% CI -6.6 to -3.8; P < 0.001). The between-groups difference was (-)0.7 (95% CI -3.3 to 1.7; P = 0.55). The between-groups comparison was not significant for the IDQOL and the CDLQI at baseline or 4, 8 and 12 months. Both treatment groups showed significant improvement in DFI and objective SCORAD at 12 months. The between-groups comparison was not significant at baseline or 4, 8 and 12 months. Significantly higher satisfaction levels were observed at 4, 8 and 12 months in the nurse practitioner group. Conclusions The level of care provided by a nurse practitioner in terms of the improvement in the eczema severity and the quality of life outcomes was comparable with that provided by a dermatologist. In addition, the parents were more satisfied with the care that was provided by a nurse practitioner.", "PMID": "19849695"}, {"title": "Contagious itch in humans: a study of visual 'transmission' of itch in atopic dermatitis and healthy subjects.", "abstract": "Anecdotal evidence suggests that 'contagious' itch occurs in daily life when we see other people itch and scratch. This phenomenon has not previously been studied systematically, and factors which can amplify itch perception were unknown.\n\nWe investigated whether exposure to visual cues of itch can induce or intensify itch in healthy subjects and patients with atopic dermatitis (AD).\n\nParticipants received histamine or a saline control delivered to the forearm and were asked to watch short video clips of people scratching. Spontaneous scratching induced by visual cues was monitored and analysed.\n\nPatients with AD reported a higher itch intensity and scratched more frequently while watching itch videos, even in the presence of mock itch stimuli.\n\nHuman susceptibility to develop itch when exposed to visual cues is confirmed; it appears to be amplified in patients with AD. These findings suggest that interpersonal social cues can dramatically alter the subjective sensory experience of itch.", "PMID": "21410682"}, {"title": "E-health in caring for patients with atopic dermatitis: a randomized controlled cost-effectiveness study of internet-guided monitoring and online self-management training.", "abstract": "The Dermatology Department of the University Medical Centre Utrecht, the Netherlands, developed an e-health portal for patients with atopic dermatitis (AD), consisting of e-consultation, a patient-tailored website, monitoring and self-management training.\n\nTo determine the cost-effectiveness of individualized e-health compared with usual face-to-face care for children and adults with AD.\n\nA randomized controlled cost-effectiveness study from a societal perspective in adults and parents of children with moderate AD. Outcomes were quality of life, severity of AD, itching and direct and indirect costs. Data were collected at baseline and at 3 and 12 months after randomization. Linear mixed models were used to analyse clinical outcomes. After multiple imputation of missing data, costs and differences in costs were calculated over a period of 1 year.\n\nIn total, 199 patients were included. There were no significant differences in disease-specific quality of life, severity of AD and intensity of itching between both groups at the three time points. The difference in direct costs between the intervention and control groups was \u20ac24 [95% confidence interval (CI) -360 to 383], whereas this difference was -\u20ac618 (95% CI -2502 to 1143) for indirect costs. Overall, individual e-health was expected to save \u20ac594 (95% CI -2545 to 1227) per patient in the first year of treatment, mainly through a reduction in work absenteeism. Uncertainty analyses revealed that the probability of e-health reducing costs was estimated to be \u2265 73%.\n\nE-health during follow-up of patients with AD is, after initial diagnosis and treatment during face-to-face contact, just as effective as usual face-to-face care with regard to quality of life and severity of disease. However, when costs are considered, e-health is likely to result in substantial cost savings. Therefore, e-health is a valuable service for patients with AD.", "PMID": "22268960"}, {"title": "Improving patient education with an eczema action plan: a randomized controlled trial.", "abstract": "", "PMID": "23553035"}], "labels": [{"PMID": "10960901", "label": "excluded"}, {"PMID": "12207593", "label": "excluded"}, {"PMID": "16112450", "label": "excluded"}, {"PMID": "17030095", "label": "excluded"}, {"PMID": "18795905", "label": "excluded"}, {"PMID": "19714267", "label": "excluded"}, {"PMID": "19849695", "label": "excluded"}, {"PMID": "21410682", "label": "excluded"}, {"PMID": "22268960", "label": "excluded"}, {"PMID": "23553035", "label": "excluded"}]}
{"metadata": {"review_pmid": "39105481"}, "inputs": {"background": "Identifying patients with COVID-19 disease who will deteriorate can be useful to assess whether they should receive intensive care, or whether they can be treated in a less intensive way or through outpatient care. In clinical care, routine laboratory markers, such as C-reactive protein, are used to assess a person's health status.", "objectives": "To assess the accuracy of routine blood-based laboratory tests to predict mortality and deterioration to severe or critical (from mild or moderate) COVID-19 in people with SARS-CoV-2.", "selection criteria": "We included studies of all designs that produced estimates of prognostic accuracy in participants who presented to outpatient services, or were admitted to general hospital wards with confirmed SARS-CoV-2 infection, and studies that were based on serum banks of samples from people. All routine blood-based laboratory tests performed during the first encounter were included. We included any reference standard used to define deterioration to severe or critical disease that was provided by the authors."}, "context": [{"title": "Clinical Characteristics of Coronavirus Disease 2019 in China.", "abstract": "Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients.\n\nWe extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death.\n\nThe median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission.\n\nDuring the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.).", "PMID": "32109013"}, {"title": "Prognostic value of NT-proBNP in patients with severe COVID-19.", "abstract": "The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China has been declared a public health emergency of international concern. The cardiac injury is a common condition among the hospitalized patients with COVID-19. However, whether N terminal pro B type natriuretic peptide (NT-proBNP) predicted outcome of severe COVID-19 patients was unknown.\n\nThe study initially enrolled 102 patients with severe COVID-19 from a continuous sample. After screening out the ineligible cases, 54 patients were analyzed in this study. The primary outcome was in-hospital death defined as the case fatality rate. Research information and following-up data were obtained from their medical records.\n\nThe best cut-off value of NT-proBNP for predicting in-hospital death was 88.64\u2009pg/mL with the sensitivity for 100% and the specificity for 66.67%. Patients with high NT-proBNP values (>\u200988.64\u2009pg/mL) had a significantly increased risk of death during the days of following-up compared with those with low values (\u226488.64\u2009pg/mL). After adjustment for potential risk factors, NT-proBNP was independently correlated with in-hospital death.\n\nNT-proBNP might be an independent risk factor for in-hospital death in patients with severe COVID-19.\n\nClinicalTrials, NCT04292964. Registered 03 March 2020.", "PMID": "32293449"}, {"title": "Risk Factors of Fatal Outcome in Hospitalized Subjects With Coronavirus Disease 2019\u00a0From a Nationwide Analysis in China.", "abstract": "The novel coronavirus disease 2019 (COVID-19) has become a global health emergency. The cumulative number of new confirmed cases and deaths are still increasing out of China. Independent predicted factors associated with fatal outcomes remain uncertain.\n\nThe goal of the current study was to investigate the potential risk factors associated with fatal outcomes from COVID-19 through a multivariate Cox regression analysis and a nomogram model.\n\nA retrospective cohort of 1,590 hospitalized patients with COVID-19 throughout China was established. The prognostic effects of variables, including clinical features and laboratory findings, were analyzed by using Kaplan-Meier methods and a Cox proportional hazards model. A prognostic nomogram was formulated to predict the survival of patients with COVID-19.\n\nIn this nationwide cohort, nonsurvivors included a higher incidence of elderly people and subjects with coexisting chronic illness, dyspnea, and laboratory abnormalities on admission compared with survivors. Multivariate Cox regression analysis showed that age\u00a0\u2265 75 years (hazard ratio [HR], 7.86; 95%\u00a0CI, 2.44-25.35), age between 65 and 74 years (HR, 3.43; 95%\u00a0CI, 1.24-9.5), coronary heart disease (HR, 4.28; 95%\u00a0CI, 1.14-16.13), cerebrovascular disease (HR, 3.1; 95%\u00a0CI, 1.07-8.94), dyspnea (HR, 3.96; 95%\u00a0CI, 1.42-11), procalcitonin level > 0.5\u00a0ng/mL (HR, 8.72; 95%\u00a0CI, 3.42-22.28), and aspartate aminotransferase level > 40 U/L (HR, 2.2; 95%\u00a0CI, 1.1-6.73) were independent risk factors associated with fatal outcome. A nomogram was established based on the results of multivariate analysis. The internal bootstrap resampling approach suggested the nomogram has sufficient discriminatory power with a C-index of 0.91 (95%\u00a0CI, 0.85-0.97). The calibration plots also showed good consistency between the prediction and the observation.\n\nThe proposed nomogram accurately predicted clinical outcomes of patients with COVID-19 based on individual characteristics. Earlier identification, more intensive surveillance, and appropriate therapy should be considered in patients at high risk.", "PMID": "32304772"}, {"title": "[An increased neutrophil/lymphocyte ratio is an early warning signal of severe COVID-19].", "abstract": "To identify the biomarkers as early warning signals for severe COVID-19.\n\nWe retrospectively analyzed the clinical data of 63 patients with COVID- 19 from Hubei Provincial Hospital of Integrated Chinese and Western Medicine, including 32 moderate cases and 31 severe cases. The demographic data, underlying diseases, clinical manifestations and laboratory test results were compared between the two groups. Logistic regression analysis was performed to identify the factors that predicted the severity of COVID-19. The receiver- operating characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) was calculated, and the area under the curve (AUC) was determined to estimate the optimal threshold of NLR for predicting severe cases of COVID-19.\n\nThe patients with moderate and server COVID-19 showed significant differences in the rate of diabetes, NLR, serum amyloid A (SSA), C-reactive protein (CRP) and serum albumin (ALB) levels (\n\nAn increased NLR can serve as an early warning signal of severe COVID-19.", "PMID": "32376581"}, {"title": "Longitudinal hematologic and immunologic variations associated with the progression of COVID-19 patients in China.", "abstract": "Crucial roles of hematologic and immunologic responses in progression of coronavirus disease 2019 (COVID-19) remain largely unclear.\n\nWe sought to address the dynamic changes in hematologic and immunologic biomarkers and their associations with severity and outcomes of COVID-19.\n\nA retrospective study including 548 patients with COVID-19 with clarified outcome (discharged or deceased) from a national cohort in China was performed. Cross-sectional and longitudinal variations were compared and the associations with different severity and outcomes were analyzed.\n\nOn admission, the counts of lymphocytes, T-cell subsets, eosinophils, and platelets decreased markedly, especially in severe/critical and fatal patients. Increased neutrophil count and neutrophils-to-lymphocytes ratio were predominant in severe/critical cases or nonsurvivors. During hospitalization, eosinophils, lymphocytes, and platelets showed an increasing trend in survivors, but maintained lower levels or dropped significantly afterwards in nonsurvivors. Nonsurvivors kept a high level or showed an upward trend for neutrophils, IL-6, procalcitonin, D-dimer, amyloid A protein, and C-reactive protein, which were kept stable or showed a downward trend in survivors. Positive correlation between CD8\n\nHematologic and immunologic impairment showed a significantly different profile between survivors and nonsurvivors in patients with COVID-19 with different severity. The longitudinal variations in these biomarkers could serve to predict recovery or fatal outcome.", "PMID": "32407836"}, {"title": "Correlation between the variables collected at admission and progression to severe cases during hospitalization among patients with COVID-19 in Chongqing.", "abstract": "Mortality is high among severe patients with 2019 novel coronavirus-infected disease (COVID-19). Early prediction of progression to severe cases is needed. We retrospectively collected patients with COVID-19 in two hospital of Chongqing from 1st January\u00a0to 29th February\u00a02020. At admission, we collected the demographics and laboratory tests to predict whether the patient would progress to severe cases in hospitalization. Severe case was confirmed when one of the following criteria occurred: (a) dyspnea, respiratory rate\u00a0\u226530 breaths/min, (b) blood oxygen saturation \u226493%, and (c) PaO", "PMID": "32470186"}, {"title": "COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection.", "abstract": "Patients with coronavirus disease 2019 (COVID-19) have elevated D-dimer levels. Early reports describe high venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC) rates, but data are limited. This multicenter retrospective study describes the rate and severity of hemostatic and thrombotic complications of 400 hospital-admitted COVID-19 patients (144 critically ill) primarily receiving standard-dose prophylactic anticoagulation. Coagulation and inflammatory parameters were compared between patients with and without coagulation-associated complications. Multivariable logistic models examined the utility of these markers in predicting coagulation-associated complications, critical illness, and death. The radiographically confirmed VTE rate was 4.8% (95% confidence interval [CI], 2.9-7.3), and the overall thrombotic complication rate was 9.5% (95% CI, 6.8-12.8). The overall and major bleeding rates were 4.8% (95% CI, 2.9-7.3) and 2.3% (95% CI, 1.0-4.2), respectively. In the critically ill, radiographically confirmed VTE and major bleeding rates were 7.6% (95% CI, 3.9-13.3) and 5.6% (95% CI, 2.4-10.7), respectively. Elevated D-dimer at initial presentation was predictive of coagulation-associated complications during hospitalization (D-dimer >2500 ng/mL, adjusted odds ratio [OR] for thrombosis, 6.79 [95% CI, 2.39-19.30]; adjusted OR for bleeding, 3.56 [95% CI, 1.01-12.66]), critical illness, and death. Additional markers at initial presentation predictive of thrombosis during hospitalization included platelet count >450 \u00d7 109/L (adjusted OR, 3.56 [95% CI, 1.27-9.97]), C-reactive protein (CRP) >100 mg/L (adjusted OR, 2.71 [95% CI, 1.26-5.86]), and erythrocyte sedimentation rate (ESR) >40 mm/h (adjusted OR, 2.64 [95% CI, 1.07-6.51]). ESR, CRP, fibrinogen, ferritin, and procalcitonin were higher in patients with thrombotic complications than in those without. DIC, clinically relevant thrombocytopenia, and reduced fibrinogen were rare and were associated with significant bleeding manifestations. Given the observed bleeding rates, randomized trials are needed to determine any potential benefit of intensified anticoagulant prophylaxis in COVID-19 patients.", "PMID": "32492712"}, {"title": "Assessment of Hypokalemia and Clinical Characteristics in Patients With Coronavirus Disease 2019 in Wenzhou, China.", "abstract": "Severe acute respiratory syndrome coronavirus 2 has caused a global outbreak of coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 binds angiotensin-converting enzyme 2 of the rennin-angiotensin system, resulting in hypokalemia.\n\nTo investigate the prevalence, causes, and clinical implications of hypokalemia, including its possible association with treatment outcomes, among patients with COVID-19.\n\nThis cohort study was conducted at Wenzhou Central Hospital and Sixth People's Hospital of Wenzhou, Wenzhou, China, from January 11, 2020, to February 15, 2020. Participants included patients who received a diagnosis of COVID-19 according to the criteria issued by the Chinese Health Bureau and were admitted to the hospital. The patients were classified as having severe hypokalemia (plasma potassium <3 mmol/L), hypokalemia (plasma potassium 3-3.5 mmol/L), and normokalemia (plasma potassium >3.5 mmol/L). The clinical features, therapy, and outcomes were compared between the 3 groups. Data analysis was conducted in March 2020.\n\nThe patients were given general support and antiviral therapy. Their epidemiological and clinical features were collected.\n\nThe prevalence of hypokalemia and response to treatment with potassium supplements were measured by analyzing plasma and urine potassium levels.\n\nOne hundred seventy-five patients (87 female patients [50%]; mean [SD] age, 45\u2009[14] years) were classified as having severe hypokalemia (31 patients [18%]), hypokalemia (64 patients [37%]), and normokalemia (80 patients [46%]). Patients with severe hypokalemia had statistically significantly higher body temperature (mean [SD], 37.6 \u00b0C [0.9 \u00b0C]) than the patients with hypokalemia (mean [SD],\u200937.2 \u00b0C\u2009[0.7 \u00b0C]; difference, 0.4 \u00b0C; 95% CI, 0.2-0.6 \u00b0C; P\u2009=\u2009.02) and the patients with normokalemia (mean [SD],\u200937.1 \u00b0C\u2009[0.8 \u00b0C]; difference, 0.5 \u00b0C; 95% CI, 0.3-0.7 \u00b0C; P\u2009=\u2009.005). Patients with higher levels of hypokalemia also had higher creatine kinase levels (severe hypokalemia, mean [SD], 200\u2009[257] U/L [median, 113 U/L; interquartile range {IQR}, 61-242 U/L]; hypokalemia, mean [SD], 97\u2009[85] U/L; and normokalemia, mean [SD], 82\u2009[57] U/L), higher creatine kinase-MB fraction (severe hypokalemia, mean [SD], 32\u2009[39] U/L [median, 14 U/L; IQR, 11-36 U/L]; hypokalemia, mean [SD], 18\u2009[15] U/L; and normokalemia, mean [SD], 15\u2009[8] U/L), higher lactate dehydrogenase levels (mean [SD], severe hypokalemia, 256\u2009[88] U/L; hypokalemia, 212\u2009[59] U/L; and normokalemia, 199\u2009[61] U/L), and higher C-reactive protein levels (severe hypokalemia, mean [SD], 29\u2009[23] mg/L; hypokalemia, mean [SD], 18\u2009[20] mg/L [median, 12, mg/L; IQR, 4-25 mg/L]; and normokalemia, mean [SD], 15\u2009[18] mg/L [median, 6 U/L; IQR, 3-17 U/L]). Of 40 severely and critically ill patients, 34 (85%) had hypokalemia. Patients with severe hypokalemia were given potassium at a dose of 40 mEq per day, for a total mean (SD) of 453 (53) mEq potassium chloride, during the hospital stay. The patients responded well to potassium supplements as they recovered.\n\nThe correction of hypokalemia is challenging because of continuous renal potassium loss resulting from the degradation of angiotensin-converting enzyme 2. The high prevalence of hypokalemia among patients with COVID-19 suggests the presence of disordered rennin-angiotensin system activity, which increases as a result of reduced counteractivity of angiotensin-converting enzyme 2, which is bound by severe acute respiratory syndrome coronavirus 2.", "PMID": "32525548"}, {"title": "Lymphocyte-to-C-Reactive Protein Ratio: A Novel Predictor of Adverse Outcomes in COVID-19.", "abstract": "Systemic inflammation elicited by a cytokine storm is considered a hallmark of coronavirus disease 2019 (COVID-19). This study aims to assess the validity and clinical utility of the lymphocyte-to-C-reactive protein (CRP) ratio (LCR), typically used for gastric carcinoma prognostication, versus the neutrophil-to-lymphocyte ratio (NLR) for predicting in-hospital outcomes in COVID-19.\n\nA retrospective cohort study was performed to determine the association of LCR and NLR with the need for invasive mechanical ventilation (IMV), dialysis, upgrade to an intensive care unit (ICU) and mortality. Independent \n\nThe mean age for NLR patients was 63.6 versus 61.6, and for LCR groups, it was 62.6 versus 63.7 years, respectively. The baseline comorbidities across all groups were comparable except that the higher LCR group had female predominance. The mean NLR was significantly higher for patients who died during hospitalization (19 vs. 7, P \u2264 0.001) and those requiring IMV (12 vs. 7, P = 0.01). Compared to alive patients, a significantly lower mean LCR was observed in patients who did not survive hospitalization (1,011 vs. 632, P = 0.04). For patients with a higher NLR (> 10), the unadjusted odds of mortality (odds ratios (ORs) 11.0, 3.6 - 33.0, P < 0.0001) and need for IMV (OR 3.3, 95% CI 1.4 - 7.7, P = 0.008) were significantly higher compared to patients with lower NLR. By contrast, for patients with lower LCR (< 100), the odds of in-hospital all-cause mortality were significantly higher compared to patients with a higher LCR (OR 0.2, 0.06 - 0.47, P = 0.001). The aORs controlled for baseline comorbidities and medications mirrored the overall results, indicating a genuinely significant correlation between these biomarkers and outcomes.\n\nA high NLR and decreased LCR value predict higher odds of in-hospital mortality. A high LCR at presentation might indicate impending clinical deterioration and the need for IMV.", "PMID": "32655735"}, {"title": "Prognostic factors in Spanish COVID-19 patients: A case series from Barcelona.", "abstract": "In addition to the lack of COVID-19 diagnostic tests for the whole Spanish population, the current strategy is to identify the disease early to limit contagion in the community.\n\nTo determine clinical factors of a poor prognosis in patients with COVID-19 infection.\n\nDescriptive, observational, retrospective study in three primary healthcare centres with an assigned population of 100,000.\n\nExamination of the medical records of patients with COVID-19 infections confirmed by polymerase chain reaction. Logistic multivariate regression models adjusted for age and sex were constructed to analyse independent predictive factors associated with death, ICU admission and hospitalization.\n\nWe included 322 patients (mean age 56.7 years, 50% female, 115 (35.7%) aged \u2265 65 years): 123 (38.2) were health workers (doctors, nurses, auxiliaries). Predictors of ICU admission or death were greater age (OR = 1.05; 95%CI = 1.03 to 1.07), male sex (OR = 2.94; 95%CI = 1.55 to 5.82), autoimmune disease (OR = 2.82; 95%CI = 1.00 to 7.84), bilateral pulmonary infiltrates (OR = 2.86; 95%CI = 1.41 to 6.13), elevated lactate-dehydrogenase (OR = 2.85; 95%CI = 1.28 to 6.90), elevated D-dimer (OR = 2.85; 95%CI = 1.22 to 6.98) and elevated C-reactive protein (OR = 2.38; 95%CI = 1.22 to 4.68). Myalgia or arthralgia (OR = 0.31; 95%CI = 0.12 to 0.70) was protective factor against ICU admission and death. Predictors of hospitalization were chills (OR = 5.66; 95%CI = 1.68 to 23.49), fever (OR = 3.33; 95%CI = 1.89 to 5.96), dyspnoea (OR = 2.92; 95%CI = 1.62 to 5.42), depression (OR = 6.06; 95%CI = 1.54 to 40.42), lymphopenia (OR = 3.48; 95%CI = 1.67 to 7.40) and elevated C-reactive protein (OR = 3.27; 95%CI = 1.59 to 7.18). Anosmia (OR = 0.42; 95%CI = 0.19 to 0.90) was the only significant protective factor for hospitalization after adjusting for age and sex.\n\nDetermining the clinical, biological and radiological characteristics of patients with suspected COVID-19 infection will be key to early treatment and isolation and the tracing of contacts.", "PMID": "32822413"}], "labels": [{"PMID": "32109013", "label": "included"}, {"PMID": "32293449", "label": "included"}, {"PMID": "32304772", "label": "included"}, {"PMID": "32376581", "label": "included"}, {"PMID": "32407836", "label": "included"}, {"PMID": "32470186", "label": "included"}, {"PMID": "32492712", "label": "included"}, {"PMID": "32525548", "label": "included"}, {"PMID": "32655735", "label": "included"}, {"PMID": "32822413", "label": "included"}]}
{"metadata": {"review_pmid": "39105474"}, "inputs": {"background": "Eczema (atopic dermatitis) is the most burdensome skin condition worldwide and cannot currently be prevented or cured. Topical anti-inflammatory treatments are used to control eczema symptoms, but there is uncertainty about the relative effectiveness and safety of different topical anti-inflammatory treatments.", "objectives": "To compare and rank the efficacy and safety of topical anti-inflammatory treatments for people with eczema using a network meta-analysis.", "selection criteria": "We included within-participant or between-participant randomised controlled trials (RCTs) in people of any age with eczema of any severity, but excluded trials in clinically infected eczema, seborrhoeic eczema, contact eczema, or hand eczema. We included topical anti-inflammatory treatments used for at least one week, compared with another anti-inflammatory treatment, no treatment, or vehicle/placebo. Vehicle is a 'carrier system' for an active pharmaceutical substance, which may also be used on its own as an emollient for dry skin. We excluded trials of topical antibiotics used alone, complementary therapies, emollients used alone, phototherapy, wet wraps, and systemic treatments."}, "context": [{"title": "A comparative clinical evaluation of a new topical steroid 'halcinonide' and hydrocortisone in steroid-responsive dermatoses.", "abstract": "Fifty patients with symmetrical, bilateral lesions of psoriasis, eczematous dermatitis, atopic dermatitis, or neurodermatitis participated in a double-blind paired comparison study in which 0-1% halcinonide (in a cream formulation containing also neomycin and nystatin) was applied to the lesions on one side of the body and 1% hydrocortisone cream to those on the opposite side for two to three weeks. The number of excellent responses to therapy showed the halcinonide combination to be significantly superior (p less than 0-01) to the control cream in all diagnostic categories if considered collectively, and in psoriasis if the responses were grouped according to diagnosis. No adverse reactions occurred during the trial.", "PMID": "1026547"}, {"title": "A comparison of once-daily application of mometasone furoate 0.1% cream compared with twice-daily hydrocortisone valerate 0.2% cream in pediatric atopic dermatitis patients who failed to respond to hydrocortisone: mometasone furoate study group.", "abstract": "", "PMID": "10487451"}, {"title": "The therapeutic efficacy of mometasone furoate cream 0.1% applied once daily vs clobetasol propionate cream 0.05% applied twice daily in chronic eczema.", "abstract": "Mometasone furoate [9a, 21-dichloro-llb, 17dihydroxy-16a-methyl-pregna-14-dione-3, 20-dione-17-(2furoate)] is a synthetic, 17-heterocyclic corticosteroid which has been shown to be highly effective as an anti-inflammatory agent which is approximately half as potent is suppressing hypothalamic-pituitary-adrenal (HPA) axis function as betamethasone valerate.\n\nThe present open, randomised, third party blinded, left-right sided study was designed to compare the therapeutic efficacy of mometasone furoate cream 0.1% with clobetasol propionate cream 0.05% applied twice daily in chronic eczema following a 3-week course of therapy.\n\nSixty consecutive patients with moderate to severe bilateral chronic eczema on the limbs were recruited into the study. The mean scores of various signs/symptoms including erythema, induration, crusting, scaling, excoriation and pruritus before and after 3 weeks treatment with mometasone furoate (MF) and clobetasol propionate (CP) cream, were compared. The baseline scores for MF and CP treated sites were almost identical. There was significant decrease in the mean scores of all signs/symptoms after 3 weeks treatment with MF and CP. There was also a significant difference in the mean scores between MF and CP treated sites after 3 weeks of treatment. The mean scores were significantly lower for CP treated sites than MF treated sites. More CP treated sites achieved \"cleared\" or \"marked improvement\" response than MF treated sites. There were more \"excellent\" or \"good\" grades on CP treated sites than MF treated sites at the end of 3 weeks of treatment. None of the patients showed any side-effects after 4 weeks of treatment.\n\nOverall, 53% of patients considered the MF treated sites to be good or excellent vs 88% for CP treated sites.", "PMID": "10489492"}, {"title": "Proof of efficacy of Kamillosan(R) cream in atopic eczema.", "abstract": "Kamillosan(R) cream contains chamomile extract as active principle manufactured from the chamomile sort Manzana which is rich in active principles and has been proved not to exhibit a chamomile-related allergen potential. For this reason Kamillosan(R) cream is suited for local therapy of atopic eczema. In a partially double-blind, randomized study carried out as a half-side comparison, Kamillosan(R) cream was tested vs. 0.5% hydrocortisone cream and the vehicle cream as placebo in patients suffering from medium-degree atopic eczema. After a 2-week treatment Kamillosan(R) cream showed a mild superiority towards 0.5% hydrocortisone and a marginal difference as compared to placebo.", "PMID": "10799352"}, {"title": "[Comparative study of efficacy and effect on plasma cortisol levels of micronised desonide cream 0.1 p. 100 versus betamethasone dipropionate cream 0.05 p. 100 In the treatment of childhood atopic dermatitis].", "abstract": "Systemic side effects of local corticosteroid therapy may occur when treating chronic inflammatory dermatoses in children. We compared the effect of micronized desonide cream 0.1 p.100 versus betamethasone dipropionate cream 0.5 p.100.\n\nA randomized double-blind trial was conducted to assess the efficacy of micronized desonide cream 0.1 p.100 (group 1) versus bethamethasone cream dipropionate 0.05 p.100 (group 2) in children treated for atopic dermatitis and to compare their effects on serum cortisol levels 8 hours after administration. Twenty-nine patients, mean age 13.8 months were included (15 in group 1 and 14 in group 2). The creams were applied twice a day from day 1 to 5 then once a day from day 6 to 7 and finally once every two days to day 15.\n\nThe two treatments were effective with a decrease in body surface area involved and an improvement in lesion score from day 5 to day 20. Cortisolemia fell off significantly for both treatments between day 0 and day 5 (group 1: Deltad5=-4.74 mg/ml, p=0.01; group 2: Deltad5=-13.06 mg/ml, p<0.0001), only for group 2 between day 0 and day 20 (Deltad20=-7.38 mg/ml, p=0.02) and to a lesser degree between day 0 and day 30 (Deltad30=-3.18 mg/ml, p=0.06). The decrease was greater in group 2 than in group 1 on day 5 (p=0.01) and to a lesser degree at day 20 (p=0.06).\n\nMicronized desonide cream 0.1 p.100 has less potential for suppressing the adrenal cortisol axis than betamethasone dipropionate cream 0.05 p.100 while the therapeutic effect on childhood atopic dermatitis is the same.", "PMID": "10930856"}, {"title": "[Treatment of Besnier's prurigo with Calmuril-hydrocortisone 1% cream and triamcinolone acetonide 0,1% cream. A controlled clinical study].", "abstract": "", "PMID": "1094657"}, {"title": "Double-blind comparison between two new topical corticosteroids, halcinonide 0.1% and clobetasol propionate cream 0.05%.", "abstract": "A new steroid, halcinonide, was compared with clobetasol propionate cream in 100 patients with a variety of skin disorders. The study was conducted as a double-blind, paired comparison with the preparations being given twice daily. Results obtained over a 14-day period of therapy showed remarkably similar efficacy for both preparations.", "PMID": "1097198"}, {"title": "Betamethasone dipropionate in psoriasis and atopic dermatitis.", "abstract": "", "PMID": "1106945"}, {"title": "The addition of topical doxepin to corticosteroid therapy: an improved treatment regimen for atopic dermatitis.", "abstract": "", "PMID": "10192169"}, {"title": "[Halcinonide-neomycin-nystatin in the treatment of dermatosis and cutaneous candidiasis].", "abstract": "Sixty-four patients were treated for inflammatory dermatoses or cutaneous candidiasis with a new corticosteroid combination drug, halcinonide-neomycin-nystatin (HNN). In 50 patients treated for psoriasis, atopic dermatitis, eczematous dermatitis, or neurodermatitis, HNN was evaluated in a double-blind, paired comparison study with hydrocortisone (HC) as the control drug. HNN was superior in 24 patients, HC was superior in 6, and the responses were equal in 18. The overall therapeutic response was Excellent with HNN in 29 patients as compared to 14 with HC. The anticandidal properties of HNN were assessed in a parallel study with iodochlorhydroxyquin-hydrocortisone (I-HC) as the control drug. The most frequently treated conditions were \"erosio interdigitalis blastomycotica\" and candidal lesions of the neck region. The response with HNN was Excellent in 7 of 14 patients as compared to 4 out of 14 treated with I-HC.", "PMID": "1035402"}], "labels": [{"PMID": "1026547", "label": "included"}, {"PMID": "10487451", "label": "included"}, {"PMID": "10489492", "label": "included"}, {"PMID": "10799352", "label": "included"}, {"PMID": "10930856", "label": "included"}, {"PMID": "1094657", "label": "included"}, {"PMID": "1097198", "label": "included"}, {"PMID": "1106945", "label": "included"}, {"PMID": "10192169", "label": "excluded"}, {"PMID": "1035402", "label": "excluded"}]}
{"metadata": {"review_pmid": "39072702"}, "inputs": {"background": "Atrial fibrillation (AF) is an increasingly prevalent heart rhythm condition in adults. It is considered a common cardiovascular condition with complex clinical management. The increasing prevalence and complexity in management underpin the need to adapt and innovate in the delivery of care for people living with AF. There is a need to systematically examine the optimal way in which clinical services are organised to deliver evidence-based care for people with AF. Recommended approaches include collaborative, organised multidisciplinary, and virtual (or eHealth/mHealth) models of care.", "objectives": "To assess the effects of clinical service organisation for AF versus usual care for people with all types of AF.", "selection criteria": "We included randomised controlled trials (RCTs), published as full texts and as abstract only, involving adults (\u2265 18 years) with a diagnosis of any type of AF. We included RCTs comparing organised clinical service, disease-specific management interventions (including e-health models of care) for people with AF that were multicomponent and multidisciplinary in nature to usual care."}, "context": [{"title": "Nurse-led care vs. usual care for patients with atrial fibrillation: results of a randomized trial of integrated chronic care vs. routine clinical care in ambulatory patients with atrial fibrillation.", "abstract": "The management of patients with atrial fibrillation (AF) is often inadequate due to deficient adherence to the guidelines. A nurse-led AF clinic providing integrated chronic care to improve guideline adherence and activate patients in their role, may effectively reduce morbidity and mortality but such care has not been tested in a large randomized trial. Therefore, we performed a randomized clinical trial to compare the AF clinic with routine clinical care in patients with AF.\n\nWe randomly assigned 712 patients with AF to nurse-led care and usual care. Nurse-led care consisted of guidelines based, software supported integrated chronic care supervised by a cardiologist. The primary endpoint was a composite of cardiovascular hospitalization and cardiovascular death. Duration of follow-up was at least 12 months. Adherence to guideline recommendations was significantly better in the nurse-led care group. After a mean of 22 months, the primary endpoint occurred in 14.3% of 356 patients of the nurse-led care group compared with 20.8% of 356 patients receiving usual care [hazard ratio: 0.65; 95% confidence interval (CI) 0.45-0.93; P= 0.017]. Cardiovascular death occurred in 1.1% in the nurse-led care vs. 3.9% in the usual care group (hazard ratio: 0.28; 95% CI: 0.09-0.85; P= 0.025). Cardiovascular hospitalization amounted (13.5 vs. 19.1%, respectively, hazard ratio: 0.66; 95% CI: 0.46-0.96, P= 0.029).\n\nNurse-led care of patients with AF is superior to usual care provided by a cardiologist in terms of cardiovascular hospitalizations and cardiovascular mortality. Trial registration information: Clinicaltrials.gov identifier number: NCT00391872.", "PMID": "22453654"}, {"title": "Nurse-led care vs. usual care for patients with atrial fibrillation: results of a randomized trial of integrated chronic care vs. routine clinical care in ambulatory patients with atrial fibrillation.", "abstract": "The management of patients with atrial fibrillation (AF) is often inadequate due to deficient adherence to the guidelines. A nurse-led AF clinic providing integrated chronic care to improve guideline adherence and activate patients in their role, may effectively reduce morbidity and mortality but such care has not been tested in a large randomized trial. Therefore, we performed a randomized clinical trial to compare the AF clinic with routine clinical care in patients with AF.\n\nWe randomly assigned 712 patients with AF to nurse-led care and usual care. Nurse-led care consisted of guidelines based, software supported integrated chronic care supervised by a cardiologist. The primary endpoint was a composite of cardiovascular hospitalization and cardiovascular death. Duration of follow-up was at least 12 months. Adherence to guideline recommendations was significantly better in the nurse-led care group. After a mean of 22 months, the primary endpoint occurred in 14.3% of 356 patients of the nurse-led care group compared with 20.8% of 356 patients receiving usual care [hazard ratio: 0.65; 95% confidence interval (CI) 0.45-0.93; P= 0.017]. Cardiovascular death occurred in 1.1% in the nurse-led care vs. 3.9% in the usual care group (hazard ratio: 0.28; 95% CI: 0.09-0.85; P= 0.025). Cardiovascular hospitalization amounted (13.5 vs. 19.1%, respectively, hazard ratio: 0.66; 95% CI: 0.46-0.96, P= 0.029).\n\nNurse-led care of patients with AF is superior to usual care provided by a cardiologist in terms of cardiovascular hospitalizations and cardiovascular mortality. Trial registration information: Clinicaltrials.gov identifier number: NCT00391872.", "PMID": "22453654"}, {"title": "Cost-effectiveness of a specialized atrial fibrillation clinic vs. usual care in patients with atrial fibrillation.", "abstract": "A recent randomized controlled trial demonstrated significant reductions in cardiovascular hospitalizations and deaths with a nurse-led integrated chronic care approach in patients with atrial fibrillation (AF) compared with usual care. The aim of the present study is to assess cost-effectiveness of this nurse-led care programme vs. usual care.\n\nA cost-effectiveness analysis was undertaken alongside the randomized controlled trial in which 712 patients were included at the Maastricht University Medical Centre, The Netherlands, and allocated to nurse-led care or usual care. Nurse-led care implied guideline-adherent management, steered by dedicated software, supervised by cardiologists. Usual care was regular outpatient care performed by cardiologists. A cost per life-year and a cost per quality-adjusted life-year (QALY) analysis was performed, both from a hospital perspective. The nurse-led care programme was associated with slightly more life-years and QALYs at a lower cost. Specifically, the nurse-led programme contributed to 0.009 QALY gains with a reduced cost of \u20ac1109 per patient and a gain of 0.02 life-years with a reduced cost of \u20ac735 per patient. Therefore, the nurse-led programme would be considered dominant. In fact, for all the possible values of willingness to pay for a QALY the nurse-led programme is considered to be more likely cost-effective than the care as usual.\n\nThe cost-effectiveness analysis in the present study demonstrated that a nurse-led integrated care approach will save costs and improve survival and quality of life, and is therefore a cost-effective management strategy for patients with AF.", "PMID": "23515338"}, {"title": "A prospective controlled trial comparing weekly self-testing and self-dosing with the standard management of patients on stable oral anticoagulation.", "abstract": "Oral anticoagulant therapy requires frequent laboratory controls of its intensity to assure therapeutic efficacy and to prevent potentially life threatening adverse events. It is generally assumed, that increasing the frequency of testing would lead to a better control of anticoagulation. We tested this hypothesis in a prospective controlled trial comparing weekly self-testing and self-dosing (self management) with the standard-management of these patients in an anticoagulation clinic. Only patients with stable anticoagulation were included into the study. We recorded 2733 weekly determinations of the intensity of anticoagulation (INR) in 49 patients on self-testing and self-dosing and 539 determinations of the INR in 53 patients on standard-management. Two intensities of anticoagulation were used in each group: a target INR of 3.5 for patients with artificial heart valves (target range: 2.5-4.5) and a target INR 2.5 (target range: 2.0-3.0) for patients with atrial fibrillation or venous thromboembolism. The deviation from the target INR, the fraction of INR determinations within the preset therapeutic range and the difference between the target INR and the actually achieved mean INR were the three major endpoints of the study. The mean deviation from the target INR was smaller in the groups of patients on self-management compared to the patients on standard-management. Individual deviations were significantly (p <0.0001) dependent on the type of management in interaction with the treatment intensity in a general linear model. Patients on weekly self-testing and self-dosing had more INR values within the therapeutic range than patients on standard-management (86.2% vs. 80.1% at INR range 2.5-4.5; 82.2 vs. 68.9 at INR range 2.0-3.0). The achieved mean INR was almost identical with the target INR in the patients on self-management but was significantly (p <0.005) below the target INR in the high intensity anticoagulation group on standard-management (target INR:3.5; achieved mean INR: 3.19; CI 0.95: 3.05-3.34). Our data show, that weekly self-testing and self-dosing leads to a better control of anticoagulation than standard treatment in an anticoagulation clinic.", "PMID": "10823258"}, {"title": "Effect of computer-aided management on the quality of treatment in anticoagulated patients: a prospective, randomized, multicenter trial of APROAT (Automated PRogram for Oral Anticoagulant Treatment).", "abstract": "We carried out a prospective, randomized trial to test whether a computer-based decision support system to initiate and maintain oral anticoagulant (OA) treatment can improve the laboratory quality of therapy.\n\nTwo separate sets of patients on oral anticoagulants, in five Italian anticoagulant clinics, were studied: 335 patients in the first three months of treatment (stabilization phase), 916 patients (775 patient-years) beyond the third month of treatment (maintenance phase). Patients were randomized to a computerized system, which included algorithms able to suggest OA dosing and to schedule appointments (computer-aided dosing) or to an arm in which OA were prescribed by the same teams of expert physicians without such algorithms (control group). Primary outcomes were: A) the percentage of patients reaching a stable state of anticoagulation during each of the first three months of treatment; B) the percentage of time individuals spent within the aimed therapeutic range (maintenance phase).\n\nPatients in the computer-aided dosing group achieved a stable state significantly faster (p<0.01) and they spent more time within the therapeutic range during maintenance (p<0.001) than controls. The favorable effect of computer-aided dosing was mainly due to a reduction of the time spent below the therapeutic range and was associated with an increase of mean INR value, of anticoagulant drug dosage, and with a reduction of the number of appointments per patient (all changes significant: p<0.001).\n\nThe computer decision-aided support improves the laboratory quality of anticoagulant treatment, both during long-term maintenance and in the early, highly unstable phase of treatment, and it also significantly reduces the number of scheduled laboratory controls.", "PMID": "11602412"}, {"title": "Improving the quality of anticoagulation of patients with atrial fibrillation in managed care organizations: results of the managing anticoagulation services trial.", "abstract": "Randomized trials have indicated that well-managed anticoagulation with warfarin could prevent more than half of the strokes related to atrial fibrillation. However, many patients with atrial fibrillation who are eligible for this therapy either do not receive it or are not maintained within an optimal prothrombin time-international normalized ratio (INR) range. We sought to determine whether an anticoagulation service within a managed care organization would be a feasible alternative for providing anticoagulation care. We performed a multi-site randomized trial in six large managed care organizations in the United States. Subjects were aged 65 years or older and had nonvalvular atrial fibrillation. At each site, physician practices were divided into two geographically defined practice clusters; each site was randomly assigned to have one intervention and one control cluster. The intervention cluster received an anticoagulation service that satisfied specifications for high-quality anticoagulation care and was coordinated through the managed care organization. Control clusters continued with their usual provider-based care. We measured the proportion of time that warfarin-treated patients in each of the clusters (intervention and control) were in the target range for the INR at baseline, and again during a follow-up period. Five of the six selected sites succeeded at developing an anticoagulation service. Patients in the intervention and control clusters had similar demographic characteristics, contraindications to warfarin, and risk factors for stroke. Among patients (n = 144 in the intervention clusters; n = 118 in the control clusters) for whom data were available during the baseline and follow-up periods, the changes in percentages of time in the target range were similar for those in the intervention clusters (baseline: 47.7%; follow-up: 55.6%) and in the control clusters (baseline: 49.1%; follow-up: 52.3%; intervention effect: 5%; 95% confidence interval: -5% to 14%; P = 0.32). Although it was feasible in a managed care organization to implement anticoagulation services that were tailored to local circumstances, provision of this service did not improve anticoagulation care compared with usual care. The effect of the anticoagulation service was limited by the utilization of the service, the degree to which the referring physician supports strict adherence to recommended target ranges for the INR, and the ability of the anticoagulation service to identify and to respond to out-of-range values promptly.", "PMID": "12106622"}, {"title": "Do anticoagulation management services improve care? Implications of the Managing Anticoagulation Services Trial.", "abstract": "An Anticoagulation Clinic Service (ACS) has been proposed as one strategy for improving warfarin treatment for patients with atrial fibrillation. In the Managing Anticoagulation Services Trial (MAST), ACSs meeting specifications for high quality care were established in six managed care organizations (MCOs) which had the patients and resources to support this initiative. The trial followed 1165 patients age >or=65 years who had atrial fibrillation as the primary reason for anticoagulation and were enrolled in a participating MCO. The 593 patients in the intervention group saw physicians in a practice cluster which had randomly been assigned to have access to an ACS. These physicians used the ACS on average for about 48% of eligible patients. The 572 patients in the control group received care from physicians in a practice cluster which could not refer patients to the ACS established for the trial but was otherwise unrestricted. The two clusters were compared on the proportion of time warfarin-treated patients were in the target range (2-3) prothrombin time-international normalized ratio (INR) during a 9-month baseline and a 9-month follow-up period. Among patients ( n = 264) for whom data were available for both periods, the changes in percentages of time in the target range were similar in the intervention cluster (baseline: 47.7%; follow-up 55.6%) and in the control cluster (baseline: 49.1%; follow-up: 52.3%; intervention effect: 5%; 95% confidence interval: -5% to 14%; P = 0.32). In both practice clusters, patients had subtherapeutic INR values (1.5 to 1.99) about one fourth of the time. Providing an ACS in a managed care setting did not appear to improve anticoagulation care over the usual care provided at the sites in this trial but could be a reasonable consideration in a practice setting where time in target range is less than 50%. A higher rate of utilization and a more aggressive stance toward subtherapeutic INR values could potentially enhance the effectiveness of an ACS.", "PMID": "15071259"}, {"title": "The value of education and self-monitoring in the management of warfarin therapy in older patients with unstable control of anticoagulation.", "abstract": "Of 125 patients aged 65 years or over, with atrial fibrillation taking warfarin for at least 12 months, with a standard deviation (SD) of prothrombin time, expressed as the International Normalized Ratio (INR) >0.5 over the previous 6 months, 40 were randomized to continue with usual clinic care and 85 to receive education about warfarin. Of these, 44 were randomized to self-monitor their INR and 41 returned to clinic. Compared with the previous 6 months there was a significant increase in percentage time within the therapeutic range for the 6 months following education [61.1 vs. 70.4; mean difference 8.8; 95% confidence interval (CI): -0.2-17.8; P = 0.054] and following education and self-monitoring (57 vs. 71.1; mean difference 14.1; 95% CI: 6.7-21.5; P < 0.001), compared with those patients following usual clinic care (60.0 vs. 63.2; mean difference 3.2; 95% CI: -7.3-13.7). Using the same comparative periods, the INR SD fell by 0.24 (P < 0.0001) in the group allocated to education and self-monitoring, 0.26 (P < 0.0001) in the group receiving education alone and 0.16 (P = 0.003) in the control group. Inter-group differences were not statistically significant (intervention groups 0.26 +/- 0.30 vs. control 0.16 +/- 0.3, P = 0.10). Quality-of-life measurements and health beliefs about warfarin were unchanged (apart from emotional role limitation) with education or education and self-monitoring. Patient education regarding anticoagulation therapy could be a cost-effective initiative and is worthy of further study.", "PMID": "15287950"}, {"title": "Self-management of oral anticoagulation in nonvalvular atrial fibrillation (SMAAF study).", "abstract": "Most patients with atrial fibrillation are at risk of suffering thromboembolic events. This risk can be reduced by twothirds by efficient anticoagulation. This prospective multi-center trial investigated whether the quality of treatment can be improved by self-management in patients with atrial fibrillations (SMAAF Study) compared to conventional patient management by the family doctor.\n\nTwo thousand patients suitable for self-management were to be randomized into the two arms of the study. In the period of investigation from December 1999 to July 2001, only 202 patients (64.3+/-9.2 years, 69.3% men) consented to participate. The study was discontinued prematurely since the number of patients was too low. As a consequence, the group comparison is confined to the evaluation of the INR values measured using the two-tailed t test.\n\nOf the 202 patients included, 101 were assigned to the self-management group (64.6+/-9.6 years, 71.4% men) and 101 (64.1+/-8.9 years, 61.4% men, n.s.) were assigned to the group managed by the family doctor. The total number of INR measurements was 2 865. This comprised 2 072 measurements in patients under self-management and 793 in the family doctor group. The values were within the target range significantly more frequently (p=0.0061) in patients under self-management (67.8%) as compared to the family doctor group (58.5%). There was a trend with regard to the time within target range, but the difference was not significant (178.8+/-126 days as compared to 155.9+/-118.4 days). In the self-management group, there were two severe hemorrhages, and there was one thromboembolic event in the family doctor group.\n\nManagement of oral anticoagulation by INR self-management in patients with atrial fibrillation is not inferior to conventional care.", "PMID": "15747040"}, {"title": "Perceived effects on patients' health of participation in the atrial fibrillation follow-up investigation of rhythm management study.", "abstract": "Patients' views about participation in clinical trials have been explored using end-of-study questionnaires for various disease entities. However, little is known about why individuals with atrial fibrillation (AF) choose to participate in clinical trials or how they view their research experience. Understanding these perceptions should provide valuable information for future studies in developing methods to enhance enrollment, optimize adherence to therapies, and maximize patient retention.\n\nThe Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Study was a randomized trial of rate-control versus rhythm-control for the management of AF. This descriptive ancillary study used a 7-item questionnaire comprising closed and open-ended items that explored: (1) perceptions of benefits from participation, (2) motivation for enrolling, and (3) satisfaction with research staff and operations.\n\nA total of 741/1,032 participants (72%) at 34 of 213 participating AFFIRM sites responded, representing 18% of the 4,060 patients enrolled. The mean follow-up of these respondents was 3.8 +/- 1.1 years. Most respondents (91%) felt that they received enough information about AFFIRM before enrolling and that the results would benefit themselves (88%) and others (91%). Most respondents felt study participation improved awareness about AF (90%) and facilitated coordination of their healthcare (89%). Virtually all were satisfied with information received from AFFIRM personnel (96%), and most (98%) reported that they had received \"good care.\" Responses were similar between randomization groups (rate-control or rhythm-control) and between those younger than 65 years and those 65 years or older. Participants in sinus rhythm at last follow-up were more likely to believe that their medical care in AFFIRM was better than what they would otherwise have received, and were more likely to perceive their treatment course as entailing fewer emergency room visits, hospitalizations, and doctor visits. Regularly scheduled appointments and ongoing availability of staff to answer questions appeared to increase participants' confidence and reduce anxiety.\n\nPatients enrolled in a long-term clinical trial for management of AF were overwhelmingly satisfied with participation.", "PMID": "16966916"}], "labels": [{"PMID": "22453654", "label": "included"}, {"PMID": "22453654", "label": "included"}, {"PMID": "23515338", "label": "included"}, {"PMID": "10823258", "label": "excluded"}, {"PMID": "11602412", "label": "excluded"}, {"PMID": "12106622", "label": "excluded"}, {"PMID": "15071259", "label": "excluded"}, {"PMID": "15287950", "label": "excluded"}, {"PMID": "15747040", "label": "excluded"}, {"PMID": "16966916", "label": "excluded"}]}
{"metadata": {"review_pmid": "38775255"}, "inputs": {"background": "Sickle cell disease (SCD) refers to a group of genetic disorders characterized by the presence of an abnormal haemoglobin molecule called haemoglobin S (HbS). When subjected to oxidative stress from low oxygen concentrations, HbS molecules form rigid polymers, giving the red cell the typical sickle shape. Antioxidants have been shown to reduce oxidative stress and improve outcomes in other diseases associated with oxidative stress. Therefore, it is important to review and synthesize the available evidence on the effect of antioxidants on the clinical outcomes of people with SCD.", "objectives": "To assess the effectiveness and safety of antioxidant supplementation for improving health outcomes in people with SCD.", "selection criteria": "We included randomized and quasi-randomized controlled trials comparing antioxidant supplementation to placebo, other antioxidants, or different doses of antioxidants, in people with SCD."}, "context": [{"title": "Reduction of pain episodes and prothrombotic activity in sickle cell disease by dietary n-3 fatty acids.", "abstract": "The effects of dietary n-3 fatty acids (n-3FAs) on the frequency of pain episodes and ex vivo blood tests of thrombosis have been evaluated in patients with sickle cell disease (SCD) utilizing a double-blind, olive oil-controlled clinical trial. Dietary n-3FA therapy (0.1 g/kg/d) was provided as menhaden fish oil (0.25 g/kg/d) containing 12% eicosapentaenoic acid (EPA), and 18% docosahexaenoic acid (DHA). Within 1 month dietary n-3FAs exchanged with n-6FAs in plasma and erythrocyte membrane phospholipids (p <0.01 in all cases). Treatment with dietary n-3FAs for 1 year reduced the frequency of pain episodes requiring presentation to the hospital from 7.8 events during the preceding year to 3.8 events/year (p <0.01; n = 5). By contrast, subjects receiving control dietary olive oil (n = 5) experienced 7.1 pain events/year, compared to 7.6 during the previous year (p >0.4). The reduction in episodes in n-3FA-treated subjects was also significant when compared to control subjects (p <0.01). Dietary n-3FA therapy was not associated with hemorrhagic, gastrointestinal or other adverse effects. Compared to 10 asymptomatic African-American controls, sickle cell subjects demonstrated significantly increased pretreatment: 1) flow cytometric expression of platelet membrane P-selectin (CD62p; p <0.01) and annexin V binding sites (p = 0.02); 2) plasma levels of platelet-specific secretory proteins platelet factor 4 (PF4) and beta-thromboglobulin (betaTG) (p <0.01 in both cases); 3) plasma products of thrombin generation, prothrombin fragment 1.2 (F1.2) and thrombin:antithrombin (TAT) complex (p <0.01 in both cases); and 4) plasma levels of thrombolytic products, D-dimer and plasmin:antiplasmin (PAP) complex (p <0.01 in both cases). Treatment with dietary n-3FAs concurrently decreased plasma levels of F1.2, D-dimer, and PAP (p <0.05, compared to olive oil controls), implying that the reduction in pain events was related to n-3FA-dependent inhibition of thrombosis. We conclude that dietary n-3FAs reduce the frequency of pain episodes perhaps by reducing prothrombotic activity in sickle cell disease.", "PMID": "11434703"}, {"title": "Effect of zinc supplementation on growth and body composition in children with sickle cell disease.", "abstract": "Poor growth and delayed maturation in children with sickle cell disease (SCD) may be due, in part, to mild zinc deficiency.\n\nThe objective was to determine the effects of zinc supplementation on growth and body composition in children with SCD.\n\nForty-two prepubertal children (20 girls and 22 boys) aged 4-10 y with SCD-SS were randomly assigned to receive 10 mg elemental Zn/d in cherry syrup (zinc group) or cherry syrup alone (control group). The 2 groups were stratified by sex and initial height status. Dietary intakes were evaluated and anthropometric, high-precision knee-height, and plasma zinc measurements were made at baseline and at 3, 6, and 12 mo. Body composition was determined every 6 mo with dual-energy X-ray absorptiometry, and z scores for anthropometric variables were computed from national reference data. Longitudinal-mixed-effects analysis was used to test for differences between the groups over the 12-mo observation period.\n\nThirty-eight children completed the study. No significant differences were observed at baseline. After 12 mo, the zinc group had significantly greater mean (+/- SE) increases in height (0.66 +/- 0.29 cm/y), sitting height (0.97 +/- 0.40 cm/y), knee height (3.8 +/- 1.2 mm/y), and arm circumference z scores (0.27 +/- 0.12 cm/y). Height-for-age and weight-for-age z scores decreased significantly by 0.11 +/- 0.04 and 0.13 +/- 0.05, respectively, in the control group but did not change significantly in the zinc group.\n\nPrepubertal children with SCD-SS may have zinc deficiency and may benefit from zinc supplementation to improve linear growth and weight gain.", "PMID": "11815322"}, {"title": "Effects of N-acetylcysteine on dense cell formation in sickle cell disease.", "abstract": "The extent to which dense and irreversible sickle cells (ISCs) contribute to vaso-occlusive episodes in sickle cell disease remains unclear. N-Acetylcysteine (NAC) inhibits dense cell and ISC formation in sickle erythrocytes in vitro and restores glutathione levels toward normal. A phase II double-blind randomized clinical trial was completed to determine the efficacy of NAC in decreasing dense cell and ISC formation, and vaso-occlusive episodes in sickle cell disease. Twenty-one subjects with a history of at least two vaso-occlusive episodes per year and 6% dense cells were enrolled. Four treatment groups were analyzed; NAC at a dose of 2,400 mg per day decreased the percent dense cells from 20.1 +/- 2.9 to 12.6 +/- 2.1 (P < 0.05) and increased red cell glutathione levels from 292.8 +/- 74.5 to 576.7 +/- 155.1 (P < 0.05). In addition, we observed a decrease in vaso-occlusive episodes from 0.03 to 0.006 episodes per person-days and a decreased in relative risk to R = 0.39. Although NAC did not significantly decrease the number of ISCs, there was a downward trend at all doses tested. In summary, NAC inhibited dense cell formation, restored glutathione levels toward normal, and decreased vaso-occlusive episodes at a well-tolerated dose of 2,400 mg per day. To determine the long-term efficacy and safety of NAC, a multicenter phase III clinical trial is required.", "PMID": "12701116"}, {"title": "Plasma zinc is an insensitive predictor of zinc status: use of plasma zinc in children with sickle cell disease.", "abstract": "This study was designed to explore the use of plasma zinc in determining zinc deficiency in children with sickle cell disease-SS (SCD-SS) as indicated by a growth response to zinc supplementation.\n\nFasting plasma zinc was assessed in children with SCD-SS (ages 4 to 10 years) who were randomly assigned to receive 10 mg zinc/d in cherry syrup (zinc) or cherry syrup alone (placebo) for 12 months. Evaluations for growth, dietary intake, and other biochemical parameters were made at baseline and 3, 6, and 12 months. Longitudinal mixed effects analysis evaluated differences between groups over 12 months.\n\nA total of 38 prepubertal children (20 male and 18 female; 18 zinc and 20 placebo) completed the study (7.1 +/- 1.7 years old). At baseline, plasma zinc was low (< or = 70 microg/dL) in 7 male subjects. Despite the significant increase in height over 12 months (+0.7 cm) with zinc supplementation (p = .019), plasma zinc did not change over the 12 months of study, and there was no association between plasma zinc and linear growth. Those children with low plasma zinc who received zinc supplementation showed improved linear growth.\n\nThese findings suggest that plasma zinc is an insensitive indicator of zinc status in children with SCD-SS. Children with low plasma zinc will benefit from zinc supplementation. However, some children with normal plasma zinc and poor growth may also have growth-limiting zinc deficiency and exhibit a growth response to zinc supplementation. Although this study focused on children with SCD-SS, results may be generalized to other pediatric clinical illnesses where nutrition-related growth failure is investigated.", "PMID": "16215013"}, {"title": "Zinc supplementation decreases oxidative stress, incidence of infection, and generation of inflammatory cytokines in sickle cell disease patients.", "abstract": "Zinc deficiency is common in adult sickle-cell disease (SCD) patients. We previously demonstrated that zinc supplementation to adult SCD patients decreased the incidences of infections and hospital admissions. We hypothesize that zinc supplementation improves T-helper cell function and decreases vascular endothelial cell activation, oxidative stress, and nuclear factor-kappa B (NF-kappaB)-DNA binding in mononuclear cells (MNCs) in SCD patients. To test this hypothesis, 36 SCD patients were recruited and randomly divided into 2 groups. One group (n = 18) received 25-mg zinc orally thrice a day for 3 months. The other group (n = 18) received placebo. The results indicate that the zinc-supplemented group had decreased incidence of infections compared with the placebo group. After zinc supplementation, red blood cell, hemoglobin (Hb), hematocrit, (Hct), plasma zinc, and antioxidant power increased; plasma nitrite and nitrate (NOx), lipid peroxidation products, DNA oxidation products, and soluble vascular cell adhesion molecule-1 decreased in the zinc-supplemented group, compared with the placebo group. Zinc-supplemented patients exhibited significant decreases in lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-alpha) and IL-1beta mRNAs, and TNF-induced nuclear factor of kappaB-DNA binding in MNCs, compared with the placebo group. Ex vivo addition of zinc to MNCs isolated from the placebo subjects decreased TNF-alpha and IL-1beta mRNAs. Zinc supplementation also increased relative levels of IL-2 and IL-2Ralpha mRNAs in phytohemagglutinin-p-stimulated MNCs. These results suggest that zinc supplementation may be beneficial to SCD patients.", "PMID": "18674741"}, {"title": "Alpha-lipoic acid modifies oxidative stress parameters in sickle cell trait subjects and sickle cell patients.", "abstract": "Oxidative stress plays a crucial role in the sickle cell disease. Alpha-lipoic acid (ALA) is a potent antioxidant that is employed in the treatment of several diseases. The objective of this study was to test the ALA effect in the sickle cell disease (SCD) treatment.\n\nSixty subjects were selected and divided into groups according to the hemoglobin profile: AA (normal), AS (SCD trait subject) and SS (SCD patient). Patients were randomized into a placebo-controlled trial and treated with either ALA (200 mg) or vehicle. Blood samples were collected before supplementation and after 3 months of treatment. Catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activities and total antioxidant status (TAS) were evaluated as measure of antioxidant defense. Lipid and protein damages were quantified by malondialdehyde (MDA) and carbonyl assays, respectively.\n\nCAT activity significantly increased in the AS group after ALA treatment and GPx activity presented significant decrease in all groups. SOD activity was not different in any group. Data on MDA and carbonyl levels showed significant reduction in the AA group with ALA treatment. TAS decreased in the same group.\n\nALA treatment protected AA individuals from oxidative damage to lipids and proteins. In SCD subjects, the dose applied was not effective to prevent the oxidative damage.", "PMID": "19231043"}, {"title": "A randomized phase II trial of Arginine Butyrate with standard local therapy in refractory sickle cell leg ulcers.", "abstract": "Sickle cell leg ulcers are often debilitating, refractory to healing, and prone to recurrence. Healing of leg ulcers was incidentally observed during dose-ranging trials of Arginine Butyrate in beta haemoglobinopathies. Here, a controlled Phase II trial was performed in sickle cell patients who had lower extremity ulcers refractory to standard care for at least 6 months. Patients were randomized to receive standard local care alone (Control Arm) or standard care with Arginine Butyrate administered 5 d/week (Treatment Arm), for 12 weeks. Ulcers were photographed weekly, traced, and ulcer areas were calculated by computerized planimetry and compared between the two study arms. Twenty-seven study courses were evaluated. Control Arm subjects had 25 ulcers with a mean area of 25\u00b77 cm(2) initially and 23\u00b72 cm(2) after 12 weeks; 2/25 (8%) healed completely. Treatment Arm subjects had 37 ulcers with a mean area of 50\u00b76 cm(2) initially and 28\u00b73 cm(2) at 12 weeks; 11/37 of these (30%) healed completely. After 3 months, proportions of ulcers which healed were 6/25 (24%) and 29/37 (78%), in the Control and Treatment Arms respectively (P < 0\u00b7001). These findings strongly suggest that Arginine Butyrate merits further evaluation for the treatment of refractory sickle cell leg ulcers in larger trials.", "PMID": "20955402"}, {"title": "N-acetylcysteine reduces oxidative stress in sickle cell patients.", "abstract": "Oxidative stress is of importance in the pathophysiology of sickle cell disease (SCD). In this open label randomized pilot study the effects of oral N-acetylcysteine (NAC) on phosphatidylserine (PS) expression as marker of cellular oxidative damage (primary end point), and markers of hemolysis, coagulation and endothelial activation and NAC tolerability (secondary end points) were studied. Eleven consecutive patients (ten homozygous [HbSS] sickle cell patients, one HbS\u03b2(0)-thalassemia patient) were randomly assigned to treatment with either 1,200 or 2,400 mg NAC daily during 6 weeks. The data indicate an increment in whole blood glutathione levels and a decrease in erythrocyte outer membrane phosphatidylserine exposure, plasma levels of advanced glycation end-products (AGEs) and cell-free hemoglobin after 6 weeks of NAC treatment in both dose groups. One patient did not tolerate the 2,400 mg dose and continued with the 1,200 mg dose. During the study period, none of the patients experienced painful crises or other significant SCD or NAC related complications. These data indicate that N-acetylcysteine treatment of sickle cell patients may reduce SCD related oxidative stress.", "PMID": "22318468"}, {"title": "N-acetylcysteine reduces oxidative stress in sickle cell patients.", "abstract": "Oxidative stress is of importance in the pathophysiology of sickle cell disease (SCD). In this open label randomized pilot study the effects of oral N-acetylcysteine (NAC) on phosphatidylserine (PS) expression as marker of cellular oxidative damage (primary end point), and markers of hemolysis, coagulation and endothelial activation and NAC tolerability (secondary end points) were studied. Eleven consecutive patients (ten homozygous [HbSS] sickle cell patients, one HbS\u03b2(0)-thalassemia patient) were randomly assigned to treatment with either 1,200 or 2,400 mg NAC daily during 6 weeks. The data indicate an increment in whole blood glutathione levels and a decrease in erythrocyte outer membrane phosphatidylserine exposure, plasma levels of advanced glycation end-products (AGEs) and cell-free hemoglobin after 6 weeks of NAC treatment in both dose groups. One patient did not tolerate the 2,400 mg dose and continued with the 1,200 mg dose. During the study period, none of the patients experienced painful crises or other significant SCD or NAC related complications. These data indicate that N-acetylcysteine treatment of sickle cell patients may reduce SCD related oxidative stress.", "PMID": "22318468"}, {"title": "No improvement in suboptimal vitamin A status with a randomized, double-blind, placebo-controlled trial of vitamin A supplementation in children with sickle cell disease.", "abstract": "Suboptimal vitamin A status is prevalent in children with type SS sickle cell disease (SCD-SS) and is associated with hospitalizations and poor growth and hematologic status. The supplemental vitamin A dose that optimizes suboptimal vitamin A status in this population is unknown.\n\nThe efficacy of Recommended Dietary Allowance (RDA) doses (based on age and sex) of vitamin A (300, 400, or 600 \u03bcg retinyl palmitate/d) or vitamin A + zinc (10 or 20 mg zinc sulfate/d) compared with placebo to optimize vitamin A status was assessed in children aged 2.0-12.9 y with SCD-SS and a suboptimal baseline serum retinol concentration (<30 \u03bcg/dL).\n\nIn this randomized, double-blind, placebo-controlled trial, vitamin A status (serum retinol, prealbumin, retinol-binding protein, and relative-dose-response test) and disease-related illness events were assessed.\n\nTwelve months of vitamin A supplementation at the doses recommended for healthy US children (based on age and sex) failed to improve serum retinol values in either group (vitamin A: n = 23; vitamin A + zinc: n = 18) compared with placebo (n = 21). By 12 mo, the increase (\u00b1SD) in serum retinol (3.6 \u00b1 2.8 \u03bcg/dL) in those taking 600 \u03bcg vitamin A/d was significantly different from the decrease (\u00b1SD; -2.8 \u00b1 2.4 \u03bcg/dL) in those taking 300 \u03bcg/d, which possibly suggests a dose-response relation (P < 0.05) with RDA doses.\n\nCompared with placebo, 12 mo of vitamin A supplementation at the RDA for healthy children did not improve serum retinol values in children with SCD-SS, which possibly suggests that higher doses are needed. However, the existence of alternative conclusions emphasizes the need for future research.", "PMID": "22952182"}], "labels": [{"PMID": "11434703", "label": "included"}, {"PMID": "11815322", "label": "included"}, {"PMID": "12701116", "label": "included"}, {"PMID": "16215013", "label": "included"}, {"PMID": "18674741", "label": "included"}, {"PMID": "19231043", "label": "included"}, {"PMID": "20955402", "label": "included"}, {"PMID": "22318468", "label": "included"}, {"PMID": "22318468", "label": "included"}, {"PMID": "22952182", "label": "included"}]}
{"metadata": {"review_pmid": "38770799"}, "inputs": {"background": "Because of wars, conflicts, persecutions, human rights violations, and humanitarian crises, about 84 million people are forcibly displaced around the world; the great majority of them live in low- and middle-income countries (LMICs). People living in humanitarian settings are affected by a constellation of stressors that threaten their mental health. Psychosocial interventions for people affected by humanitarian crises may be helpful to promote positive aspects of mental health, such as mental well-being, psychosocial functioning, coping, and quality of life. Previous reviews have focused on treatment and mixed promotion and prevention interventions. In this review, we focused on promotion of positive aspects of mental health.", "objectives": "To assess the effects of psychosocial interventions aimed at promoting mental health versus control conditions (no intervention, intervention as usual, or waiting list) in people living in LMICs affected by humanitarian crises.", "selection criteria": "Randomised controlled trials (RCTs) comparing psychosocial interventions versus control conditions (no intervention, intervention as usual, or waiting list) to promote positive aspects of mental health in adults and children living in LMICs affected by humanitarian crises. We excluded studies that enrolled participants based on a positive diagnosis of mental disorder (or based on a proxy of scoring above a cut-off score on a screening measure)."}, "context": [{"title": "Effectiveness and specificity of a classroom-based group intervention in children and adolescents exposed to war in Lebanon.", "abstract": "The purpose of this study was to examine the effectiveness and specificity of a classroom-based psychosocial intervention after war. All students (n=2500) of six villages in Southern Lebanon designated as most heavily exposed to war received a classroom-based intervention delivered by teachers, consisting of cognitive-behavioural and stress inoculation training strategies. A random sample of treated students (n=101) and a matched control group (n=93) were assessed one month post-war and one year later. Mental disorders and psychosocial stressors were assessed using the Diagnostic Interview for Children and Adolescents - Revised with children and parents. War exposure was measured using the War Events Questionnaire. The prevalence of major depressive disorder (MDD), separation anxiety disorder (SAD) and post-traumatic stress disorder (PTSD) was examined pre-war, one month post-war (pre-intervention), and one year post-war. Specificity of treatment was determined by rating teachers' therapy diaries. The rates of disorders peaked one month post-war and decreased over one year. There was no significant effect of the intervention on the rates of MDD, SAD or PTSD. Post-war MDD, SAD and PTSD were associated with pre-war SAD and PTSD, family violence parameters, financial problems and witnessing war events. These findings have significant policy and public health implications, given current practices of delivering universal interventions immediately post-war.", "PMID": "18560511"}, {"title": "School-based mental health intervention for children affected by political violence in Indonesia: a cluster randomized trial.", "abstract": "Little is known about the efficacy of mental health interventions for children exposed to armed conflicts in low- and middle-income settings. Childhood mental health problems are difficult to address in situations of ongoing poverty and political instability.\n\nTo assess the efficacy of a school-based intervention designed for conflict-exposed children, implemented in a low-income setting.\n\nA cluster randomized trial involving 495 children (81.4% inclusion rate) who were a mean (SD) age of 9.9 (1.3) years, were attending randomly selected schools in political violence-affected communities in Poso, Indonesia, and were screened for exposure (> or = 1 events), posttraumatic stress disorder, and anxiety symptoms compared with a wait-listed control group. Nonblinded assessment took place before, 1 week after, and 6 months after treatment between March and December 2006.\n\nFifteen sessions, over 5 weeks, of a manualized, school-based group intervention, including trauma-processing activities, cooperative play, and creative-expressive elements, implemented by locally trained paraprofessionals.\n\nWe assessed psychiatric symptoms using the Child Posttraumatic Stress Scale, Depression Self-Rating Scale, the Self-Report for Anxiety Related Disorders 5-item version, and the Children's Hope Scale, and assessed function impairment as treatment outcomes using standardized symptom checklists and locally developed rating scales.\n\nCorrecting for clustering of participants within schools, we found significantly more improvement in posttraumatic stress disorder symptoms (mean change difference, 2.78; 95% confidence interval [CI], 1.02 to 4.53) and maintained hope (mean change difference, -2.21; 95% CI, -3.52 to -0.91) in the treatment group than in the wait-listed group. Changes in traumatic idioms (stress-related physical symptoms) (mean change difference, 0.50; 95% CI, -0.12 to 1.11), depressive symptoms (mean change difference, 0.70; 95% CI, -0.08 to 1.49), anxiety (mean change difference, 0.12; 95% CI, -0.31 to 0.56), and functioning (mean change difference, 0.52; 95% CI, -0.43 to 1.46) were not different between the treatment and wait-listed groups.\n\nIn this study of children in violence-affected communities, a school-based intervention reduced posttraumatic stress symptoms and helped maintain hope, but did not reduce traumatic-stress related symptoms, depressive symptoms, anxiety symptoms, or functional impairment.\n\nisrctn.org Identifier: ISRCTN25172408.", "PMID": "18698064"}, {"title": "Preparing families of children with special health care needs for disasters: an education intervention.", "abstract": "Children with special health care needs pose a special challenge in post-disaster response. Current research suggests that the general population is not adequately prepared for a major disaster event, with members of vulnerable populations even less prepared. The purpose of this study was to determine the short-term effectiveness of a brief patient education intervention aimed at increasing levels of disaster preparedness among families of special health care needs children. One hundred twenty-one families were randomly assigned to either intervention or intervention plus incentive group. Families were surveyed prior to the intervention using a previously published instrument on family preparedness, and at 30-45 days post-intervention. A Preparedness Score was assigned to each family based on the number of items completed on the preparedness instrument. Significant differences were found between pre- and posttest scores for families that received the intervention, regardless of whether or not an incentive item was provided. Posttest scores were significantly higher than pretest scores, suggesting that the intervention was successful in increasing short-term overall levels of family preparedness in this population.", "PMID": "22583028"}, {"title": "Does combining infant stimulation with emergency feeding improve psychosocial outcomes for displaced mothers and babies? A controlled evaluation from northern Uganda.", "abstract": "Combined psychosocial and nutrition interventions improve the development of infants. However, there is a paucity of studies examining the effectiveness of such interventions in humanitarian settings. This article examines the impact of combining a group-based psychosocial intervention with an existing emergency feeding program for internally displaced mothers in Northern Uganda. The intervention consisted of mother and baby group sessions and home visits for mothers attending 3 emergency feeding centers. Psychosocial outcomes were compared with a contrast group of mothers who received nutritional support alone. The outcomes investigated were infant stimulation and maternal mood. After controlling for the effects of interview site and baseline scores, mothers in the intervention group (n = 70) showed greater involvement with their babies, more availability of play materials, and less sadness and worry at follow-up in comparison to the contrast group (n = 77). The intervention was acceptable to the mothers and easily taught. A proportion of the mothers chose to continue the intervention spontaneously with other mothers in their neighbourhoods. Further research needs to be done to validate these preliminary findings and explore the longer term impact on child growth and intellectual development as well as maternal mood.", "PMID": "22880973"}, {"title": "Group mental health interventions in civilian populations in war-conflict areas: a Lebanese pilot study.", "abstract": "Cognitive behavioral (CB) group therapy is an effective therapeutic intervention to treat war-related trauma. The aim of this pilot study was to describe the effects of conducting CB group therapy in a civilian population exposed to war in southern Lebanon.\n\nParticipants presenting with psychiatric symptoms attended an 8-week CB group therapy intervention adapted to the Lebanese culture. Observations from therapists' field notes were reviewed and grouped into commonalities.\n\nA majority of the total participants (N = 10) reported satisfaction with the CB therapy and a decrease in symptoms. Field notes revealed positive group interactions (i.e., sharing information, cohesiveness), therapeutic benefits (i.e., symptom identification, destigmatizing mental illness, learning coping strategies), and barriers to attendance (i.e., stigma, personal constraints).\n\nCB group therapy is a promising intervention for civilian survivors of war trauma. Challenges to conducting such interventions in a war-conflict area are discussed. Future research and intervention planning should address challenges faced during this study to better meet mental health needs.", "PMID": "24464029"}, {"title": "Effectiveness RCT of a CBT intervention for youths who lost parents in the Sichuan, China, earthquake.", "abstract": "Many children who lost parents in the 2008 earthquake in Sichuan Province, China, experienced symptoms of posttraumatic stress disorder (PTSD) and depression. This randomized controlled study compared the treatment effectiveness of short-term cognitive-behavioral therapy (CBT) with a general supportive intervention and with a control group of nontreatment. METHODS; Thirty-two Chinese adolescents were randomly assigned to three treatment groups. Participants were compared for psychological resilience (Connor-Davidson Resilience Scale), symptoms of PTSD (Children's Revised Impact of Events Scale), and depression (Center for Epidemiologic Studies Depression Scale) at baseline, after treatment, and three-month follow-up.\n\nCBT was effective in reducing PTSD and depressive symptoms and improved psychological resilience. General support was more effective than no intervention in improving psychological resilience.\n\nShort-term CBT group intervention seems to be a robust intervention for natural disaster victims. Short-term CBT group intervention was more effective than the general supportive intervention and the no-treatment group in enhancing psychological resilience and reducing PTSD and depression among adolescents who had lost parents in the earthquake. The general supportive intervention was effective only in improving psychological resilience.", "PMID": "24492904"}, {"title": "School-based mental health intervention for children in war-affected Burundi: a cluster randomized trial.", "abstract": "Armed conflicts are associated with a wide range of impacts on the mental health of children and adolescents. We evaluated the effectiveness of a school-based intervention aimed at reducing symptoms of posttraumatic stress disorder, depression, and anxiety (treatment aim); and improving a sense of hope and functioning (preventive aim).\n\nWe conducted a cluster randomized trial with 329 children in war-affected Burundi (aged 8 to 17 (mean 12.29 years, standard deviation 1.61); 48% girls). One group of children (n = 153) participated in a 15-session school-based intervention implemented by para-professionals, and the remaining 176 children formed a waitlist control condition. Outcomes were measured before, one week after, and three months after the intervention.\n\nNo main effects of the intervention were identified. However, longitudinal growth curve analyses showed six favorable and two unfavorable differences in trajectories between study conditions in interaction with several moderators. Children in the intervention condition living in larger households showed decreases on depressive symptoms and function impairment, and those living with both parents showed decreases on posttraumatic stress disorder and depressive symptoms. The groups of children in the waitlist condition showed increases in depressive symptoms. In addition, younger children and those with low levels of exposure to traumatic events in the intervention condition showed improvements on hope. Children in the waitlist condition who lived on their original or newly bought land showed improvements in hope and function impairment, whereas children in the intervention condition showed deterioration on these outcomes.\n\nGiven inconsistent effects across studies, findings do not support this school-based intervention as a treatment for posttraumatic stress disorder and depressive symptoms in conflict-affected children. The intervention appears to have more consistent preventive benefits, but these effects are contingent upon individual (for example, age, gender) and contextual (for example, family functioning, state of conflict, displacement) variables. Results suggest the potential benefit of school-based preventive interventions particularly in post-conflict settings.\n\nThe study was registered as ISRCTN42284825.", "PMID": "24690470"}, {"title": "The Youth Readiness Intervention for war-affected youth.", "abstract": "Mental disorders are among the largest contributors to the global burden of disease. Since the cessation of the Sierra Leonean civil war in 2002, there have been few mental health resources available for war-affected youth. Co-occurring psychological problems are commonly reported by youth in the post-conflict setting, suggesting a need for evidence-based interventions that cater to comorbid psychological difficulties. This feasibility study outlines the implementation and evaluation of a mixed-methods approach for developing and piloting a culturally grounded group mental health treatment-the Youth Readiness Intervention (YRI)-for war-affected Sierra Leonean youth.\n\nParticipating youth (N\u00a0= 32; 50% female; ages, 15-24 years) were allocated to one of four gender- and age-stratified groups, facilitated by gender-matched Sierra Leonean interventionists. The intervention comprised adapted cognitive behavioral therapy techniques to address issues pertinent to war-affected youth. Analyses comprised assessments of reliable symptom change, mental health, functional adaptation, and interventionist fidelity outcomes.\n\nThe YRI was found to be acceptable, feasible and associated with reliable changes in internalizing and externalizing symptoms and improvements in functional impairments and emotion regulation (mean effect size, d\u00a0= .64).\n\nYouth struggling with the mental health consequences of past trauma due to war merit special attention. The YRI presents a feasible and acceptable intervention for use in this low resource setting. A randomized controlled trial is planned to further test intervention effectiveness and scalability.", "PMID": "26003574"}, {"title": "Effectiveness of Trauma-Focused Cognitive Behavioral Therapy Among Trauma-Affected Children in Lusaka, Zambia: A Randomized Clinical Trial.", "abstract": "Orphans and vulnerable children (OVC) are at high risk for experiencing trauma and related psychosocial problems. Despite this, no randomized clinical trials have studied evidence-based treatments for OVC in low-resource settings.\n\nTo evaluate the effectiveness of lay counselor-provided trauma-focused cognitive behavioral therapy (TF-CBT) to address trauma and stress-related symptoms among OVC in Lusaka, Zambia.\n\nThis randomized clinical trial compared TF-CBT and treatment as usual (TAU) (varying by site) for children recruited from August 1, 2012, through July 31, 2013, and treated until December 31, 2013, for trauma-related symptoms from 5 community sites within Lusaka, Zambia. Children were aged 5 through 18 years and had experienced at least one traumatic event and reported significant trauma-related symptoms. Analysis was with intent to treat.\n\nThe intervention group received 10 to 16 sessions of TF-CBT (n = 131). The TAU group (n = 126) received usual community services offered to OVC.\n\nThe primary outcome was mean item change in trauma and stress-related symptoms using a locally validated version of the UCLA Posttraumatic Stress Disorder Reaction Index (range, 0-4) and functional impairment using a locally developed measure (range, 0-4). Outcomes were measured at baseline and within 1 month after treatment completion or after a waiting period of approximately 4.5 months after baseline for TAU.\n\nAt follow-up, the mean item change in trauma symptom score was -1.54 (95% CI, -1.81 to -1.27), a reduction of 81.9%, for the TF-CBT group and -0.37 (95% CI, -0.57 to -0.17), a reduction of 21.1%, for the TAU group. The mean item change for functioning was -0.76 (95% CI, -0.98 to -0.54), a reduction of 89.4%, and -0.54 (95% CI, -0.80 to -0.29), a reduction of 68.3%, for the TF-CBT and TAU groups, respectively. The difference in change between groups was statistically significant for both outcomes (P <\u2009.001). The effect size (Cohen d) was 2.39 for trauma symptoms and 0.34 for functioning. Lay counselors participated in supervision and assessed whether the intervention was provided with fidelity in all 5 community settings.\n\nThe TF-CBT adapted for Zambia substantially decreased trauma and stress-related symptoms and produced a smaller improvement in functional impairment among OVC having experienced high levels of trauma.\n\nclinicaltrials.gov Identifier: NCT01624298.", "PMID": "26111066"}, {"title": "Community-based mental health treatments for survivors of torture and militant attacks in Southern Iraq: a randomized control trial.", "abstract": "Systematic violence is a long-standing problem in Iraq. Research indicates that survivors often experience multiple mental health problems, and that there is a need for more rigorous research that targets symptoms beyond post-traumatic stress (PTS). Our objective was to test the effectiveness of two counseling therapies in Southern Iraq in addressing multiple mental health problems among survivors of systematic violence: (1) a transdiagnostic intervention (Common Elements Treatment Approach or CETA); and (2) cognitive processing therapy (CPT). The therapies were provided by non-specialized health workers since few MH professionals are available to provide therapy in Iraq.\n\nThis was a randomized, parallel, two site, two-arm (1:1 allocation), single-blinded, wait-list controlled (WLC) trial of CETA in one site (99 CETA, 50 WLC), and CPT in a second site (129 CPT, 64 WLC). Eligibility criteria were elevated trauma symptoms and experience of systematic violence. The primary and secondary outcomes were trauma symptoms and dysfunction, respectively, with additional assessment of depression and anxiety symptoms. Non-specialized health workers (community mental health worker, CMHW) provided the interventions in government-run primary health centers. Treatment effects were determined using longitudinal, multilevel models with CMHW and client as random effects, and a time by group interaction with robust variance estimation, to test for the net difference in mean score for each outcome between the baseline and follow up interview. Multiple imputation techniques were used to account for missingness at the item level and the participant level. All analyses were conducted using Stata 12.\n\nThe CETA intervention showed large effect sizes for all outcomes. The CPT intervention showed moderate effects sizes for trauma and depression, with small to no effect for anxiety or dysfunction, respectively.\n\nBoth CETA and CPT appear to benefit survivors of systematic violence in Southern Iraq by reducing multiple mental health symptoms, with CETA providing a very large benefit across a range of symptoms. Non-specialized health workers were able to treat comorbid symptoms of trauma, depression and anxiety, and dysfunction among survivors of systematic violence who have limited access to mental health professionals. The trial further supports the use of evidence-based therapies in lower-resource settings.\n\nThis trial was registered at ClinicalTrials.gov on 16 July 2010 with an identifier of NCT01177072 as the Study of Effectiveness of Mental Health Interventions among Torture Survivors in Southern Iraq. The study protocol can be downloaded from the following website: http://tinyurl.com/CETA-Iraq-Protocol . In the protocol, the CETA intervention is given a different name: components-based intervention or CBI.", "PMID": "26467303"}], "labels": [{"PMID": "18560511", "label": "excluded"}, {"PMID": "18698064", "label": "excluded"}, {"PMID": "22583028", "label": "excluded"}, {"PMID": "22880973", "label": "excluded"}, {"PMID": "24464029", "label": "excluded"}, {"PMID": "24492904", "label": "excluded"}, {"PMID": "24690470", "label": "excluded"}, {"PMID": "26003574", "label": "excluded"}, {"PMID": "26111066", "label": "excluded"}, {"PMID": "26467303", "label": "excluded"}]}
{"metadata": {"review_pmid": "38763518"}, "inputs": {"background": "Prevention of obesity in adolescents is an international public health priority. The prevalence of overweight and obesity is over 25% in North and South America, Australia, most of Europe, and the Gulf region. Interventions that aim to prevent obesity involve strategies that promote healthy diets or 'activity' levels (physical activity, sedentary behaviour and/or sleep) or both, and work by reducing energy intake and/or increasing energy expenditure, respectively. There is uncertainty over which approaches are more effective, and numerous new studies have been published over the last five years since the previous version of this Cochrane Review.", "objectives": "To assess the effects of interventions that aim to prevent obesity in adolescents by modifying dietary intake or 'activity' levels, or a combination of both, on changes in BMI, zBMI score and serious adverse events.", "selection criteria": "Randomised controlled trials in adolescents (mean age 12 years and above but less than 19 years), comparing diet or 'activity' interventions (or both) to prevent obesity with no intervention, usual care, or with another eligible intervention, in any setting. Studies had to measure outcomes at a minimum of 12 weeks post baseline. We excluded interventions designed primarily to improve sporting performance."}, "context": [{"title": "New Moves: a school-based obesity prevention program for adolescent girls.", "abstract": "This study tests the feasibility of an innovative school-based program for obesity prevention among adolescent girls. New Moves was implemented as a multicomponent, girls-only, high-school physical education class.\n\nSix schools were equally randomized into intervention and control conditions. Data were collected at baseline, postintervention, and 8-month follow-up to assess program impact on physical activity, eating patterns, self-perceptions, and body mass index (BMI) among 89 girls in the intervention and 112 girls in the control conditions. Program evaluation also included interviews with school staff, parent surveys, and participant interviews and process evaluation surveys.\n\nThe feasibility of implementing New Moves was high, as indicated by strong satisfaction among participants, parents, and school staff, and by program sustainability. Participants perceived a positive program impact on their physical activity, eating patterns, and self-image. Girls in the intervention significantly progressed in their stage of behavioral change for physical activity from baseline to follow-up. However, for the majority of outcome variables, differences between intervention and control schools at postintervention and follow-up were not statistically significant.\n\nNew Moves was well received and fills a needed niche within school physical education programs. An expanded intervention and evaluation is needed to enhance and assess long-term program effectiveness.", "PMID": "12799128"}, {"title": "Improvements in heart health behaviors and reduction in coronary artery disease risk factors in urban teenaged girls through a school-based intervention: the PATH program.", "abstract": "We sought to assess the effects of a school-based intervention program on cardiovascular disease risk factors in urban girls.\n\nWe compared heart health knowledge, health behaviors, cardiovascular risk factors, and physical fitness among a group of 442 multiethnic teenaged girls (310 experimental participants vs 132 control participants). Testing was conducted before and after a 12-week program of vigorous exercises integrated with lectures and discussions on diet, exercise, stress, and smoking.\n\nSignificant differences in body fat, systolic and diastolic blood pressure, heart health knowledge, and whether breakfast was eaten were observed between experimental participants and control participants.\n\nAn integrated program of exercise and heart health-related lectures and discussions had a beneficial effect on health knowledge, health behaviors, and onset of risk factors for coronary artery disease among urban girls.", "PMID": "15333311"}, {"title": "Promotion of physical activity among high-school girls: a randomized controlled trial.", "abstract": "Many adolescent girls fail to meet national guidelines for physical activity, and the prevalence of obesity is increasing among this group. Our study examined the effects of a comprehensive school-based intervention on physical activity among high-school girls.\n\nA group-randomized controlled field trial was conducted at 24 high schools. A school-based sample of 2744 girls (48.7% African American, 46.7% White) participated in a measurement protocol when they were in eighth and then ninth grade. A comprehensive physical activity intervention was designed to change the instructional program and the school environment to increase support for physical activity among girls.\n\nAt follow-up, 45% of girls in the intervention schools and 36% of girls in the control schools reported vigorous physical activity during an average of 1 or more 30-minute time blocks per day over a 3-day period.\n\nA comprehensive school-based intervention can increase regular participation in vigorous physical activity among high-school girls.", "PMID": "16118370"}, {"title": "Fit for Life Boy Scout badge: outcome evaluation of a troop and Internet intervention.", "abstract": "This study reports the results of a 9-week intervention on the physical activity levels of adolescent males.\n\nParticipants were 473 10- to 14-year-old Houston Boy Scouts (42 troops) with troops randomly assigned to intervention or control conditions. Data were collected in spring (16 troops) and fall (26 troop) waves during 2003. Intervention participants received a 9-week troop and Internet program to increase physical activity skills, self-efficacy and goal-setting. Physical activity was assessed at baseline, end of the intervention (Post#1) and post-6 months (Post#2) by accelerometer. Minutes of sedentary, light and moderate to vigorous physical activity were calculated. Repeated measure analyses were performed to test differences in physical activity over time between groups with participants nested in troops.\n\nA three-way interaction (group * time * wave) that approached significance (P = 0.051) indicated a 12-min reduction in sedentary behavior among spring intervention participants. A significant three-way interaction (P = 0.011) (group * time * wave) indicated a 12-min increase in light intensity activity among the spring intervention group.\n\nParticipation in the Fit for Life badge program resulted in a trend towards a small decrease in sedentary behavior and increased light intensity physical activity among spring participants only. There was no effect on moderate to vigorous physical activity.", "PMID": "16458955"}, {"title": "Randomized controlled trial of a primary care and home-based intervention for physical activity and nutrition behaviors: PACE+ for adolescents.", "abstract": "Many adolescents do not meet national guidelines for participation in regular moderate or vigorous physical activity (PA); limitations on sedentary behaviors; or dietary intake of fruits and vegetables, fiber, or total dietary fat. This study evaluated a health care-based intervention to improve these behaviors.\n\nRandomized controlled trial.\n\nPrimary care with follow-up at home.\n\nEight hundred seventy-eight adolescent girls and boys aged 11 to 15 years.\n\nTwo experimental conditions: (1) Primary care, office-based, computer-assisted diet and PA assessment and stage-based goal setting followed by brief health care provider counseling and 12 months of monthly mail and telephone counseling and (2) a comparison condition addressing sun exposure protection.\n\nMinutes per week of moderate plus vigorous PA measured by self-report and accelerometer; self-report of days per week of PA and sedentary behaviors; and percentage of energy from fat and servings per day of fruits and vegetables measured by three 24-hour diet recalls. Body mass index (calculated as weight in kilograms divided by the square of height in meters) was a secondary outcome.\n\nCompared with adolescents in the sun protection condition, girls and boys in the diet and PA intervention significantly reduced sedentary behaviors (intervention vs control change, 4.3 to 3.4 h/d vs 4.2 to 4.4 h/d for girls, respectively [P = .001]; 4.2 to 3.2 h/d vs 4.2 to 4.3 h/d for boys, respectively [P = .001]). Boys reported more active days per week (intervention vs control change: 4.1 to 4.4 d/wk vs 3.8 to 3.8 d/w, respectively [P = .01]), and the number of servings of fruits and vegetables for girls approached significance (intervention vs control change, 3.5 to 4.2 servings/d vs 3.5 to 3.9 servings/d, respectively [P = .07]). No intervention effects were seen with percentage of calories from fat or minutes of PA per week. Percentage of adolescents meeting recommended health guidelines was significantly improved for girls for consumption of saturated fat (intervention vs control change, 23.4% to 41.0% vs 18.5% to 31%, respectively [relative risk, 1.33; 95% confidence interval, 1.01-1.68]) and for boys' participation in d/wk of PA (intervention vs control change, 45.3% to 55.4% vs 41.9% to 38.0%, respectively [relative risk, 1.47; 95% confidence interval, 1.19-1.75]). No between-group differences were seen in body mass index.\n\nImprovements in some diet, PA, and sedentary behaviors in adolescents can be enabled through the use of a 1-year, integrated intervention using the computer, health provider counseling, mail, and telephone. The amount of intervention received may contribute to its efficacy.", "PMID": "16461867"}, {"title": "Environmental interventions for eating and physical activity: a randomized controlled trial in middle schools.", "abstract": "Our objective was to evaluate the effects of environmental, policy, and social marketing interventions on physical activity and fat intake of middle school students on campus.\n\nTwenty-four middle schools were randomly assigned to intervention or control conditions. Baseline measures were collected in spring 1997, and interventions were conducted during the 1997-1998 and 1998-1999 school years SETTING/PARTICIPATION: The schools had mean enrollments of 1109, with 44.5% nonwhite students. Over 2 years, physical activity interventions were designed to increase physical activity in physical education classes and throughout the school day. Nutrition interventions were designed to provide and market low-fat foods at all school food sources, including cafeteria breakfasts and lunches, a la carte sources, school stores, and bag lunches. School staff and students were engaged in policy change efforts, but there was no classroom health education.\n\nPrimary outcomes were measured by direct observation and existing records.\n\nRandomized regression models (N =24 schools) revealed a significant intervention effect for physical activity for the total group (p <0.009) and boys (p <0.001), but not girls (p <0.40). The intervention was not effective for total fat (p <0.91) or saturated fat (p <0.79). Survey data indicated that the interventions reduced reported body mass index for boys (p <0.05).\n\nEnvironmental and policy interventions were effective in increasing physical activity at school among boys but not girls. The interventions were not effective in reducing fat intake at school. School environmental and policy interventions have the potential to improve health behavior of the student population, but barriers to full implementation need to be better understood and overcome.", "PMID": "12657338"}, {"title": "Evaluation of a two-year middle-school physical education intervention: M-SPAN.", "abstract": "School physical education (PE) is highly recommended as a means of promoting physical activity, and randomized studies of health-related PE interventions in middle schools have not been reported. We developed, implemented, and assessed an intervention to increase physical activity during middle-school PE classes.\n\nTwenty-four middle schools (approximately 25,000 students, 45% nonwhite) in Southern California participated in a randomized trial. Schools were assigned to intervention (N = 12) or control (N = 12) conditions, and school was the unit of analysis. A major component of the intervention was a 2-yr PE program, which consisted of curricular materials, staff development, and on-site follow-up. Control schools continued usual programs. Student activity and lesson context were observed in 1849 PE lessons using a validated instrument during baseline and intervention years 1 and 2.\n\nThe intervention significantly (P = 0.02) improved student moderate to vigorous physical activity (MVPA) in PE, by approximately 3 min per lesson. Effects were cumulative; by year 2 intervention schools increased MVPA by 18%. Effect sizes were greater for boys (d = 0.98; large) than girls (d = 0.68; medium).\n\nA standardized program increased MVPA in middle schools without requiring an increase in frequency or duration of PE lessons. Program components were well received by teachers and have the potential for generalization to other schools. Additional strategies may be needed for girls.", "PMID": "15292747"}, {"title": "Girls on the move program to increase physical activity participation.", "abstract": "Because physical inactivity poses serious health risks, interventions are urgently needed to reverse the increasingly sedentary lifestyles of adolescent girls.\n\nThe aim of this study was to determine the feasibility of \"Girls on the Move,\" an individually tailored computerized physical activity (PA) program plus nurse counseling intervention, in increasing PA.\n\nA pretest-posttest control group design was used with 77 racially diverse sedentary girls in Grades 6, 7, and 8 from two middle schools. Each of the instructional grades was randomly assigned to either an intervention or control condition. After completing computerized questionnaires, each girl in the control group received a handout listing the PA recommendations. To encourage PA, each girl in the intervention group received computerized, individually tailored feedback messages based on her responses to the questionnaires, individual counseling from the school's pediatric nurse practitioner (PNP), and telephone calls and mailings from a trained research assistant. At 12 weeks, girls in both groups responded to the questionnaires.\n\nNo differences in self-reported PA emerged between the intervention and control groups at Weeks 1 (baseline) and 12 (postintervention). Repeated measures ANOVA showed a significant interaction between group and time for social support for PA, F(1, 69) = 5.73, p = .019, indicating that the intervention group had significantly greater social support across time than did the control group. From baseline to postintervention, social support increased for the intervention group but decreased for the control group.\n\nReasons for the lack of significant differences between the groups on the PA measures were cited. Important information that could inform subsequent studies that test interventions to increase youth PA was acquired from conducting this study. Future efforts to increase PA participation might include this approach for enhancing social support for PA.", "PMID": "16708045"}, {"title": "Enhancing physical and social environments to reduce obesity among public housing residents: rationale, trial design, and baseline data for the Healthy Families study.", "abstract": "Intervention programs that change environments have the potential for greater population impact on obesity compared to individual-level programs. We began a cluster randomized, multi-component multi-level intervention to improve weight, diet, and physical activity among low-socioeconomic status public housing residents. Here we describe the rationale, intervention design, and baseline survey data. After approaching 12 developments, ten were randomized to intervention (n=5) or assessment-only control (n=5). All residents in intervention developments are welcome to attend any intervention component: health screenings, mobile food bus, walking groups, cooking demonstrations, and a social media campaign; all of which are facilitated by community health workers who are residents trained in health outreach. To evaluate weight and behavioral outcomes, a subgroup of female residents and their daughters age 8-15 were recruited into an evaluation cohort. In total, 211 households completed the survey (RR=46.44%). Respondents were Latino (63%), Black (24%), and had \u2264 high school education (64%). Respondents reported \u22642 servings of fruits & vegetables/day (62%), visiting fast food restaurants 1+ times/week (32%), and drinking soft drinks daily or more (27%). The only difference between randomized groups was race/ethnicity, with more Black residents in the intervention vs. control group (28% vs. 19%, p=0.0146). Among low-socioeconomic status urban public housing residents, we successfully recruited and randomized families into a multi-level intervention targeting obesity. If successful, this intervention model could be adopted in other public housing developments or entities that also employ community health workers, such as food assistance programs or hospitals. ", "PMID": "25139728"}, {"title": "A national school-based health lifestyles interventions among Chinese children and adolescents against obesity: rationale, design and methodology of a randomized controlled trial in China.", "abstract": "The prevalence of obesity among children and adolescents has been rapidly rising in Mainland China in recent decades, both in urban and rural areas. There is an urgent need to develop effective interventions to prevent childhood obesity. Limited rigid data regarding children and adolescent overweight prevention in China are available. A national random controlled school-based obesity intervention program was developed in the mainland of China.\n\nThe study was designed as a national multi-centered cluster randomized controlled trial involving more than 70,000 children and adolescents aged 7-18 years from 7 provinces in China. In each center, about 12-16 primary and secondary schools, with totally at least 10000 participants were randomly selected (Primary: Secondary\u2009=\u20091:1). All of the selected schools were randomly allocated to either intervention or control group (Intervention: Control\u2009=\u20091:1).The multi-components school-based and family-involved scheme was conducted within the intervention group for 9\u00a0month, while students in the control group followed their usual health practice. The intervention consisted of four components: a) Create supportive school and family environment, b) Health lifestyles education and related compulsory physical activities, c) Instruct and promote school physical education, d) Self-monitor obesity related behaviors. Four types of outcomes including anthropometric, behavioral, blood chemical and physical fitness were measured to assess the effectiveness of the intervention program.\n\nThis is the first and largest multi-centered school-based obesity intervention program with the consideration of geographical and social-demographic characteristics of the rapidly increased obesity prevalence of Chinese children and adolescent. The intervention is based on Social Cognitive Theory and Social-Ecological Model of Health, and follows a stepwise approach guided by PRECEDE-PROCEED (P-P) Model and Intervention Map. The results of and lesson learned from this study will help guide future school-based national childhood obesity prevention programs in Mainland China.\n\nJanuary 22, 2015;\n\nNCT02343588.", "PMID": "25885323"}], "labels": [{"PMID": "12799128", "label": "included"}, {"PMID": "15333311", "label": "included"}, {"PMID": "16118370", "label": "included"}, {"PMID": "16458955", "label": "included"}, {"PMID": "16461867", "label": "included"}, {"PMID": "12657338", "label": "excluded"}, {"PMID": "15292747", "label": "excluded"}, {"PMID": "16708045", "label": "excluded"}, {"PMID": "25139728", "label": "excluded"}, {"PMID": "25885323", "label": "excluded"}]}
{"metadata": {"review_pmid": "38763517"}, "inputs": {"background": "Prevention of obesity in children is an international public health priority given the prevalence of the condition (and its significant impact on health, development and well-being). Interventions that aim to prevent obesity involve behavioural change strategies that promote healthy eating or 'activity' levels (physical activity, sedentary behaviour and/or sleep) or both, and work by reducing energy intake and/or increasing energy expenditure, respectively. There is uncertainty over which approaches are more effective and numerous new studies have been published over the last five years, since the previous version of this Cochrane review.", "objectives": "To assess the effects of interventions that aim to prevent obesity in children by modifying dietary intake or 'activity' levels, or a combination of both, on changes in BMI, zBMI score and serious adverse events.", "selection criteria": "Randomised controlled trials in children (mean age 5 years and above but less than 12 years), comparing diet or 'activity' interventions (or both) to prevent obesity with no intervention, usual care, or with another eligible intervention, in any setting. Studies had to measure outcomes at a minimum of 12 weeks post baseline. We excluded interventions designed primarily to improve sporting performance."}, "context": [{"title": "Reducing obesity via a school-based interdisciplinary intervention among youth: Planet Health.", "abstract": "To evaluate the impact of a school-based health behavior intervention known as Planet Health on obesity among boys and girls in grades 6 to 8.\n\nRandomized, controlled field trial with 5 intervention and 5 control schools. Outcomes were assessed using preintervention (fall 1995) and follow-up measures (spring 1997), including prevalence, incidence, and remission of obesity.\n\nA group of 1295 ethnically diverse grade 6 and 7 students from public schools in 4 Massachusetts communities.\n\nStudents participated in a school-based interdisciplinary intervention over 2 school years. Planet Health sessions were included within existing curricula using classroom teachers in 4 major subjects and physical education. Sessions focused on decreasing television viewing, decreasing consumption of high-fat foods, increasing fruit and vegetable intake, and increasing moderate and vigorous physical activity.\n\nObesity was defined as a composite indicator based on both a body mass index and a triceps skinfold value greater than or equal to age- and sex-specific 85th percentiles. Because schools were randomized, rather than students, the generalized estimating equation method was used to adjust for individual-level covariates under cluster randomization.\n\nThe prevalence of obesity among girls in intervention schools was reduced compared with controls, controlling for baseline obesity (odds ratio, 0.47; 95% confidence interval, 0.24-0.93; P = .03), with no differences found among boys. There was greater remission of obesity among intervention girls vs. control girls (odds ratio, 2.16; 95% confidence interval, 1.07-4.35; P = .04). The intervention reduced television hours among both girls and boys, and increased fruit and vegetable consumption and resulted in a smaller increment in total energy intake among girls. Reductions in television viewing predicted obesity change and mediated the intervention effect. Among girls, each hour of reduction in television viewing predicted reduced obesity prevalence (odds ratio, 0.85; 95% confidence interval, 0.75-0.97; P = .02).\n\nPlanet Health decreased obesity among female students, indicating a promising school-based approach to reducing obesity among youth.", "PMID": "10201726"}, {"title": "Increasing fruit and vegetable intake and decreasing fat and sugar intake in families at risk for childhood obesity.", "abstract": "The goal of this study was to evaluate the effect of a parent-focused behavioral intervention on parent and child eating changes and on percentage of overweight changes in families that contain at least one obese parent and a non-obese child.\n\nFamilies with obese parents and non-obese children were randomized to groups in which parents were provided a comprehensive behavioral weight-control program and were encouraged to increase fruit and vegetable intake or decrease intake of high-fat/high-sugar foods. Child materials targeted the same dietary changes as their parents without caloric restriction.\n\nChanges over 1 year showed that treatment influenced targeted parent and child fruit and vegetable intake and high-fat/high-sugar intake, with the Increase Fruit and Vegetable group also decreasing their consumption of high-fat/high-sugar foods. Parents in the increased fruit and vegetable group showed significantly greater decreases in percentage of overweight than parents in the decreased high-fat/high-sugar group.\n\nThese results suggest that focusing on increasing intake of healthy foods may be a useful approach for nutritional change in obese parents and their children.", "PMID": "11323442"}, {"title": "Evaluation of implementation and effect of primary school based intervention to reduce risk factors for obesity.", "abstract": "To implement a school based health promotion programme aimed at reducing risk factors for obesity and to evaluate the implementation process and its effect on the school.\n\nData from 10 schools participating in a group randomised controlled crossover trial were pooled and analysed.\n\n10 primary schools in Leeds.\n\n634 children (350 boys and 284 girls) aged 7-11 years.\n\nResponse rates to questionnaires, teachers' evaluation of training and input, success of school action plans, content of school meals, and children's knowledge of healthy living and self reported behaviour.\n\nAll 10 schools participated throughout the study. 76 (89%) of the action points determined by schools in their school action plans were achieved, along with positive changes in school meals. A high level of support for nutrition education and promotion of physical activity was expressed by both teachers and parents. 410 (64%) parents responded to the questionnaire concerning changes they would like to see implemented in school. 19 out of 20 teachers attended the training, and all reported satisfaction with the training, resources, and support. Intervention children showed a higher score for knowledge, attitudes, and self reported behaviour for healthy eating and physical activity.\n\nThis programme was successfully implemented and produced changes at school level that tackled risk factors for obesity.", "PMID": "11691758"}, {"title": "Randomised controlled trial of primary school based intervention to reduce risk factors for obesity.", "abstract": "To assess if a school based intervention was effective in reducing risk factors for obesity.\n\nGroup randomised controlled trial.\n\n10 primary schools in Leeds.\n\n634 children aged 7-11 years.\n\nTeacher training, modification of school meals, and the development of school action plans targeting the curriculum, physical education, tuck shops, and playground activities.\n\nBody mass index, diet, physical activity, and psychological state.\n\nVegetable consumption by 24 hour recall was higher in children in the intervention group than the control group (weighted mean difference 0.3 portions/day, 95% confidence interval 0.2 to 0.4), representing a difference equivalent to 50% of baseline consumption. Fruit consumption was lower in obese children in the intervention group (-1.0, -1.8 to -0.2) than those in the control group. The three day diary showed higher consumption of high sugar foods (0.8, 0.1 to 1.6)) among overweight children in the intervention group than the control group. Sedentary behaviour was higher in overweight children in the intervention group (0.3, 0.0 to 0.7). Global self worth was higher in obese children in the intervention group (0.3, 0.3 to 0.6). There was no difference in body mass index, other psychological measures, or dieting behaviour between the groups. Focus groups indicated higher levels of self reported behaviour change, understanding, and knowledge among children who had received the intervention.\n\nAlthough it was successful in producing changes at school level, the programme had little effect on children's behaviour other than a modest increase in consumption of vegetables.", "PMID": "11691759"}, {"title": "Girls health Enrichment Multi-site Studies (GEMS): new approaches to obesity prevention among young African-American girls.", "abstract": "The Girls health Enrichment Multi-site Studies (GEMS) is an obesity prevention research program sponsored by the National Heart, Lung, and Blood Institute (NHLBI), targeting young African-American girls. Expert groups have suggested that the high prevalence of obesity in African-American women could be a contributing factor to their excess morbidity and mortality from cardiovascular disease compared to women from other ethnic groups. To address the issue of obesity and its origins in African-American women, the NHLBI Growth and Health Study (NGHS) was initiated to investigate factors related to the development of obesity and associated cardiovascular disease risk factors in a cohort of young African-American and White girls, aged 9 and 10 years. Findings from NGHS, and the realization that obesity had become a major public health problem, subsequently led to a 2-phase, 7-year collaborative obesity prevention research program, the Girls health Enrichment Multi-site Studies (GEMS). Initiated in 1999, Phase 1 of GEMS was conducted collaboratively among 4 participating field centers, a coordinating center, and the NHLBI project office to conduct formative assessment research and to pilot test, over a 12-week period, interventions that might be effective in reducing the rate of weight gain in African-American girls, aged 8-10 years. Over a 2-year period, Phase 2 of GEMS will test the interventions that appear most promising in preventing excessive weight gain in young African-American girls. The experiences of the GEMS pilot studies will help guide future intervention research for obesity prevention beginning in childhood. This report describes the background and rationale for the GEMS initiative. This journal supplement describes the experiences of the GEMS Phase 1 program.", "PMID": "12713206"}, {"title": "Common design elements of the Girls health Enrichment Multi-site Studies (GEMS).", "abstract": "The Girls health Enrichment Multi-site Studies (GEMS) was a multi-center research program created for the purpose of testing interventions designed to prevent excess weight gain by African-American girls, as they enter and proceed through puberty. However, GEMS was not a \"multi-center clinical trial\" in the usual sense. Although these studies applied similar eligibility criteria, observed a similar follow-up schedule, and followed a similar measurement protocol, important differences existed, as well. Each field center developed its own intervention(s) and corresponding control, and tailored its study to the specific hypothesis being tested. Therefore, the study populations were somewhat different, with recruitment strategies that varied accordingly, and supplemental evaluations appropriate to the specific interventions were conducted on a site-specific basis. The purpose of this paper is to describe the common design elements of the GEMS Phase 1 pilot studies. This report presents the basic study design, a brief overview of the interventions, the measurements taken and their rationale, and procedures both for compiling the collaborative database, and performing site-specific analyses.", "PMID": "12713207"}, {"title": "The Fun, Food, and Fitness Project (FFFP): the Baylor GEMS pilot study.", "abstract": "The Girls health Enrichment Multisite Studies (GEMS) Fun, Food, and Fitness Project (FFFP) was designed to prevent obesity among 8-year-old African-American girls.\n\nTwelve-week, two-arm parallel group randomized controlled pilot study.\n\nSummer day camp and homes in Houston, Texas.\n\nThirty-five girls and their parents or caregivers were randomly assigned to treatment (N=19) or control groups (N=16).\n\nGirls in the intervention group attended a special 4-week summer day camp, followed by a special 8-week home Internet intervention for the girls and their parents. Control group girls attended a different 4-week summer day camp, followed by a monthly home Internet intervention, neither of which components included the GEMS-FFFP enhancements.\n\nBody mass index (BMI), consumption of fruit, 100% fruit juice, and vegetables (FJV), physical activity.\n\nAfter adjusting for baseline BMI, there were no significant differences in BMI between treatment and control group girls, either at the end of the 4-week summer day camp, or after the full 12-week intervention. By the end of the summer camp, the subgroup of treatment group girls heavier at baseline exhibited a trend (P<.08) toward lower BMI, compared to their heavier counterparts in the control group. Overall results at the end of the 12-week program demonstrated substantial, although not significant, differences between treatment and control groups in the hypothesized directions. On average, less than half the treatment sample logged onto the Website, which limited intervention dose.\n\nSummer day camp appears to offer promise for initiating health behavior change. Effective methods must be developed and tested to enhance log-on rates among healthy children and their parents before Internet programs can achieve their potential.", "PMID": "12713209"}, {"title": "Child- and parent-targeted interventions: the Memphis GEMS pilot study.", "abstract": "To assess the feasibility, acceptability, and outcomes of 2 versions of a culturally relevant, family-based intervention to prevent excess weight gain in pre-adolescent African-American girls.\n\nThree-arm, 12-week parallel group randomized controlled pilot trial.\n\nCommunity centers in Memphis, Tennessee.\n\nSixty African-American girls, aged 8 to 10 years, with a body mass index (BMI) > or = 25th percentile of the CDC growth charts, along with their parents/caregivers.\n\nThe active interventions involved highly interactive weekly group sessions with either girls (child-targeted program) or parents/caregivers (parent-targeted program). Content focused on knowledge and behavior change skills to promote healthy eating and increased physical activity. The comparison intervention focused on global self-esteem.\n\nGiven the lack of power and the limited time frame of the pilot study, outcomes were evaluated on the basis of implementation measures and changes in physical activity (accelerometer data), and in consumption of sweetened beverages and water, as estimated from questionnaires. Changes in body mass index, waist circumference, and body composition were also examined.\n\nThe Memphis GEMS pilot intervention met all recruitment, retention, implementation, and participation goals, and was given high rating by both participants and interventionists. With respect to the comparison intervention, girls in both the child-targeted and parent-targeted interventions demonstrated a trend toward reduced body mass index and waist circumference. In addition, girls in the active intervention groups reduced their consumption of sweetened beverages by 34%, increased their level of moderate-to-vigorous activity by 12%, and increased their serving; of water by 1.5%.\n\nThe findings from this pilot study demonstrated the feasibility, perceived acceptability, and efficacy of culturally relevant, obesity prevention interventions for pre-adolescent African-American girls and their parents/caregivers.", "PMID": "12713210"}, {"title": "Evaluation of the institutionalization of the coordinated approach to child health (CATCH) in a U.S./Mexico border community.", "abstract": "El Paso Coordinated Approach to Child Health (El Paso CATCH) was evaluated in 24 schools for outcome measures of moderate to vigorous physical activity (MVPA) during physical education (PE), content of PE lessons, content of school meals, and numerous process measures. Chi-square analyses compared frequency data across time for activity during PE and percentage fat in school meals. Descriptive summaries were used for process questionnaire results. Data were also compared to CATCH program goals. For most intervention schools, El Paso CATCH significantly increased MVPA, decreased fat in school meals, and decreased sodium in school breakfasts. However, some schools were not meeting the fat content goals for school lunches, and no schools met the vigorous physical activity (VPA) goals for PE or the sodium goals for school lunches.", "PMID": "12137238"}, {"title": "Adoption and institutionalization of the Child and Adolescent Trial for Cardiovascular Health (CATCH) in El Paso, Texas.", "abstract": "One goal of national health-promotion research is to disseminate and institutionalize experimentally tested programs in local communities. In 1997, the national Child and Adolescent Trial for Cardiovascular Health (CATCH) was chosen by the Paso del Norte Health Foundation as their first community-wide preventive health initiative for the El Paso, Texas/Ju\u00e1rez, M\u00e9xico border region. With help from researchers at the University of Texas at Houston, evaluators from the University of Texas at El Paso, and the Region 19 Educational Services Center, CATCH was implemented in 18 Title I pilot schools. Known as the Coordinated Approach to Child Health 5 years later, the El Paso CATCH program has been embraced by the border community and reaches 108 elementary schools from New Mexico to West Central Texas. There are also plans to implement CATCH in Ju\u00e1rez. This article describes the institutionalization of CATCH in a predominately Hispanic, low income border region.", "PMID": "14610985"}], "labels": [{"PMID": "10201726", "label": "included"}, {"PMID": "11323442", "label": "included"}, {"PMID": "11691758", "label": "included"}, {"PMID": "11691759", "label": "included"}, {"PMID": "12713206", "label": "included"}, {"PMID": "12713207", "label": "included"}, {"PMID": "12713209", "label": "included"}, {"PMID": "12713210", "label": "included"}, {"PMID": "12137238", "label": "excluded"}, {"PMID": "14610985", "label": "excluded"}]}
{"metadata": {"review_pmid": "38757544"}, "inputs": {"background": "Global Burden of Disease studies identify hearing loss as the third leading cause of years lived with a disability. Their estimates point to large societal and individual costs from unaddressed hearing difficulties. Workplace noise is an important modifiable risk factor; if addressed, it could significantly reduce the global burden of disease. In practice, providing hearing protection devices (HPDs) is the most common intervention to reduce noise exposure at work. However, lack of fit of HPDs, especially earplugs, can greatly limit their effectiveness. This may be the case for 40% of users. Testing the fit and providing instructions to improve noise attenuation might be effective. In the past two decades, hearing protection fit-test systems have been developed and evaluated in the field. They are called field attenuation estimation systems. They measure the noise attenuation obtained by individual workers using HPDs. If there is a lack of fit, instruction for better fit is provided, and may lead to better noise attenuation obtained by HPDs.", "objectives": "To assess: (1) the effects of field attenuation estimation systems and associated training on the noise attenuation obtained by HPDs compared to no instruction or to less instruction in workers exposed to noise; and (2) whether these interventions promote adherence to HPD use.", "selection criteria": "We included randomised controlled trials (RCTs), cluster-RCTs, controlled before-after studies (CBAs), and interrupted time-series studies (ITSs) exploring HPD fit testing in workers exposed to noise levels of more than 80 A-weighted decibels (or dBA) who use hearing protection devices. The unit 'dBA' reports on the use of a frequency-weighting filter to adjust sound measurement results to better reflect how human ears process sound. The outcome noise attenuation had to be measured either as a personal attenuation rating (PAR), PAR pass rate, or both. PAR pass rate is the percentage of workers who passed a pre-established level of sufficient attenuation from their HPDs, identified on the basis of their individual noise exposure."}, "context": [{"title": "How hearing conservation training format impacts personal attenuation ratings in U.S. Marine Corps Training Recruits.", "abstract": "The purpose of this fit-testing study in the field was to systematically compare three Hearing Protection Device (HPD) fit-training methods and determine whether they differ in the acquisition of HPD fitting skill and resulting amount of earplug attenuation.\n\nSubjects were randomly assigned to receive HPD fit-training using one of three training methods: \n\nUS Marine training recruits (\n\nThe post-training HPD fit-test passing rate differed by training method, with pass rates ranging from 50% (current) to nearly 92% (eHPD). The difference between group delta PAR values were significantly higher (>9\u2009dB) in both the eHPD and integrated methods compared to the current method.\n\nThe HPD fit-training methods that teach \"what right feels like\" (eHPD and integrated) provided a greater number of trainees with the skill to achieve noise attenuation values required for impulse noise exposures encountered during basic training. The attenuation achieved by those methods was significantly greater than the current training method.", "PMID": "32924674"}, {"title": "Training in using earplugs or using earplugs with a higher than necessary noise reduction rating? A randomized clinical trial.", "abstract": "Noise-induced hearing loss (NIHL) is one of the most common occupational diseases and the second most common cause of workers' claims for occupational injuries.\n\nDue to high prevalence of NIHL and several reports of improper use of hearing protective devices (HPDs), we conducted this study to compare the effect of face-to-face training in effective use of earplugs with appropriate NRR to overprotection of workers by using earplugs with higher than necessary noise reduction rating (NRR).\n\nIn a randomized clinical trial, 150 workers referred to occupational medicine clinic were randomly allocated to three arms---a group wearing earplugs with an NRR of 25 with no training in appropriate use of the device; a group wearing earplugs with an NRR of 25 with training; another group wearing earplugs with an NRR of 30, with no training. Hearing threshold was measured in the study groups by real ear attenuation at threshold (REAT) method. This trial is registered with Australian New Zealand clinical trials Registry, number ACTRN00363175.\n\nThe mean \u00b1 SD age of the participants was 28 \u00b1 5 (range: 19-39) years. 42% of participants were female. The mean noise attenuation in the group with training was 13.88 dB, significantly higher than those observed in other groups. The highest attenuation was observed in high frequencies (4, 6, and 8 kHz) in the group with training.\n\nTraining in appropriate use of earplugs significantly affects the efficacy of earplugs---even more than using an earplug with higher NRR.", "PMID": "25270008"}, {"title": "Variability of real-world hearing protector attenuation measurements.", "abstract": "The attenuation provided by a hearing protection device (HPD) in the field is usually estimated by applying a derating factor to the laboratory-determined noise reduction rating (NRR) of the HPD. However, attenuation is highly dependent on individual-specific HPD fit. Prediction of an individual's attenuation depends on the accuracy of the measurement system and the variability of attenuation over time (e.g. after HPD refitting). Variability in attenuation and attenuation test systems has not been adequately characterized to allow for such an assessment. This study compared attenuation measurements made with two systems, Real-Ear-at-Threshold (REAT) and Microphone-in-Real-Ear (MIRE), on 20 workers using two earplugs (foam and custom-molded). Workers' perceptions of the earplugs were also evaluated. Individuals' attenuation results were summarized as personal attenuation ratings (PARs, similar to NRRs). Variability in PARs from between-subject, within-subject and within-day (i.e. repeated tests on a subject without earplug refitting) differences was assessed and used to present the lower confidence limit, or uncertainty factor (UF), of an average individual's attenuation. The custom-molded earplug PARs achieved a higher mean percentage of labeled attenuation than did the foam earplug with both test systems. The custom-molded earplugs also had higher overall acceptance among workers. MIRE PAR levels were lower than REAT levels for both earplugs, but the relationship between the two test systems was highly variable. The MIRE system had lower within-day variability than the REAT system. One individual's MIRE results were highly influential; removal of these results greatly reduced the UF for the custom-molded earplug/MIRE combination. UFs ranged from 8.8 to 13.5 dB. These findings highlight the importance of evaluating variability in individual-specific protection results for personal protective equipment like HPDs, rather than relying on single measurements.", "PMID": "16782739"}, {"title": "Relationship between comfort and attenuation measurements for two types of earplugs.", "abstract": "Noise-induced hearing loss is almost always preventable if properly fitted hearing protectors are worn to reduce exposure. Many individuals choose not to wear hearing protection because it may interfere with effective communication in the workplace or it may be uncomfortable. Hearing protector comfort has not received the same amount of attention as noise reduction capability. The present study was conducted to evaluate the comfort level of two different types of insert earplugs as well as the attenuation levels achieved by the earplugs. Attenuation levels were obtained with a commercially available earplug fit-test system, and the comfort ratings were obtained by questionnaire. The primary research objective was to determine whether hearing protector comfort was related to measured attenuation values. A linear mixed effects model provided evidence for an inverse relationship between comfort and attenuation.", "PMID": "21368433"}, {"title": "Acceptance of a semi-custom hearing protector by manufacturing workers.", "abstract": "", "PMID": "22050444"}, {"title": "Noise attenuation of earplugs as measured by hREAT and F-MIRE methods in a Japanese metal manufacturing plant.", "abstract": "The aim of this study was to compare the noise attenuation (NA) properties of earplugs by using the headphone-based real-ear-attenuation-at-threshold (hREAT) and field microphone-in-real-ear (F-MIRE) techniques.\n\nThe subjects were 89 male workers (mean age: 44.8 \u00b1 12.1 yr) exposed to noise above 85 dBA (mean noise exposure period: 14.3 \u00b1 11.3 yr) in a Japanese nonferrous metal manufacturing plant. They were confirmed to have pure-tone air-conduction hearing threshold levels (HTLs). The hREAT and F-MIRE NA values were measured by a Rion AG-20A and a 3M E-A-Rfit, respectively.\n\nThe NA values could not be measured by hREAT for four workers (hREAT-group). The mean NA of the earplugs for subjects for whom hREAT measurements were possible (hREAT+ group) was 26.0 \u00b1 10.0 dB. The NA of the earplugs could be measured for all subjects using F-MIRE, and the NAs of the hREAT- and hREAT+ groups were 9.5 \u00b1 8.7 and 21.0 \u00b1 7.3 dB. The mean HTL value at 500 Hz to 2 kHz was 45.8 \u00b1 3.1 dB for the hREAT- group, which was significantly lower than the value for the hREAT+ group, 18.0 \u00b1 8.6 dB.\n\nBecause there is a difference between the NA values obtained by hREAT and F-MIRE, it may be necessary to compensate for this difference. In addition, workers with hearing loss and the length of the measurement time need to be taken into consideration. Finally the F-MIRE method may be useful for educating workers about using earplugs in noisy workplaces.", "PMID": "22673642"}, {"title": "[Measurement of real personal noise attenuation using earplugs with the E-A-Rfit system].", "abstract": "The assessment of efficiency of hearing protection devices (HPDs), conducted above statutory limits, must be made using a standardized method while devices are worn; however, standardized and suitable laboratory conditions are difficult to encounter at the workplace. To overcome this problem, there are methods of measurement at the workplace such as \"field-microphone-in-real-ear\" (F-MIRE).\n\nThe study was concerned with the measurement of real noise attenuation using earplugs and a new evaluation system: we checked the difference between \"real\" attenuation (at workplace) and \"theorical\" attenuation (reproduced in the laboratory) as stated by the manufacturer.\n\nWe used the E-A-Rfit computerized method, which measures the loss of attenuation of earplugs in the ear, calculating the difference of sound pressure between an \"outside\" microphone and an \"inside\" one, in relation to the same earplug. The measurements at the workplace were carried out on eight subjects with good hearing levels (aged between 20 and 25 years), who were trained to wear the devices correctly. After the tests carried out with the E-A-Rfit system, which does not require a subjective answer, we obtained graphs and tables showing real noise attenuation.\n\nWe propose a comparison between hearing threshold for frequency, personal attenuation rating (PAR) and single number rating (SNR, provided by manufacturer): a difference of 10 dB (PAR 27 db vs. SNR 37 dB) was clearly evident although dissimilar methods were used to obtain such values. The instrument is rapid, simple and objective to use and also allows personalized information and training for every worker.", "PMID": "23879065"}, {"title": "[Assessment of the impulse noise attenuation by earplugs in metalworking processes].", "abstract": "The aim of the study was to answer the question of whether earplugs provide sufficient protection in the exposure to impulse noise generated during metalworking processes.\n\nThe noise generated by die forging hammer and punching machine was characterized. Using an acoustic test fixture, noise parameters (LCpeak, LAmax) under 24 earplugs, foam, winged and no-roll, were measured. Octave band method was used to calculate values of LAeq under earplugs.\n\nIt was found that in the case of punching machine the exposure limit value of A-weighted noise exposure level, normalized to an 8-h working day (LEX, 8h = 94.8 dB) of noise present at the workstation, was exceeded, while in the case of die forging hammer both the exposure limit value of this parameter (LEX, 8h = 108.3 dB) and the exposure limit value of peak sound pressure level (LCpeak = 148.9 dB) were exceeded. The assessment of noise parameters (LCpeak, LAmax, LAeq) under earplugs revealed that the noise attenuation can be insufficient, sufficient, or too high.\n\nEarplugs can be suitable hearing protection devices in metalworking processes. Of the 24 earplugs included in this study, 9 provided appropriate noise attenuation in the case of tested die forging hammer and 10 in the case of tested punching machine.", "PMID": "25090849"}, {"title": "Training on hearing protector insertion improves noise attenuation.", "abstract": "To determine the efficacy of hearing protector insertion by comparing attenuation values measured by objective (MIRE) and subjective (REAT) methods in groups with and without training.\n\nThe study included 80 male subjects assigned to experimental (with training) and control (without training) groups. The following procedures were performed: occupational history, objective and subjective assessment of hearing protectors. Only subjects in the experimental group received training and guidance on proper hearing protector insertion.\n\nAttenuation values were significantly higher in the experimental group than in the control group at all frequencies (500, 1000, 2000, and 4000 Hz) investigated through the objective (MIRE) and subjective (REAT) methods. In addition, attenuation values in the control group were lower than those provided by the hearing protector manufacturer.\n\nBoth objective and subjective attenuation tests demonstrated the efficacy of training on insertion of hearing protectors because the group that received training on proper hearing protection insertion exhibited higher attenuation values than the untrained group.", "PMID": "26691614"}, {"title": "Evaluation of the hearing protector in a real work situation using the field-microphone-in-real-ear method.", "abstract": "Purpose To evaluate the effectiveness of the attenuation of a hearing protector (HP) in a real work situation using the field-microphone-in-real-ear method (f-MIRE). Methods Eighteen individuals of both genders (mean age of 47.17\u00b18 years) participated in this study. In the workplace, the personal attenuation level of the HP was assessed using the f-MIRE method, followed by orientation about the importance of using the HP, cleaning and storing the device, and training for effective placement. Results The analyses showed a significant statistic attenuation for all of the collected data (total noise, by frequency band and dose) when the noise levels in the lapel microphone and the probe microphone were compared. In the comparison of the attenuation values provided by the manufacturer and those found in this study, we observed higher values for the manufacturer in all frequency bands. No difference was observed for the noise levels in the different activities and times evaluated. Conclusion The findings of this study enabled us to know the personal level of attenuation of the HP during a real work situation, which was within the limits of tolerance. It was also possible to collect information about the environmental noise to which these workers are exposed. We noticed situations where this level exceeded the safety values, and therefore it is recommended the use of the HP. It is important that more studies are conducted using the f-MIRE method, because it may be an ally to assess the effectiveness of the HP attenuation in the workplace. ", "PMID": "27191871"}], "labels": [{"PMID": "32924674", "label": "included"}, {"PMID": "25270008", "label": "included"}, {"PMID": "16782739", "label": "excluded"}, {"PMID": "21368433", "label": "excluded"}, {"PMID": "22050444", "label": "excluded"}, {"PMID": "22673642", "label": "excluded"}, {"PMID": "23879065", "label": "excluded"}, {"PMID": "25090849", "label": "excluded"}, {"PMID": "26691614", "label": "excluded"}, {"PMID": "27191871", "label": "excluded"}]}
{"metadata": {"review_pmid": "38726883"}, "inputs": {"background": "Magnesium sulphate is a common therapy in perinatal care. Its benefits when given to women at risk of preterm birth for fetal neuroprotection (prevention of cerebral palsy for children) were shown in a 2009 Cochrane review. Internationally, use of magnesium sulphate for preterm cerebral palsy prevention is now recommended practice. As new randomised controlled trials (RCTs) and longer-term follow-up of prior RCTs have since been conducted, this review updates the previously published version.", "objectives": "To assess the effectiveness and safety of magnesium sulphate as a fetal neuroprotective agent when given to women considered to be at risk of preterm birth.", "selection criteria": "We included RCTs and cluster-RCTs of women at risk of preterm birth that assessed prenatal magnesium sulphate for fetal neuroprotection compared with placebo or no treatment. All methods of administration (intravenous, intramuscular, and oral) were eligible. We did not include studies where magnesium sulphate was used with the primary aim of preterm labour tocolysis, or the prevention and/or treatment of eclampsia."}, "context": [{"title": "Umbilical cord serum ionized magnesium level and total pediatric mortality.", "abstract": "To estimate whether higher magnesium levels in umbilical cord blood at delivery are associated with increased total pediatric (fetal + neonatal + postneonatal) mortality.\n\nDuring the Magnesium and Neurologic Endpoints Trial, in addition to randomizing mothers having preterm labor into arms containing magnesium sulfate, other tocolytic agents, or saline controls, we obtained biologic specimens at delivery, including umbilical cord venous blood on which was determined the serum ionized magnesium level using the AVL 988-4 analyzer (Graz, Austria). Laboratory results were then matched with the pediatric mortalities. The study power was based on the anticipated reductions in neonatal intraventricular hemorrhage related to magnesium usage from 18.9% to 4.4%. For alpha =.05, 1-beta (power)=80%, two tailed, the total number of infants needed would be 140.\n\nOf 149 mothers who gave permission for randomization, ionized magnesium levels were available for 82 children. Seven deaths occurred (one immediately before delivery, three as neonates, and three in the postneonatal period). The median level of ionized magnesium among the seven dead children was 0.76 mmol/L; among the 75 survivors, the median level of ionized magnesium was 0.55 mmol/L (Mann-Whitney U test, P =.03). Using multivariable logistic regression analysis, the association remained statistically significant when controlling for possible confounding factors (adjusted odds ratio 7.7, 95% confidence interval 1.2, 47.6, P =.03).\n\nThese findings of a dose response between serum ionized magnesium and deaths in children increase our concern about the improper use of tocolytic magnesium.", "PMID": "11430960"}, {"title": "Association between maternal serum ionized magnesium levels at delivery and neonatal intraventricular hemorrhage.", "abstract": "To determine whether magnesium sulfate (MgSO(4)) exposure is associated with a reduced risk for neonatal intraventricular hemorrhage (IVH).\n\nIn a randomized, controlled trial, women in preterm labor were randomly assigned to receive MgSO(4), \"other\" tocolytic, or saline control. At delivery, we collected maternal antecubital and umbilical cord blood for determination of serum ionized magnesium levels. Neonatal IVH was diagnosed by cranial ultrasonogram.\n\nAmong 144 infants, 24 were diagnosed with IVH. Using crude intention-to-treat analysis, we found that 18% (13/74) of survivors exposed after birth to MgSO(4) had IVH compared with 16% (11/70) of babies who were not exposed. Infants who had IVH were more likely to have been delivered by mothers with higher serum ionized magnesium (Mg) levels (0.75 vs 0.56 mmol/L) (P =.01). Using multivariable logistic regression, we confirmed that higher Mg levels are a significant predictor of neonatal IVH (adjusted odds ratio, 15.8; 95% CI, 1.4-175.0) even when adjusted for birth weight, gestational age, antenatal hemorrhage, and neonatal glucocorticoid exposure.\n\nIn mothers with preterm labor, our data indicate that antenatal MgSO(4) exposure may be associated with an increased risk for IVH among their newborns.", "PMID": "12032519"}, {"title": "Association between the use of antenatal magnesium sulfate in preterm labor and adverse health outcomes in infants.", "abstract": "The purpose of this study was to determine whether the use of antenatal magnesium sulfate prevents adverse outcomes (neonatal intraventricular hemorrhage, periventricular leucomalacia, death, and cerebral palsy).\n\nIn a controlled trial, we randomized mothers in preterm labor to magnesium sulfate, \"other\" tocolytic, or placebo. At delivery, umbilical cord blood was collected for the later determination of serum ionized magnesium levels. Neonatal cranial ultrasound scans were obtained periodically for the diagnosis of intraventricular hemorrhage and periventricular leucomalacia. Among survivors, the diagnosis of cerebral palsy was made at age 18 months.\n\nChildren with adverse outcomes had higher umbilical cord magnesium levels at delivery. In regression models that controlled for confounders, which included very low birth weight, magnesium remained a significant risk factor (adjusted odds ratio, 3.7; 95% CI, 1.1-11.9; P =.03).\n\nContrary to original hypotheses, this randomized trial found that the use of antenatal magnesium sulfate was associated with worse, not better, perinatal outcome in a dose-response fashion.", "PMID": "12066082"}, {"title": "Components of the systemic fetal inflammatory response syndrome as predictors of impaired neurologic outcomes in children.", "abstract": "The purpose of this study was to compare interleukin-6 and funisitis as predictors of impaired neurologic outcomes in children by performing a secondary analysis on data that were collected prospectively for another purpose.\n\nWe examined umbilical cords for funisitis and obtained cord blood for interleukin-6 levels. A psychomotor developmental index score was determined for each child at age 18 months.\n\nThe prevalence (46%) of elevated interleukin-6 levels (> or = 10 pg/mL) among children with low psychomotor developmental index scores (<100) was not significantly different from that of children with normal scores (47%). Among children with funisitis (n = 21), the median psychomotor developmental index score was 94; for children without funisitis (n = 92), it was 99 (P <.02). When the data were regressed for confounding, funisitis remained significant (adjusted odds ratio, 1.3; 95% CI, 1.1-1.9). Furthermore, funisitis was a more specific predictor of low psychomotor developmental index scores (P <.001), although elevated interleukin-6 levels were more sensitive.\n\nWhen used for the prediction of impaired neurologic outcomes in children, funisitis has better specificity and thus a better positive predictive value than does interleukin-6.", "PMID": "12824976"}, {"title": "Effect of magnesium sulfate given for neuroprotection before preterm birth: a randomized controlled trial.", "abstract": "Prenatal magnesium sulfate may reduce the risk of cerebral palsy or death in very preterm infants.\n\nTo determine the effectiveness of magnesium sulfate given for neuroprotection to women at risk of preterm birth before 30 weeks' gestation in preventing pediatric mortality and cerebral palsy.\n\nRandomized controlled trial at 16 tertiary hospitals in Australia and New Zealand with stratification by center and multiple pregnancy. A total of 1062 women with fetuses younger than 30 weeks' gestation for whom birth was planned or expected within 24 hours were enrolled from February 1996 to September 2000 with follow-up of surviving children at a corrected age of 2 years.\n\nWomen were randomly assigned to receive a loading infusion of 8 mL (4 g [16 mmol] of 0.5 g/mL of magnesium sulfate solution or isotonic sodium chloride solution [0.9%]) for 20 minutes followed by a maintenance infusion of 2 mL/h for up to 24 hours.\n\nRates of total pediatric mortality, cerebral palsy, and the combined outcome of death or cerebral palsy at a corrected age of 2 years.\n\nData were analyzed for 1047 (99%) 2-year survivors. Total pediatric mortality (13.8% vs 17.1%; relative risk [RR], 0.83; 95% confidence interval [CI], 0.64-1.09), cerebral palsy in survivors (6.8% vs 8.2%; RR, 0.83; 95% CI, 0.54-1.27), and combined death or cerebral palsy (19.8% vs 24.0%; RR, 0.83; 95% CI, 0.66-1.03) were less frequent for infants exposed to magnesium sulfate, but none of the differences were statistically significant. Substantial gross motor dysfunction (3.4% vs 6.6%; RR, 0.51; 95% CI, 0.29-0.91) and combined death or substantial gross motor dysfunction (17.0% vs 22.7%; RR, 0.75; 95% CI, 0.59-0.96) were significantly reduced in the magnesium group.\n\nMagnesium sulfate given to women immediately before very preterm birth may improve important pediatric outcomes. No serious harmful effects were seen.", "PMID": "14645308"}, {"title": "Antenatal risk factors associated with the development of lenticulostriate vasculopathy (LSV) in neonates.", "abstract": "To determine the antenatal risk factors associated with neonatal lenticulostriate vasculopathy (LSV).\n\nWomen in preterm labor were randomized to magnesium sulfate (MgSO4), other tocolytic, or saline control. The surviving babies underwent head ultrasounds (HUS) (weeks of life 1, 2, and 4) and periodic developmental examinations (months 4, 8, 12, and 18).\n\nOf 140 infants, 17.1% (24) had neonatal intraventricular hemorrhage (IVH), and 10.0% (14) had LSV (half of the latter (7 of 14) had both IVH and LSV). In a regression model in which other risk factors were controlled for, the association between antenatal exposures to tocolytic MgSO4 >or=50 g and LSV were significant (adjusted odds ratio (OR), 8.3; 95% confidence interval (CI), 1.5 to 45.0; p=0.01).\n\nBased on our data and their analyses, we infer that antenatal exposure to high-dosage, tocolytic MgSO4 may be associated with LSV.", "PMID": "15496867"}, {"title": "Magnesium sulphate given before very-preterm birth to protect infant brain: the randomised controlled PREMAG trial*.", "abstract": "To evaluate whether magnesium sulphate (MgSO(4)) given to women at risk of very-preterm birth would be neuroprotective in preterm newborns and would prevent neonatal mortality and severe white-matter injury (WMI).\n\nA randomised study.\n\nEighteen French tertiary hospitals. Population Women with fetuses of gestational age < 33 weeks whose birth was planned or expected within 24 hours were enrolled from July 1997 to July 2003 with follow up of infants until hospital discharge. METHODS Five hundred and seventy-three mothers were randomly assigned to receive a single 40-ml infusion of 0.1 g/ml of MgSO(4) (4 g) solution or isotonic 0.9% saline (placebo) over 30 minutes. This study is registered as an International Standard Randomised Controlled Trial, number 00120588.\n\nThe primary endpoints were rates of severe WMI or total mortality before hospital discharge, and their combined outcome. Analyses were based on intention to treat.\n\nAfter 6 years of enrolment, the trial was stopped. Data from 688 infants were analysed. Comparing infants who received MgSO(4) or placebo, respectively, total mortality (9.4 versus 10.4%; OR: 0.79, 95% CI 0.44-1.44), severe WMI (10.0 versus 11.7%; OR: 0.78, 95% CI 0.47-1.31) and their combined outcomes (16.5 versus 17.9%; OR: 0.86, 95% CI 0.55-1.34) were less frequent for the former, but these differences were not statistically significant. No major maternal adverse effects were observed in the MgSO(4) group.\n\nAlthough our results are inconclusive, improvements of neonatal outcome obtained with MgSO(4) are of potential clinical significance. More research is needed to assess the protective effect of MgSO(4) alone or in combination with other neuroprotective molecules.", "PMID": "17169012"}, {"title": "Benefit of magnesium sulfate given before very preterm birth to protect infant brain.", "abstract": "", "PMID": "18166581"}, {"title": "[Effect of magnesium sulphate on mortality and neurologic morbidity of the very-preterm newborn (of less than 33 weeks) with two-year neurological outcome: results of the prospective PREMAG trial].", "abstract": "To evaluate whether magnesium sulphate (MgSO(4)) given to women at risk of very-preterm birth would be neuroprotective in preterm newborns.\n\nIn 18 French centres, women with fetuses of gestational age less than 33 weeks whose birth was expected within 24 hours were randomised from 1993 to 2003 with follow-up of infants until two years of age after discharge. They received a single injection of 0.1 mg/l de MgSO(4) (4g) or isotonic 0.9% saline over 30 minutes. This study is registered as an International Standard Randomised Controlled Trial, number 00120588. Analyses were based on intention to treat.\n\nData from 688 infants were analysed of which 606 were followed up and 10 were lost to follow-up. Comparing infants who received MgSO(4) or placebo, respectively, has shown a decrease of all primary endpoints (total mortality, severe white matter injury and their combined outcome) and of all secondary endpoints (motor dysfunction, cerebral palsy, cognitive dysfunction and their combined outcomes at two years of age) in the MgSO(4) group. The decrease was nearly significant or significant for gross motor dysfunction (OR: 0.65 [0.41-1.02]) and combined criteria: death and cerebral palsy (OR: 0.65 [0.42-1.03]); death and gross motor dysfunction (OR: 0.62 [0.41-0.93]); death, cerebral palsy and cognitive dysfunction (OR: 0.68 [0.47-1.00]). No major maternal adverse effects were observed in the MgSO(4) group.\n\nGiven its beneficial effects and safety, the use of prenatal low-dose MgSO(4) for preventing neurodisabilities of very-preterm infants should be discussed either as a stand-alone treatment or as part of a combination treatment, at least in the context of clinical trials.", "PMID": "18337147"}, {"title": "A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy.", "abstract": "Research suggests that fetal exposure to magnesium sulfate before preterm birth might reduce the risk of cerebral palsy.\n\nIn this multicenter, placebo-controlled, double-blind trial, we randomly assigned women at imminent risk for delivery between 24 and 31 weeks of gestation to receive magnesium sulfate, administered intravenously as a 6-g bolus followed by a constant infusion of 2 g per hour, or matching placebo. The primary outcome was the composite of stillbirth or infant death by 1 year of corrected age or moderate or severe cerebral palsy at or beyond 2 years of corrected age.\n\nA total of 2241 women underwent randomization. The baseline characteristics were similar in the two groups. Follow-up was achieved for 95.6% of the children. The rate of the primary outcome was not significantly different in the magnesium sulfate group and the placebo group (11.3% and 11.7%, respectively; relative risk, 0.97; 95% confidence interval [CI], 0.77 to 1.23). However, in a prespecified secondary analysis, moderate or severe cerebral palsy occurred significantly less frequently in the magnesium sulfate group (1.9% vs. 3.5%; relative risk, 0.55; 95% CI, 0.32 to 0.95). The risk of death did not differ significantly between the groups (9.5% vs. 8.5%; relative risk, 1.12; 95% CI, 0.85 to 1.47). No woman had a life-threatening event.\n\nFetal exposure to magnesium sulfate before anticipated early preterm delivery did not reduce the combined risk of moderate or severe cerebral palsy or death, although the rate of cerebral palsy was reduced among survivors. (ClinicalTrials.gov number, NCT00014989.)", "PMID": "18753646"}], "labels": [{"PMID": "11430960", "label": "included"}, {"PMID": "12032519", "label": "included"}, {"PMID": "12066082", "label": "included"}, {"PMID": "12824976", "label": "included"}, {"PMID": "14645308", "label": "included"}, {"PMID": "15496867", "label": "included"}, {"PMID": "17169012", "label": "included"}, {"PMID": "18166581", "label": "included"}, {"PMID": "18337147", "label": "included"}, {"PMID": "18753646", "label": "included"}]}
{"metadata": {"review_pmid": "38712709"}, "inputs": {"background": "Collaborative care for severe mental illness (SMI) is a community-based intervention that promotes interdisciplinary working across primary and secondary care. Collaborative care interventions aim to improve the physical and/or mental health care of individuals with SMI. This is an update of a 2013 Cochrane review, based on new searches of the literature, which includes an additional seven studies.", "objectives": "To assess the effectiveness of collaborative care approaches in comparison with standard care (or other non-collaborative care interventions) for people with diagnoses of SMI who are living in the community.", "selection criteria": "Randomised controlled trials (RCTs) where interventions described as 'collaborative care' were compared with 'standard care' for adults (18+ years) living in the community with a diagnosis of SMI. SMI was defined as schizophrenia, other types of schizophrenia-like psychosis or bipolar affective disorder. The primary outcomes of interest were: quality of life, mental state and psychiatric admissions at 12 months follow-up."}, "context": [{"title": "Predictors of outcome in a primary care depression trial.", "abstract": "Previous treatment trials have found that approximately one third of depressed patients have persistent symptoms. We examined whether depression severity, comorbid psychiatric illness, and personality factors might play a role in this lack of response.\n\nRandomized trial of a stepped collaborative care intervention versus usual care.\n\nHMO in Seattle, Wash.\n\nPatients with major depression were stratified into severe (N = 149) and mild to moderate depression (N = 79) groups prior to randomization.\n\nA multifaceted intervention targeting patient, physician, and process of care, using collaborative management by a psychiatrist and primary care physician.\n\nPatients with more severe depression had a higher risk for panic disorder (odds ratio [OR], 5.8), loneliness (OR, 2.6), and childhood emotional abuse (OR, 2.1). Among those with less severe depression, intervention patients showed significantly improved depression outcomes over time compared with those in usual care (z = -3.06, P<.002); however, this difference was not present in the more severely depressed groups (z = 0.61, NS). Although the group with severe depression showed differences between the intervention and control groups from baseline to 3 months that were similar to the group with less severe depression (during the acute phase of the intervention), these differences disappeared by 6 months.\n\nInitial depression severity, comorbid panic disorder, and other psychosocial vulnerabilities were associated with a decreased response to the collaborative care intervention. Although the intervention was appropriate for patients with moderate depression, individuals with higher levels of depression may require a longer continuation phase of therapy in order to achieve optimal depression outcomes.", "PMID": "11119182"}, {"title": "Integrated medical care for patients with serious psychiatric illness: a randomized trial.", "abstract": "This randomized trial evaluated an integrated model of primary medical care for a cohort of patients with serious mental disorders.\n\nA total of 120 individuals enrolled in a Veterans Affairs (VA) mental health clinic were randomized to receive primary medical care through an integrated care initiative located in the mental health clinic (n = 59) or through the VA general medicine clinic (n = 61). Veterans who obtained care in the integrated care clinic received on-site primary care and case management that emphasized preventive medical care, patient education, and close collaboration with mental health providers to improve access to and continuity of care. Analyses compared health process (use of medical services, quality of care, and satisfaction) and outcomes (health and mental health status and costs) between the groups in the year after randomization.\n\nPatients treated in the integrated care clinic were significantly more likely to have made a primary care visit and had a greater mean number of primary care visits than those in the usual care group. They were more likely to have received 15 of the 17 preventive measures outlined in clinical practice guidelines. Patients assigned to the integrated care clinic had a significantly greater improvement in health as measured by the physical component summary score of the 36-Item Short-Form Health Survey than patients assigned to the general medicine clinic (4.7 points vs -0.3 points, P<.001). There were no significant differences between the 2 groups in any of the measures of mental health symptoms or in total health care costs.\n\nOn-site, integrated primary care was associated with improved quality and outcomes of medical care.", "PMID": "11545670"}, {"title": "Design and implementation of a randomized trial evaluating systematic care for bipolar disorder.", "abstract": "Everyday care of bipolar disorder typically falls short of evidence-based practice. This report describes the design and implementation of a randomized trial evaluating a systematic program to improve quality and continuity of care for bipolar disorder.\n\nComputerized records of a large health plan were used to identify all patients treated for bipolar disorder. Following a baseline diagnostic assessment, eligible and consenting patients were randomly assigned to either continued usual care or a multifaceted intervention program including: development of a collaborative treatment plan, monthly telephone monitoring by a dedicated nurse care manager, feedback of monitoring results and algorithm-based medication recommendations to treating mental health providers, as-needed outreach and care coordination, and a structured psychoeducational group program (the Life Goals Program by Bauer and McBride) delivered by the nurse care manager. Blinded assessments of clinical outcomes, functional outcomes, and treatment process were conducted every 3 months for 24 months.\n\nA total of 441 patients (64% of those eligible) consented to participate and 43% of enrolled patients met criteria for current major depressive episode, manic episode, or hypomanic episode. An additional 39% reported significant subthreshold symptoms, and 18% reported minimal or no current mood symptoms. Of patients assigned to the intervention program, 94% participated in telephone monitoring and 70% attended at least one group session.\n\nIn a population-based sample of patients treated for bipolar disorder, approximately two-thirds agreed to participate in a randomized trial comparing alternative treatment strategies. Nearly all patients accepted regular telephone monitoring and over two-thirds joined a structured group program. Future reports will describe clinical effectiveness and cost-effectiveness of the intervention program compared with usual care.", "PMID": "12190711"}, {"title": "Treating patients with medically unexplained symptoms in primary care.", "abstract": "There are no proven, comprehensive treatments in primary care for patients with medically unexplained symptoms (MUS) even though these patients have high levels of psychosocial distress, medical disability, costs, and utilization. Despite extensive care, these common patients often become worse.\n\nWe sought to identify an effective, research-based treatment that can be conducted by primary care personnel.\n\nWe used our own experiences and files, consulted with experts, and conducted an extensive review of the literature to identify two things: 1). effective treatments from randomized controlled trials for MUS patients in primary care and in specialty settings; and 2). any type of treatment study in a related area that might inform primary care treatment, for example, depression, provider-patient relationship.\n\nWe developed a multidimensional treatment plan by integrating several areas of the literature: collaborative/stepped care, cognitive-behavioral treatment, and the provider-patient relationship. The treatment is designed for primary care personnel (physicians, physician assistants, nurse practitioners) and deployed intensively at the outset; visit intervals are progressively increased as stability and improvement occur.\n\nProviding a comprehensive treatment plan for chronic, high-utilizing MUS patients removes one barrier to treating this common problem effectively in primary care by primary care personnel.", "PMID": "12823656"}, {"title": "Collaborative care improves health outcomes in older people with depression and arthritis.", "abstract": "", "PMID": "15107341"}, {"title": "Care satisfaction, hope, and life functioning among adults with bipolar disorder: data from the first 1000 participants in the Systematic Treatment Enhancement Program.", "abstract": "The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) is designed to evaluate the longitudinal outcome of patients with bipolar disorder. The STEP-BD disease-management model is built on evidence-based practices and a collaborative care approach designed to maximize specific and nonspecific treatment mechanisms. This prospective study examined the longitudinal relationships between patients' satisfaction with care, levels of hope, and life functioning in the first 1000 patients to enter STEP-BD.\n\nThe study used scores from the Care Satisfaction Questionnaire, Beck Hopelessness Scale, Range of Impaired Functioning Tool, Young Mania Rating Scale, and Montgomery-Asberg Depression Rating Scale at 5 time points during a 1-year interval. Analyses tested mediational pathways between care satisfaction, hope, and life functioning, depression, and mania using mixed-effects (random and fixed) regression models.\n\nIncreases in care satisfaction were associated with decreased hopelessness (P < .01) but not related to symptoms of depression or mania. Similarly, decreased hopelessness was associated with better life functioning (P < .01) but not related to symptoms of depression or mania. Depression was independently associated with poorer life functioning (P < .0001).\n\nThis study provided support for the hypothesized mediational pathway between care satisfaction, hopelessness, and life functioning. Findings suggest that providing care that maximizes patient hope may be important. By so doing, patients might overcome the learned helplessness/hopelessness that often accompanies a cyclical illness and build a realistic illness-management strategy.", "PMID": "15723025"}, {"title": "Can collaborative care address the needs of low-income Latinas with comorbid depression and cancer? Results from a randomized pilot study.", "abstract": "In a pilot study, 55 low-income Latina patients with breast or cervical cancer and comorbid depression were randomly assigned to receive collaborative care as part of the Multifaceted Oncology Depression Program or usual care. Relative to patients in the usual care condition, patients receiving collaborative care were more likely to show>or=50% improvement in depressive symptoms as measured by the Personal Health Questionnaire (OR=4.51, 95% CI=1.07-18.93). Patients in the collaborative care program were also more likely to show improvement in emotional well-being (increase of 2.15) as measured by the Functional Assessment of Cancer Therapy Scale than were those receiving usual care (decrease of 0.50) (group difference=2.65, 95% CI: 0.18-5.12). Despite health system, provider, and patient barriers to care, these initial results suggest that patients in public sector oncology clinics can benefit from onsite depression treatment.", "PMID": "15883143"}, {"title": "A trial of problem-solving by community mental health nurses for anxiety, depression and life difficulties among general practice patients. The CPN-GP study.", "abstract": "To compare the effectiveness of community mental health nurse (CMHN) problem-solving and generic CMHN care, against usual general practitioner (GP) care in reducing symptoms, alleviating problems, and improving social functioning and quality of life for people living in the community with common mental disorders; and to undertake a cost comparison of each CMHN treatment compared with usual GP care.\n\nA pragmatic, randomised controlled trial with three arms: CMHN problem-solving, generic CMHN care and usual GP care.\n\nGeneral practices in two southern English counties were included in the study. CMHNs were employed by local NHS trusts providing community mental health services.\n\nParticipants were GP patients aged 18--65 years with a new episode of anxiety, depression or reaction to life difficulties and had to score at least 3 points on the General Health Questionnaire-12 screening tool. Symptoms had to be present for a minimum of 4 weeks but no longer than 6 months.\n\nPatients were randomised to one of three groups: (1) CMHN problem-solving treatment, (2) generic CMHN treatment, or (3) usual GP care. All three groups of patients remained free to consult their GPs throughout the course of the study, and could be prescribed psychotropic drug treatments.\n\nPatients were assessed at baseline, and 8 weeks and 26 weeks after randomisation. The primary outcome measure was psychological symptoms measured on the Clinical Interview Schedule -- Revised. Other measures included social functioning, health-related quality of life, problem severity and satisfaction. The economic outcomes were evaluated with a cost--utility analysis.\n\nTwenty-four CMHNs were trained to provide problem-solving under supervision, and another 29 were referred patients for generic support. In total, 247 patients were randomised to the three arms of the study, referred by 98 GPs in 62 practices. All three groups of patients were greatly improved by the 8-week follow-up. No significant differences were found between the groups at 8 weeks or 26 weeks in symptoms, social functioning or quality of life. Greater satisfaction with treatment was found in the CMHN groups. CMHN care represented a significant additional health service cost and there were no savings in sickness absence.\n\nThe study found that specialist mental health nurse support is no better than support from GPs for patients with anxiety, depression and reactions to life difficulties. The results suggest that healthcare providers could consider adopting policies of restricting referrals of unselected patients with common mental disorders to specialist CMHNs, although there may be other roles in primary care that CMHNs could play effectively. Further research should address the predictors of chronicity in common mental disorders and target extra treatment. More research is also needed into the effectiveness and cost-effectiveness of problem-solving treatment for other disorders, of facilitated self-help treatments for common mental disorders and of CMHN care for people with severe and enduring mental illnesses, as well as the prevention of mental disorders.", "PMID": "16153354"}, {"title": "A trial of problem-solving by community mental health nurses for anxiety, depression and life difficulties among general practice patients. The CPN-GP study.", "abstract": "To compare the effectiveness of community mental health nurse (CMHN) problem-solving and generic CMHN care, against usual general practitioner (GP) care in reducing symptoms, alleviating problems, and improving social functioning and quality of life for people living in the community with common mental disorders; and to undertake a cost comparison of each CMHN treatment compared with usual GP care.\n\nA pragmatic, randomised controlled trial with three arms: CMHN problem-solving, generic CMHN care and usual GP care.\n\nGeneral practices in two southern English counties were included in the study. CMHNs were employed by local NHS trusts providing community mental health services.\n\nParticipants were GP patients aged 18--65 years with a new episode of anxiety, depression or reaction to life difficulties and had to score at least 3 points on the General Health Questionnaire-12 screening tool. Symptoms had to be present for a minimum of 4 weeks but no longer than 6 months.\n\nPatients were randomised to one of three groups: (1) CMHN problem-solving treatment, (2) generic CMHN treatment, or (3) usual GP care. All three groups of patients remained free to consult their GPs throughout the course of the study, and could be prescribed psychotropic drug treatments.\n\nPatients were assessed at baseline, and 8 weeks and 26 weeks after randomisation. The primary outcome measure was psychological symptoms measured on the Clinical Interview Schedule -- Revised. Other measures included social functioning, health-related quality of life, problem severity and satisfaction. The economic outcomes were evaluated with a cost--utility analysis.\n\nTwenty-four CMHNs were trained to provide problem-solving under supervision, and another 29 were referred patients for generic support. In total, 247 patients were randomised to the three arms of the study, referred by 98 GPs in 62 practices. All three groups of patients were greatly improved by the 8-week follow-up. No significant differences were found between the groups at 8 weeks or 26 weeks in symptoms, social functioning or quality of life. Greater satisfaction with treatment was found in the CMHN groups. CMHN care represented a significant additional health service cost and there were no savings in sickness absence.\n\nThe study found that specialist mental health nurse support is no better than support from GPs for patients with anxiety, depression and reactions to life difficulties. The results suggest that healthcare providers could consider adopting policies of restricting referrals of unselected patients with common mental disorders to specialist CMHNs, although there may be other roles in primary care that CMHNs could play effectively. Further research should address the predictors of chronicity in common mental disorders and target extra treatment. More research is also needed into the effectiveness and cost-effectiveness of problem-solving treatment for other disorders, of facilitated self-help treatments for common mental disorders and of CMHN care for people with severe and enduring mental illnesses, as well as the prevention of mental disorders.", "PMID": "16153354"}, {"title": "Attitudes regarding the collaborative practice model and treatment adherence among individuals with bipolar disorder.", "abstract": "An emerging literature suggests that a collaborative care model, in which patients are active managers of their illness within a supportive social environment, is a beneficial approach for individuals with bipolar disorder. One aspect of treatment that is often suboptimal among individuals with bipolar disorder is treatment adherence. Establishing an ideal collaborative model may offer an opportunity to enhance treatment adherence among individuals with bipolar disorder. This paper presents results from a qualitative exploration of patients' attitudes towards the collaborative care model and how individuals with bipolar disorder perceive treatment adherence within the context of the collaborative care model. All participants were actively enrolled in outpatient treatment at a Community Mental Health Center and part of a larger study that evaluated the Life Goals Program, a manual-driven structured group psychotherapy for bipolar disorder that is based on the collaborative practice model. The Life Goals Program is designed to assist individuals to participate more effectively in the management of their bipolar illness and to improve their social and work-related problems. Individuals were queried regarding their opinions on the ingredients for an effective client-provider relationship. Quantitative data were collected on baseline treatment adherence as well. Individuals treated for bipolar disorder in a community mental health clinic identified 12 key elements that they felt were critical ingredients to a positive collaborative experience with their mental health care provider. The authors conceptualized these elements around 3 emerging themes: patient-centered qualities, provider-centered qualities, and interactional qualities. Individuals with bipolar disorder perceived the ideal collaborative model as one in which the individual has specific responsibilities such as coming to appointments and sharing information, whereas the provider likewise has specific responsibilities such as keeping abreast of current \"state-of-the-arf\" prescribing practices and being a good listener. Treatment adherence was identified as a self-managed responsibility within the larger context of the collaborative model. Individuals with bipolar disorder in this study placed substantial emphasis on the interactional component within the patient-provider relationship, particularly with respect to times when the individual may be more symptomatic and more impaired. It is important that clinicians and care providers gather information related to patients' perceptions of the patient-provider relationship when designing or evaluating services aimed at enhancing treatment adherence.", "PMID": "16175758"}], "labels": [{"PMID": "11119182", "label": "excluded"}, {"PMID": "11545670", "label": "excluded"}, {"PMID": "12190711", "label": "excluded"}, {"PMID": "12823656", "label": "excluded"}, {"PMID": "15107341", "label": "excluded"}, {"PMID": "15723025", "label": "excluded"}, {"PMID": "15883143", "label": "excluded"}, {"PMID": "16153354", "label": "excluded"}, {"PMID": "16153354", "label": "excluded"}, {"PMID": "16175758", "label": "excluded"}]}
{"metadata": {"review_pmid": "38695628"}, "inputs": {"background": "Respiratory distress occurs in up to 7% of newborns, with respiratory support (RS) provided invasively via an endotracheal (ET) tube or non-invasively via a nasal interface. Invasive ventilation increases the risk of lung injury and chronic lung disease (CLD). Using non-invasive strategies, with or without minimally invasive surfactant, may reduce the need for mechanical ventilation and the risk of lung damage in newborn infants with respiratory distress.", "objectives": "To evaluate the benefits and harms of nasal high-frequency ventilation (nHFV) compared to invasive ventilation via an ET tube or other non-invasive ventilation methods on morbidity and mortality in preterm and term infants with or at risk of respiratory distress.", "selection criteria": "Randomised controlled trials (RCTs), cluster- or quasi-RCTs of nHFV in newborn infants with respiratory distress compared to invasive or non-invasive ventilation."}, "context": [{"title": "Nasal high frequency percussive ventilation versus nasal continuous positive airway pressure in transient tachypnea of the newborn: a pilot randomized controlled trial (NCT00556738).", "abstract": "To determine whether nasal high frequency percussive ventilation (NHFPV) would decrease duration of transient tachypnea of the newborn (TTN) compared to nasal continuous positive airway pressure (NCPAP) in newborn infants.\n\nA prospective, unmasked, randomized, controlled clinical trial was conducted in 46 eligible newborn infants who were hospitalized for TTN in the University Hospital of Bordeaux (France) between 2007 and 2009. Infants born by cesarian section \u226537 GA, \u22652,000 g with diagnosis of TTN and with a transcutaneous saturation <90% at 20\u2009min after birth were eligible. Infants were randomized to either NHFPV or NCPAP. The primary endpoint was a reduction of the duration of TTN. Secondary endpoints were the duration of oxygen therapy and the minimal level required to obtain a saturation between 90% and 96% integrated into an index which included a time factor: [(FiO2 -21)/time of O2 therapy].\n\nIn the NHFPV group the duration of TTN was half the time of NCPAP group (105\u2009min\u2009\u00b1\u200920 and 377\u2009min\u2009\u00b1\u2009150, respectively; P\u2009<\u20090.0001). There was a significant decrease in duration of oxygen supplementation in the NHFPV group (6.3\u2009min\u2009\u00b1\u20093.3) compared to the NCPAP group (19.1\u2009min\u2009\u00b1\u20098.1; P\u2009<\u20090.001), and a significant decrease in level of oxygen supplementation [(FiO2 -0.21)/time of O2 therapy] in the NHFPV group (0.29\u2009min(-1) \u2009\u00b1\u20090.16) compared to the NCPAP group (0.46\u2009min(-1) \u2009\u00b1\u20090.50; P\u2009<\u20090.001). There was no complication and NHFPV was as well tolerated as NCPAP.\n\nNHFPV is well tolerated and more effective than NCPAP in treatment of TTN. NHFPV might be a novel and safe tool to manage TTN. Pediatr Pulmonol.", "PMID": "20963833"}, {"title": "Non-invasive high-frequency ventilation versus bi-phasic continuous positive airway pressure (BP-CPAP) following CPAP failure in infants <1250\u2009g: a pilot randomized controlled trial.", "abstract": "Non-invasive high-frequency ventilation (NIHFV), a relatively new modality, is gaining popularity despite limited data. We sought to evaluate the effectiveness of NIHFV versus bi-phasic continuous positive airway pressure (BP-CPAP) in preterm infants failing CPAP.\n\nInfants with BW<1250\u2009g on CPAP were randomly assigned to NIHFV or BP-CPAP if they met pre-determined criteria for CPAP failure. Infants were eligible for randomization after 72\u2009h age and until 2000\u2009g. Guidelines for adjustment of settings and criteria for failure of assigned mode were implemented. The primary aim was to assess feasibility of a larger trial. In addition, failure of assigned non-invasive respiratory support (NRS) mode, invasive mechanical ventilation (MV) 72\u2009h and 7 days post-randomization, and bronchopulmonary dysplasia (BPD) were assessed.\n\nThirty-nine infants were randomized to NIHFV (N=16) or BP-CPAP (N=23). There were no significant differences in mean (s.d.) postmenstrual age (28.6 (1.5) versus 29.0 (2.3) weeks, P=0.47), mean (s.d.) weight at randomization (965.0 (227.0) versus 958.1 (310.4)\u2009g, P=0.94) or other baseline demographics between the groups. Failure of assigned NRS mode was lower with NIHFV (37.5 versus 65.2%, P=0.09), although not statistically significant. There were no differences in rates of invasive MV 72\u2009h and 7 days post-randomization or BPD.\n\nNIHFV was not superior to BP-CPAP in this pilot study. Effectiveness of NIHFV needs to be proven in larger multi-center, appropriately powered trials before widespread implementation.", "PMID": "27684415"}, {"title": "Non-invasive high-frequency ventilation versus bi-phasic continuous positive airway pressure (BP-CPAP) following CPAP failure in infants <1250\u2009g: a pilot randomized controlled trial.", "abstract": "Non-invasive high-frequency ventilation (NIHFV), a relatively new modality, is gaining popularity despite limited data. We sought to evaluate the effectiveness of NIHFV versus bi-phasic continuous positive airway pressure (BP-CPAP) in preterm infants failing CPAP.\n\nInfants with BW<1250\u2009g on CPAP were randomly assigned to NIHFV or BP-CPAP if they met pre-determined criteria for CPAP failure. Infants were eligible for randomization after 72\u2009h age and until 2000\u2009g. Guidelines for adjustment of settings and criteria for failure of assigned mode were implemented. The primary aim was to assess feasibility of a larger trial. In addition, failure of assigned non-invasive respiratory support (NRS) mode, invasive mechanical ventilation (MV) 72\u2009h and 7 days post-randomization, and bronchopulmonary dysplasia (BPD) were assessed.\n\nThirty-nine infants were randomized to NIHFV (N=16) or BP-CPAP (N=23). There were no significant differences in mean (s.d.) postmenstrual age (28.6 (1.5) versus 29.0 (2.3) weeks, P=0.47), mean (s.d.) weight at randomization (965.0 (227.0) versus 958.1 (310.4)\u2009g, P=0.94) or other baseline demographics between the groups. Failure of assigned NRS mode was lower with NIHFV (37.5 versus 65.2%, P=0.09), although not statistically significant. There were no differences in rates of invasive MV 72\u2009h and 7 days post-randomization or BPD.\n\nNIHFV was not superior to BP-CPAP in this pilot study. Effectiveness of NIHFV needs to be proven in larger multi-center, appropriately powered trials before widespread implementation.", "PMID": "27684415"}, {"title": "Noninvasive high-frequency oscillatory ventilation versus nasal continuous positive airway pressure in preterm infants with moderate-severe respiratory distress syndrome: A preliminary report.", "abstract": "The aim of this study was to compare the effect of noninvasive high-frequency oscillatory ventilation (nHFOV) with nasal continuous positive airway pressure (nCPAP) in preterm infants with moderate-severe respiratory distress syndrome (RDS) after surfactant administration via INSURE (intubation, surfactant, extubation) method on the need for invasive mechanical ventilation (IMV).\n\nA total of 81 infants with a gestational age (GA) of 28-34 weeks were eligible and were randomized to nCPAP (n\u2009=\u200942) or to nHFOV (n\u2009=\u200939). The need for IMV was the primary outcome. The incidence of bronchopulmonary dysplasia (BPD), occurrence of intraventricular hemorrhage (IVH), and air leaks, and mortality were considered as secondary outcomes.\n\nA total 76 infants finally completed the study. The need for IMV was significantlylower in the nHFOV group compared with the nCPAP group(24.3% vs 56.4%, P\u2009<\u20090.01). The incidence of IVH, air leaks or BPD was similar between the two groups. In addition, the mortality rate was not statistically different.\n\nIn this prospective, randomized controlled study, nHFOV significantly reduced the need for IMV as compared with nCPAP in preterm infants with moderate-severe RDS without increase in adverse effects.", "PMID": "28672094"}, {"title": "Response to 'Non-invasive high frequency ventilation and the errors from the past: designing simple trials neglecting complex respiratory physiology'.", "abstract": "", "PMID": "28904404"}, {"title": "Effective elimination of carbon dioxide by nasopharyngeal high-frequency ventilation.", "abstract": "", "PMID": "11127504"}, {"title": "Nasal high-frequency ventilation for premature infants.", "abstract": "To assess the use of nasal high-frequency ventilation (HFV) to provide noninvasive ventilatory support for very low birthweight (VLBW) infants.\n\nVLBW infants, >7 days of age on nasal continuous positive airway pressure (CPAP), were placed on nasal HFV for 2 h using the Infant Star high-frequency ventilator (Mallinckrodt, Inc., St. Louis, MO, USA). Mean airway pressure was set to equal the previous level of CPAP, and amplitude was adjusted to obtain chest wall vibration. Capillary blood was sampled before starting HFV and after 2 h to determine change in pH and partial pressure of carbon dioxide (pCO(2)).\n\nFourteen subjects were studied, 10 males and 4 females. Gestational age was 26-30 weeks (median 27). Age at study was 18-147 days (median 30). Median birth weight was 955 g; median weight at study was 1605 g. Nasal CPAP pressure was 4-7 cm H(2)O (mean 5). Amplitude was 30-60 (median 50). After 2 h, PCO(2) (mean 45 torr) was significantly lower than initial PCO(2) (mean 50 torr) (p = 0.01), and pH had increased significantly (7.40 vs. 7.37, p = 0.04).\n\nNasal HFV is effective in decreasing pCO(2) in stable premature infants requiring nasal CPAP support. Long-term use of nasal HFV requires further study.", "PMID": "18549418"}, {"title": "Elective high-frequency oscillatory ventilation in preterm infants with respiratory distress syndrome: an individual patient data meta-analysis.", "abstract": "Despite the considerable amount of evidence from randomized controlled trials and meta-analyses, uncertainty remains regarding the efficacy and safety of high-frequency oscillatory ventilation as compared to conventional ventilation in the early treatment of respiratory distress syndrome in preterm infants. This results in a wide variation in the clinical use of high-frequency oscillatory ventilation for this indication throughout the world. The reasons are an unexplained heterogeneity between trial results and a number of unanswered, clinically important questions. Do infants with different risk profiles respond differently to high-frequency oscillatory ventilation? How does the ventilation strategy affect outcomes? Does the delay--either from birth or from the moment of intubation--to the start of high-frequency oscillation modify the effect of the intervention? Instead of doing new trials, those questions can be addressed by re-analyzing the individual patient data from the existing randomized controlled trials.\n\nA systematic review with meta-analysis based on individual patient data. This involves the central collection, validation and re-analysis of the original individual data from each infant included in each randomized controlled trial addressing this question.The study objective is to estimate the effect of high-frequency oscillatory ventilation on the risk for the combined outcome of death or bronchopulmonary dysplasia or a severe adverse neurological event. In addition, it will explore whether the effect of high-frequency oscillatory ventilation differs by the infant's risk profile, defined by gestational age, intrauterine growth restriction, severity of lung disease at birth and whether or not corticosteroids were given to the mother prior to delivery. Finally, it will explore the importance of effect modifying factors such as the ventilator device, ventilation strategy and the delay to the start of high-frequency ventilation.\n\nAn international collaborative group, the PreVILIG Collaboration (Prevention of Ventilator Induced Lung Injury Group), has been formed with the investigators of the original randomized trials to conduct this systematic review. In the field of neonatology, individual patient data meta-analysis has not been used previously. Final results are expected to be available by the end of 2009.", "PMID": "19445701"}, {"title": "Weaning of neonates from mechanical ventilation by use of nasopharyngeal high-frequency oscillatory ventilation: a preliminary study.", "abstract": "To investigate the feasibility of nasopharyngeal high-frequency oscillatory ventilation (nHFOV) immediately after extubation in difficult-to-wean preterm infants.\n\nThis was an observational study of 20 mechanically ventilated neonates [median (range) birth weight 635 (382-1020)g, median gestational age 25.3 (23.7-27.6) weeks] at high risk for extubation failure. Nine infants had failed at least one previous extubation. Fourteen infants were given hydrocortisone. All 20 infants were extubated into nHFOV, with a mean airway pressure of 8 cmH(2)O, an amplitude of 20 cmH(2)O, and a frequency of 10 Hz.\n\n\u2003Infants remained on nHFOV for a median duration of 136.5 (7.0-456.0) h until further weaning to continuous positive airway pressure (n\u200a=14) or reintubation (n\u200a=\u200a6). Reintubation was performed in 1 of 11 infants who had not experienced any previous extubation, and in five of nine infants who had experienced at least one previous extubation (P < 0.05). PaCO(2) was virtually unchanged from preextubation levels 2 h after extubation, but declined significantly at 32 h from 59.8 (45.0-92.3) mmHg to 50.7 (39.8-74.4) mmHg (P < 0.01). PaCO(2) returned to preextubation levels upon discontinuation of nHFOV.\n\nThis small observational study demonstrates that nHFOV can be successfully applied to wean premature infants from ventilator support.", "PMID": "21612570"}, {"title": "Use of noninvasive high-frequency ventilation in the neonatal intensive care unit: a retrospective review.", "abstract": "The aim of the article is to review the effectiveness of neonatal noninvasive high-frequency ventilation (NIHFV) in preventing endotracheal mechanical ventilation.\n\nRetrospective case series including all 79 instances of NIHFV use at four participating centers between July 2010 and September 2012.\n\nIn 73% of cases, NIHFV was used as rescue after another noninvasive mode, and prophylactically (postextubation) in the remainder. In 58% of cases, infants transitioned to another noninvasive mode, without requiring intubation. There were significant reductions in the mean (SD) number of apneas, bradycardias, or desaturations (over 6 hours) (3.2 [0.4] vs. 1.2 [0.3]; p\u2009<\u20090.001), FiO2 (48 [3] vs. 40 [2]%; p\u2009<\u20090.001) and CO2 levels (74 [6] vs. 62 [4] mm Hg; p\u2009=\u20090.025] with NIHFV. No NIHFV-related complications were noted.\n\nNIHFV is a promising NIV mode that may help prevent or delay intubation and deserves further clinical research.", "PMID": "24915560"}], "labels": [{"PMID": "20963833", "label": "included"}, {"PMID": "27684415", "label": "included"}, {"PMID": "27684415", "label": "included"}, {"PMID": "28672094", "label": "included"}, {"PMID": "28904404", "label": "included"}, {"PMID": "11127504", "label": "excluded"}, {"PMID": "18549418", "label": "excluded"}, {"PMID": "19445701", "label": "excluded"}, {"PMID": "21612570", "label": "excluded"}, {"PMID": "24915560", "label": "excluded"}]}
{"metadata": {"review_pmid": "38597256"}, "inputs": {"background": "Dengue is a global health problem of high significance, with 3.9 billion people at risk of infection. The geographic expansion of dengue virus (DENV) infection has resulted in increased frequency and severity of the disease, and the number of deaths has increased in recent years. Wolbachia,an intracellular bacterial endosymbiont, has been under investigation for several years as a novel dengue-control strategy. Some dengue vectors (Aedes mosquitoes) can be transinfected with specific strains of Wolbachia, which decreases their fitness (ability to survive and mate) and their ability to reproduce, inhibiting the replication of dengue. Both laboratory and field studies have demonstrated the potential effect of Wolbachia deployments on reducing dengue transmission, and modelling studies have suggested that this may be a self-sustaining strategy for dengue prevention, although long-term effects are yet to be elucidated.", "objectives": "To assess the efficacy of Wolbachia-carrying Aedes speciesdeployments (specifically wMel-, wMelPop-, and wAlbB- strains of Wolbachia) for preventing dengue virus infection.", "selection criteria": "Randomized controlled trials (RCTs), including cluster-randomized controlled trials (cRCTs), conducted in dengue endemic or epidemic-prone settings were eligible. We sought studies that investigated the impact of Wolbachia-carrying Aedes deployments on epidemiological or entomological dengue-related outcomes, utilizing either the population replacement or population suppression strategy."}, "context": [{"title": "Update to the AWED (Applying Wolbachia to Eliminate Dengue) trial study protocol: a cluster randomised controlled trial in Yogyakarta, Indonesia.", "abstract": "The AWED (Applying Wolbachia to Eliminate Dengue) trial is a parallel, two-arm, non-blinded cluster randomised controlled trial that is under way in Yogyakarta, Indonesia, with the aim of measuring the efficacy of Wolbachia-infected Aedes aegypti deployments in reducing dengue incidence in an endemic setting. Enrolment began in January 2018 and is ongoing. The original study protocol was published in April 2018. Here, we describe amendments that have been made to the study protocol since commencement of the trial.\n\nThe key protocol amendments are (1) a revised study duration with planned end of participant enrolment in August 2020, (2) the addition of new secondary objectives (i) to estimate serotype-specific efficacy of the Wolbachia intervention and (ii) to compare Ae. aegypti abundance in intervention versus untreated clusters, (3) an additional exposure classification for the per-protocol analysis where the Wolbachia exposure index is calculated using only the cluster-level Wolbachia prevalence in the participant's cluster of residence, (4) power re-estimation using a multinomial sampling method that better accounts for randomness in sampling, and (5) the addition of two trial stopping rules to address the potential for persistently low rates of virologically confirmed dengue case enrolment and Wolbachia contamination into untreated clusters. Additional minor changes to the protocol are also described.\n\nThe findings from this study will provide the first experimental evidence for the efficacy of Wolbachia in reducing dengue incidence. Enrolment in the trial will conclude this year (2020) and results will be reported shortly thereafter.\n\nClinicalTrials.gov, identifier: NCT03055585. Registered on 14 February 2017. Last updated 22 March 2020.", "PMID": "32450914"}, {"title": "The AWED trial (Applying Wolbachia to Eliminate Dengue) to assess the efficacy of Wolbachia-infected mosquito deployments to reduce dengue incidence in Yogyakarta, Indonesia: study protocol for a cluster randomised controlled trial.", "abstract": "Dengue and other arboviruses transmitted by Aedes aegypti mosquitoes, including Zika and chikungunya, present an increasing public health challenge in tropical regions. Current vector control strategies have failed to curb disease transmission, but continue to be employed despite the absence of robust evidence for their effectiveness or optimal implementation. The World Mosquito Program has developed a novel approach to arbovirus control using Ae. aegypti stably transfected with Wolbachia bacterium, with a significantly reduced ability to transmit dengue, Zika and chikungunya in laboratory experiments. Modelling predicts this will translate to local elimination of dengue in most epidemiological settings. This study protocol describes the first trial to measure the efficacy of Wolbachia in reducing dengue virus transmission in the field.\n\nThe study is a parallel, two-arm, non-blinded cluster randomised controlled trial conducted in a single site in Yogyakarta, Indonesia. The aim is to determine whether large-scale deployment of Wolbachia-infected Ae. aegypti mosquitoes leads to a measurable reduction in dengue incidence in treated versus untreated areas. The primary endpoint is symptomatic, virologically confirmed dengue virus infection of any severity. The 26 km\n\nThe findings from this study will provide the first experimental evidence for the efficacy of Wolbachia in reducing dengue incidence. Together with observational evidence that is accumulating from pragmatic deployments of Wolbachia in other field sites, this will provide valuable data to estimate the effectiveness of this novel approach to arbovirus control, inform future cost-effectiveness estimates, and guide plans for large-scale deployments in other endemic settings.\n\nClinicalTrials.gov, identifier: NCT03055585 . Registered on 14 February 2017.", "PMID": "29855331"}, {"title": "Reanalysis of cluster randomised trial data to account for exposure misclassification using a per-protocol and complier-restricted approach.", "abstract": "The intention-to-treat (ITT) analysis of the Applying Wolbachia to Eliminate Dengue (AWED) trial estimated a protective efficacy of 77.1% for participants resident in areas randomised to receive releases of wMel-infected Aedes aegypti mosquitoes, an emerging dengue preventive intervention. The limiting assumptions of ITT analyses in cluster randomised trials and the mobility of mosquitoes and humans across cluster boundaries indicate the primary analysis is likely to underestimate the full public health benefit. Using spatiotemporally-resolved data on the distribution of Wolbachia mosquitoes and on the mobility of AWED participants (n = 6306), we perform complier-restricted and per-protocol re-examinations of the efficacy of the Wolbachia intervention. Increased intervention efficacy was estimated in all analyses by the refined exposure measures. The complier-restricted analysis returned an estimated efficacy of 80.7% (95% CI 65.9, 89.0) and the per-protocol analysis estimated 82.7% (71.7, 88.4) efficacy when comparing participants with an estimated wMel exposure of ", "PMID": "38755197"}, {"title": "Disruption of spatiotemporal clustering in dengue cases by wMel Wolbachia in Yogyakarta, Indonesia.", "abstract": "Dengue exhibits focal clustering in households and neighborhoods, driven by local mosquito population dynamics, human population immunity, and fine scale human and mosquito movement. We tested the hypothesis that spatiotemporal clustering of homotypic dengue cases is disrupted by introduction of the arbovirus-blocking bacterium Wolbachia (wMel-strain) into the Aedes aegypti mosquito population. We analysed 318 serotyped and geolocated dengue cases (and 5921 test-negative controls) from a randomized controlled trial in Yogyakarta, Indonesia of wMel deployments. We find evidence of spatial clustering up to 300\u00a0m among the 265 dengue cases (3083 controls) in the untreated trial arm. Participant pairs enrolled within 30\u00a0days and 50\u00a0m had a 4.7-fold increase (compared to 95% CI on permutation-based null distribution: 0.1, 1.2) in the odds of being homotypic (i.e. potentially transmission-related) as compared to pairs occurring at any distance. In contrast, we find no evidence of spatiotemporal clustering among the 53 dengue cases (2838 controls) resident in the wMel-treated arm. Introgression of wMel Wolbachia into Aedes aegypti mosquito populations interrupts focal dengue virus transmission leading to reduced case incidence; the true intervention effect may be greater than the 77% efficacy measured in the primary analysis of the Yogyakarta trial.", "PMID": "35701454"}, {"title": "Baseline Characterization of Dengue Epidemiology in Yogyakarta City, Indonesia, before a Randomized Controlled Trial of ", "abstract": "Dengue is endemic in Indonesia. Here, we describe the epidemiology of dengue in the city of Yogyakarta, Central Java, as a prelude to implementation of a cluster-randomized trial of ", "PMID": "30226138"}, {"title": "Aedes aegypti abundance and insecticide resistance profiles in the Applying Wolbachia to Eliminate Dengue trial.", "abstract": "The Applying Wolbachia to Eliminate Dengue (AWED) trial was a parallel cluster randomised trial that demonstrated Wolbachia (wMel) introgression into Ae. aegypti populations reduced dengue incidence. In this predefined substudy, we compared between treatment arms, the relative abundance of Ae. aegypti and Ae. albopictus before, during and after wMel-introgression. Between March 2015 and March 2020, 60,084 BG trap collections yielded 478,254 Ae. aegypti and 17,623 Ae. albopictus. Between treatment arms there was no measurable difference in Ae. aegypti relative abundance before or after wMel-deployments, with a count ratio of 0.96 (95% CI 0.76, 1.21) and 1.00 (95% CI 0.85, 1.17) respectively. More Ae. aegypti were caught per trap per week in the wMel-intervention arm compared to the control arm during wMel deployments (count ratio 1.23 (95% CI 1.03, 1.46)). Between treatment arms there was no measurable difference in the Ae. albopictus population size before, during or after wMel-deployment (overall count ratio 1.10 (95% CI 0.89, 1.35)). We also compared insecticide resistance phenotypes of Ae. aegypti in the first and second years after wMel-deployments. Ae. aegypti field populations from wMel-treated and untreated arms were similarly resistant to malathion (0.8%), permethrin (1.25%) and cyfluthrin (0.15%) in year 1 and year 2 of the trial. In summary, we found no between-arm differences in the relative abundance of Ae. aegypti or Ae. albopictus prior to or after wMel introgression, and no between-arm difference in Ae. aegypti insecticide resistance phenotypes. These data suggest neither Aedes abundance, nor insecticide resistance, confounded the epidemiological outcomes of the AWED trial.", "PMID": "35442957"}, {"title": "Efficacy of Wolbachia-Infected Mosquito Deployments for the Control of Dengue.", "abstract": "We conducted a cluster-randomized trial involving releases of \n\nAfter successful introgression of \n\nIntrogression of ", "PMID": "34107180"}, {"title": "Field evaluation of the establishment potential of wMelPop Wolbachia in Australia and Vietnam for dengue control.", "abstract": "Introduced Wolbachia bacteria can influence the susceptibility of Aedes aegypti mosquitoes to arboviral infections as well as having detrimental effects on host fitness. Previous field trials demonstrated that the wMel strain of Wolbachia effectively and durably invades Ae. aegypti populations. Here we report on trials of a second strain, wMelPop-PGYP Wolbachia, in field sites in northern Australia (Machans Beach and Babinda) and central Vietnam (Tri Nguyen, Hon Mieu Island), each with contrasting natural Ae. aegypti densities.\n\nMosquitoes were released at the adult or pupal stages for different lengths of time at the sites depending on changes in Wolbachia frequency as assessed through PCR assays of material collected through Biogents-Sentinel (BG-S) traps and ovitraps. Adult numbers were also monitored through BG-S traps. Changes in Wolbachia frequency were compared across hamlets or house blocks.\n\nReleases of adult wMelPop-Ae. aegypti resulted in the transient invasion of wMelPop in all three field sites. Invasion at the Australian sites was heterogeneous, reflecting a slower rate of invasion in locations where background mosquito numbers were high. In contrast, invasion across Tri Nguyen was relatively uniform. After cessation of releases, the frequency of wMelPop declined in all sites, most rapidly in Babinda and Tri Nguyen. Within Machans Beach the rate of decrease varied among areas, and wMelPop was detected for several months in an area with a relatively low mosquito density.\n\nThese findings highlight challenges associated with releasing Wolbachia-Ae. aegypti combinations with low fitness, albeit strong virus interference properties, as a means of sustainable control of dengue virus transmission.", "PMID": "26510523"}, {"title": "Female Adult Aedes albopictus Suppression by Wolbachia-Infected Male Mosquitoes.", "abstract": "Dengue, chikungunya and zika viruses are pathogens with an increasing global impact. In the absence of an approved vaccine or therapy, their management relies on controlling the mosquito vectors. But traditional controls are inadequate, and the range of invasive species such as Aedes albopictus (Asian Tiger Mosquito) is expanding. Genetically modified mosquitoes are being tested, but their use has encountered regulatory barriers and public opposition in some countries. Wolbachia bacteria can cause a form of conditional sterility, which can provide an alternative to genetic modification or irradiation. It is unknown however, whether openly released, artificially infected male Ae. albopictus can competitively mate and sterilize females at a level adequate to suppress a field population. Also, the unintended establishment of Wolbachia at the introduction site could result from horizontal transmission or inadvertent female release. In 2014, an Experimental Use Permit from the United States Environmental Protection Agency approved a pilot field trial in Lexington, Kentucky, USA. Here, we present data showing localized reduction of both egg hatch and adult female numbers. The artificial Wolbachia type was not observed to establish in the field. The results are discussed in relation to the applied use of Wolbachia-infected males as a biopesticide to suppress field populations of Ae. albopictus.", "PMID": "27659038"}, {"title": "Establishment of Wolbachia Strain wAlbB in Malaysian Populations of Aedes aegypti for Dengue Control.", "abstract": "Dengue has enormous health impacts globally. A novel approach to decrease dengue incidence involves the introduction of Wolbachia endosymbionts that block dengue virus transmission into populations of the primary vector mosquito, Aedes aegypti. The wMel Wolbachia strain has previously been trialed in open releases of Ae. aegypti; however, the wAlbB strain has been shown to maintain higher density than wMel at high larval rearing temperatures. Releases of Ae. aegypti mosquitoes carrying wAlbB were carried out in 6 diverse sites in greater Kuala Lumpur, Malaysia, with high endemic dengue transmission. The strain was successfully established and maintained at very high population frequency at some sites or persisted with additional releases following fluctuations at other sites. Based on passive case monitoring, reduced human dengue incidence was observed in the release sites when compared to control sites. The wAlbB strain of Wolbachia provides a promising option as a tool for dengue control, particularly in very hot climates.", "PMID": "31761702"}], "labels": [{"PMID": "32450914", "label": "included"}, {"PMID": "29855331", "label": "included"}, {"PMID": "38755197", "label": "included"}, {"PMID": "35701454", "label": "included"}, {"PMID": "30226138", "label": "included"}, {"PMID": "35442957", "label": "included"}, {"PMID": "34107180", "label": "included"}, {"PMID": "26510523", "label": "excluded"}, {"PMID": "27659038", "label": "excluded"}, {"PMID": "31761702", "label": "excluded"}]}
{"metadata": {"review_pmid": "38597126"}, "inputs": {"background": "Midwives are primary providers of care for childbearing women globally and there is a need to establish whether there are differences in effectiveness between midwife continuity of care models and other models of care. This is an update of a review published in 2016.", "objectives": "To compare the effects of midwife continuity of care models with other models of care for childbearing women and their infants.", "selection criteria": "All published and unpublished trials in which pregnant women are randomly allocated to midwife continuity of care models or other models of care during pregnancy and birth."}, "context": [{"title": "Satisfaction with midwife-managed care in different time periods: a randomised controlled trial of 1299 women.", "abstract": "To compare women's satisfaction with midwife-managed care with 'shared care' over three different time periods.\n\nRandomised controlled trial.\n\nGlasgow Royal Maternity Hospital, Glasgow, UK.\n\n1299 women experiencing normal pregnancy (consent rate: 82%). Six hundred and forty-eight women were randomised to midwife-managed care and 651 to 'shared care'.\n\nThree self-report questionnaires were sent to women's homes. The questionnaires examined: satisfaction with antenatal care at 34-35 weeks' gestation, and satisfaction with intrapartum, hospital- and home-based postnatal care at seven weeks postnatally. The third questionnaire reviewed satisfaction with intrapartum care seven months after delivery.\n\nWomen in both groups were satisfied. However, women in the midwife-managed group were more highly satisfied in relation to the dimensions examined: relationships with staff, information transfer, choices and decisions, and social support. The differences between the two groups were evident for all time periods (i.e. antenatal, intrapartum and postnatal periods) and were sustained at seven-month follow-up. This is illustrated in the mean scores for relationships with staff, as measured at 34-35 weeks' gestation (possible range -2; very negative attitudes to 2; very positive attitudes). Women in the midwife-managed group scored a mean of 1.22 compared to 0.74 for the 'shared care' group (mean diff: 0.48; 95% CI: 0.42 to 0.55). While women in both groups were more likely to make positive rather than negative comments in open-ended questions, the midwife-managed group were more likely to make positive comments whereas the 'shared care' group were more likely to make negative comments.\n\nMidwife-managed care for healthy pregnant women which is integrated into existing services improves satisfaction with antenatal, intrapartum and postnatal care.", "PMID": "10382476"}, {"title": "Incorporating cultural diversity in randomised controlled trials in midwifery.", "abstract": "The randomised controlled trial is currently the 'gold standard' that guides health-care practices. The implementation of new models of midwifery care often relies on results from randomised controlled trials. However, many randomised controlled trials exclude women who do not speak English or are designed in such a way that cultural diversity is not facilitated. This can mean that the sample is not representative of the population from which it was drawn or to which it will be applied. Culturally diverse representation can be achieved through a number of strategies. These include utilising health-care interpreters, ensuring materials are translated into common community languages and engaging the local community. These strategies can be used to ensure that the sample in a randomised controlled trial is culturally and linguistically diverse, and representative of the community. We have conducted a randomised controlled trial of a community-based model of midwifery providing continuity of care in a culturally diverse population. A number of issues in the conduct of a trial within a culturally diverse society are discussed in this paper. The trial will be used to illustrate some of the strategies used to ensure that the sample represented the population from which it was drawn.", "PMID": "11080460"}, {"title": "A randomised study of midwifery caseload care and traditional 'shared-care'.", "abstract": "To evaluate caseload midwifery care in comparison to traditional 'shared care'.\n\nComparative study with area randomisation.\n\nDistrict general hospital in England.\n\n'Known carer at delivery,' 'normal vaginal delivery' and 'obstetric intervention'.\n\nAll pregnant women delivering in the six areas chosen for the study.\n\nA highly significant difference was found between caseload and traditional care groups in terms of level of 'known carer at delivery' (696/770 94.7%; cf. 52/735 (6.7%), p < 0.001). However, no differences in 'normal vaginal delivery' rates were found (542/770 (70%) cf. 509/735 (69%). There were fewer 'obstetric interventions' in the caseload group, particularly epidural analgesia (80/770 (10%) cf. 110/735 (15%) p = 0.01) and oxytocin augmentation (351/77 (46%) cf. 387/735 (53%), p = 0.01). There were no significant differences found in terms of neonatal outcome.\n\nCaseload midwifery results in high levels of 'known carer at delivery' which appears to be associated with a reduction in augmentation and epidural rates but which were not associated with an increase in normal vaginal delivery rate.", "PMID": "11080465"}, {"title": "The costs of alternative types of routine antenatal care for low-risk women: shared care vs care by general practitioners and community midwives.", "abstract": "To compare the costs to the health service, women and their families of routine antenatal care provided by either traditional obstetrician-led shared care or general practitioner (GP)/community midwife care.\n\nA multicentre randomized controlled trial in 51 general practices linked to nine maternity hospitals in Scotland: 1667 low-risk pregnant women provided information on costs to the health service. 704 of these women provided information on non-health service costs.\n\nGP/midwife antenatal care was found to cost statistically significantly less than shared care. This was the case for investigations carried out at routine antenatal visits (GP/midwife = 87.25 Pounds, shared care = 91.15 Pounds, P = 0.05), staffing costs at routine antenatal visits (GP/midwife = 127.76 Pounds, shared care = 131.09 Pounds, P = 0.001), and non-health service costs incurred by women and their companions (GP/midwife = 118.53 Pounds, shared care = 133.49 Pounds, P = 0.001). While non-routine care in the GP/midwife arm of the trial costs less than in the shared care arm, the difference was not statistically significant (GP/midwife = 83.74 Pounds, shared care = 94.43 Pounds, P = 0.46). The total societal cost of antenatal care was 417.28 Pounds per women in the GP/midwife arm of the trial and 450.19 Pounds in the shared care arm of the trial. This difference was statistically significant (P < 0.001). The application of sensitivity analysis did not change these results.\n\nGP/midwife antenatal care is a satisfactory option for low-risk pregnant women in Scotland provided that clinical outcomes and women's satisfaction are at least the same as those of women with shared care.", "PMID": "10180859"}, {"title": "A randomized controlled trial comparing midwife-managed care and obstetrician-managed care for women assessed to be at low risk in the initial intrapartum period.", "abstract": "To compare the efficacy of midwife-managed care and obstetrician-managed care for women assessed to be at low risk in the initial intrapartum period.\n\n1,050 women assessed to be at low risk on admission to labour ward in the Prince of Wales Hospital participated in this study. By computer-generated random allocation, 563 (54%) women were assigned to Group A (experimental) under midwifery care, and 487 (46%) women to Group B (control) under obstetrician care. The outcomes and complications between the 2 groups were compared. Data were analyzed by 2 x 2 contingency tables and Chi-square.\n\n150 (26.6%) women in the experimental group were taken over by the obstetricians. 46 (30.7%) women were transferred to obstetrician-management for the preference of epidural analgesia. The other reasons for taken over the remaining 104 (69.3%) women were fetal distress, poor progress of labour, complications in first or second stage of labour. The experimental group had less oxytocic augmentation (Chi-square = 7.49, p = 0.006) and the insertion of intravenous infusion (Chi-square = 5.34, p = 0.02). Both groups had similar outcomes on normal delivery, operative vaginal delivery, caesarean section and complications.\n\nMidwife-managed care is as safe as obstetrician-managed care for women who were assessed to be at low risk in the intrapartum period. Routine visit by obstetrician is not necessary and the midwives are able to detect complications in the course of labour and alert the obstetrician for taking the necessary action.", "PMID": "10379125"}, {"title": "A randomised controlled trial comparing birthing centre care with delivery suite care in Adelaide, Australia.", "abstract": "Birthing centre care offers women with a low risk of complication in pregnancy an alternative to conventional care for the birthing of their baby. It is important these two forms of care are appropriately assessed. A randomised controlled trial comparing the newly opened birthing centre with the established conventional delivery suite was conducted at the then Queen Victoria Hospital, Adelaide, South Australia. The outcomes measured included maternal satisfaction, costs and clinical outcomes both for mother and baby which related to the need for Caesarean section, episiotomy or tear rate and method of feeding. Two hundred and one women attending the hospital's antenatal clinic were randomly allocated to either birthing centre or delivery suite care. One hundred women were allocated to the birthing centre. No differences were found in either group related to clinical outcomes or costs. The only difference in maternal satisfaction was the choice women made for their next birth. More women in the birthing centre group felt they were encouraged to breastfeed immediately after birth. While the numbers in this study were too small to detect any but large differences in outcome, birthing centre care should remain an option for women and further studies undertaken with larger numbers.", "PMID": "11065032"}, {"title": "Does birth center care during a woman's first pregnancy have any impact on her future reproduction?", "abstract": "Women's experiences of childbirth may affect their future reproduction, and the model of care affects their experiences, suggesting that a causal link may exist between model of care and future reproduction. The study objective was to examine whether the birth center model of care during a woman's first pregnancy affects whether or not she has a second baby, and on the spacing to the next birth.\n\nBetween October 1989 and July 1993, a total of 1860 women at low medical risk in early pregnancy, who participated in a randomized controlled trial of in-hospital birth center care versus standard care, gave birth. The 1063 primiparas in the trial, 543 in the birth center group and 520 in the standard care group, were included in a secondary analysis in which women's personal identification codes were linked to the Swedish National Birth Register, which included information about their subsequent birth during the following 7 to 10 years. Time to an event curves were constructed by means of the Kaplan Meier method.\n\nThe observation period after the first birth was on average 8.8 years in the birth center group and 8.7 years in the standard care group. No statistical difference was found between the groups in time to second birth, which was 2.85 and 2.82 years, respectively (median; log-rank 1.26; p=0.26).\n\nA woman's model of care, such as birth center care, during her first pregnancy does not seem to be a sufficiently important factor to affect subsequent reproduction in Sweden.", "PMID": "12153648"}, {"title": "Effectiveness of certified nurse-midwives. A prospective evaluation study.", "abstract": "A prospective evaluation study of the effectiveness of the services of certified nurse-midwives demonstrated that in a hospital setting the care of low-risk maternity patients provided by nurse-midwives was as effective as the provided by house staff physicians. A total of 438 low-risk maternity patients were studied. Selected outcomes pertaining to the prenatal period, labor and delivery, and early infancy demonstrated, with two exceptions, no significant differences. The two exceptions were: (1) overcompliance with appointment attendance was more common among the nurse-midwifery group of patients; (2) a higher rate of forceps delivery was reported among the house staff group of patients.", "PMID": "1247054"}, {"title": "Swedish women's interest in home birth and in-hospital birth center care.", "abstract": "In Sweden, few alternatives to a hospital birth are available, and little is known about consumer interest in alternative birth care. The aim of this study was to determine women's interest in home birth and in-hospital birth center care in Sweden, and to describe the characteristics of these women.\n\nAll Swedish-speaking women booked for antenatal care during 3 weeks during 1 year were invited to participate in the study. Three questionnaires, completed after the first booking visit in early pregnancy, at 2 months, and 1 year after the birth, asked about the women's interest in two alternative birth options and a wide range of possible explanatory variables.\n\nConsent to participate in the study was given by 3283 women (71% of all women eligible). The rates of response to the three questionnaires were 94, 88, and 88 percent, respectively. One percent of participants consistently expressed an interest in home birth on all three occasions, and 8 percent expressed an interest in birth center care. A regression analysis showed five factors that were associated with an interest in home birth: a wish to have the baby's siblings (OR 20.2; 95% CI 6.2-66.5) and a female friend (OR 15.2; 95% CI 6.2-37.4) present at the birth, not wanting pharmacological pain relief during labor and birth (OR 4.7; 95% CI 1.4-15.3), low level of education (OR 4.5; 95% CI 1.8-11.4), and dissatisfaction with medical aspects of intrapartum care (OR 3.6; 95% CI 1.4-9.2). An interest in birth center care was associated with experience of being in control during labor and birth (OR 8.3; 95% CI 3.2-21.6), not wanting pharmacological pain relief (OR 2.3; 95% CI 1.3-4.1), and a preference to have a known midwife at the birth (OR 2.2; 95% CI 1.6-2.9).\n\nIf Swedish women were offered free choice of place of birth, the home birth rate would be 10 times higher, and the 20 largest hospitals would need to have a birth center. Women interested in alternative models of care view childbirth as a social and natural event, and their needs should be considered.", "PMID": "12581035"}, {"title": "Antenatal care of low risk obstetric patients by midwives. A randomised controlled trial.", "abstract": "To assess the practicality, acceptability to patients and salary costs of the antenatal care of low risk obstetric patients by midwives.\n\nA randomised controlled trial.\n\nThe antenatal clinic at Westmead Hospital, a teaching hospital of the University of Sydney in western Sydney.\n\nFrom January 1989 until November 1990, 89 women booking for full antenatal care at Westmead Hospital and classified as low risk were randomly allocated to one of two groups. Group 1 (43 patients) had their antenatal care provided by registered midwives. Group 2 (46 patients) had their antenatal care provided by an obstetrician (either Visiting Medical Officer or Staff Specialist) in a routine hospital antenatal clinic.\n\nPatients in the midwives' clinic were seen by an obstetrician at their first visit to the antenatal clinic and again at 30 weeks and at 40 weeks.\n\nThese were the salary costs of each clinic and the patients' levels of satisfaction. Maternal and neonatal indicators, delivery details and analgesic requirements were also considered. These indicators were planned before data collection commenced.\n\nThe major differences found were a 28% to 68% salary cost saving and that patients cared for by midwives showed appreciation of the continuity of care and information given at the midwives' clinic.\n\nThe care of low risk obstetric patients by midwives in a midwives' clinic showed salary cost savings and high patient acceptance.", "PMID": "1635487"}], "labels": [{"PMID": "10382476", "label": "included"}, {"PMID": "11080460", "label": "included"}, {"PMID": "11080465", "label": "included"}, {"PMID": "10180859", "label": "excluded"}, {"PMID": "10379125", "label": "excluded"}, {"PMID": "11065032", "label": "excluded"}, {"PMID": "12153648", "label": "excluded"}, {"PMID": "1247054", "label": "excluded"}, {"PMID": "12581035", "label": "excluded"}, {"PMID": "1635487", "label": "excluded"}]}
{"metadata": {"review_pmid": "38577875"}, "inputs": {"background": "Depression and anxiety occur frequently (with reported prevalence rates of around 40%) in individuals with coronary heart disease (CHD), heart failure (HF) or atrial fibrillation (AF) and are associated with a poor prognosis, such as decreased health-related quality of life (HRQoL), and increased morbidity and mortality. Psychological interventions are developed and delivered by psychologists or specifically trained healthcare workers and commonly include cognitive behavioural therapies and mindfulness-based stress reduction. They have been shown to reduce depression and anxiety in the general population, though the exact mechanism of action is not well understood. Further, their effects on psychological and clinical outcomes in patients with CHD, HF or AF are unclear.", "objectives": "To assess the effects of psychological interventions (alone, or with cardiac rehabilitation or pharmacotherapy, or both) in adults who have a diagnosis of CHD, HF or AF, compared to no psychological intervention, on psychological and clinical outcomes.", "selection criteria": "We included randomised controlled trials (RCTs) comparing psychological interventions with no psychological intervention for a minimum of six months follow-up in adults aged over 18 years with a clinical diagnosis of CHD, HF or AF, with or without depression or anxiety. Studies had to report on either depression or anxiety or both."}, "context": [{"title": "Treatment of depression after coronary artery bypass surgery: a randomized controlled trial.", "abstract": "There has been little research on the treatment of depression after coronary artery bypass surgery.\n\nTo test the efficacy of 2 nonpharmacological interventions for depression after coronary artery bypass surgery compared with usual care.\n\nA 12-week, randomized, single-blind clinical trial with outcome evaluations at 3, 6, and 9 months.\n\nOutpatient research clinic at Washington University School of Medicine, St Louis, Missouri.\n\nOne hundred twenty-three patients who met the DSM-IV criteria for major or minor depression within 1 year after surgery.\n\nTwelve weeks of cognitive behavior therapy or supportive stress management. Approximately half of the participants were taking nonstudy antidepressant medications.\n\nRemission of depression, defined as a score of less than 7 on the 17-item Hamilton Rating Scale for Depression.\n\nRemission of depression occurred by 3 months in a higher proportion of patients in the cognitive behavior therapy (71%) and supportive stress-management (57%) arms than in the usual care group (33%) (chi(2)(2) = 12.22, P = .002). Covariate-adjusted Hamilton scores were lower in the cognitive behavior therapy (mean [standard error], 5.5 [1.0]) and the supportive stress-management (7.8 [1.0]) arms than in the usual care arm (10.7 [1.0]) at 3 months. The differences narrowed at 6 months, but the remission rates differed again at 9 months (73%, 57%, and 35%, respectively; chi(2)(2) = 12.02, P = .003). Cognitive behavior therapy was superior to usual care at most points on secondary measures of depression, anxiety, hopelessness, stress, and quality of life. Supportive stress management was superior to usual care only on some of the measures.\n\nBoth cognitive behavior therapy and supportive stress management are efficacious for treating depression after coronary artery bypass surgery, relative to usual care. Cognitive behavior therapy had greater and more durable effects than supportive stress management on depression and several secondary psychological outcomes.\n\nclinicaltrials.gov Identifier: NCT00042198.", "PMID": "19349308"}, {"title": "Randomised controlled trial of a secondary prevention program for myocardial infarction patients ('ProActive Heart'): study protocol. Secondary prevention program for myocardial infarction patients.", "abstract": "Coronary heart disease (CHD) is a significant cause of health and economic burden. Secondary prevention programs play a pivotal role in the treatment and management of those affected by CHD although participation rates are poor due to patient, provider, health system and societal-level barriers. As such, there is a need to develop innovative secondary prevention programs to address the treatment gap. Telephone-delivered care is convenient, flexible and has been shown to improve behavioural and clinical outcomes following myocardial infarction (MI). This paper presents the design of a randomised controlled trial to evaluate the efficacy of a six-month telephone-delivered secondary prevention program for MI patients (ProActive Heart).\n\n550 adult MI patients have been recruited over a 14 month period (December 2007 to January 2009) through two Brisbane metropolitan hospitals, and randomised to an intervention or control group (n = 225 per group). The intervention commences within two weeks of hospital discharge delivered by study-trained health professionals ('health coaches') during up to 10 x 30 minute scripted telephone health coaching sessions. Participants also receive a ProActive Heart handbook and an educational resource to use during the health coaching sessions. The intervention focuses on appropriate modification of CHD risk factors, compliance with pharmacological management, and management of psychosocial issues. Data collection occurs at baseline or prior to commencement of the intervention (Time 1), six months follow-up or the completion of the intervention (Time 2), and at 12 months follow-up for longer term outcomes (Time 3). Primary outcome measures include quality of life (Short Form-36) and physical activity (Active Australia Survey). A cost-effective analysis of the costs and outcomes for patients in the intervention and control groups is being conducted from the perspective of health care costs to the government.\n\nThe results of this study will provide valuable new information about an innovative telephone-delivered cost-effective secondary prevention program for MI patients.", "PMID": "19426524"}, {"title": "Rationale and design of WEBCARE: a randomized, controlled, web-based behavioral intervention trial in cardioverter-defibrillator patients to reduce anxiety and device concerns and enhance quality of life.", "abstract": "The implantable cardioverter defibrillator (ICD) is generally well accepted, but 25-33% of patients experience clinical levels of anxiety, depression, and impaired quality of life (QoL) following implantation. Few trials in ICD patients have investigated whether behavioral intervention may mitigate the development of these adjustment problems. We present the rationale and study design of the WEB-based distress management program for implantable CARdioverter dEfibrillator patients (WEBCARE) trial.\n\nWEBCARE is a multi-center, multi-disciplinary, randomized, controlled behavioral intervention trial designed to examine the effectiveness of a web-based approach in terms of reducing levels of anxiety and device concerns and enhancing QoL. Consecutive patients hospitalized for the implantation of an ICD will be approached for study participation while in hospital and randomized to the intervention arm (n = 175) versus usual care (n = 175) at baseline (5-10 days post implantation). Patients will complete assessments of patient-centered outcomes at baseline, 14, 26, and 52 weeks after implantation. Patients randomized to the intervention arm will receive a 12-week web-based behavioral intervention starting 2 weeks after implantation. Primary endpoints include (i(i)) patient-centered outcomes (i.e., anxiety, depression, ICD acceptance, QoL); (i(ii)) health care utilization; and (i(iii)) cost-effectiveness. All primary endpoints will be assessed with standardized and validated disease-specific or generic questionnaires. Secondary endpoints include (ii(i)) cortisol awakening response; and (ii(ii)) ventricular arrhythmias.\n\nWEBCARE will show whether a behavioral intervention using a web-based approach is feasible and effective in reducing anxiety and ICD concerns and improving QoL in ICD patients.\n\nhttp://www.ClinicalTrials.gov. Identifier: NCT00895700.", "PMID": "20030843"}, {"title": "Evaluating the angina plan in patients admitted to hospital with angina: a randomized controlled trial.", "abstract": "The aim of this trial was to evaluate the Angina Plan (AP), a cognitive-behavioral nurse-facilitated self-help intervention against standard care (SC). A randomized controlled trial of 218 patients hospitalized with angina assessed participants predischarge and 6 months later. Data were collected during a structured interview using validated questionnaires, self-report, and physiological measurement to assess between group changes in mood, knowledge and misconceptions, cardiovascular risk, symptoms, quality of life, and health service utilization. The intention-to-treat (ITT) analysis found no reliable effects on anxiety and depression at 6 months. AP participants reported increased knowledge, less misconceptions, reduced body mass index (BMI), an increase in self-reported exercise, less functional limitation, and improvements in general health perceptions and social and leisure activities compared to those receiving SC. Sensitivity analysis excluding participants with high baseline depression revealed a statistical significant reduction in depression levels in AP compared to the SC participants. Analysis excluding participants receiving cardiac surgery or angioplasty removed the ITT effects on physical limitation, self-reported exercise and general health perceptions and the improvements seen in social and leisure activities, while adaptive effects on knowledge, misconceptions and BMI remained and between-group changes in depression approached significance. Initiating the AP in a secondary care setting for patients with new and existing angina produces similar benefits to those reported in newly diagnosed primary care patients. Further evaluation is required to examine the extent of observed effects in the longer term. ", "PMID": "20041881"}, {"title": "Enhanced depression care for patients with acute coronary syndrome and persistent depressive symptoms: coronary psychosocial evaluation studies randomized controlled trial.", "abstract": "Depressive symptoms are an established predictor of mortality and major adverse cardiac events (defined as nonfatal myocardial infarction or hospitalization for unstable angina or urgent/emergency revascularizations) in patients with acute coronary syndrome (ACS). This study was conducted to determine the acceptability and efficacy of enhanced depression treatment in patients with ACS.\n\nA 3-month observation period to identify patients with ACS and persistent depressive symptoms was followed by a 6-month randomized controlled trial. From January 1, 2005, through February 29, 2008, 237 patients with ACS from 5 hospitals were enrolled, including 157 persistently depressed patients randomized to intervention (initial patient preference for problem-solving therapy and/or pharmacotherapy, then a stepped-care approach; 80 patients) or usual care (77 patients) and 80 nondepressed patients who underwent observational evaluation. The primary outcome was patient satisfaction with depression care. Secondary outcomes were depressive symptom changes (assessed with the Beck Depression Inventory), major adverse cardiac events, and death.\n\nAt the end of the trial, the proportion of patients who were satisfied with their depression care was higher in the intervention group (54% of 80) than in the usual care group (19% of 77) (odds ratio, 5.4; 95% confidence interval [CI], 2.2-12.9 [P < .001]). The Beck Depression Inventory score decreased significantly more (t(155) = 2.85 [P = .005]) for intervention patients (change, -5.7; 95% CI, -7.6 to -3.8; df = 155) than for usual care patients (change, -1.9; 95% CI, -3.8 to -0.1; df = 155); the depression effect size was 0.59 of the standard deviation. At the end of the trial, 3 intervention patients and 10 usual care patients had experienced major adverse cardiac events (4% and 13%, respectively; log-rank test, chi(2)(1) = 3.93 [P = .047]), as well as 5 nondepressed patients (6%) (for the intervention vs nondepressed cohort, chi(2)(1) = 0.48 [P = .49]).\n\nEnhanced depression care for patients with ACS was associated with greater satisfaction, a greater reduction in depressive symptoms, and a promising improvement in prognosis.\n\nclinicaltrials.gov Identifier: NCT00158054.", "PMID": "20386003"}, {"title": "A randomized controlled trial of secondary prevention of anxiety and distress in a German sample of patients with an implantable cardioverter defibrillator.", "abstract": "To evaluate a minimal, easy, accessible intervention targeting anxiety and reduced quality of life in patients with an implantable cardioverter defibrillator (ICD). An estimated 24% to 87% of patients experience anxiety, and 10% to 15% have reduced quality of life.\n\nA total of 119 ICD patients were assigned randomly to usual medical aftercare (n = 63) or additional psychological treatment (n = 56) comprising of written information on medical and psychological consequences of an ICD plus 6 months of individual phone counseling. Treatment efficacy was evaluated by comparing T0 (immediately after implantation) and T1 (6 months later) assessments.\n\nAlthough 75% of patients considered the program helpful, age moderated treatment efficacy. As indicated by triple interactions, only in the treatment group, anxiety (HADS-Anxiety, p < .01), psychological distress (SCL-K-9, p < .02), and somatic quality of life (SF-36-PCS, p < .01) improved in ICD patients aged <65 years but deteriorated in older patients (age, 65-75 years). Frequency of ICD discharges was associated with a symptom increase from T0 to T1 in all patients (HADS-Depression, CAQ-Avoidance, and ICD-Constraints; all p < .05).\n\nOur findings confirm that psychological treatments cannot be expected to have uniformly positive effects in ICD patients. Our minimal intervention may have adequately addressed ICD-related concerns in younger patients but may have fostered problems in older patients with fewer concerns. Therefore, our findings warrant custom treatment with particular attention to the elderly as well as patients with frequent ICD discharges.", "PMID": "20410252"}, {"title": "Combined exercise and cognitive behavioral therapy improves outcomes in patients with heart failure.", "abstract": "The purpose of this study is to compare the effectiveness of a combined 12-week home-based exercise (EX)/cognitive behavioral therapy (CBT) program (n=18) with CBT alone (n=19), EX alone (n=20), and with usual care (UC, n=17) in stable New York Heart Association Class II to III heart failure (HF) patients diagnosed with depression.\n\nDepressive symptom severity [Hamilton Rating Scale for Depression (HAM-D)], physical function [6-min walk test (6MWT)], and health-related quality of life (HRQOL) (Minnesota Living with Heart Failure Questionnaire) were evaluated at baseline (T1), after the 12-week intervention/control (T2), and following a 3-month telephone follow-up (T3). A repeated measures analysis of variance was used to determine group differences. Depression severity was dichotomized as minor (HAM-D, 11-14) and moderate-to-major depression (HAM-D, >/=15), and group intervention and control responses were also evaluated on that basis.\n\nThe greatest reduction in HAM-D scores over time occurred in the EX/CBT group (-10.4) followed by CBT (-9.6), EX (-7.3), and UC (-6.2), but none were statistically significant. The combined group showed a significant increase in 6-min walk distance at 24 weeks (F=13.5, P<.001). Among all groups with moderate-to-major depression, only those in CBT/EX had sustained lower HAM-D scores at 12 and 24 weeks, 6MWT distances were significantly greater at 12 (P=.018) and 24 (P=.013) weeks, and the greatest improvement in HRQOL also occurred.\n\nInterventions designed to improve both physical and psychological symptoms may provide the best method for optimizing functioning and enhancing HRQOL in patients with HF.", "PMID": "20624510"}, {"title": "A randomised, feasibility trial of a tele-health intervention for acute coronary syndrome patients with depression ('MoodCare'): study protocol.", "abstract": "Coronary heart disease (CHD) and depression are leading causes of disease burden globally and the two often co-exist. Depression is common after Myocardial Infarction (MI) and it has been estimated that 15-35% of patients experience depressive symptoms. Co-morbid depression can impair health related quality of life (HRQOL), decrease medication adherence and appropriate utilisation of health services, lead to increased morbidity and suicide risk, and is associated with poorer CHD risk factor profiles and reduced survival. We aim to determine the feasibility of conducting a randomised, multi-centre trial designed to compare a tele-health program (MoodCare) for depression and CHD secondary prevention, with Usual Care (UC).\n\nOver 1600 patients admitted after index admission for Acute Coronary Syndrome (ACS) are being screened for depression at six metropolitan hospitals in the Australian states of Victoria and Queensland. Consenting participants are then contacted at two weeks post-discharge for baseline assessment. One hundred eligible participants are to be randomised to an intervention or a usual medical care control group (50 per group). The intervention consists of up to 10 \u00d7 30-40 minute structured telephone sessions, delivered by registered psychologists, commencing within two weeks of baseline screening. The intervention focuses on depression management, lifestyle factors (physical activity, healthy eating, smoking cessation, alcohol intake), medication adherence and managing co-morbidities. Data collection occurs at baseline (Time 1), 6 months (post-intervention) (Time 2), 12 months (Time 3) and 24 months follow-up for longer term effects (Time 4). We are comparing depression (Cardiac Depression Scale [CDS]) and HRQOL (Short Form-12 [SF-12]) scores between treatment and UC groups, assessing the feasibility of the program through patient acceptability and exploring long term maintenance effects. A cost-effectiveness analysis of the costs and outcomes for patients in the intervention and control groups is being conducted from the perspective of health care costs to the government.\n\nThis manuscript presents the protocol for a randomised, multi-centre trial to evaluate the feasibility of a tele-based depression management and CHD secondary prevention program for ACS patients. The results of this trial will provide valuable new information about potential psychological and wellbeing benefits, cost-effectiveness and acceptability of an innovative tele-based depression management and secondary prevention program for CHD patients experiencing depression.\n\nAustralia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12609000386235.", "PMID": "21349204"}, {"title": "Short-term effect of motivational interviewing on clinical and psychological outcomes and health-related quality of life in cardiac rehabilitation patients with poor motivation in Hong Kong: a randomized controlled trial.", "abstract": "Motivational interviewing (MI) is effective in promoting behavioural changes in patients with substance abuse and smoking. However, its effectiveness on health outcomes in cardiac rehabilitation patients is unclear.\n\nA randomized controlled trial.\n\nA total of 146 patients assessed as having poor motivation attended a cardiac rehabilitation programme from February 2008 to June 2010. Patients (n\u2009=\u200973) in the control group received usual care while those in the experimental group (n\u2009=\u200973) received usual care plus four sessions of MI, each lasting 30-45\u2009min. Clinical and psychological outcomes and health-related quality of life were measured at baseline and 3 months after entering the programme. Descriptive statistics, independent t-test, Pearson Chi-squared test, and generalized estimating equations models were used to analyse the data.\n\nThere was no significant difference between the two groups on clinical outcomes (all p-values >0.05). Patients in the experimental group had higher increases in health-related quality of life (SF-36) scores in the aspects of general health (4.74, 95% CI 0.04-9.44; p\u2009=\u20090.048) and role limitation due to emotional problems (8.80, 95% CI 1.16-16.43; p\u2009=\u20090.024). However, they reported significantly higher increases in anxiety levels (Hospital Anxiety and Depression Scale) than those in the control group (0.96, 95% CI 0.09-1.83; p\u2009=\u20090.030).\n\nThe short-term effectiveness of MI on clinical outcomes and health-related quality of life in poorly motivated cardiac rehabilitation patients is limited. MI, however, was shown to increase anxiety levels of patients during the study period (3 months). More evidence is needed to better understand this phenomenon in the future studies.", "PMID": "21960653"}, {"title": "Dyads affected by chronic heart failure: a randomized study evaluating effects of education and psychosocial support to patients with heart failure and their partners.", "abstract": "Chronic heart failure (CHF) causes great suffering for both patients and their partners. The aim of this study was to evaluate the effects of an integrated dyad care program with education and psychosocial support to patients with CHF and their partners during a postdischarge period after acute deterioration of CHF.\n\nOne hundred fifty-five patient-caregiver dyads were randomized to usual care (n = 71) or a psychoeducation intervention (n = 84) delivered in 3 modules through nurse-led face-to-face counseling, computer-based education, and other written teaching materials to assist dyads to develop problem-solving skills. Follow-up assessments were completed after 3 and 12 months to assess perceived control, perceived health, depressive symptoms, self-care, and caregiver burden.\n\nBaseline sociodemographic and clinical characteristics of dyads in the experimental and control groups were similar at baseline. Significant differences were observed in patients' perceived control over the cardiac condition after 3 (P < .05) but not after 12 months, and no effect was seen for the caregivers.No group differences were observed over time in dyads' health-related quality of life and depressive symptoms, patients' self-care behaviors, and partners' experiences of caregiver burden.\n\nIntegrated dyad care focusing on skill-building and problem-solving education and psychosocial support was effective in initially enhancing patients' levels of perceived control. More frequent professional contact and ongoing skills training may be necessary to have a higher impact on dyad outcomes and warrants further research.", "PMID": "22555264"}], "labels": [{"PMID": "19349308", "label": "included"}, {"PMID": "19426524", "label": "included"}, {"PMID": "20030843", "label": "included"}, {"PMID": "20041881", "label": "included"}, {"PMID": "20386003", "label": "included"}, {"PMID": "20410252", "label": "included"}, {"PMID": "20624510", "label": "included"}, {"PMID": "21349204", "label": "included"}, {"PMID": "21960653", "label": "included"}, {"PMID": "22555264", "label": "included"}]}
{"metadata": {"review_pmid": "38533994"}, "inputs": {"background": "Cardiovascular diseases (CVDs) are the leading cause of death globally, accounting for almost 18 million deaths annually. People with CVDs have a five times greater chance of suffering a recurrent cardiovascular event than people without known CVDs. Although drug interventions have been shown to be cost-effective in reducing the risk of recurrent cardiovascular events, adherence to medication remains suboptimal. As a scalable and cost-effective approach, mobile phone text messaging presents an opportunity to convey health information, deliver electronic reminders, and encourage behaviour change. However, it is uncertain whether text messaging can improve medication adherence and clinical outcomes. This is an update of a Cochrane review published in 2017.", "objectives": "To evaluate the benefits and harms of mobile phone text messaging for improving medication adherence in people with CVDs compared to usual care.", "selection criteria": "We included randomised controlled trials (RCTs) with participants with established arterial occlusive events. We included trials investigating interventions using short message service (SMS) or multimedia messaging service (MMS) with the aim of improving adherence to medication for the secondary prevention of cardiovascular events. The comparator was usual care. We excluded cluster-RCTs and quasi-RCTs."}, "context": [{"title": "The effect of short message system (SMS) reminder on adherence to a healthy diet, medication, and cessation of smoking among adult patients with cardiovascular diseases.", "abstract": "Cardiovascular Disease is the leading cause of death worldwide. Non-adherence to a recommended regimen among patients with Cardiovascular Diseases represents a significant problem which could lead to an increase in Cardiovascular Diseases.\n\nThis study aimed to assess the effects of Short Message System (SMS) reminders on adherence to a healthy diet, medication, and cessation of smoking among adult patients with Cardiovascular Diseases.\n\nRandomized controlled trial design with three groups was used for this study. A non-probability convenient sample of 160 patients was recruited in this study. The participants were assigned randomly to an experimental group (received SMS regarding adherence to a healthy diet, medication, and smoking cessation), placebo group (received general messages) and control group (routine care). Morisky 8-Item Medication Adherence Scale (MMAS), Mediterranean Diet Adherence Screener (MEDAS), and Readiness to Quit Ladder, were used to assess patients' adherence to medication, adherence to Mediterranean diet, and smoking cessation, respectively. The outcomes were assessed at the beginning of the study and three months later, following completion of the intervention.\n\nOne way ANONVA was used to assess the study hypothesis. Significant differences between study groups found in terms of adherence to medication (p=.001) and adherence to a healthy diet (p=.000); however, no significant difference was found between groups, in terms of intention to quit smoking, and/or the number of cigarettes smoked (p=\u2009.327), (p=.34), respectively.\n\nIt is documented that SMS is effective in improving adherence to a healthy diet and medication. SMS could be a promising solution for management of different chronic diseases.\n\nIt is recommended to apply Short Message System (SMS) via cellphone services to improve patient's adherence to a healthy diet and medication. However, further research is needed to support the effectiveness of SMS.", "PMID": "28034414"}, {"title": "The effectiveness of daily SMS reminders in pharmaceutical care of older adults on improving patients' adherence to antihypertensive medication (SPPA): study protocol for a randomized controlled trial.", "abstract": "Despite a variety of efficient and cost-effective antihypertensive medication, hypertension remains a serious health and economic burden. High consumption of cardiovascular drugs in the Slovak Republic does result neither in better hypertension control nor in significant decrease in cardiovascular mortality. At the same time, Slovakia has alarmingly low patients' adherence to medication intake. Studies have shown the efficiency of short messaging service (SMS) reminders to improve patients' adherence and health outcomes at low costs. Since SMS is popular among Slovaks, this approach may be feasible also in Slovakia. The primary objective is to assess if daily SMS reminders of antihypertensive medication intake provided by pharmacists in addition to the standard pharmaceutical care increase the proportion of adherent older hypertensive ambulatory patients.\n\nThe SPPA trial is a pragmatic randomized parallel group (1:1) trial in 300 older hypertensive patients carried out in community pharmacies in Slovakia. Trial pharmacies will be selected from all main regions of Slovakia. Trial intervention comprises daily personalized SMS reminders of medication intake embedded into usual pharmaceutical practice. The primary outcome is a combined adherence endpoint consisting of subjective self-reported medication adherence via the eight-item Morisky Medication Adherence Scale (MMAS-8) and objective pill count rate. Secondary outcomes include: change in the MMAS-8; comparison of adherence rates using pill count; change in systolic blood pressure; and patient satisfaction. Also, direct treatment costs will be evaluated and a cost-effectiveness analysis will be carried out.\n\nThe SPPA trial engages community pharmacists and mobile health (mHealth) technologies via evidence-based pharmaceutical care to efficiently and cost-effectively addresses current main healthcare challenges: high prevalence of hypertension; overconsumption of cardiovascular medicines; low adherence to medication treatment; and resulting uncontrolled blood pressure. The results may identify new possibilities and capacities in healthcare with low additional costs and high value to patients.\n\nClinicalTrials.gov, NCT03105687 . Registered on 07 March 2017.", "PMID": "28720121"}, {"title": "The Effect of Interactive Text Message Follow-up on Health Promoting Lifestyle of Patients with Acute Coronary Syndrome.", "abstract": "Lifestyle modification is an essential factor in the promotion of health in patients with acute coronary syndrome (ACS). One of the interventions to promote lifestyle is interactive follow-up, which, according to the traditional methods, requires spending significant amount of time and cost. Therefore, this study aimed to determine the effectiveness of interactive text message follow-up on health promoting lifestyle of patients with ACS.\n\nThis was a randomized controlled trial among 100 patients suffering from ACS during October-February 2016. The participants were randomly assigned to the experimental and control groups. Collection of data on lifestyle was performed before, 3, and 4 months after the beginning of the intervention using Walker's Health Promoting lifestyle questionnaire. Six messages were sent to the intervention groups each week, and participants asked the questions by sending text message, each week 1 message were sent to the control group for 12 weeks. The statistical analysis of data was performed using independent \n\nBefore the intervention, there was no significant difference between the mean score of lifestyle of the two groups, however, 3 months and 4 months after the beginning of the intervention, the mean score of lifestyle in the intervention group was significantly higher than that of the control group (\n\nThe interactive text message follow-up is effective in promoting the lifestyle of patients with ACS and can be considered in the planning of follow-up of patients with ACS.", "PMID": "28904541"}, {"title": "MEDication reminder APPs to improve medication adherence in Coronary Heart Disease (MedApp-CHD) Study: a randomised controlled trial protocol.", "abstract": "The growing number of smartphone health applications available in the app stores makes these apps a promising tool to help reduce the global problem of non-adherence to long-term medications. However, to date, there is limited evidence that available medication reminder apps are effective. This study aims to determine the impact of medication reminder apps on adherence to cardiovascular medication when compared with usual care for people with coronary heart disease (CHD) and to determine whether an advanced app compared with a basic app is associated with higher adherence.\n\nRandomised controlled trial with follow-up at 3 months to evaluate the feasibility and effectiveness of medication reminder apps on medication adherence compared with usual care. An estimated sample size of 156 patients with CHD will be randomised to one of three groups (usual care group, basic medication reminder app group and advanced medication reminder app group). The usual care group will receive standard care for CHD with no access to a medication reminder app. The basic medication reminder app group will have access to a medication reminder app with a basic feature of providing simple daily reminders with no interactivity. The advanced medication reminder app group will have access to a medication reminder app with additional interactive and customisable features. The primary outcome is medication adherence measured by the eight-item Morisky Medication Adherence Scale at 3 months. Secondary outcomes include clinical measurements of blood pressure and cholesterol levels, and medication knowledge. A process evaluation will also be performed to assess the feasibility of the intervention by evaluating the acceptability, utility and engagement with the apps.\n\nEthical approval has been obtained from the Western Sydney Local Health Network Human Research Ethics Committee (AU/RED/HREC/1/WMEAD/3). Study findings will be disseminated via usual scientific forums.\n\nACTRN12616000661471; Pre-results.", "PMID": "28993388"}, {"title": "Using Mobile Health Intervention to Improve Secondary Prevention of Coronary Heart Diseases in China: Mixed-Methods Feasibility Study.", "abstract": "Coronary heart disease (CHD) is the leading cause of cardiovascular mortality worldwide, yet implementation of evidence-based strategies for secondary prevention remains suboptimal.\n\nThis study aimed to evaluate the feasibility, specifically the usability and acceptability, and estimate the preliminary effectiveness of a mobile health (mHealth) intervention targeting both physicians and patients to improve adherence to evidence-based medications and lifestyle modifications.\n\nWe conducted a 12-week pre-post interventional pilot study at two sites in Shanghai and Hainan, China. Physicians used the app designed in this study to prescribe evidence-based medicines and record patient information. Eligible and consenting patients received automatic text messages or voice calls 4 to 5 times per week for 12 weeks on medication adherence and healthy behaviors. Interviews were conducted among 10 physicians and 24 patients at the two sites for their thoughts on medication adherence and feedback on the usability and acceptability. Questions on usability and acceptability were also asked in a patient follow-up survey. With regard to estimating effectiveness, the primary outcome was medication adherence (as estimated by the Morisky Green Levine Scale) at 12 weeks. Secondary outcomes included physical activity, smoking status, fruits and vegetables consumption, and facility visit frequency.\n\nInterview findings and patient survey showed the good usability and acceptability of the intervention. Among 190 patients who completed the intervention, there was a significant increase in medication adherence (odds ratio [OR] 1.80, 95% CI 1.14-2.85). The study also showed decrease of smokers' percentage (-5%, P=.05), increase of daily vegetables consumption frequency (+0.3/day, P=.01), and community health care center visit frequency (+3 in 3 months, P=.04). The following site-specific differences were noted: medication adherence appeared to increase in Hainan (OR 14.68, 95% CI 5.20-41.45) but not in Shanghai (OR 0.61, 95% CI 0.33-1.12).\n\nOur study demonstrated that the intervention was feasible in both a tertiary care center and an urban community health center in China. Preliminary results from pre-post comparison suggest the possibility that provider and patient-linked mHealth interventions may improve medication adherence and lifestyle modifications among CHD patients, especially in resource-scarce settings. Randomized controlled trials are needed to verify the findings.", "PMID": "29371178"}, {"title": "Improving Refill Adherence in Medicare Patients With Tailored and Interactive Mobile Text Messaging: Pilot Study.", "abstract": "Nonadherence is a major concern in the management of chronic conditions such as hypertension, cardiovascular disease, and diabetes where patients may discontinue or interrupt their medication for a variety of reasons. Text message reminders have been used to improve adherence. However, few programs or studies have explored the benefits of text messaging with older populations and at scale. In this paper, we present a program design using tailored and interactive text messaging to improve refill rates of partially adherent or nonadherent Medicare members of a large integrated health plan.\n\nThe aim of this 3-month program was to gain an understanding of whether tailored interactive text message dialogues could be used to improve medication refills in Medicare patients with one or more chronic diseases.\n\nWe used the mPulse Mobile interactive text messaging solution with partially adherent and nonadherent Medicare patients (ie, over age 65 years or younger with disabilities) of Kaiser Permanente Southern California (KP), a large integrated health plan, and compared refill rates of the text messaging group (n=12,272) to a group of partially adherent or nonadherent Medicare patients at KP who did not receive text messages (nontext messaging group, n=76,068). Both groups were exposed to other forms of refill and adherence outreach including phone calls, secure emails, and robo-calls from December 2016 to February 2017.\n\nThe text messaging group and nontext messaging group were compared using an independent samples t test to test difference in group average of refill rates. There was a significant difference in medication refill rates between the 2 groups, with a 14.07 percentage points higher refill rate in the text messaging group (P<.001).\n\nThe results showed a strong benefit of using this text messaging solution to improve medication refill rates among Medicare patients. These findings also support using interactive text messaging as a cost-effective, convenient, and user-friendly solution for patient engagement. Program outcomes and insights can be used to enhance the design of future text-based solutions to improve health outcomes and promote adherence and long-term behavior change.", "PMID": "29382623"}, {"title": "The effects of a lifestyle-focused text-messaging intervention on adherence to dietary guideline recommendations in patients with coronary heart disease: an analysis of the TEXT ME study.", "abstract": "A healthy diet is an important component of secondary prevention of coronary heart disease (CHD). The TEXT ME study was a randomised clinical trial of people with CHD that were randomised into standard care or a text-message programme in addition to standard care. This analysis aimed to: 1) assess the effects of the intervention onadherence to the dietary guideline recommendations; 2) assess the consistency of effect across sub-groups; and 3) assess whether adherence to the dietary guideline recommendations mediated the improvements in objective clinical outcomes.\n\nDietary data were collected using a self-report questionnaire to evaluate adherence to eight dietary guideline recommendations in Australia, including consumption of vegetables, fruits, fish, type of fat used for cooking and in spreads, takeaway food, salt and standard alcohol drinks. The primary outcome of this analysis was the proportion of patients adhering to \u2265\u00a04 dietary guideline recommendations concomitantly and each recommendation was assessed individually as secondary outcomes. Data were analysed using log-binomial regression for categorical variables and analysis of covariance for continuous variables.\n\nAmong 710 patients, 54% were adhering to \u2265\u00a04 dietary guideline recommendations (intervention 53% vs control 56%, p\u2009=\u20090.376) at baseline. At six months, the intervention group had a significantly higher proportion of patients adhering to \u2265\u00a04 recommendations (314, 93%) compared to the control group (264, 75%, RR 1.23, 95% CI 1.15-1.31, p\u2009<\u20090.001). In addition, the intervention patients reported consuming higher amounts of vegetables, fruits, and fish per week; less takeaway foods per week; and greater salt intake control. The intervention had a similar effect in all sub-groups tested. There were significant mediational effects of the increase in adherence to the recommendations for the association between the intervention and LDL-cholesterol (p\u2009<\u20090.001) and body mass index (BMI) at six months follow-up (p\u2009=\u20090.005).\n\nA lifestyle-focused text-message programme improved adherence to the dietary guideline recommendations, and specifically improved self-reported consumption of vegetables, fruits, fish, takeaway foods and salt intake. Importantly, these improvements partially mediated improvements in LDL-cholesterol and BMI. This simple and scalable text-messaging intervention could be used as a strategy to improve diet in people with CHD.\n\nAustralia and New Zealand Clinical Trials Registry ACTRN12611000161921 . Registered on 10 February 2011.", "PMID": "29792202"}, {"title": "Medication reminder applications to improve adherence in coronary heart disease: a randomised clinical trial.", "abstract": "The aim of the MEDication reminder APPs to improve medication adherence in Coronary Heart Disease Study was to evaluate the effectiveness and feasibility of using publicly available high-quality medication reminder applications (apps) to improve medication adherence compared with usual care in patients with coronary heart disease (CHD). An additional aim was to examine whether an app with additional features improved adherence further.\n\nPatients with CHD (n=163) were randomised to one of three groups: (1) usual care, (2) a basic app or (3) an advanced app with interactive/customisable features. The primary analysis compared usual care versus app use on the primary outcome of the 8-item Morisky Medication Adherence Scale (MMAS-8) at 3\u2009months. Secondary outcomes included blood pressure and cholesterol levels.\n\nThe mean age was 57.9 years and 87.7% were male. At 3\u2009months, patients using an app had higher adherence (mean MMAS-8 score 7.11) compared with the usual care group (mean MMAS-8 score 6.63) with a mean difference between groups of 0.47 (95% CI 0.12 to 0.82, p=0.008). There was no significant difference in patients using the basic app versus the advanced app (mean difference -0.16, 95%\u2009CI -0.56 to 0.24, p=0.428). There were no significant differences in secondary clinical outcome measures.\n\nPatients with CHD who used medication reminder apps had better medication adherence compared with usual care, and using apps with additional features did not improve this outcome further. These data suggest medication apps are likely to help patients with chronic health conditions adhere to medicines, but further examination of whether such benefits are sustained is warranted.\n\nACTRN12616000661471; Results.", "PMID": "30150326"}, {"title": "Text messaging support for patients with diabetes or coronary artery disease (SupportMe): protocol for a pragmatic randomised controlled trial.", "abstract": "Low-cost interventions providing self-management support are needed for people with coronary artery disease (CAD) and diabetes. Mobile phone text messaging provides a potential vehicle for this. The SupportMe Trial aims to assess the feasibility of embedding a text messaging programme into routine clinical practice and will determine if this improves cardiovascular risk factor and diabetes control among patients with CAD or type 2 diabetes.\n\nSupportMe is a randomised controlled trial to be conducted within the framework of a health district-wide integrated care programme for people with CAD or type 2 diabetes mellitus. One thousand subjects will be recruited, with at least 500 in each group. Intervention subjects will receive four text messages a week for 6 months, which provide advice, motivation, information and support for disease management and healthy behaviour. The primary outcome is systolic blood pressure at 6 months. Secondary outcomes include body mass index, waist circumference, low-density lipoprotein cholesterol, physical activity levels, dietary intake, quality of life, mood and smoking cessation, and for subjects with diabetes, glycosylated haemoglobin and fasting serum glucose. A process and economic evaluation will also be conducted.\n\nThe study has been approved by the Western Sydney Local Health District Human Research Ethics Committee (AU RED HREC/16/WMEAD/331). Results will be disseminated via the scientific forums including peer-reviewed publications and presentations at national and international conferences.\n\nACTRN12616001689460.", "PMID": "31221870"}, {"title": "The effect of text message reminders on medication adherence among patients with coronary heart disease: A systematic review and meta-analysis.", "abstract": "To determine the effectiveness of text message reminders (TMR) on medication adherence (MA) and to investigate the effects of TMR on clinical outcomes.\n\nThe PubMed, Cochrane library, EMbase, and China Biology Medicine databases were searched for randomized-controlled trials with TMR as the intervention for patients with coronary heart disease. Two reviewers independently extracted data and assessed the risk of bias. Meta-analysis was conducted using Stata 15.0 software.\n\nIn total, 1678 patients in 6 trials were included. Compared with the control group, the MA was 2.85 times greater among the intervention group (RR [relative risk] 2.85; 95% confidence interval [CI] 1.07-7.58). TMR reduced systolic blood pressure (BP) (weighted mean difference) = -6.51; 95% CI -9.79 to -3.23), cholesterol (standard mean difference = -0.26; 95% CI -0.4 to -0.12) and increased the number of patients with BP <140/90 mm Hg (RR 1.39; 95% CI 1.26-1.54).\n\nTMR significantly promoted MA and reduced systolic BP, cholesterol level, and body mass index, but had no effect on mortality, diastolic BP, or lipoproteins. However, substantial heterogeneity existed in our analyses.", "PMID": "31876709"}], "labels": [{"PMID": "28034414", "label": "excluded"}, {"PMID": "28720121", "label": "excluded"}, {"PMID": "28904541", "label": "excluded"}, {"PMID": "28993388", "label": "excluded"}, {"PMID": "29371178", "label": "excluded"}, {"PMID": "29382623", "label": "excluded"}, {"PMID": "29792202", "label": "excluded"}, {"PMID": "30150326", "label": "excluded"}, {"PMID": "31221870", "label": "excluded"}, {"PMID": "31876709", "label": "excluded"}]}
{"metadata": {"review_pmid": "38511668"}, "inputs": {"background": "Active case finding (ACF) refers to the systematic identification of people with tuberculosis in communities and amongst populations who do not present to health facilities, through approaches such as door-to-door screening or contact tracing. ACF may improve access to tuberculosis diagnosis and treatment for the poor and for people remote from diagnostic and treatment facilities. As a result, ACF may also reduce onward transmission. However, there is a need to understand how these programmes are experienced by communities in order to design appropriate services.", "objectives": "To synthesize community views on tuberculosis active case finding (ACF) programmes in low- and middle-income countries.", "selection criteria": "This review synthesized qualitative research and mixed-methods studies with separate qualitative data. Eligible studies explored community experiences, perceptions, or attitudes towards ACF programmes for tuberculosis in any endemic low- or middle-income country, with no time restrictions."}, "context": [{"title": "Knowledge, attitudes and practice concerning tuberculosis in a growing industrialised area in Myanmar.", "abstract": "Factories in industrial zones in Yangon, Myanmar, one of the 22 high tuberculosis (TB) burden countries.\n\nTo assess workers' knowledge about TB, their health-seeking behaviour, acceptability of TB screening and predictors for approval of the dismissal of TB patients.\n\nIn a cross-sectional survey, structured interviews with 349 factory workers were followed by 27 in-depth interviews and two focus group discussions with employers.\n\nAmong 349 workers, 95% perceived TB as being curable, 50% correctly reported air as the main mode of transmission  and 68% were aware of free treatment. Although 88% perceived screening before employment as necessary, only 14% underwent screening; 96% were willing to undergo contact screening for TB, but only 55% could afford it; 33% agreed with the dismissal of workers with TB, which was associated with  lower education, shorter time in employment, not having a history of TB contact and unwillingness to work with an index TB case due to fear and lack of knowledge.\n\nMore effective communication strategies towards factory workers are needed to increase workers' knowledge about  transmission and reduce stigma. Employers should be sensitised to protect employees with TB and invest in preventive activities.", "PMID": "22640446"}, {"title": "Tuberculosis case finding: evaluation of a paper slip method to trace contacts.", "abstract": "South Africa has the third highest tuberculosis (TB) burden in the world. Intensified case finding, recommended by WHO, is one way to control TB.\n\nTo evaluate the effectiveness and acceptability of a paper slip method for TB contact tracing.\n\nTB patients were offered paper slips to give to their contacts, inviting them for TB screening. The number of contacts screened and the proportion diagnosed with TB was calculated. Contacts that returned to the clinic after receiving the slips were interviewed. A focus group discussion (FGD) with TB patients was held to determine their acceptability.\n\nFrom 718 paper slips issued, a 26% TB contact tracing rate was found, with a 12% case detection rate. The majority (68%) of contacts were screened within 2 weeks of receiving the slip. Age and gender were not significantly associated with time to screening. 16% of the contacts screened did not reside with the TB patients. 98% of the contacts said the method was acceptable. FGD findings show that this method is acceptable and may prevent stigma associated with TB/HIV.\n\nThis simple, inexpensive method yields high contact tracing and case detection rates and potentially would yield additional benefits outside households.", "PMID": "24073277"}, {"title": "Patient and community experiences of tuberculosis diagnosis and care within a community-based intervention in Ethiopia: a qualitative study.", "abstract": "The Ethiopian TB control programme relies on passive case finding of TB cases. The predominantly rural-based population in Ethiopia has limited access to health facilities creating barriers to TB services. An intervention package aimed to bring TB diagnosis and treatment services closer to communities has been implemented through partnership with health extension workers (HEWs). They undertook advocacy, communication and social mobilization (ACSM) activities, identified symptomatic individuals, collected sputum, prepared smears and fixed slides at community level. Field supervisors supported HEWs by delivering smeared slides to the laboratory, feeding back results to the HEWs and following up smear-negative cases. Patients diagnosed with TB initiated treatment in the community, they were supported by supervisors and HEWs through the local health post. Case notification increased from 64 to 127/100,000 population/year.\n\nThis qualitative study assessed community members' treatment seeking behaviour and their perceptions of the intervention. In-depth interviews (n=36) were undertaken with participants in six districts. Participants were clients of the community-based intervention, currently on TB treatment or those screened negative for TB. Transcripts were translated to English and a thematic analytical framework was developed guided by the different steps symptomatic individuals take within the intervention package. Coding was done and queries run using NVivo software.\n\nPrior to the intervention many patients with chronic cough did not access TB services. Participants described difficulties they faced in accessing district level health facilities that required travel outside their communities. Giving sputum samples and receiving results from within their home communities was appreciated by all participants. The intervention had a high level of acceptability; particularly clear benefits emerged for poor women and men and those too weak to travel. Some participants appeared to prefer a diagnosis of TB, this is likely because receiving a negative smear microscopy result brought further uncertainty and necessitated seeking further investigation.\n\nThere is evidence rural populations with high levels of poverty, and in particular women, are at high risk of unmet health needs and undiagnosed TB. Embedding TB services within communities was an acceptable approach for vulnerable groups experiencing poor access to health facilities. In the Ethiopian context this approach can facilitate early diagnosis and improve treatment outcomes.", "PMID": "25885789"}, {"title": "Challenges from Tuberculosis Diagnosis to Care in Community-Based Active Case Finding among the Urban Poor in Cambodia: A Mixed-Methods Study.", "abstract": "While community-based active case finding (ACF) for tuberculosis (TB) holds promise for increasing early case detection among hard-to-reach populations, limited data exist on the acceptability of active screening. We aimed to identify barriers and explore facilitators on the pathway from diagnosis to care among TB patients and health providers.\n\nMixed-methods study. We administered a survey questionnaire to, and performed in-depth interviews with, TB patients identified through ACF from poor urban settlements in Phnom Penh, Cambodia. Additionally, we conducted focus group discussions and in-depth interviews with community and public health providers involved in ACF, respectively.\n\nAcceptance of home TB screening was strong among key stakeholders due to perceived reductions in access barriers and in direct and indirect patient costs. Privacy and stigma were not an issue. To build trust and facilitate communication, the participation of community representatives alongside health workers was preferred. Most health providers saw ACF as complementary to existing TB services; however, additional workload as a result of ACF was perceived as straining operating capacity at public sector sites. Proximity to a health facility and disease severity were the strongest determinants of prompt care-seeking. The main reasons reported for delays in treatment-seeking were non-acceptance of diagnosis, high indirect costs related to lost income/productivity and transportation expenses, and anticipated side-effects from TB drugs.\n\nTB patients and health providers considered home-based ACF complementary to facility-based TB screening. Strong engagement with community representatives was believed critical in gaining access to high risk communities. The main barriers to prompt treatment uptake in ACF were refusal of diagnosis, high indirect costs, and anticipated treatment side-effects. A patient-centred approach and community involvement were essential in mitigating barriers to care in marginalised communities.", "PMID": "26222545"}, {"title": "Barriers to the diagnosis of childhood tuberculosis: a qualitative study.", "abstract": "In 2012, Peru's National Tuberculosis Program (NTP) reported that children aged 0-14 years accounted for 7.9% of the country's tuberculosis (TB) incidence. This figure is likely an underestimate due to suboptimal diagnosis of childhood TB.\n\nTo identify barriers to childhood TB diagnosis in Lima, Peru.\n\nUsing semi-structured guides, moderators conducted in-depth interviews with four NTP administrators and five pulmonologists specializing in TB and 10 focus groups with 53 primary care providers, community health workers (CHWs), and parents and/or guardians of pediatric TB patients. Two authors independently performed inductive thematic analysis and identified emerging themes.\n\nParticipants identified five barriers to childhood TB diagnosis: ignorance and stigma among the community, insufficient contact investigation, limited access to diagnostic tests, inadequately trained health center staff, and provider shortages.\n\nRecent efforts to increase childhood TB detection have centered on the development of new technologies. However, our findings demonstrate that many diagnostic barriers are rooted in socio-economic and health system problems. Potential solutions include implementing multimedia campaigns and community education to reduce ignorance and stigma, prioritizing contact investigation for high-risk households, and training primary care providers and CHWs to recognize and evaluate childhood TB.", "PMID": "26459524"}, {"title": "Barriers to tuberculosis care: a qualitative study among Somali pastoralists in Ethiopia.", "abstract": "At the dawn of the third millennium, while the control of the second biggest infectious killer in the world (tuberculosis [TB]) is an international priority, millions of pastoralist communities in the Horn of Africa are struggling to access TB care. Prompt diagnosis and treatment of pastoralist TB patients remain to be a challenge in TB control programs in many countries in this region, where pastoralism is a common means of livelihood. Better understanding of community perceptions of TB and its management could help identify reasons for the delay in diagnosis of TB among pastoral communities. The aim of this study is to explore barriers delaying diagnosis among pastoralist TB patients in the Somali Regional State (SRS) of Ethiopia.\n\nA qualitative study, including 19 respondents was conducted in the SRS of Ethiopia. Participatory Rural Appraisal (PRA) and informal interview techniques were employed to explore pastoralists' migration patterns, their perceptions of TB and their access to TB services. The influence of these factors on the delay of TB patients in receiving biomedical diagnosis was then assessed.\n\nWe found that lack of access to formal health services as well as traditional beliefs leading to self treatment were barriers to prompt bio-medical diagnosis of TB among pastoralist TB patients in the SRS of Ethiopia. This study highlights that limited access to TB control programs is the most important barrier in early seeking of biomedical diagnosis of TB among pastoral communities with nomadic pastoralist being the most affected.\n\nDiagnostic and treatment facilities should be established in strategic villages that pastoralist can reach in both dry and wet seasons. Such facilities may alleviate the observed long distance to health facilities and thus long delay in diagnosis of TB. This strategy should be compounded with a community based TB control approach, whereby basic medical training on TB management such as provision of health education, drug distribution and observations is provided to local traditional healers and religious leaders. This approach may improve pastoralists' perceptions of TB, hence eliminating the observed traditional believes associated with TB in pastoralists' context of the SRS.", "PMID": "20353599"}, {"title": "Comparison of two active case-finding strategies for community-based diagnosis of symptomatic smear-positive tuberculosis and control of infectious tuberculosis in Harare, Zimbabwe (DETECTB): a cluster-randomised trial.", "abstract": "Control of tuberculosis in settings with high HIV prevalence is a pressing public health priority. We tested two active case-finding strategies to target long periods of infectiousness before diagnosis, which is typical of HIV-negative tuberculosis and is a key driver of transmission.\n\nClusters of neighbourhoods in the high-density residential suburbs of Harare, Zimbabwe, were randomised to receive six rounds of active case finding at 6-monthly intervals by either mobile van or door-to-door visits. Randomisation was done by selection of discs of two colours from an opaque bag, with one disc to represent every cluster, and one colour allocated to each intervention group before selection began. In both groups, adult (\u226516 years) residents volunteering chronic cough (\u22652 weeks) had two sputum specimens collected for fluorescence microscopy. Community health workers and cluster residents were not masked to intervention allocation, but investigators and laboratory staff were masked to allocation until final analysis. The primary outcome was the cumulative yield of smear-positive tuberculosis per 1000 adult residents, compared between intervention groups; analysis was by intention to treat. The secondary outcome was change in prevalence of culture-positive tuberculosis from before intervention to before round six of intervention in 12% of randomly selected households from the two intervention groups combined; analysis was based on participants who provided sputum in the two prevalence surveys. This trial is registered, number ISRCTN84352452.\n\n46 study clusters were identified and randomly allocated equally between intervention groups, with 55\u2008741 adults in the mobile van group and 54,691 in the door-to-door group at baseline. HIV prevalence was 21% (1916/9060) and in the 6 months before intervention the smear-positive case notification rate was 2\u00b78 per 1000 adults per year. The trial was completed as planned with no adverse events. The mobile van detected 255 smear-positive patients from 5466 participants submitting sputum compared with 137 of 4711 participants identified through door-to-door visits (adjusted risk ratio 1\u00b748, 95% CI 1\u00b711-1\u00b796, p=0\u00b70087). The overall prevalence of culture-positive tuberculosis declined from 6\u00b75 per 1000 adults (95% CI 5\u00b71-8\u00b73) to 3\u00b77 per 1000 adults (2\u00b76-5\u00b70; adjusted risk ratio 0\u00b759, 95% CI 0\u00b740-0\u00b789, p=0\u00b70112).\n\nWide implementation of active case finding, particularly with a mobile van approach, could have rapid effects on tuberculosis transmission and disease.\n\nWellcome Trust.", "PMID": "20923715"}, {"title": "Evaluation of active tuberculosis case finding through symptom screening and sputum microscopy of close contacts in Shandong, China.", "abstract": "To evaluate the effect of active case finding through symptom screening and sputum microscopy of close contacts in a Fidelis (Fund for Innovative DOTS Expansion through Local Initiatives to Stop TB) project.\n\nSecondary data from all 35 counties were collected during implementation and used. They comprised new cases identified, number of close contacts screened and their relationships. Fifty-four in-depth interviews were conducted with staff from key stakeholders.\n\nA total of 13 310 symptomatic contacts of 5255 index cases were screened, and 90 new smear-positive cases were detected with a yield rate of 0.7%. The yield rate of close contacts was positively associated with smear grades of the index cases (P<0.01). Close contacts of cases, such as classmates and workmates, who lived in a closed contained setting, had a higher yield rate than family members (P<0.001). Gaps in project implementation such as training, incentives and sputum collection were identified through in-depth interviews.\n\nThe yield rate of close-contact screening of 0.7% was similar to other findings in China. There was a higher yield from screening of close contacts in congregated settings like schools and workshops. Future active case finding projects should provide clear operational guidelines and adequate training.", "PMID": "21848577"}, {"title": "Model alternative strategies for tuberculosis and Human immune deficiency virus case-finding in hard-to-reach populations in rural Eastern Nigeria.", "abstract": "Since roughly half of all cases of active tuberculosis (TB) and Human immune deficiency virus (HIV) infection currently go undetected, there is a compelling need to pursue research aimed at improving case-finding, particularly among hard-to-reach populations.\n\nTo identify and simplify TB/HIV case finding in Eastern Nigeria.\n\nThis study involved an extensive pre-intervention Knowledge, Aptitude, Behavioural, Practice (KABP) Survey which revealed the specific limitations to TB/HIV case-finding using semi-structured questionnaires, key informant interviews and focus group discussions. The second component investigated the role of existing strategies and resources in the study area, and identified ways of optimizing these strategies and also provided alternative strategies. The third phase evaluated the performance of the different strategies and the most effective methods of optimizing their use.\n\nThe pre- intervention KABP Survey showed that the majority of the population could ill afford the costs imposed by delays in TB/HIV diagnosis and treatment. Most of the patients dropped out completely at any stage on the path to successful treatment due to several reasons. Working at motor parks, accepted stop points and several other ways were found as effective methods of reaching the hard-to-reach population.\n\nFindings from this study can be used for designing appropriate TB/HIV management and case- finding training materials for the training and use of TB/HIV health workers as well as providing information on TB/HIV case finding for National policy. Thorough consideration of the findings and subsequent implementation of them are highly recommended.", "PMID": "22786857"}, {"title": "High levels of vulnerability and anticipated stigma reduce the impetus for tuberculosis diagnosis in Cape Town, South Africa.", "abstract": "Prolonged diagnostic and treatment delays, particularly in settings experiencing concomitant human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics, undermine global TB control efforts. Current TB control policy in South Africa, as organized through the National TB Control Programme (NTP), relies on the voluntary presentation of TB suspects to local clinics for diagnosis, i.e. passive case finding (PCF). In 2005 a participatory study suggested that popular interpretation and perception of TB within eight South African township sites in and around Cape Town, all carrying a high burden of HIV and undiagnosed TB, undermine PCF. Both people's association of TB with dirt and squalor, and the anticipation of HIV-related stigma, combine to impede TB diagnosis. Respondents conveyed TB as unavoidable; this perception is expressed in the context of vulnerability where so much-including dirt-is largely beyond the control of local residents. The lack of control has a disempowering effect, reducing the drive for seeking treatment. In addition, low confidence in patient confidentiality and anticipated HIV-related stigma act as direct deterrents to TB diagnosis and treatment. In conclusion, we wish to draw attention to high levels of disease stigma and vulnerability, and how these undermine PCF. Public health interventions that wish to improve case detection should aim to: (1) emphasize how early treatment improves outcome and can curb ongoing transmission; (2) combat a sense of communal vulnerability to TB; (3) address anticipated HIV-TB stigma; and (4) improve the quality of care provided at local diagnostic services, addressing low levels of patient confidentiality. ", "PMID": "22945548"}], "labels": [{"PMID": "22640446", "label": "included"}, {"PMID": "24073277", "label": "included"}, {"PMID": "25885789", "label": "included"}, {"PMID": "26222545", "label": "included"}, {"PMID": "26459524", "label": "included"}, {"PMID": "20353599", "label": "excluded"}, {"PMID": "20923715", "label": "excluded"}, {"PMID": "21848577", "label": "excluded"}, {"PMID": "22786857", "label": "excluded"}, {"PMID": "22945548", "label": "excluded"}]}
{"metadata": {"review_pmid": "38441440"}, "inputs": {"background": "People with cancer are 1.4 times more likely to be unemployed than people without a cancer diagnosis. Therefore, it is important to investigate whether programmes to enhance the return-to-work (RTW) process for people who have been diagnosed with cancer are effective. This is an update of a Cochrane review first published in 2011 and updated in 2015.", "objectives": "To evaluate the effectiveness of non-medical interventions aimed at enhancing return to work (RTW) in people with cancer compared to alternative programmes including usual care or no intervention.", "selection criteria": "We included randomised controlled trials (RCTs) and cluster-RCTs on the effectiveness of psycho-educational, vocational, physical or multidisciplinary interventions enhancing RTW in people with cancer. The primary outcome was RTW measured as either RTW rate or sick leave duration measured at 12 months' follow-up. The secondary outcome was quality of life (QoL)."}, "context": [{"title": "Improving quality of life in men with prostate cancer: a randomized controlled trial of group education interventions.", "abstract": "Men who were recently treated for prostate cancer (N=250) were randomly assigned to a control group, a group education intervention (GE), or a group education-plus-discussion intervention (GED). Both GE and GED increased prostate cancer knowledge. In the year postintervention, men in the GED condition were less bothered by sexual problems than men in the control condition, and they were more likely to remain steadily employed (93.0%) than men in the GE (75.6%) or control (72.5%) conditions. Among noncollege graduates, GED and GE resulted in better physical functioning than the control condition, and GED resulted in more positive health behaviors than the control or GE condition. Among college graduates, controls were comparable with the GE and GED groups in physical functioning and positive health behaviors.", "PMID": "14570527"}, {"title": "Preoperative biofeedback assisted behavioral training to decrease post-prostatectomy incontinence: a randomized, controlled trial.", "abstract": "We tested the effectiveness of preoperative biofeedback assisted behavioral training for decreasing the duration and severity of incontinence, and improving quality of life in the 6 months following radical prostatectomy.\n\nWe performed a prospective, randomized, controlled trial comparing preoperative behavioral training to usual care. The volunteer sample included 125 men 53 to 68 years old who elected radical prostatectomy for prostate cancer. Patients were stratified according to age and tumor differentiation, and randomized to 1 preoperative session of biofeedback assisted behavioral training plus daily home exercise or a usual care control condition, consisting of simple postoperative instructions to interrupt the urinary stream. The main outcome measurements were duration of incontinence (time to continence), as derived from bladder diaries, incontinence severity (the proportion with severe/continual leakage), pad use, Incontinence Impact Questionnaire, psychological distress (Hopkins Symptom Checklist) and health related quality of life (Medical Outcomes Study Short Form Health Survey).\n\nPreoperative behavioral training significantly decreased time to continence (p = 0.03) and the proportion of patients with severe/continual leakage at the 6-month end point (5.9% vs 19.6%, p = 0.04). There were also significant differences between the groups for self-reported urine loss with coughing (22.0% vs 51.1%, p = 0.003), sneezing (26.0% vs 48.9%, p = 0.02) and getting up from lying down (14.0% vs 31.9%, p = 0.04). No differences were found on return to work and usual activities or quality of life measures.\n\nPreoperative behavioral training can hasten the recovery of urine control and decrease the severity of incontinence following radical prostatectomy.", "PMID": "16406909"}, {"title": "Is education an effective management strategy for reducing cancer-related fatigue?", "abstract": "The use of education is recommended to teach patients self-care behaviours to reduce cancer-related fatigue, however, there is little evidence of its effectiveness or optimal timing. This educationally based cancer-related fatigue intervention trial, CAN-FIT, aimed to reduced severity of fatigue in radiotherapy patients.\n\nOne hundred and ten participants aged\u226518 years undergoing curative radiotherapy were randomly assigned to receive (1) pre- and post-radiotherapy fatigue education and support (RFES); (2) pre-RFES only; (3) post-RFES only; or (4) no RFES (standard care). Data collection occurred at pre- and post- radiotherapy and at 6-weeks follow-up.\n\nThe intervention was not associated with reduction in fatigue levels at any assessment point. Significant changes were seen with secondary activity-based outcomes: Physical activity participation: Pre-RFES was associated with significantly greater increase in vigorous [Assessment (Ax)1-Ax2: 1.05 (0.24, 1.86) p<0.01: Ax2-Ax3: 1.24, (0.44, 2.03) p<0.01] and moderate physical activity participation [Ax1-Ax2: 1.4 (0.53, 2.26) p<0.01]. Post-RFES was associated with significant improvements in walking levels [Ax1-Ax3: 5.82 (0.07, 11.56) p<0.05] compared with no pre-RFES. Paid and unpaid employment: Pre-RFES was associated with slower return to pre-treatment levels of paid work [Ax2-Ax3: -0.72 (-1.41, -0.04) p<0.05] than no pre-RFES. Post-RFES was associated with decreased levels of unpaid work [Ax1-Ax3: 561.79 (51.21, 1,072.37) p<0.05] compared with no post-RFES.\n\nThe CAN-FIT programme did not significantly improve the primary outcome, level of fatigue, regardless of when it was delivered, however, significant changes were observed in activity-based outcomes. Further investigations into educationally based programmes should target activity participation rather than changes in underlying fatigue to improve overall patient health.", "PMID": "20694822"}, {"title": "Effectiveness of a hospital-based work support intervention for female cancer patients - a multi-centre randomised controlled trial.", "abstract": "One key aspect of cancer survivorship is return-to-work. Unfortunately, many cancer survivors face problems upon their return-to-work. For that reason, we developed a hospital-based work support intervention aimed at enhancing return-to-work. We studied effectiveness of the intervention compared to usual care for female cancer patients in a multi-centre randomised controlled trial.\n\nBreast and gynaecological cancer patients who were treated with curative intent and had paid work were randomised to the intervention group (n\u200a=\u200a65) or control group (n\u200a=\u200a68). The intervention involved patient education and support at the hospital and improvement of communication between treating and occupational physicians. In addition, we asked patient's occupational physician to organise a meeting with the patient and the supervisor to make a concrete gradual return-to-work plan. Outcomes at 12 months of follow-up included rate and time until return-to-work (full or partial), quality of life, work ability, work functioning, and lost productivity costs. Time until return-to-work was analyzed with Kaplan-Meier survival analysis.\n\nReturn-to-work rates were 86% and 83% (p\u200a=\u200a0.6) for the intervention group and control group when excluding 8 patients who died or with a life expectancy of months at follow-up. Median time from initial sick leave to partial return-to-work was 194 days (range 14-435) versus 192 days (range 82-465) (p\u200a=\u200a0.90) with a hazard ratio of 1.03 (95% CI 0.64-1.6). Quality of life and work ability improved statistically over time but did not differ statistically between groups. Work functioning and costs did not differ statistically between groups.\n\nThe intervention was easily implemented into usual psycho-oncological care and showed high return-to-work rates. We failed to show any differences between groups on return-to-work outcomes and quality of life scores. Further research is needed to study which aspects of the intervention are useful and which elements need improvement.\n\nNederlands Trial Register (NTR) 1658.", "PMID": "23717406"}, {"title": "Case management vocational rehabilitation for women with breast cancer after surgery: a feasibility study incorporating a pilot randomised controlled trial.", "abstract": "There is a paucity of methodologically robust vocational rehabilitation (VR) intervention trials. This study assessed the feasibility and acceptability of a VR trial of women with breast cancer to inform the development of a larger interventional study.\n\nWomen were recruited in Scotland and randomised to either a case management VR service or to usual care. Data were collected on eligibility, recruitment and attrition rates to assess trial feasibility, and interviews conducted to determine trial acceptability. Sick leave days (primary outcome) were self-reported via postal questionnaire every 4 weeks during the first 6 months post-surgery and at 12 months. Secondary outcome measures were change in employment pattern, quality of life and fatigue.\n\nOf the 1,114 women assessed for eligibility, 163 (15%) were eligible. The main reason for ineligibility was age (>65 years, n = 637, 67%). Of those eligible, 111 (68%) received study information, of which 23 (21%) consented to participate in the study. Data for 18 (78%) women were analysed (intervention: n = 7; control: n = 11). Participants in the intervention group reported, on average, 53 fewer days of sick leave over the first 6 months post-surgery than those in the control group; however, this difference was not statistically significant (p = 0.122; 95% confidence interval -15.8, 122.0). No statistically significant differences were found for secondary outcomes. Interviews with trial participants indicated that trial procedures, including recruitment, randomisation and research instruments, were acceptable.\n\nConducting a pragmatic trial of effectiveness of a VR intervention among cancer survivors is both feasible and acceptable, but more research about the exact components of a VR intervention and choice of outcomes to measure effectiveness is required. VR to assist breast cancer patients in the return to work process is an important component of cancer survivorship plans.\n\nISRCTN29666484.", "PMID": "23768153"}, {"title": "Effect of Low-Intensity Physical Activity and Moderate- to High-Intensity Physical Exercise During Adjuvant Chemotherapy on Physical Fitness, Fatigue, and Chemotherapy Completion Rates: Results of the PACES Randomized Clinical Trial.", "abstract": "We evaluated the effectiveness of a low-intensity, home-based physical activity program (Onco-Move) and a moderate- to high-intensity, combined supervised resistance and aerobic exercise program (OnTrack) versus usual care (UC) in maintaining or enhancing physical fitness, minimizing fatigue, enhancing health-related quality of life, and optimizing chemotherapy completion rates in patients undergoing adjuvant chemotherapy for breast cancer.\n\nWe randomly assigned patients who were scheduled to undergo adjuvant chemotherapy (N = 230) to Onco-Move, OnTrack, or UC. Performance-based and self-reported outcomes were assessed before random assignment, at the end of chemotherapy, and at the 6-month follow-up. We used generalized estimating equations to compare the groups over time.\n\nOnco-Move and OnTrack resulted in less decline in cardiorespiratory fitness (P < .001), better physical functioning (P \u2264 .001), less nausea and vomiting (P = .029 and .031, respectively) and less pain (P = .003 and .011, respectively) compared with UC. OnTrack also resulted in better outcomes for muscle strength (P = .002) and physical fatigue (P < .001). At the 6-month follow-up, most outcomes returned to baseline levels for all three groups. A smaller percentage of participants in OnTrack required chemotherapy dose adjustments than those in the UC or Onco-Move groups (P = .002). Both intervention groups returned earlier (P = .012), as well as for more hours per week (P = .014), to work than the control group.\n\nA supervised, moderate- to high-intensity, combined resistance and aerobic exercise program is most effective for patients with breast cancer undergoing adjuvant chemotherapy. A home-based, low-intensity physical activity program represents a viable alternative for women who are unable or unwilling to follow the higher intensity program.", "PMID": "25918291"}, {"title": "[Effects of a Phone-Based Follow-Up Care After Inpatient Rehabilitation for Breast Cancer Patients - A Randomized Controlled Trial].", "abstract": "", "PMID": "28599338"}, {"title": "EMLA reduces acute and chronic pain after breast surgery for cancer.", "abstract": "A significant percentage of women undergoing breast surgery for cancer may develop neuropathic pain in the chest, and/or ipsilateral axilla and/or upper medial arm, with impairment in performing daily occupational activities. We designed this study to determine if the perioperative application of EMLA (eutectic mixture of local anesthetics; AstraZeneca) cream in the breast and axilla area reduces analgesic requirements, as well as the acute and chronic pain after breast surgery.\n\nForty-six female patients scheduled for breast surgery received randomly 5 g of EMLA or placebo on the sternal area 5 minutes before surgery, and 15 g on the supraclavicular area and axilla at the end of the operation. Treatment with EMLA cream (20 g) or placebo was also applied daily on the 4 days after surgery. In the postanesthesia care unit (PACU), 3, 6, 9, and 24 hours after surgery, and on the second to sixth day postoperatively, pain was assessed by visual analogue scale (VAS) at rest and after movement, and postoperative analgesic requirements were recorded. Three months later, patients were asked if they had pain in the chest wall, axilla and/or medial upper arm, decreased sensation, if they required analgesics at home, and for the intensity of pain.\n\nAcute pain at rest and with movement did not differ between the EMLA and control groups, and the analgesics consumed during the first 24 hours were the same for the EMLA and control groups. However, time to the first analgesia requirement was longer (P = .04), and codeine and paracetamol consumption during the second to fifth days was less (P = .001, and P = .004, respectively) in the EMLA versus the control group. Three months postoperatively, pain in the chest wall, axilla, and the total incidence and the intensity of chronic pain were significantly less in the EMLA versus the control group (P = .004, P = .025, P = .002 and P = .003, respectively). The use of analgesics at home and abnormal sensations did not differ between the 2 groups.\n\nThe application of EMLA to patients undergoing breast surgery for cancer reduced the postoperative analgesic requirements and the incidence and intensity of chronic pain.", "PMID": "10925929"}, {"title": "Sentinel lymph node biopsy results in less postoperative morbidity compared with axillary lymph node dissection for breast cancer.", "abstract": "This study was designed to compare the postoperative morbidity and socioeconomic impact of sentinel lymph node biopsy (SLNB) with axillary lymph node dissection (ALND) in patients with early stage breast cancer.\n\nA prospective, nonrandomized, controlled study was designed to include patients who underwent breast conservation surgery and SLNB +/- ALND. Group A consisted of patients who had a negative SLNB and did not go on to completion ALND. Group B consisted of patients who underwent a SLNB followed by a completion ALND because either (1) their sentinel node contained cancer or (2) they were within the validation phase of our institution's sentinel lymph node protocol. Patients were evaluated with a questionnaire and underwent a standardized physical examination to determine arm circumference.\n\nData were obtained from 96 patients with a mean follow-up period of 15 months (range 8 to 29). Significant differences were seen in subjective measurements of arm complaints and arm numbness (P <0.001), with fewer complaints reported in group A. The difference in mid-bicep and antecubital fossa circumferences was significant when comparing the ratio of the procedure arm with the nonprocedure arm and when subtracting the nonprocedure arm from the procedure arm (P <0.003 and P <0.016, respectively) in favor of group A. Axillary surgery was performed as an outpatient procedure in 88% of group A patients, compared with 15% in group B (P <0.001). Furthermore, 71% of group A patients returned to \"normal activity\" in less than 4 days, in comparison with 7% of group B (P <0.001).\n\nSLNB results in less postoperative morbidity in terms of subjective arm complaints and mid-arm swelling. Expeditious return to work or normal activity after SLNB has potentially significant socioeconomic consequences.", "PMID": "11869698"}, {"title": "\"Between men\": patient perceptions and priorities in a rehabilitation program for men with prostate cancer.", "abstract": "The objective of the study is to compare consumer aspects of an informative, a physical, and a combined informative and physical rehabilitation program included in the \"Between men\" project for newly diagnosed prostate cancer patients. A consecutive series of patients was randomized. Programs were especially developed for prostate cancer patients. The format was 7 weekly sessions. The results show that the perceived benefits of relaxation was greater in the combination group than in the physical training group only. In comparison with the physical group more patients in the informative groups (information and information+physical training) rated the knowledge received as very important. The majority of patients (90%) was of the opinion that the \"Between men\" programs, should be continued. Independent of the actual program given, patients opted for the combination program or information alone but not the physical training alone program.", "PMID": "12642201"}], "labels": [{"PMID": "14570527", "label": "included"}, {"PMID": "16406909", "label": "included"}, {"PMID": "20694822", "label": "included"}, {"PMID": "23717406", "label": "included"}, {"PMID": "23768153", "label": "included"}, {"PMID": "25918291", "label": "included"}, {"PMID": "28599338", "label": "included"}, {"PMID": "10925929", "label": "excluded"}, {"PMID": "11869698", "label": "excluded"}, {"PMID": "12642201", "label": "excluded"}]}
{"metadata": {"review_pmid": "38438116"}, "inputs": {"background": "Admission avoidance hospital at home provides active treatment by healthcare professionals in the patient's home for a condition that would otherwise require acute hospital inpatient care, and always for a limited time period. This is the fourth update of this review.", "objectives": "To determine the effectiveness and cost of managing patients with admission avoidance hospital at home compared with inpatient hospital care.", "selection criteria": "Randomised controlled trials recruiting participants aged 18 years and over. Studies comparing admission avoidance hospital at home with acute hospital inpatient care."}, "context": [{"title": "Hospital in the home: a randomised controlled trial.", "abstract": "To compare treatment of acute illness at home and in hospital, assessing safety, effect on geriatric complications, and patient/carer satisfaction.\n\nRandomised controlled trial.\n\nA tertiary referral hospital affiliated with the University of New South Wales.\n\n100 patients (69% older than 65 years) with a variety of acute conditions, who were assessed in the emergency department as requiring admission to hospital.\n\nPatients were allocated at random to be treated by a hospital-in-the-home (HIH) service in their usual residence or to be admitted to hospital.\n\nGeriatric complications (confusion, falls, urinary incontinence or retention, faecal incontinence or constipation, phlebitis and pressure areas), patient/carer satisfaction, adverse events, and death.\n\nThere was a lower incidence of confusion (0 v. 20.4% [95% CI, 9.1%-31.7%]; P = 0.0005), urinary complications (incontinence or retention) (2.0% [95% CI, -1.8%, 5.8%] v. 16.3% [95% CI, 6.0%, 26.6%]; P = 0.01), and bowel complications (incontinence or constipation) (0 v. 22.5% [95% CI, 10.7%, 34.1%]; P = 0.0003) among HIH-treated patients. No significant difference in number of adverse events and deaths (to 28 days after discharge) in the two groups was found (although numbers were small). Patient and carer satisfaction was significantly higher in the HIH group.\n\nHome treatment appears to provide a safe alternative to hospitalisation for selected patients, and may be preferable for some older patients. We found high levels of both patient and carer satisfaction with home treatment.", "PMID": "10078179"}, {"title": "Randomised controlled trial of effectiveness of Leicester hospital at home scheme compared with hospital care.", "abstract": "To compare effectiveness of patient care in hospital at home scheme with hospital care.\n\nPragmatic randomised controlled trial.\n\nLeicester hospital at home scheme and the city's three acute hospitals.\n\n199 consecutive patients referred to hospital at home by their general practitioner and assessed as being suitable for admission. Six of 102 patients randomised to hospital at home refused admission, as did 23 of 97 allocated to hospital.\n\nHospital at home or hospital inpatient care.\n\nMortality and change in health status (Barthel index, sickness impact profile 68, EuroQol, Philadelphia geriatric morale scale) assessed at 2 weeks and 3 months after randomisation. The main process measures were service inputs, discharge destination, readmission rates, length of initial stay, and total days of care.\n\nHospital at home group and hospital group showed no significant differences in health status (median scores on sickness impact profile 68 were 29 and 30 respectively at 2 weeks, and 24 and 26 at 3 months) or in dependency (Barthel scores 15 and 14 at 2 weeks and 16 for both groups at 3 months). At 3 months' follow up, 26 (25%) of hospital at home group had died compared with 30 (31%) of hospital group (relative risk 0. 82 (95% confidence interval 0.52 to 1.28)). Hospital at home group required fewer days of treatment than hospital group, both in terms of initial stay (median 8 days v 14.5 days, P=0.026) and total days of care at 3 months (median 9 days v 16 days, P=0.031).\n\nHospital at home scheme delivered care as effectively as hospital, with no clinically important differences in health status. Hospital at home resulted in significantly shorter lengths of stay, which did not lead to a higher rate of subsequent admission.", "PMID": "10591717"}, {"title": "Economic evaluation of hospital at home versus hospital care: cost minimisation analysis of data from randomised controlled trial.", "abstract": "To compare the costs of admission to a hospital at home scheme with those of acute hospital admission.\n\nCost minimisation analysis within a pragmatic randomised controlled trial.\n\nHospital at home scheme in Leicester and the city's three acute hospitals.\n\n199 consecutive patients assessed as being suitable for admission to hospital at home for acute care during the 18 month trial period (median age 84 years).\n\nHospital at home or hospital inpatient care.\n\nCosts to NHS, social services, patients, and families during the initial episode of treatment and the three months after admission.\n\nMean (median) costs per episode (including any transfer from hospital at home to hospital) were similar when analysed by intention to treat-hospital at home 2569 pounds sterling (1655 pounds sterling), hospital ward 2881 pounds sterling (2031 pounds sterling), bootstrap mean difference -305 (95% confidence interval -1112 to 448). When analysis was restricted to those who accepted their allocated place of care, hospital at home was significantly cheaper-hospital at home 2557 pounds sterling(1710 pounds sterling), hospital ward 3660 pounds sterling (2903 pounds sterling), bootstrap mean difference -1071 (-1843 to -246). At three months the cost differences were sustained. Costs with all cases included were hospital at home 3671 pounds sterling (2491 pounds sterling), hospital ward 3877 pounds sterling (3405 pounds sterling), bootstrap mean difference -210 (-1025 to 635). When only those accepting allocated care were included the costs were hospital at home 3698 pounds sterling (2493 pounds sterling), hospital ward 4761 pounds sterling (3940 pounds sterling), bootstrap mean difference -1063 (-2044 to -163); P=0.009. About 25% of the costs for episodes of hospital at home were incurred through transfer to hospital. Costs per day of care were higher in the hospital at home arm (mean 207 pounds sterling v 134 pounds sterling in the hospital arm, excluding refusers, P<0.001).\n\nHospital at home can deliver care at similar or lower cost than an equivalent admission to an acute hospital.", "PMID": "10591720"}, {"title": "Home or hospital? An evaluation of the costs, preferences, and outcomes of domiciliary chemotherapy.", "abstract": "This study compares the costs and outcomes of domiciliary and hospital-based chemotherapy, using a prospective randomized cross-over design. Eighty-seven eligible patients were recruited from oncology services at two metropolitan hospitals in Sydney, Australia. Forty patients completed study evaluation requirements, having two months of chemotherapy in each location (home and hospital). The domiciliary service was staffed by hospital-based oncology nurses. Marginal costs of domiciliary treatment over hospital treatment were estimated from the health service perspective. Home-based care was more expensive, largely due to extra nurse time. About half of the eligible patients (n = 87) and 73 percent of the evaluated patients (n = 40) preferred domiciliary care. Most evaluated patients and their informal carers were satisfied with the medical care provided, regardless of location. Patient needs were well met in either location, and no differences were found in quality of life. At current throughput rates, providing chemotherapy in the home was more expensive than providing it in hospital. However, if the demand for chemotherapy were to exceed ward capacity by up to 50 percent, moving chemotherapy into the home could provide a less costly strategy for the expansion of a chemotherapy service without compromising patient outcomes.", "PMID": "11109181"}, {"title": "The effectiveness of community-based rehabilitation for stroke patients who remain at home: a pilot randomized trial.", "abstract": "To assess the effectiveness of community-based rehabilitation for stroke patients who were not admitted to hospital in South London.\n\nRandomized controlled trial.\n\nPatients' homes in South London.\n\nStroke patients not admitted to hospital after a stroke.\n\nRehabilitation at home by rehabilitation team for up to three months or usual care.\n\nThe primary outcome measure was the Barthel score. Secondary measures included the Motricity Index, Rivermead ADL, Hospital Anxiety and Depression score and Nottingham Health Profile.\n\nForty-three patients who remained at home were randomized to rehabilitation team (23) or 'usual' care (20). The mean number of physiotherapy sessions was three (range 1-14) for the rehabilitation team group and two for the usual care group. Patients (with a deficit) in the rehabilitation arm of the trial were more likely to receive occupational, physical and speech therapy than those in the control arm (p = 0.03, 0.01 and 0.008, respectively). For those patients actually receiving therapy, there was no evidence that the amount received differed between the groups. However, the number of patients in each of these comparisons was very small. The outcome for patients in the rehabilitation team arm of the trial was nonsignificantly higher (0.05 < p < 0.2) than for those in the control arm for the areas of Nottingham Health Profile, anxiety, depression, caregiver strain and the proportion of patients living at home. Based on the data observed here, a trial with approximately 150 patients in each arm would be needed to have adequate power to detect a 33% difference between intervention and control groups in these outcomes.\n\nCommunity therapy support for patients not admitted to hospital is feasible but to determine whether it is cost- or clinically effective would require trials of adequate size.", "PMID": "11128729"}, {"title": "Myocardial infarction: a comparison between home and hospital care for patients.", "abstract": "To compare the results of home and hospital treatment in men aged under 70 years who had suffered acute myocardial infarction within 48 hours 1895 patients were considered for study in four centres in south-west England. Four-hundred-and-fifty patients were randomly allocated to receive care either at home by their family doctor or in hospital, initially in an intensive care unit. The randomised treatment groups were similar in age, history of cardiovascular disease, and incidence of hypotension when first examined. They were followed up for up to a year after onset. The mortality rate at 28 days was 12% for the random home group and 14% for the random hospital group; the corresponding figures at 330 days were 20% and 27%. On average, older patients and those without initial hypotension fared rather better under home care. The patients who underwent randomisation were similar to those whose place of care was not randomised, except that the non-randomised group contained a higher proportion of initially hypotensive patients, whose prognosis was poor wherever treated. These results confirm and extend our preliminary findings. Home care is a proper form of treatment for many patients with acute myocardial infarction, particularly those over 60 years and those with an uncomplicated attack seen by general practitioners.", "PMID": "1268490"}, {"title": "Initiation of home mechanical ventilation at home: a randomised controlled trial of efficacy, feasibility and costs.", "abstract": "Home mechanical ventilation (HMV) in the Netherlands is normally initiated in hospital, but this is expensive and often a burden for the patient. In this randomised controlled study we investigated whether initiation of HMV at home in patients with chronic respiratory failure is non-inferior to an in hospital based setting.\n\nSeventy-seven patients were included, of which 38 patients started HMV at home. All patients were diagnosed with chronic respiratory failure due to a neuromuscular or thoracic cage disease. Primary outcome was the arterial carbon dioxide (PaCO2) while quality of life and costs were secondary outcomes. Telemonitoring was used in the home group to provide therapeutic information, for example; transcutaneous carbon dioxide, oxygen saturation and ventilator information, to the caregivers. Follow-up was six months.\n\nPaCO2, improved by 0.72 (SE\u00a0\u00b1\u00a00.16) kPa in the hospital group and by 0.91 (\u00b10.20) in the home group, both improvements being significant and the latter clearly not inferior. There were also significant improvements in quality of life in both groups, again not being inferior with home treatment.\n\nThis study is the first to show that initiation of HMV at home in a selective group of patients with chronic respiratory failure is as effective for gas exchange and quality of life as hospital initiation. In addition we found that it is safe, technically feasible and that more than \u20ac 3000 per patient can be saved compared to our standard care.", "PMID": "25081652"}, {"title": "Effectiveness of temporary positive expiratory pressure (T-PEP) at home and at hospital in patients with severe chronic obstructive pulmonary disease.", "abstract": "Temporary positive airway pressure (T-PEP) is a tool recently introduced in the treatment of chronic obstructive pulmonary disease (COPD) or bronchiectasis. It demonstrated encouraging results also in severe COPD patients. The aim of this study is verify if adding T-PEP to best bronchodilator therapy both in clinic and home administering could reduce disease exacerbations and improve lung function in patients with severe COPD.\n\nA total of 142 patients with severe COPD (FEV1 <50%) were enrolled; 120 were randomized in three groups: a group treated with T-PEP at home, a group with T-PEP at hospital and a group with medical therapy only (control group). Number of acute exacerbations COPD (AECOPD) after 1 month and 3 months were the primary outcomes. Secondary outcomes were changes in respiratory function parameters (FVC, FEV1, TLC, RV), arterial blood gases, dyspnea and health status assessment scales (Modified Medical Research Council (MMRC), Breathlessness, Cough and Sputum scale (BCSS) and COPD Assessment Test (CAT). The time of daily use of the T-PEP was registered as well as its acceptance using a Likert scale.\n\nNinety-nine patients completed the study. Both the groups who used T-PEP showed a statistical lower number of AECOPD after 1 month and 3 months (P<0.01). Some respiratory functional parameters improved in the two groups treated with T-PEP (FVC, FEV1, RV) (P<0.02) and dyspnea and health status assessment scales (MMRC, BCSS, CAT) (P<0.04; P<0.01; P<0.009). The time of daily using was similar in the two T-PEP groups. Patients treated at home showed a greater acceptance than those treated at hospital (Likert scale 4.7 \n\nPatients treated with T-PEP showed a lower number of AECOPD. T-PEP improves functional respiratory parameters and improves dyspnea and health status assessment scales. No adherence difference in hospital and home treatment was found. Patients preferred home treatment.", "PMID": "27867566"}, {"title": "Controlled trial of a home-care service for acute stroke patients.", "abstract": "In a controlled trial of a home-care service available for the first 6 months after acute stroke, 440 patients received the new service and 417 patients were in the control group. The trial group used more hospital bed days, had a slightly higher admission rate, and did not show better emotional adjustment to stroke than the control group. There was no difference between the 2 groups in stress on relatives. Functional recovery was equal in the 2 groups. A quarter of patients managed at home in each group were severely disabled. Providing a new service does not necessarily alter clinical decisions in the short term, and care should be taken before expanding domiciliary services to reduce hospital use.", "PMID": "2857372"}, {"title": "Home initiation of chronic non-invasive ventilation in COPD patients with chronic hypercapnic respiratory failure: a randomised controlled trial.", "abstract": "Chronic non-invasive ventilation (NIV) has become evidence-based care for stable hypercapnic COPD patients. While the number of patients increases, home initiation of NIV would greatly alleviate the healthcare burden. We hypothesise that home initiation of NIV with the use of telemedicine in stable hypercapnic COPD is non-inferior to in-hospital NIV initiation.\n\nSixty-seven stable hypercapnic COPD patients were randomised to initiation of NIV in the hospital or at home using telemedicine. Primary outcome was daytime arterial carbon dioxide pressure (PaCO\n\nHome NIV initiation was non-inferior to in-hospital initiation (adjusted mean difference in PaCO\n\nThis is the first study showing that home initiation of chronic NIV in stable hypercapnic COPD patients, with the use of telemedicine, is non-inferior to in-hospital initiation, safe and reduces costs by over 50%.\n\nNCT02652559.", "PMID": "31484786"}], "labels": [{"PMID": "10078179", "label": "included"}, {"PMID": "10591717", "label": "included"}, {"PMID": "10591720", "label": "included"}, {"PMID": "11109181", "label": "excluded"}, {"PMID": "11128729", "label": "excluded"}, {"PMID": "1268490", "label": "excluded"}, {"PMID": "25081652", "label": "excluded"}, {"PMID": "27867566", "label": "excluded"}, {"PMID": "2857372", "label": "excluded"}, {"PMID": "31484786", "label": "excluded"}]}
{"metadata": {"review_pmid": "38438114"}, "inputs": {"background": "Worldwide there is an increasing demand for Hospital at Home as an alternative to hospital admission. Although there is a growing evidence base on the effectiveness and cost-effectiveness of Hospital at Home, health service managers, health professionals and policy makers require evidence on how to implement and sustain these services on a wider scale.", "objectives": "(1) To identify, appraise and synthesise qualitative research evidence on the factors that influence the implementation of Admission Avoidance Hospital at Home and Early Discharge Hospital at Home, from the perspective of multiple stakeholders, including policy makers, health service managers, health professionals, patients and patients' caregivers. (2) To explore how our synthesis findings relate to, and help to explain, the findings of the Cochrane intervention reviews of Admission Avoidance Hospital at Home and Early Discharge Hospital at Home services.", "selection criteria": "We included qualitative studies and mixed-methods studies with qualitative data collection and analysis methods examining the implementation of new or existing Hospital at Home services from the perspective of different stakeholders."}, "context": [{"title": "Rehabilitation at home after stroke: a descriptive study of an individualized intervention.", "abstract": "To describe the content of a programme involving early hospital discharge and continued rehabilitation at home after stroke.\n\nQuantitative and qualitative descriptive study of an intervention within the context of a randomized controlled trial.\n\nHuddinge University Hospital, Stockholm, Sweden.\n\nForty-one patients, moderately impaired after stroke, rehabilitated by a team of six occupational, physical, and speech and language therapists.\n\nThe average duration of the programme was 14 weeks, the mean number of home visits 12, and the median total time consumption 23 hours and 20 minutes, of which face-to-face contact with the patient constituted 54%. The rehabilitation process was pursued by the patient and the therapist in partnership. Supported by the team the therapists incorporated a wider domain of activities than usual and left a considerable amount of the training to self-directed activities. The most common foci of the visits were speech and communication, ADL activities and ambulation. When planning the intervention the therapists paid attention to discrepancies between the desires and abilities of the patient on the one hand and environmental demands on the other - discrepancies detected through observation of the patient in the home environment.\n\nThe home environment offers therapists working in a team opportunities to adopt a behaviour that enables patients with moderate neurological impairments after stroke to resume responsibility and influence over their rehabilitation process, resulting in an individualized rehabilitation programme that varies in duration, content and frequency of home visits.", "PMID": "11128731"}, {"title": "Evaluation of patients' satisfaction with hospital-at-home care.", "abstract": "On July 1, 1997, in the Canton of Vaud, Switzerland, a pilot experiment of Hospital-at-Home Care (H-Hcare) was set up for a 2-year period at four sites to measure patients' satisfaction with this type of health care. Out of 174 patients referred to the H-Hcare program for a wide range of treatments, 107 were medical patients admitted for heart failure, community acquired pneumonia, or for an infectious disease requiring i.v.-antibiotherapy; 95 of these agreed to express H-Hcare satisfaction and dissatisfactions during a semistructured interview conducted 6 weeks after admission. H-Hcare was considered a viable alternative to hospitalization when the illness is not too serious, and for patients who are still independent and need little care. When patients are more severely ill, they prefer to go to hospital to avoid overburdening their caregivers and to feel more secure.", "PMID": "11233588"}, {"title": "Patient and carer satisfaction with 'hospital at home': quantitative and qualitative results from a randomised controlled trial.", "abstract": "'Hospital At Home' schemes are set to increase in the United Kingdom (UK) in response to the NHS Plan. To date, little detailed work has been done on the acceptability of these schemes to patients and their carers.\n\nTo compare Hospital at Home patient and carer satisfaction with hospital care.\n\nPragmatic randomised controlled trial.\n\nConsecutive patients assessed as suitablefor the Leicester Hospital at Home scheme were randomised to Hospital at Home or one of three acute hospitals in the city.\n\nPatient satisfaction was assessed two weeks after randomisation, or at discharge if later using a six-item questionnaire. Patients' and carers' views of the services were assessed by semistructured interviews.\n\nOne hundred and two patients were randomised to Hospital at Home and 97 to hospital. Forty-eight (47%) patients in the Hospital at Home arm and 35 (36%) in the hospital arm completed the satisfaction questionnaire, representing 96% and 85% of those eligible, respectively. Total scores were significantly higher in the Hospital at Home (median = 15) than in the hospital group (median = 12). (P<0.001, Mann-Whitney U-test.) Responses to all six questions favoured Hospital at Home, with all but one of these differences being statistically significant. In the Hospital at Homegroup, 24 patients and 18 of their carers were interviewed; in the hospital group 18 patients and seven of their carers were interviewed. Themes emerging from these interviews were that patients appreciated the more personal care and better communication offered by Hospital at Home and placed great value on staying at home, which was seen to be therapeutic. Patients largely felt safe in Hospital at Home, although some would have felt safer in hospital. Some patients and carers felt that better medical care would have been provided in hospital. Carers felt that the workload imposed by Hospital at Home was no greater than by hospital admission and that the relief from care duties at home would be counterbalanced by the added strain of hospital visiting.\n\nPatient satisfaction was greater with Hospital at Home than with hospital. Reasons included a more personal style of care and a feeling that staying at home was therapeutic. Carers did not feel that Hospital at Home imposed an extra workload.", "PMID": "11791829"}, {"title": "Using cost-effectiveness analysis to compare Hospital at Home and in-patient interventions. Part 1.", "abstract": "An economic analysis was conducted as an integral part of a comparison of the effectiveness and suitability of Hospital at Home (HaH) and in-patient interventions. The sample comprised of 109 adult primary total joint replacement patients and 21 of their coresident informal carers. The paper is presented in two parts. Part 1 includes the background and rationale for the study and the findings from the comparison of the effectiveness of the two interventions using multiple data collection sources. Data were collected using questionnaires, audit and semi-structured interviews. Hospital at Home was found to be significantly more effective in terms of patient satisfaction and reduced joint stiffness and as least as effective as in-patient care in relation to levels of joint pain, joint disability and incidence of postoperative complications. In addition informal carers reported 107 positive comments compared with 36 negative comments related to HaH care and all except one of the 21 carers would choose HaH again in preference to in-patient care.", "PMID": "12519245"}, {"title": "Sooner and healthier: a randomised controlled trial and interview study of an early discharge rehabilitation service for older people.", "abstract": "Hospitals are under pressure from admissions of increasing numbers of older people. Older people may suffer unnecessary activity limitation after acute illnesses through lack of appropriate rehabilitation.\n\nTo evaluate an early discharge and rehabilitation service for older people.\n\nA randomised controlled trial comparing an early discharge and rehabilitation with standard hospital aftercare. Outcome measures assessed at 3 and 12 months were the Barthel Index, Nottingham Extended Activities of Daily Living and EuroQol (for patients) the General Health Questionnaire (for patients and carers). Use of services over 12 months was recorded. An interview study of patients and staff was conducted.\n\nThe early discharge and rehabilitation service offered a home-based rehabilitation and care programme for up to 4 weeks.\n\n370 hospitalised older medical and surgical patients were included in the randomised controlled trial. Twenty patients and 11 staff were interviewed.\n\nSubjects in the early discharge rehabilitation service group used fewer days in hospital at 3 months (mean difference 9, median difference 4 days, 95% CI of median difference 2-8). At 3 months the early discharge and rehabilitation service patients had better Barthel scores (mean difference 1.2, 95% CI 0.4-1.9), Nottingham Extended Activities of Daily Living kitchen scores (mean difference 1.2, 95% CI 0.2-2.3), Nottingham Extended Activities of Daily Living domestic scores (mean difference 1.1, 95% CI 0.2-2.0) and General Health Questionnaire scores (mean difference 2.4, 95% CI 0.7-4.1). Significant Nottingham Extended Activities of Daily Living domestic and General Health Questionnaire benefits remained at 12 months. The early discharge and rehabilitation service carers had better General Health Questionnaire scores at 3 months (mean difference 2.0, 95% CI 0.1-3.8). The interviews suggested that the early discharge and rehabilitation service was patient-centred, set clear goals, worked as a team, and considered physical, psychological, social and environmental issues. It was found to be highly satisfactory.\n\nSome older people can be discharged from hospital sooner, with better health outcomes using a well-staffed and organised patient-centred early discharge service providing rehabilitation.", "PMID": "15082429"}, {"title": "A mixed method study to compare use and experience of hospital care and a nurse-led acute respiratory assessment service offering home care to people with an acute exacerbation of chronic obstructive pulmonary disease.", "abstract": "Over the past 10 years hospital at home schemes for the treatment of an acute exacerbation of Chronic Obstructive Pulmonary Disease have proliferated throughout developed countries. For selected patients treatment at home is no less advantageous in terms of readmission rates and length of stay than treatment in hospital. Although care at home might seem to be a more desirable option than admission to hospital, little is known about care preferences and how people exercise service choice.\n\n1. to determine patients' recent use of and satisfaction with health care services during exacerbations of Chronic Obstructive Pulmonary Disease. 2. To determine and compare patients' and families' perceived future care preferences. 3. To complete an in-depth exploration of care experiences and preferences with a subset of respondents and their families.\n\nA mixed method design was used consisting of a postal survey and in-depth qualitative interviews with a subset of questionnaire respondents.\n\nAn outreach service provided by a large university hospital within Scotland, UK.\n\nOne hundred and four out-patients registered with the Acute Respiratory Assessment Service and who had experienced hospital inpatient care during the past year, and their families. A subset of respondents was invited to take part in qualitative interviews.\n\nThe majority of respondents indicated a preference for the home care service, and this was positively associated with high coping skills. There was a strong relationship between personal and family preferences. There was no linear relationship between a clinical measure of severity of lung disease and service use or care preferences. Results from the qualitative interviews endorsed and explained these findings.\n\nA range of factors combined to influence service use at a particular point in time, implying a need for increased self-management support from nurses and increased service provision.", "PMID": "16157339"}, {"title": "A comparison of a hospital-based and two home-based rehabilitation programmes.", "abstract": "This paper compares the service models of three different types of rehabilitation programmes provided in Victoria, Australia: One hospital-based and two types of rehabilitation in the home (RITH).\n\nNine focus group interviews were conducted with multidisciplinary staff working in rehabilitation teams in one hospital-based and eight RITH programmes. Additional data were collected for 164 clients and 75 carers from eight of these programmes at admission, discharge and three months post discharge. Interviews were conducted with 32 clients and 14 carers.\n\nThe criteria for admission and model of rehabilitation adopted in the three programmes were similar. There were differences in programme aims, characteristics of the clients admitted and the type and level of therapy clients received, both between hospital and home-based programmes and between the three programmes. In general, staff and clients saw the home as providing a relevant context that enabled individualized, goal directed therapy for medically stable rehabilitation clients. The hospital offered an opportunity to socialize with others and specialized equipment.\n\nResults of this study suggest clients and carers require a mix of hospital and home-based rehabilitation that is able to respond to their needs and preferences at each phase of the rehabilitation continuum.", "PMID": "17453984"}, {"title": "The invisible contract: shifting care from the hospital to the home.", "abstract": "The ageing population and associated burgeoning health care costs have resulted in a shift of care from institutional settings to home and community-based care. As one example, rehabilitation-in-the-home (RITH) programs are becoming increasingly prevalent. These programs either substitute or supplement in-hospital treatment by providing multidisciplinary rehabilitation and support services in the client's own home. This paper investigates the impact of RITH programs on informal carers. Semi-structured interviews carried out with caregivers and staff revealed a complex and contradictory interpretation of informal caring. Analysis of carers' interviews revealed: an assumption by themselves and others (including RITH staff) that they would provide care; the intimate, arduous and relentless work of caring; lack of consultation about discharge; lack of recognition and reimbursement; and low levels of program support for them as carers. Carers are integral to the successful rehabilitation of the client, but they occupy a marginal status within the program. An invisible contract consigns to them substantial care-work that was previously provided by the hospital. Informal carers in RITH programs can be seen as disenfranchised care contractors. This has implications for policy makers, program managers and researchers.", "PMID": "17470039"}, {"title": "Using a multi-method, user centred, prospective hazard analysis to assess care quality and patient safety in a care pathway.", "abstract": "Care pathways can be complex, often involving multiple care providers and as such are recognised as containing multiple opportunities for error. Prospective hazard analysis methods may be useful for evaluating care provided across primary and secondary care pathway boundaries. These methods take into account the views of users (staff and patients) when determining where potential hazards may lie. The aim of this study is to evaluate the feasibility of prospective hazard analysis methods when assessing quality and safety in care pathways that lie across primary and secondary care boundaries.\n\nDevelopment of a process map of the care pathway for patients entering into a Chronic Obstructive Pulmonary Disease (COPD) supported discharge programme. Triangulation of information from: care process mapping, semi-structured interviews with COPD patients, semi-structured interviews with COPD staff, two round modified Delphi study and review of prioritised quality and safety challenges by health care staff.\n\nInterview themes emerged under the headings of quality of care and patient safety. Quality and safety concerns were mostly raised in relation to communication, for example, communication with other hospital teams. The three highest ranked safety concerns from the modified Delphi review were: difficulties in accessing hospital records, information transfer to primary care and failure to communicate medication changes to primary care.\n\nThis study has demonstrated the feasibility of using mixed methods to review the quality and safety of care in a care pathway. By using multiple research methods it was possible to get a clear picture of service quality variations and also to demonstrate which points in the care pathway had real potential for patient safety incidents or system failures to occur. By using these methods to analyse one condition specific care pathway it was possible to uncover a number of hospital level problems. A number of safety challenges were systems related; these were therefore difficult to improve at care team level. Study results were used by National Health Service (NHS) stakeholders to implement solutions to problems identified in the review.", "PMID": "17577401"}, {"title": "Implementation of the concept of home hospitalisation for heart patients by means of telehomecare technology: integration of clinical tasks.", "abstract": "To explore how the implementation of the concept 'Home hospitalisation of heart patients' by means of telehomecare technology influences the integration of clinical tasks across healthcare sectors.\n\nInter-organisational theory.\n\nThe case study approach was applied. Triangulations of data collection techniques were used: documentary materials, participant observation, qualitative and focus group interviews.\n\nThe clinical decision-making and task solving became multidisciplinary and integrated with the implementation of telehomecare and, therefore, complex in terms of the prescription and adjustment of patient medicine. Workflows between healthcare professionals across sectors changed from sequential to collective client flows. Pre-existing procedures for patient care, treatment, and responsibility were challenged. In addition, the number of tasks for the district nurses increased. Integration in the clinical task-solving area increases fragmentation in the knowledge technologies in a network perspective.\n\nImplementing the concept of 'Home hospitalisation of heart patients' by means of telehomecare technology will result in a more integrated clinical task-solving process that involves healthcare professionals from various sectors. Overall, the integration of clinical tasks between hospital and district nursing will result in a direct benefit for the heart patients.", "PMID": "17627299"}], "labels": [{"PMID": "11128731", "label": "included"}, {"PMID": "11233588", "label": "included"}, {"PMID": "11791829", "label": "included"}, {"PMID": "12519245", "label": "included"}, {"PMID": "15082429", "label": "included"}, {"PMID": "16157339", "label": "included"}, {"PMID": "17453984", "label": "included"}, {"PMID": "17470039", "label": "included"}, {"PMID": "17577401", "label": "included"}, {"PMID": "17627299", "label": "included"}]}
{"metadata": {"review_pmid": "38426600"}, "inputs": {"background": "The number of older people is increasing worldwide and public expenditure on residential aged care facilities (ACFs) is expected to at least double, and possibly triple, by 2050. Co-ordinated and timely care in residential ACFs that reduces unnecessary hospital transfers may improve residents' health outcomes and increase satisfaction with care among ACF residents, their families and staff. These benefits may outweigh the resources needed to sustain the changes in care delivery and potentially lead to cost savings. Our systematic review comprehensively and systematically presents the available evidence of the effectiveness, safety and cost-effectiveness of alternative models of providing health care to ACF residents.", "objectives": "Main objective To assess the effectiveness and safety of alternative models of delivering primary or secondary health care (or both) to older adults living in ACFs. Secondary objective To assess the cost-effectiveness of the alternative models.", "selection criteria": "We included individual and cluster-randomised trials, and cost/cost-effectiveness data collected alongside eligible effectiveness studies. Eligible study participants included older people who reside in an ACF as their place of permanent abode and healthcare professionals delivering or co-ordinating the delivery of healthcare at ACFs. Eligible interventions focused on either ways of delivering primary or secondary health care (or both) or ways of co-ordinating the delivery of this care. Eligible comparators included usual care or another model of care. Primary outcomes were emergency department visits, unplanned hospital admissions and adverse effects (defined as infections, falls and pressure ulcers). Secondary outcomes included adherence to clinical guideline-recommended care, health-related quality of life of residents, mortality, resource use, access to primary or specialist healthcare services, any hospital admissions, length of hospital stay, satisfaction with the health care by residents and their families, work-related satisfaction and work-related stress of ACF staff."}, "context": [{"title": "Nursing interventions for depression in newly admitted nursing home residents.", "abstract": "", "PMID": "10362971"}, {"title": "Multifaceted shared care intervention for late life depression in residential care: randomised controlled trial.", "abstract": "To evaluate the effectiveness of a population based, multifaceted shared care intervention for late life depression in residential care.\n\nRandomised controlled trial, with control and intervention groups studied one after the other and blind follow up after 9.5 months.\n\nPopulation of residential facility in Sydney living in self care units and hostels.\n\n220 depressed residents aged >/=65 without severe cognitive impairment.\n\nThe shared care intervention included: (a) multidisciplinary consultation and collaboration, (b) training of general practitioners and carers in detection and management of depression, and (c) depression related health education and activity programmes for residents. The control group received routine care.\n\nGeriatric depression scale.\n\nIntention to treat analysis was used. There was significantly more movement to \"less depressed\" levels of depression at follow up in the intervention than control group (Mantel-Haenszel stratification test, P=0.0125). Multiple linear regression analysis found a significant intervention effect after controlling for possible confounders, with the intervention group showing an average improvement of 1.87 points on the geriatric depression scale compared with the control group (95% confidence interval 0.76 to 2.97, P=0.0011).\n\nThe outcome of depression among elderly people in residential care can be improved by multidisciplinary collaboration, by enhancing the clinical skills of general practitioners and care staff, and by providing depression related health education and activity programmes for residents.", "PMID": "10480824"}, {"title": "Two models of restorative nursing care in the nursing home: designated versus integrated restorative nursing assistants.", "abstract": "A 6-month clinical trial was conducted to evaluate two models of restorative nursing care designed to improve mobility in nursing home residents. The models were compared on number of residents enrolled, documentation of nursing assistant (NA) compliance, and nursing staff satisfaction. The designated model, which relied on one specially trained NA to perform restorative activities on the unit, resulted in higher rates of enrollment, compliance, and staff satisfaction compared with the integrated model, which relied on regular staff NAs who were trained to incorporate restorative activities into their daily routines.", "PMID": "10601898"}, {"title": "Value-added outcomes: the use of advanced practice nurses in long-term care facilities.", "abstract": "The purpose of this study was to determine the effect on clinical outcomes for newly admitted nursing home residents when advanced practice gerontological nurses (APNs) worked with staff to implement scientifically based protocols for incontinence, pressure ulcers, depression, and aggressive behavior. Use of APNs in this manner differs from the usual way APNs have been used in nursing homes, in which their primary focus has been to augment the physician's role. The APN treatment was randomly assigned to two nursing homes and usual care was assigned to a third. Trajectories from admission to 6 months revealed that residents with APN input into their care (n = 86) experienced significantly greater improvement or less decline in incontinence, pressure ulcers, and aggressive behavior, and they had higher mean composite trajectory scores compared with residents receiving usual care (n = 111). Significantly less deterioration in affect was noted in cognitively impaired residents in the treatment group. Findings suggest that APNs can be effective links between current scientific knowledge about clinical problems and nursing home staff.", "PMID": "11131082"}, {"title": "Better care in nursing homes: advanced practice nurses' strategies for improving staff use of protocols.", "abstract": "This article describes a set of strategies used by gerontologic advanced practice nurses (GAPNs) in three nursing homes to integrate the use of protocols into the daily care of residents. The protocols were developed as part of a larger study on the quality of care in nursing homes carried out by nurse researchers at the University of Minnesota and funded by the National Institute of Nursing Research (R01-NR03490). The GAPNs worked regularly with nursing home staff to incorporate aspects of protocols into daily care routines for residents with four specific problems common in elderly residents of nursing homes: pressure ulcers, incontinence, depression, and aggressive behavior. Outcomes of the larger study showed that residents with these four problems had better outcomes in the homes in which care was planned by the GAPNs using protocols that were integrated into the daily routines of staff.", "PMID": "11188464"}, {"title": "Secure Internet video conferencing for assessing acute medical problems in a nursing facility.", "abstract": "Although video-based teleconferencing is becoming more widespread in the medical profession, especially for scheduled consultations, applications for rapid assessment of acute medical problems are rare. Use of such a video system in a nursing facility may be especially beneficial, because physicians are often not immediately available to evaluate patients. We have assembled and tested a portable, wireless conferencing system to prepare for a randomized trial of the system s influence on resource utilization and satisfaction. The system includes a rolling cart with video conferencing hardware and software, a remotely controllable digital camera, light, wireless network, and battery. A semi-automated paging system informs physicians of patient s study status and indications for conferencing. Data transmission occurs wirelessly in the nursing home and then through Internet cables to the physician s home. This provides sufficient bandwidth to support quality motion images. IPsec secures communications. Despite human and technical challenges, this system is affordable and functional.", "PMID": "11825286"}, {"title": "Case management model or case manager type? That is the question.", "abstract": "Case management models have been categorized many different ways, but classification into two generic models is proposed here: an interrogative model that relies on intense oversight with expected cost reduction and a patient advocacy model that relies on a brokering arrangement for services in the best interest of the patient. A randomized trial in an elderly, functionally impaired population resulted in the implementation of a patient advocacy model and suggests that this model results in increased service use and costs, but that increased survival rates may justify the additional cost.", "PMID": "12083179"}, {"title": "The value of specialist clinical assessment of older people prior to entry to care homes.", "abstract": "to ascertain the value of employing a specialist clinician's contribution to the assessment of older people prior to care home entry.\n\nrandomised controlled trial.\n\n256 older people at risk of care home entry were randomly allocated to either a control group, who received the usual care management assessment, or to an experimental group who, in addition, received a clinical assessment by a geriatrician or old age psychiatrist. The value of the additional assessment was evaluated by an analysis of clinical recommendations, questionnaires eliciting the views of stakeholders and research interviews with older people and their carers at initial assessment and 6 months. Data on service use and costs over 6 months and on destination at 6 and 12 months were also collected.\n\nthe clinical assessment uncovered covert morbidity previously unknown to care managers particularly in respect of cognitive impairment and was adjudged acceptable to the different stakeholders involved. Those receiving the clinical assessment experienced less deterioration in their physical functioning, had less contact with nursing homes and emergency services and their carers experienced reduced levels of distress. Overall, the costs of care for those receiving the assessment were no greater with NHS costs actually lower.\n\nthe potential benefits in involving specialist clinicians in the assessment process include identifying previously undiagnosed conditions and enhancing care managers' decision making. Such an assessment could be provided at a modest marginal cost. The approach is fully compatible with proposals for the role of the community geriatrician and commensurate with current good clinical practice in old age psychiatry.", "PMID": "14695860"}, {"title": "Identifying undiagnosed dementia in residential care veterans: comparing telemedicine to in-person clinical examination.", "abstract": "Dementia is a common but frequently undiagnosed problem in aging. Barriers to early diagnosis include a lack of routine screening for dementia and a lack of access to specialty consultative services. We conducted a pilot study to see if telemedicine could provide reliable, accurate geriatric consultative services to evaluate patients for dementia who were residing at remote sites.\n\nThis was a prospective cohort study that compared the diagnostic reliability of telemedicine to an in-person examination for dementia. Eligible subjects were residents of a Washington State Veterans' Home, age 60 years or older, with no prior diagnosis of dementia. Eligible subjects were screened for dementia using the 7-Minute Screen. Veterans who screened positive and consented to participate in the study received an in-person neuropsychiatric evaluation at baseline, and then both telemedicine and in-person examinations for dementia conducted by experienced geriatric psychiatrists. The accuracy of the telemedicine diagnosis was estimated by comparing it to the diagnosis from the clinical examination. Three geriatric psychiatrists who were blinded to the results of the clinical examination conducted the telemedicine and in-person examinations. We also assessed attitudes of the subjects and geriatric psychiatrists towards the telemedicine sessions.\n\nEighteen of 85 subjects screened were 'positive' for dementia on the 7 Minute Screen. Of these, 16 consented to participate in the telemedicine study. Twelve of the 16 subjects were subsequently diagnosed with dementia by the telemedicine examination. The telemedicine diagnoses were in 100% agreement with the diagnoses from the in-person clinical examinations. Moreover, the subjects reported a high degree of satisfaction with the telemedicine experience and that they would like to have further care through telemedicine in the future. The geriatric psychiatrists reported technical difficulties with the audio-visual quality of telemedicine in the initial phases of the project that resolved as familiarity with the telemedicine equipment increased. None of these problems had an adverse impact on the diagnostic accuracy of telemedicine.\n\nWe found that telemedicine was as accurate as an in-person clinical examination in establishing the diagnosis of dementia. In addition, subjects reported a high degree of satisfaction with telemedicine and a willingness to participate in telemedicine clinical care in the future. Given the large increase in the aging population and the shortage of geriatric psychiatrists nationally, it appears that telemedicine may be a promising means to expand the availability of geriatric psychiatric consultation to remote areas.", "PMID": "14758575"}, {"title": "The assessment of a hospital-based care management model for long-term care services.", "abstract": "The purpose of this research was to assess the effectiveness of a hospital-based care management model on disabled elderly people. A before-and-after quasi- experimental design was adopted. A total of 331 disabled elderly people, residing in the Da-An District of Taipei City, participated in the study. Among them, 166 received care management, while the other 165 did not. The latter served as controls. Baseline and follow-up data collection were carried out before and after care management intervention. Logistic regression analysis was used to test the effects of care management on medical care expenditure, self-rated health, and satisfaction with long-term care arrangement. The results showed that those under care management, compared to the controls, were more likely to experience a decrease in medical care expenditure, and less likely to have a decrease in satisfaction with long-term care. The effects were statistically significant. However, there was no effect on self-rated health. The findings show that hospital-based care management is a viable option and has the potential to become an important segment in the delivery of long-term care services. More effort should be expended in its development and in the evaluation of its effectiveness.", "PMID": "15619182"}], "labels": [{"PMID": "10362971", "label": "excluded"}, {"PMID": "10480824", "label": "excluded"}, {"PMID": "10601898", "label": "excluded"}, {"PMID": "11131082", "label": "excluded"}, {"PMID": "11188464", "label": "excluded"}, {"PMID": "11825286", "label": "excluded"}, {"PMID": "12083179", "label": "excluded"}, {"PMID": "14695860", "label": "excluded"}, {"PMID": "14758575", "label": "excluded"}, {"PMID": "15619182", "label": "excluded"}]}
{"metadata": {"review_pmid": "38421211"}, "inputs": {"background": "Choosing an optimal reconstruction method is pivotal for patients with gastric cancer undergoing distal gastrectomy. The uncut Roux-en-Y reconstruction, a variant of the conventional Roux-en-Y approach (or variant of the Billroth II reconstruction), employs uncut devices to occlude the afferent loop of the jejunum. This modification is designed to mitigate postgastrectomy syndrome and enhance long-term functional outcomes. However, the comparative benefits and potential harms of this approach compared to other reconstruction techniques remain a topic of debate.", "objectives": "To assess the benefits and harms of uncut Roux-en-Y reconstruction after distal gastrectomy in patients with gastric cancer.", "selection criteria": "We included randomised controlled trials (RCTs) and quasi-RCTs comparing uncut Roux-en-Y reconstruction versus other reconstructions after distal gastrectomy for gastric cancer. The comparison groups encompassed other reconstructions such as Billroth I, Billroth II (with or without Braun anastomosis), and Roux-en-Y reconstruction."}, "context": [{"title": "Improvement of the Roux limb function using a new type of \"uncut Roux\" limb.", "abstract": "The Roux stasis syndrome is characterized by symptoms of upper gut stasis following Roux-en-Y gastrojejunostomy. The aim of this study was to compare a new type of uncut Roux-en-Y gastrojejunostomy with the conventional Roux-en-Y gastrojejunostomy after subtotal gastrectomy.\n\n51 patients (31 men and 20 women) had the conventional Roux-en-Y reconstruction and 54 patients (38 men and 16 women) had the new type of uncut Roux-en-Y reconstruction. The new type of uncut Roux-en-Y gastrojejunostomy consisted of an artificial jejunal occlusion and a short Roux limb (20 to 30 cm).\n\nThe criteria included one of the four following conditions at the time of follow-up: chronic abdominal pain, postprandial fullness, persistent nausea, and intermittent vomiting that are worsened by eating. According to the criteria, the Roux stasis syndrome occurred in 19 patients (37.3%) with conventional Roux-en-Y reconstruction, and in 10 patients (18.5%) with uncut Roux-en-Y reconstruction (P = 0.033).\n\nA new type of Roux operation is able to alleviate not only the Roux stasis syndrome but also alkaline reflux gastritis or esophagitis by preserving motility of the Roux limb and diversion of duodenal juice from the gastric remnant.", "PMID": "11036137"}, {"title": "Total Laparoscopic Uncut Roux-en-Y for Radical Distal Gastrectomy: An Interim Analysis of a Randomized, Controlled, Clinical Trial.", "abstract": "The traditional Billroth II and Roux-en-Y anastomosis after laparoscopic distal gastrectomy for gastric cancer are associated with bile reflux gastritis and roux stasis syndrome, respectively. The uncut Roux-en-Y gastrojejunostomy can decrease the incidence of these complications by blocking the entry of bile and pancreatic juice into the residual stomach and retaining the impulses originating from the duodenum. The purpose of the present study was to compare the short-term outcomes of uncut Roux-en-Y (URY) and Billroth II combined Braun (BB) anastomosis.\n\nIn this prospective, multi-center, two-arm randomized controlled trial, 124 patients with advanced distal gastric cancer were randomized into two groups: URY (n\u2009=\u200962) and BB (n\u2009=\u200962) groups.\n\nThe mean gastric juice pH was significantly lower in the URY group compared with the BB group (3.94\u2009\u00b1\u20090.71 vs. 5.83\u2009\u00b1\u20090.91, P\u2009<\u20090.0001). The bile reflux gastritis at 3\u00a0months (P\u2009<\u20090.0001) and 6\u00a0months (P\u2009=\u20090.002) was significantly more frequent in the BB group. No recanalization occurred in the URY group, and no significant difference was found between the two groups in terms of mean operative time (P\u2009=\u20090.69), mean time to perform anastomosis (P\u2009=\u20090.86), mean estimated blood loss (P\u2009=\u20090.77), mean number of harvested lymph nodes (P\u2009=\u20090.90), time to first passage of flatus or defecation (P\u2009=\u20090.87), postoperative hospital stay (P\u2009=\u20090.83), and the incidence of postoperative complications (P\u2009=\u20090.70).\n\nURY anastomosis is associated with a significantly lower incidence of bile reflux gastritis and roux stasis syndrome compared with BB anastomosis.", "PMID": "32556870"}, {"title": "Laparoscopic uncut Roux-en-Y for radical distal gastrectomy: the study protocol for a multirandomized controlled trial.", "abstract": "Gastric cancer is the third most common cause of cancer-related deaths and is the fifth highest incidence of cancer worldwide, especially in Eastern Asia, Central and Eastern Europe, and South America. Currently, surgery is the only curative treatment for gastric cancer; however, digestive tract reconstruction after distal gastrectomy for gastric cancer is controversial due to the postoperative complications such as reflux gastritis. There is an increasing trend toward laparoscopic uncut Roux-en-Y (URY) for radical gastrectomy. However, evidence on the feasibility of this procedure in patients undergoing laparoscopic radical distal gastrectomy is still absent. Thus, a prospective randomized trial is warranted. This is a prospective, multicenter, two-arm randomized controlled trial in which 210 patients will be randomly assigned to two groups: laparoscopic URY (n=105) and laparoscopic Billroth II plus Braun anastomosis (n=105). Each participant must be pathologically diagnosed with gastric cancer and undergo laparoscopic radical gastrectomy at Xijing Hospital and other four hospitals. The laparoscopic URY procedure is based on the Billroth II gastrojejunostomy plus Braun anastomosis, and then blocked the jejunum input loop at the stump-jejunal anastomosis. The patients' demographic and pathological characteristics will be recorded. The total and oral nutritional intake, general data, total serum protein, serum albumin, blood glucose, and temperature will be recorded before surgery and at the time of hospitalization. Postoperative adverse events will also be recorded, as well as at follow-up appointments at three months and six months after surgery. The rate of reflux gastritis will represent the primary endpoint, and other secondary endpoints, which are all recorded.", "PMID": "30863178"}, {"title": "Tranditional Roux-en-Y vs Uncut Roux-en-Y in Laparoscopic Distal Gastrectomy: a Randomized Controlled Study.", "abstract": "Traditional Roux-en-Y may cause Roux-en-Y stasis syndrome (RSS), and Uncut Roux-en-Y was proposed to solve this problem. However, because afferent loop recanalization may occur after surgery, its clinical application remains controversial. The purpose of this study was to compare the long-term outcomes of these two gastrointestinal reconstruction methods.\n\nA total of 108 patients who received laparoscopic-assisted distal gastrectomy (LADG) were enrolled; 57 were randomly\u00a0divided into the Uncut Roux-en-Y (URY) group, and 51 were divided into the Roux-en-Y (RY) group. Patients were followed up for 1\u00a0year to evaluate variables, including the following: (1) Assessments for RSS; (2) Preoperative and postoperative Gastrointestinal Symptom Rating Scale (GSRS) scores; (3) Postoperative gastroscopy to assess the occurrence of reflux esophagitis (Los Angeles classification), residual gastritis and bile reflux 1\u00a0year after surgery; and (4) Upper gastrointestinal radiography to evaluate whether recanalization occurred in patients in the URY group after surgery.\n\nAt 1\u00a0year after surgery, a total of 42 patients (73.7%) developed afferent loop recanalization. The incidence of RSS was not different between the two groups (OR, 1.301 [95% CI, 0.482 to 3.509]; P\u2009=\u20090.603P\u2009=\u20090.603). The GSRS score was higher in the URY group (P\u2009<\u20090.001). Postoperative gastroscopy showed that the incidence of bile reflux (P\u2009<\u20090.001) and the grade of residual gastritis (P\u2009<\u20090.001) were significantly higher in the URY group, but the grade of reflux esophagitis was not significantly different (P\u2009=\u20090.447, [95% CI, 0.437 to 0.457]P\u2009=\u20090.397).\n\nCompared with traditional Roux-en-Y anastomosis, due to the high recanalization rate, the URY group developed more severe gastrointestinal symptoms, the incidence of bile reflux and the grade of residual gastritis increased and the incidence of postoperative RSS was not reduced.", "PMID": "36917403"}, {"title": "To cut or not to cut? A prospective randomized controlled trial on short-term outcomes of the uncut Roux-en-Y reconstruction for gastric cancer.", "abstract": "Roux-en-Y (R-Y) anastomoses have been widely used in distal gastrectomy, while the incidence of Roux stasis syndrome remains common. Uncut R-Y anastomosis maintains the neuromuscular continuity, thus avoiding the ectopic pacemaker of the Roux limb and reducing the occurrence of Roux stasis. However, retrospective studies of Uncut R-Y anastomosis remain scarce and randomized controlled trials have not been reported.\n\nWe conducted a randomized controlled trial to compare the surgical safety, nutritional status, and postoperative quality of life (QOL) between uncut and classic Roux-en-Y (R-Y) reconstruction patients. Patients with Stage I gastric cancer were randomly enrolled and underwent laparoscopic distal gastrectomy followed by uncut or classic R-Y reconstruction. Body mass index and blood test were used to evaluate the nutritional status. QOL was evaluated using European Organization for Research and Treatment of Cancer QOL Questionnaire (STO22) and laboratory examinations at postoperative month (POM) 3, 6, 9, and 12. Computed tomography scanning was used to evaluate the skeletal muscle index (SMI) at POM 6 and 12. Endoscopy was performed at POM 12.\n\nOperation time, blood loss, time to recovery, complication morbidities, and overall survival were similar between the two groups. Compared with the classic R-Y group, the uncut R-Y group displayed a significantly decreased QOL at POM 9, possibly due to loop recanalization, determined to be occupied 34.2% of the uncut R-Y group. Post-exclusion of recanalization, the QOL was still higher in the classic R-Y group than in the uncut R-Y group, despite their hemoglobin and total protein levels being better than those in the classic R-Y group. Preoperative pre-albumin level and impaired fasting glycemia significantly correlated with the postoperative recanalization.\n\nWe found no significant benefit of uncut over classic R-Y reconstruction which challenges the superiority of the uncut R-Y reconstruction.\n\nClinicalTrials.gov Identifier: NCT02644148.", "PMID": "37160808"}, {"title": "Randomized controlled trial of uncut Roux-en-Y ", "abstract": "To identify which technique is better for avoiding biliary reflux and gastritis between uncut Roux-en-Y and Billroth II reconstruction.\n\nA total of 158 patients who underwent laparoscopy-assisted distal gastrectomy for gastric cancer at the First Hospital of Jilin University (Changchun, China) between February 2015 and February 2016 were randomized into two groups: uncut Roux-en-Y (group U) and Billroth II group (group B). Postoperative complications and relevant clinical data were compared between the two groups.\n\nAccording to the randomization table, each group included 79 patients. There was no significant difference in postoperative complications between groups U and B (7.6% \n\nCompared with Billroth II reconstruction, uncut Roux-en-Y reconstruction is secure and feasible, and can effectively reduce the incidence of alkaline reflux, residual gastritis, and heartburn. Despite the incidence of recanalization, uncut Roux-en-Y should be widely applied.", "PMID": "28974902"}], "labels": [{"PMID": "11036137", "label": "included"}, {"PMID": "32556870", "label": "included"}, {"PMID": "30863178", "label": "included"}, {"PMID": "36917403", "label": "included"}, {"PMID": "37160808", "label": "included"}, {"PMID": "28974902", "label": "included"}]}
{"metadata": {"review_pmid": "38415871"}, "inputs": {"background": "Adolescent idiopathic scoliosis (AIS) is a pathology that changes the three-dimensional shape of the spine and trunk. While AIS can progress during growth and cause cosmetic issues, it is usually asymptomatic. However, a final spinal curvature above the critical threshold of 30\u00b0 increases the risk of health problems and curve progression in adulthood. The use of therapeutic exercises (TEs) to reduce the progression of AIS and delay or avoid other, more invasive treatments is still controversial.", "objectives": "To evaluate the effectiveness of TE, including generic therapeutic exercises (GTE) and physiotherapeutic scoliosis-specific exercises (PSSE) in treating AIS, compared to no treatment, other non-surgical treatments, or between treatments.", "selection criteria": "Randomised controlled trials (RCTs) comparing TE with no treatment, other non-surgical treatments (braces, electrical stimulation, manual therapy), and different types of exercises. In the previous version of the review, we also included observational studies. We did not include observational studies in this update since we found sufficient RCTs to address our study aims."}, "context": [{"title": "Active self-correction and task-oriented exercises reduce spinal deformity and improve quality of life in subjects with mild adolescent idiopathic scoliosis. Results of a randomised controlled trial.", "abstract": "To evaluate the effect of a programme of active self-correction and task-oriented exercises on spinal deformities and health-related quality of life (HRQL) in patients with mild adolescent idiopathic scoliosis (AIS) (Cobb angle <25\u00b0).\n\nThis was a parallel-group, randomised, superiority-controlled study in which 110 patients were randomly assigned to a rehabilitation programme consisting of active self-correction, task-oriented spinal exercises and education (experimental group, 55 subjects) or traditional spinal exercises (control group, 55 subjects). Before treatment, at the end of treatment (analysis at skeletal maturity), and 12 months later (follow-up), all of the patients underwent radiological deformity (Cobb angle), surface deformity (angle of trunk rotation) and HRQL evaluations (SRS-22 questionnaire). A linear mixed model for repeated measures was used for each outcome measure.\n\nThere were main effects of time (p < 0.001), group (p < 0.001) and time by group interaction (p < 0.001) on radiological deformity: training in the experimental group led to a significant improvement (decrease in Cobb angle of >5\u00b0), whereas the control group remained stable. Analysis of all of the secondary outcome measures revealed significant effects of time, group and time by group interaction in favour of the experimental group.\n\nThe programme of active self-correction and task-oriented exercises was superior to traditional exercises in reducing spinal deformities and enhancing the HRQL in patients with mild AIS. The effects lasted for at least 1 year after the intervention ended.", "PMID": "24682356"}, {"title": "Effect of a preoperative protocol of aerobic physical therapy on the quality of life of patients with adolescent idiopathic scoliosis: a randomized clinical study.", "abstract": "Patients with adolescent idiopathic scoliosis (AIS) have lower potential for physical activity because of lung dysfunction and lower muscle strength, which can be reversed by the cardiorespiratory and musculoskeletal conditioning provided by standardized physical activities. We conducted a study to determine if a preoperative protocol of aerobic exercise would improve quality of life (QoL) both before and after training and if there would be any differences between patients who received the therapy and those who did not. Patients with the indication of surgical correction of AIS were randomized to receive or not receive a 4-month preoperative course of aerobic physical training. At baseline and after 4 months, they were evaluated with the Short Form-36 questionnaire (SF-36). QoL scores improved for the study group but did not change for the control group. In all QoL domains, the study group's mean score increased significantly between baseline and 4 months. We concluded that the proposed preoperative physical therapy protocol improved the QoL of patients with AIS.", "PMID": "24945482"}, {"title": "Effect of Schroth exercises on curve characteristics and clinical outcomes in adolescent idiopathic scoliosis: protocol for a multicentre randomised controlled trial.", "abstract": "The promising results of Schroth scoliosis-specific exercises for adolescent idiopathic scoliosis found in low-quality studies will be strengthened by confirmation in a randomised controlled trial.\n\n1. Are Schroth exercises combined with standard care for 6 months more effective than standard care alone in improving radiographic and clinical outcomes for adolescents with idiopathic scoliosis? 2. Will the outcomes of the control group (who will be offered Schroth therapy delayed by 6 months) improve after 6 months of Schroth therapy? 3. Are the effects maintained 6 months after discontinuing the supervised intervention?\n\nThis is an assessor-blinded and statistician-blinded randomised controlled trial with transfer of the controls to the exercise group after 6 months.\n\nTwo hundred and fifty-eight consecutive adolescents with idiopathic scoliosis, aged 10 to 16 years, treated with or without a brace, with curves between 10 and 45 deg Cobb and Risser sign \u2264 3 will be recruited from three scoliosis clinics.\n\nCombined with standard care, the Schroth group will receive five individual training sessions, followed by weekly group classes and daily home exercises for 6 months.\n\nControls will only receive standard care consisting of observation or bracing, and will be offered Schroth therapy 6 months later.\n\nCurve severity (Cobb angle) and vertebral rotation will be assessed from radiographs at baseline, 6 and 12 months. Secondary clinical outcomes (back muscle endurance, surface topography measures of posture, and self-reported perceived spinal appearance and quality of life) will be assessed at baseline, and every 3 months until 1-year follow-up.\n\nData will be analysed using intention-to-treat linear mixed models.\n\nThe results will demonstrate whether Schroth exercises combined with standard of care can improve outcomes in adolescents with idiopathic scoliosis. This study has potential to influence clinical practice worldwide, where exercises are not routinely prescribed for adolescents with idiopathic scoliosis.", "PMID": "25439713"}, {"title": "The efficacy of three-dimensional Schroth exercises in adolescent idiopathic scoliosis: a randomised controlled clinical trial.", "abstract": "To compare the efficacy of three-dimensional (3D) Schroth exercises in patients with adolescent idiopathic scoliosis.\n\nA randomised-controlled study.\n\nAn outpatient exercise-unit and in a home setting.\n\nFifty-one patients with adolescent idiopathic scoliosis.\n\nForty-five patients with adolescent idiopathic scoliosis meeting the inclusion criteria were divided into three groups. Schroth's 3D exercises were applied to the first group in the clinic and were given as a home program for the second group; the third group was the control.\n\nScoliosis angle (Cobb method), angle of rotation (scoliometer), waist asymmetry (waist - elbow distance), maximum hump height of the patients and quality of life (QoL) (SRS-23) were assessed pre-treatment and, at the 6(th), 12(th) and 24(th) weeks.\n\nThe Cobb (-2.53\u00b0; P=0.003) and rotation angles (-4.23\u00b0; P=0.000) significantly decreased, which indicated an improvement in the clinic exercise group compared to the other groups. The gibbosity (-68.66mm; P=0.000) and waist asymmetry improved only in the clinic exercise group, whereas the results of the other groups worsened. QoL did not change significantly in either group.\n\nAccording to the results of this study the Schroth exercise program applied in the clinic under physiotherapist supervision was superior to the home exercise and control groups; additionally, we observed that scoliosis progressed in the control group, which received no treatment.", "PMID": "25780260"}, {"title": "The effect of Schroth exercises added to the standard of care on the quality of life and muscle endurance in adolescents with idiopathic scoliosis-an assessor and statistician blinded randomized controlled trial: \"SOSORT 2015 Award Winner\".", "abstract": "In North America, care recommendations for adolescents with small idiopathic scoliosis (AIS) curves include observation or bracing. Schroth scoliosis-specific exercises have demonstrated promising results on various outcomes in uncontrolled studies. This randomized controlled trial (RCT) aimed to determine the effect of Schroth exercises combined with the standard of care on quality-of-life (QOL) outcomes and back muscle endurance (BME) compared to standard of care alone in patients with AIS.\n\nFifty patients with AIS, aged 10-18 years, with curves 10-45 \u00b0, recruited from a scoliosis clinic were randomized to receive standard of care or supervised Schroth exercises plus standard of care for 6 months. Schroth exercises were taught over five sessions in the first two weeks. A daily home program was adjusted during weekly supervised sessions. The assessor and the statistician were blinded. Outcomes included the Biering-Sorensen (BME) test, Scoliosis Research Society (SRS-22r) and Spinal Appearance Questionnaires (SAQ) scores. Intention-to-treat (ITT) and per protocol (PP) linear mixed effects models were analyzed. Because ITT and PP analyses produced similar results, only ITT is reported.\n\nAfter 3\u00a0months, BME in the Schroth group improved by 32.3\u00a0s, and in the control by 4.8\u00a0s. This 27.5\u00a0s difference in change between groups was statically significant (95 % CI 1.1 to 53.8\u00a0s, p\u2009=\u20090.04). From 3 to 6\u00a0months, the self-image improved in the Schroth group by 0.13 and deteriorated in the control by 0.17 (0.3, 95 % CI 0.01 to 0.59, p\u2009=\u20090.049). A difference between groups for the change in the SRS-22r pain score transformed to its power of four was observed from 3 to 6\u00a0months (85.3, 95 % CI 8.1 to 162.5, p\u2009=\u20090.03), where (SRS-22 pain score)(4) increased by 65.3 in the Schroth and decreased by 20.0 in the control group. Covariates: age, self-efficacy, brace-wear, Schroth classification, and height had significant main effects on some outcomes. Baseline ceiling effects were high: SRS-22r (pain\u2009=\u200918.4\u00a0%, function\u2009=\u200928.6\u00a0%), and SAQ (prominence\u2009=\u200926.5\u00a0%, waist\u2009=\u200929.2\u00a0%, chest\u2009=\u200946.9\u00a0%, trunk shift\u2009=\u200912.2\u00a0% and shoulders\u2009=\u200918.4\u00a0%).\n\nSupervised Schroth exercises provided added benefit to the standard of care by improving SRS-22r pain, self-image scores and BME. Given the high prevalence of ceiling effects on SRS-22r and SAQ questionnaires' domains, we hypothesize that in the AIS population receiving conservative treatments, different QOL questionnaires with adequate responsiveness are needed.\n\nSchroth Exercise Trial for Scoliosis NCT01610908.", "PMID": "26413145"}, {"title": "Effects of Schroth and Pilates exercises on the Cobb angle and weight distribution of patients with scoliosis.", "abstract": "[Purpose] The purpose of this study was to compare the effect of Schroth and Pilates exercises on the Cobb angle and body weight distribution of patients with idiopathic scoliosis. [Subjects] Twenty-four scoliosis patients with a Cobb angle of \u226520\u00b0 were divided into the Schroth exercise group (SEG, n = 12) and the Pilates exercise group (PEG, n = 12). [Methods] The SEG and PEG performed Schroth and Pilates exercises, respectively, three times a week for 12 weeks. The Cobb angle was measured in the standing position with a radiography apparatus, and weight load was measured with Gait View Pro 1.0. [Results] In the intragroup comparison, both groups showed significant changes in the Cobb angle. For weight distribution, the SEG showed significant differences in the total weight between the concave and convex sides, but the PEG did not show significant differences. Furthermore, in the intragroup comparison, the SEG showed significant differences in the changes in the Cobb angle and weight distribution compared with the PEG. [Conclusion] Both Schroth and Pilates exercises were effective in changing the Cobb angle and weight distribution of scoliosis patients; however, the intergroup comparison showed that the Schroth exercise was more effective than the Pilates exercise. ", "PMID": "27134403"}, {"title": "Schroth Physiotherapeutic Scoliosis-Specific Exercises Added to the Standard of Care Lead to Better Cobb Angle Outcomes in Adolescents with Idiopathic Scoliosis - an Assessor and Statistician Blinded Randomized Controlled Trial.", "abstract": "The North American non-surgical standard of care for adolescent idiopathic scoliosis (AIS) includes observation and bracing, but not exercises. Schroth physiotherapeutic scoliosis-specific exercises (PSSE) showed promise in several studies of suboptimal methodology. The Scoliosis Research Society calls for rigorous studies supporting the role of exercises before including it as a treatment recommendation for scoliosis.\n\nTo determine the effect of a six-month Schroth PSSE intervention added to standard of care (Experimental group) on the Cobb angle compared to standard of care alone (Control group) in patients with AIS.\n\nFifty patients with AIS aged 10-18 years, with curves of 10\u00b0-45\u00b0 and Risser grade 0-5 were recruited from a single pediatric scoliosis clinic and randomized to the Experimental or Control group. Outcomes included the change in the Cobb angles of the Largest Curve and Sum of Curves from baseline to six months. The intervention consisted of a 30-45 minute daily home program and weekly supervised sessions. Intention-to-treat and per protocol linear mixed effects model analyses are reported.\n\nIn the intention-to-treat analysis, after six months, the Schroth group had significantly smaller Largest Curve than controls (-3.5\u00b0, 95% CI -1.1\u00b0 to -5.9\u00b0, p = 0.006). Likewise, the between-group difference in the square root of the Sum of Curves was -0.40\u00b0, (95% CI -0.03\u00b0 to -0.8\u00b0, p = 0.046), suggesting that an average patient with 51.2\u00b0 at baseline, will have a 49.3\u00b0 Sum of Curves at six months in the Schroth group, and 55.1\u00b0 in the control group with the difference between groups increasing with severity. Per protocol analyses produced similar, but larger differences: Largest Curve = -4.1\u00b0 (95% CI -1.7\u00b0 to -6.5\u00b0, p = 0.002) and [Formula: see text] (95% CI -0.8 to 0.2, p = 0.006).\n\nSchroth PSSE added to the standard of care were superior compared to standard of care alone for reducing the curve severity in patients with AIS.\n\nNCT01610908.", "PMID": "28033399"}, {"title": "[Effect of asymmetric respiratory exercise therapy on respiratory system function; evaluation using spirometric examination in children with idiopathic scoliosis].", "abstract": "Current work presents the results of spirometric examinations in 124 children aged 5 to 16 years (mean age 12.1 years) suffering from idiopathic scoliosis. Children were treated according to asymmetric respiratory exercises method applied in period of 24 days. Healthy children living in Upper Silesia industrial region were the control group. Examined scoliotic group was characterized by generally mild lung function impairment, although the values of spirometric indexes tended to deplete with time of duration and severity of the scoliosis. Especially the tendency of the forced expiratory volume in first second (FEV1) decrease was apparent, as well as maximal expiratory flows MEF50 and MEF25, in conjunction with Cobb angle increase. Slight but evident increase of forced vital capacity (FVC) and FEV1 was observed as a result of rehabilitation utilizing asymmetric respiratory exercises method.", "PMID": "11247401"}, {"title": "The role of measured resistance exercises in adolescent scoliosis.", "abstract": "Twenty adolescent patients (18 girls and 2 boys) with scoliosis ranging from 15 degrees-41 degrees in their major curve were treated with a progressive resistive training program for torso rotation. All patients demonstrated an asymmetry of rotation strength measured on specialized equipment, and surface electrode electromyograms showed inhibition of lumbar paraspinal muscles. Sixteen of 20 patients demonstrated curve reduction, and no patient showed an increase in curve.", "PMID": "12597221"}, {"title": "Incidence of curvature progression in idiopathic scoliosis patients treated with scoliosis in-patient rehabilitation (SIR): an age- and sex-matched controlled study.", "abstract": "The goal of this study is to test the hypothesis that physiotherapy-based intervention can reduce incidence of progression in children with IS. Two independent patient groups matched by age and sex at diagnosis were analysed using the outcome parameter, incidence of progression (> or =5 degrees ). One group was untreated and the other received scoliosis in-patient rehabilitation (SIR). Incidence of progression in groups of untreated patients ranged from 1.5-fold (71.2% vs 46.7%) to 2.9-fold (55.8% vs 19.2%) higher than in groups of patients treated with SIR, even when SIR-treated groups included patients with more severe curvatures. Statistically, the differences were highly significant. Efforts to test the hypothesis that physical therapies addressing postural imbalance can be used effectively in the treatment of IS have been limited. The results of this study are consistent with the possibility that a supervized programme of exercise-based therapies can reduce incidence of progression in children with IS.", "PMID": "12745892"}], "labels": [{"PMID": "24682356", "label": "included"}, {"PMID": "24945482", "label": "included"}, {"PMID": "25439713", "label": "included"}, {"PMID": "25780260", "label": "included"}, {"PMID": "26413145", "label": "included"}, {"PMID": "27134403", "label": "included"}, {"PMID": "28033399", "label": "included"}, {"PMID": "11247401", "label": "excluded"}, {"PMID": "12597221", "label": "excluded"}, {"PMID": "12745892", "label": "excluded"}]}
{"metadata": {"review_pmid": "38415846"}, "inputs": {"background": "Oral submucous fibrosis (OSF) is a chronic disease of the oral cavity that causes progressive constriction of the cheeks and mouth accompanied by severe pain and reduced mouth opening. OSF has a significant impact on eating and swallowing, affecting quality of life. There is an increased risk of oral malignancy in people with OSF. The main risk factor for OSF is areca nut chewing, and the mainstay of treatment has been behavioural interventions to support habit cessation. This review is an update of a version last published in 2008.", "objectives": "To evaluate the benefits and harms of interventions for the management of oral submucous fibrosis.", "selection criteria": "We considered randomised controlled trials (RCTs) of adults with a biopsy-confirmed diagnosis of OSF treated with systemic, locally delivered or topical drugs at any dosage, duration or delivery method compared against placebo or each other. We considered surgical procedures compared against other treatments or no active intervention. We also considered other interventions such as physiotherapy, ultrasound or alternative therapies."}, "context": [{"title": "Pentoxifylline therapy: a new adjunct in the treatment of oral submucous fibrosis.", "abstract": "This study was designed to determine the effect of pentoxifylline (Trental) on the clinical and pathologic course of oral submucous fibrosis. This drug is a methylxanthine derivative that has vasodilating properties and was envisaged to increase mucosal vascularity.\n\nThis investigation was conducted as a randomized clinical trial incorporating a control group (Standard drug group SDG, multivitamin, and local heat therapy) in comparison to pentoxifylline test cases (Experimental drug group EDG, 400mg 3 times daily, as coated, sustained release tablets). The stipulated treatment period was 7 months and a total of 29 cases of advanced fibrosis (14 test subjects and 15 age and sex matched diseased controls) were included in this study and 100% compliance was reported at the end ofthe test period.\n\nMild gastric irritation that could be managed by diet protocols was the only untoward symptom reported during this trial. Review of the patients and controls was done at an interval of 30 days and subjective and objective measurements were recorded. The follow up data at each visit with respect to each other and to base-line values was calibrated using a nonparametric test of Mann-Whitney (Kruskal-Wallis test). Significant comparisons with regard to improvement were recorded as objective criteria of mouth opening (t=11.285, p= 0.000), tongue protrusion (t= 3.898, p = 0.002), and relief from perioral fibrotic bands (p = 0.0001554). Subjective symptoms of intolerance to spices (p = 0.0063218), burning sensation of mouth (p = 0.0005797), tinnitus (p=0.000042), difficulty in swallowing (p=0.0000714). and difficulty in speech (p=0.0000020) were also recorded significant improvement at the end of the trial period.\n\nThis pilot investigation points to the effectiveness of pentoxifylline as an adjunct therapy in the routine management of oral submucous fibrosis.", "PMID": "17217216"}, {"title": "Efficacy of lycopene in the management of oral submucous fibrosis.", "abstract": "To evaluate the efficacy of oral lycopene therapy in patients with oral submucous fibrosis and to compare these effects with a placebo.\n\nFifty-eight patients with oral submucous fibrosis formed the population for the study and were randomly divided into 3 groups, evaluated weekly over a 2-month period. Patients of group A (n = 21) received 16 mg of lycopene, those of group B (n = 19) received 16 mg of lycopene along with biweekly intralesional steroid injections, and those of group C (n = 18) were given a placebo. Paired and unpaired t tests were used for statistical evaluation.\n\nMouth-opening values for the patients showed an average increase of 3.4 mm, 4.6 mm, and 0.0 mm for patients in groups A, B, and C, respectively. These values were statistically found to be highly significant.\n\nThe observed effects suggest that lycopene can and should be used as a first line of therapy in the initial management of oral submucous fibrosis.", "PMID": "17234537"}, {"title": "Physiotherapeutic treatment improves oral opening in oral submucous fibrosis.", "abstract": "In oral submucous fibrosis (OSF) fibrous bands and burning mucosal pain restrict oral opening to limit speech and eating. The pathogenesis of OSF remains unclear, while surgical and pharmacological treatments have limited success, and are often inaccessible in communities using areca nut where OSF is prevalent. Improved outcomes are reported for surgical treatment when followed by physiotherapy. We tested the hypothesis that physiotherapy alone can modify tissue remodelling in OSF to increase oral opening.\n\nFifty-four Nepali OSF patients were managed for 4 months in three randomly assigned groups receiving either: five times daily physiotherapy by inter-positioning tongue spatulas between teeth and adding a new spatula every 5-10 days; local injection of hyaluronidase with steroids; or no active treatment.\n\nMore males presented with OSF than females (p < 0.05). All patients reported reduced opening and 47% had mucosal pain. Progressive mucosal involvement was always in the same order, starting with the soft palate, and then progressing to the fauces, unilateral buccal mucosa, bilateral buccal mucosa, floor of mouth and finally lip mucosa (p < 0.006). Physiotherapy improved oral opening (p < 0.0005), but not oral pain, while no clear improvement was seen in untreated patients as well as patients managed by injection.\n\nWe conclude OSF in the Nepali population progresses in a predictable pattern, and that physiotherapy is effective for increasing the oral opening. We further suggest physiotherapy can be readily used to improve OSF in communities with otherwise limited health resources.", "PMID": "18673417"}, {"title": "Oral administration of milk from cows immunized with human intestinal bacteria leads to significant improvements of symptoms and signs in patients with oral submucous fibrosis.", "abstract": "Previous studies have shown that the local and systemic upregulation of fibrogenic cytokines and downregulation of antifibrotic cytokine are central to the pathogenesis of oral submucous fibrosis (OSF). The milk from cows immunized with human intestinal bacteria (immune milk) contains an anti-inflammatory component that may suppress the inflammatory reaction and modulate cytokine production. Therefore, it was decided to test whether immune milk may have some beneficial effects on controlling the symptoms and signs in OSF patients.\n\nIn this preliminary study, 26 OSF patients who received immune milk treatment (45 g of immune milk powder twice a day) for 3 months and oral habit intervention were included in the experimental group. Another 20 OSF patients who received only oral habit intervention served as the control group.\n\nWe found that the interincisor distance was significantly improved (> or =3 mm of the baseline measurement) in 18 of the 26 (69.2%) OSF patients in the experimental group at exit. However, in the control group none of the OSF patients had an increase in interincisor distance greater than 2 mm. In addition, disappearance or significant improvement of symptoms at exit was observed in 80% (16/20) of the patients with intolerance to spicy foods (P < 0.001) and 72.2% (13/18) of the patients with xerostomia (P < 0.005) in the experimental group, compared with 17.6% (3/17) of the patients with improvement of intolerance to spicy foods and 15.4% (2/13) of the patients with improvement of xerostomia in the control group. Partial regression of concomitant oral leukoplakia or erythroplakia (judged from the size reduction of the lesions) at exit was noted in 71.4% (5/7) of the patients in the experimental group (P < 0.05), compared with none (0/5) of the patients with improvement in the control group.\n\nWe conclude that oral administration of immune milk leads to significant improvements of symptoms and signs in OSF patients.", "PMID": "11722712"}, {"title": "Extended nasolabial flaps in the management of oral submucous fibrosis.", "abstract": "We evaluated the use of extended nasolabial flaps and coronoidectomy in the management of 47 randomly selected patients with histologically confirmed oral submucous fibrosis. They all had interincisal opening of less than 25 mm and were treated by bilateral release of fibrous bands, coronoidectomy or coronoidotomy, and extended grafting with a nasolabial flap. All patients had postoperative physiotherapy, and were followed up for 2 years. Their interincisal opening improved significantly from a mean of 14 mm (range 3-23) to a mean of 41 mm (range 23-55). The procedure was effective in the management of patients with oral submucous fibrosis, the main disadvantage being the extraoral scars.", "PMID": "18995935"}, {"title": "Retrospective comparison of surgical treatment modalities in 100 patients with oral submucous fibrosis.", "abstract": "Oral submucous fibrosis has been a scourge of southeastern Asia and its residents since time immemorial. Scores of medicinal agents, singly and in combination, have been tried with not very encouraging results. In this study, therefore, we have restricted ourselves to different surgical modalities in the management of this condition and have tried to lay down indications of each surgical procedure.\n\nA total of 100 patients of oral submucous fibrosis were included in this study and randomly allocated to different surgical groups, 25 patients per group. After excision of fibrous bands, group I had buccal fat pad graft, group II had tongue flap, group III had nasolabial fold flap, and group IV had split skin graft for correction of mucosal defect created after incising the fibrous bands.\n\nMean preoperative mouth opening was 14.82 (SD 4.38) mm and ranged between 4.00 and 25.00 mm. Statistically there was no significant difference among the 4 groups (P = .996). Mean postoperative mouth opening at 1 week was 35.79 (3.53) mm, ranging between 24.00 and 42.00 mm. Mean postoperative mouth opening at 1 month in group I was 36.36 (2.64) mm, in group II 35.36 (29) mm, in group III 35.64 (2.94) mm, and in group IV 35.80 (3.24) mm. Total score for pain, esthetics, and function at 1 month after surgery was highest (11.29) in group I, indicating better results.\n\nThe results were very encouraging, and we were able to lay down specific indications for each procedure. However, we believe buccal fat pad rotation is superior to other procedures, because it offers ease of surgery, can be performed under local anesthesia as a day care procedure, shows little postoperative morbidity, and has good patient acceptance, and there appear to be no contraindications to its use.", "PMID": "19217007"}, {"title": "Lack of reliable evidence for oral submucous fibrosis treatments.", "abstract": "Searches were made for relevant studies using the Cochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials, Medline, Embase and IndMED (bibliographic database of Indian biomedical journals). There were no language restrictions.\n\nRandomised controlled trials were to be selected if they compared surgery, systemic or topical medicines, or other interventions, to manage the symptoms of oral submucous fibrosis (OSF).\n\nTwo authors independently assessed trial quality and extracted trial data. Disagreements were resolved by consultation with a third author. Attempts were made to contact study authors where necessary for clarification and for additional information. Because of limited poor quality data, only a descriptive summary of the results of the included trials was carried out.\n\nTwo trials, involving 87 participants, evaluated either lycopene in conjunction with intralesional injections of a steroid, and pentoxifylline in combination with mouth-stretching exercises and heat. There were no reports of toxicity to the interventions but some side-effects, which were mostly gastric irritation to pentoxifylline, were noted.\n\nThe lack of reliable evidence for the effectiveness of any specific interventions for the management of OSF is illustrated by the paucity, and poor methodological quality, of trials retrieved for this review.", "PMID": "19322218"}, {"title": "Drug treatment of oral submucous fibrosis: a review of the literature.", "abstract": "To review the literature on drug treatment of oral submucous fibrosis.\n\nAn electronic search was performed for articles published from January 1960 to August 2008.\n\nOnly 17 publications were searched, and 15 publications showed a high level of evidence (6 randomized controlled trials, 4 clinical trials/controlled clinical trials, and 5 other experimental studies), with a total of 1,224 patients.\n\nFew studies with high levels of evidence were found. It is quite difficult to compare or even combine their outcomes in a scientifically meaningful manner. Because of insufficient research data, there is a need for high-quality randomized, controlled trials in this area of medicine.", "PMID": "19531426"}, {"title": "A systematic review of medical interventions for oral submucous fibrosis and future research opportunities.", "abstract": "Oral Diseases (2011) 17 (Suppl. 1), 42-57 Oral submucous fibrosis (OSF) is a chronic, insidious disease caused by areca nut use, and is associated with both significant morbidity (including pain and reduced oral opening) and an increased risk for malignancy. This systematic review explored and updated the current medical (i.e., non-surgical) interventions available for the management of OSF. Of the 27 published medical interventions, there were four randomized controlled trials. The overall quality of these randomized controlled studies was assessed using the GRADE approach and significant limitations that challenged the conclusions were found. However, this review was valuable in terms of identifying opportunities to provide recommendations for future research, in terms of the populations to research, the types of interventions needed, the types of outcomes to be measured, the study designs needed, and the infrastructure required to conduct studies. The next step is to initiate a pathway for a low-cost research plan leading to the development of a brief protocol for future clinical trials in this field, with an emphasis on conducting studies in regions of the world where OSF is prevalent.", "PMID": "21382138"}, {"title": "Use of buccal fat pad for treatment of oral submucous fibrosis.", "abstract": "The aim of this study was to clinically evaluate the application of pedicled buccal fat pad (BFP) in the surgical management of stage III and IV oral submucous fibrosis (OSMF).\n\nTwenty-eight cases of clinically and histologically diagnosed cases of OSMF were divided into 2 groups: group I (n = 15) and group II (n = 13), corresponding to clinical stage III and stage IV, respectively. All the patients underwent incision of fibrotic bands and coverage of the buccal defect with a pedicled BFP flap. Both groups were analyzed separately for mouth opening (interincisal distance in millimeters) preoperatively and 1 year postoperatively, time taken for epithelialization of BFP, time taken for establishment of normal contour, and changes in symptoms (painful ulcerations, burning sensation, and intolerance to spices) 1 year after grafting.\n\nThe mean preoperative mouth opening was 19.6 mm (SD, 2.43) in group I and 12.92 mm (SD, 1.21) in group II. The mean postoperative mouth opening after 1 year was 35 mm in group I (SD, 1.96) and 31.76 mm in group II (SD, 1.97). The time taken for epithelialization of BFP was 4 weeks in group I and 5 weeks in group II. The mean time taken for establishment of normal contour after grafting was 12.25 weeks (SD, 1.42) in group I and 15.07 weeks (SD, 1.26) in group II. In 2 cases in group II, there was remission of painful ulcerations, burning sensation, and intolerance to spices.\n\nBFP is reliable for the treatment of OSMF.", "PMID": "21549481"}], "labels": [{"PMID": "17217216", "label": "included"}, {"PMID": "17234537", "label": "included"}, {"PMID": "18673417", "label": "included"}, {"PMID": "11722712", "label": "excluded"}, {"PMID": "18995935", "label": "excluded"}, {"PMID": "19217007", "label": "excluded"}, {"PMID": "19322218", "label": "excluded"}, {"PMID": "19531426", "label": "excluded"}, {"PMID": "21382138", "label": "excluded"}, {"PMID": "21549481", "label": "excluded"}]}
{"metadata": {"review_pmid": "38415786"}, "inputs": {"background": "Massage is widely used for neck pain, but its effectiveness remains unclear.", "objectives": "To assess the benefits and harms of massage compared to placebo or sham, no treatment or exercise as an adjuvant to the same co-intervention for acute to chronic persisting neck pain in adults with or without radiculopathy, including whiplash-associated disorders and cervicogenic headache.", "selection criteria": "We included randomised controlled trials (RCTs) comparing any type of massage with sham or placebo, no treatment or wait-list, or massage as an adjuvant treatment, in adults with acute, subacute or chronic neck pain."}, "context": [{"title": "Randomised trial of acupuncture compared with conventional massage and \"sham\" laser acupuncture for treatment of chronic neck pain.", "abstract": "To compare the efficacy of acupuncture and conventional massage for the treatment of chronic neck pain.\n\nProspective, randomised, placebo controlled trial.\n\nThree outpatient departments in Germany.\n\n177 patients aged 18-85 years with chronic neck pain.\n\nPatients were randomly allocated to five treatments over three weeks with acupuncture (56), massage (60), or \"sham\" laser acupuncture (61).\n\nmaximum pain related to motion (visual analogue scale) irrespective of direction of movement one week after treatment.\n\nrange of motion (3D ultrasound real time motion analyser), pain related to movement in six directions (visual analogue scale), pressure pain threshold (pressure algometer), changes of spontaneous pain, motion related pain, global complaints (seven point scale), and quality of life (SF-36). Assessments were performed before, during, and one week and three months after treatment. Patients' beliefs in treatment were assessed.\n\nOne week after five treatments the acupuncture group showed a significantly greater improvement in motion related pain compared with massage (difference 24.22 (95% confidence interval 16.5 to 31.9), P=0.0052) but not compared with sham laser (17.28 (10.0 to 24.6), P=0.327). Differences between acupuncture and massage or sham laser were greater in the subgroup who had had pain for longer than five years (n=75) and in patients with myofascial pain syndrome (n=129). The acupuncture group had the best results in most secondary outcome measures. There were no differences in patients' beliefs in treatment.\n\nAcupuncture is an effective short term treatment for patients with chronic neck pain, but there is only limited evidence for long term effects after five treatments.", "PMID": "11431299"}, {"title": "Immediate effects of inhibitive distraction on active range of cervical flexion in patients with neck pain: a pilot study.", "abstract": "The purpose of this pilot study was to examine the immediate effects of a manual therapy technique called Inhibitive Distraction (ID) on active range of motion (AROM) for cervical flexion in patients with neck pain with or without concomitant headache. A secondary objective of this study was to see whether patient subgroups could be identified who might benefit more from ID by studying variables such as age, pain intensity, presence of headache, or pre-intervention AROM. We also looked at patients' ability to identify pre- to post-intervention changes in their ability to actively move through a range of motion. Forty subjects (mean age 34.7 years; range 16-48 years) referred to a physical therapy clinic due to discomfort in the neck region were randomly assigned to an experimental and a control group. We used the CROM goniometer to measure pre- and post-intervention cervical flexion AROM in the sagittal plane within a single treatment session. The between-group difference in AROM increase was not statistically significant at P<0.05 with a mean post-intervention increase in ROM of 2.4 degrees (SD 6.2 degrees ) for the experimental group and 1.2 degrees (SD 5.8 degrees ) for the placebo group. We were also unable to identify potential subgroups more likely to respond to ID, although a trend emerged for greater improvement in chronic patients with headaches, lower pain levels, and less pre-intervention AROM. In the experimental group and in both groups combined, subjects noting increased AROM indeed had a significantly greater increase in AROM than those subjects not noting improvement. In conclusion, this study did not confirm immediate effects of ID on cervical flexion AROM but did provide indications for potential subgroups likely to benefit from this technique. Recommendations are provided with regard to future research and clinical use of the technique studied.", "PMID": "19066648"}, {"title": "Comparative effects of acupressure at local and distal acupuncture points on pain conditions and autonomic function in females with chronic neck pain.", "abstract": "Acupressure on local and distal acupuncture points might result in sedation and relaxation, thereby reducing chronic neck pain. The aim was to investigate the effect of acupressure at local (LP) and distal acupuncture points (DP) in females with chronic neck pain. Thirty-three females were assigned to three groups: the control group did not receive any stimuli, the LP group received acupressure at local acupuncture points, GB 21, SI 14 and SI 15, and the DP group received acupressure at distal acupuncture points, LI 4, LI 10 and LI 11. Verbal rating scale (VRS), Neck Disability Index (NDI), State-Trait Anxiety Inventory (STAI), muscle hardness (MH), salivary alpha-amylase (sAA) activity, heart rate (HR), heart rate variability (HRV) values and satisfaction due to acupressure were assessed. VRS, NDI, STAI and MH values decreased after acupressure in the LP and the DP group. HR decreased and the power of high frequency (HF) component of HRV increased after acupressure in only the LP group. Although acupressure on not only the LP but also the DP significantly improved pain conditions, acupressure on only the LP affected the autonomic nervous system while acupuncture points per se have different physical effects according to location.", "PMID": "20953433"}, {"title": "The efficacy of an integrated neuromuscular inhibition technique on upper trapezius trigger points in subjects with non-specific neck pain: a randomized controlled trial.", "abstract": "Currently, large levels of practice variability exist regarding the clinical deactivation of trigger points. Manual physical therapy has been identified as a potential means of resolving active trigger points; however, to date the ideal treatment approach has yet to be elucidated. The purpose of this clinical trial was to compare the effects of two manual treatment regimens on individuals with upper trapezius trigger points. Sixty patients, 19-38 years of age with non-specific neck pain and upper trapezius trigger points, were randomized into one of two, 4 week physical therapy programs. One group received muscle energy techniques while the second group received an integrated neuromuscular inhibition technique (INIT) consisting of muscle energy techniques, ischemic compression, and strain-counterstrain (SCS). Outcomes including a visual analog pain scale (VAS), the neck disability index (NDI), and lateral cervical flexion range of motion (ROM) were collected at baseline, 2 and 4 weeks after the initiation of therapy. Results revealed large pre-post-effect sizes within the INIT group (Cohen's d \u200a=\u200a 0.97, 0.94 and 0.97). Additionally, significantly greater improvements in pain and neck disability and lateral cervical flexion ROM were detected in favor of the INIT group (0.29-0.57, 0.57-1.12 and 0.29-0.57) at a 95% CI respectively. The findings of this study indicate the potential benefit of an integrated approach in deactivating upper trapezius trigger points. Further research should be performed to investigate the long-term benefits of the current treatment approach.", "PMID": "21655422"}, {"title": "Strain-counterstrain to treat restrictions of the mobility of the cervical spine in patients with neck pain: a sham-controlled randomized trial.", "abstract": "Strain-counterstrain is an osteopathic technique which is widely used for treating mobility restrictions in the neck. We aimed to investigate whether a single strain-counterstrain intervention is more effective than a sham intervention in improving restricted cervical range of motion in patients with neck pain.\n\n61 adult patients with neck pain and restricted cervical mobility were randomly allocated to receive either a single strain-counterstrain intervention or a sham treatment. After outcome measurement all patients received full individualized osteopathic treatment. Mobility of the cervical spine was measured by a blinded observer using the Cervical Range of Motion (CROM) tool. In addition, patients rated pain intensity and assessed the treatment effect. The main outcome measure was the sum of changes in mobility restriction (in %) after treatment compared to normal mobility.\n\nAll patients completed the study. Mobility restriction decreased by 2.0% (SD 6.9%) in the group receiving strain-counterstrain treatment and 0.6% (SD 5.7%) in the group receiving sham treatment (mean difference 1.5%, 95% confidence interval -1.7 to 4.8%; p=0.35). There were no significant differences between groups for secondary outcomes. After receiving the full osteopathic treatment the group initially receiving strain-counterstrain improved by another 4.2% (7.0%; p=0.003) and the group initially receiving sham by another 5.6% (SD 6.8%; p<0.001).\n\nStrain-counterstrain as a single intervention did not have immediate effects on mobility and pain over a sham treatment. Future studies should probably focus on the investigation of full osteopathic treatment.", "PMID": "23374199"}, {"title": "Short-term changes in median nerve neural tension after a suboccipital muscle inhibition technique in subjects with cervical whiplash: a randomised controlled trial.", "abstract": "To assess the immediate effect of a suboccipital muscle inhibition (SMI) technique on: (a) neck pain, (b) elbow extension range of motion during the upper limb neurodynamic test of the median nerve (ULNT-1), and (c) grip strength in subjects with cervical whiplash; and determine the relationships between key variables.\n\nRandomised, single-blind, controlled clinical trial.\n\nFaculty of Nursing, Physiotherapy and Podiatry, University of Seville, Spain.\n\nForty subjects {mean age 34 years [standard deviation (SD) 3.6]} with Grade I or II cervical whiplash and a positive response to the ULNT-1 were recruited and distributed into two study groups: intervention group (IG) (n=20) and control group (CG) (n=20).\n\nThe IG underwent the SMI technique for 4minutes and the CG received a sham (placebo) intervention. Measures were collected immediately after the intervention.\n\nThe primary outcome was elbow range of motion during the ULNT-1, measured with a goniometer. The secondary outcomes were self-perceived neck pain (visual analogue scale) and free-pain grip strength, measured with a digital dynamometer.\n\nThe mean baseline elbow range of motion was 116.0\u00b0 (SD 10.2) for the CG and 130.1\u00b0 (SD 7.8) for the IG. The within-group comparison found a significant difference in elbow range of motion for the IG [mean difference -15.4\u00b0, 95% confidence interval (CI) -20.1 to -10.6; P=0.01], but not for the CG (mean difference -4.9\u00b0, 95% CI -11.8 to 2.0; P=0.15). In the between-group comparison, the difference in elbow range of motion was significant (mean difference -10.5\u00b0, 95% CI -18.6 to -2.3; P=0.013), but the differences in grip strength (P=0.06) and neck pain (P=0.38) were not significant.\n\nThe SMI technique has an immediate positive effect on elbow extension in the ULNT-1. No immediate effects on self-perceived cervical pain or grip strength were observed.", "PMID": "24405830"}, {"title": "Five-week outcomes from a dosing trial of therapeutic massage for chronic neck pain.", "abstract": "This trial was designed to evaluate the optimal dose of massage for individuals with chronic neck pain.\n\nWe recruited 228 individuals with chronic nonspecific neck pain from an integrated health care system and the general population, and randomized them to 5 groups receiving various doses of massage (a 4-week course consisting of 30-minute visits 2 or 3 times weekly or 60-minute visits 1, 2, or 3 times weekly) or to a single control group (a 4-week period on a wait list). We assessed neck-related dysfunction with the Neck Disability Index (range, 0-50 points) and pain intensity with a numerical rating scale (range, 0-10 points) at baseline and 5 weeks. We used log-linear regression to assess the likelihood of clinically meaningful improvement in neck-related dysfunction (\u22655 points on Neck Disability Index) or pain intensity (\u226530% improvement) by treatment group.\n\nAfter adjustment for baseline age, outcome measures, and imbalanced covariates, 30-minute treatments were not significantly better than the wait list control condition in terms of achieving a clinically meaningful improvement in neck dysfunction or pain, regardless of the frequency of treatments. In contrast, 60-minute treatments 2 and 3 times weekly significantly increased the likelihood of such improvement compared with the control condition in terms of both neck dysfunction (relative risk = 3.41 and 4.98, P = .04 and .005, respectively) and pain intensity (relative risk = 2.30 and 2.73; P = .007 and .001, respectively).\n\nAfter 4 weeks of treatment, we found multiple 60-minute massages per week more effective than fewer or shorter sessions for individuals with chronic neck pain. Clinicians recommending massage and researchers studying this therapy should ensure that patients receive a likely effective dose of treatment.", "PMID": "24615306"}, {"title": "Randomized clinical trial assessing whether additional massage treatments for chronic neck pain improve 12- and 26-week outcomes.", "abstract": "This is the first study to systematically evaluate the value of a longer treatment period for massage. We provide a framework of how to conceptualize an optimal dose in this challenging setting of nonpharmacologic treatments.\n\nThe aim was to determine the optimal dose of massage for neck pain.\n\nTwo-phase randomized trial for persons with chronic nonspecific neck pain. Primary randomization to one of five groups receiving 4 weeks of massage (30 minutes 2x/or 3x/wk or 60 minutes 1x, 2x, or 3x/wk). Booster randomization of participants to receive an additional six massages, 60 minutes 1x/wk, or no additional massage.\n\nA total of 179 participants from Group Health and the general population of Seattle, WA, USA recruited between June 2010 and August 2011 were included.\n\nPrimary outcomes self-reported neck-related dysfunction (Neck Disability Index) and pain (0-10 scale) were assessed at baseline, 12, and 26 weeks. Clinically meaningful improvement was defined as greater than or equal to 5-point decrease in dysfunction and greater than or equal to 30% decrease in pain from baseline.\n\nClinically meaningful improvement for each primary outcome with both follow-up times was analyzed using adjusted modified Poisson generalized estimating equations (GEEs). Secondary analyses for the continuous outcomes used linear GEEs.\n\nThere were no observed differences by primary treatment group at 12 or 26 weeks. Those receiving booster dose had improvements in both dysfunction and pain at 12 weeks (dysfunction: relative risk [RR]=1.56 [1.08-2.25], p=.018; pain: RR=1.25 [0.98-1.61], p=.077), but those were nonsignificant at 26 weeks (dysfunction: RR=1.22 [0.85-1.74]; pain: RR=1.09 [0.82-1.43]). Subgroup analysis by primary and booster treatments found the booster dose only effective among those initially randomized to one of the 60-minute massage groups.\n\n\"Booster\" doses for those initially receiving 60 minutes of massage should be incorporated into future trials of massage for chronic neck pain.", "PMID": "26096474"}, {"title": "Cervical and scapulothoracic stabilization exercises with and without connective tissue massage for chronic mechanical neck pain: A prospective, randomised controlled trial.", "abstract": "This study was planned to assess and compare the effectiveness of cervical and scapulothoracic stabilization exercise treatment with and without connective tissue massage (CTM) on pain, anxiety, and the quality of life in patients with chronic mechanical neck pain (MNP). Sixty patients with chronic MNP (18-65 years) were recruited and randomly allocated into stabilization exercise with (Group 1, n\u00a0=\u00a030) and without the CTM (Group 2, n\u00a0=\u00a030). The program was carried out for 12 sessions, 3 days/week in 4 weeks. Pain intensity with Visual Analog Scale, pressure pain threshold with digital algometer (JTech Medical Industries, ZEVEX Company), level of anxiety with Spielberger State Trait Anxiety Inventory, and quality of life with Short Form-36 were evaluated before and after the treatment. After the program, pain intensity and the level of anxiety decrease, physical health increase in Group 1 and 2 were found (p\u00a0<\u00a00.05). Pressure pain threshold and mental health increase were detected in only Group 1 (p\u00a0<\u00a00.05). The intergroup comparison showed that significant difference in pain intensity at night, pressure pain threshold, state anxiety and mental health were seen in favor of Group 1 (p\u00a0<\u00a00.05). The study suggested that stabilization exercises with and without the CTM might be a useful treatment for patients with chronic MNP. However, stabilization exercises with CTM might be superior in improving pain intensity at night, pressure pain threshold, state anxiety and mental health compared to stabilization exercise alone. ", "PMID": "26211422"}, {"title": "Craniosacral Therapy for the Treatment of Chronic Neck Pain: A Randomized Sham-controlled Trial.", "abstract": "With growing evidence for the effectiveness of craniosacral therapy (CST) for pain management, the efficacy of CST remains unclear. This study therefore aimed at investigating CST in comparison with sham treatment in chronic nonspecific neck pain patients.\n\nA total of 54 blinded patients were randomized into either 8 weekly units of CST or light-touch sham treatment. Outcomes were assessed before and after treatment (week 8) and again 3 months later (week 20). The primary outcome was the pain intensity on a visual analog scale at week 8; secondary outcomes included pain on movement, pressure pain sensitivity, functional disability, health-related quality of life, well-being, anxiety, depression, stress perception, pain acceptance, body awareness, patients' global impression of improvement, and safety.\n\nIn comparison with sham, CST patients reported significant and clinically relevant effects on pain intensity at week 8 (-21 mm group difference; 95% confidence interval, -32.6 to -9.4; P=0.001; d=1.02) and at week 20 (-16.8 mm group difference; 95% confidence interval, -27.5 to -6.1; P=0.003; d=0.88). Minimal clinically important differences in pain intensity at week 20 were reported by 78% within the CST group, whereas 48% even had substantial clinical benefit. Significant between-group differences at week 20 were also found for pain on movement, functional disability, physical quality of life, anxiety and patients' global improvement. Pressure pain sensitivity and body awareness were significantly improved only at week 8. No serious adverse events were reported.\n\nCST was both specifically effective and safe in reducing neck pain intensity and may improve functional disability and the quality of life up to 3 months after intervention.", "PMID": "26340656"}], "labels": [{"PMID": "11431299", "label": "included"}, {"PMID": "19066648", "label": "included"}, {"PMID": "20953433", "label": "included"}, {"PMID": "21655422", "label": "included"}, {"PMID": "23374199", "label": "included"}, {"PMID": "24405830", "label": "included"}, {"PMID": "24615306", "label": "included"}, {"PMID": "26096474", "label": "included"}, {"PMID": "26211422", "label": "included"}, {"PMID": "26340656", "label": "included"}]}
{"metadata": {"review_pmid": "38411279"}, "inputs": {"background": "Management of congenital hemophilia A and B is by prophylactic or on-demand replacement therapy with clotting factor concentrates. The effects of newer non-clotting factor therapies such as emicizumab, concizumab, marstacimab, and fitusiran compared with existing standards of care are yet to be systematically reviewed.", "objectives": "To assess the effects (clinical, economic, patient-reported, and adverse outcomes) of non-clotting factor therapies for preventing bleeding and bleeding-related complications in people with congenital hemophilia A or B compared with prophylaxis with clotting factor therapies, bypassing agents, placebo, or no prophylaxis.", "selection criteria": "Randomized controlled trials (RCTs) evaluating people with congenital hemophilia A or B with and without inhibitors, who were treated with non-clotting factor therapies to prevent bleeds."}, "context": [{"title": "Hemostatic effect of a monoclonal antibody mAb 2021 blocking the interaction between FXa and TFPI in a rabbit hemophilia model.", "abstract": "Hemophilia is treated by IV replacement therapy with Factor VIII (FVIII) or Factor IX (FIX), either on demand to resolve bleeding, or as prophylaxis. Improved treatment may be provided by drugs designed for subcutaneous and less frequent administration with a reduced risk of inhibitor formation. Tissue factor pathway inhibitor (TFPI) down-regulates the initiation of coagulation by inhibition of Factor VIIa (FVIIa)/tissue factor/Factor Xa (FVIIa/TF/FXa). Blockage of TFPI inhibition may facilitate thrombin generation in a hemophilic setting. A high-affinity (K(D) = 25pM) mAb, mAb 2021, against TFPI was investigated. Binding of mAb 2021 to TFPI effectively prevented inhibition of FVIIa/TF/FXa and improved clot formation in hemophilia blood and plasma. The binding epitope on the Kunitz-type protease inhibitor domain 2 of TFPI was mapped by crystallography, and showed an extensive overlap with the FXa contact region highlighting a structural basis for its mechanism of action. In a rabbit hemophilia model, an intravenous or subcutaneous dose significantly reduced cuticle bleeding. mAb 2021 showed an effect comparable with that of rFVIIa. Cuticle bleeding in the model was reduced for at least 7 days by a single intravenous dose of mAb 2021. This study suggests that neutralization of TFPI by mAb 2021 may constitute a novel treatment option in hemophilia.", "PMID": "22563084"}, {"title": "Pharmacokinetics of an anti-TFPI monoclonal antibody (concizumab) blocking the TFPI interaction with the active site of FXa in Cynomolgus monkeys after iv and sc administration.", "abstract": "Concizumab (mAb 2021) is a monoclonal IgG4 antibody (mAb) that binds to the Kunitz-type protease inhibitor (KPI) 2 domain of TFPI thereby blocking the interaction of this domain with the active site of FXa. The objective of the present study was to characterize the pharmacokinetics of concizumab in Cynomolgus monkeys after intravenous (iv) and subcutaneous (sc) administration.\n\nData from two studies were included in the modelling, all in all data from 52 monkeys distributed into 9 groups. Three groups received three escalating sc doses of concizumab with a one week dosing interval, two groups were administered a single dose, and four groups received multiple doses over 13 weeks of concizumab. The plasma concentration was measured using a standard ELISA, and pharmacokinetic data were analysed using NONMEM.\n\nThe pharmacokinetics of concizumab were characterised by a high bioavailability (93%) after sc administration. The time course of the elimination of concizumab from the circulation was well described by the proposed target mediated drug disposition (TMDD) model. The clearance of concizumab was estimated to be 0.14 ml/h/kg, the target clearance was characterized by a 50% saturation level of 0.54 \u03bcg/ml (Km), and the clearance at target saturation was estimated to be 11 \u03bcg/h/kg.\n\nConcizumab displays a typical TMDD profile with important implications for a putative treatment regime in haemophilia patients. Compared to current standard haemophilia treatment, concizumab has a high bioavailability after sc administration and may provide a viable alternative to intravenous dosing for the treatment of haemophilia.", "PMID": "24568891"}, {"title": "Safety and pharmacokinetics of anti-TFPI antibody (concizumab) in healthy volunteers and patients with hemophilia: a randomized first human dose trial.", "abstract": "Prophylaxis with either intravenous (i.v.) factor VIII (FVIII) or FIX is the gold standard of care for patients with severe hemophilia. A monoclonal antibody (concizumab) targeting tissue factor pathway inhibitor (TFPI) that can be administered subcutaneously (s.c.) has the potential to alter current concepts of prophylaxis in hemophilia.\n\nTo evaluate the safety and describe the pharmacokinetics and pharmacodynamics of single-dose concizumab in healthy volunteers and patients with hemophilia A or B.\n\nIn this first human dose, phase 1, multicenter, randomized, double-blind, placebo-controlled trial escalating single i.v. (0.5-9000\u00a0\u03bcg\u00a0kg(-1) ) or s.c. (50-3000\u00a0\u03bcg\u00a0kg(-1) ) doses of concizumab were administered to healthy volunteers (n\u00a0=\u00a028) and hemophilia patients (n\u00a0=\u00a024).\n\nConcizumab had a favorable safety profile after single i.v. or s.c. administration. There were no serious adverse events and no anti-concizumab antibodies. No clinically relevant changes in platelets, prothrombin time, activated partial thromboplastin time, fibrinogen, or antithrombin were found. A dose-dependent procoagulant effect of concizumab was seen as increased levels of D-dimers and prothrombin fragment 1\u00a0+\u00a02. Nonlinear pharmacokinetics of concizumab was observed due to target-mediated clearance. A maximum mean AUC0-\u221e of 33\u00a0960\u00a0h\u00a0\u03bcg\u00a0mL(-1) and a maximum mean concentration of 247\u00a0\u03bcg\u00a0mL(-1) was measured at the highest dose.\n\nConcizumab showed a favorable safety profile after i.v. or s.c. administration and nonlinear pharmacokinetics was observed due to target-mediated clearance. A concentration-dependent procoagulant effect of concizumab was observed, supporting further study into the potential use of s.c. concizumab for hemophilia treatment.", "PMID": "25641556"}, {"title": "A bispecific antibody mimicking factor VIII in hemophilia A therapy.", "abstract": "Serious issues in current hemostatic treatment of hemophilia A are the requirement for frequent intravenous administrations of factor (F) VIII, FVIII inhibitor development, and hemostatic treatment for patients with this inhibitor. For the purpose of overcoming these challenges, the FVIIIa-substituting bispecific antibody against FIXa/FX (ACE910, INN emicizumab) was produced. Emicizumab demonstrated marked hemostatic effects on both ongoing and spontaneous joint bleeding in the acquired hemophilia A primate model. The clinical phase 1 study designed to assess the pharmacokinetics, pharmacodynamics and safety of emicizumab has been initiated. Severe emicizumab-related adverse events were minimal. The t1/2 was approximately 30 days, and bleeding events were significantly decreased by weekly subcutaneous administration in severe hemophilia A patients, independently of the presence of the inhibitor. Currently, the phase 1/2 extension study is ongoing. We anticipate that emicizumab will show the benefits of prophylactic efficacy with subcutaneous administration at a much lower frequency.", "PMID": "27384849"}, {"title": "WFH 2016 World Congress Abstracts, Orlando, Florida, USA, July 24-28, 2016.", "abstract": "", "PMID": "27396676"}, {"title": "Abstracts of the 57th Annual Scientific Meeting of the British Society for Haematology, 27-29 March 2017, Brighton, UK.", "abstract": "", "PMID": "28297073"}, {"title": "Targeting of Antithrombin in Hemophilia A or B with RNAi Therapy.", "abstract": "Current hemophilia treatment involves frequent intravenous infusions of clotting factors, which is associated with variable hemostatic protection, a high treatment burden, and a risk of the development of inhibitory alloantibodies. Fitusiran, an investigational RNA interference (RNAi) therapy that targets antithrombin (encoded by SERPINC1), is in development to address these and other limitations.\n\nIn this phase 1 dose-escalation study, we enrolled 4 healthy volunteers and 25 participants with moderate or severe hemophilia A or B who did not have inhibitory alloantibodies. Healthy volunteers received a single subcutaneous injection of fitusiran (at a dose of 0.03 mg per kilogram of body weight) or placebo. The participants with hemophilia received three injections of fitusiran administered either once weekly (at a dose of 0.015, 0.045, or 0.075 mg per kilogram) or once monthly (at a dose of 0.225, 0.45, 0.9, or 1.8 mg per kilogram or a fixed dose of 80 mg). The study objectives were to assess the pharmacokinetic and pharmacodynamic characteristics and safety of fitusiran.\n\nNo thromboembolic events were observed during the study. The most common adverse events were mild injection-site reactions. Plasma levels of fitusiran increased in a dose-dependent manner and showed no accumulation with repeated administration. The monthly regimen induced a dose-dependent mean maximum antithrombin reduction of 70 to 89% from baseline. A reduction in the antithrombin level of more than 75% from baseline resulted in median peak thrombin values at the lower end of the range observed in healthy participants.\n\nOnce-monthly subcutaneous administration of fitusiran resulted in dose-dependent lowering of the antithrombin level and increased thrombin generation in participants with hemophilia A or B who did not have inhibitory alloantibodies. (Funded by Alnylam Pharmaceuticals; ClinicalTrials.gov number, NCT02035605 .).", "PMID": "28691885"}, {"title": "Emicizumab Prophylaxis in Hemophilia A with Inhibitors.", "abstract": "", "PMID": "29188944"}, {"title": "Emicizumab Prophylaxis in Hemophilia A with Inhibitors.", "abstract": "", "PMID": "29188947"}, {"title": "Long-term safety and efficacy of emicizumab in a phase 1/2 study in patients with hemophilia A with or without inhibitors.", "abstract": "Emicizumab (ACE910), a recombinant humanized bispecific monoclonal antibody, provides factor VIII (FVIII) cofactor bridging function to restore hemostasis in people with hemophilia A. In a phase 1 trial involving 18 Japanese patients with severe hemophilia A, once-weekly subcutaneous administration of emicizumab 0.3, 1, or 3 mg/kg (cohorts 1, 2, and 3, respectively) was well tolerated and substantially reduced annualized bleeding rates (ABRs) in the presence or absence of FVIII inhibitors. The current study represents an open-label, long-term extension of the previously reported 12-week phase 1 study, in which 16 of 18 patients continued to receive emicizumab for up to 33.3 months. Long-term emicizumab treatment was well tolerated, with no thromboembolic events reported and no neutralizing antiemicizumab antibodies developing during the course of the study. Plasma concentrations of emicizumab increased in a dose-proportional manner, with activated partial thromboplastin times remaining short. In cohorts 1, 2, and 3, respectively, median ABRs remained low at 1.4, 0.2, and 0 compared with 4.4, 0, and 0 in the 12-week study. Overall, 8 patients experienced no bleeding events (6 patients with and 2 patients without FVIII inhibitors); dose up-titration resulted in further reduction in ABRs in patients with suboptimal bleeding control; and the episodic use of clotting factors to control bleeding was reduced. In conclusion, long-term emicizumab treatment demonstrated a favorable safety profile with encouraging efficacy, irrespective of the presence of FVIII inhibitors, in patients with hemophilia A. This study was registered at www.clinicaltrials.jp as #JapicCTI-132195.", "PMID": "29296836"}], "labels": [{"PMID": "22563084", "label": "excluded"}, {"PMID": "24568891", "label": "excluded"}, {"PMID": "25641556", "label": "excluded"}, {"PMID": "27384849", "label": "excluded"}, {"PMID": "27396676", "label": "excluded"}, {"PMID": "28297073", "label": "excluded"}, {"PMID": "28691885", "label": "excluded"}, {"PMID": "29188944", "label": "excluded"}, {"PMID": "29188947", "label": "excluded"}, {"PMID": "29296836", "label": "excluded"}]}
{"metadata": {"review_pmid": "38411248"}, "inputs": {"background": "Cystic fibrosis (CF) is a life-limiting genetic condition, affecting over 90,000 people worldwide. CF affects several organs in the body, but airway damage has the most profound impact on quality of life (QoL) and survival. Causes of lower airway infection in people with CF are, most notably, Staphylococcus aureus in the early course of the disease and Pseudomonas aeruginosa at a later stage. Macrolide antibiotics, e.g. azithromycin and clarithromycin, are usually taken orally, have a broad spectrum of action against gram-positive (e.g. S aureus) and some gram-negative bacteria (e.g. Haemophilus influenzae), and may have a modifying role in diseases involving airway infection and inflammation such as CF. They are well-tolerated and relatively inexpensive, but widespread use has resulted in the emergence of resistant bacteria. This is an updated review.", "objectives": "To assess the potential effects of macrolide antibiotics on clinical status in terms of benefit and harm in people with CF. If benefit was demonstrated, we aimed to assess the optimal type, dose and duration of macrolide therapy.", "selection criteria": "We included randomised controlled trials of macrolide antibiotics in adults and children with CF. We compared them to: placebo; another class of antibiotic; another macrolide antibiotic; or the same macrolide antibiotic at a different dose or type of administration."}, "context": [{"title": "Effect of long term treatment with azithromycin on disease parameters in cystic fibrosis: a randomised trial.", "abstract": "Relentless chronic pulmonary inflammation is the major contributor to morbidity and mortality in patients with cystic fibrosis (CF). While immunomodulating therapies such as prednisolone and ibuprofen may be beneficial, their use is limited by side effects. Macrolides have immunomodulatory properties and long term use dramatically improves prognosis in diffuse panbronchiolitis, a condition with features in common with the lung disease of CF.\n\nTo determine if azithromycin (AZM) improves clinical parameters and reduces inflammation in patients with CF, a 3 month prospective randomised double blind, placebo controlled study of AZM (250 mg/day) was undertaken in adults with CF. Monthly assessment included lung function, weight, and quality of life (QOL). Blood and sputum collection assessed systemic inflammation and changes in bacterial flora. Respiratory exacerbations were treated according to the policy of the CF Unit.\n\nSixty patients were recruited (29 men) of mean (SD) age 27.9 (6.5) years and initial forced expiratory volume in 1 second (FEV1) 56.6 (22.3)% predicted. FEV1% and forced vital capacity (FVC)% predicted were maintained in the AZM group while in the placebo group there was a mean (SE) decline of -3.62 (1.78)% (p=0.047) and -5.73 (1.66)% (p=0.001), respectively. Fewer courses of intravenous antibiotics were used in patients on AZM (0.37 v 1.13, p=0.016). Median C reactive protein (CRP) levels declined in the AZM group from 10 to 5.4 mg/ml but remained constant in the placebo group (p<0.001). QOL improved over time in patients on AZM and remained unchanged in those on placebo (p=0.035).\n\nAZM in adults with CF significantly improved QOL, reduced CRP levels and the number of respiratory exacerbations, and reduced the rate of decline in lung function. Long term AZM may have a significant impact on morbidity and mortality in patients with CF. Further studies are required to define frequency of dosing and duration of benefit.", "PMID": "11867823"}, {"title": "Long term azithromycin in children with cystic fibrosis: a randomised, placebo-controlled crossover trial.", "abstract": "The macrolide antibiotic azithromycin has anti-inflammatory properties potentially beneficial in cystic fibrosis. Since findings of open pilot studies seemed to show clinical benefit, we undertook a formal trial.\n\n41 children with cystic fibrosis, aged 8-18 years, and with a median forced expiratory volume in 1 s (FEV1) of 61% (range 33-80%) participated in a 15-month randomised double-blind, placebo-controlled crossover trial. They received either azithromycin (bodyweight < or =40 kg: 250 mg daily, >40 kg: 500 mg daily) or placebo for 6 months. After 2 months of washout, the treatments were crossed over. The primary outcome was median relative difference in FEV1 between azithromycin and placebo treatment periods. Sputum cultures, sputum interleukin 8 and neutrophil elastase, exercise testing, quality of life, antibiotic use, and pulmonary exacerbation rates were secondary outcome measures. Side-effects were assessed by pure tone audiometry and liver function tests. Analysis was by intention-to-treat.\n\nMedian relative difference in FEV1 between azithromycin and placebo was 5.4% (95% CI 0.8-10.5). 13 of 41 patients improved by more than 13% and five of 41 deteriorated by more than 13% (p=0.059). Forced vital capacity and mid-expiratory flow did not significantly change overall. 17 of 41 patients had 24 fewer oral antibiotic courses when on azithromycin than when taking placebo, and five had six extra courses (p=0.005). Sputum bacterial densities, inflammatory markers, exercise tolerance, and subjective well-being did not change. There were no noticeable side-effects.\n\nA 4-6-month trial of azithromycin is justified in children with cystic fibrosis who do not respond to conventional treatment. The mechanism of action remains unknown.", "PMID": "12383667"}, {"title": "Long term azithromycin in children with cystic fibrosis: a randomised, placebo-controlled crossover trial.", "abstract": "The macrolide antibiotic azithromycin has anti-inflammatory properties potentially beneficial in cystic fibrosis. Since findings of open pilot studies seemed to show clinical benefit, we undertook a formal trial.\n\n41 children with cystic fibrosis, aged 8-18 years, and with a median forced expiratory volume in 1 s (FEV1) of 61% (range 33-80%) participated in a 15-month randomised double-blind, placebo-controlled crossover trial. They received either azithromycin (bodyweight < or =40 kg: 250 mg daily, >40 kg: 500 mg daily) or placebo for 6 months. After 2 months of washout, the treatments were crossed over. The primary outcome was median relative difference in FEV1 between azithromycin and placebo treatment periods. Sputum cultures, sputum interleukin 8 and neutrophil elastase, exercise testing, quality of life, antibiotic use, and pulmonary exacerbation rates were secondary outcome measures. Side-effects were assessed by pure tone audiometry and liver function tests. Analysis was by intention-to-treat.\n\nMedian relative difference in FEV1 between azithromycin and placebo was 5.4% (95% CI 0.8-10.5). 13 of 41 patients improved by more than 13% and five of 41 deteriorated by more than 13% (p=0.059). Forced vital capacity and mid-expiratory flow did not significantly change overall. 17 of 41 patients had 24 fewer oral antibiotic courses when on azithromycin than when taking placebo, and five had six extra courses (p=0.005). Sputum bacterial densities, inflammatory markers, exercise tolerance, and subjective well-being did not change. There were no noticeable side-effects.\n\nA 4-6-month trial of azithromycin is justified in children with cystic fibrosis who do not respond to conventional treatment. The mechanism of action remains unknown.", "PMID": "12383667"}, {"title": "Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial.", "abstract": "Treatment strategies for cystic fibrosis (CF) lung disease include antibiotics, mucolytics, and anti-inflammatory therapies. Increasing evidence suggests that macrolide antibiotics might be beneficial in patients with CF.\n\nTo determine if an association between azithromycin use and pulmonary function exists in patients with CF.\n\nA multicenter, randomized, double-blind, placebo-controlled trial conducted from December 15, 2000, to May 2, 2002, at 23 CF care centers in the United States.\n\nOf the 251 screened participants with a diagnosis of CF, 185 (74%) were randomized. Eligibility criteria included age 6 years or older, infection with Pseudomonas aeruginosa for 1 or more years, and a forced expiratory volume in 1 second (FEV1) of 30% or more. Participants were stratified by FEV1 (> or =60% predicted vs <60% predicted), weight of less than 40 kg vs 40 kg or more, and CF center.\n\nThe active group (n = 87) received 250 mg (weight <40 kg) or 500 mg (weight > or =40 kg) of oral azithromycin 3 days a week for 168 days; placebo group (n = 98) received identically packaged tablets.\n\nChange in FEV1 from day 0 to completion of therapy at day 168 and determination of safety. Secondary outcomes included pulmonary exacerbations and weight gain.\n\nThe azithromycin group had a mean 0.097-L (SD, 0.26) increase in FEV1 at day 168 compared with 0.003 L (SD, 0.23) in the placebo group (mean difference, 0.094 L; 95% confidence interval [CI], 0.023-0.165; P =.009). Nausea occurred in 17% more participants in the azithromycin group (P =.01), diarrhea in 15% more (P =.009), and wheezing in 13% more (P =.007). Participants in the azithromycin group had less risk of experiencing an exacerbation than participants in the placebo group (hazard ratio, 0.65; 95% CI, 0.44-0.95; P =.03) and weighed at the end of the study an average 0.7 kg more than participants receiving placebo (95% CI, 0.1-1.4 kg; P =.02).\n\nAzithromycin treatment was associated with improvement in clinically relevant end points and should be considered for patients with CF who are 6 years or older and chronically infected with P aeruginosa.", "PMID": "14519709"}, {"title": "Effect of long-term treatment with azithromycin on disease parameters in cystic fibrosis.", "abstract": "", "PMID": "14679744"}, {"title": "Effect of clarithromycin on airway obstruction and inflammatory markers in induced sputum in cystic fibrosis: a pilot study.", "abstract": "To determine whether macrolide antibiotics improve pulmonary function and decrease airway inflammation in cystic fibrosis (CF), we treated 10 patients (females; aged 19-26 years, all colonized with P. aeruginosa, none with atypical Mycobacteria) with 3 weeks of placebo, followed by 6 weeks of clarithromycin (500 mg BID) in a single-blind prospective study. We also determined the safety of sputum induction and the reproducibility of assessing inflammatory markers in induced sputum. Subjects performed spirometry and underwent sputum induction (12-min inhalation of 3% saline) at 3-week intervals. We found that sputum induction was well-tolerated. We also found that the reproducibility was high for neutrophil (PMN) number (R = 0.87, P = 0.009), interleukin (IL)-8 (R = 0.73, P < 0.05, free neutrophil elastase (NE) (R = 0.82, P < 0.05), and myeloperoxidase (MPO) levels (R = 0.86, P < 0.05), but was less so for tumor necrosis factor (TNF)-alpha (R = -0.15, P = 0.7). We found no significant difference in pulmonary function after 6 weeks of treatment with clarithromycin (FEV(1) (% predicted) (mean +/- SEM), 2.2 +/- 0.9 (60 +/- 24%) vs. 2.3 +/- 1 (61 +/- 29%)), and no significant differences in any of the inflammatory indices measured. The median (and range) values before and after treatment for indices of airway inflammation in the induced sputum samples were: for PMNs, 8 (1-326) and 21 (0.2 -175) x 10(6) cells/mL sputum; for IL-8, 156 (24-656) and 202 (16-680) ng/mL; for free NE, 260 (31-1,264) and 237 (49-1,048) microg/mL; for TNF-alpha, 20 (7-128) and 35 (17-87) pg/mL; and for MPO, 169 (13-960) and 195 (14-816) microg/mL. We conclude that clarithromycin is not uniformly effective in improving airway obstruction or in decreasing airway inflammation in patients with CF.", "PMID": "11416873"}, {"title": "Long term azithromycin therapy in cystic fibrosis patients: a study on drug levels and sputum properties.", "abstract": "Following reports on the treatment of diffuse panbronchiolitis (DPB), recent studies demonstrate that long term therapy with azithromycin (AZM) is effective in cystic fibrosis (CF) patients. However, the underlying mechanisms remain uncertain. Some macrolides, including AZM, display inhibition of virulence factors and other antipseudomonal effects at subinhibitory levels in vitro.\n\nDrug doses used for CF and DPB therapy were investigated to determine whether they achieve corresponding sputum drug levels in CF patients in vivo.\n\nIn an open, prospective study, 14 CF patients with chronic Pseudomonas aeruginosa airway infection received 250 mg AZM either daily ('high dose') or twice weekly ('low dose') for 12 weeks. Viscoelasticity of sputum was assessed by magnetic microrheology.\n\nAZM accumulated in sputum by two orders of magnitude over a period of four weeks. In the following steady state, median AZM concentrations in sputum were 9.5 microg/mL (0.6 to 79.3 microg/mL, interquartiles 1.4 to 33.4 microg/mL) and 0.5 microg/mL (range less than 0.1 [below detection level] to 5.2 microg/mL, interquartiles 0.2 to 1.4 microg/mL) in the high and low dose groups, respectively. Viscoelasticity improved in all patients but one.\n\nThe findings suggest that antipseudomonal activity has to be considered among the potential mechanisms of macrolide therapy. Further, viscoelasticity may be a valuable parameter in future clinical trials.", "PMID": "15045047"}, {"title": "Anti-inflammatory and immunomodulating effects of clarithromycin in patients with cystic fibrosis lung disease.", "abstract": "Macrolide antibiotics are widely used in the treatment of suppurative lung diseases including cystic fibrosis (CF), the most common inherited fatal disease in the Caucasian population. This condition is characterized by secondary Pseudomonas infection resulting in neutrophil infiltration within the airways. The aim of the study was to investigate the evolution of inflammatory process in CF patients receiving long-term clarithromycin therapy.\n\nTwenty-seven CF patients (mean age, 12 years) were enrolled into the study. Beside the basic therapy the patients were treated with clarithromycin at a dose of 250 mg every other day orally. All patients were routinely examined every 3 months. Blood and sputum were collected before clarithromycin treatment and then again 3, 6 and 12 months after the drug prescription. Cytokine concentrations (tumor necrosis factor-alpha, interleukin-8, interleukin-4, interferon-gamma) in the sputum and plasma were assayed. Peripheral blood lymphocyte response to phytohemagglutinin was also evaluated.\n\nClarithromycin treatment resulted in a marked reduction of the cytokine levels both in the sputum and plasma specimens. At the same time, the interferon-gamma/interleukin-4 ratio has been significantly elevated. In addition, a sustained increase of peripheral blood lymphocyte response to phytohemagglutinin was demonstrated. These changes were associated with a significant improvement of the lung function.\n\nThe beneficial effect of the prolonged treatment of CF patients with a 14-membered ring macrolide antibiotic clarithromycin seems to be associated not only with down-regulation of the inflammatory response, but also with immunological changes including the switch from Th2 to Th1 type response.", "PMID": "15203552"}, {"title": "Effect of macrolides on in vivo ion transport across cystic fibrosis nasal epithelium.", "abstract": "Fourteen- and 15-member macrolide antibiotics are under investigation as potential therapeutic agents for cystic fibrosis (CF). The nonantibiotic mechanisms of action of these compounds in CF are not understood. We used nasal potential difference (NPD) measurements to test the effect of macrolides on airway epithelial ion (chloride, sodium) transport of CF mice and humans. We tested clarithromycin and azithromycin in mice, and clarithromycin in patients with CF. Baseline and post-treatment NPD was measured in two strains (C57Bl6 and BalbC) of CF transmembrane regulator \"knockout\" and littermate control mice, and in DeltaF508/DeltaF508 mice. In addition, NPD was measured in 18 human subjects with CF (17 DeltaF-508/DeltaF-508 and 1 DeltaF-508/other) who were undergoing a 12-month, randomized, double-blind crossover study of the effects of clarithromycin on pulmonary outcome in CF. Neither clarithromycin nor azithromycin affected ion transport characteristics of normal or CF nasal epithelium in either mouse or humans. We conclude that the apparent beneficial effects of macrolides on pulmonary outcome in CF are not mediated by their modulation of ion transport.", "PMID": "15657462"}, {"title": "Combination antibiotic susceptibility testing to treat exacerbations of cystic fibrosis associated with multiresistant bacteria: a randomised, double-blind, controlled clinical trial.", "abstract": "We did a randomised, double-blind, controlled clinical trial to prospectively assess whether use of combination antibiotic susceptibility testing improved clinical outcomes in patients with acute pulmonary exacerbations of cystic fibrosis who were infected with multiresistant bacteria.\n\n251 patients with cystic fibrosis who were chronically infected with multiresistant gram negative bacteria gave sputum at 3-month intervals for conventional culture and sensitivity tests and for combination antibiotic susceptibility tests using multiple combination bactericidal antibiotic testing (MCBT). Patients who developed an exacerbation of pulmonary disease were randomised to receive a 14-day course of any two blinded intravenous antibiotics chosen on the basis of either results from conventional sputum culture and sensitivity testing or the result of MCBT. The primary outcome was time from randomisation until the patient's next pulmonary exacerbation. Analysis was by intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN60187870.\n\n132 patients had a pulmonary exacerbation and were randomised during the 4.5-year study period. The time to next pulmonary exacerbation was not prolonged in the MCBT-treated group (hazard ratio 0.86 in favour of the conventionally-treated group, 95% CI 0.60-1.23, p=0.40). There was no difference between the groups in treatment failure rate. After 14 days of intravenous antibiotic therapy, changes in lung function, dyspnoea, and sputum bacterial density were similar in both groups.\n\nAntibiotic therapy directed by combination antibiotic susceptibility testing did not result in better clinical and bacteriological outcomes compared with therapy directed by standard culture and sensitivity techniques. The non-bactericidal effects of antibiotic therapy might play an important part in determining improvement in patients with cystic fibrosis pulmonary exacerbations.", "PMID": "16084254"}], "labels": [{"PMID": "11867823", "label": "included"}, {"PMID": "12383667", "label": "included"}, {"PMID": "12383667", "label": "included"}, {"PMID": "14519709", "label": "included"}, {"PMID": "14679744", "label": "included"}, {"PMID": "11416873", "label": "excluded"}, {"PMID": "15045047", "label": "excluded"}, {"PMID": "15203552", "label": "excluded"}, {"PMID": "15657462", "label": "excluded"}, {"PMID": "16084254", "label": "excluded"}]}
{"metadata": {"review_pmid": "38375882"}, "inputs": {"background": "Obesity is considered to be a risk factor for various diseases, and its incidence has tripled worldwide since 1975. In addition to potentially being at risk for adverse health outcomes, people with overweight or obesity are often stigmatised. Behaviour change interventions are increasingly delivered as mobile health (m-health) interventions, using smartphone apps and wearables. They are believed to support healthy behaviours at the individual level in a low-threshold manner.", "objectives": "To assess the effects of integrated smartphone applications for adolescents and adults with overweight or obesity.", "selection criteria": "Participants were adolescents and adults with overweight or obesity. Eligible interventions were integrated smartphone apps using at least two behaviour change techniques. The intervention could target physical activity, cardiorespiratory fitness, weight loss, healthy diet, or self-efficacy. Comparators included no or minimal intervention (NMI), a different smartphone app, personal coaching, or usual care. Eligible studies were randomised controlled trials of any duration with a follow-up of at least three months."}, "context": [{"title": "Adherence to a smartphone application for weight loss compared to website and paper diary: pilot randomized controlled trial.", "abstract": "There is growing interest in the use of information communication technologies to treat obesity. An intervention delivered by smartphone could be a convenient, potentially cost-effective, and wide-reaching weight management strategy. Although there have been studies of texting-based interventions and smartphone applications (apps) used as adjuncts to other treatments, there are currently no randomized controlled trials (RCT) of a stand-alone smartphone application for weight loss that focuses primarily on self-monitoring of diet and physical activity.\n\nThe aim of this pilot study was to collect acceptability and feasibility outcomes of a self-monitoring weight management intervention delivered by a smartphone app, compared to a website and paper diary.\n\nA sample of 128 overweight volunteers were randomized to receive a weight management intervention delivered by smartphone app, website, or paper diary. The smartphone app intervention, My Meal Mate (MMM), was developed by the research team using an evidence-based behavioral approach. The app incorporates goal setting, self-monitoring of diet and activity, and feedback via weekly text message. The website group used an existing commercially available slimming website from a company called Weight Loss Resources who also provided the paper diaries. The comparator groups delivered a similar self-monitoring intervention to the app, but by different modes of delivery. Participants were recruited by email, intranet, newsletters, and posters from large local employers. Trial duration was 6 months. The intervention and comparator groups were self-directed with no ongoing human input from the research team. The only face-to-face components were at baseline enrollment and brief follow-up sessions at 6 weeks and 6 months to take anthropometric measures and administer questionnaires.\n\nTrial retention was 40/43 (93%) in the smartphone group, 19/42 (55%) in the website group, and 20/43 (53%) in the diary group at 6 months. Adherence was statistically significantly higher in the smartphone group with a mean of 92 days (SD 67) of dietary recording compared with 35 days (SD 44) in the website group and 29 days (SD 39) in the diary group (P<.001). Self-monitoring declined over time in all groups. In an intention-to-treat analysis using baseline observation carried forward for missing data, mean weight change at 6 months was -4.6 kg (95% CI -6.2 to -3.0) in the smartphone app group, -2.9 kg (95% CI -4.7 to -1.1) in the diary group, and -1.3 kg (95% CI -2.7 to 0.1) in the website group. BMI change at 6 months was -1.6 kg/m(2) (95% CI -2.2 to -1.1) in the smartphone group, -1.0 kg/m(2) (95% CI -1.6 to -0.4) in the diary group, and -0.5 kg/m(2) (95% CI -0.9 to 0.0) in the website group. Change in body fat was -1.3% (95% CI -1.7 to -0.8) in the smartphone group, -0.9% (95% CI -1.5 to -0.4) in the diary group, and -0.5% (95% CI -0.9 to 0.0) in the website group.\n\nThe MMM app is an acceptable and feasible weight loss intervention and a full RCT of this approach is warranted.\n\nClinicalTrials.gov NCT01744535; http://clinicaltrials.gov/ct2/show/NCT01744535 (Archived by WebCite at http://www.webcitation.org/6FEtc3PVB).", "PMID": "23587561"}, {"title": "Weight loss intervention for young adults using mobile technology: design and rationale of a randomized controlled trial - Cell Phone Intervention for You (CITY).", "abstract": "The obesity epidemic has spread to young adults, leading to significant public health implications later in adulthood. Intervention in early adulthood may be an effective public health strategy for reducing the long-term health impact of the epidemic. Few weight loss trials have been conducted in young adults. It is unclear what weight loss strategies are beneficial in this population.\n\nTo describe the design and rationale of the NHLBI-sponsored Cell Phone Intervention for You (CITY) study, which is a single center, randomized three-arm trial that compares the impact on weight loss of 1) a behavioral intervention that is delivered almost entirely via cell phone technology (Cell Phone group); and 2) a behavioral intervention delivered mainly through monthly personal coaching calls enhanced by self-monitoring via cell phone (Personal Coaching group), each compared to 3) a usual care, advice-only control condition.\n\nA total of 365 community-dwelling overweight/obese adults aged 18-35 years were randomized to receive one of these three interventions for 24 months in parallel group design. Study personnel assessing outcomes were blinded to group assignment. The primary outcome is weight change at 24 [corrected] months. We hypothesize that each active intervention will cause more weight loss than the usual care condition. Study completion is anticipated in 2014.\n\nIf effective, implementation of the CITY interventions could mitigate the alarming rates of obesity in young adults through promotion of weight loss. ClinicalTrial.gov: NCT01092364.", "PMID": "24462568"}, {"title": "Weight loss intervention for young adults using mobile technology: design and rationale of a randomized controlled trial - Cell Phone Intervention for You (CITY).", "abstract": "The obesity epidemic has spread to young adults, leading to significant public health implications later in adulthood. Intervention in early adulthood may be an effective public health strategy for reducing the long-term health impact of the epidemic. Few weight loss trials have been conducted in young adults. It is unclear what weight loss strategies are beneficial in this population.\n\nTo describe the design and rationale of the NHLBI-sponsored Cell Phone Intervention for You (CITY) study, which is a single center, randomized three-arm trial that compares the impact on weight loss of 1) a behavioral intervention that is delivered almost entirely via cell phone technology (Cell Phone group); and 2) a behavioral intervention delivered mainly through monthly personal coaching calls enhanced by self-monitoring via cell phone (Personal Coaching group), each compared to 3) a usual care, advice-only control condition.\n\nA total of 365 community-dwelling overweight/obese adults aged 18-35 years were randomized to receive one of these three interventions for 24 months in parallel group design. Study personnel assessing outcomes were blinded to group assignment. The primary outcome is weight change at 24 [corrected] months. We hypothesize that each active intervention will cause more weight loss than the usual care condition. Study completion is anticipated in 2014.\n\nIf effective, implementation of the CITY interventions could mitigate the alarming rates of obesity in young adults through promotion of weight loss. ClinicalTrial.gov: NCT01092364.", "PMID": "24462568"}, {"title": "Adaptive intervention design in mobile health: Intervention design and development in the Cell Phone Intervention for You trial.", "abstract": "The obesity epidemic has spread to young adults, and obesity is a significant risk factor for cardiovascular disease. The prominence and increasing functionality of mobile phones may provide an opportunity to deliver longitudinal and scalable weight management interventions in young adults. The aim of this article is to describe the design and development of the intervention tested in the Cell Phone Intervention for You study and to highlight the importance of adaptive intervention design that made it possible. The Cell Phone Intervention for You study was a National Heart, Lung, and Blood Institute-sponsored, controlled, 24-month randomized clinical trial comparing two active interventions to a usual-care control group. Participants were 365 overweight or obese (body mass index\u226525\u2009kg/m2) young adults.\n\nBoth active interventions were designed based on social cognitive theory and incorporated techniques for behavioral self-management and motivational enhancement. Initial intervention development occurred during a 1-year formative phase utilizing focus groups and iterative, participatory design. During the intervention testing, adaptive intervention design, where an intervention is updated or extended throughout a trial while assuring the delivery of exactly the same intervention to each cohort, was employed. The adaptive intervention design strategy distributed technical work and allowed introduction of novel components in phases intended to help promote and sustain participant engagement. Adaptive intervention design was made possible by exploiting the mobile phone's remote data capabilities so that adoption of particular application components could be continuously monitored and components subsequently added or updated remotely.\n\nThe cell phone intervention was delivered almost entirely via cell phone and was always-present, proactive, and interactive-providing passive and active reminders, frequent opportunities for knowledge dissemination, and multiple tools for self-tracking and receiving tailored feedback. The intervention changed over 2 years to promote and sustain engagement. The personal coaching intervention, alternatively, was primarily personal coaching with trained coaches based on a proven intervention, enhanced with a mobile application, but where all interactions with the technology were participant-initiated.\n\nThe complexity and length of the technology-based randomized clinical trial created challenges in engagement and technology adaptation, which were generally discovered using novel remote monitoring technology and addressed using the adaptive intervention design. Investigators should plan to develop tools and procedures that explicitly support continuous remote monitoring of interventions to support adaptive intervention design in long-term, technology-based studies, as well as developing the interventions themselves.", "PMID": "26229119"}, {"title": "Cell phone intervention for you (CITY): A randomized, controlled trial of behavioral weight loss intervention for young adults using mobile technology.", "abstract": "To determine the effect on weight of two mobile technology-based (mHealth) behavioral weight loss interventions in young adults.\n\nRandomized, controlled comparative effectiveness trial in 18- to 35-year-olds with BMI\u2009\u2265\u200925 kg/m(2) (overweight/obese), with participants randomized to 24 months of mHealth intervention delivered by interactive smartphone application on a cell phone (CP); personal coaching enhanced by smartphone self-monitoring (PC); or Control.\n\nThe 365 randomized participants had mean baseline BMI of 35 kg/m(2) . Final weight was measured in 86% of participants. CP was not superior to Control at any measurement point. PC participants lost significantly more weight than Controls at 6 months (net effect -1.92 kg [CI -3.17, -0.67], P\u2009=\u20090.003), but not at 12 and 24 months.\n\nDespite high intervention engagement and study retention, the inclusion of behavioral principles and tools in both interventions, and weight loss in all treatment groups, CP did not lead to weight loss, and PC did not lead to sustained weight loss relative to Control. Although mHealth solutions offer broad dissemination and scalability, the CITY results sound a cautionary note concerning intervention delivery by mobile applications. Effective intervention may require the efficiency of mobile technology, the social support and human interaction of personal coaching, and an adaptive approach to intervention design.", "PMID": "26530929"}, {"title": "Cell phone intervention for you (CITY): A randomized, controlled trial of behavioral weight loss intervention for young adults using mobile technology.", "abstract": "To determine the effect on weight of two mobile technology-based (mHealth) behavioral weight loss interventions in young adults.\n\nRandomized, controlled comparative effectiveness trial in 18- to 35-year-olds with BMI\u2009\u2265\u200925 kg/m(2) (overweight/obese), with participants randomized to 24 months of mHealth intervention delivered by interactive smartphone application on a cell phone (CP); personal coaching enhanced by smartphone self-monitoring (PC); or Control.\n\nThe 365 randomized participants had mean baseline BMI of 35 kg/m(2) . Final weight was measured in 86% of participants. CP was not superior to Control at any measurement point. PC participants lost significantly more weight than Controls at 6 months (net effect -1.92 kg [CI -3.17, -0.67], P\u2009=\u20090.003), but not at 12 and 24 months.\n\nDespite high intervention engagement and study retention, the inclusion of behavioral principles and tools in both interventions, and weight loss in all treatment groups, CP did not lead to weight loss, and PC did not lead to sustained weight loss relative to Control. Although mHealth solutions offer broad dissemination and scalability, the CITY results sound a cautionary note concerning intervention delivery by mobile applications. Effective intervention may require the efficiency of mobile technology, the social support and human interaction of personal coaching, and an adaptive approach to intervention design.", "PMID": "26530929"}, {"title": "Smartphone Technology and Text Messaging for Weight Loss in Young Adults: A Randomized Controlled Trial.", "abstract": "Using smartphone technology and text messaging for health is a growing field. This type of technology is well integrated into the lives of young adults. However, few studies have tested the effect of this type of technology to promote weight loss in young adults OBJECTIVE:: The purpose of this study is to test the effectiveness of a behaviorally based smartphone application for weight loss combined with text messaging from a health coach on weight, body mass index (BMI), and waist circumference in young adults as compared with a control condition.\n\nSixty-two young adults, aged 18 to 25 years, were randomized to receive (1) a smartphone application + health coach intervention and counseling sessions or (2) control condition with a counseling session. All outcome measures were tested at baseline and 3 months. These included weight, BMI, waist circumference, dietary habits, physical activity habits, and self-efficacy for healthy eating and physical activity.\n\nThe sample was 71% female and 39% white, with an average age of 20 years and average BMI of 28.5 kg/m. Participants in the smartphone + health coach group lost significantly more weight (P = .026) and had a significant reduction in both BMI (P = .024) and waist circumference (P < .01) compared with controls.\n\nThe results of this weight loss trial support the use of smartphone technology and feedback from a health coach on improving weight in a group of diverse young adults.", "PMID": "26646593"}, {"title": "Tweets, Apps, and Pods: Results of the 6-month Mobile Pounds Off Digitally (Mobile POD) randomized weight-loss intervention among adults.", "abstract": "Previous interventions have shown promising results using theory-based podcasts to deliver a behavioral weight-loss intervention.\n\nThe objective of our study was to examine whether a combination of podcasting, mobile support communication, and mobile diet monitoring can assist people in weight loss.\n\nIn this 6-month, minimal contact intervention, overweight (n = 96, body mass index 32.6 kg/m(2)) adults were recruited through television advertisements and email listservs and randomly assigned to Podcast-only or Podcast+Mobile groups. Both groups received 2 podcasts per week for 3 months and 2 minipodcasts per week for months 3-6. In addition to the podcasts, the Podcast+Mobile group was also instructed to use a diet and physical activity monitoring application (app) on their mobile device and to interact with study counselors and other participants on Twitter.\n\nWeight loss did not differ by group at 6 months: mean -2.7% (SD 5.6%) Podcast+Mobile, n = 47; mean -2.7% (SD 5.1%) Podcast, n = 49; P = .98. Days/week of reported diet monitoring did not differ between Podcast+Mobile (mean 2.3, SD 1.9 days/week) and Podcast groups (mean 1.9, SD 1.7 days/week; P = .28) but method of monitoring did differ. Podcast+Mobile participants were 3.5 times more likely than the Podcast group to use an app to monitor diet (P = .01), whereas the majority of Podcast participants reported using the Web (14/41, 34%) or paper (12/41, 29%). There were more downloads per episode in the Podcast+Mobile group (1.4/person) than in the Podcast group (1.1/person; P < .001). The number of podcasts participants reported downloading over the 6-month period was significantly moderately correlated with weight loss in both the Podcast+Mobile (r = -.46, P = .001) and the Podcast (r = -.53, P < .001) groups. Podcast+Mobile participants felt more user control at 3 months (P = .02), but not at 6 months, and there was a trend (P = .06) toward greater elaboration among Podcast+Mobile participants. There were significant differences in reported source of social support between groups. More Podcast participants relied on friends (11/40, 28% vs 4/40, 10%; P = .045) whereas Podcast+Mobile participants relied on online sources (10/40, 25% vs 0/40; P = .001).\n\nResults confirm and extend previous findings showing a minimally intensive weight-loss intervention can be delivered via podcast, but prompting and mobile communication via Twitter and monitoring app without feedback did not enhance weight loss.\n\nClinicaltrials.gov NCT01139255; http://clinicaltrials.gov/ct2/show/NCT01139255 (Archived by WebCite at http://www.webcitation.org/625OjhiDy).", "PMID": "22186428"}, {"title": "Tweets, Apps, and Pods: Results of the 6-month Mobile Pounds Off Digitally (Mobile POD) randomized weight-loss intervention among adults.", "abstract": "Previous interventions have shown promising results using theory-based podcasts to deliver a behavioral weight-loss intervention.\n\nThe objective of our study was to examine whether a combination of podcasting, mobile support communication, and mobile diet monitoring can assist people in weight loss.\n\nIn this 6-month, minimal contact intervention, overweight (n = 96, body mass index 32.6 kg/m(2)) adults were recruited through television advertisements and email listservs and randomly assigned to Podcast-only or Podcast+Mobile groups. Both groups received 2 podcasts per week for 3 months and 2 minipodcasts per week for months 3-6. In addition to the podcasts, the Podcast+Mobile group was also instructed to use a diet and physical activity monitoring application (app) on their mobile device and to interact with study counselors and other participants on Twitter.\n\nWeight loss did not differ by group at 6 months: mean -2.7% (SD 5.6%) Podcast+Mobile, n = 47; mean -2.7% (SD 5.1%) Podcast, n = 49; P = .98. Days/week of reported diet monitoring did not differ between Podcast+Mobile (mean 2.3, SD 1.9 days/week) and Podcast groups (mean 1.9, SD 1.7 days/week; P = .28) but method of monitoring did differ. Podcast+Mobile participants were 3.5 times more likely than the Podcast group to use an app to monitor diet (P = .01), whereas the majority of Podcast participants reported using the Web (14/41, 34%) or paper (12/41, 29%). There were more downloads per episode in the Podcast+Mobile group (1.4/person) than in the Podcast group (1.1/person; P < .001). The number of podcasts participants reported downloading over the 6-month period was significantly moderately correlated with weight loss in both the Podcast+Mobile (r = -.46, P = .001) and the Podcast (r = -.53, P < .001) groups. Podcast+Mobile participants felt more user control at 3 months (P = .02), but not at 6 months, and there was a trend (P = .06) toward greater elaboration among Podcast+Mobile participants. There were significant differences in reported source of social support between groups. More Podcast participants relied on friends (11/40, 28% vs 4/40, 10%; P = .045) whereas Podcast+Mobile participants relied on online sources (10/40, 25% vs 0/40; P = .001).\n\nResults confirm and extend previous findings showing a minimally intensive weight-loss intervention can be delivered via podcast, but prompting and mobile communication via Twitter and monitoring app without feedback did not enhance weight loss.\n\nClinicaltrials.gov NCT01139255; http://clinicaltrials.gov/ct2/show/NCT01139255 (Archived by WebCite at http://www.webcitation.org/625OjhiDy).", "PMID": "22186428"}, {"title": "A smartphone-supported weight loss program: design of the ENGAGED randomized controlled trial.", "abstract": "Obesity remains a major public health challenge, demanding cost-effective and scalable weight management programs. Delivering key treatment components via mobile technology offers a potential way to reduce expensive in-person contact, thereby lowering the cost and burden of intensive weight loss programs. The ENGAGED study is a theory-guided, randomized controlled trial designed to examine the feasibility and efficacy of an abbreviated smartphone-supported weight loss program.\n\nNinety-six obese adults (BMI 30-39.9 kg/m2) will be randomized to one of three treatment conditions: (1) standard behavioral weight loss (STND), (2) technology-supported behavioral weight loss (TECH); or (3) self-guided behavioral weight loss (SELF). All groups will aim to achieve a 7% weight loss goal by reducing calorie and fat intake and progressively increasing moderate intensity physical activity to 175 minutes/week. STND and TECH will attend 8 group sessions and receive regular coaching calls during the first 6 months of the intervention; SELF will receive the Group Lifestyle Balance Program DVD's and will not receive coaching calls. During months 1-6, TECH will use a specially designed smartphone application to monitor dietary intake, body weight, and objectively measured physical activity (obtained from a Blue-tooth enabled accelerometer). STND and SELF will self-monitor on paper diaries. Linear mixed modeling will be used to examine group differences on weight loss at months 3, 6, and 12. Self-monitoring adherence and diet and activity goal attainment will be tested as mediators.\n\nENGAGED is an innovative weight loss intervention that integrates theory with emerging mobile technologies. We hypothesize that TECH, as compared to STND and SELF, will result in greater weight loss by virtue of improved behavioral adherence and goal achievement.\n\nNCT01051713.", "PMID": "23194256"}], "labels": [{"PMID": "23587561", "label": "included"}, {"PMID": "24462568", "label": "included"}, {"PMID": "24462568", "label": "included"}, {"PMID": "26229119", "label": "included"}, {"PMID": "26530929", "label": "included"}, {"PMID": "26530929", "label": "included"}, {"PMID": "26646593", "label": "included"}, {"PMID": "22186428", "label": "excluded"}, {"PMID": "22186428", "label": "excluded"}, {"PMID": "23194256", "label": "excluded"}]}
{"metadata": {"review_pmid": "38372447"}, "inputs": {"background": "Infliximab is a monoclonal antibody that binds and neutralises tumour necrosis factor-alpha (TNF-\u03b1) which is present in high levels in the blood serum, mucosa and stool of patients with Crohn's disease.", "objectives": "To determine the efficacy and safety of infliximab for maintaining remission in patients with Crohn's disease.", "selection criteria": "Randomised controlled trials (RCTs) in which infliximab was compared to placebo or another active comparator for maintenance, remission, or response in patients with Crohn's disease."}, "context": [{"title": "Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn's disease.", "abstract": "Infliximab, an anti-tumor necrosis factor monoclonal antibody, rapidly reduces signs and symptoms of active Crohn's disease. The aim of this study was to determine whether repeated infusions of infliximab would effectively and safely maintain the remitting benefit.\n\nThe efficacy, safety, pharmacokinetics, and immunogenicity of 4 repeated treatments with 10 mg/kg infliximab given every 8 weeks were compared with the effects of placebo in a randomized, double-blind, placebo-controlled, parallel group trial. Seventy-three patients with active Crohn's disease who had not adequately responded to conventional therapies and then had demonstrated a clinical response (>/=70-point decrease in the Crohn's Disease Activity Index) to an initial infusion of infliximab (or placebo) were studied.\n\nRetreatment with infliximab maintained the clinical benefit through the retreatment period and 8 weeks after the last infusion in nearly all patients retreated with infliximab. Median values for Crohn's Disease Activity Index, inflammatory bowel disease questionnaire (a quality of life measurement), and serum C-reactive protein concentration were maintained at remission levels with infliximab retreatment, but not with placebo retreatment. Retreatment with infliximab every 8 weeks maintained serum infliximab concentration and was well tolerated with a low incidence of immunogenicity. One case of lymphoma and 1 case of suspected lupus were reported; the complete long-term safety profile of infliximab requires additional clinical investigation.\n\nLong-term treatment with infliximab showed efficacy and tolerability in managing symptoms of patients with active Crohn's disease not responding to conventional treatments.", "PMID": "10500056"}, {"title": "Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial.", "abstract": "We did a randomised controlled trial to assess the benefit of maintenance infliximab therapy in patients with active Crohn's disease who respond to a single infusion of infliximab.\n\n573 patients with a score of at least 220 on the Crohn's disease activity index (CDAI) received a 5 mg/kg intravenous infusion of infliximab at week 0. After assessment of response at week 2, patients were randomly assigned repeat infusions of placebo at weeks 2 and 6 and then every 8 weeks thereafter until week 46 (group I), repeat infusions of 5 mg/kg infliximab at the same timepoints (group II), or 5 mg/kg infliximab at weeks 2 and 6 followed by 10 mg/kg (group III). The prespecified co-primary endpoints were the proportion of patients who responded at week 2 and were in remission (CDAI <150) at week 30 and the time to loss of response up to week 54 in patients who responded. Analyses of the co-primary endpoints were by intention to treat.\n\n335 (58%) patients responded to a single infusion of infliximab within 2 weeks. At week 30, 23 of 110 (21%) group I patients were in remission, compared with 44 of 113 (39%) group II (p=0.003) and 50 of 112 (45%) group III (p=0.0002) patients. Thus, patients in groups II and III combined were more likely to sustain clinical remission than patients in group I (odds ratio 2.7, 95% CI 1.6-4.6). Throughout the 54-week trial, the median time to loss of response was 38 weeks (IQR 15 to >54) and more than 54 weeks (21 to >54) for groups II and III, respectively, compared with 19 weeks (10-45) for group I (p=0.002 and p=0.0002, respectively). Infliximab safety was consistent with that seen in other trials of infliximab in Crohn's disease and rheumatoid arthritis. In particular, the incidence of serious infections was similar across treatment groups.\n\nPatients with Crohn's disease who respond to an initial dose of infliximab are more likely to be in remission at weeks 30 and 54, to discontinue corticosteroids, and to maintain their response for a longer period of time, if infliximab treatment is maintained every 8 weeks.", "PMID": "12047962"}, {"title": "The effects of infliximab maintenance therapy on health-related quality of life.", "abstract": "The ACCENT I study evaluated the long term effects of infliximab as maintenance therapy for patients with Crohn's disease. Health-related quality of life (HRQL) was also assessed in the trial.\n\nIn ACCENT I, a total of 573 patients received a single infusion of 5 mg/kg infliximab at baseline. After assessment of response at wk 2, patients were randomly assigned repeat infusions of placebo at wk 2 and 6 and then every 8 wk thereafter until wk 46 (single dose), repeat infusions of 5 mg/kg of infliximab at the same time points (5 mg/kg maintenance), or 5 mg/kg of infliximab at wk 2 and 6 followed by 10 mg/kg (10 mg/kg maintenance). HRQL analyses presented include the 335 patients classified as wk-2 responders. The treatment regimens were compared with regard to their change from baseline in the IBDQ and Short Form-36 (SF-36) scores.\n\nBaseline scores indicated substantial impairment in HRQL. Throughout the study, all IBDQ and SF-36 scores were improved at all time points compared to baseline. After wk 10 and through wk 54, these improvements were greater in the two infliximab maintenance groups than in the single-dose group. The mean change from baseline to wk 54 in total IBDQ was greater in the 5-mg/kg maintenance group (22.1, p < 0.05) and 10-mg/kg maintenance group (30.2, p < 0.001) than in the single-dose group (8.9). Similarly, the mean change from baseline to wk 54 in the PCS of the SF-36 was greater in the 5-mg/kg maintenance group (6.1, p < 0.05) and 10-mg/kg maintenance group (7.2, p < 0.01) than in the single-dose group (2.5).\n\nInfliximab therapy provides substantially improved HRQL as measured by both the disease-specific IBDQ and the generic SF-36. A maintenance regimen of either 5 mg/kg or 10 mg/kg of infliximab is more effective than a single 5-mg/kg infliximab infusion in sustaining this benefit.", "PMID": "14572573"}, {"title": "Infliximab for the treatment of fistulas in patients with Crohn's disease.", "abstract": "Enterocutaneous fistulas are a serious complication of Crohn's disease and are difficult to treat. Infliximab, a chimeric monoclonal antibody to tumor necrosis factor alpha, has recently been developed as a treatment for Crohn's disease. We conducted a randomized, multicenter, double-blind, placebo-controlled trial of infliximab for the treatment of fistulas in patients with Crohn's disease.\n\nThe study included 94 adult patients who had draining abdominal or perianal fistulas of at least three months' duration as a complication of Crohn's disease. Patients were randomly assigned to receive one of three treatments: placebo (31 patients), 5 mg of infliximab per kilogram of body weight (31 patients), or 10 mg of infliximab per kilogram (32 patients); all three were to be administered intravenously at weeks 0, 2, and 6. The primary end point was a reduction of 50 percent or more from base line in the number of draining fistulas observed at two or more consecutive study visits. A secondary end point was the closure of all fistulas.\n\nSixty-eight percent of the patients who received 5 mg of infliximab per kilogram and 56 percent of those who received 10 mg per kilogram achieved the primary end point, as compared with 26 percent of the patients in the placebo group (P=0.002 and P=0.02, respectively). In addition, 55 percent of the patients assigned to receive 5 mg of infliximab per kilogram and 38 percent of those assigned to 10 mg per kilogram had closure of all fistulas, as compared with 13 percent of the patients assigned to placebo (P=0.001 and P=0.04, respectively). The median length of time during which the fistulas remained closed was three months. More than 60 percent of patients in all the groups had adverse events. For patients treated with infliximab, the most common were headache, abscess, upper respiratory tract infection, and fatigue.\n\nInfliximab is an efficacious treatment for fistulas in patients with Crohn's disease.", "PMID": "10228190"}, {"title": "Infliximab (REMICADE) therapy in the treatment of pediatric Crohn's disease.", "abstract": "The aim of this study was to assess the efficacy and safety of a single infusion of infliximab in the treatment of pediatric Crohn's disease (CD).\n\nA total of 21 pediatric CD patients were enrolled at seven study centers and randomized to receive a single infusion of infliximab 1 mg/kg (n = 6), 5 mg/kg (n = 7), or 10 mg/kg (n = 8) over at least 2 hrs at week 0 in this multicenter, open-label, dose-blinded trial. Efficacy assessments, including the Pediatric Crohn's Disease Activity Index (PCDAI), modified CDAI, C-reactive protein concentration (CRP), and erythrocyte sedimentation rate (ESR) determinations, were made at screening and at weeks 1, 2, 4, 8, and 12. Adverse events were assessed throughout study participation.\n\nImprovements in the PCDAI, modified CDAI, ESR, and CRP were observed with all infliximab doses, beginning at week 1. On average, all treated patients experienced approximately 50% improvement in the PCDAI by week 2. By week 12, the PCDAI remained approximately 30% improved from baseline. During the study, all 21 patients (100%) achieved a clinical response, and 10 patients (48%) achieved clinical remission. There were no infusion reactions in any of the treatment arms.\n\nThe results of this trial suggest that infliximab may be safe and effective as short-term therapy of medically refractory moderate to severe CD in a pediatric population.", "PMID": "12738464"}, {"title": "Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn's disease in children.", "abstract": "The REACH study evaluated the safety and efficacy of infliximab in children with moderately to severely active Crohn's disease.\n\nPatients (n = 112) with a Pediatric Crohn's Disease Activity Index (PCDAI) score >30 received infliximab 5 mg/kg at weeks 0, 2, and 6. Patients responding to treatment at week 10 were randomized to infliximab 5 mg/kg every 8 or 12 weeks through week 46. A concurrent immunomodulator was required. Clinical response (decrease from baseline in the PCDAI score > or =15 points; total score < or =30) and clinical remission (PCDAI score < or =10 points) were evaluated at weeks 10, 30, and 54.\n\nAt week 10, 99 of 112 (88.4%) patients responded to infliximab (95% confidence interval: [82.5%, 94.3%]) and 66 of 112 (58.9%) patients achieved clinical remission (95% confidence interval: [49.8%, 68.0%]). At week 54, 33 of 52 (63.5%) and 29 of 52 (55.8%) patients receiving infliximab every 8 weeks did not require dose adjustment and were in clinical response and clinical remission, respectively, compared with 17 of 51 (33.3%) and 12 of 51 (23.5%) patients receiving treatment every 12 weeks (P = .002 and P < .001, respectively).\n\nPediatric patients responding to an induction regimen of infliximab were more likely to be in clinical response and remission at week 54 without dose adjustment when their maintenance therapy was given every 8 weeks rather than every 12 weeks. Allowing for dose intensification in the case of relapse, remission rates, but not response rates, at week 54 were superior with every 8-week dosing compared with every 12-week dosing.", "PMID": "17324398"}, {"title": "Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial.", "abstract": "Most patients who have active Crohn's disease are treated initially with corticosteroids. Although this approach usually controls symptoms, many patients become resistant to or dependent on corticosteroids, and long exposure is associated with an increased risk of mortality. We aimed to compare the effectiveness of early use of combined immunosuppression with conventional management in patients with active Crohn's disease who had not previously received glucocorticoids, antimetabolites, or infliximab.\n\nWe did a 2-year open-label randomised trial at 18 centres in Belgium, Holland, and Germany between May, 2001, and January, 2004. We randomly assigned 133 patients to either early combined immunosuppression or conventional treatment. The 67 patients assigned to combined immunosuppression received three infusions of infliximab (5 mg/kg of bodyweight) at weeks 0, 2, and 6, with azathioprine. We gave additional treatment with infliximab and, if necessary, corticosteroids, to control disease activity. 66 patients assigned to conventional management received corticosteroids, followed, in sequence, by azathioprine and infliximab. The primary outcome measures were remission without corticosteroids and without bowel resection at weeks 26 and 52. Analysis was by modified intention to treat. This trial was registered with ClinicalTrials.gov, number NCT00554710.\n\nFour patients (two in each group) did not receive treatment as per protocol. At week 26, 39 (60.0%) of 65 patients in the combined immunosuppression group were in remission without corticosteroids and without surgical resection, compared with 23 (35.9%) of 64 controls, for an absolute difference of 24.1% (95% CI 7.3-40.8, p=0.0062). Corresponding rates at week 52 were 40/65 (61.5%) and 27/64 (42.2%) (absolute difference 19.3%, 95% CI 2.4-36.3, p=0.0278). 20 of the 65 patients (30.8%) in the early combined immunosuppression group had serious adverse events, compared with 19 of 64 (25.3%) controls (p=1.0).\n\nCombined immunosuppression was more effective than conventional management for induction of remission and reduction of corticosteroid use in patients who had been recently diagnosed with Crohn's disease. Initiation of more intensive treatment early in the course of the disease could result in better outcomes.", "PMID": "18295023"}, {"title": "[Maintenance treatment by anti-tumor necrosis factor monoclonal antibody in Crohn's disease--long-term effects and safety].", "abstract": "", "PMID": "18460853"}, {"title": "Efficacy of infliximab in pediatric Crohn's disease: a randomized multicenter open-label trial comparing scheduled to on demand maintenance therapy.", "abstract": "Infliximab (IFX) is efficacious in inducing remission in severe forms of pediatric Crohn's disease (CD). Adult studies indicate that IFX is also safe and well tolerated as maintenance therapy. The present study aimed to evaluate in a prospective manner the efficacy and safety of IFX as maintenance therapy of severe pediatric CD comparing scheduled and \"on demand\" treatment strategies.\n\nForty children with CD (nonpenetrating, nonstricturing as well as penetrating forms, mean age: 13.9 +/- 2.2 years) with a severe flare-up (Harvey-Bradshaw Index [HBI] > or =5, erythrocyte sedimentation rate [ESR] >20 mm/h) despite well-conducted immunomodulator therapy (n = 36 azathioprine, n = 1 mercaptopurine, n = 3 methotrexate) combined with steroids were included in this randomized, multicenter, open-label study. Three IFX infusions (5 mg/kg) were administered at week (W)0/W2/W6. At W10, clinical remission (HBI <5) and steroid withdrawal were analyzed and IFX responders were randomized to maintenance therapy over 1 year: group A, scheduled every 2 months; group B, \"on demand\" on relapse.\n\nIn all, 34/40 children came into remission during IFX induction therapy (HBI: 6.7 +/- 2.5 (WO) vs. 1.1 +/- 1.5 (W10); P < 0.001). At the end of phase 2, 15/18 (83%) patients were in remission in group A compared to 8/13 (61%) children in group B (P < 0.01), with a mean HBI of 0.5 versus 3.2 points (group A versus B, P = 0.011). In group A, 3/13 (23.1%) children experienced a relapse compared to 11/12 (92%) children in group B. No severe adverse event occurred during this trial.\n\nIFX is well tolerated and safe as maintenance therapy for pediatric CD, with a clear advantage when used on a scheduled 2-month basis compared to an \"on demand\" basis.", "PMID": "19023899"}, {"title": "Infliximab prevents Crohn's disease recurrence after ileal resection.", "abstract": "Crohn's disease commonly recurs after intestinal resection. We evaluated whether the administration of infliximab after resective intestinal surgery for Crohn's disease reduces postoperative recurrence.\n\nWe randomly assigned 24 patients with Crohn's disease who had undergone ileocolonic resection to receive intravenous infliximab (5 mg/kg), administered within 4 weeks of surgery and continued for 1 year, or placebo. The primary end point was the proportion of patients with endoscopic recurrence at 1 year. Secondary end points were clinical recurrence and remission and histologic recurrence.\n\nThe rate of endoscopic recurrence at 1 year was significantly lower in the infliximab group (1 of 11 patients; 9.1%) compared with the placebo group (11 of 13 patients; 84.6%) (P = .0006). There was a nonsignificant higher proportion of patients in clinical remission in the infliximab group (8 of 10; 80.0%) compared with the placebo group (7 of 13; 53.8%) (P = .38). The histologic recurrence rate at 1 year was significantly lower in the infliximab group (3 of 11 patients; 27.3%) compared with the placebo group (11 of 13 patients; 84.6%) (P = .01). The occurrence of adverse events was similar between the placebo and infliximab groups, and none occurred in the immediate postoperative period.\n\nAdministration of infliximab after intestinal resective surgery was effective at preventing endoscopic and histologic recurrence of Crohn's disease.", "PMID": "19109962"}], "labels": [{"PMID": "10500056", "label": "included"}, {"PMID": "12047962", "label": "included"}, {"PMID": "14572573", "label": "included"}, {"PMID": "10228190", "label": "excluded"}, {"PMID": "12738464", "label": "excluded"}, {"PMID": "17324398", "label": "excluded"}, {"PMID": "18295023", "label": "excluded"}, {"PMID": "18460853", "label": "excluded"}, {"PMID": "19023899", "label": "excluded"}, {"PMID": "19109962", "label": "excluded"}]}
{"metadata": {"review_pmid": "38358047"}, "inputs": {"background": "Interventions incorporating meditation to address stress, anxiety, and depression, and improve self-management, are becoming popular for many health conditions. Stress is a risk factor for cardiovascular disease (CVD) and clusters with other modifiable behavioural risk factors, such as smoking. Meditation may therefore be a useful CVD prevention strategy.", "objectives": "To determine the effectiveness of meditation, primarily mindfulness-based interventions (MBIs) and transcendental meditation (TM), for the primary and secondary prevention of CVD.", "selection criteria": "We included randomised controlled trials (RCTs) of 12 weeks or more in adults at high risk of CVD and those with established CVD. We explored four comparisons: MBIs versus active comparators (alternative interventions); MBIs versus non-active comparators (no intervention, wait list, usual care); TM versus active comparators; TM versus non-active comparators."}, "context": [{"title": "Effects of stress reduction on carotid atherosclerosis in hypertensive African Americans.", "abstract": "African Americans suffer disproportionately higher cardiovascular disease mortality rates than do whites. Psychosocial stress influences the development and progression of atherosclerosis. Carotid intima-media thickness (IMT) is a valid surrogate measure for coronary atherosclerosis, is a predictor of coronary outcomes and stroke, and is associated with psychosocial stress factors. Stress reduction with the Transcendental Meditation (TM) program decreases coronary heart disease risk factors and cardiovascular mortality in African Americans. B-mode ultrasound is useful for the noninvasive evaluation of carotid atherosclerosis.\n\nThis randomized controlled clinical trial evaluated the effects of the TM program on carotid IMT in hypertensive African American men and women, aged >20 years, over a 6- to 9-month period. From the initially enrolled 138 volunteers, 60 subjects completed pretest and posttest carotid IMT data. The assigned interventions were either the TM program or a health education group. By use of B-mode ultrasound, mean maximum IMT from 6 carotid segments was used to determine pretest and posttest IMT values. Regression analysis and ANCOVA were performed.\n\nAge and pretest IMT were found to be predictors of posttest IMT values and were used as covariates. The TM group showed a significant decrease of -0.098 mm (95% CI -0. 198 to 0.003 mm) compared with an increase of 0.054 mm (95% CI -0.05 to 0.158 mm) in the control group (P=0.038, 2-tailed).\n\nStress reduction with the TM program is associated with reduced carotid atherosclerosis compared with health education in hypertensive African Americans. Further research with this stress-reduction technique is warranted to confirm these preliminary findings.", "PMID": "10700487"}, {"title": "Behavioral treatment of hypertensive heart disease in African Americans: rationale and design of a randomized controlled trial.", "abstract": "African Americans experience higher morbidity and mortality than Whites do as a result of hypertension and associated cardiovascular disease. Chronic psychosocial stress has been considered an important contributing factor to these high rates. The authors describe the rationale and design for a planned randomized controlled trial comparing Transcendental Meditation, a stress-reduction technique, with lifestyle education in the treatment of hypertension and hypertensive heart disease in urban African Americans. They pretested 170 men and women aged 20 to 70 years over a 3-session baseline period, with posttests at 6 months. Outcomes included clinic and ambulatory blood pressure, quality of life, left ventricular mass measured by M-mode echocardiography, left ventricular diastolic function measured by Doppler, and carotid atherosclerosis measured by beta-mode ultrasound. This trial was designed to evaluate the hypothesis that a selected stress reduction technique is effective in reducing hypertension and hypertensive heart disease in African Americans.", "PMID": "11763829"}, {"title": "A randomized controlled trial of stress reduction in African Americans treated for hypertension for over one year.", "abstract": "Psychosocial stress has been implicated in the disproportionately higher rates of hypertension among African Americans. This randomized controlled trial compared the effects of two stress reduction techniques and a health education control program on hypertension during a period of 1 year in African-American men and women (N = 150, mean age 49 +/- 10 years, mean blood pressure (BP) = 142/95 mm Hg) at an urban community health center.\n\nInterventions included 20 min twice a day of Transcendental Meditation (TM) or progressive muscle relaxation (PMR), or participation in conventional health education (HE) classes. All subjects continued usual medical care. Outcomes assessed were systolic BP and diastolic BP at 3, 6, 9, and 12 months after treatment, analyzed by repeated measures ANCOVA.\n\nThe TM group showed decreases in systolic BP/diastolic BP of -3.1/-5.7 mm Hg compared to -0.5/-2.9 mm Hg for PMR or HE, (P = .12 to .17 for systolic BP, P = .01 for diastolic BP). In addition the TM group demonstrated reduced use of antihypertensive medication relative to increases for PMR (P = .001) and HE (P = .09) groups. Group analysis by gender showed that women practicing TM had decreased BP (-7.3/-6.9 mm Hg) significantly more than women practicing PMR (0.7/-2.7 mm Hg) or HE (-.07/-3.0 mm Hg) (P .01 to .03). The change in men praticing TM (0.2 /-4.7 mm Hg) was greater than men practicing HE (-0.9/-2.0 mm Hg) for diastolic BP only (P = .09,) and not different from PMR men (-2.0/-3.1).\n\nA selected stress reduction approach, the Transcendental Meditation program, may be useful as an adjunct in the long-term treatment of hypertension in African Americans.", "PMID": "15691622"}, {"title": "Effects of a randomized controlled trial of transcendental meditation on components of the metabolic syndrome in subjects with coronary heart disease.", "abstract": "The metabolic syndrome is thought to be a contributor to coronary heart disease (CHD), and components of the syndrome have been identified as possible therapeutic targets. Previous data implicate neurohumoral activation related to psychosocial stress as a contributor to the metabolic syndrome. The aim of this study was to evaluate the efficacy of transcendental meditation (TM) on components of the metabolic syndrome and CHD.\n\nWe conducted a randomized, placebo-controlled clinical trial of 16 weeks of TM or active control treatment (health education), matched for frequency and time, at an academic medical center in a total of 103 subjects with stable CHD. Main outcome measures included blood pressure, lipoprotein profile, and insulin resistance determined by homeostasis model assessment (calculated as follows: [(fasting plasma glucose level [in milligrams per deciliter] x fasting plasma insulin level [in microunits per milliliter]) x 0.0552]/22.5); endothelial function measured by brachial artery reactivity testing; and cardiac autonomic system activity measured by heart rate variability.\n\nThe TM group had beneficial changes (measured as mean +/- SD) in adjusted systolic blood pressure (-3.4 +/- 2.0 vs 2.8 +/- 2.1 mm Hg; P = .04), insulin resistance (-0.75 +/- 2.04 vs 0.52 +/- 2.84; P = .01), and heart rate variability (0.10 +/- 0.17 vs -0.50 +/- 0.17 high-frequency power; P = .07) compared with the health education group, respectively. There was no effect of brachial artery reactivity testing.\n\nUse of TM for 16 weeks in CHD patients improved blood pressure and insulin resistance components of the metabolic syndrome as well as cardiac autonomic nervous system tone compared with a control group receiving health education. These results suggest that TM may modulate the physiological response to stress and improve CHD risk factors, which may be a novel therapeutic target for the treatment of CHD.", "PMID": "16772250"}, {"title": "A randomized controlled trial on effects of the Transcendental Meditation program on blood pressure, psychological distress, and coping in young adults.", "abstract": "Psychological distress contributes to the development of hypertension in young adults. This trial assessed the effects of a mind-body intervention on blood pressure (BP), psychological distress, and coping in college students.\n\nThis was a randomized controlled trial (RCT) of 298 university students randomly allocated to either the Transcendental Meditation (TM) program or wait-list control. At baseline and after 3 months, BP, psychological distress, and coping ability were assessed. A subgroup of 159 subjects at risk for hypertension was analyzed similarly.\n\nChanges in systolic BP (SBP)/diastolic BP (DBP) for the overall sample were -2.0/-1.2 mm Hg for the TM group compared to +0.4/+0.5 mm Hg for controls (P = 0.15, P = 0.15, respectively). Changes in SBP/DBP for the hypertension risk subgroup were -5.0/-2.8 mm Hg for the TM group compared to +1.3/+1.2 mm Hg for controls (P = 0.014, P = 0.028, respectively). Significant improvements were found in total psychological distress, anxiety, depression, anger/hostility, and coping (P values < 0.05). Changes in psychological distress and coping correlated with changes in SBP (P values < 0.05) and DBP (P values < 0.08).\n\nThis is the first RCT to demonstrate that a selected mind-body intervention, the TM program, decreased BP in association with decreased psychological distress, and increased coping in young adults at risk for hypertension. This mind-body program may reduce the risk for future development of hypertension in young adults.", "PMID": "19798037"}, {"title": "Testing the effectiveness of a mindfulness-based intervention to reduce emotional distress in outpatients with diabetes (DiaMind): design of a randomized controlled trial.", "abstract": "Approximately 20-40% of outpatients with diabetes experience elevated levels of emotional distress, varying from disease-specific distress to general symptoms of anxiety and depression. The patient's emotional well-being is related to other unfavorable outcomes, like reduced quality of life, sub-optimal self-care, impaired glycemic control, higher risk of complications, and increased mortality rates. The purpose of this study is to test the effectiveness of a new diabetes-specific, mindfulness-based psychological intervention. First, with regard to reducing emotional distress; second, with respect to improving quality of life, dispositional mindfulness, and self-esteem of patients with diabetes; third, with regard to self-care and clinical outcomes; finally, a potential effect modification by clinical and personality characteristics will be explored.\n\nThe Diabetes and Mindfulness study (DiaMind) is a randomized controlled trial. Patients with diabetes with low levels of emotional well-being will be recruited from outpatient diabetes clinics. Eligible patients will be randomized to an intervention group or a wait-list control group. The intervention group will receive the mindfulness program immediately, while the control group will receive the program eight months later. The primary outcome is emotional distress (anxiety, stress, depressive symptoms), for which data will be collected at baseline, four weeks, post intervention, and after six months follow-up. In addition, self-report data will be collected on quality of life, dispositional mindfulness, self-esteem, self-care, and personality, while complications and glycemic control will be assessed from medical files and blood pressure will be measured. Group differences will be analyzed with repeated measures analysis of covariance.The study is supported by grants from the Dutch Diabetes Research Foundation and Tilburg University and has been approved by a medical ethics committee.\n\nIt is hypothesized that emotional well-being, quality of life, dispositional mindfulness, self-esteem, self-care, and blood pressure will improve significantly more in the mindfulness group compared to the control group. Results of this study can contribute to a better care for patients with diabetes with lowered levels of emotional well-being. It is expected that the first results will become available in 2012.\n\nDutch Trial Register NTR2145.", "PMID": "21349184"}, {"title": "Buddhist group therapy for diabetes patients with depressive symptoms.", "abstract": "The objective of this study was to assess the effect of Buddhist group therapy on patients with type 2 diabetes who had depressive symptoms. A quasi-experimental design study using a control group with matching technique was conducted. After informed consent was obtained, the \"Nine questions for assessing depressive disorder symptom\" (Isan language) was used to determine the patient's condition. A total of 62 patients with type 2 diabetes who had depressive symptoms were assigned to either the experimental group (n = 32) or the control group (n = 32). Patients in the experimental group were divided further into four groups (8 patients per group) and attended the Buddhist group therapy. The intervention consisted of a weekly Buddhist group gathering lasting 2 hours for 6 weeks plus home meditation practices. Patients in the control group received treatment as usual. Both groups received standard physician treatment, including medication. Physicians did not know who was in either the control or experimental groups. Results show that 6 months after the intervention, 65.6% and 100% of patients in the control group and experimental group, respectively, returned to normal level. The intention-to-treat analysis, which included two participants in the experimental group lost follow-up, yielded a small reduction in the number of patients who returned to normal level (93.8%). With intention-to-treat analysis, the relative risk on depressive symptoms between the experimental and control groups was 6.5 (95% confidence interval, 1.4-30.6). Qualitative data from the experimental group supported that there were therapeutic group factors involved. However, patients realized the truth of being oneself and also accepted their current living condition. In conclusion, this program is effective in reducing depressive symptoms.", "PMID": "21621733"}, {"title": "Mindfulness training for smoking cessation: results from a randomized controlled trial.", "abstract": "Cigarette smoking is the leading cause of preventable death in the world, and long-term abstinence rates remain modest. Mindfulness training (MT) has begun to show benefits in a number of psychiatric disorders, including depression, anxiety and more recently, in addictions. However, MT has not been evaluated for smoking cessation through randomized clinical trials.\n\n88 treatment-seeking, nicotine-dependent adults who were smoking an average of 20cigarettes/day were randomly assigned to receive MT or the American Lung Association's freedom from smoking (FFS) treatment. Both treatments were delivered twice weekly over 4 weeks (eight sessions total) in a group format. The primary outcomes were expired-air carbon monoxide-confirmed 7-day point prevalence abstinence and number of cigarettes/day at the end of the 4-week treatment and at a follow-up interview at week 17.\n\n88% of individuals received MT and 84% of individuals received FFS completed treatment. Compared to those randomized to the FFS intervention, individuals who received MT showed a greater rate of reduction in cigarette use during treatment and maintained these gains during follow-up (F=11.11, p=.001). They also exhibited a trend toward greater point prevalence abstinence rate at the end of treatment (36% vs. 15%, p=.063), which was significant at the 17-week follow-up (31% vs. 6%, p=.012).\n\nThis initial trial of mindfulness training may confer benefits greater than those associated with current standard treatments for smoking cessation.", "PMID": "21723049"}, {"title": "Mindfulness Intervention for Stress Eating to Reduce Cortisol and Abdominal Fat among Overweight and Obese Women: An Exploratory Randomized Controlled Study.", "abstract": "Psychological distress and elevated cortisol secretion promote abdominal fat, a feature of the Metabolic Syndrome. Effects of stress reduction interventions on abdominal fat are unknown. Forty-seven overweight/obese women (mean BMI = 31.2) were randomly assigned to a 4-month intervention or waitlist group to explore effects of a mindfulness program for stress eating. We assessed mindfulness, psychological distress, eating behavior, weight, cortisol awakening response (CAR), and abdominal fat (by dual-energy X-ray absorptiometry) pre- and posttreatment. Treatment participants improved in mindfulness, anxiety, and external-based eating compared to control participants. Groups did not differ on average CAR, weight, or abdominal fat over time. However, obese treatment participants showed significant reductions in CAR and maintained body weight, while obese control participants had stable CAR and gained weight. Improvements in mindfulness, chronic stress, and CAR were associated with reductions in abdominal fat. This proof of concept study suggests that mindfulness training shows promise for improving eating patterns and the CAR, which may reduce abdominal fat over time.", "PMID": "21977314"}, {"title": "Changes in stress, eating, and metabolic factors are related to changes in telomerase activity in a randomized mindfulness intervention pilot study.", "abstract": "Psychological distress and metabolic dysregulation are associated with markers of accelerated cellular aging, including reduced telomerase activity and shortened telomere length. We examined whether participation in a mindfulness-based intervention, and, secondarily, improvements in psychological distress, eating behavior, and metabolic factors are associated with increases in telomerase activity in peripheral blood mononuclear cells (PBMCs).\n\nWe enrolled 47 overweight/obese women in a randomized waitlist-controlled pilot trial (n=47) of a mindfulness-based intervention for stress eating and examined changes in telomerase activity from pre- to post-intervention. In secondary analyses, changes in telomerase activity across the sample were examined in relation to pre- to post-intervention changes in psychological distress, eating behavior, and metabolic factors (weight, serum cortisol, fasting glucose and insulin, and insulin resistance).\n\nBoth groups increased in mean telomerase activity over 4 months in intent-to-treat and treatment efficacy analyses (p<0.001). Nonsignificant trends showed that greater attendance was associated with increases in telomerase, and telomerase increases were 18% higher among 'as treated' participants compared to controls. Across groups, changes in chronic stress, anxiety, dietary restraint, dietary fat intake, cortisol, and glucose were negatively correlated with changes in telomerase activity. In exploratory analyses, decreases in dietary fat intake partially mediated the association between dietary restraint and telomerase activity with marginal significance.\n\nWhile there was no clear effect of the intervention on telomerase activity, there was a striking pattern of correlations between improvements in psychological distress, eating behavior, and metabolic health and increases in telomerase activity. These findings suggest that telomerase activity may be in part regulated by levels of both psychological and metabolic stress.", "PMID": "22169588"}], "labels": [{"PMID": "10700487", "label": "included"}, {"PMID": "11763829", "label": "included"}, {"PMID": "15691622", "label": "included"}, {"PMID": "16772250", "label": "included"}, {"PMID": "19798037", "label": "included"}, {"PMID": "21349184", "label": "included"}, {"PMID": "21621733", "label": "included"}, {"PMID": "21723049", "label": "included"}, {"PMID": "21977314", "label": "included"}, {"PMID": "22169588", "label": "included"}]}
{"metadata": {"review_pmid": "38357958"}, "inputs": {"background": "Stimulant use disorder is a continuously growing medical and social burden without approved medications available for its treatment. Psychosocial interventions could be a valid approach to help people reduce or cease stimulant consumption. This is an update of a Cochrane review first published in 2016.", "objectives": "To assess the efficacy and safety of psychosocial interventions for stimulant use disorder in adults.", "selection criteria": "We included randomised controlled trials (RCTs) comparing any psychosocial intervention with no intervention, treatment as usual (TAU), or a different intervention in adults with stimulant use disorder."}, "context": [{"title": "Continuing care for cocaine dependence: comprehensive 2-year outcomes.", "abstract": "This report presents 2-year outcome data from an outpatient continuing care study in which cocaine-dependent patients (N = 132) were randomly assigned to either standard group counseling (STND) or individualized relapse prevention (RP). Data on cocaine outcomes during the 6-month treatment phase of the study were presented in an earlier report (J. R. McKay, A. I. Alterman, J. S. Cacciola, M. R. Rutherford, & C. P. O'Brien, 1997). In the present report, a continuing care condition main effect was obtained on only 1 of 8 outcome variables examined. However, patients who endorsed a goal of absolute abstinence on entering continuing care had better cocaine use outcomes in RP than in STND, whereas the opposite was the case for those with less stringent abstinence goals. In addition, patients with current cocaine or alcohol dependence on entering continuing care who received RP had better cocaine use outcomes in Months 1-6 and better alcohol use outcomes in Months 13-24 than those in STND.", "PMID": "10369063"}, {"title": "The effectiveness of the Minnesota Model approach in the treatment of adolescent drug abusers.", "abstract": "The treatment outcome of drug-abusing adolescents treated with a 12-Step approach.\n\nThe study compares drug use outcome data at 6 and 12 months post-treatment among three groups of adolescents: those who completed treatment, those who did not and those on a waiting list. Also, among treatment completers, residential and outpatient samples were compared on outcome.\n\nThe treatment site is located in the Minneapolis/St Paul area of Minnesota.\n\nTwo hundred and forty-five drug clinic-referred adolescents (12-18 years old), all of whom met at least one DSM-III-R substance dependence disorder. One hundred and seventy-nine subjects received either complete or incomplete 12-Step, Minnesota Model treatment and 66 were waiting list subjects.\n\nIn addition to demographics and clinical background variables, measures included treatment involvement, treatment setting and drug use frequency at intake and follow-up.\n\nAbsolute and relative outcome analyses indicated that completing treatment was associated with far superior outcome compared to those who did not complete treatment or receive any at all. The percentage of treatment completers who reported either abstinence or a minor lapse for the 12 months following treatment was 53%, compared to 15 and 28% for the incompleter and waiting list groups, respectively.\n\nFavorable treatment outcome for drug abuse was about two to three times more likely if treatment was completed. Also, there were no outcome differences between residential and outpatient groups. Alcohol was the most common drug used during the follow-up period, despite cannabis being the preferred drug at intake.", "PMID": "10829335"}, {"title": "Brief coping skills treatment for cocaine abuse: 12-month substance use outcomes.", "abstract": "Patients (N = 108) in a study of cocaine-specific coping skills training (CST), which was found to reduce cocaine use during a 3-month follow-up, were followed for an additional 9 months. CST involved coping skills training in the context of high-risk situations. Control treatment used meditation-relaxation. Both were added to comprehensive private substance abuse treatment. Patients in CST who relapsed had significantly fewer cocaine use days than did the control group during the first 6 months, then both conditions did equally well. Patients in CST also drank alcohol more frequently in the last 6 months than did contrast patients but did not differ in heavy drinking days. For cocaine use outcomes, no interaction of treatment was found with gender, education, route of administration, drug use severity, sociopathy, or depression. Implications include the need to investigate different lengths and combinations of treatment.", "PMID": "10883569"}, {"title": "A reinforcement-based therapeutic workplace for the treatment of drug abuse: six-month abstinence outcomes.", "abstract": "This study evaluated a novel drug abuse treatment, the Therapeutic Workplace. In this treatment, patients are paid to perform jobs or to participate in job training. Salary is linked to abstinence by requiring patients to provide drug-free urine samples to gain access to the workplace. Pregnant and postpartum drug abuse patients (N = 40) were randomly assigned to a Therapeutic Workplace or usual care control group. Therapeutic Workplace participants were invited to work 3 hr every weekday for 6 months and could earn up to $4,030 in vouchers for abstinence, workplace attendance, and performance. On average, 45% of participants attended the workplace per day. Relative to controls, the Therapeutic Workplace nearly doubled patients' abstinence from opiates and cocaine (33% vs. 59% of thrice-weekly urine samples drug negative, respectively, p < .05). The Therapeutic Workplace can effectively treat heroin and cocaine abuse in pregnant and postpartum women.", "PMID": "11519628"}, {"title": "A dose response study of cognitive behavioral therapy in cocaine abusers.", "abstract": "In order to evaluate the effect of frequency of counseling sessions, we studied retention, cocaine use and craving, and psychiatric symptoms of 68 cocaine-dependent outpatients randomly assigned to twice weekly, once weekly, or biweekly sessions in a 12-week treatment program that utilized manual-based, individual cognitive behavioral psychotherapy. All participants were tested and monitored twice a week. Retention was comparable among treatment groups, and improvement was found regardless of counseling frequency. Cocaine use (urine toxicology and self-report), cocaine craving (VAS), and total psychiatric symptoms (SCL-90) decreased by modest but statistically significant (p < 0.05) amounts in all treatment groups. Findings suggest that cognitive behavioral therapy is effective in reducing cocaine use even if a less intensive schedule is used.", "PMID": "12392805"}, {"title": "The effectiveness of telephone-based continuing care in the clinical management of alcohol and cocaine use disorders: 12-month outcomes.", "abstract": "This study of continuing care for substance dependent patients compared a telephone-based monitoring and brief counseling intervention (TEL) with 2 face-to-face interventions, relapse prevention (RP) and standard 12-step group counseling (STND). The participants were graduates of intensive outpatient programs who had current dependence on alcohol and/or cocaine. Self-report, collateral, and biological measures of alcohol and cocaine use were obtained over a 12-month follow-up. The treatment groups did not differ on abstinence-related outcomes in the complete sample (N = 359) or on cocaine use outcomes in participants with cocaine dependence (n = 268). However, in participants with alcohol dependence only (n = 91), TEL produced better alcohol use outcomes than STND on all measures examined and better outcomes than RP on some of the measures.", "PMID": "15612844"}, {"title": "The effectiveness of telephone-based continuing care for alcohol and cocaine dependence: 24-month outcomes.", "abstract": "Telephone-based disease management protocols have shown promise in improving outcomes in a number of medical and psychiatric disorders, but this approach to continuing care has received little study in alcohol- and drug-dependent individuals.\n\nTo compare telephone-based continuing care with 2 more intensive face-to-face continuing care interventions.\n\nA randomized 3-group clinical trial with a 2-year follow-up.\n\nTwo outpatient substance abuse treatment programs, one community-based and the other at a Veterans Affairs medical center facility.\n\nAlcohol- and/or cocaine-dependent patients (N = 359) who had completed 4-week intensive outpatient programs.\n\nThree 12-week continuing care treatments: weekly telephone-based monitoring and brief counseling contacts combined with weekly supportive group sessions in the first 4 weeks (TEL), twice-weekly cognitive-behavioral relapse prevention (RP), and twice-weekly standard group counseling (STND).\n\nPercentage of days abstinent from alcohol and cocaine, total abstinence from alcohol and cocaine, negative consequences of substance use, cocaine urine toxicological results, and gamma-glutamyltransferase.\n\nParticipants in TEL had higher rates of total abstinence over the follow-up than those in STND (P<.05). In alcohol-dependent participants, 24-month gamma-glutamyltransferase levels were lower in TEL than in RP (P = .005). In cocaine-dependent participants, there was a significant group x time interaction (P = .03) in which the rate of cocaine-positive urine samples increased more rapidly in RP as compared with TEL. On percentage of days abstinent or negative consequences of substance use, TEL did not differ from RP or STND. Participants with high scores on a composite risk indicator, based on co-occurring alcohol and cocaine dependence and poor progress toward achieving intensive outpatient program goals, had better total abstinence outcomes up to 21 months if they received STND rather than TEL, whereas those with lower scores had higher abstinence rates in TEL than in STND (P = .04).\n\nTelephone-based continuing care appears to be an effective form of step-down treatment for most patients with alcohol and cocaine dependence who complete an initial stabilization treatment, compared with more intensive face-to-face interventions. However, high-risk patients may have better outcomes if they first receive group counseling continuing care after completing intensive outpatient programs.", "PMID": "15699297"}, {"title": "Reinforcement-based therapy: 12-month evaluation of an outpatient drug-free treatment for heroin abusers.", "abstract": "This controlled study examined the efficacy of reinforcement-based therapy (RBT) for producing enhanced abstinence outcomes over 12 months in opioid-dependent patients exiting a brief residential detoxification. Patients were randomly assigned upon completing their medically managed taper (i.e., detoxification) to RBT (N=66) or usual care (N=64) referral to community treatment programs. The 6-month RBT program offered an array of abstinence-based incentives including rent payment for recovery housing, program-led recreational activities and skills training for procuring employment. RBT produced significantly higher self-report and urinalysis-confirmed rates of abstinence from opioids and cocaine relative to usual care at 1 (42% versus 15%) and 3 (38% versus 17%) months during treatment but not at 6 or 12 months after enrollment. The RBT but not the usual care group showed significant increases in the number of days worked and the amount of legal income earned at 3, 6 and 12 months. The results of this randomized study suggest that an intensive reinforcement-based therapy that includes abstinence-based recovery housing is a promising approach; however, further research is needed to determine the role of treatment intensity and the specific efficacy of RBT's component parts.", "PMID": "16002021"}, {"title": "Motivationally enhanced group counseling for substance users in a soup kitchen: a randomized clinical trial.", "abstract": "Soup kitchens tend to serve residentially unstable adults characterized by a high prevalence of substance abuse. In this study, 289 soup kitchen guests who reported drug or alcohol problems were randomly assigned to information and referral (I&R) plus peer advocacy (peers encouraging subjects to participate in other services) (N = 139) or to an experimental 12-session motivational group (three sessions per week for 4 weeks) followed by a 36-session cognitive-behavioral group (three sessions per week for 12 weeks), plus I&R and peer advocacy. Mean age was 42; 82% male; 68% African-American; 81% unstable residence; 14% HIV+. Experimentals were significantly more likely than the controls to have increased their participation in some type of substance abuse intervention during the follow-up period. In addition, experimentals were significantly more likely than controls to have reduced both drinking and heavy drinking at follow-up (there was no difference between groups in reduction of cocaine use). Interaction analysis indicated that the experimental intervention was more effective for participants with higher rather than lower substance abuse severity at baseline. These results support the concept that motivationally enhanced group counseling, provided as a low-threshold outreach intervention, can help to increase participation in formal treatment and 12-step groups and to reduce substance abuse, particularly for those starting with high severity of use.", "PMID": "16157232"}, {"title": "A randomized clinical trial of a new behavioral treatment for drug abuse in people with severe and persistent mental illness.", "abstract": "Drug abuse by people with severe mental disorder is a significant public health problem for which there is no empirically validated treatment.\n\nTo evaluate the efficacy of a new behavioral treatment for drug abuse in this population: Behavioral Treatment for Substance Abuse in Severe and Persistent Mental Illness (BTSAS).\n\nParticipants were randomly assigned to 6 months of treatment in either BTSAS or a manualized control condition: Supportive Treatment for Addiction Recovery (STAR).\n\nTreatment was conducted in community-based outpatient clinics and a Veterans Affairs medical center in Baltimore, Md.\n\nParticipants were 129 stabilized outpatients meeting DSM criteria for drug dependence (cocaine, heroin, or cannabis) and serious mental illness: 39.5% met DSM-IV criteria for schizophrenia or schizoaffective disorder; 55.8%, for major affective disorders; and the remainder met criteria for severe and persistent mental illness and other Axis I disorders.\n\nBoth treatments were administered by trained health care professionals in small groups, twice a week for 6 months. The BTSAS program is a social learning intervention that includes motivational interviewing, a urinalysis contingency, and social skills training. The control condition, STAR, is a supportive group discussion treatment. Main Outcome Measure The primary outcome measure was urinalysis results from twice-weekly treatment sessions.\n\nThe BTSAS program was significantly more effective than STAR in percentage of clean urine test results, survival in treatment, and attendance at sessions. The BTSAS program also had significant effects on important community-functioning variables, including hospitalization; money available for living expenses; and quality of life.\n\nThe BTSAS program is an efficacious treatment. Further work needs to be done to increase the proportion of eligible patients who are able to become engaged in treatment.", "PMID": "16585472"}], "labels": [{"PMID": "10369063", "label": "excluded"}, {"PMID": "10829335", "label": "excluded"}, {"PMID": "10883569", "label": "excluded"}, {"PMID": "11519628", "label": "excluded"}, {"PMID": "12392805", "label": "excluded"}, {"PMID": "15612844", "label": "excluded"}, {"PMID": "15699297", "label": "excluded"}, {"PMID": "16002021", "label": "excluded"}, {"PMID": "16157232", "label": "excluded"}, {"PMID": "16585472", "label": "excluded"}]}
{"metadata": {"review_pmid": "38353936"}, "inputs": {"background": "Patients who present with problems with definitive dialysis access (arteriovenous fistula (AVF) or arteriovenous graft (AVG)) become catheter dependent (temporary access), a condition that often carries a higher risk of infections, central venous occlusions and recurrent hospitalisations. For AVG, primary patency rates are reported to be 30% to 90% in patients undergoing thrombectomy or thrombolysis. According to the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) guidelines, surgery is preferred when the cause of the thrombosis is a stenosis at the site of the anastomosis in thrombosed AVF. The European Best Practice Guidelines (EBPG) reported that thrombosed AVF may be preferably treated with endovascular techniques, but when the cause of thrombosis is in the anastomosis, surgery provides better results with re-anastomosis. Therefore, there is a need to carry out a systematic review to determine the effectiveness and safety of the intervention for thrombosed fistulae.", "objectives": "This review aims to establish the efficacy and safety of interventions for failed AVF and AVG in patients receiving haemodialysis (HD).", "selection criteria": "The review included randomised controlled trials (RCTs) and quasi-RCTs in people undergoing HD treatment using AVF or AVG presenting with clinical or haemodynamic evidence of thrombosis. Patients had to have used an AVF or AVG at least once."}, "context": [{"title": "Comparison of the angiojet rheolytic catheter to surgical thrombectomy for the treatment of thrombosed hemodialysis grafts. Peripheral AngioJet Clinical Trial.", "abstract": "To compare the clinical effectiveness of the AngioJet F105 rheolytic catheter to that of surgical thrombectomy for the treatment of thrombosed hemodialysis grafts.\n\nThis was a multicenter, prospective, randomized trial comparing technical success, primary patency, and complication rates. A total of 153 patients were enrolled: 82 patients in the AngioJet group and 71 patients in the surgical thrombectomy group. Patient follow-up was performed 24-48 hours, 1 month, and 6 months after the procedures.\n\nTechnical success, as defined by the patient's ability to undergo hemodialysis treatment, was 73.2% for the AngioJet group and 78.8% for the surgical thrombectomy group (P = .41). The primary patency rates of the AngioJet group were 32%, 21%, and 15% at 1, 2, and 3 months, respectively. The primary patency rates for the surgical group were 41%, 32%, and 26% at 1, 2, and 3 months, respectively. This difference approached statistical significance (P = .053). The groups had similar complication rates-14.6% in the AngioJet group and 14.1% in the surgery group-although the surgery group had more major complications (11.3%). In the AngioJet group, there was a transient increase in plasma-free hemoglobin, which normalized within 24-48 hours.\n\nThe AngioJet F105 catheter provides similar clinical results when compared to surgical thrombectomy for the treatment of thrombosed hemodialysis grafts. The difference in patency rates between these two techniques approached statistical significance. In addition, results of both thrombectomy methods were inferior to those suggested by the Dialysis Outcomes Quality Initiative guidelines.", "PMID": "10527197"}, {"title": "Synthetic dialysis shunts: thrombolysis with the Cragg thrombolytic brush catheter.", "abstract": "To evaluate the effectiveness of the Cragg thrombolytic brush catheter for declotting of synthetic arteriovenous dialysis shunts.\n\nIn this randomized controlled trial, 77 patients with synthetic forearm loop shunts that were thrombosed were randomly assigned to undergo pharmacomechanical thrombolysis with a pulsed spray (n = 34) or a thrombolytic brush catheter (n = 43). The following findings were evaluated: declotting time, urokinase dose, procedure time, complications, and shunt patency at the first dialysis session and at 3 months. All data were collected prospectively in an unblinded manner.\n\nThe total amount of urokinase used, including secondary interventions, was 243,657 IU with the catheter versus 476,563 IU with the pulsed spray (P = .001). At 15 minutes, clot lysis was successful in 66% of the patients with the catheter versus in 19% with the pulsed spray (P = .001). At 30 minutes, clot lysis was successful in 98% with the catheter versus 47% with the pulsed spray (P = .001). Procedure complication rates and patency at 3 months were similar for the catheter and the pulsed-spray groups.\n\nUse of the Cragg catheter with urokinase offered faster and more complete clot lysis than did use of the pulsed spray with urokinase. The amount of urokinase used with the catheter was half that used with the pulsed spray. Shunt patency at 3 months was similar for the two treatment methods.", "PMID": "10540659"}, {"title": "Endovascular versus surgical treatment for thrombosed hemodialysis grafts: A prospective, randomized study.", "abstract": "The objective of this study was to compare clinical outcome and costs for two widely used treatment strategies for hemodialysis graft thrombosis.\n\nDuring a 4-year period, 80 patients with thrombosed dialysis grafts were randomly assigned to surgical thrombectomy with or without graft revision (SURG) or thrombolytic therapy with urokinase with the pulse-spray technique (ENDO), with adjunctive percutaneous transluminal angioplasty as indicated. All the procedures were performed in an endovascular operating suite with fistulography. The clinical and cost data were tabulated, and the outcome was analyzed with the life-table method.\n\nFifty-six women and 24 men ranged in age from 33 to 90 years (mean, 63.7 years). The patients had undergone a mean of 2.8 prior access procedures in the ipsilateral extremity. All the grafts were upper extremity expanded polytetrafluoroethylene grafts. Lesions that were presumed to be the primary cause of graft thrombosis were identified in 73 of 80 grafts, and 60 of these were at the venous anastomosis. The procedure time averaged 99 minutes for the patients in the SURG group and 113 minutes for the patients in the ENDO group (P =.12). Eleven patients in the ENDO group crossed over to surgical revision as compared with two patients in the SURG group who required adjunctive percutaneous transluminal angioplasty (P =.005). The mean cost of treatment (including room and supply costs but not professional fees) was significantly higher for the ENDO group than for the SURG group ($2945 vs $1512; P <.001). There were no procedure-related complications in either group. At a median follow-up time of 24 months, there was no difference in primary or assisted primary patency between groups, which averaged 6 and 7 months, respectively.\n\nAlthough thrombolytic therapy combined with endovascular treatment can extend the life of dialysis grafts with results similar to surgical revision, there is a high rate of technical failure necessitating surgery and a substantially higher cost for thrombolysis.", "PMID": "10587385"}, {"title": "Regarding \"Endovascular versus surgical treatment for thrombosed hemodialysis: a prospective, randomized study\".", "abstract": "", "PMID": "11054238"}, {"title": "Hydrodynamic thrombectomy system versus pulse-spray thrombolysis for thrombosed hemodialysis grafts: a multicenter prospective randomized comparison.", "abstract": "To evaluate the safety and efficacy of a hydrodynamic thrombectomy system in a prospective, multicenter randomized comparison with pulse-spray thrombolysis in hemodialysis grafts.\n\nNine centers enrolled 120 adult patients with recently (</=14 days) thrombosed hemodialysis grafts. Graft venography was used to confirm occlusion in 62 patients randomly assigned to thrombectomy and 58 to thrombolysis. For thrombolysis, a mixture of 5,000 U of heparin and 250,000 U of urokinase was distributed throughout the thrombus, first to the venous then to the arterial graft end. For thrombectomy, the catheter was passed in the same sequence. Technical success was removal of 80% or more of thrombus. Clinical success was technical success plus the ability to dialyze. Also assessed were total procedure time, thrombus treatment time, procedure-related blood loss, other complications, and 30- and 90-day outcomes.\n\nPatient demographics were comparable. Technical success rates were 95% (59 of 62) for thrombectomy and 90% (52 of 58) for thrombolysis (P: =.31). Clinical success rates were 89% (55 of 62) and 81% (47 of 58), respectively (P: =.24). At 30 days, 69% (43 of 62) and 66% (38 of 58), respectively, could be dialyzed through the graft (P: =.70); at 90 days, the rates were 40% (25 of 62) and 41% (24 of 58), respectively (P: =.91). None of these differences or those for procedure-related blood loss and early and late complications were statistically significant. Thrombus treatment times of 16.8 minutes for thrombectomy and 23.4 minutes for thrombolysis were significantly different (P: <.01).\n\nThe hydrodynamic thrombectomy system is at least as efficacious and safe as pulse-spray thrombolysis but shortens thrombus treatment time.", "PMID": "11110928"}, {"title": "Gianturco self-expanding stent in the treatment of stenosis in dialysis access grafts.", "abstract": "This study evaluated the effectiveness of the Gianturco endovascular stent in preserving graft patency following percutaneous transvenous angioplasty (PTVA) of stenotic lesions occurring at the graft-vein anastomosis in hemodialysis patients with polytetrafluoroethylene grafts. Fifty-eight patients having 50% or greater stenosis were randomly divided into a treatment group (N = 28) and a concurrent control group (N = 30) following PTVA. In the treatment group, a stent was placed following dilatation. Graft thrombosis, the need for surgical revision, or the need for a repeat PTVA were used as end point events. The period of time from the PTVA/stent procedure to the end point event was referred to as the duration of efficacy (DE). By life table analysis, the DE for the treatment group was 100% at 30 days, 91% at 60 days, 85% at 90 days, 72% at 180 days, and 17% at 360 days. Comparison of the characteristics and results obtained in the treatment group and that of the concurrent control group revealed no significant difference in any parameter prior to treatment, in the response to PTVA, or in the DE of the procedure performed. It was concluded that the stent offered no advantage in the treatment of the graft-vein anastomosis stenotic lesion affecting PTFE dialysis access grafts.", "PMID": "8479123"}, {"title": "Pulmonary embolism from pulse-spray pharmacomechanical thrombolysis of clotted hemodialysis grafts: urokinase versus heparinized saline.", "abstract": "To compare the frequency and extent of pulmonary embolism (PE) occurring during pulse-spray pharmacomechanical thrombolysis (PSPMT) of clotted hemodialysis grafts with use of either urokinase (UK) or heparinized saline (HS). Postintervention primary patency and complication rates were compared for each method of thrombolysis.\n\nTwenty-seven patients were enrolled in this prospective, randomized, double-blind study evaluating PE with two PSPMT agents. The doses of heparin were similar between groups. The only variable was that one group of patients received UK and the other received HS. In two cases, the venous anastomosis could not be crossed. Eleven patients were treated with UK and 14 with HS. Nuclear medicine perfusion lung scans were performed before treatment and after graft declotting procedures. Lung perfusion was quantified to 10% of a pulmonary segment (0 = normal perfusion, 1 = segmental perfusion defect), with nine segments counted for each lung.\n\nBaseline nuclear medicine perfusion lung scan results were abnormal (> or = 20% segmental perfusion defect) in 19 patients (70.4%). New PE (one or more pulmonary segments) occurred in two patients treated with UK (18.2%) and nine patients treated with HS (64.3%; P = .04). All cases of PE were asymptomatic. Quantitative global pulmonary perfusion analyses revealed that treatment with UK improved flow to 0.2 +/- 2.0 pulmonary segments, whereas treatment with HS decreased perfusion to 1.0 +/- 1.7 segments (P = .16, NS). Although postintervention primary patency rates were similar according to life-table analysis (P = .76, NS), complication rates were higher with use of HS (n = 4, 28.6%) than with use of UK (n = 2, 18.2%) (P = .6, NS).\n\nAll PE were asymptomatic during PSPMT, but treatment with UK reduced the rate of PE and tended to result in smaller defects in lung scan results. Most patients undergoing hemodialysis have abnormal baseline perfusion scan results, but PSPMT with UK improved many of them. The postintervention primary patency rates were similar between groups, but complications were more frequent after treatment with HS.", "PMID": "11041470"}, {"title": "Thrombosed hemodialysis grafts: percutaneous mechanical balloon declotting versus thrombolysis.", "abstract": "To compare a technique of mechanical balloon declotting of thrombosed hemodialysis grafts with conventional pulsed-spray thrombolysis.\n\nForty patients had 53 episodes of graft thrombosis over a 19-month period. Twenty-nine grafts were randomly treated with thrombolysis with urokinase and 24 grafts with mechanical declotting by placement of crossed balloon catheters within the graft. Patency was determined by retrospective review of hemodialysis records.\n\nSuccessful hemodialysis for 1 week after the procedure was achieved in 21 (88%) of the 24 grafts treated mechanically and 26 (90%) of 29 grafts treated with thrombolysis. Continuous pulse oximetry showed no change in oxygen saturation in either group, and no clinical signs or symptoms of pulmonary embolism were noted. Average total procedure times were 2.2 hours for mechanical declotting and 3.5 hours for thrombolysis (P < .05). Probability of patency (mechanical vs thrombolysis) was 42% vs 45% at 3 months, 36% vs 25% at 6 months, and 8% vs 4% at 12 months. One major complication of ulnar artery embolization occurred in the thrombolysis group.\n\nMechanical declotting of hemodialysis grafts is faster and as effective as thrombolysis.", "PMID": "7784593"}, {"title": "Clinical and Economic Benefits of Stent Grafts in Dysfunctional and Thrombosed Hemodialysis Access Graft Circuits in the REVISE Randomized Trial.", "abstract": "To compare reinterventions and associated costs to maintain arteriovenous graft hemodialysis access circuits after rescue with percutaneous transluminal angioplasty (PTA), with or without concurrent Viabahn stent grafts, over 24 months.\n\nThis multicenter (n\u00a0= 30 sites) study evaluated reintervention number, type, and cost in 269 patients randomized to undergo placement of stent grafts or PTA alone. Outcomes were 24-month average cumulative number of reinterventions, associated costs, and total costs for all patients and in 4 groups based on index treatment and clinical presentation (thrombosed or dysfunctional).\n\nOver 24 months, the patients in the stent graft arm had a 27% significant reduction in the average number of reinterventions within the circuit compared to the PTA arm (3.7 stent graft vs 5.1 PTA; P\u00a0= .005) and similar total costs ($27,483 vs $28,664; P\u00a0= .49). In thrombosed grafts, stent grafts significantly reduced the number of reinterventions (3.7 stent graft vs 6.2 PTA; P\u00a0= .022) and had significantly lower total costs compared to the PTA arm ($30,329 vs $37,206; P\u00a0= .027). In dysfunctional grafts, no statistical difference was observed in the number of reinterventions or total costs (3.7 stent graft vs 4.4 PTA; P\u00a0= .12, and $25,421 stent graft and $22,610 PTA; P\u00a0= .14).\n\nOver 24 months, the use of stent grafts significantly reduced the number of reinterventions for all patients, driven by patients presenting with thrombosed grafts. Compared to PTA, stent grafts reduced overall treatment costs for patients presenting with thrombosed grafts and had similar costs for stenotic grafts.", "PMID": "30717951"}, {"title": "Balloon angioplasty versus Viabahn stent graft for treatment of failing or thrombosed prosthetic hemodialysis grafts.", "abstract": "To compare the results of stent graft placement to balloon angioplasty for the treatment of stenosis at the venous anastomosis of failing and thrombosed prosthetic hemodialysis grafts.\n\nThis prospective, multicenter trial included 293 patients randomized (1:1) to the stent graft (n\u00a0= 145) or balloon angioplasty (n\u00a0= 148) group for treatment of stenosis at the venous anastomosis of dysfunctional (n\u00a0= 164) or thrombosed (n\u00a0= 129) hemodialysis grafts. The primary study end point was target lesion primary patency at 6\u00a0months; participants were followed for up to 24\u00a0months. Primary patency of the access circuit was a secondary end point. Statistical analysis of effectiveness was performed using both the intent-to-treat population and the effectiveness-per-protocol (EPP) populations for primary patency end points. Statistical analysis of additional effectiveness end points was performed using the EPP population.\n\nThe 6-month target lesion primary patency was statistically greater in the stent graft group than the balloon angioplasty group (intent-to-treat, 51.6% vs 34.2% [P\u00a0= .006]; EPP, 52.9% vs 35.5% [P\u00a0= .008]). Compared with the angioplasty group, the stent graft group increased the median time from the index procedure to the next intervention on the target lesion by 95\u00a0days (203 vs 108 days). Patients with dysfunctional (stenotic) grafts had higher target lesion primary patency compared with patients with thrombosed grafts regardless of treatment (EPP, stent graft, 64.6% vs 36.1% and balloon angioplasty, 45.8% vs 23.5%). When compared with angioplasty, using a stent graft for treatment of a venous anastomotic stenosis of a thrombosed graft increased the 6-month target lesion primary patency by 53.6% (EPP, 36.1% vs 23.5%).\n\nWhen compared with balloon angioplasty, a stent graft provided superior target lesion primary patency at 6\u00a0months for treatment of venous anastomotic stenoses of dysfunctional and thrombosed prosthetic hemodialysis grafts.", "PMID": "27353358"}], "labels": [{"PMID": "10527197", "label": "included"}, {"PMID": "10540659", "label": "included"}, {"PMID": "10587385", "label": "included"}, {"PMID": "11054238", "label": "included"}, {"PMID": "11110928", "label": "included"}, {"PMID": "8479123", "label": "excluded"}, {"PMID": "11041470", "label": "excluded"}, {"PMID": "7784593", "label": "excluded"}, {"PMID": "30717951", "label": "excluded"}, {"PMID": "27353358", "label": "excluded"}]}
{"metadata": {"review_pmid": "38353301"}, "inputs": {"background": "Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) causes progressive or relapsing weakness and numbness of the limbs, which lasts for at least two months. Uncontrolled studies have suggested that intravenous immunoglobulin (IVIg) could help to reduce symptoms. This is an update of a review first published in 2002 and last updated in 2013.", "objectives": "To assess the efficacy and safety of intravenous immunoglobulin in people with chronic inflammatory demyelinating polyradiculoneuropathy.", "selection criteria": "We selected randomised controlled trials (RCTs) and quasi-RCTs that tested any dose of IVIg versus placebo, plasma exchange, or corticosteroids in people with definite or probable CIDP."}, "context": [{"title": "Randomized controlled trial of IVIg in untreated chronic inflammatory demyelinating polyradiculoneuropathy.", "abstract": "To determine the efficacy of IV immunoglobulin (IVIg) given patients with untreated chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).\n\nA randomized, double-blind, multicenter, investigator-initiated study compared IVIg (Aventis Behring LLC, King of Prussia, PA) with placebo (5% albumin). On days 1, 2, and 21, IVIg (1 g/kg) or placebo was given. The primary outcome measure was the change in muscle strength from baseline to day 42, using the average muscle score (AMS). Secondary outcome measures included change from baseline AMS at days 10 and 21, the Hughes' functional disability scale, forced vital capacity (FVC), and nerve conduction studies (NCS) of four motor nerves (median, ulnar, peroneal, and tibial).\n\nThe patients (n = 33) were randomized. Of these, 30 (14 women, 16 men, aged 54 +/- 20 years, range 13 to 82) received IVIg and 23 were given placebo (12 women, 11 men, aged 50 +/- 18 years, range 23 to 73). Baseline AMS values of the groups were similar (IVIg 7.06 +/- 1.31 versus placebo 7.28 +/- 1.18, p = 0.53). There were two dropouts in placebo group and one in the IVIg group. Mean AMS improved at day 42 comparing IVIg with placebo (0.63 versus -0.1, p = 0.006). Improved strength was seen by day 10. The placebo group lost strength over this same interval. In the IVIg, 11 subjects improved by the functional disability scale; none worsened. This differed (p = 0.019) from those in the placebo-treated group (two improved, two got worse, remainder unchanged). Forced vital capacity did not improve with IVIg treatment. IVIg improved ulnar motor distal latency (p = 0.005), tibial distal compound muscle amplitude (p = 0.003), and peroneal nerve conduction velocity (p = 0.03).\n\nIVIg improves strength in patients with untreated CIDP by day 10 with continued benefit through day 42; more than one third improve by at least a functional grade on a disability scale. This study provides data supporting IVIg as the initial treatment for CIDP.", "PMID": "11222785"}, {"title": "Randomized controlled trial of intravenous immunoglobulin versus oral prednisolone in chronic inflammatory demyelinating polyradiculoneuropathy.", "abstract": "This multicenter, randomized, double-blind, crossover trial compared a six week course of oral prednisolone tapering from 60 mg to 10 mg daily with intravenous immunoglobulin (IVIg) 2.0 g/kg given over one to two days for treating chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Twenty-four of the thirty-two randomized patients completed both treatment periods. Both treatments produced significant improvements in the primary outcome measure, change in an 11-point disability scale two weeks after randomization. There was slightly, but not significantly, more improvement after IVIg than with prednisolone, the mean difference between the groups in change in disability grade being 0.16 (95% CI = -0.35 to 0.66). There were also slightly, but not significantly, greater improvements favoring IVIg in the secondary outcome measures: time to walk 10 meters after two weeks and improvement in disability grade after six weeks. Results may have been biased against IVIg by the eight patients who did not complete the second arm of the trial. A serious adverse event (psychosis) attributable to treatment occurred in one patient while on prednisolone and in none with IVIg.", "PMID": "11506402"}, {"title": "Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial.", "abstract": "Short-term studies suggest that intravenous immunoglobulin might reduce disability caused by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but long-term effects have not been shown. We aimed to establish whether 10% caprylate-chromatography purified immune globulin intravenous (IGIV-C) has short-term and long-term benefit in patients with CIDP.\n\n117 patients with CIDP who met specific neurophysiological inflammatory neuropathy cause and treatment (INCAT) criteria participated in a randomised, double-blind, placebo-controlled, response-conditional crossover trial. IGIV-C (Gamunex) or placebo was given every 3 weeks for up to 24 weeks in an initial treatment period, and patients who did not show an improvement in INCAT disability score of 1 point or more received the alternate treatment in a crossover period. The primary outcome was the percentage of patients who had maintained an improvement from baseline in adjusted INCAT disability score of 1 point or more through to week 24. Patients who showed an improvement and completed 24 weeks of treatment were eligible to be randomly re-assigned in a blinded 24-week extension phase. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00220740.\n\nDuring the first period, 32 of 59 (54%) patients treated with IGIV-C and 12 of 58 (21%) patients who received placebo had an improvement in adjusted INCAT disability score that was maintained through to week 24 (treatment difference 33.5%, 95% CI 15.4-51.7; p=0.0002). Improvements from baseline to endpoint were also recorded for grip strength in the dominant hand (treatment difference 10.9 kPa, 4.6-17.2; p=0.0008) and the non-dominant hand (8.6 kPa, 2.6-14.6; p=0.005). Results were similar during the crossover period. During the extension phase, participants who continued to receive IGIV-C had a longer time to relapse than did patients treated with placebo (p=0.011). The incidence of serious adverse events per infusion was 0.8% (9/1096) with IGIV-C versus 1.9% (11/575) with placebo. The most common adverse events with IGIV-C were headache, pyrexia, and hypertension.\n\nThis study, the largest reported trial of any CIDP treatment, shows the short-term and long-term efficacy and safety of IGIV-C and supports use of IGIV-C as a therapy for CIDP.", "PMID": "18178525"}, {"title": "Intravenous immunoglobulin versus intravenous methylprednisolone for chronic inflammatory demyelinating polyradiculoneuropathy: a randomised controlled trial.", "abstract": "Intravenous immunoglobulin (IVIg) and corticosteroids are effective as initial treatment in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but little is known about the comparative risk-benefit profile of their long-term use in this disease. We compared the efficacy and tolerability of 6-month therapy with IVIg versus that with intravenous methylprednisolone.\n\nWe did a multicentre, randomised, double-blind, placebo controlled, parallel-group study in patients with CIDP. We assessed efficacy and tolerability of IVIg (0\u00b75 g/kg per day for 4 consecutive days) and intravenous methylprednisolone (0\u00b75 g in 250 mL sodium chloride solution per day for 4 consecutive days) given every month for 6 months. Eligible patients had to be in an active or stationary phase of the disease. Allocation to treatment was centrally managed with a computer-generated, 1:1 randomisation scheme with a sequential block size of four. All patients and assessors were unaware of the treatment assignment. After therapy discontinuation, patients were followed up for 6 months to assess relapses. The primary outcome was the difference in the number of patients discontinuing either therapy owing to inefficacy or intolerance. Secondary endpoints included the difference in the proportion of patients experiencing adverse events or worsening after therapy discontinuation. This study is registered with EUDRACT, number 2005-001136-76.\n\n45 patients (24 IVIg, 21 intravenous methylprednisolone) completed the study; one was excluded for inappropriate inclusion. More patients stopped methylprednisolone (11 [52%] of 21) than IVIg (three [13%] of 24; relative risk 0\u00b754, 95% CI 0\u00b734-0\u00b787; p=0\u00b70085). When adjusted for sex, age, disease duration, comorbidity, modified Rankin scale and ONLS scores at enrolment, and previous treatment with IVIg and steroids, the difference between the two groups remained significant (odds ratio 7\u00b77, 95% CI 1\u00b77-33\u00b79; p=0\u00b70070). Reasons for discontinuation were lack of efficacy (eight in the methylprednisolone group vs three in the IVIg group), adverse events (one in the methylprednisolone group), or voluntary withdrawal (two in the methylprednisolone group). Two patients on IVIg died during follow-up after the 6-month assessment. The proportion of patients with adverse events did not differ between the intravenous methylprednisolone group (14 [67%] of 21) and the IVIg group (11 [46%] of 24; p=0\u00b71606). After therapy discontinuation, more patients on IVIg worsened and required further therapy (eight [38%] of 21) than did those on methylprednisolone (none of ten; p=0\u00b70317).\n\nTreatment of CIDP with IVIg for 6 months was less frequently discontinued because of inefficacy, adverse events, or intolerance than was treatment with intravenous methylprednisolone. The longer-term effects of these treatments on the course of CIDP need to be addressed in future studies.\n\nKedrion.", "PMID": "22578914"}, {"title": "A plasma exchange versus immune globulin infusion trial in chronic inflammatory demyelinating polyradiculoneuropathy.", "abstract": "Chronic inflammatory demyelinating polyradiculoneuropathy is a paralytic syndrome, causing considerable disability and even death. In controlled clinical trials, plasma exchange prevented or ameliorated neurological deficits, but the efficacy of immune globulin infusion remains unproved. Also unknown is whether immune globulin infusion is as effective, or more effective, than plasma exchange and what dosages and frequencies are best. In this observer-blinded study, using some objective end points not subject to bias (e.g., summated compound muscle action potential), 20 patients with progressive or static polyneuropathy were randomly assigned to receive either of the two treatments for 6 weeks, followed by a washout period, and then were assigned to receive the other treatment. Plasma exchange (twice a week for 3 weeks then once a week for 3 weeks) and immune globulin infusion (0.4 gm/kg once a week for 3 weeks, then 0.2 gm/kg once a week for the next 3 weeks) were used. End points assessed before and after treatment schedules were neurological disability score; muscle weakness of the neurological disability score; summated compound muscle action potentials of ulnar, median, and peroneal nerves; summated sensory nerve action potentials of ulnar and sural nerves; and vibratory detection threshold of the great toe using CASE IV. Observers were masked as to treatment used. Of 20 patients, 13 received both treatments whereas 4 did not worsen sufficiently to receive the second treatment--1 patient left the study during and 2 after the first treatment to receive unscheduled treatment elsewhere.(ABSTRACT TRUNCATED AT 250 WORDS)", "PMID": "7998769"}, {"title": "Intravenous immunoglobulin treatment in patients with chronic inflammatory demyelinating polyneuropathy: a double blind, placebo controlled study.", "abstract": "Patients with a clinical diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) were randomised in a double-blind, placebo-controlled multicentre trial to investigate whether high-dose intravenous immunoglobulin treatment (IVIg) for 5 consecutive days has a beneficial effect. Fifteen patients were randomised to IVIg and 13 to placebo. In the IVIg treatment group 4 patients improved and 3 patients in the placebo group. The degree of improvement of the patients in the IVIg treatment group was no different from the patients in the placebo group. Electrophysiological studies did not show significant differences between the groups. Since a previously performed cross-over trial showed that a selected group of CIDP patients responded better to IVIg than to placebo, it is concluded that we need better criteria to select CIDP patients for treatment with IVIg.", "PMID": "8429321"}, {"title": "Intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy. A double-blind, placebo-controlled, cross-over study.", "abstract": "Thirty patients with definite or probable chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) of chronic progressive (16 patients) or relapsing (14 patients) course were randomly assigned to receive intravenous immunoglobulin (IvIg) 0.4 g per kg body weight or a placebo treatment on 5 consecutive days in a double-blind, cross-over trial. Neurological function was monitored by serial quantitative assessments [neurological disability score (NDS); clinical grade (CG) and grip strength (GS) measurements] and by electrophysiological studies before and after each treatment period. Twenty-five patients completed both treatment periods. A comparison of the observed changes in clinical outcome measures revealed statistically significant differences in favour of IvIg, with (mean +/- SD) improvements in NDS by 24.4 +/- 5.4 points (P < 0.002) in CG by 1 +/- 0.3 points (P < 0.001) in GS by +6.3 +/- 1.7 kg (P < 0.005), whereas scores were unchanged or worse with placebo. A secondary two-groups analysis of the first trial period included all 30 patients; 16 patients had been randomly assigned to IvIg and 14 to placebo treatments. Again significant differences in favour of IvIg were observed in all the clinical end-points: improvement in NDS was 35.6 +/- 25 points (P < 0.0001), in CG it was 1.3 +/- 1.9 points (P < 0.002) and in GS +9.8 +/- 7.7 kg (P < 0.001), whereas all scores worsened with placebo. Of the 30 patients, 19 (63%) improved with IvIg treatments; nine out of 16 patients (56%) with chronic progressive CIDP, and 10 out of 14 patients (71%) with relapsing CIDP (differences were not statistically significant). A placebo response was seen in five patients. Comparison of paired electrophysiological measurements before and 4 weeks after IvIg treatments revealed statistically significant improvements in the summed motor conduction velocities (sigma MCV; P < -0.0001) and in the summed compound muscle action potentials (CMAP) evoked with proximal stimulation (sigma proximal CMAP, P < 0.03) of median, ulnar, peroneal and tibial nerves. Eight of nine IvIg responders with chronic progressive CIDP improved gradually to normal function with a single 5 day course of IvIg; in five of these, small doses of prednisone were prescribed during follow-up. In 10 IvIg responders with relapsing CIDP, improvements lasted a median 6 weeks (range 3-22 weeks) and was reproducible with open label treatments. All 10 patients have been maintained and stabilized with IvIg pulse therapy of 1 g per kg body weight or less, given as a single infusion prior to the expected relapse. A beneficial response to IvIg was found to be most likely in patients with acute relapse or with disease of one year or less. Patients with predominantly sensory signs did not improve.", "PMID": "8813271"}, {"title": "[The clinical usefulness of high-dose intravenous immunoglobulin therapy for chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy].", "abstract": "To explore the optimum dose of intravenous immunoglobulin (i.v.Ig) for treating patients with chronic inflammatory demyelinating polyrneuropathy and multifocal motor neuropathy, we compared the usefulness of i.v.Ig among 3 treatment doses. Fifty-nine patients were randomly divided into three treatment dosage groups: 20 patients for Group I using 50 mg/kg/day x 5 days, 19 patients Group II using 200 mg/kg/day x 5 days, and 20 patients Group III using 400 mg/kg/day x 5 days. We assessed clinically and electrophysiologically the effectiveness of the treatment at 5 weeks after the initial infusion. For patients in Group I and II who had not improved (or worsened) with the first treatment, we gave a one-step larger dose in the second treatment (i.e. 200 mg/kg/day x 5 days for those who had been given 50 mg/kg/day x 5 days, 400 mg/kg/day x 5 days for those who had been given 200 mg/kg/day x 5 days) after more than 9 weeks. We found that 15% of the patients in Group I, 21% in Group II and 60% in Group III improved dose-dependently with the first intravenous immunoglobulin treatment. Seven (47%) of 16 patients in Group I and 4 (40%) of 11 patients in Group II improved after the second treatment with larger doses. Adverse reactions including chill sensation, fever, skin eruption and increase in blood GOT and GPT levels were transient and mild. One patient in Group III developed left hemiparesis showing the small infarction in the right thalamus during the course of the treatment, but the symptom was mild. In conclusion, the high-dose intravenous immunoglobulin therapy (400 mg/kg/day x 5 days) is useful for treating patients with CIDP and MMN, although care must be taken of the risk of causing cerebral infarctions.", "PMID": "10198901"}, {"title": "A pilot study to compare the use of the Excorim staphylococcal protein immunoadsorption system and IVIG in chronic inflammatory demyelinating polyneuropathy.", "abstract": "Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune mediated neuropathy responding to immunomodulation with IVIG or plasma exchange (PE). We tested the efficacy and safety of selective immunoglobulin removal by Excorim immunoadsorption (IA) in a pilot trial in CIDP patients randomized to monthly IA or IVIG treatments for 6 months. Response rates at 2 and 6 months were greater with IA due to longer disease duration and greater disability at baseline in the patients receiving IVIG. IA appears to be a safe and efficacious therapy for patients with CIDP, but an appropriately powered clinical trial with stratification for disease duration is required.", "PMID": "16239123"}, {"title": "Efficacy and safety of Privigen(\u00ae) in patients with chronic inflammatory demyelinating polyneuropathy: results of a prospective, single-arm, open-label Phase III study (the PRIMA study).", "abstract": "This prospective, multicenter, single-arm, open-label Phase III study aimed to evaluate the efficacy and safety of Privigen(\u00ae) (10% liquid human intravenous immunoglobulin [IVIG], stabilized with L-proline) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Patients received one induction dose of Privigen (2 g/kg body weight [bw]) and up to seven maintenance doses (1 g/kg bw) at 3-week intervals. The primary efficacy endpoint was the responder rate at completion, defined as improvement of \u22651 point on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale. The preset success criterion was the responder rate being \u226535%. Of the 31 screened patients, 28 patients were enrolled including 13 (46.4%) IVIG-pretreated patients. The overall responder rate at completion was 60.7% (95% confidence interval [CI]: 42.41%-76.43%). IVIG-pretreated patients demonstrated a higher responder rate than IVIG-na\u00efve patients (76.9% vs. 46.7%). The median (25%-75% quantile) INCAT score improved from 3.5 (3.0-4.5) points at baseline to 2.5 (1.0-3.0) points at completion, as did the mean (standard deviation [SD]) maximum grip strength (66.7 [37.24] kPa vs. 80.9 [31.06] kPa) and the median Medical Research Council sum score (67.0 [61.5-72.0] points vs. 75.5 [71.5-79.5] points). Of 108 adverse events (AEs; 0.417 AEs per infusion), 95 AEs (88.0%) were mild or moderate in intensity and resolved by the end of study. Two serious AEs of hemolysis were reported that resolved after discontinuation of treatment. Thus, Privigen provided efficacious and well-tolerated induction and maintenance treatment in patients with CIDP.", "PMID": "23781960"}], "labels": [{"PMID": "11222785", "label": "included"}, {"PMID": "11506402", "label": "included"}, {"PMID": "18178525", "label": "included"}, {"PMID": "22578914", "label": "included"}, {"PMID": "7998769", "label": "included"}, {"PMID": "8429321", "label": "included"}, {"PMID": "8813271", "label": "included"}, {"PMID": "10198901", "label": "excluded"}, {"PMID": "16239123", "label": "excluded"}, {"PMID": "23781960", "label": "excluded"}]}
{"metadata": {"review_pmid": "38353289"}, "inputs": {"background": "Variation in blood pressure levels display circadian rhythms. Complete 24-hour blood pressure control is the primary goal of antihypertensive treatment and reducing adverse cardiovascular outcomes is the ultimate aim. This is an update of the review first published in 2011.", "objectives": "To evaluate the effectiveness of administration-time-related effects of once-daily evening versus conventional morning dosing antihypertensive drug therapy regimens on all-cause mortality, cardiovascular mortality and morbidity, total adverse events, withdrawals from treatment due to adverse effects, and reduction of systolic and diastolic blood pressure in people with primary hypertension.", "selection criteria": "We included randomised controlled trials (RCTs) comparing the administration-time-related effects of evening with morning dosing monotherapy regimens in people with primary hypertension. We excluded people with known secondary hypertension, shift workers or people with white coat hypertension."}, "context": [{"title": "Morning versus evening amlodipine treatment: effect on circadian blood pressure profile in essential hypertensive patients.", "abstract": "OBJECTIVE: To determine the antihypertensive efficacy and the potential impact on circadian blood pressure pattern of morning versus evening administration of amlodipine to essential hypertensive patients. METHODS: Twelve mild-to-moderate essential hypertensives were investigated in this open, randomized cross-over study. Blood pressure and heart rate were measured by use of ambulatory blood pressure monitoring after a wash-out period of 1 week and after treatment schedules with 5 mg amlodipine once a day either at 0800 h or at 2000 h for 3 weeks. Effects were evaluated by linear and rhythm analysis using the ABPM-FIT program. RESULTS: Both morning and evening administrations of amlodipine significantly (P < 0.01) reduced the elevated systolic and diastolic blood pressures during daytime. However, due to baseline values being lower during night-time, a significant (P < 0.05) reduction was observed only in systolic, not in diastolic, blood pressure. Maximal blood pressure values were significantly (P </= 0.01) decreased by both treatment regimens, whereas nightly minimum values remained unchanged. The early morning rise in blood pressure was decreaseed after morning and slightly more pronounced aftger evening dosing of amlodipine. Though both amlodipine treatments more effectively reduced daytime blood pressure levels, the circadian profile was not greatly affected. Amlodipine treatment had no effect on heart rate. CONCLUSION: The results demonstrate that, independently from the dosing time, the long-acting calcium antagonist amlodipine sufficiently reduced blood pressure in essential hypertensive patients without increasing the nightly drop. The drug-induced decrase in the early morning rise in blood pressure may be advantageous in reducing the early morning cardiovascular risk.", "PMID": "10212327"}, {"title": "Differential effects of morning and evening dosing of nisoldipine ER on circadian blood pressure and heart rate.", "abstract": "The time of administration of once-daily antihypertensive agents may have a significant impact on blood pressure control during awake and sleep periods. Using 24-h ambulatory monitoring, we compared the effects of morning and evening dosing of the long-acting dihydropyridine calcium channel blocker, nisoldipine extended-release (ER), on circadian blood pressure (BP) and heart rate in patients with mild-to-moderate hypertension. After completing a 3-week placebo run-in period, 85 patients were randomized to morning versus evening nisoldipine ER treatment at a fixed 20-mg dose. Patients were treated for 4 weeks, followed by crossover to the alternate dosing regimen for 4 additional weeks. Twenty-four-hour ambulatory monitoring was performed at baseline and at 4 and 8 weeks after randomization. Awake and sleep times were determined by electronic activity recorders (Actigraphy). Similar least-squares (+/-SE) mean changes from baseline in 24-h BP (systolic BP/diastolic BP: -11.9/-7.4 +/- 0.6/0.5 v -11.6/-6.5 +/- 0.6/0.5 mm Hg) and heart rate (1.0/1.7 +/- 0.4/0.4 beats/min) occurred with morning and evening administration, respectively. A significantly greater effect on awake diastolic BP (systolic BP/diastolic BP: -12.6/-8.1 +/- 0.7/0.4 v -11.3/-6.4 +/- 0.7/0.4 mm Hg; P = .16/.01) was observed with morning dosing compared with evening dosing. In addition, small increases in sleep and early morning heart rate were seen with evening compared with morning administration of nisoldipine (sleep, 3.1 +/- 0.4 v 0.4 +/- 0.4 beats/min; P < .001; early morning, 3.5 +/- 0.7 v 0.5 +/- 0.7 beats/min; P = .002). These differential effects on awake BP and sleep heart rate were also observed in patients who had normal (dippers) and elevated (nondippers) BP values during sleep. Appropriate evaluation of the efficacy and safety of long-acting antihypertensive agents is essential when evening administration is being considered. In the present study, the timing of nisoldipine ER administration had no effect on mean changes in BP and heart rate over a 24-h period. However, nisoldipine ER had some differential effects during sleep and awake periods with morning relative to evening dosing.", "PMID": "10480474"}, {"title": "Efficacy and safety of a once daily graded-release diltiazem formulation in essential hypertension.", "abstract": "The efficacy and safety of a chronotherapeutic, graded-release diltiazem HCl extended-release (GRD) 120-, 240-, 360- and 540-mg dose administered once-daily at bedtime (10 PM) were evaluated in a 7-week randomized, double-blind comparison to placebo and to GRD 360 mg administered once-daily at 8 AM in 478 patients with moderate-to-severe essential hypertension.\n\nWe assessed the change from baseline to end point in trough diastolic blood pressure (DBP) at 6 PM to 10 PM and in mean DBP from 6 AM to 12 noon between GRD 360 mg PM and GRD 360 mg AM, measured by ambulatory BP monitoring (ABPM).\n\nBedtime doses of GRD showed dose-related mean reductions in trough DBP that were significant for GRD doses of 240 mg and higher. Bedtime GRD 360 mg was associated with a significantly greater reduction in mean DBP between 6 AM and 12 noon compared to morning GRD 360 mg with a least squares mean for treatment difference of -3.3 mm Hg (P =.0004). Similar dose-related and significant reductions in systolic BP (SBP) and heart rate (HR) were obtained. Incidence of adverse events (AEs) for all GRD groups (44.5%) was less than that obtained for the placebo group (49.3%). The 540-mg group showed an incidence of AEs (43.5%) similar to that observed for the 240-mg group (42.6%).\n\nThe GRD dose-dependently significantly reduces BP and HR over the 24-h interval after once-daily bedtime dosing. Further greater reductions were obtained between 6 AM and 12 noon, when circadian BP is highest, compared to morning administration of the same dose. The 540-mg GRD was safe, well tolerated, and offers further therapeutic option for patients with severe hypertension who required additional BP control.", "PMID": "12517683"}, {"title": "[Preventive chronotherapy with capoten in hypertensive outpatients].", "abstract": "The study was made of effectiveness of preventive chronotherapy (PC) and comparative benefit of preventive CT vs conventional therapy (CT) in 47 patients with essential hypertension (EH) stage I, II and III. The group on PC consisted of 25 patients. Capoten was given in a single dose from 12.5 to 50 mg 24 hours before the acrophase of blood pressure (BP). BP was measured 4-5 times a day for 4 days according to N. S. Korotkov's technique before the treatment and for the first 4 days of capoten treatment. A course of preventive CT was to continue for 30 days.", "PMID": "10234946"}, {"title": "[Time-dependent effects of ramipril in patients with hypertension of 2 stage].", "abstract": "Time-related effects of ramipril were studied in 30 patients with essential hypertension stage II. Central hemodynamics, chronostructure of circadian rhythms of systolic, diastolic and mean arterial pressure, heart rate, double product were assessed before and after ramipril intake throughout 24 hours. The patients were randomized into 3 equal groups by time of ramipril administration: morning, afternoon and evening. Ramipril was given in dose 5 mg at 8 a.m., 14.00 or 17.00 and 20.00 p.m. Some hemodynamic parameters were measured each 4 hours. The data were analyzed using variation statistics and cosinor-analysis. Hypotensive effect of ramipril appeared approximately the same. Hemodynamics responded better after the evening intake of the drug.", "PMID": "10635654"}, {"title": "Baseline Characteristics and Early Blood Pressure Control in the CONVINCE Trial.", "abstract": "-Blood pressure (BP) control rates around the world are suboptimal. Part 2 of the National Health and Nutrition Educational Survey (NHANES) III indicates that only 27.4% of hypertensive Americans aged 18 to 74 years have a BP of <140/90 mm Hg. We wanted to assess BP control during the first 2 years and to describe the baseline characteristics of patients enrolled in the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Study, an international clinical trial that compares outcomes in hypertensive patients randomized to initial treatment with either controlled-onset extended-release verapamil or the investigator's choice of atenolol or hydrochlorothiazide. At randomization, BP was <140/90 mm Hg in only 20.3% of the 16 602 subjects (average+/-SD age 65.6+/-7.4 years; 56% women, 84% white/7% black/7% Hispanic). The average BP at enrollment was 148/85 mm Hg for patients taking BP medications (n=13 879) and 161/94 mm Hg for previously untreated patients (n=2723). After medication titration, with a transtelephonic computer that recommended an increase in the dose or number of antihypertensive agents whenever the BP was 140/90 mm Hg, 84.8% of the subjects attained the goal BP. During 2 years of treatment, BP control was maintained in 67% to 69% of the subjects (69% to 71% for systolic BP of <140 mm Hg and 90% for diastolic BP of <90 mm Hg). These data suggest that the control of systolic BP is more difficult than the control of diastolic BP. The US national goal of having 50% of hypertensives with a BP of <140/90 mm Hg may be achievable if a forced titration strategy is used. Interested investigators, free care and medications, and well-educated subjects may make the attainment of such a goal easier in the CONVINCE study than in the general population.", "PMID": "11208750"}, {"title": "Management of antihypertensive treatment with Lisinopril: a chronotherapeutic approach.", "abstract": "Risk for cardiovascular events seems to be higher in the early morning, also as consequence of a rise in blood pressure (BP) values due to the characteristic circadian pattern of BP variability. Therefore, a suitable therapeutic BP control should be tightest during the early morning. On the basis of the ambulatory blood pressure monitoring (ABPM) studies, it has been previously demonstrated that the antihypertensive effect of once daily drug, generally administrated in the morning, decreases at the end of the dosing period. A chronotherapeutic approach to the management of hypertension (this field has been pourly investigated so far) would allow the assessment of the optimum timing of drug dosing, according to the circadian BP rhythm and to the chronorisk maps, in hypertensive patients affected by associated vascular pathologies. This would increase the therapeutic effects. The aim of this study was to assess BP changes due to ACE-inhibitor (Lisinopril 20 mg/die) once daily administration at three different times (8.00 AM, 4.00 PM, 10.00 PM), in order to optimise the dosing time. 40 subjects (mean age +/- SD: 45 +/- 10) affected by primary mild to moderate hypertension were submitted to ABPM for 24 hours, by means of Spacelabs 90207, before and after pharmacological treatment. Patients were randomised to take the drug at 8.00 AM, 4.00 PM or 10.00 PM, and they repeated ABPM every two months, by changing the dosing time. The chronobiological analysis showed: 1) a sensible decrease both in Systolic (S)BP and Diastolic (D)BP without affecting the circadian rhythm, in all evaluations; 2) a greater reduction of SBP and DBP from 6.00 AM to 11.00 AM, period in which cardiovascular risk is higher, after 10.00 PM dosing; 3) no other sensible reduction in SBP and DBP occurred after night administration as compared to that caused by other dosing times. Lisinopril administration at 10.00 PM. has been shown to be much more useful since, although BP circadian rhythm was unmodified, it protects hypertensive patients from both vascular chronorisk and Cruickshank effect (J-curve). Therefore, a chronobiologist antihypertensive treatment in order to increase the therapeutic effect already obtained with the traditional statistic methods.", "PMID": "11261739"}, {"title": "[Controlled release diltiazem in monotherapy of hypertension--time of drug administration and circadian blood pressure pattern].", "abstract": "30 patients with primary mild to moderate hypertension (DBP 95-110 mm Hg) were treated with long acting diltiazem (120 or 240 mg) once daily in the morning (7.00-8.00 a.m.) for at least 3 weeks and after that the administration time was changed to evening dose (19.00-20.00 p.m.) for next 3 weeks. 24-hours ABPM was performed in all patients on the last day of each period. Obtained recordings were compared in different periods of time: total 24 hours, 6.00-23.00, 23.00-6.00, 4.30-8.00, 5.00-11.00, 20.00-2.00. Mean values of systolic and diastolic blood pressure, heart rate and pressure load (defined as percentage of records above 140/90 mm Hg in day and above 120/80 mm Hg at night) did not differ significantly between investigated dosage regimens. The evening administration of diltiazem did not produce greater decrease of BP at night than the morning dose. For this reason slow release formulation of diltiazem (oxycardil in doses of 120 to 240 mg) can be safely administered in the evening if needed.", "PMID": "11424664"}, {"title": "[Advantages of capoten chronotherapy of patients with hypertension in an outpatient setting].", "abstract": "To compare the efficiency of a short course of preventive chronotherapy and traditional therapy with capoten in an outpatient setting.\n\nForty-two patients with stage II essential hypertension were divided into 2 groups: 20 controls were treated with capoten in a dose of 12.5-50 mg 3 times a day and 22 received capoten once a day in the same single dose 1.5-2 h before arterial pressure (AP) acrophase. Central hemodynamics was studied by echocardiography, regional hemodynamics by reheoencephalography before and at the end of therapy.\n\nIn the control group AP normalized after capoten therapy in 3 patients, decreased by at least 10% but did not normalize in 9, and did not change in 8 patients. The results in the chronotherapy group were as follows: AP normalized in 5, decreased by at least 15% in 13, and did not change in 4 patients. Normalization of daily profiles of hemodynamic values and more favorable shifts in the cerebral bloodflow were more often seen in patients who received chronotherapy.\n\nCapoten chronotherapy of patients with essential hypertension, carried out in an outpatient setting, is obviously preferable to traditional treatment: no side effects were observed and a better hypotensive effect was attained with lower total dose.", "PMID": "11878051"}, {"title": "Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial.", "abstract": "Hypertensive patients are often given a calcium antagonist to reduce cardiovascular disease risk, but the benefit compared with other drug classes is controversial.\n\nTo determine whether initial therapy with controlled-onset extended-release (COER) verapamil is equivalent to a physician's choice of atenolol or hydrochlorothiazide in preventing cardiovascular disease.\n\nDouble-blind, randomized clinical trial conducted at 661 centers in 15 countries. A total of 16 602 participants diagnosed as having hypertension and who had 1 or more additional risk factors for cardiovascular disease were enrolled between September 1996 and December 1998 and followed up until December 31, 2000. After a mean of 3 years of follow-up, the sponsor closed the study before unblinding the results.\n\nInitially, 8241 participants received 180 mg of COER verapamil and 8361 received either 50 mg of atenolol or 12.5 mg of hydrochlorothiazide. Other drugs (eg, diuretic, beta-blocker, or an angiotensin-converting enzyme inhibitor) could be added in specified sequence if needed.\n\nFirst occurrence of stroke, myocardial infarction, or cardiovascular disease-related death.\n\nSystolic and diastolic blood pressure were reduced by 13.6 mm Hg and 7.8 mm Hg for participants assigned to the COER verapamil group and by 13.5 and 7.1 mm Hg for partcipants assigned to the atenolol or hydrochlorothiazide group. There were 364 primary cardiovascular disease-related events that occurred in the COER verapamil group vs 365 in atenolol or hydrochlorothiazide group (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.88-1.18; P =.77). For fatal or nonfatal stroke, the HR was 1.15 (95% CI, 0.90-1.48); for fatal or nonfatal myocardial infarction, 0.82 (95% CI, 0.65-1.03); and for cardiovascular disease-related death, 1.09 (95% CI, 0.87-1.37). The HR was 1.05 (95% CI, 0.95-1.16) for any prespecified cardiovascular disease-related event and 1.08 (95% CI, 0.93-1.26) for all-cause mortality. Nonstroke hemorrhage was more common with participants in the COER-verapamil group (n = 118) compared with the atenolol or hydrochlorothiazide group (n = 79) (HR, 1.54 [95% CI, 1.16-2.04]; P =.003). More cardiovascular disease-related events occurred between 6 AM and noon in both the COER verapamil (99/277) and atenolol or hydrochlorothiazide (88/274) groups; HR, 1.15 (95% CI, 0.86-1.53).\n\nThe CONVINCE trial did not demonstrate equivalence of a COER verapamil-based antihypertensive regimen compared with a regimen beginning with a diuretic or beta-blocker. When considered in the context of other trials of calcium antagonists, these data indicate that the effectiveness of calcium-channel therapy in reducing cardiovascular disease is similar but not better than diuretic or beta-blocker treatment.", "PMID": "12709465"}], "labels": [{"PMID": "10212327", "label": "included"}, {"PMID": "10480474", "label": "included"}, {"PMID": "12517683", "label": "included"}, {"PMID": "10234946", "label": "excluded"}, {"PMID": "10635654", "label": "excluded"}, {"PMID": "11208750", "label": "excluded"}, {"PMID": "11261739", "label": "excluded"}, {"PMID": "11424664", "label": "excluded"}, {"PMID": "11878051", "label": "excluded"}, {"PMID": "12709465", "label": "excluded"}]}
{"metadata": {"review_pmid": "38348930"}, "inputs": {"background": "Infants born preterm are at increased risk of cognitive and motor impairments compared with infants born at term. Early developmental interventions for preterm infants are targeted at the infant or the parent-infant relationship, or both, and may focus on different aspects of early development. They aim to improve developmental outcomes for these infants, but the long-term benefits remain unclear. This is an update of a Cochrane review first published in 2007 and updated in 2012 and 2015.", "objectives": "Primary objective To assess the effect of early developmental interventions compared with standard care in prevention of motor or cognitive impairment for preterm infants in infancy (zero to < three years), preschool age (three to < five years), and school age (five to < 18 years). Secondary objective To assess the effect of early developmental interventions compared with standard care on motor or cognitive impairment for subgroups of preterm infants, including groups based on gestational age, birthweight, brain injury, timing or focus of intervention and study quality.", "selection criteria": "Studies included randomised, quasi-randomised controlled trials (RCTs) or cluster-randomised trials of early developmental intervention programmes that began within the first 12 months of life for infants born before 37 weeks' gestational age (GA). Interventions could commence as an inpatient but had to include a post discharge component for inclusion in this review. Outcome measures were not prespecified, other than that they had to assess cognitive outcomes, motor outcomes or both. The control groups in the studies could receive standard care that would normally be provided."}, "context": [{"title": "Neurodevelopment until the adjusted age of 2 years in extremely low birth weight infants after early intervention--a case-control study.", "abstract": "A total of 104 infants with birth weights of less than 1000 grams were enrolled in this prospective case-control study in order to examine the effect of occupational therapy based on sensory integration (SI) and neurodevelopmental therapy (NDT) on neurological development. The children were grouped as matched pairs on the basis of a set of developmental risks assessed at the age of 3 months. The intervention children had a weekly session of 60 minutes of occupational therapy from the corrected age of 6 months up to 12 months. All the children were examined at the corrected age of 3, 6, 9, 12, 18 and 24 months. The neurodevelopment of the cases and the controls did not differ essentially and the only significant difference was found in the social development of the children at the age of 12 months to the advantage of the intervention group. It is concluded that this amount of occupational therapy in at-risk children does not have a relevant effect on neurological development.", "PMID": "10048099"}, {"title": "One-year outcome of auditory-tactile-visual-vestibular intervention in the neonatal intensive care unit: effects of severe prematurity and central nervous system injury.", "abstract": "Thirty-seven infants with severe central nervous system injury or extreme prematurity were randomly assigned to a multisensory (auditory-tactile-visual-vestibular) intervention or control group. Intervention began in the hospital at 33 weeks' postconceptional age and continued twice daily in the home until 2 months' corrected age. Mother-infant interactions during feedings were videotaped, and the Bayley Scales of Infant Development were administered. Control mothers stimulated their infants more during feeding, but these significant differences dissipated by 4 months. The presence of periventricular leukomalacia was associated with significantly poorer mental development, regardless of group assignment. Experimental infants tended to exhibit better motor and mental performance and had 23% fewer cerebral palsy diagnoses at 1 year, but these trends were not statistically significant. The type of brain injury was more important in determining 1-year developmental outcome than type of postnatal experience, suggesting that periventricular leukomalacia presents a major challenge for infant development.", "PMID": "11453445"}, {"title": "Cognitive performance and attachment patterns at four years of age in extremely low birth weight infants after early intervention.", "abstract": "This study aims at assessing the effects of an early occupational therapy intervention on the cognitive development and the development of attachment patterns in ELBW infants. The intervention, given weekly at home from six months to 12 months, aimed at supporting parent-child interaction and enhancing motor control and coordination. The study population consisted of 100 ELBW infants matched in pairs in accordance to their pre-perinatal risk scores and allocated successively to intervention or non-intervention groups. Cognitive development was assessed with the Bayley Scales at age two and with the WPPSI at age four. Attachment to primary caregiver was assessed with the Preschool Assessment of Attachment (PAA). Cognitive performance was within age norms in both groups at both ages. Intervention did not show any effect on cognitive performance at the age of two years. At the age of four years, cognitive level was overall, and most notably for verbal performance, higher in the intervention group than in the control group. There was an over-representation of the so-called atypical attachment patterns (those not fitting the normative A, B, or C categories) in the control group. The results are discussed in terms of finding more global ways to support the development of at risk pre-term children.", "PMID": "11469284"}, {"title": "Effect of a developmental program on motor performance in infants born preterm.", "abstract": "A randomised controlled trial was conducted to evaluate the effect of a motor developmental program in improving motor performance in Thai infants born preterm. Eighty-four preterm born infants were randomly assigned to either a control or intervention group. Additionally, 27 low-risk preterm infants were included forming a comparative group for this study. From term equivalent age to four months adjusted age, all infants had their motor performance assessed monthly with the Test of Infant Motor Performance by one of the physiotherapist research assistants blind to group assignment and infants' adjusted age. In addition, the intervention infants received a developmental program at each monthly visit. Motor performance for each group plotted against age revealed linear trends of progression. The intervention group showed the greatest improvement. Two-way repeated measures ANOVA revealed significant differences across age and among groups. Scheff\u00e9 comparisons indicated that the mean differences between each pair of the three groups were significant and supported the finding of greater improvement of the intervention infants over the control group. Thus the results suggest that the intervention program is likely to have beneficial effects when offered to a similar population of preterm born infants.", "PMID": "11552873"}, {"title": "Early intervention promotes intellectual development of premature infants: a preliminary report. Early Intervention of Premature Infants Cooperative Research Group.", "abstract": "To evaluate the effect of early intervention on the intellectual development of the premature infants.\n\nPremature infants at gestational age of 28-36.9 weeks were randomly divided into two groups: intervention and conventional care groups. Normal newborn infants during the same period were included in the control group (routine care). Up to March 1996, 156 cases were over the age 1.5-2 years (corrected age), 52 in the intervention group, 51 in the conventional care group and 53 in the normal control group. Parents were taught to carry out the 0-2 year intervention program, which included motor, cognitive, speech development and social behavior. Every three months, height, weight and head circumference were measured. At the age of one and a half and two years, all infants in the three groups received infant development tests of Child Development Center of China (CDCC) scale. The examiner did not know which infant had received intervention.\n\nThere was no significant difference in biological factors among the two premature groups and in cultural and social factors among the three groups. Intelligence tests at the age of one and a half and two years showed that the average mental development index (MDI) in the intervention group was 13.8 and 14.6 higher than those in the conventional care group and the differences were significant. The psychomotor development index (PDI) was 5.2 and 4.7 higher but the differences were not significant. The MDI and PDI in the intervention group and normal control were quite close, but at two years, the MDI and PDI in the intervention group were 5.7 and 7.3 higher than those in the normal control and the differences were significant (P < 0.05). Compared with the normal control, the MDI in conventional care group at one and a half and two years of age were 11.5 and 8.9 lower. The difference was very significant. There were four cases of mental retardation, whose mental development index (MDI) was less then 70 in the conventional care group, but none in the intervention group.\n\nEarly intervention can promote intellectual development of the premature infants and may be beneficial to the prevention of mental retardation. Early and intensive intervention can produce better results. Bringing parent's initiative into full play through deepening their understanding of the importance of early intervention is the key to success.", "PMID": "11605609"}, {"title": "Improving cognitive development of low-birth-weight premature infants with the COPE program: a pilot study of the benefit of early NICU intervention with mothers.", "abstract": "The purpose of this pilot study was to evaluate the effectiveness of a parent-focused intervention program (COPE) on infant cognitive development and maternal coping. A randomized clinical trial was conducted with 42 mothers of low-birth-weight (LBW) premature infants hospitalized in a neonatal intensive care unit (NICU), with follow-up at 3 months' and 6 months' corrected ages. COPE mothers received the four-phase educational-behavioral program that began 2-4 days postbirth and continued through 1 week following discharge from the NICU. Comparison mothers received audiotaped information during the same four time frames. Results indicated that COPE infants had significantly higher mental development scores at a 3 months' corrected age (M = 100.3) than did the comparison infants (M = 93.9), and this difference widened at 6 months' corrected age, with COPE infants scoring 14 points higher. COPE mothers were significantly less stressed by the NICU sights and sounds and had significantly stronger beliefs about what behaviors and characteristics to expect from their premature infants. Findings from this study support the need for further testing of early NICU interventions with parents to determine their effectiveness on parental coping and infant developmental outcomes.", "PMID": "11746067"}, {"title": "Early physiotherapy intervention in premature infants.", "abstract": "Preterm infants are more likely to have disabling cerebral palsy (CP) than term infants. It has been reported that early therapeutic approaches may be appropriate for infants at risk of neuromotor dysfunction, to minimize the degree of future handicaps. Two hundred and twenty-nine infants born at less than 34 weeks' gestation, with birth weight < or = 2,000 g, cared for in the neonatal intensive care unit of Hacettepe University Hospital between January 1997-June 1999 were included in this study. Of the 229 infants initially included, 39 (17%) were dropped from the study within the first 12 months' assessment, due to lack of participation from the families. Thirty of the remaining 190 infants were found to have perinatal hypoxia or abnormal neurosonography, and were taken as the group at risk of development of CP, thus receiving early intervention therapy; these are listed as \"premature at risk\". The study group consisted of 160 infants not considered at risk. These were randomly paired into two groups of 80 infants, one that was given early interventional therapy, and the control group that received no program. Eleven of the 30 infants at risk, 2 of the 80 infants from the intervention group, and 4 of the 80 from the control group were diagnosed as having CP within the first six months of life. There was no difference in the age of loss or acquisition of reflexes and general abilities between the intervention and control groups. There was no difference in the prevalence of CP between the intervention and control groups. In conclusion this study showed no effect of early intervention in premature babies without risk of CP other than prematurity.", "PMID": "12405434"}, {"title": "Is early occupational therapy in extremely preterm infants of benefit in the long run?", "abstract": "A total of 126 infants with extremely low birth weight (ELBW; <1000 g) were enrolled in a prospective case-control study in order to examine the effect of occupational therapy based on sensory integration (SI) and neurodevelopmental therapy (NDT) on neurological development. The children were grouped as matched pairs on the basis of determined developmental risk scores assessed at the age of 3 months. The intervention children had a 6-month period of weekly occupational therapy from the corrected age of 6-12 months. The follow-up showed that the social development of the intervention children was significantly better at the age of 12 months, but at the age of 2 years the groups had equal developmental scores in neurological, neuropsychological and speech therapy assessments. The Miller assessment for pre-schoolers (MAP) performed in a total of 96 (92%) of the study children at the age of 4 years failed to demonstrate any significant differences between the groups. It is concluded that this amount of occupational therapy in ELBW infants does not have any detectable effect on long-term neurological development.", "PMID": "12490052"}, {"title": "Effects of early intervention on cognitive function of low birth weight preterm infants.", "abstract": "The Infant Health and Development Program is a randomized clinical trial to test the efficacy of educational and family support services and pediatric follow-up, offered during the first 3 years of life, in reducing the incidence of developmental delay in low birth weight preterm infants at eight clinical sites (N = 985). It was hypothesized that larger intervention effects would be found for the domains in which low birth weight preterm infants are known to have problems, specifically visual-motor and spatial skills and receptive language skills. These analyses explore the effects of the Infant Health and Development Program on different domains of cognitive functioning. Cognitive domains are identified by means of factor analysis of the intelligence tests used at 12, 24, and 36 months (Bayley Scales of Infant Development (including the Mental and Motor scales) at 12 and 24 months; the Stanford-Binet, Peabody Picture Vocabulary Test, and Beery Test of Visual Motor Intergration at 36 months). Our results reveal that, although intervention benefits accrue across cognitive domains at 24 and 36 months, gains are most pronounced for receptive language and visual-motor and spatial skills.", "PMID": "1538279"}, {"title": "Effect of an early intervention programme on low birthweight infants with cerebral injuries.", "abstract": "To determine the effect of an early intervention programme (EIP) on low birthweight infants with cerebral injuries.\n\nSubjects were 23 high-risk low birthweight infants (periventricular leukomalacia 15, intraventricular haemorrhage 5, both 3) receiving care in the neonatal intensive care unit (NICU) at Nagasaki University Hospital. Subjects were randomly assigned to the EIP group (n = 12) or the control group (n = 11). Participants in the EIP group received a Neonatal Behavioral Assessment scale (NBAS)-based intervention combined with developmental support designed to enhance the infants' development and the quality of the parent-infant relationship. The control group received routine medical nursing care without the EIP. The EIP began prior to discharge from the NICU and lasted until 6 months of corrected age. All children were examined on the NBAS preintervention and again at 44 weeks postconceptional age. Maternal anxiety status (STAI) and maternal feelings of confidence in dealing with her baby (LCC) were measured pre and postintervention. Mental and motor development was assessed postintervention using the Bayley Scale of Infant Development.\n\nOrientation and State Regulation of infant behavioural profiles, the STAI and LCC scores significantly improved in the EIP group (mean difference (95% CI): Orientation 0.7 (0.4, 1.1), State Regulation 0.9 (0.3, 1.5), STAI -5.5 (- 9.1, -1.9, LCC 5.3 (4.2, 6.5)), but not in the control group. Bayley mental developmental index (MDI) score in the EIP group was higher than in the control group, but there was no significant difference between the two groups (mean difference (95% CI): MDI 8.5 (- 0.8, 17.8), PDI 6.7 (- 1.9, 15.4)).\n\nThe EIP has beneficial effects on neonatal neurobehavioural development and maternal mental health of low birthweight infants with cerebral injuries. This evidence suggests that short-term changes in maternal mental health and infant neurobehaviour promoted by an EIP may serve to initiate a positive interaction between parents and infants.", "PMID": "15569286"}], "labels": [{"PMID": "10048099", "label": "included"}, {"PMID": "11453445", "label": "included"}, {"PMID": "11469284", "label": "included"}, {"PMID": "11552873", "label": "included"}, {"PMID": "11605609", "label": "included"}, {"PMID": "11746067", "label": "included"}, {"PMID": "12405434", "label": "included"}, {"PMID": "12490052", "label": "included"}, {"PMID": "1538279", "label": "included"}, {"PMID": "15569286", "label": "included"}]}
{"metadata": {"review_pmid": "38348912"}, "inputs": {"background": "Abortions prior to 14 weeks are among the most common outpatient surgical procedures performed on people capable of becoming pregnant. Various methods have been used to control pain; however, many people still experience pain with the procedure.", "objectives": "To evaluate the benefits and harms of local anaesthesia given for pain control during surgical abortion at less than 14 weeks' gestation.", "selection criteria": "We selected effectiveness and comparative effectiveness randomized controlled trials that studied local anaesthesia with common local anaesthetics and administration routes given for pain control in surgical abortion at less than 14 weeks' gestation using uterine aspiration. Outcomes included intraoperative pain, patient satisfaction, and adverse events."}, "context": [{"title": "Paracetamol 1 g given rectally at the end of minor gynaecological surgery is not efficacious in reducing postoperative pain.", "abstract": "We studied the analgesic effects of 1 g paracetamol given rectally at the end of surgery in a prospective, randomised, double-blind study.\n\nOne hundred and forty ASA I-II women scheduled for elective termination of pregnancy under general anaesthesia were randomly allocated to receive paracetamol or placebo. All patients had standardised anaesthesia with propofol, fentanyl and oxygen in nitrous oxide. Postoperative pain was assessed by VAS score.\n\nWe could find no difference regarding postoperative pain, need for analgesics or time to discharge between the groups.\n\nThe routine use of 1 g paracetamol given rectally at the end of surgery after termination of pregnancy seems not to be justified.", "PMID": "10081528"}, {"title": "Analgesia for termination of pregnancy.", "abstract": "", "PMID": "10488349"}, {"title": "Omission of nitrous oxide from a propofol-based anesthetic does not affect the recovery of women undergoing outpatient gynecologic surgery.", "abstract": "Although nitrous oxide (N2O) is used commonly during anesthesia, clinically relevant advantages-disadvantages of using this agent are not well established in the ambulatory setting. This study in women undergoing ambulatory gynecologic surgery compares outcomes in patients administered total intravenous anesthesia with propofol versus the propofol plus N2O. The primary outcome was the time to home readiness. Secondary outcomes included the incidence of postanesthetic adverse events.\n\nWomen presenting for elective ambulatory termination of pregnancy or gynecologic laparoscopy were induced with an intravenous sleep dose of propofol and fentanyl. After induction, subjects were randomly allocated to maintenance anesthesia with propofol alone or propofol plus 65% N2O. Patients were assessed by a blinded observer in the postanesthetic care unit at 20-min intervals to determine home readiness. Postoperative pain and nausea were measured with visual analog scales. Postoperative analgesics and antiemetics were recorded. The incidence of adverse events occurring after hospital discharge was assessed by a telephone interview 24 h postoperatively.\n\nA total of 740 patients received propofol alone, and 750 patients received propofol plus N2O. Mean home readiness times were not significantly different between treatment groups. There were no significant differences between groups in pain scores, nausea scores, analgesia administration, or antiemetic administration before discharge. There were no significant differences in the frequency of adverse events for 24 h after discharge from hospital.\n\nOmission of N2O from a propofol-based anesthetic for ambulatory gynecologic surgery does not affect time to home readiness or the incidence of postoperative adverse events up to 24 h after discharge from hospital. (Key words: Awareness; outpatient surgery; total intravenous anesthesia.)", "PMID": "10910478"}, {"title": "No effect of preoperative paracetamol and codeine suppositories for pain after termination of pregnancies in general anaesthesia.", "abstract": "Outpatient surgery demands rapid recovery and satisfied patients. The purpose of the study was to investigate whether rectal premedication with paracetamol and codeine would reduce the need of rescue analgesics, reduce the postoperative pain experience and result in faster eligibility for discharge. Ninety pregnant patients scheduled for day-case surgery with evacuation of the uterine cavity were randomly assigned into two groups. The paracetamol and codeine group was given a suppository with 60 mg of codeine and 800 mg of paracetamol together with standard premedication of intramuscular midazolam 0.08 mg/kg. The placebo group was given a placebo suppository and midazolam. All patients underwent the surgical procedure under general anaesthesia with alfentanil 15 microg/kg and propofol 1.5-2 mg/kg. There were no statistically significant differences between the groups in the postoperative pain experience as judged by Visual Analogue Scale (VAS-scale), verbal scale or the need for rescue analgesic medication with ketobemidone. Most of the patients experienced little postoperative pain with more than 70% scoring less than 20 mm on a VAS-scale from 0-100 mm at any time during the postoperative period. The paracetamol and codeine patients were significantly more sleepy at 30 min postoperatively. There were no differences between the groups in postoperative nausea or vomiting and no difference in discharge eligibility. The use of pre-operative suppository with paracetamol 800 mg and codeine 60 mg is unnecessary in this group of patients.", "PMID": "10957701"}, {"title": "Diazepam as a sedative in induced abortion.", "abstract": "In 136 patients, who underwent induced abortion by the vacuum curettage method under local anaesthesia (paracervical block), the effect of 10 mg diazepam intravenously as preoperative sedative was investigated for its ability to abolish the subjective experience of pain. The trial was carried out as a paired sample, random, allocation, double-blind, fixed dose trial, and the statistical method was sequential analysis. Thirty-six pairs showed no difference and were excluded. After 32 pairs (24 A preferences and 8 O preferences), diazepam showed a significant superiority to placebo (p less than 0.05) (Fig. 1.) Amnesia for the procedure was reported by about one-quarter of the diazepam-treated patients, and in practically all cases the sedative effect had subsided 1-3 hours after the operation.\n\nDiazepam has been reported to reduce pain and discomfort and in many cases to produce a total amnesia.  The drug was tested with 136 patients undergoing vacuum curettage for abortion.  About 1/2 hour before the pro cedure, patients received premedication with 50 mg pethidine sc.  At the beginning of the procedure, half the patients received 10 mg diazepam iv , and the other half a placebo.  Paracervical block was then used with 1 % carbocaine.  After 3 minutes, the cervix was dilated with a Hegar dila tor, the uterine contents were removed by the suction curette, and .2 mg methyl-ergometrine maleate (Methergin) was given iv.  At 1-3 hours posto peratively, patients were asked if the operation had been painful.  In 36 instances no preference was shown between results.  In 32 instances w here a preference was shown diazepam was considered superior to the plac ebo in reducing pain and discomfort in 24 patients.  In 18 of the 68 pat ients treated with diazepam, there was total amnesia for the procedure.  However, 2 patients receiving the placebo also had amnesia.  At 1-3 hours after the procedure, 4 patients in the diazepam group and 3 in the placebo group were slightly somnolent.  With the dose used, the procedure can be done on an outpatient basis.", "PMID": "1099860"}, {"title": "Paracervical block with etidocaine for out-patient abortion.", "abstract": "Paracervical block using etidocaine 0.5 % and 1.0 % without adrenaline proved to be an effective anaesthetic procedure for first trimester abortion performed by surgical dilatation of the cervix and subsequent vacuum suction. Three blocks out of 24 were inadequate, probably due to inaccurate deposition of the local anaesthetic. There were two adverse reactions, possibly as a result of inadvertant intravascular injection. The need for long-acting agents for the present indication is questioned.", "PMID": "1101603"}, {"title": "Auxiliary pain relief during suction curettage.", "abstract": "", "PMID": "1116357"}, {"title": "Is pain prophylaxis in minor gynaecological surgery of clinical value? a double-blind placebo controlled study of paracetamol 1 g versus lornoxicam 8 mg given orally.", "abstract": "Methods: In a prospective randomised placebo controlled double-blind study 210 ASA I-II women scheduled for elective termination of pregnancy received 1 g paracetamol, 8 mg lornoxicam or placebo orally 60 min before anaesthesia which was standardised with propofol, fentanyl and oxygen in nitrous oxide 1:2. Postoperative pain was assessed by VAS-score at 30 and 60 min after end of surgery and at discharge as primary endpoints. Need for rescue medication and time to discharge were secondary endpoints. Results: All patients had an uncomplicated course. Overall pain intensity was low, however, the patients pretreated with lornoxicam had significantly less pain after surgery, no difference could however, be seen in need for rescue medication or time to discharge between the three groups. Conclusion: General pain prophylaxis may be argued in minor gynaecological surgical procedures where postoperative pain is of low intensity. If general prophylaxis is to be given in minor gynaecological surgery, a non steroidal anti-inflammatory (NSAID) such as lornoxicam, seems more efficacious as compared to a standard dose of 1 g paracetamol.", "PMID": "11454488"}, {"title": "A randomized controlled trial of fentanyl for abortion pain.", "abstract": "Our aim was to find out whether intravenous fentanyl was effective in reducing the pain of first-trimester abortion.\n\nThis randomized controlled trial included 825 women attending a nonhospital abortion facility. Some women chose standard care. Women who did not choose standard care were randomly assigned to receive either 50 to 100 microg of fentanyl, a placebo, or no intervention. With SAS software and a mixed effects analysis of variance model with covariates, we compared mean pain scores of the fentanyl and placebo groups to detect a difference of at least 1 point on an 11-point pain scale.\n\nThe mean pain score of the fentanyl group was 1.0 point less than that of the placebo group (95% confidence interval, 3.7-4.3) and 0.9 point less than that of the observational group (95% confidence interval, 4.7-5.1). This pain reduction was statistically significant, but the women who were studied wanted a 2-point reduction from fentanyl.\n\nFentanyl, when compared with the placebo, reduced abortion pain by 1.0 point on an 11-point scale. This reduction was of questionable clinical significance and was less than desired by the women included in the study.", "PMID": "11483912"}, {"title": "A randomized, double blind, placebo-controlled study to investigate the use of conscious sedation in conjunction with paracervical block for reducing pain in termination of first trimester pregnancy by suction evacuation.", "abstract": "This study evaluated the role of conscious sedation in pain relief during termination of first trimester pregnancy by suction evacuation (SE) under local anaesthesia.\n\nA hundred women undergoing SE before 12 weeks gestation were randomized by computer using the sealed envelope method to receive placebo (saline) or conscious sedation (2 mg midazolam and 25 microg fentanyl) i.v. 5 min before cervical dilatation. Paracervical block was given to all patients, 2 min later. Pain scores during and after SE, post-operative side-effects and satisfaction level were compared.\n\nNo statistically significant differences in pain scores were found between the two groups. Post-operative side-effects such as dizziness (P = 0.015) and drowsiness (P < 0.001) were significantly more severe in the conscious sedation group. However, patients in the conscious sedation group reported better satisfaction levels than the control group (P = 0.003).\n\nThe use of conscious sedation significantly improved patient satisfaction during termination of first trimester pregnancy by SE under local anaesthesia, despite a lack of improvement in pain relief and the presence of increased severe dizziness/drowsiness in the post-operative period.", "PMID": "11980742"}], "labels": [{"PMID": "10081528", "label": "excluded"}, {"PMID": "10488349", "label": "excluded"}, {"PMID": "10910478", "label": "excluded"}, {"PMID": "10957701", "label": "excluded"}, {"PMID": "1099860", "label": "excluded"}, {"PMID": "1101603", "label": "excluded"}, {"PMID": "1116357", "label": "excluded"}, {"PMID": "11454488", "label": "excluded"}, {"PMID": "11483912", "label": "excluded"}, {"PMID": "11980742", "label": "excluded"}]}
{"metadata": {"review_pmid": "38345088"}, "inputs": {"background": "Pressure ulcers are localized injuries to the skin or the underlying tissue, or both, and are common in older and immobile people, people with diabetes, vascular disease, or malnutrition, as well as those who require intensive or palliative care. People with pressure ulcers often suffer from severe pain and exhibit social avoidance behaviours. The prevention and treatment of pressure ulcers involves strategies to optimize hydration, circulation, and nutrition. Adequate nutrient intake can reduce the risk factor of malnutrition and promote wound healing in existing pressure ulcers. However, it is unclear which nutrients help prevent and treat pressure ulcers. This is an update of an earlier Cochrane Review.", "objectives": "To evaluate the benefits and harms of nutritional interventions (special diets, supplements) for preventing and treating pressure ulcers in people with or without existing pressure ulcers compared to standard diet or other nutritional interventions.", "selection criteria": "We included randomized controlled trials (RCTs) in people with or without existing pressure ulcers, that compared nutritional interventions aimed at preventing or treating pressure ulcers with standard diet or other types of nutritional interventions."}, "context": [{"title": "Pressure sores and tube feeding in patients with a fracture of the hip: a randomized clinical trial.", "abstract": "Pressure sores are a frequent problem, especially in elderly patients. Nutritional status may influence the incidence, progression and severity of pressure sores, data, however, are contradictory (1). The purpose of this study was to determine the effect of supplemental feeding on the nutritional status and the development and severity of pressure sores. The effect of supplemental feeding overnight (tube +) on patients with a fracture of the hip and a high pressure-sore risk score, was studied in a randomized clinical trial. The control group (tube -) had no supplemental feeding. After informed consent, 140 patients were randomized, and 129 of these took part in the trial (62 tube +, and 67 tube -). Protein and energy intake, haemoglobin, serum albumin, total serum protein and pressure-sore grade were measured at admission and after 1 and 2 weeks. Of the 62 patients randomized for tube feeding (tube +), only 25 tolerated their tube for more than 1 week and 16 for 2 weeks. Nevertheless, energy and protein intake was significantly higher in the tube + group (P < 0.001). This, however, did not significantly influence total serum protein, serum albumin and development and severity of pressure sores after 1 and 2 weeks. Comparison of the actually tube fed group (n=25 at 1 week, n = 16 at 2 weeks) and the control group showed a 2-3 times higher protein and energy intake (P < 0.0001), and a significantly higher total serum protein and serum albumin after 1 and 2 weeks in the actually tube fed group (all P < 0.001). Pressure-sore development and severity were not significantly influenced in the actually tube fed group. We conclude that we were not able to show a significant decrease in development and severity of pressure sores, because the nasogastric tube for supplemental feeding was not well tolerated in this patient group. Nevertheless, tube feeding overnight does result in a significant higher protein and energy intake, and has a significant effect on nutritional status in the actually tube-fed group. Other means of supplemental feeding will have to be used in order to answer the question of whether supplemental feeding can decrease development and severity of pressure sores.", "PMID": "10205352"}, {"title": "A multi-center trial of the effects of oral nutritional supplementation in critically ill older inpatients. GAGE Group. Groupe Aquitain Geriatrique d'Evaluation.", "abstract": "The purpose of this study was to assess the effect of nutritional supplementation on dietary intake and on pressure ulcer development in critically ill older patients. The multi-center trial involved 19 wards stratified according to specialty and recruitment for critically ill older patients; 9 wards were randomly selected for nutritional intervention (nutritional intervention group), consisting of the daily distribution of two oral supplements, with each supplement containg 200 kcal, for 15 d. Pressure ulcer incidence was prospectively recorded for grades I (erythema), II (superficial broken skin), and III (subcutaneous lesion) for 15 d. Nutritional intake was monitored by using estimates in units of quarters validated by comparison with weight measurement. There were 672 subjects older than 65 y, and 295 were in the nutritional intervention group versus 377 in the control group. The patients were similar for age, sex ratio, and C-reactive protein. In comparison with the control group, the nutritional intervention group included more patients with stroke, heart failure, and dyspnea and fewer with antecedent falls, delirium, lower limb fractures, and digestive disease. The nutritional intervention group had a lower risk of pressure ulcers according to the Norton score but was less dependent (Kuntzman score) and had a lower serum albumin level. During the trial, energy and protein intakes were higher in the nutritional intervention group (day 2: 1081 +/- 595 kcal versus 957 +/- 530 kcal, P = 0.006; 45.9 +/- 27.8 g protein versus 38.3 +/- 23.8 g protein in the control group, P < 0.001). At 15 d, the cumulative incidence of pressure ulcers was 40.6% in the nutritional intervention group versus 47.2% in the control group. The proportion of grade I cases relative to the total number of cases was 90%. Multivariate analysis, taking into account all diagnoses, potential risk factors, and the intra-ward correlation, indicated that the independent risk factors of developing a pressure ulcer during this period were: serum albumin level at baseline, for 1 g/L decrease: 1.05 (95% confidence interval: 1.02 to 1.07, P < 0.001); Kuntzmann score at baseline, for 1-point increase: 1.22 (0.32 to 4.58, P = 0.003); lower limb fracture: 2.68 (1.75 to 4.11, P < 0.001); Norton score < 10 versus > 14: 1.28 (1.01 to 1.62, P = 0.04); and belonging to the control group: 1.57 (1.03 to 2.38, P = 0.04). In conclusion, it was possible to increase the dietary intake of critically ill elderly subjects by systematic use of oral supplements. This intervention was associated with a decreased risk of pressure ulcer incidence.", "PMID": "10674226"}, {"title": "Impact on pressure ulcer healing of an arginine-enriched nutritional solution in patients with severe cognitive impairment.", "abstract": "", "PMID": "11431045"}, {"title": "A randomised, double-blind assessment of the effect of nutritional supplementation on the prevention of pressure ulcers in hip-fracture patients.", "abstract": "Malnutrition is a risk factor for development of pressure ulcers (PU). Nutritional supplementation may thus reduce the incidence of PU. We investigated the effect of nutritional supplementation on incidence of PU in hip-fracture patients at risk of developing PU.\n\nHip-fracture patients (n=103) were included in this double-blind, randomised, placebo-controlled trial. They received 400 ml daily of a supplement enriched with protein, arginine, zinc and antioxidants (n=51) or a non-caloric, water-based placebo supplement (n=52). Presence and stage of PU were assessed daily for 28 days or until discharge (median: 10 days during supplementation).\n\nIncidence of PU was not different between supplement (55%) and placebo (59%), but incidence of PU stage II showed a 9% difference (difference: 0.091; 95% CI: 0.07-0.25) between supplement (18%) and placebo (28%). Of patients developing PU 57% developed it by the second day. Time of onset (days) showed a trend (P=0.090) towards later onset of PU with supplement (3.6+/-0.9) than placebo (1.6+/-0.9).\n\nHip-fracture patients develop PU at an early stage. Nutritional supplementation may not prevent PU at this stage, but contributes possibly to a delayed onset and progression of PU. Nutritional supplementation may be more effective if initiated earlier.", "PMID": "12880608"}, {"title": "A randomised, double-blind assessment of the effect of nutritional supplementation on the prevention of pressure ulcers in hip-fracture patients.", "abstract": "Malnutrition is a risk factor for development of pressure ulcers (PU). Nutritional supplementation may thus reduce the incidence of PU. We investigated the effect of nutritional supplementation on incidence of PU in hip-fracture patients at risk of developing PU.\n\nHip-fracture patients (n=103) were included in this double-blind, randomised, placebo-controlled trial. They received 400 ml daily of a supplement enriched with protein, arginine, zinc and antioxidants (n=51) or a non-caloric, water-based placebo supplement (n=52). Presence and stage of PU were assessed daily for 28 days or until discharge (median: 10 days during supplementation).\n\nIncidence of PU was not different between supplement (55%) and placebo (59%), but incidence of PU stage II showed a 9% difference (difference: 0.091; 95% CI: 0.07-0.25) between supplement (18%) and placebo (28%). Of patients developing PU 57% developed it by the second day. Time of onset (days) showed a trend (P=0.090) towards later onset of PU with supplement (3.6+/-0.9) than placebo (1.6+/-0.9).\n\nHip-fracture patients develop PU at an early stage. Nutritional supplementation may not prevent PU at this stage, but contributes possibly to a delayed onset and progression of PU. Nutritional supplementation may be more effective if initiated earlier.", "PMID": "12880608"}, {"title": "Arginine supplementation is well tolerated but does not enhance mitogen-induced lymphocyte proliferation in elderly nursing home residents with pressure ulcers.", "abstract": "Immune function declines with age, increasing risk for infection and delaying wound healing. Arginine enhances immune function and healing of standardized wounds in healthy elderly persons. The purpose of this study was to determine what level of arginine supplementation was orally and metabolically tolerated and effective in enhancing immune function in elderly persons with pressure ulcers.\n\nResidents with one or more pressure ulcers were recruited from two local nursing homes. Subjects were randomized to receive 0 g (n = 10; age, 82 +/- 3 years), 8.5 g (n = 11; 81 +/- 3 years), or 17 g (n = 11; 87 +/- 2 years) of supplemental arginine each day for 4 weeks. Oral tolerance, ie, absence of nausea, vomiting, abdominal distention, or diarrhea, was assessed daily. Metabolic tolerance was assessed weekly by evaluating serum electrolytes. Lymphocyte proliferation to phytohemagglutinin and interleukin 2 production were measured at baseline and after 4 weeks of supplementation as indicators of immune function.\n\nSupplemental arginine significantly increased plasma arginine levels and was orally and metabolically tolerated with no complaints of abdominal distress or no clinically relevant changes in electrolyte levels among groups. Lymphocyte proliferation and interleukin 2 production were significantly different between nursing homes. When data from nursing homes were considered individually, arginine supplementation did not enhance the proliferative response. In subjects from nursing home 2 only, there was a 38% and 75% decrease (p < .05) in lymphocyte proliferation with 8.5 and 17 g of supplemental arginine, respectively. Interleukin 2 production was no different among supplementation groups.\n\nPharmacologic doses of arginine were well tolerated but did not enhance lymphocyte proliferation or interleukin 2 production in nursing home residents with pressure ulcers. CLINICAL RELEVANCY: Enteral formulas supplemented with pharmacologic levels of arginine are frequently administered to elderly persons. This study demonstrates that the very old can tolerate these nitrogen loads if baseline renal function is normal and fluid intake is encouraged. Further research needs to be completed investigating the effect of arginine supplementation on immune function in this population before recommending arginine use.", "PMID": "11011783"}, {"title": "Vitamin C and pressure ulcers.", "abstract": "", "PMID": "12151986"}, {"title": "Does vitamin C supplementation promote pressure ulcer healing?", "abstract": "", "PMID": "14560282"}, {"title": "Zinc supplementation: yea or nay?", "abstract": "", "PMID": "14581813"}, {"title": "Does oral supplementation with vitamins A or E promote healing of chronic wounds?", "abstract": "", "PMID": "14615755"}], "labels": [{"PMID": "10205352", "label": "included"}, {"PMID": "10674226", "label": "included"}, {"PMID": "11431045", "label": "included"}, {"PMID": "12880608", "label": "included"}, {"PMID": "12880608", "label": "included"}, {"PMID": "11011783", "label": "excluded"}, {"PMID": "12151986", "label": "excluded"}, {"PMID": "14560282", "label": "excluded"}, {"PMID": "14581813", "label": "excluded"}, {"PMID": "14615755", "label": "excluded"}]}
{"metadata": {"review_pmid": "38345071"}, "inputs": {"background": "Acute and chronic postoperative pain are important healthcare problems, which can be treated with a combination of opioids and regional anaesthesia. The erector spinae plane block (ESPB) is a new regional anaesthesia technique, which might be able to reduce opioid consumption and related side effects.", "objectives": "To compare the analgesic effects and side effect profile of ESPB against no block, placebo block or other regional anaesthetic techniques.", "selection criteria": "Randomised controlled trials (RCTs) investigating adults undergoing surgery with general anaesthesia were included. We included ESPB in comparison with no block, placebo blocks or other regional anaesthesia techniques irrespective of language, publication year, publication status or technique of regional anaesthesia used (ultrasound, landmarks or peripheral nerve stimulator). Quasi-RCTs, cluster-RCTs, cross-over trials and studies investigating co-interventions in either arm were excluded."}, "context": [{"title": "Ultrasound guided erector spinae plane block reduces postoperative opioid consumption following breast surgery: A randomized controlled study.", "abstract": "To evaluate the analgesic effect of ultrasound-guided erector spinae plane (ESP) block in breast cancer surgery.\n\nRandomized controlled, single-blinded trial.\n\nOperating room.\n\nFifty ASA I-II patients aged 25-65 and scheduled for elective breast cancer surgery were included in the study.\n\nPatients were randomized into two groups, ESP and control. Single-shot ultrasound (US)-guided ESP block with 20\u202fml 0.25% bupivacaine at the T4 vertebral level was performed preoperatively to all patients in the ESP group. The control group received no intervention. Patients in both groups were provided with intravenous patient-controlled analgesia device containing morphine for postoperative analgesia.\n\nMorphine consumption and numeric rating scale (NRS) pain scores were recorded at 1, 6, 12 and 24\u202fh postoperatively.\n\nMorphine consumption at postoperative hours 1, 6, 12 and 24 decreased significantly in the ESP group (p\u202f<\u202f0.05 for each time interval). Total morphine consumption decreased by 65% at 24\u202fh compared to the control group (5.76\u202f\u00b1\u202f3.8\u202fmg vs 16.6\u202f\u00b1\u202f6.92\u202fmg). There was no statistically significant difference between the groups in terms of NRS scores.\n\nOur study findings show that US-guided ESP block exhibits a significant analgesic effect in patients undergoing breast cancer surgery. Further studies comparing different regional anesthesia techniques are needed to identify the optimal analgesia technique for this group of patients.", "PMID": "29980005"}, {"title": "Comparison of continuous thoracic epidural analgesia with bilateral erector spinae plane block for perioperative pain management in cardiac surgery.", "abstract": "Continuous thoracic epidural analgesia (TEA) is compared with erector spinae plane (ESP) block for the perioperative pain management in patients undergoing cardiac surgery for the quality of analgesia, incentive spirometry, ventilator duration, and intensive care unit (ICU) duration.\n\nA prospective, randomized comparative clinical study was conducted. A total of 50 patients were enrolled, who were randomized to either Group A: TEA (n = 25) or Group B: ESP block (n = 25). Visual analog scale (VAS) was recorded in both the groups during rest and cough at the various time intervals postextubation. Both the groups were also compared for incentive spirometry, ventilator, and ICU duration. Statistical analysis was performed using the independent Student's t-test. A value of P < 0.05 was considered statistically significant.\n\nomparable VAS scores were revealed at 0 h, 3 h, 6 h, and 12 h (P > 0.05) at rest and during cough in both the groups. Group A had a statistically significant VAS score than Group B (P \u2264 0.05) at 24 h, 36 h, and 48 h but mean VAS in either of the Group was \u22644 both at rest and during cough. Incentive spirometry, ventilator, and ICU duration were comparable between the groups.\n\nESP block is easy to perform and can serve as a promising alternative to TEA in optimal perioperative pain management in cardiac surgery.", "PMID": "30052229"}, {"title": "Bilateral Erector Spinae Plane Block for Acute Post-Surgical Pain in Adult Cardiac Surgical Patients: A Randomized Controlled Trial.", "abstract": "To examine the analgesic efficacy of bilateral erector spinae plane (ESP) block compared with conventional treatment for pain after cardiac surgery in adult patients.\n\nA prospective, randomized, controlled, single-blinded study.\n\nSingle-center tertiary teaching hospital.\n\nOne hundred and six adult patients undergoing elective cardiac surgery with cardiopulmonary bypass.\n\nPatients were randomized into 2 groups. Patients in group 1 (ESP block group, n\u202f=\u202f53) received ultrasound-guided bilateral ESP block with 3\u00a0mg/kg of 0.375% ropivacaine before anesthesia induction at the T6 transverse process level. Patients in group 2 (paracetamol and tramadol group, n\u202f=\u202f53) received paracetamol (1 gm every 6 hours) and tramadol (50\u00a0mg every 8 hours) intravenously in the postoperative period. The primary study outcome was to evaluate pain at rest using an 11-point numeric rating scale (NRS). Mann-Whitney U test was used for comparing NRS scores.\n\nThe postoperative pain level after extubation and duration of analgesia during which NRS was <\u00a04 of 10 was compared between the groups. The median pain score at rest after extubation in group 1 was 0 of 10 until hour 6, 3 of 10 at hour 8, and 4 of 10 at hours 10 and 12 postextubation. These were significantly less in comparison with group 2 (p\u202f=\u202f0.0001). Patients in group 1 had a significantly higher mean duration of analgesia (8.98 \u00b1 0.14 hours), during which NRS was < 4 of 10, compared with group 2 (4.60 \u00b1 0.12 hours) (p\u202f=\u202f0.0001).\n\nESP block safely provided significantly better pain relief at rest for longer duration as compared to intravenous paracetamol and tramadol.", "PMID": "30055991"}, {"title": "Comparison of the effects of modified pectoral nerve block and erector spinae plane block on postoperative opioid consumption and pain scores of patients after radical mastectomy surgery: A prospective, randomized, controlled trial.", "abstract": "Breast cancer is the most common malignancy of women all over the world. In this study, we compared the effects of ultrasound-guided modified pectoral nerve (PECS) block and erector spinae plane (ESP) block on postoperative opioid consumption, pain scores, and intraoperative fentanyl need of patients undergoing unilateral modified radical mastectomy surgery.\n\nSingle-blinded, prospective, randomized, efficacy study.\n\nTertiary university hospital, postoperative recovery room and surgical ward.\n\nForty patients (ASA I-II) were allocated to two groups. After exclusion, 38 patients were included in the final analysis (18 patients in the PECS groups and 20 in the ESP group).\n\nModified pectoral nerve block was performed in the PECS group and erector spinae plane block was performed in the ESP group.\n\nPostoperative tramadol consumption and pain scores were compared between the groups. Also, intraoperative fentanyl need was measured.\n\nPostoperative tramadol consumption was 132.78\u202f\u00b1\u202f22.44\u202fmg in PECS group and 196\u202f\u00b1\u202f27.03\u202fmg in ESP group (p\u202f=\u202f0.001). NRS scores at the 15th and 30th\u202fmin were similar between the groups. However, median NRS scores were significantly lower in PECS group at the postoperative 60th\u202fmin, 120th\u202fmin, 12th\u202fhour and 24th\u202fhour (p\u202f=\u202f0.024, p\u202f=\u202f0.018, p\u202f=\u202f0.021 and p\u202f=\u202f0.011 respectively). Intraoperative fentanyl need was 75\u202fmg in PECS group and 87.5\u202fmg in ESP group. The difference was not statistically significant (p\u202f=\u202f0.263).\n\nModified PECS block reduced postoperative tramadol consumption and pain scores more effectively than ESP block after radical mastectomy surgery.", "PMID": "30396100"}, {"title": "Ultrasound-Guided Bilateral Erector Spinae Block Versus Tumescent Anesthesia for Postoperative Analgesia in Patients Undergoing Reduction Mammoplasty: A Randomized Controlled Study.", "abstract": "The aim of this prospective, randomized, double-blind study was to compare the tumescent anesthesia method and erector spinae block with respect to postoperative analgesia consumption, pain scores and patient satisfaction, in patients receiving breast reduction surgery under general anesthesia.\n\nThe study included 44 females, aged 20-65\u00a0years, who were to undergo breast reduction surgery, without adjunctive liposuction on the breast. Using the closed envelope method, the patients were randomly separated into two groups to receive tumescent anesthesia or erector spinae block (ESB). Patients in the ESB group received the block before general anesthesia by a single anesthetist (G.\u00d6.).\n\nThe 24-h tramadol consumption with PCA, which was the primary outcome of the study, was determined to be statistically significantly less in the ESB group (p\u2009<\u20090.001). The NRS scores were compared at 30\u00a0min postoperatively and then at 1, 2, 4, 6, 12 and 24\u00a0h. At all the measured time points, the pain scores of the ESB group were statistically significantly lower (p\u2009<\u20090.001). Additional analgesia was required by one patient in the ESB group and by seven patients in the tumescent group and was applied as 1\u00a0g paracetamol. The requirement for additional analgesia was statistically significantly lower in the ESB group (p\u2009<\u20090.024). Patient satisfaction was statistically significantly better in the ESB group (p\u2009<\u20090.001).\n\nAccording to the results of this study, bilateral ESB performed under ultrasound guidance in breast reduction surgery was more effective than tumescent anesthesia concerning postoperative analgesia consumption and pain scores. ESB could be an appropriate, effective and safe postoperative analgesia method for patients undergoing reduction mammoplasty surgery.\n\nThis journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .", "PMID": "30535555"}, {"title": "Comparison of Ultrasound-Guided Lumbar Erector Spinae Plane Block and Transmuscular Quadratus Lumborum Block for Postoperative Analgesia in Hip and Proximal Femur Surgery: A Prospective Randomized Feasibility Study.", "abstract": "Lumbar Erector spinae Plane block (L-ESPB) is a modification of a recently described block. Both L-ESPB and Transmuscular Quadratus Lumborum block (QLB-T) have been reported to provide effective postoperative analgesia in hip and proximal femur surgery. Herein, we compare the effectiveness of L-ESPB and QLB-T in providing postoperative analgesia in patients undergoing hip and femur operations.\n\nDouble-blinded, prospective, randomized, feasibility study.\n\nTertiary university hospital, postoperative recovery room and ward.\n\nA total of 72 patients (American Society of Anesthesiology physical status classification II-III) were recruited. After exclusion, 60 patients were allocated to three equal groups (control, L-ESB and QLB-t).\n\nStandard multimodal analgesia was performed in the control group while L-ESPB or QLB-T was performed in the block groups.\n\nPain intensity between groups was compared using Numeric Rating Scores. Furthermore, tramadol consumption and additional rescue analgesic requirement was measured.\n\nThere was no difference between demographic data or type of surgery. While there was no difference in Numeric Rating Scale (NRS) score at any hour between the block groups; NRS scores at the 1\n\nWhile L-ESPB and QLB-T have similar effect, they improve analgesia quality in patients undergoing hip and proximal femoral surgery when compared to standard intravenous analgesia regimen.", "PMID": "30662115"}, {"title": "Ultrasound-Guided Erector Spinae Plane Block in Patients Undergoing Open Epigastric Hernia Repair: A Prospective Randomized Controlled Study.", "abstract": "Hernia repair is associated with considerable postoperative pain. We studied the analgesic efficacy of bilateral ultrasound-guided erector spinae plane block in patients undergoing open midline epigastric hernia repair (T6-T9).\n\nSixty patients 18-65 years of age were randomly allocated into 2 groups. Patients in the erector spinae plane block group received bilateral ultrasound-guided erector spinae plane block at the level of T7 transverse process using 20 mL of bupivacaine 0.25% on each side, while the control group received bilateral sham erector spinae plane block using 1 mL of normal saline. All patients underwent general anesthesia for surgery. Pain severity (visual analog scale), consumption of intraoperative fentanyl, time to first request of rescue analgesia, and postoperative pethidine consumption were recorded over the first 24 hours postoperatively.\n\nAt 2 hours postoperatively, the visual analog scale pain score was significantly lower in the erector spinae plane block group compared to the control group (estimated main effect of 2.53; P < .001; 95% CI, 1.8-3.2) and remained lower until 12 hours postoperatively (P < .001 from postanesthesia care unit admission to 4 hours postoperatively, .001 at 6 hours, .025 at 8 hours, and .043 at 12 hours). At 18 and 24 hours, visual analog scale pain scores were not significantly different between both groups (P = .634 and .432, respectively). Four patients in the erector spinae plane block group required intraoperative fentanyl compared to 27 patients in control group. The median (quartiles) of intraoperative fentanyl consumption in the erector spinae plane block group was significantly lower (0 \u00b5g [0-0 \u00b5g]) compared to that of the control group (94 \u00b5g [74-130 \u00b5g]). Ten patients in the erector spinae plane block group required postoperative rescue pethidine compared to 25 patients in control group. The median [quartiles] of postoperative rescue pethidine consumption was significantly lower in the erector spinae plane block group (0 mg [0-33 mg]) compared to that of the control group (83 mg [64-109 mg]). Time to first rescue analgesic request was significantly prolonged in the erector spinae plane block group compared to control group (P < .001).\n\nUltrasound-guided bilateral erector spinae plane block provided lower postoperative visual analog scale pain scores and decreased consumption of both intraoperative fentanyl and postoperative rescue analgesia for patients undergoing open epigastric hernia repair.", "PMID": "30801359"}, {"title": "Ultrasound-guided erector spinae plane block versus oblique subcostal transversus abdominis plane block for postoperative analgesia of adult patients undergoing laparoscopic cholecystectomy: Randomized, controlled trial.", "abstract": "Laparoscopic cholecystectomy (LC) is a frequently applied minimally invasive surgery. Intraoperative access is provided with small keyhole entries on the abdominal wall. However, LC causes moderate to severe postoperative pain. The subcostal approach of TAP block was described by Hebbard et al. for postoperative analgesia especially for upper abdominal surgeries. Ultrasound-guided erector spinae plane (US-ESP) block is a novel technique targeting ventral rami, dorsal rami and rami communicantes of the spinal nerves.\n\nSingle-blinded, prospective, randomized study.\n\nTertiary university hospital, postoperative recovery room and surgical ward.\n\nSeventy-six patients (ASA I-II) were divided into two equal groups. After applying the exclusion criteria, 68 patients were included in final analysis (34 patients in ESP group and 34 in OSTAP group).\n\nErector spinae plane block was performed in the ESP group and oblique subcostal transversus abdominis block was performed in the OSTAP group.\n\nPostoperative tramadol consumption and pain scores between groups were compared. In addition, intraoperative fentanyl need was measured.\n\nPostoperative tramadol consumption was 139.1\u202f\u00b1\u202f21.9\u202fmg in the ESP group and 199.4\u202f\u00b1\u202f27.7\u202fmg in the OSTAP group (mean difference 60.29\u202fmg, 95% confidence interval - 72.40 to - 48.19; p\u202f<\u202f0.001). NRS scores at almost all time-points were lower in the ESP group according to the repeated measures analysis. Integration of AUC and Mann Whitney U test results have revealed that there was no time wise difference between ESP and OSTAP groups even though NRS scores by itself and time-wise linear area under curve scores were higher in the OSTAP group compare to ESP group. There were no differences in intraoperative fentanyl need.\n\nUltrasound-guided ESP block reduced postoperative tramadol consumption and pain scores more effectively than OSTAP block after laparoscopic cholecystectomy surgery.", "PMID": "30851501"}, {"title": "Ultrasound-Guided Serratus Plane Block Versus Erector Spinae Block for Postoperative Analgesia After Video-Assisted Thoracoscopy: A Pilot Randomized Controlled Trial.", "abstract": "There is no gold standard for the management of postoperative pain after video-assisted thoracoscopic surgery (VATS). Interfascial nerve blocks were proposed as simple and effective options.\n\nThe present pilot randomized trial aimed to compare the perioperative analgesic effect of ultrasound-guided erector spinae plane block (ESB) with serratus plane block (SPB) in patients undergoing VATS.\n\nUniversity hospitals.\n\nSixty adult patients scheduled to undergo VATS were enrolled in the study.\n\nPatients were randomly assigned in a 1:1 ratio to receive either single-shot ultrasound-guided ESB or SPB.\n\nThe primary outcomes were pain severity, time to first postoperative analgesia, and intraoperative and postoperative analgesic requirements. Data analysis was performed with MedCalc, Version 15.8 (MedCalc, Ostend, Belgium. The ESB group showed a significantly lower VAS\n\nESB provided superior analgesia and longer time to first required analgesic than did SPB.", "PMID": "30930141"}, {"title": "Evaluation of Ultrasound-Guided Erector Spinae Plane Block and Oblique Subcostal Transversus Abdominis Plane Block in Laparoscopic Cholecystectomy: Randomized, Controlled, Prospective Study.", "abstract": "Oblique subcostal transversus abdominis plane block (OSTAP) is a recently described regional anesthetic technique used in upper abdominal surgeries such as laparoscopic cholecystectomy (LC). Erector spinae plane block (ESPB) has also been reported for postoperative analgesia in LC.\n\nWe aimed to compare the effectiveness of OSTAP and ESPB in providing postoperative analgesia in patients undergoing these surgeries.\n\nThis study was designed as a double-blinded, prospective, randomized, efficiency study in a tertiary university hospital, postoperative recovery room, and ward.\n\nA total of 72 patients were recruited and 60 patients were randomized into three equal groups (ESPB, OSTAP, and control group). Pain intensity between groups was compared using Numeric Rating Scale (NRS) scores. In addition, consumption of paracetamol and tramadol and additional rescue analgesic requirement were measured. Standard multimodal analgesia was performed in all groups, while ESPB block was also performed in Group ESPB and OSTAP block was also performed in group OSTAP.\n\nDescriptive statistics were expressed as mean \u00b1 standard deviation. Independent \n\nNRS was lower in block groups during the first 3 h. There was no difference in NRS scores at other hours. Analgesic consumption and rescue analgesic requirement were lower in groups ESPB and OSTAP when compared to those of control group. Block groups were similar.\n\nBilateral ultrasound-guided ESPB and OSTAP performed at the end of LC lead to akin analgesia requirement and improve the quality of multimodal analgesia.", "PMID": "31031480"}], "labels": [{"PMID": "29980005", "label": "included"}, {"PMID": "30052229", "label": "included"}, {"PMID": "30055991", "label": "included"}, {"PMID": "30396100", "label": "included"}, {"PMID": "30535555", "label": "included"}, {"PMID": "30662115", "label": "included"}, {"PMID": "30801359", "label": "included"}, {"PMID": "30851501", "label": "included"}, {"PMID": "30930141", "label": "included"}, {"PMID": "31031480", "label": "excluded"}]}
{"metadata": {"review_pmid": "38334217"}, "inputs": {"background": "Morton's neuroma (MN) is a painful neuropathy resulting from a benign enlargement of the common plantar digital nerve that occurs commonly in the third webspace and, less often, in the second webspace of the foot. Symptoms include burning or shooting pain in the webspace that extends to the toes, or the sensation of walking on a pebble. These impact on weight-bearing activities and quality of life.", "objectives": "To assess the benefits and harms of interventions for MN.", "selection criteria": "We included all randomised, parallel-group trials (RCTs) of any intervention compared with placebo, control, or another intervention for MN. We included trials where allocation occurred at the level of the individual or the foot (clustered data). We included trials that confirmed MN through symptoms, a clinical test, and an ultrasound scan (USS) or magnetic resonance imaging (MRI)."}, "context": [{"title": "A prospective randomized controlled trial of plantar versus dorsal incisions for operative treatment of primary Morton's neuroma.", "abstract": "There are a great number of studies on the outcome of surgery for Morton's neuroma. However, there is a lack of controlled trials to determine the outcome in general and for the 2 most used surgical approaches. This prospective and randomized trial studied the outcome and adverse events of resected primary Morton's neuromas, comparing plantar and dorsal incisions.\n\nSeventy-six patients were randomized to treatment with either a plantar or a dorsal incision by 2 senior surgeons. Questionnaires were evaluated and physical examinations performed at baseline and at 3 and 12 months postoperatively by the treating surgeon and at a mean of 34 months (range, 28-42 months) by an independent surgeon. The follow-up rate was 93%.\n\nHistological examination of specimens verified resection of nerves in all cases except 1, which was in the dorsal group (artery). The main outcome variable, pain at daily activities, was significantly reduced by 96% (plantar) and 97% (dorsal) and restrictions in daily activities were reduced by 77% (plantar) and 67% (dorsal) at the final follow-up. Scar tenderness was noted by 3% (plantar) and 0% (dorsal) at the final evaluation. Clinically good results with surgery were noted in 87% (plantar) and 83% (dorsal) of cases. There were 5 complications in the plantar group and 6 in the dorsal group, with a difference in type of complications.\n\nThis study demonstrated 87% (plantar) and 83% (dorsal) clinically good outcomes and no significant differences between the procedures in regard to pain, restrictions in daily activities, and scar tenderness. However, there was a difference between the groups in the type of complications.\n\nLevel I, prospective randomized trial.", "PMID": "23564425"}, {"title": "Methylprednisolone injections for the treatment of Morton neuroma: a patient-blinded randomized trial.", "abstract": "Morton neuroma is a common cause of neuralgia affecting the web spaces of the toes. Corticosteroid injections are commonly administered as a first-line therapy, but the evidence for their effectiveness is weak. Our primary research aim was to determine whether corticosteroid injection is an effective treatment for Morton neuroma compared with an anesthetic injection as a placebo control.\n\nWe performed a pragmatic, patient-blinded randomized trial set within hospital orthopaedic outpatient clinics in Edinburgh, United Kingdom. One hundred and thirty-one participants with Morton neuroma (mean age, fifty-three years; 111 [85%] female) were randomized to receive either corticosteroid and anesthetic (1 mL methylprednisolone [40 mg] and 1 mL 2% lignocaine) or anesthetic alone (2 mL 1% lignocaine). An ultrasonographic image was obtained before treatment, and injections were performed with the needle placed under ultrasonographic guidance. The primary outcome was the difference in patient global assessment of foot health between the two groups at three months after injection. This was measured with use of a 100-unit visual analog scale (VAS) anchored by \"best imaginable health state\" and \"worst imaginable health state.\"\n\nCompared with the control group, global assessment of foot health in the corticosteroid group was significantly better at three months (mean difference, 14.1 scale points [95% confidence interval, 5.5 to 22.8 points]; p = 0.002). The difference between the groups was also significant at one month. Significant and nonsignificant improvements associated with the corticosteroid injection were observed for measures of pain, function, and patient global assessment of general health at one and three months after injection. The size of the neuroma as determined by ultrasonography did not significantly influence the treatment effect.\n\nCorticosteroid injections for Morton neuroma can be of symptomatic benefit for at least three months.", "PMID": "23636185"}, {"title": "Extracorporeal Shockwave Therapy in Patients with Morton's Neuroma A Randomized, Placebo-Controlled Trial.", "abstract": "The aim of this study was to evaluate the efficacy of extracorporeal shockwave therapy (ESWT) for the treatment of Morton's neuroma by measuring changes in patient pain, function, and neuroma size.\n\nPatients with Morton's neuroma were randomly assigned to either the ESWT group or the sham stimulation group. Outcome measures, including visual analog scale (VAS) and American Orthopaedic Foot and Ankle Society lesser toes (AOFAS) scores, were assessed at baseline and 1 and 4 weeks after treatment. The Johnson satisfaction test was also performed 1 and 4 weeks after treatment. The neuroma diameter was measured using ultrasonography at baseline and 4 weeks after treatment.\n\nPatients receiving ESWT exhibited significantly decreased VAS scores 1 and 4 weeks after treatment relative to baseline, and AOFAS scores were significantly improved 4 weeks after treatment relative to baseline. In the sham stimulation group, VAS and AOFAS scores showed no significant changes at any time after treatment. Neither group showed significant changes in Johnson satisfaction test results or neuroma diameter.\n\nThese results suggest that ESWT may reduce pain in patients with Morton's neuroma.", "PMID": "27031544"}, {"title": "Interdigital neuroma: intermuscular neuroma transposition compared with resection.", "abstract": "This prospective, randomized study compares the treatment of an interdigital neuroma (IDN) by the standard resection operation with a technique in which the IDN is transposed into the inter-muscular space between the adductor hallucis and the interossei muscles after division of the digital nerves distal to the IDN. The resection group contained 22 patients and 22 neuromas and the transposition group contained 22 patients and 23 neuromas. An interviewer, blinded as to the operative technique used, telephoned each patient preoperatively, and at 1 month, 3 months, 6 months, 12 months, and 36-48 months postoperatively. The interviewer recorded the patient's reported pain level on a numerical rating scale of 0 to 100. In the resection group the average pain level was slightly lower through the first 6 month period, but at the 12 month review the resection group had a slightly higher average pain level . At the 36-48 month survey the resection group again reported a greater average pain level and fewer asymptomatic patients. It was concluded that it is unnecessary to excise the IDN to obtain excellent relief of pain. It was also concluded that transposition of the IDN into an intermuscular position between the adductor hallucis and the interossei muscles produced significantly better long term results than did the standard resection operation.", "PMID": "10739150"}, {"title": "Morton neuroma: comparative results of two conservative methods.", "abstract": "The initial treatment of Morton neuromas consists of conservative methods that include shoe modifications and steroid injections. The purpose of this prospective study was to compare the efficacy of these two methods to determine which is more effective as the initial treatment method.\n\nEighty-two patients with Morton neuromas were randomly assigned to receive either footwear modification with orthoses or steroid injections as initial treatment. Outcomes were evaluated at 1 month, 6 months, and 12 months.\n\nPatient satisfaction was significantly better (p < 0.01) in the group treated with steroid injections than those treated with shoe modifications at all three followup intervals. At 12-month followup, 82% of those treated with steroid injections had complete or partial relief of pain compared to 63% of those treated with footwear modifications alone.\n\nSteroid injections as initial treatment and shoe modifications with steroid injections at 6 months appear to give better results in Morton neuromas than shoe modifications alone, but the difference in the two groups were not statistically significant at one year followup.", "PMID": "16045848"}, {"title": "Extracorporeal shockwave therapy for interdigital neuroma: a randomized, placebo-controlled, double-blind trial.", "abstract": "We sought to evaluate the safety and effectiveness of extracorporeal shockwave therapy as a therapeutic treatment for destroying Morton's neuroma.\n\nTwenty-five patients (25 feet) were included in the study. Indications for participation were more than 8 months of conservative care with a visual analog scale pain score of 4 or greater. The mean overall pain score on a modified visual analog scale was 6.9 preoperatively.\n\nThirteen patients were randomized to the active group and 12 to the sham group. Two patients in the sham group were lost to follow-up. Post-treatment evaluations were performed at 1, 6, and 12 weeks by a blinded investigator (L.W.). The end point evaluation parameter was the reduction in visual analog scale score. The treatment group showed a significant difference before and after extracorporeal shockwave therapy (P < .0001). The sham group did not have a significant difference after 12 weeks (P = .1218).\n\nExtracorporeal shockwave therapy is a possible alternative to surgical excision for Morton's neuroma.", "PMID": "19448168"}, {"title": "Extracorporeal shockwave therapy for interdigital neuroma: a randomized, placebo-controlled, double-blind trial.", "abstract": "", "PMID": "19767558"}, {"title": "Extracorporeal shockwave therapy for interdigital neuroma: a randomized, placebo-controlled, double-blind trial.", "abstract": "", "PMID": "19767558"}, {"title": "Extracorporeal shockwave therapy for interdigital neuroma: a randomized, placebo-controlled, double-blind trial.", "abstract": "", "PMID": "19767560"}, {"title": "A randomized, double-blind, placebo-controlled trial of injected capsaicin for pain in Morton's neuroma.", "abstract": "Intermetatarsal neuroma or Morton's neuroma is a painful condition of the foot resulting from an entrapment of the common digital nerve typically in the third intermetatarsal space. The pain can be severe and especially problematic with walking. Treatment options are limited and surgery may lead to permanent numbness in the toes. Capsaicin, the pungent ingredient of hot peppers, produces analgesia by inducing retraction of nociceptive afferents from the area of innervation and is effective in treating certain neuropathic pain disorders. A randomized double-blind placebo-controlled study was conducted to test the efficacy, tolerability, and safety of a single 0.1 mg dose of capsaicin vs placebo injected into the region of the neuroma. A total of 58 subjects diagnosed with Morton's neuroma with foot pain \u22654 (0-10 numerical pain rating scale) were injected with 2 mL of lidocaine into the intermetatarsal space proximal to the neuroma to provide local anesthesia. After 5 minutes, 0.1 mg capsaicin or placebo was injected into the intermetatarsal space containing the painful neuroma. Average foot pain was rated for 2 weeks before through 4 weeks after injection. At weeks 1 and 4, the decrease in pain was significantly greater in the subjects treated with capsaicin (P = 0.021 and P = 0.019, respectively). A trend toward significance was noted at weeks 2 and 3. Improvements in functional interference scores and reductions in oral analgesic use were also seen in the capsaicin-treated group. These findings suggest that injection of capsaicin is an efficacious treatment option for patients with painful intermetatarsal neuroma. ", "PMID": "26963851"}], "labels": [{"PMID": "23564425", "label": "included"}, {"PMID": "23636185", "label": "included"}, {"PMID": "27031544", "label": "included"}, {"PMID": "10739150", "label": "excluded"}, {"PMID": "16045848", "label": "excluded"}, {"PMID": "19448168", "label": "excluded"}, {"PMID": "19767558", "label": "excluded"}, {"PMID": "19767558", "label": "excluded"}, {"PMID": "19767560", "label": "excluded"}, {"PMID": "26963851", "label": "excluded"}]}
{"metadata": {"review_pmid": "38323679"}, "inputs": {"background": "Cognitive behavioural therapy (CBT) can be effective in people with schizophrenia when provided in combination with antipsychotic medication. It remains unclear whether CBT could be safely and effectively offered in the absence of concomitant antipsychotic therapy.", "objectives": "To investigate the effects of CBT for schizophrenia when administered without concomitant pharmacological treatment with antipsychotics.", "selection criteria": "We included randomised controlled trials (RCTs) in people with schizophrenia comparing CBT without antipsychotics to standard care, standard care without antipsychotics, or the combination of CBT and antipsychotics."}, "context": [{"title": "Cognitive therapy: at last an alternative to antipsychotics?", "abstract": "", "PMID": "24508319"}, {"title": "Cognitive therapy for people with schizophrenia spectrum disorders not taking antipsychotic drugs: a single-blind randomised controlled trial.", "abstract": "Antipsychotic drugs are usually the first line of treatment for schizophrenia; however, many patients refuse or discontinue their pharmacological treatment. We aimed to establish whether cognitive therapy was effective in reducing psychiatric symptoms in people with schizophrenia spectrum disorders who had chosen not to take antipsychotic drugs.\n\nWe did a single-blind randomised controlled trial at two UK centres between Feb 15, 2010, and May 30, 2013. Participants aged 16-65 years with schizophrenia spectrum disorders, who had chosen not to take antipsychotic drugs for psychosis, were randomly assigned (1:1), by a computerised system with permuted block sizes of four or six, to receive cognitive therapy plus treatment as usual, or treatment as usual alone. Randomisation was stratified by study site. Outcome assessors were masked to group allocation. Our primary outcome was total score on the positive and negative syndrome scale (PANSS), which we assessed at baseline, and at months 3, 6, 9, 12, 15, and 18. Analysis was by intention to treat, with an ANCOVA model adjusted for site, age, sex, and baseline symptoms. This study is registered as an International Standard Randomised Controlled Trial, number 29607432.\n\n74 individuals were randomly assigned to receive either cognitive therapy plus treatment as usual (n=37), or treatment as usual alone (n=37). Mean PANSS total scores were consistently lower in the cognitive therapy group than in the treatment as usual group, with an estimated between-group effect size of -6.52 (95% CI -10.79 to -2.25; p=0.003). We recorded eight serious adverse events: two in patients in the cognitive therapy group (one attempted overdose and one patient presenting risk to others, both after therapy), and six in those in the treatment as usual group (two deaths, both of which were deemed unrelated to trial participation or mental health; three compulsory admissions to hospital for treatment under the mental health act; and one attempted overdose).\n\nCognitive therapy significantly reduced psychiatric symptoms and seems to be a safe and acceptable alternative for people with schizophrenia spectrum disorders who have chosen not to take antipsychotic drugs. Evidence-based treatments should be available to these individuals. A larger, definitive trial is needed.\n\nNational Institute for Health Research.", "PMID": "24508320"}, {"title": "CBT could benefit patients with schizophrenia who do not take medication, research says.", "abstract": "", "PMID": "24516073"}, {"title": "Cognitive behavioural therapy-a valid alternative to antipsychotics for psychosis?", "abstract": "", "PMID": "29605186"}, {"title": "Antipsychotic drugs versus cognitive behavioural therapy versus a combination of both in people with psychosis: a randomised controlled pilot and feasibility study.", "abstract": "Little evidence is available for head-to-head comparisons of psychosocial interventions and pharmacological interventions in psychosis. We aimed to establish whether a randomised controlled trial of cognitive behavioural therapy (CBT) versus antipsychotic drugs versus a combination of both would be feasible in people with psychosis.\n\nWe did a single-site, single-blind pilot randomised controlled trial in people with psychosis who used services in National Health Service trusts across Greater Manchester, UK. Eligible participants were aged 16 years or older; met ICD-10 criteria for schizophrenia, schizoaffective disorder, or delusional disorder, or met the entry criteria for an early intervention for psychosis service; were in contact with mental health services, under the care of a consultant psychiatrist; scored at least 4 on delusions or hallucinations items, or at least 5 on suspiciousness, persecution, or grandiosity items on the Positive and Negative Syndrome Scale (PANSS); had capacity to consent; and were help-seeking. Participants were assigned (1:1:1) to antipsychotics, CBT, or antipsychotics plus CBT. Randomisation was done via a secure web-based randomisation system (Sealed Envelope), with randomised permuted blocks of 4 and 6, stratified by gender and first episode status. CBT incorporated up to 26 sessions over 6 months plus up to four booster sessions. Choice and dose of antipsychotic were at the discretion of the treating consultant. Participants were followed up for 1 year. The primary outcome was feasibility (ie, data about recruitment, retention, and acceptability), and the primary efficacy outcome was the PANSS total score (assessed at baseline, 6, 12, 24, and 52 weeks). Non-neurological side-effects were assessed systemically with the Antipsychotic Non-neurological Side Effects Rating Scale. Primary analyses were done by intention to treat; safety analyses were done on an as-treated basis. The study was prospectively registered with ISRCTN, number ISRCTN06022197.\n\nOf 138 patients referred to the study, 75 were recruited and randomly assigned-26 to CBT, 24 to antipsychotics, and 25 to antipsychotics plus CBT. Attrition was low, and retention high, with only four withdrawals across all groups. 40 (78%) of 51 participants allocated to CBT attended six or more sessions. Of the 49 participants randomised to antipsychotics, 11 (22%) were not prescribed a regular antipsychotic. Median duration of total antipsychotic treatment was 44\u00b75 weeks (IQR 26-51). PANSS total score was significantly reduced in the combined intervention group compared with the CBT group (-5\u00b765 [95% CI -10\u00b737 to -0\u00b793]; p=0\u00b7019). PANSS total scores did not differ significantly between the combined group and the antipsychotics group (-4\u00b752 [95% CI -9\u00b730 to 0\u00b726]; p=0\u00b7064) or between the antipsychotics and CBT groups (-1\u00b713 [95% CI -5\u00b781 to 3\u00b755]; p=0\u00b7637). Significantly fewer side-effects, as measured with the Antipsychotic Non-neurological Side Effects Rating Scale, were noted in the CBT group than in the antipsychotics (3\u00b722 [95% CI 0\u00b758 to 5\u00b787]; p=0\u00b7017) or antipsychotics plus CBT (3\u00b799 [95% CI 1\u00b736 to 6\u00b764]; p=0\u00b7003) groups. Only one serious adverse event was thought to be related to the trial (an overdose of three paracetamol tablets in the CBT group).\n\nA head-to-head clinical trial of CBT versus antipsychotics versus the combination of the two is feasible and safe in people with first-episode psychosis.\n\nNational Institute for Health Research.", "PMID": "29605187"}, {"title": "Antipsychotic drugs versus cognitive behavioural therapy versus a combination of both in people with psychosis: a randomised controlled pilot and feasibility study.", "abstract": "Little evidence is available for head-to-head comparisons of psychosocial interventions and pharmacological interventions in psychosis. We aimed to establish whether a randomised controlled trial of cognitive behavioural therapy (CBT) versus antipsychotic drugs versus a combination of both would be feasible in people with psychosis.\n\nWe did a single-site, single-blind pilot randomised controlled trial in people with psychosis who used services in National Health Service trusts across Greater Manchester, UK. Eligible participants were aged 16 years or older; met ICD-10 criteria for schizophrenia, schizoaffective disorder, or delusional disorder, or met the entry criteria for an early intervention for psychosis service; were in contact with mental health services, under the care of a consultant psychiatrist; scored at least 4 on delusions or hallucinations items, or at least 5 on suspiciousness, persecution, or grandiosity items on the Positive and Negative Syndrome Scale (PANSS); had capacity to consent; and were help-seeking. Participants were assigned (1:1:1) to antipsychotics, CBT, or antipsychotics plus CBT. Randomisation was done via a secure web-based randomisation system (Sealed Envelope), with randomised permuted blocks of 4 and 6, stratified by gender and first episode status. CBT incorporated up to 26 sessions over 6 months plus up to four booster sessions. Choice and dose of antipsychotic were at the discretion of the treating consultant. Participants were followed up for 1 year. The primary outcome was feasibility (ie, data about recruitment, retention, and acceptability), and the primary efficacy outcome was the PANSS total score (assessed at baseline, 6, 12, 24, and 52 weeks). Non-neurological side-effects were assessed systemically with the Antipsychotic Non-neurological Side Effects Rating Scale. Primary analyses were done by intention to treat; safety analyses were done on an as-treated basis. The study was prospectively registered with ISRCTN, number ISRCTN06022197.\n\nOf 138 patients referred to the study, 75 were recruited and randomly assigned-26 to CBT, 24 to antipsychotics, and 25 to antipsychotics plus CBT. Attrition was low, and retention high, with only four withdrawals across all groups. 40 (78%) of 51 participants allocated to CBT attended six or more sessions. Of the 49 participants randomised to antipsychotics, 11 (22%) were not prescribed a regular antipsychotic. Median duration of total antipsychotic treatment was 44\u00b75 weeks (IQR 26-51). PANSS total score was significantly reduced in the combined intervention group compared with the CBT group (-5\u00b765 [95% CI -10\u00b737 to -0\u00b793]; p=0\u00b7019). PANSS total scores did not differ significantly between the combined group and the antipsychotics group (-4\u00b752 [95% CI -9\u00b730 to 0\u00b726]; p=0\u00b7064) or between the antipsychotics and CBT groups (-1\u00b713 [95% CI -5\u00b781 to 3\u00b755]; p=0\u00b7637). Significantly fewer side-effects, as measured with the Antipsychotic Non-neurological Side Effects Rating Scale, were noted in the CBT group than in the antipsychotics (3\u00b722 [95% CI 0\u00b758 to 5\u00b787]; p=0\u00b7017) or antipsychotics plus CBT (3\u00b799 [95% CI 1\u00b736 to 6\u00b764]; p=0\u00b7003) groups. Only one serious adverse event was thought to be related to the trial (an overdose of three paracetamol tablets in the CBT group).\n\nA head-to-head clinical trial of CBT versus antipsychotics versus the combination of the two is feasible and safe in people with first-episode psychosis.\n\nNational Institute for Health Research.", "PMID": "29605187"}, {"title": "Cognitive Behavioral Therapy for antipsychotic-free schizophrenia spectrum disorders: Does therapy dose influence outcome?", "abstract": "This study investigated the effect of \"dose\" and the components of Cognitive Behavioral Therapy (CBT) on treatment effects. It is a secondary analysis of the ACTION (Assessment of Cognitive Therapy Instead of Neuroleptics) trial which investigated CBT for people with schizophrenia spectrum disorders that chose not to take antipsychotic medication. Using instrumental variable methods, we found a \"dose-response\" such that each CBT session attended, reduced the primary outcome measure (the PANSS total score) by approximately 0.6 points (95% CI -1.20 to -0.06, p\u202f=\u202f0.031). This suggests that length of therapy is important for those that receive CBT in the absence of antipsychotic medication. Secondly, using principal stratification we examined the process variables that modified treatment effects. Findings revealed that those who received a longitudinal formulation in the first 4 sessions of CBT had poorer treatment effects than those who did not, however this finding was not statistically significant (95% CI -37.244, 6.677, p\u202f=\u202f0.173). However, it is important to note that these findings were evident in an exploratory analysis with a small sample. Future larger scale studies are needed to help understand components of effective treatment.", "PMID": "30017459"}, {"title": "Staged treatment and acceptability guidelines in early psychosis study (STAGES): A randomized placebo controlled trial of intensive psychosocial treatment plus or minus antipsychotic medication for first-episode psychosis with low-risk of self-harm or aggression. Study protocol and baseline characteristics of participants.", "abstract": "It is now necessary to investigate whether recovery in psychosis is possible without the use of antipsychotic medication. This study will determine (1) whether a first-episode psychosis (FEP) group receiving intensive psychosocial interventions alone can achieve symptomatic remission and functional recovery; (2) whether prolonging the duration of untreated psychosis (DUP) in a sub-group according to randomisation will be associated with a poorer outcome and thereby establish whether the relationship between DUP and outcome is causative; and (3) whether neurobiological changes observed in FEP are associated with the psychotic disorder or antipsychotic medication. Baseline characteristics of participants will be presented.\n\nThis study is a triple-blind randomized placebo-controlled non-inferiority trial. The primary outcome is the level of functioning measured by the Social and Occupational Functioning Assessment Scale at 6\u2009months. This study is being conducted at the Early Psychosis Prevention and Intervention Centre, Melbourne and includes young people aged 15 to 24\u2009years with a DSM-IV psychotic disorder, a DUP less than 6\u2009months and not high risk for suicide or harm to others. Strict discontinuation criteria are being applied. Participants are also undergoing three 3-Tesla-MRI scans.\n\nNinety participants have been recruited and baseline characteristics are presented.\n\nStaged treatment and acceptability guidelines in early psychosis will determine whether antipsychotic medications are indicated in all young people with a FEP and whether antipsychotic medication can be safely delayed. Furthermore, the relative contribution of psychotic illness and antipsychotic medication in terms of structural brain changes will also be elucidated. The findings will inform clinical practice guidelines.", "PMID": "30024100"}, {"title": "Staged treatment and acceptability guidelines in early psychosis study (STAGES): A randomized placebo controlled trial of intensive psychosocial treatment plus or minus antipsychotic medication for first-episode psychosis with low-risk of self-harm or aggression. Study protocol and baseline characteristics of participants.", "abstract": "It is now necessary to investigate whether recovery in psychosis is possible without the use of antipsychotic medication. This study will determine (1) whether a first-episode psychosis (FEP) group receiving intensive psychosocial interventions alone can achieve symptomatic remission and functional recovery; (2) whether prolonging the duration of untreated psychosis (DUP) in a sub-group according to randomisation will be associated with a poorer outcome and thereby establish whether the relationship between DUP and outcome is causative; and (3) whether neurobiological changes observed in FEP are associated with the psychotic disorder or antipsychotic medication. Baseline characteristics of participants will be presented.\n\nThis study is a triple-blind randomized placebo-controlled non-inferiority trial. The primary outcome is the level of functioning measured by the Social and Occupational Functioning Assessment Scale at 6\u2009months. This study is being conducted at the Early Psychosis Prevention and Intervention Centre, Melbourne and includes young people aged 15 to 24\u2009years with a DSM-IV psychotic disorder, a DUP less than 6\u2009months and not high risk for suicide or harm to others. Strict discontinuation criteria are being applied. Participants are also undergoing three 3-Tesla-MRI scans.\n\nNinety participants have been recruited and baseline characteristics are presented.\n\nStaged treatment and acceptability guidelines in early psychosis will determine whether antipsychotic medications are indicated in all young people with a FEP and whether antipsychotic medication can be safely delayed. Furthermore, the relative contribution of psychotic illness and antipsychotic medication in terms of structural brain changes will also be elucidated. The findings will inform clinical practice guidelines.", "PMID": "30024100"}, {"title": "Suicidal Ideation in People With Psychosis Not Taking Antipsychotic Medication: Do Negative Appraisals and Negative Metacognitive Beliefs Mediate the Effect of Symptoms?", "abstract": "Between 5% and 10% of people with psychosis will die by suicide, a rate which is 20-75 times higher than the general population. This risk is even greater in those not taking antipsychotic medication. We examined whether negative appraisals of psychotic experiences and negative metacognitive beliefs about losing mental control mediated a relationship between psychotic symptoms and suicidal ideation in this group. Participants were diagnosed with schizophrenia spectrum disorders, antipsychotic-free for 6 months at baseline, and were participating in an 18-month randomized controlled trial of cognitive therapy vs treatment as usual. We conducted a series of mediation analyses with bootstrapping on baseline (N = 68), follow-up data (9-18 mo; n = 49), and longitudinal data (n = 47). Concurrent general symptoms were directly associated with suicidal ideation at baseline, and concurrent negative symptoms were directly associated with suicidal ideation at 9-18 months. Concurrent positive, negative, general, and overall symptoms were each indirectly associated with suicidal ideation via negative appraisals and/or negative metacognitive beliefs, at baseline and 9-18 months, except for negative symptoms at baseline. Controlling for baseline suicidal ideation and treatment allocation, baseline general symptoms were indirectly associated with later suicidal ideation, via baseline negative appraisals and negative metacognitive beliefs. Baseline negative metacognitive beliefs also had a direct association with later suicidal ideation. These findings suggest the clinical assessment of suicidal ideation in psychosis may be enhanced by considering metacognitive beliefs about the probability and consequences of losing mental control.", "PMID": "30388270"}], "labels": [{"PMID": "24508319", "label": "included"}, {"PMID": "24508320", "label": "included"}, {"PMID": "24516073", "label": "included"}, {"PMID": "29605186", "label": "included"}, {"PMID": "29605187", "label": "included"}, {"PMID": "29605187", "label": "included"}, {"PMID": "30017459", "label": "included"}, {"PMID": "30024100", "label": "included"}, {"PMID": "30024100", "label": "included"}, {"PMID": "30388270", "label": "included"}]}
{"metadata": {"review_pmid": "38323659"}, "inputs": {"background": "Giant cell arteritis (GCA) is a systemic, inflammatory vasculitis primarily affecting people over the age of 50 years. GCA is treated as a medical emergency due to the potential for sudden, irreversible visual loss. Temporal artery biopsy (TAB) is one of the five criteria of the American College of Rheumatology (ACR) 1990 classification, which is used to aid the diagnosis of GCA. TAB is an invasive test, and it can be slow to obtain a result due to delays in performing the procedure and the time taken for histopathologic assessment. Temporal artery ultrasonography (US) has been demonstrated to show findings in people with GCA such as the halo sign (a hypoechoic circumferential wall thickening due to oedema), stenosis or occlusion that can help to confirm a diagnosis more swiftly and less invasively, but requiring more subjective interpretation. This review will help to determine the role of these investigations in clinical practice.", "objectives": "To evaluate the sensitivity and specificity of the halo sign on temporal artery US, using the ACR 1990 classification as a reference standard, to investigate whether US could be used as triage for TAB. To compare the accuracy of US with TAB in the subset of paired studies that have obtained both tests on the same patients, to investigate whether it could replace TAB as one of the criteria in the ACR 1990 classification.", "selection criteria": "We included all participants with clinically suspected GCA who were investigated for the presence of the halo sign on temporal artery US, using the ACR 1990 criteria as a reference standard. We included studies with participants with a prior diagnosis of polymyalgia rheumatica. We excluded studies if participants had had two or more weeks of steroid treatment prior to the investigations. We also included any comparative test accuracy studies of the halo sign on temporal artery US versus TAB, with use of the 1990 ACR diagnostic criteria as a reference standard. Although we have chosen to use this classification for the purpose of the meta-analysis, we accept that it incorporates unavoidable incorporation bias, as TAB is itself one of the five criteria. This increases the specificity of TAB, making it difficult to compare with US. We excluded case-control studies, as they overestimate accuracy, as well as case series in which all participants had a prior diagnosis of GCA, as they can only address sensitivity and not specificity."}, "context": [{"title": "[Horton's temporal arteritis: diagnosis using color Doppler ultrasonography].", "abstract": "", "PMID": "10021874"}, {"title": "[The significance of color duplex ultrasonography for the diagnosis of temporal arteritis].", "abstract": "We examined the usefulness of color duplex ultrasonography in patients suspected of having temporal arteritis. Five patients, who were all aged 70 or older, developed a new onset of localized headache with temporal artery abnormalities, and had an elevated erythrocyte sedimentation rate of > 100 mm/hour. The final diagnoses were temporal arteritis in three patients, polymyalgia rheumatica in one, and probable healed temporal arteritis in one. Color duplex ultrasonography showed stenoses, which were confirmed histologically as well, in the superficial temporal artery of all patients. The characteristic findings of active temporal arteritis were, however, demonstrated in only three biopsy specimens, and in the remaining two the stenoses were thought to be related to previous arteritis. The hypoechoic halo, which has been reported to be a characteristic finding of color duplex ultrasonography in active temporal arteritis, was detected in only one patient with active temporal arteritis and another one with probable healed temporal arteritis. No stenoses were demonstrated in the superficial temporal arteries of 30 control subjects (20 with at least one risk factor of atherosclerosis and 10 without it). Color duplex ultrasonography can therefore be considered a powerful method for detecting stenoses in the superficial temporal artery. Its ability to identify their etiology is, however, unsatisfactory, so that temporal artery biopsy remains undoubtedly the most reliable test for etiological evaluation. We thus recommend color duplex ultrasonography as a supplementary method for the diagnosis of temporal arteritis, because it can provide useful information concerning the appropriate site of temporal artery biopsy.", "PMID": "10655758"}, {"title": "[Value of color-coded duplex ultrasound in patients with polymyalgia rheumatica without signs of temporal arteritis].", "abstract": "Recent studies have described characteristic sonographic signs in patients with manifest temporal arteritis (TA). It was the aim of this study to determine whether sonography can identify TA without clinical signs but biopsy evidence of giant-cell arteritis in patients with rheumatic polymyalgia (RP).\n\n22 patients (14 women, 8 men; average age 67.4 +/- 9.1 years) with RP but no clinical signs of TA were prospectively examined for TA by colour-coded duplex sonography (ATL HDI 3000, linear 12-5 Mhz) before temporal artery biopsy was taken. If there was clinical suspicion of extratemporal involvement, other vessels were also examined selectively. The biopsy was taken from a site identified by the sonography. A definitive diagnosis of TA was made only if there was a positive biopsy.\n\nIn seven of the 22 patients (32%) sonography showed an echo-poor halo around the lumen of the temporal artery. Five of these seven patients also had histological evidence of giant-cell arteritis. Conversely, all of the five patients had abnormal sonographic findings, namely a marked halo with a minimal thickness of 0.7 mm. Two of the five patients also had temporal artery stenosis, i.e. there was a 100% sensitivity and 80% specificity with respect to the halo sign in conformance with the histology. Two patients with TA were also shown sonographically to have stenosis in arteries of the shoulder girdle and arm. Stenoses in the renal and mesenteric arteries as well of the coeliac trunk were demonstrated in one patient.\n\nColour-coded sonography with a high-frequency transducer head probably provides reliable diagnosis of TA in patients with RP, even in the absence of clinical signs of vascular inflammation. It remains to be proven whether sonography without biopsy is reliable enough for the diagnosis and treatment of asymptomatic TA.", "PMID": "11098235"}, {"title": "The suitability of the ultrasound biomicroscope for establishing texture in giant cell arteritis.", "abstract": "To establish whether ultrasound biomicroscope (UBM) is a helpful tool in locating the arterial segment responsible in patients with segmental attacks in giant cell arteritis\n\nThe superficial temporal arteries of 19 patients with suspected giant cell arteritis were examined with the UBM before biopsy.\n\n20 specimens provided the histological proof of giant cell arteritis in five patients. Side differences, a dark perivascular halo, and high reflexivity of the intra-arterial space were found.\n\nit is assumed that there are two types of arteritic inflammation: (1) the occlusion of intra-arterial space due to intimal fibrosis (UBM: high reflexive \"filling\"), and (2) inflammation of the perivascular zone with oedematous thickening and infiltration of the media (UBM: dark halo) and its combination. UBM is helpful in obtaining an indication of the side and segment for biopsy.", "PMID": "11466252"}, {"title": "Incidence of temporal arteritis in patients with polymyalgia rheumatica: a prospective study using colour Doppler ultrasonography of the temporal arteries.", "abstract": "To determine the incidence of temporal arteritis (TA) in patients with polymyalgia rheumatica (PMR) using colour Doppler ultrasonography of the temporal arteries.\n\nUltrasonography was performed in all 127 consecutive patients with newly diagnosed, active PMR seen between 1994 and 2000 and in 127 age- and sex-matched controls.\n\nOf 102 patients with \"pure\" PMR, 8% had ultrasonographic findings arousing suspicion of concomitant active TA (specific halo sign and/or positive histology in 7%; histologically proven TA in 4%). Twenty-five patients had clinical signs of both PMR and TA. Histology and sonography were negative in three of these patients. Of the controls, none had a halo sign and four had stenoses.\n\nUltrasonography of the temporal arteries is a new, non-invasive method of diagnosing concomitant TA in patients with PMR.", "PMID": "11792879"}, {"title": "[Color duplex ultrasound of the temporal artery: replacement for biopsy in temporal arteritis].", "abstract": "The diagnosis of temporal arteritis (TA) is generally confirmed by biopsy. To investigate the diagnostic accuracy of color duplex sonography (CDS), both temporal arteries of 20 patients with suspected TA were prospectively insonated prior to biopsy. Detection of >or=1 hypoechogenic perivascular halo was used as CDS criterion, a temporal artery biopsy and the criteria of the American College of Rheumatology (ACR) as references. The frequency of halo disappearance after 3 months of steroid therapy was also studied. CDS showed TA in 6, biopsy in 12 and ACR criteria in 15 patients. CDS sensitivity was 50 and 40%, and specificity 100%, using the biopsy and the ACR criteria, respectively. After 3 months of steroid treatment, 1 patient still showed halos. In conclusion, detection of halos confirms, whereas the absence of halos does not exclude the diagnosis of TA suggesting that ultrasound may replace biopsy in single patients with typical clinical signs and symptoms and a halo.", "PMID": "11901283"}, {"title": "The utility of color duplex ultrasonography in the diagnosis of temporal arteritis.", "abstract": "Temporal arteritis (TA) is frequently diagnosed with nonspecific clinical characteristics, followed by a temporal artery biopsy to confirm the presence of vasculitis. Consequently, numerous screening surgical biopsies are performed with a high negative-biopsy rate. A prospective study was performed evaluating color duplex ultrasound scan (CDU) as the preferred method for the diagnosis of vasculitis in the evaluation of suspected TA.\n\nThirty-two patients with suspected TA on the basis of clinical criteria were evaluated with CDU before a temporal artery biopsy. The presence of a hypoechoic \"halo,\" suggesting edema of the inflamed vessel, and inflammatory stenoses were noted. Histologic examinations of standard temporal artery biopsies then were performed, and the results were compared with the CDU findings. In addition, a metaanalysis was performed to identify articles related to the use of ultrasound scan in the detection of TA.\n\nAll patients completed a bilateral CDU examination of the temporal arteries, and in 75% of patients biopsied, no evidence of vasculitis was found at histologic examination. When CDU examined for halo alone as the determinant for disease, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), compared with histologic confirmation of TA, were 85.7%, 92.0%, 75.0%, and 95.8%, respectively. With the criteria for a halo sign present, an inflammatory stenosis present, or both present on CDU, the sensitivity, specificity, positive predictive value, and NPV were 100%, 80.0%, 58.3%, and 100%, respectively.\n\nCDU is a superior noninvasive method of determining the presence of vasculitis when compared with routine surgical biopsy. Examination of the temporal artery with CDU can effectively predict which patient will need surgical biopsy. The utility of CDU in the diagnosis of TA is maintained by a high sensitivity in detecting patients with the disease and also by a high NPV that can eliminate patients who would not benefit from biopsy.", "PMID": "12469046"}, {"title": "The utility of color duplex ultrasonography in the diagnosis of temporal arteritis.", "abstract": "Temporal arteritis (TA) is frequently diagnosed with nonspecific clinical characteristics, followed by a temporal artery biopsy to confirm the presence of vasculitis. Consequently, numerous screening surgical biopsies are performed with a high negative-biopsy rate. A prospective study was performed evaluating color duplex ultrasound scan (CDU) as the preferred method for the diagnosis of vasculitis in the evaluation of suspected TA.\n\nThirty-two patients with suspected TA on the basis of clinical criteria were evaluated with CDU before a temporal artery biopsy. The presence of a hypoechoic \"halo,\" suggesting edema of the inflamed vessel, and inflammatory stenoses were noted. Histologic examinations of standard temporal artery biopsies then were performed, and the results were compared with the CDU findings. In addition, a metaanalysis was performed to identify articles related to the use of ultrasound scan in the detection of TA.\n\nAll patients completed a bilateral CDU examination of the temporal arteries, and in 75% of patients biopsied, no evidence of vasculitis was found at histologic examination. When CDU examined for halo alone as the determinant for disease, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), compared with histologic confirmation of TA, were 85.7%, 92.0%, 75.0%, and 95.8%, respectively. With the criteria for a halo sign present, an inflammatory stenosis present, or both present on CDU, the sensitivity, specificity, positive predictive value, and NPV were 100%, 80.0%, 58.3%, and 100%, respectively.\n\nCDU is a superior noninvasive method of determining the presence of vasculitis when compared with routine surgical biopsy. Examination of the temporal artery with CDU can effectively predict which patient will need surgical biopsy. The utility of CDU in the diagnosis of TA is maintained by a high sensitivity in detecting patients with the disease and also by a high NPV that can eliminate patients who would not benefit from biopsy.", "PMID": "12469046"}, {"title": "Comparison between color duplex ultrasonography and histology of the temporal artery in cranial arteritis (giant cell arteritis).", "abstract": "Duplex sonography of the temporal artery may be helpful in the diagnosis of cranial arteritis.\n\nThe superficial temporal arteries of 36 patients with cranial arteritis or suspected arteritis were examined using both duplex ultrasonography (US) and biopsy. The data of these patients were divided into two groups. Group A consisted of 24 patients (66.7%) with definite positive results using duplex (US) and Group B of 12 patients (33.3%) who showed a suspicious or negative ultrasonographic result.\n\nIn all patients of Group A, the histological findings corresponded with the ultrasonographic changes in the inflamed artery. - The characteristic ultrasonographic sign was a dark halo around the lumen of the temporal arteries. There was a high correlation between a bilateral halo found by US with an ocular involvement. Ten out of 14 patients with a bilateral halo (71.4%) showed a distinct involvement of the optic nerve or retina. - The characteristic histological signs were infiltration of the vessel wall by inflammatory cells, mainly lymphocytes. Group B: The biopsies of the superficial temporal arteries were positive in 8 patients (66.7 %), negative in 4 other patients (33.3%).\n\nPatients with a distinct halo, demonstrated by US, also showed corresponding pronounced inflammatory cell infiltration of the vessel wall. Patients with no ultrasonographic changes presented histological signs of initial inflammation such as isolated inflammatory cells around the vasa vasorum and/or in the adventitial layer.", "PMID": "12578748"}, {"title": "[Color duplex ultrasound of the temporal artery: replacement for biopsy in temporal arteritis].", "abstract": "", "PMID": "12592058"}], "labels": [{"PMID": "10021874", "label": "excluded"}, {"PMID": "10655758", "label": "excluded"}, {"PMID": "11098235", "label": "excluded"}, {"PMID": "11466252", "label": "excluded"}, {"PMID": "11792879", "label": "excluded"}, {"PMID": "11901283", "label": "excluded"}, {"PMID": "12469046", "label": "excluded"}, {"PMID": "12469046", "label": "excluded"}, {"PMID": "12578748", "label": "excluded"}, {"PMID": "12592058", "label": "excluded"}]}
{"metadata": {"review_pmid": "38319008"}, "inputs": {"background": "Initial arch wires are the first arch wires inserted into fixed appliance at the beginning of orthodontic treatment. With a number of different types of orthodontic arch wires available for initial tooth alignment, it is important to understand which are most efficient and which cause the least amount of root resorption and pain during the initial aligning stage of treatment. This is the third update of a Cochrane review first published in 2010.", "objectives": "To assess the effects of initial arch wires for the alignment of teeth with fixed orthodontic braces, in terms of the rate of tooth alignment, amount of root resorption accompanying tooth movement, and intensity of pain experienced by patients during the initial alignment stage of treatment.", "selection criteria": "We included randomised controlled trials (RCTs) of different initial arch wires used to align teeth with fixed orthodontic braces. We included people with full-arch fixed orthodontic appliances on the upper arch, lower arch, or both arches."}, "context": [{"title": "The pain and discomfort experienced during orthodontic treatment: a randomized controlled clinical trial of two initial aligning arch wires.", "abstract": "A randomized controlled clinical trial was performed to compare the nature, prevalence, intensity, and duration of pain related to the use of a relatively recently developed superelastic arch wire and a more traditional multistranded steel arch wire. Other factors likely to influence the pain experience were also investigated. Forty-three subjects participated in the study, the pain response being assessed by each of the visual analogue scales, the questionnaires, and an analgesic consumption record. In 18 of the 43 subjects a standardized preliminary dental extraction procedure was used as a control. Subsequent to the random allocation of an initial arch wire in 43 patients, 22 of them underwent a second arch wire in the opposing arch, the wire again being determined by random allocation. It was found that the prevalence, intensity, and duration of pain after the insertion of the two types of wire was similar but much greater than in the postextraction control phase. The pain score peaked on the morning after the placement of the arch wire, lasting typically for 5 to 6 days. The pain and discomfort experienced after the insertion of the second arch wire was similar to that of the first, no conditioning response being evident. Overall a diurnal variation was found with a tendency to an increase in pain in the evenings and nights, although this did not greatly affect sleep. The pain response was found to be highly and consistently subjective, not related to the dental arch, crowding, sex, or social class; however, a statistically significant association was found between the age and the pain experienced.", "PMID": "1456222"}, {"title": "Perception of pain during orthodontic treatment with fixed appliances.", "abstract": "The aims of this study were to investigate the initial time at which pain occurs after insertion of two initial wires of different sizes, the duration of the pain, the areas affected within the mouth, the level of self-medication, the effect of this pain on daily life, and whether gender is important in the perception of pain. The study group consisted of 109 patients (52 boys, 57 girls) with a mean chronological age of 13.6 years for boys and 14.7 years for girls. Insertion of either a 0.014 or 0.016 inch wire was by random selection. Following insertion of the archwires, a questionnaire comprising a total of 49 questions was given to the patients. They described the time of initial pain in the first question, answered the next 24 questions as 'yes' or 'no', and used a visual analogue scale for the final 24 questions. No significant differences were found in terms of gender, in the perception period of initial pain as regards the areas affected within the mouth or the effect of pain on daily living when the 0.014 and 0.016 inch wire groups were compared at 6 hours, 1, 2, 3, 4, 5, 6 and 7 days. At 24 hours, which was found to be statistically significant, more pain relief was used in the 0.014 inch archwire group. The results show that in both groups, initial pain was perceived at 2 hours, peaked at 24 hours and had decreased by day 3.", "PMID": "14994886"}, {"title": "Alleviation of mandibular anterior crowding with copper-nickel-titanium vs nickel-titanium wires: a double-blind randomized control trial.", "abstract": "The purpose of this study was to investigate the efficiency of copper-nickel-titanium (CuNiTi) vs nickel-titanium (NiTi) archwires in resolving crowding of the anterior mandibular dentition.\n\nSixty patients were included in this single-center, single-operator, double-blind randomized trial. All patients were bonded with the In Ovation-R self-ligating bracket (GAC, Central Islip, NY) with a 0.022-in slot, and the amount of crowding of the mandibular anterior dentition was assessed by using the irregularity index. The patients were randomly allocated into 2 groups of 30 patients, each receiving a 0.016-in CuNiTi 35 degrees C (Ormco, Glendora, Calif) or a 0.016-in NiTi (ModernArch, Wyomissing, Pa) wire. The type of wire selected for each patient was not disclosed to the provider or the patient. The date that each patient received a wire was recorded, and all patients were followed monthly for a maximum of 6 months. Demographic and clinical characteristics between the 2 wire groups were compared with the t test or the chi-square test and the Fisher exact test. Time to resolve crowding was explored with statistical methods for survival analysis, and alignment rate ratios for wire type and crowding level were calculated with Cox proportional hazards multivariate modeling.\n\nThe type of wire (CuNiTi vs NiTi) had no significant effect on crowding alleviation (129.4 vs 121.4 days; hazard ratio, 1.3; P >0.05). Severe crowding (>5 on the irregularity index) showed a significantly higher probability of crowding alleviation duration relative to dental arches with a score of <5 (138.5 vs 113.1 days; hazard ratio, 2.2; P=0.02).\n\nThe difference of the loading pattern of wires in laboratory and clinical conditions might effectively eliminate the laboratory-derived advantage of CuNiTi wires.", "PMID": "19651336"}, {"title": "Comparison of superelastic NiTi and multistranded stainless steel wires in initial alignment.", "abstract": "", "PMID": "2084149"}, {"title": "A clinical trial of aligning archwires.", "abstract": "The physical properties of a super-elastic archwire alloy (Titanol) and Nitinol were investigated by the means of a bending test. It was found that the alloy possessed super-elastic properties. A clinical trial was then carried out to compare the properties of two types of aligning archwire. Two groups of 20 patients with crowded dentitions were randomly allocated either Titanol or Nitinol, a conventional nickel-titanium alloy aligning archwire. High quality alginate impressions were taken after archwire placement in Edgewise fixed appliances and were repeated after a mean period of 35 days. The impressions were cast in dental stone and digitized using the Reflex Metrograph. The contact points of the teeth of the labial segments, together with four stable points in the rugae were recorded. This enabled the co-ordinates for the sequential study models to be superimposed upon one another, allowing tooth movement in three dimensions to be calculated. The measurement error expressed as error variance was 0.028 mm. The coefficient of reliability was 97 per cent. When tooth movement was analysed the mean movement per contact point for Titanol was 1.7 mm and for Nitinol 1.42 mm. This difference was not statistically significant (P less than 0.05, t-test). However, a clinical impression was that the super-elastic archwire proved superior to the Nitinol, because it was more readily engaged into grossly displaced teeth.", "PMID": "2086257"}, {"title": "Which orthodontic archwire sequence? A randomized clinical trial.", "abstract": "The aim of this study was to compare three orthodontic archwire sequences. One hundred and fifty-four 10- to 17-year-old patients were treated in three centres and randomly allocated to one of three groups: A = 0.016-inch nickel titanium (NiTi), 0.018 x 0.025-inch NiTi, and 0.019 x 0.025-inch stainless steel (SS); B = 0.016-inch NiTi, 0.016-inch SS, 0.020-inch SS, and 0.019 x 0.025-inch SS; and C = 0.016 x 0.022-inch copper (Cu) NiTi, 0.019 x 0.025-inch CuNiTi, and 0.019 x 0.025-inch SS. At each archwire change and for each arch, the patients completed discomfort scores on a seven-point Likert scale at 4 hours, 24 hours, 3 days, and 1 week. Time in days and the number of visits taken to reach a 0.019 x 0.025-inch SS working archwires were calculated. A periapical radiograph of the upper left central incisor was taken at the start of the treatment and after placement of the 0.019 x 0.025-inch SS wire so root resorption could be assessed. There were no statistically significant differences between archwire sequences A, B, or C for patient discomfort (P > 0.05) or root resorption (P = 0.58). The number of visits required to reach the working archwire was greater for sequence B than for A (P = 0.012) but this could not be explained by the increased number of archwires used in sequence B.", "PMID": "17041083"}, {"title": "A clinical comparison of three aligning archwires in terms of alignment efficiency: A prospective clinical trial.", "abstract": "To clinically evaluate the effectiveness of three orthodontic aligning archwires in relation to tooth alignment speed during the initial alignment stage of treatment.\n\nA consecutive sample of 74 patients requiring lower only or upper and lower fixed orthodontic appliances were randomly allocated into three different archwires (0.014-inch superelastic nickel-titanium [NiTi], 0.014-inch thermoelastic NiTi, or 0.014-inch conventional NiTi). Good quality impressions were taken of the lower arch before archwire placement (T0) and at designated serial stages of alignment (every 2\u00a0weeks: T2, T4, T6, \u2026, T16). The change in tooth alignment was measured in millimeters from the resultant casts using Little's irregularity index. Demographic and clinical differences among the three groups were compared with the chi-square or analysis of variance (ANOVA) test. The difference in the change of lower anterior tooth alignment over time among the three groups was explored with a Split Plot ANOVA (SPANOVA, or within- and between-groups ANOVA). The Kruskal-Wallis nonparametric test was used when data were not normally distributed.\n\nThe SPANOVA and Wilks Lambda Multivariate test confirmed that the wire type had no influence on the rate of change in alignment (P \u200a=\u200a .98).\n\nThe three forms of NiTi wires were similar in terms of their alignment efficiency during the initial aligning stage of orthodontic fixed appliance therapy.", "PMID": "25090135"}, {"title": "Clinical Efficiency of Two Sequences of Orthodontic Wires to Correct Crowding of the Lower Anterior Teeth.", "abstract": "This study compared time to correction of mandibular anterior crowding using two arch wire sequences, one with conventional nickel-titanium (NiTi) arch wires and the other with conventional and NiTi heat-activated arch wires. Twenty-two boys and girls (mean age: 16.68 \u00b1 2.66) with moderate crowding (3-6 mm) were assigned randomly to one of two groups and followed up for five months (six assessments) when arch wires were changed. Time to crowding correction was analyzed statistically using the Kaplan-Meier method. Data were collected during the five-month follow-up, and time to correction was compared between groups using the log rank test. At the end of follow-up, mandibular crowding was corrected in 100% of the cases in the group treated with the sequence that included NiTi heat-activated arch wires, whereas about 30% of those treated with NiTi arch wires were not completely corrected. There was a significant difference in time to complete treatment between groups (log rank = 5.996; p < 0.05). In the group treated with the sequence that included heat-activated wires, alignment and leveling of mandibular anterior teeth were completed earlier than in the group treated only with conventional NiTi arch wires. Clinical trial registration is found at RBR-7g5zng.", "PMID": "26176018"}, {"title": "Pain experience during initial alignment with three types of nickel-titanium archwires: a prospective clinical trial.", "abstract": "To clinically evaluate the pain intensity during the week following initial placement of three different orthodontic aligning archwires.\n\nA consecutive sample of 75 patients requiring upper and lower fixed orthodontic appliances were alternately allocated into three different archwires (0.014-inch superelastic NiTi, 0.014-inch thermoelastic NiTi or 0.014-inch conventional NiTi). Assessments of pain/discomfort were made on a daily basis over the first 7-day period after bonding by means of visual analog scale and consumption of analgesics. The maximum pain score was recorded. The possible associations between age, gender, degree of crowding, and teeth irregularity and the pain intensity were also examined. Demographic and clinical differences between the three groups were compared with chi-square test or analysis of variance (ANOVA) test.\n\nNo statistically significant differences were found in the pain intensity when the three aligning NiTi archwires were compared (P \u200a=\u200a .63). No significant differences in pain perception were found in terms of gender, age, lower arch crowding, and incisor irregularity. The intake of analgesics was the least in the superelastic NiTi group.\n\nThe three forms of NiTi wires were similar in terms of pain intensity during the initial aligning stage of orthodontic fixed appliance therapy. Gender, age, and the degree of crowding have no effect on the perceived discomfort experienced by patients undergoing fixed orthodontic treatment.", "PMID": "26516711"}, {"title": "Mandibular dental arch changes with active self-ligating brackets combined with different archwires.", "abstract": "The aim was to compare mandibular arch and incisor inclinational changes by comparing active self-ligating brackets used with different forms of archwires with a control group in nonextraction cases.\n\nThe sample of 50 patients with Class I malocclusion was divided into three groups: Group I was treated with active self-ligating brackets (Nexus, Ormco/Orange, CA, USA) used with Damon arch form copper nickel-titanium (Cu-NiTi) and stainless steel (SS) wires; Group II was treated with interactive self-ligating bracket system (Empower, American Orthodontics, Sheboygan, Wis, USA) used with standard Cu-NiTi and SS wires; and Group III was treated with Roth prescribed conventional brackets (Forestadent, Pforzheim, Germany) with standard Cu-NiTi and SS wires which was designed as a control group. Changes in dimension of mandibular arch and inclination of incisors were assessed on dental models and lateral cephalometric radiographs at pretreatment (T1) and posttreatment (T2) periods. Paired-t test and one-way analysis of variance were used to perform intragroup and intergroup comparisons, respectively.\n\nIn all groups, an average increase of transversal distances occurred from pretreatment to the posttreatment period (P < 0.05). However, mandibular arch length increase was significantly different among the Groups I-III (P = 0.008) and I-II (P = 0.006). No significant intergroup difference was found with regard to incisor inclinational changes.\n\nBracket type had no significant effect on the mandibular dimensional or incisor inclination changes. Besides this, archwire type had only little effect on the treatment results as active self-ligating bracket with Damon archwires increased mandibular arch length greater than other groups.", "PMID": "29735855"}], "labels": [{"PMID": "1456222", "label": "included"}, {"PMID": "14994886", "label": "included"}, {"PMID": "19651336", "label": "included"}, {"PMID": "2084149", "label": "included"}, {"PMID": "2086257", "label": "included"}, {"PMID": "17041083", "label": "excluded"}, {"PMID": "25090135", "label": "excluded"}, {"PMID": "26176018", "label": "excluded"}, {"PMID": "26516711", "label": "excluded"}, {"PMID": "29735855", "label": "excluded"}]}
{"metadata": {"review_pmid": "38318932"}, "inputs": {"background": "The prevalence of gallstones varies between less than 1% and 64% in different populations and is thought to be increasing in response to changes in nutritional intake and increasing obesity. Some people with gallstones have no symptoms but approximately 2% to 4% develop them each year, predominantly including severe abdominal pain. People who experience symptoms have a greater risk of developing complications. The main treatment for symptomatic gallstones is cholecystectomy. Traditionally, a low-fat diet has also been advised to manage gallstone symptoms, but there is uncertainty over the evidence to support this.", "objectives": "To evaluate the benefits and harms of modified dietary fat intake in the treatment of gallstone disease in people of any age.", "selection criteria": "We included randomised clinical trials (irrespective of language, blinding, or status) in people with gallstones diagnosed using ultrasonography or conclusive imaging methods. We excluded participants diagnosed with another condition that may compromise dietary fat tolerance. We excluded trials where data from participants with gallstones were not reported separately from data from participants who did not have gallstones. We included trials that investigated other interventions (e.g. trials of drugs or other dietary (non-fat) components) providing that the trial groups had received the same proportion of drug or other dietary (non-fat) components in the intervention."}, "context": [{"title": "A randomised, single blinded trial, assessing the effect of a two week preoperative very low calorie diet on laparoscopic cholecystectomy in obese patients.", "abstract": "Laparoscopic cholecystectomy (LC) can be technically challenging in the obese. The primary aim of the trial was to establish whether following a Very Low Calorie Diet (VLCD) for two weeks pre-operatively reduces operation time. Secondary outcomes included perceived operative difficulty and length of hospital stay.\n\nA single-blinded, randomized controlled trial of consecutive patients with symptomatic gallstones and BMI >30\u00a0kg/m(2) 46 patients were randomized to a VLCD or normal diet for two weeks prior to LC. Food diaries were used to document dietary intake. The primary outcome measure was operation time. Secondary outcomes were length of stay, weight change operative complications, day case rates and perceived difficulty of operation.\n\nThe VLCD was well tolerated and had significantly greater preoperative weight loss (3.48\u00a0kg vs. 0.98\u00a0kg; p\u00a0<\u00a00.0001). Median operative time was significantly reduced by 6\u00a0min in the VLCD group (25 vs. 31\u00a0min; p\u00a0=\u00a00.0096). There were no differences in post-operative complications, length of stay, or day case rates between the groups. Dissection of Calot's triangle was deemed significantly easier in the VLCD group.\n\nA two week VLCD prior to elective laparoscopic cholecystectomy in obese patients is safe, well tolerated and was shown to significantly reduce pre-operative weight and operative time.\n\n61630192. http://www.isrctn.com/ISRCTN61630192 Trial registration.", "PMID": "27154810"}, {"title": "Effect of dietary cholesterol on biliary lipids in patients with gallstones and normal subjects.", "abstract": "The purpose of this study was to determine the effect of dietary cholesterol on biliary lipids in subjects with and without gallstones. Twelve patients with asymptomatic gallstones (six men, six women) were assigned diets containing 500, 750, and 1000 mg cholesterol daily for 3-wk periods in random sequence. Seven healthy women similarly were assigned diets containing 500 and 1000 mg cholesterol daily. With increasing dietary cholesterol in patients with gallstones, biliary saturation indices and molar percents of cholesterol and phospholipids increased significantly while molar percent of biliary bile acids decreased significantly. With increasing dietary cholesterol in healthy women, the biliary saturation index and molar percent of cholesterol increased significantly; the mean saturation index exceeded unity on the diet containing 1000 mg cholesterol daily. In conclusion, augmented dietary cholesterol for brief periods increased biliary cholesterol saturation in subjects with and without gallstones.", "PMID": "4036847"}, {"title": "The effect of diet on bile acid kinetics and biliary lipid secretion in gallstone patients treated with ursodeoxycholic acid.", "abstract": "Effects of specific dietary alterations in patients with radiolucent gallstones treated with ursodeoxycholic acid (UDCA, 750 mg at bedtime) were investigated. Patients were allocated randomly to one of four diets: standard (500 mg cholesterol/day), low-cholesterol (250 mg/day), added-bran (30 g/day), or substituted medium-chain triglycerides (MCT) oil (20% of fat). Dietary intake and good compliance were verified by computerized analysis of dietary diaries. Bile-acid kinetics (26 patients) or secretion of biliary lipids (23 other patients) were determined at enrollment and at 6 and 9 mo, respectively, during treatment. Although MCT further decreased the UDCA-induced decrease in the synthesis of chenodeoxycholic acid, it did not lessen desaturation of bile. Otherwise, compared to the standard diet, no experimental diet significantly altered the UDCA-induced increase of the pools of total bile acids and UDCA or the UDCA-induced decrease in synthesis of bile acids and in biliary secretion or saturation of cholesterol. If these dietary manipulations facilitate dissolution of gallstones by UDCA, they do so by other mechanisms.", "PMID": "3004189"}, {"title": "Effect of diet on dissolution of gallstones by ursodeoxycholic acid, including a comparison between ultrasonography and cholecystography.", "abstract": "", "PMID": "3014318"}, {"title": "Low-cholesterol diet: enhancement of effect of CDCA in patients with gall stones.", "abstract": "Fifteen patients with gall stones who were taking chenodeoxycholic acid(CDCA) 15 mg/kg at bedtime participated in two separate experiments to investigate the effects of altering sterol intake on the cholesterol saturation index (SI) of fasting gall-bladder bile. In experiment I the 15 patients on an unrestricted diet had a SI of 0.87 +/- 0.04 (mean +/- SE of mean), which fell to 0.75 +/- 0.04 after one week in hospital on a diet of 100 mg cholesterol daily. In experiment II seven of the patients were given four different dietary regimens lasting one month each in random order as outpatients. On a diet of 600 mg of cholesterol daily the mean SI was 0.72 +/- 0.05, which fell to 0.67 +/- 0.05 when the patients were put on a 100 mg cholesterol diet. The addition of plant sterols (3 g daily) to both diets raised the mean SIs to 0.80 +/- 0.05 and 0.77 +/- 0.05 respectively. The percentage CDCA in bile was unaffected by alterations in the cholesterol and plant sterol intakes. We conclude that a low-cholesterol diet but not a high intake of plant sterols enhances the effect of CDCA in patients with gall stones.", "PMID": "709092"}, {"title": "Minimum effective dose of chenic acid for gallstone patients: reduction with bedtime administration and low cholesterol diet.", "abstract": "The aim of this study was to determine whether bedtime administration and a low cholesterol diet reduce the minimum effective dose of chenodeoxycholic (chenic) acid, defined as the dose giving a mean cholesterol saturation index of 0.8. Dose response studies were carried out in 10 patients with radiolucent gallstones in a functioning gallbladder during three different treatment regimens. On each regimen, all patients received three different doses of chenodeoxycholic acid in random order for one month each. Bedtime chenic acid plus a low cholesterol diet gave the greatest reduction in saturation index. A significant dose/response relationship was found on each regimen. On the conventional regimen of mealtime chenic acid, the minimum effective dose was 14 mg/kg/day; on bedtime chenic acid it was 12.4 mg/kg/day; and on bedtime chenic acid plus low cholesterol diet it was further reduced to 8.4 mg/kg/day (p less than 0.01). There was a dose-related increase in bowel frequency, which was absent at 10.6 mg/kg/day and below. We conclude that administration of chenic acid at bedtime with a low cholesterol diet enables the minimum effective dose for gallstone dissolution to be approximately halved, thus preventing diarrhoea and reducing the cost of treatment.", "PMID": "7076005"}, {"title": "[Optimization of diet therapy in patients with gallstones complicated with obesity and impaired glucose tolerance].", "abstract": "It was investigated the influence of a diet with lower glycaemic index on clinico-metabolic parameters in obese patients with gallstones and impaired glucose tolerance. The results investigations indicated that the lowering of glycaemic index and the caloric reduction of diet have a beneficial effects on dynamic of parameters of functional status of liver and gallbladder. It was noted the increase of medical effect of diet in correction of obesity and impaired parameters of carbohydrate and lipid metabolism in this patients in process of dietotherapy.", "PMID": "14619611"}, {"title": "Effect of the type of dietary fat on biliary lipid composition and bile lithogenicity in humans with cholesterol gallstone disease.", "abstract": "The effect of the type of dietary fat on bile lipids and lithogenicity is unclear. This study compared the effects of two dietary oils that differed in fatty acid profile on biliary lipid composition in humans.\n\nFemale patients who had cholesterol gallstones and were scheduled for elective cholecystectomy were studied. For 30 d before surgery, subjects were kept on diets that contained olive oil (olive oil group, n = 9) or sunflower oil (sunflower oil group, n = 9) as the main source of fat. Gallbladder bile and stones were sampled at surgery. After cholecystectomy, duodenal samples were collected by nasoduodenal intubation during fasting and after administration of mixed liquid meals that included the corresponding dietary oil. Duodenal and gallbladder bile samples were analyzed for cholesterol, phospholipids, and total bile acids by established methods. Individual bile acid conjugates in gallbladder bile were measured by high-performance liquid chromatography. Gallstones were analyzed by semiquantitative polarizing light microscopy.\n\nDespite marked differences in the absolute concentration of biliary lipids and total lipid content, manipulation of dietary fat ingestion did not influence the cholesterol saturation or the profile of individual bile acids in gallbladder bile obtained from patients who had gallstones. All but one subject had mixed cholesterol stones. A cholesterol saturation index of hepatic bile in fasted cholecystectomized patients was similar in both dietary groups and indicative of supersaturation. In response to the test meal, the cholesterol saturation index decreased significantly in patients given the olive oil diet, reaching values lower than one at 120 min postprandially. In contrast, hepatic bile secreted by patients who consumed sunflower oil appeared supersaturated (cholesterol saturation index >1.5) throughout the experiment.\n\nOur results suggest that the type of dietary fat habitually consumed can influence bile composition in humans. In gallbladder, this influence was noted in the presence of more concentrated bile in the olive oil group. However, this was not translated into a modification of cholesterol saturation, which is likely due to the fact that cholesterol gallstones were present by the time the dietary intervention started. The finding that a typical postprandial variation in hepatic bile lithogenicity occurred only in olive oil patients was revealing. While keeping in mind the methodologic limitations of this part of the study, some gastrointestinal and metabolic mechanisms for this effect are discussed.", "PMID": "15797676"}, {"title": "[Gastrointestinal function following cholecystectomy].", "abstract": "Randomized studies of the physiological and clinical consequences of cholecystectomy for uncomplicated gallbladder stones are very scarce. Bile acid malabsorption is increased postoperatively, probably giving rise to diarrhea in a few sensitive individuals. Preexisting abdominal distension and fat intolerance most often persist postoperatively. In adequately selected patients, abdominal pain may subside in 75% or more. The presence of functional bowel disease should always be considered in patients with uncomplicated gallstones.", "PMID": "16014213"}, {"title": "Randomized study for assessment of hypolipidic diet in digestive symptoms immediately following laparoscopic cholecystectomy.", "abstract": "To validate the need for prescribing low-fat diet in the prevention or reduction of dyspeptic symptoms in the postoperative period in patients undergoing laparoscopic cholecystectomy.\n\nWe selected 40 patients, free of liver or pancreatic disease, biliary gallstones, gastritis, ulcer, diabetes and dyslipidemia, who were divided into two groups. We conducted dietary anamnesis, identification of dyspepsia before the onset of cholelithiasis and guidance on appropriate postoperatively feeding (normal or low-fat). We used the chi-square test and Pearson correlation for statistical assessment, considering p d\" 0.05 as significant.\n\nWhen comparing the two groups of patients without preoperative dyspepsia, it was observed that in group I seven patients (63.6%) were asymptomatic and in group II, four (66.7%). In group I, four (36.4%) had onset of symptoms and in group II, two (33.3%), p = 0.684. When correlating the two groups with preoperative dyspeptic symptoms, it was observed that there was permanence, appearance or disappearance of symptoms postoperatively, p = 0.114.\n\nThere was no significant effect of low-fat diet in the prevention of gastrointestinal symptoms, especially in preoperatively asymptomatic patients. Thus, there is no need of a low-fat diet. So, it is up to the surgeon to evaluate each patient individually and adjust the diet to his/her needs and clinical conditions.", "PMID": "23912367"}], "labels": [{"PMID": "27154810", "label": "included"}, {"PMID": "4036847", "label": "included"}, {"PMID": "3004189", "label": "included"}, {"PMID": "3014318", "label": "included"}, {"PMID": "709092", "label": "included"}, {"PMID": "7076005", "label": "included"}, {"PMID": "14619611", "label": "excluded"}, {"PMID": "15797676", "label": "excluded"}, {"PMID": "16014213", "label": "excluded"}, {"PMID": "23912367", "label": "excluded"}]}
{"metadata": {"review_pmid": "38318883"}, "inputs": {"background": "Growth hormone (GH)-secreting pituitary adenoma is a severe endocrine disease. Surgery is the currently recommended primary therapy for patients with GH-secreting tumours. However, non-surgical therapy (pharmacological therapy and radiation therapy) may be performed as primary therapy or may improve surgical outcomes.", "objectives": "To assess the effects of surgical and non-surgical interventions for primary and salvage treatment of GH-secreting pituitary adenomas in adults.", "selection criteria": "Randomised controlled trials (RCTs) and quasi-RCTs of more than 12 weeks' duration, reporting on surgical, pharmacological, radiation, and combination interventions for GH-secreting pituitary adenomas in any healthcare setting."}, "context": [{"title": "Effectiveness of slow-release lanreotide in previously operated and untreated patients with GH-secreting pituitary macroadenoma.", "abstract": "The aim of this study was to verify whether treatment with slow-release lanreotide (SRL) before surgery is useful in the management of patients with GH-secreting pituitary macroadenoma. Twenty untreated acromegalics were enrolled randomly in two groups. Ten patients (group 1: 2 males and 8 females aged 44.5 +/- 4.3 years) underwent surgery via transsphenoidal access. Only one of them was cured by surgery, whereas the other nine were treated with SRL. In the other ten patients (group 2: 3 males and 7 females aged 43.2 +/- 12.3 years), transsphenoidal surgery followed SRL treatment. Surgery induced the normalization of GH and IGF-1 levels in four group 2 patients - three of them had shown an evident shrinkage of the tumor after SRL treatment. After surgery, group 1 showed a significant decrease of mean IGF-1 (580 +/- 63 vs. 789 +/- 64 ng/ml, p < 0.02), but not of GH values (26.1 +/- 9.8 vs. 44.8 +/- 19.3 ng/ml, NS); the cured patient was excluded from the following evaluations. Group 2 showed an evident, but not significant, decrease of both GH and IGF-1 values compared to values measured at the end of medical treatment (GH: 22.4 +/- 9.7 vs. 7.7 +/- 4.7 ng/ml, NS. IGF-1: 570 +/- 69 vs. 402 +/- 58 ng/ml, NS). Gonadal, thyroid and adrenal impairment was evident in six, four and no patients in group 1 and in three, two and one patients in group 2, respectively. SRL 30 mg was administered every 14 days for three months and then every 10 days until the 6th month. Before SRL treatment, mean GH and IGF-1 levels did not differ significantly in group 1 vs. group 2 (GH: 29.3 +/- 10.5 vs. 43.4 +/- 22.0 ng/ml; IGF-1: 633 +/- 38 vs. 778 +/- 83 ng/ml). In group 1, a significant decrease of serum GH, but not of IGF-1 levels, was achieved at the end of 1st trimester of SRL (GH: 17.6 +/- 5.4 ng/ml, p < 0.05. IGF-1: 540 +/- 48 ng/ml, NS), whereas a significant decrease in both GH and IGF-1 values was evident during the 2nd trimester (GH: 6.1 +/- 3.0 ng/ml, p < 0.05. IGF-1: 433 +/- 74 ng/ml, p < 0.02). Serum GH levels, measured during the 2nd trimester of SRL therapy, were also significantly lower than levels measured at the end of the 1st trimester (p < 0.05). Group 2 serum GH and IGF-1 levels were not significantly decreased at the end of the 1st trimester (GH: 27.2 +/- 12.1 ng/ml, NS. IGF-1: 698 +/- 74 ng/ml, NS), whereas only serum IGF-1 (570 +/- 69 ng/ml, p < 0.05) was significantly reduced during the 2nd trimester of SRL (GH: 22.4 +/- 9.7 ng/ml, NS). Serum GH and IGF-I fell in the normal range in 4 patients in group 1 and one in group 2 at the end of the second trimester of SRL therapy. Independently of the trial applied, the mean clinical score level ameliorated significantly in both groups (group 1: p < 0.0005; group 2: p < 0.0001). In both groups, the proportion of patients complaining of headache and tissue swelling and the score level of headache, tissue swelling and excessive sweating decreased significantly. In group 1 the score level of fatigue and arthralgia also decreased significantly. In conclusion, this study proves that in patients with GH-secreting pituitary macroadenoma: (i) surgery followed by SRL induces a better clinical and biochemical status than SRL alone; (ii) SRL treatment before surgery ameliorates the clinical and biochemical outcome and reduces the prevalence of hypopituitarism due to surgery.", "PMID": "11607883"}, {"title": "Preoperative octreotide treatment in newly diagnosed acromegalic patients with macroadenomas increases cure short-term postoperative rates: a prospective, randomized trial.", "abstract": "Surgery is the primary treatment of acromegaly. However, it often fails to cure the patient. New strategies that improve surgical outcome are needed.\n\nOur objective was to investigate whether 6-month preoperative treatment with octreotide improves the surgical outcome in newly diagnosed acromegalic patients.\n\nDuring a 5-yr period (1999-2004), all newly diagnosed acromegalic patients between 18 and 80 yr of age in Norway were screened and invited to participate in the study. A total of 62 patients was included in the Preoperative Octreotide Treatment of Acromegaly study.\n\nAfter a baseline evaluation, patients were randomized directly to transsphenoidal surgery (n = 30) or pretreatment with octreotide (n = 32) 20 mg im every 28th day for 6 months before transsphenoidal surgery. Cure was evaluated 3 months postoperatively primarily by IGF-I levels.\n\nAccording to the IGF-I criteria, 14 of 31 (45%) pretreated patients vs. seven of 30 (23%) patients with direct surgery were cured by surgery (P = 0.11). In patients with microadenomas (< or = 10 mm), one of five (20%) pretreated vs. three of five (60%) with direct surgery were cured (P = 0.52). In patients with macroadenomas, 13 of 26 (50%) pretreated vs. four of 25 (16%) with direct surgery were cured (P = 0.017).\n\nSix-month preoperative octreotide treatment might improve surgical cure rate in newly diagnosed acromegalic patients with macroadenomas. These results have to be confirmed in future studies.", "PMID": "18492760"}, {"title": "Does octreotide treatment improve the surgical results of macro-adenomas in acromegaly? A randomized study.", "abstract": "It is not clear whether the pre-operative treatment of GH-secreting pituitary adenomas with Octreotide improves the surgical remission rates of acromegaly. In a prospective controlled study the results of transsphenoidal surgery in newly diagnosed GH-secreting macro-adenomas were compared in patients with (n = 11, group A) and without (n = 13, group B) preoperative Octreotide treatment. During the treatment with a daily dosage of 470 +/- 160 micrograms Octreotide for 16.5 +/- 10 weeks, the GH- and IGF-1-values of group A dropped significantly from 38.9 +/- 34.1 to 6.8 +/- 4.9 micrograms/l and from 2.7 +/- 1 to 1.7 +/- 0.7 arbitrary units respectively. The adenoma-shrinkage from 5.9 +/- 5.8 to 4.7 +/- 4.9 cm3 missed statistical significance by little. There was no statistically significant difference between the postoperative acromegaly remission rates of 55% in group A and 69% in group B. Of the adenomas that postoperatively were not in remission, 80% in group A and 75% in group B disclosed an infiltrative growth pattern not influenced by the Octreotide pretreatment. All other patients not cured presented with initial GH-values of > 50 micrograms/l. There was no statistically significant difference between the postoperative anterior pituitary function in the two patient groups. In this study Octreotide was not beneficial in improving the results of GH-secreting pituitary macro-adenoma surgery. However, larger prospective controlled studies are needed to address this issue.", "PMID": "10352750"}, {"title": "A comparison between octreotide-LAR and lanreotide-SR in the chronic treatment of acromegaly.", "abstract": "At present long-acting somatostatin analogs represent the first-line medical treatment of acromegaly. These drugs produce stable suppression of GH in most sensitive patients and IGF-I normalization in many; they also increase the compliance of acromegalic patients. The recent availability of octreotide (OC)-LAR, a somatostatin analog to be administered at 28-day intervals, has prompted us to compare, in the same group of patients, its effects and those of another somatostatin analog already available, lanreotide-SR (LSR, to be administered at 14-day intervals).\n\nTwelve somatostatin analog-sensitive acromegalic patients with active disease were enrolled in a prospective open sequential study after giving their informed consent. After chronic treatment with LSR (6-24 months), the patients were changed to treatment with OC-LAR, without wash-out. LSR had been administered at individually tailored dosages (30 mg i.m. at 7-21-day intervals, median 10 days - every 7 days in seven patients, 10 days in two patients, 14 days in two patients and 21 days in one patient) according to GH and IGF-I responses. Disease stability was obtained, as shown by maximal GH/IGF-I suppression without any significant hormonal change between the last two control measurements. OC-LAR was administered i.m. at 28-day intervals six times at the dosage of 20 mg for the first three times and 10 or 30 mg for the last three times (according to individual GH/IGF-I responses). GH (mean of three, hourly samples) and IGF-I concentrations were evaluated on the same day as each administration of the drug, before its injection.\n\nGH and IGF-I values were significantly decreased by LSR treatment. GH decreased from 41.6 +/- 14.6 microg/l (mean +/- s.e.) to 7.2 +/- 1.5 microg/l (P < 0.02), whereas IGF-I values declined from 959 +/- 95 microg/l to 460 +/- 61 microg/l (P < 0.00001), expressed as absolute values, and from 287 +/- 30% to 137 +/- 19% expressed as percentage of the upper limit of normal range (% ULNR). At the end of the last cycle, OC-LAR treatment achieved a significant further suppression both in GH (to 5.1 +/- 1.1 microg/l, P < 0.05 compared with LSR) and in IGF-I concentrations (to 374 +/- 60 microg/l, P<0.05 compared with LSR, and to 112 +/- 19% as % ULNR). LSR decreased GH concentrations to less than 2.5 microg/l in one patient and normalized IGF-I concentrations in four patients. OC-LAR decreased GH concentrations to less than 2.5 microg/l in four patients and normalized or near-normalized IGF-I concentrations (i.e. to < 110% ULNR) in eight patients.\n\nThese preliminary results show that the once-monthly OC-LAR administration schedule proved more efficacious than LSR given every 7-21 days, in a greater number of acromegalic patients.", "PMID": "10474124"}, {"title": "Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant.", "abstract": "Patients with acromegaly are currently treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be ineffective and have adverse effects. Pegvisomant is a genetically engineered growth hormone-receptor antagonist that blocks the action of growth hormone.\n\nWe conducted a 12-week, randomized, double-blind study of three daily doses of pegvisomant (10 mg, 15 mg, and 20 mg) and placebo, given subcutaneously, in 112 patients with acromegaly.\n\nThe mean (+/-SD) serum concentration of insulin-like growth factor I (IGF-I) decreased from base line by 4.0+/-16.8 percent in the placebo group, 26.7+/-27.9 percent in the group that received 10 mg of pegvisomant per day, 50.1+/-26.7 percent in the group that received 15 mg of pegvisomant per day, and 62.5+/-21.3 percent in the group that received 20 mg of pegvisomant per day (P<0.001 for the comparison of each pegvisomant group with placebo), and the concentrations became normal in 10 percent, 54 percent, 81 percent, and 89 percent of patients, respectively (P<0.001 for each comparison with placebo). Among patients treated with 15 mg or 20 mg of pegvisomant per day, there were significant decreases in ring size, soft-tissue swelling, the degree of excessive perspiration, and fatigue. The score fortotal symptoms and signs of acromegaly decreased significantly in all groups receiving pegvisomant (P< or =0.05). The incidence of adverse effects was similar in all groups.\n\nOn the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement.", "PMID": "10770982"}, {"title": "Growth hormone receptor antagonist therapy in acromegalic patients resistant to somatostatin analogs.", "abstract": "Transsphenoidal surgical resection is the primary therapy for acromegaly caused by GH secreting pituitary adenomas. Medical therapy for patients not controlled by surgery includes primarily somatostatin analogs and secondarily dopamine agonists, both of which inhibit pituitary growth hormone secretion. A novel GH receptor antagonist (pegvisomant) binds to hepatic GH receptors and inhibits peripheral insulin-like growth factor-1 generation. Six patients resistant to maximal doses of octreotide therapy received pegvisomant - three received placebo or pegvisomant 30 mg or 80 mg weekly for 6 weeks and three received placebo and pegvisomant 10-20 mg/d for 12 weeks. Thereafter, all patients received daily pegvisomant injections of doses determined by titrating IGF-1 levels. Serum total IGF-1 levels were normalized in all six acromegalic patients previously shown to be resistant to somatostatin analogs via a novel mechanism of peripheral GH receptor antagonism. The GH receptor antagonist is a useful treatment for patients harboring GH-secreting tumors who are resistant to octreotide.", "PMID": "10946911"}, {"title": "Optimal dosage interval for depot somatostatin analogue therapy in acromegaly requires individual titration.", "abstract": "The recent introduction of the depot somatostatin analogues octreotide LAR and lanreotide represent major advances in the medical treatment of acromegaly. However, it is uncertain whether the recommended dose intervals of 4 weeks and 10-14 days, respectively, are applicable to all patients.\n\nTo determine the optimum intervals between depot injections of either octreotide LAR and lanreotide for the suppression of serum GH and IGF-I in patients with acromegaly. Twenty-seven patients with acromegaly were randomly allocated to receive either three injections at 4 week intervals of octreotide LAR (n = 18) or five injections at 14 day intervals of lanreotide (n = 11); two patients participated in both arms. Prior to the first injection, at 4 and 6 weeks after the last injection of LAR, and at 10, 14 and 21 days after the last injection of lanreotide, serum mean GH and IGF-I levels were measured.\n\nIn the LAR-treated group, at 4 and 6 weeks after the third injection 13 patients (72%) and 12 patients (67%), respectively, had a mean GH < 5 mU/l. IGF-I was normalized in 12 and 11 patients at these times. In the lanreotide-treated group, five (45%), four (36%) and three (27%) patients, respectively, had a GH < 5 mU/l at 10, 14 and 21 days after the last injection and eight, six and five patients had a normal serum IGF-I.\n\nThere is marked variability in individual patient responses to depot somatostatin analogues. The establishment of optimal drug intervals requires careful assessment. For octreotide LAR many patients may be as adequately controlled with 6 weekly injections as with 4 weekly injections. It is important to measure serum GH profiles at intervals after initiating therapy with these drugs to individualize doses for each patient and hence minimize cost.", "PMID": "11155094"}, {"title": "Long-term effects of lanreotide SR and octreotide LAR on tumour shrinkage and GH hypersecretion in patients with previously untreated acromegaly.", "abstract": "The therapeutic efficacy of lanreotide SR and octreotide LAR has been studied widely in patients treated previously with neurosurgery and/or radiotherapy. These therapies limit the evaluation of the long-term effects of somatostatin analogues on tumour shrinkage. Neurosurgical and radiotherapy treatments cause irreversible anatomical changes in pituitary morphology, which can make accurate evaluation of tumour shrinkage difficult. The aim of this study was to investigate the therapeutic efficacy of lanreotide SR and octreotide LAR in previously untreated patients with acromegaly. We aimed to investigate the long-term effects of these drugs on tumour shrinkage and growth hormone (GH) hypersecretion without the confounding influences of previous therapy.\n\nTwenty-three newly diagnosed patients with acromegaly (14 women, nine men) with active disease began the study; of these, three were lost for follow-up, leaving a total of 20 patients to complete the study. Patients were assigned randomly to lanreotide SR (12 patients) and octreotide LAR (eight patients), and the randomization stratified patients to assure a balance between the groups with respect to baseline tumour dimension, age and sex. Tumour volume was evaluated by magnetic resonance imaging of the sella, and calculated with the rotating ellipsoid formula. A morphological and biochemical evaluation was performed at baseline, 12 and 24 months after beginning lanreotide SR and octreotide LAR treatment. A reduction of tumour volume of at least 10% was considered significant.\n\nBiochemical control increased progressively throughout the study in patients with microadenomas more than in patients with macroadenomas (70% vs. 10%; P < 0.05) and without a difference between lanreotide SR and octreotide LAR (41.0% vs. 37.5%; P not significant). After 12 months of treatment, mean tumour shrinkage was 28.3 +/- 18.0%. A greater reduction was observed in macro- vs. microadenomas (40.5 +/- 17.0% vs. 16.1 +/- 8.0%, respectively; P < 0.05). No statistical difference in the tumour shrinking effects of lanreotide SR vs. octreotide LAR was observed (26.5 +/- 17.3% vs. 31.1 +/- 16.1%, respectively). At the 24th month of therapy, no further overall shrinkage was observed, compared to the 12-month evaluation (31.9 +/- 17.2% vs. 28.3 +/- 18.0%) at which there was no difference between lanreotide SR and octreotide LAR (30.0 +/- 17.2% vs. 34.8 +/- 16.5%, respectively).\n\nThis study showed that the new long-acting somatostatin analogues, lanreotide SR and octreotide LAR, cause significant shrinkage of pituitary GH-secreting adenomas in previously untreated patients with acromegaly. This effect was more marked in macroadenomas than microadenomas, and did not correlate with control of GH hypersecretion.", "PMID": "11849248"}, {"title": "Cardiovascular risk factors in acromegaly before and after normalization of serum IGF-I levels with the GH antagonist pegvisomant.", "abstract": "Acromegaly is associated with premature cardiovascular mortality. GH replacement therapy decreases inflammatory markers of cardiovascular risk, but little is known about these markers in patients with acromegaly. The GH receptor antagonist, pegvisomant, reduces IGF-I levels in 98% of patients treated. We investigated the effects of GH receptor blockade on inflammatory and other cardiovascular risk markers in active acromegaly. Forty-eight patients with acromegaly and 47 age- and body mass index-matched controls were included. The study consisted of 3 parts: a cross-sectional study, a prospective randomized 12-wk placebo-controlled study, and a longitudinal open-label study of up to 18 months of pegvisomant treatment. After baseline evaluation, patients with acromegaly were randomized to placebo (n = 14), 10 mg (n = 12), 15 mg (n = 10), or 20 mg (n = 12) daily pegvisomant for 12 wk. Subsequently, all patients received at least 10 mg pegvisomant daily for up to 18 months, with dose adjustments to achieve a normal IGF-I level. Anthropometry, GH, IGF-I, and pegvisomant levels were measured monthly. C-reactive protein (CRP), IL-6, homocysteine, lipoprotein(a), glucose, insulin, triglycerides, total cholesterol, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol were determined at baseline, 4 and 12 wk in the placebo-controlled study and at 3-month intervals (during which IGF-I levels were normal) in the longitudinal study. In the cross-sectional study, patients had lower CRP than did controls [median, 0.3 (range, 0.2-0.8) vs. 2.0 (0.6-3.7) mg/liter; P < 0.0001] and had higher insulin [78.6 (55.8-130.2) vs. 54.5 (36.6-77.5) pM, P = 0.0051]. IL-6, homocysteine, triglycerides, lipoprotein(a), LDL cholesterol and HDL cholesterol were not different between groups. In the placebo-controlled study, CRP increased in patients treated with 20 mg pegvisomant, compared with placebo (mean +/- SEM, 13.7 +/- 3.6 vs. 0.5 +/- 3.3 mg/liter; P = 0.010). There were no significant differences in IL-6, homocysteine, glucose, insulin, triglyceride, total cholesterol, LDL cholesterol and HDL cholesterol levels. In the longitudinal open-label study (median duration, 15.6 months), CRP increased by 2.0 +/- 0.5 mg/liter (P = 0.0002). Total cholesterol and triglycerides increased (0.22 +/- 0.11 mM, P = 0.050; and 0.25 +/- 0.09 mM, P = 0.007, respectively), whereas lipoprotein(a) decreased (-70 +/- 33 mg/liter, P = 0.039). Glucose, insulin, homocysteine, HDL cholesterol, and IL-6 did not change. We conclude that patients with active acromegaly have lower CRP and higher insulin levels than healthy controls. Administration of pegvisomant increases CRP levels. We propose that GH secretory status is an important determinant of serum CRP levels, although additional studies are needed to determine the mechanism and significance of this finding.", "PMID": "11932303"}, {"title": "Presurgical octreotide treatment in acromegaly.", "abstract": "The aim of this study was to determine the role of octreotide administration in acromegalic patients as a preparation for selective adenomectomy using transsphenoidal route. Octreotide was administered for 3 to 6 weeks before surgery in 12 patients and for 4 to 39 months in 25 patients. The clinical response was judged as excellent or good in 10 of 12 patients from group I and in 23 of 25 patients from group II. Marked reduction (ie, greater than 50% of initial values) in serum growth hormone (GH) levels was seen in all patients, with levels to less than 5 micrograms/L in 68% of patients and less than 2 micrograms/L in 27%. Insulin-like growth factor 1 (IGF-1) levels decreased to within normal limits in half the cases. During long-term treatment, an escape phenomenon could be seen. Varying degrees of tumor shrinkage were seen in more than 50% of cases. During surgery, with regard to the relative ease or difficulty in removing the tumor, the consistency of the tumor and the separation of normal from pathological tissue, no significant difference was observed between patients given octreotide and those from control series. Morphological changes in adenomatous tissue were rather small. The surgical outcome was similar in the pretreated series as in the control series, except in enclosed adenomas, which showed a tendency to a higher success rate. Since octreotide improves both the clinical condition and hormonal parameters and induces varying degrees of tumor shrinkage, it is potentially useful as an adjunct to surgery. Morphological data suggest that octreotide exercises a functional inhibitory effect on GH release.", "PMID": "1518434"}], "labels": [{"PMID": "11607883", "label": "included"}, {"PMID": "18492760", "label": "included"}, {"PMID": "10352750", "label": "excluded"}, {"PMID": "10474124", "label": "excluded"}, {"PMID": "10770982", "label": "excluded"}, {"PMID": "10946911", "label": "excluded"}, {"PMID": "11155094", "label": "excluded"}, {"PMID": "11849248", "label": "excluded"}, {"PMID": "11932303", "label": "excluded"}, {"PMID": "1518434", "label": "excluded"}]}
{"metadata": {"review_pmid": "38314898"}, "inputs": {"background": "Meibomian gland dysfunction (MGD) is the most common underlying cause of dry eye disease (DED). MGD leads to pathological alteration of the composition or quantity of meibum, or both, which subsequently results in tear evaporation and the typical signs and symptoms associated with DED. The LipiFlow Thermal Pulsation System (LipiFlow) is a medical device used to treat MGD in office; however, it is unclear if LipiFlow can outperform other DED treatments.", "objectives": "To evaluate the effectiveness of LipiFlow for treating DED signs and symptoms and the safety of LipiFlow compared with sham or other available treatments for MGD in adults.", "selection criteria": "We included studies conducted in adults (over 18 years of age) with DED or MGD as defined by the primary trial investigators. We imposed no restrictions on race, ethnicity, or sex. We considered trials involving contact lens wearers if they were equally represented between groups."}, "context": [{"title": "[Meibomian gland dysfunction: a comparative study of modern treatments].", "abstract": "To evaluate a thermal pulsation treatment compared to a warming eyelid device for the management of meibomian gland dysfunction.\n\nThirty patients were randomized into two groups: the first had a treatment with MeiboPatch(\u00ae) on a daily basis for three months while the second had a single treatment with LipiFlow(\u00ae). The evaluation focused on a classical approach but also on a modern approach of the ocular surface (interferometry lipid layer LipiView(\u00ae)), analysis of the tear film by Oquas(\u00ae) (osmolarity by TearLab(\u00ae)) before treatment, then a month and three months later.\n\nBoth treatments proved to be effective with almost three times more functional meibomian glands at 3 months in the LipiFlow group and almost twice more in the MeiboPatch group (P<0.05) but the LipiFlow allows a more rapid improvement at the first month of treatment. Functional scores and classic exploration of the ocular surface except the Schirmer test also undergo a significant improvement in both groups after three months of treatment.\n\nThe combination of heat applied to the inner eyelid surface, together with simultaneous expression of the glands, during a single 12-minute treatment shows to be highly effective in treating cases of meibomian gland disease. Whilst results were excellent, and continued lid hygiene remains advised, the benefit of being able to simultaneous address potential compliance issues relating to ongoing treatment is significant. The convenience of a single 12-minute treatment versus an ongoing daily heating regime was shown to be highly desirable and a welcome relief in our patients' busy lifestyles.", "PMID": "24656693"}, {"title": "Comparison of a single-dose vectored thermal pulsation procedure with a 3-month course of daily oral doxycycline for moderate-to-severe meibomian gland dysfunction.", "abstract": "The aim of this study was to compare the efficacy of a single bilateral 12-minute vectored thermal pulsation (VTP) procedure versus daily oral doxycycline for 3 months for moderate-to-severe meibomian gland dysfunction (MGD).\n\nThis prospective, randomized, parallel-group, single-masked study included 28 subjects who received either a single-dose VTP or 3 months of doxycycline treatment. At baseline and 3 months post treatment, all subjects were evaluated for the following: dry eye symptoms with a standard dry eye questionnaire (the Standard Patient Evaluation for Eye Dryness [SPEED]), meibomian gland (MG) function by counting the number of glands yielding liquid secretion with the MG evaluator (MGE), tear breakup time (TBUT) and corneal and conjunctival staining.\n\nIn the VTP group, at 3 months, there was a significant improvement in MG function (4.00\u00b11.47 to 7.73\u00b15.53), SPEED score (11.00\u00b13.30 to 5.42\u00b12.15), TBUT (6.26\u00b12.01 to 8.44\u00b11.81), corneal staining (0.38\u00b10.50 to 0.12\u00b10.33) and conjunctival staining (1.69\u00b11.93 to 0.62\u00b10.85). In the doxycycline group, there was a significant improvement in MG function (4.63\u00b11.41 to 10.63\u00b15.91), SPEED score (13.42\u00b14.17 to 9.42\u00b15.47) and conjunctival staining (2.38\u00b11.88 to 1.13\u00b11.51), but the improvement in TBUT (6.90\u00b12.56 to 7.59\u00b12.03) and corneal staining (0.21\u00b10.41 to 0.13\u00b10.34) was not statistically significant (\n\nA single 12-minute bilateral VTP procedure was significantly more effective than the 3-month daily course of oral doxycycline at improving the dry eye symptoms secondary to MGD. A single 12-minute VTP treatment was at least as effective as a dose of doxycycline for 3 months, in improving MG function and all measured signs of MGD. Given the minimal risk profile of the single VTP procedure over long-term doxycycline use, a single VTP presents a favorable alternative to long-term antibiotic use.", "PMID": "29398903"}, {"title": "A 6-Week, Prospective, Randomized, Single-Masked Study of Lifitegrast Ophthalmic Solution 5% Versus Thermal Pulsation Procedure for Treatment of Inflammatory Meibomian Gland Dysfunction.", "abstract": "Meibomian gland dysfunction (MGD) is present in most cases of dry eye disease. MGD involves both inflammatory and obstructive etiologies. We compared efficacy and safety of treatment to reduce inflammation (lifitegrast) versus obstruction [thermal pulsation procedure (TPP)] in patients with inflammatory MGD over 42 days.\n\nThis was a single-center, 6-week, prospective, randomized, single-masked study of adults with inflammatory MGD, defined as having all of the following: burning, stinging, dryness; thickened secretions or occlusion of glands; eyelid redness; and elevated matrix metalloproteinase-9. Patients received lifitegrast ophthalmic solution 5% twice daily for 42 days or one TPP treatment at day 0. Seven symptoms and 8 objective measures of dry eye disease were assessed.\n\nOverall, 40 of 50 randomized patients (80%) were women with mean (SD) age 65.8 (8.9) years. Lifitegrast-treated (n = 25) versus TPP-treated (n = 25) patients had greater improvement from baseline to day 42 in eye dryness [mean (SD) change from baseline: -1.05 (0.79), lifitegrast; -0.48 (0.96), TPP; P = 0.0340], corneal staining [-0.55 (0.80), lifitegrast; 0.12 (1.09), TPP; P = 0.0230], and eyelid redness [-0.77 (0.43), lifitegrast; -0.38 (0.58), TPP; P = 0.0115]; trend favored lifitegrast for best corrected visual acuity and gland patency. Unexpectedly, TPP treatment did not improve lipid layer thickness or gland patency compared with lifitegrast. No adverse events were reported.\n\nAlthough MGD is often considered a disease of gland obstruction, these findings demonstrate antiinflammatory treatment with lifitegrast significantly improved patient symptoms and signs compared with treatment for obstruction (TPP). Lifitegrast should be included in treatment for inflammatory MGD.", "PMID": "31895884"}, {"title": "Comparison of the iLUX and the LipiFlow for the Treatment of Meibomian Gland Dysfunction and Symptoms: A Randomized Clinical Trial.", "abstract": "To compare the effects of eyelid treatment with the iLUX MGD Treatment System and the LipiFlow Thermal Pulsation System on objective and subjective parameters of meibomian gland function and symptoms.\n\nIn this randomized, open-label, controlled, multicenter clinical trial, both eyes of 142 patients aged \u226518 years with Ocular Surface Disease Index (OSDI) scores \u226523, total meibomian gland scores (MGS) \u226412 in the lower eyelid of each eye, and tear break-up time (TBUT) <10 s were randomized 1:1 to iLUX or LipiFlow treatment, with stratification by test center. The primary effectiveness endpoints were changes in total MGS (masked) and TBUT from baseline to 4 weeks. The secondary effectiveness endpoint was changed in OSDI score from baseline to 4 weeks.\n\nBoth devices significantly improved effectiveness outcomes, with no differences between the two devices. At the 4-week visit, mean MGS, TBUT, and OSDI scores improved at least 16.9 \u00b1 11.5, 2.6 \u00b1 3.2 s, and 28.0 \u00b1 22.8, respectively, across treatment groups and treated eyes. Four device/procedure-related events occurred in the iLUX group, compared with none in the LipiFlow group, but there were no device-related adverse events that involved changes in lid margins, eyelids, or lash integrity. Corneal staining, intraocular pressure, and visual acuity did not differ in the two groups.\n\nBoth treatments produced significant improvements in meibomian gland function and symptoms. For all effectiveness measures, there were no statistically significant differences between the two treatments.", "PMID": "32103887"}, {"title": "The Efficacy Between Conventional Lid Hygiene and Additional Thermal Pulsatile System in Meibomian Gland Dysfunction Patients Treated with Long-Term Anti-Glaucoma Medications in a Randomized Controlled Trial.", "abstract": "To evaluate the efficacy of additional thermal pulsatile system compared to standard lid hygiene alone in meibomian gland dysfunction (MGD) patients who are using long-term anti-glaucoma medications.\n\nWell-controlled glaucoma patients who used anti-glaucoma medications for at least 1 year and had MGD were enrolled and randomized between a study group who received thermal pulsatile system (Lipiflow\n\nOf 60 participants who underwent randomization, 48 completed the study. At the 6-month mark, this study could not demonstrate any significant difference between groups in both primary and secondary outcomes. However, there was significant improvement from baseline in both groups of the following outcomes: meibomian gland expression score, OSDI score, LLT, and meibography score. No serious adverse event was found in this study.\n\nAn additional single thermal pulsatile system treatment with standard lid hygiene significantly improved meibomian gland assessment score and subjective symptoms at 6 months. Any difference between additional thermal pulsatile system treatment and lid hygiene alone was not found in this study. The results may suggest more chronic MGD and more damaged meibomian gland induced by long-term anti-glaucoma medications.", "PMID": "33061275"}, {"title": "TearCare for the Treatment of Meibomian Gland Dysfunction in Adult Patients With Dry Eye Disease: A Masked Randomized Controlled Trial.", "abstract": "#PURPOSE: The aim of this study was to demonstrate the safety and effectiveness of a single TearCare procedure compared with a single LipiFlow procedure in treatment of the dry eye disease associated with meibomian gland dysfunction.\n#METHODS: In a multicenter, masked, randomized controlled trial, 135 subjects received a single TearCare (TC) treatment (n = 67) or a single LipiFlow (LF) treatment (n = 68) at baseline and were followed up for 1 month posttreatment. Tear film breakup time, meibomian gland function, and corneal and conjunctival staining scores were assessed as dry eye signs at baseline, 2 weeks, and 1 month; dry eye symptoms were assessed using the Ocular Surface Disease Index, Symptom Assessment in Dry Eye, and eye dryness questionnaires at baseline and 1 month.\n#RESULTS: At 1 month posttreatment, both groups demonstrated significant improvements (P < 0.0001) in mean tear film breakup time and meibomian gland secretion score to 3.0 \u00b1 4.4 and 11.2 \u00b1 11.1 in the TC group and 2.6 \u00b1 3.3 and 11.0 \u00b1 10.4 in the LF group, respectively. The mean eye dryness, Symptom Assessment in Dry Eye, and Ocular Surface Disease Index scores were significantly reduced (P < 0.0001) by 35.4 \u00b1 34.1, 38.2 \u00b1 31.0, and 27.9 \u00b1 20.5 in the TC group and 34.9 \u00b1 26.9, 38.0 \u00b1 25.9, and 23.4 \u00b1 17.7 in the LF group, respectively. There were no statistically significant differences for any result between the groups. However, the TC group demonstrated numerically greater improvements consistently in all signs and symptoms. Device-related ocular adverse events were reported in 3 patients in the TC group (superficial punctate keratitis, chalazion, and blepharitis) and 4 patients in the LF group (blepharitis, 2 cases of foreign body sensation, and severe eye dryness).\n#CONCLUSIONS: A single TearCare treatment significantly alleviates the signs and symptoms of dry eye disease in patients with meibomian gland dysfunction and is equivalent in its safety and effectiveness profile to LipiFlow treatment as shown in this 1-month follow-up study.", "PMID": "34581297"}, {"title": "Effect of a Novel Thermostatic Device on Meibomian Gland Dysfunction: A Randomized Controlled Trial in Chinese Patients.", "abstract": "Meibomian gland dysfunction (MGD) is a common eye condition that causes excessive evaporation of tears by changing the tear film composition. Current treatments often fail to produce satisfactory results, which is mostly due to poor patient adherence. This study aimed to evaluate the effectiveness and safety of the MiBoFlo Thermoflo\u00ae on both subjective symptoms and objective signs in Chinese patients with MGD.\n\nThis prospective, randomized, controlled clinical trial included 108 eyes of 54 patients with MGD who were recruited in Beijing Tongren Hospital and randomized 1:1 to MiBoFlo (n\u2009=\u200954 eyes) or LipiFlow\u00ae (n\u2009=\u200954 eyes) treatment group. In the MiBoFlo group, patients received three 10-min treatments, each spaced 2\u00a0weeks apart, and the treatment was followed by eyelid compression each time. Patients in the LipiFlow group received a single 12-min treatment. The primary parameters measured included changes in Ocular Surface Disease Index (OSDI) score, Meibomian Glands Yielding Liquid Secretion (MGYLS) score, and Meibomian Glands Secretion (MGS) score from baseline to 2\u00a0months. The secondary parameters included tear meniscus height (TMH), non-invasive keratograph break-up time (NIKBUT), corneal fluorescein staining (CFS), and meibomian glands (MG) loss from baseline to 2\u00a0months. Safety parameters include visual acuity (VA), intraocular pressure (IOP), anterior segment, and facial skin.\n\nThe OSDI, MGYLS, and MGS scores all improved from baseline to 1\u00a0month in both MiBoFlo and LipiFlow groups, and these improvements were maintained at 2\u00a0months. CFS score, NIKBUT, and MG loss showed no significant change in both groups.\n\nAs a portable and comfortable device, MiBoFlo can improve the treatment of MGD and achieve a sustained improvement in both symptoms and meibomian gland function lasting at least 2\u00a0months.", "PMID": "34822140"}, {"title": "Comparison of Two Thermal Pulsation Systems in the Treatment of Meibomian Gland Dysfunction: A Randomized, Multicenter Study.", "abstract": "#SIGNIFICANCE: Given the significance of meibomian gland dysfunction subjects in evaporative dry eye, its chronic and progressive nature, limited promising treatment options, and novel treatment techniques are important. This randomized clinical study evaluated the noninferiority of SYSTANE iLux with LipiFlow in meibomian gland dysfunction treatment at 12 months.\n#PURPOSE: This study aimed to demonstrate noninferiority of SYSTANE iLux compared with LipiFlow at 12 months after single treatment in meibomian gland dysfunction subjects with evaporative dry eye.\n#METHODS: In this prospective, randomized, multicenter, assessor-masked, parallel-group trial, subjects (N = 236; aged \u226518 years) with meibomian gland score (MGS) of \u226412 in lower eyelids, noninvasive tear breakup time (NITBUT; first breakup) of <10 seconds, and Impact of Dry Eye on Everyday Life-Symptom Bother (IDEEL-SB) module score of >16 were randomized (1:1) to receive SYSTANE iLux (n = 119) or LipiFlow (n = 117). Subjects attended a total of eight visits, including screening, treatment, and follow-up visits at 2 weeks and at 1, 3, 6, 9, and 12 months/exit, to evaluate change from baseline in MGS, NITBUT, IDEEL-SB module score, and safety outcomes.\n#RESULTS: A total of 227 subjects completed the study (mean \u00b1 standard deviation age, 57.3 \u00b1 13.8 years). At 12 months, least squares mean change from baseline in MGS was similar between iLux and LipiFlow (17.4 \u00b1 1.97 vs. 17.8 \u00b1 1.98). Noninferiority of SYSTANE iLux compared with LipiFlow in change from baseline in MGS (95% lower confidence limit of least squares mean difference, >-5), NITBUT (>-2.5 seconds), and IDEEL-SB score (95% upper confidence limit, <12) was achieved at all post-treatment visits. No other serious ocular or device-related adverse events were reported.\n#CONCLUSIONS: The treatment outcomes with SYSTANE iLux were noninferior to LipiFlow during the 12-month follow-up in subjects with dry eye-associated meibomian gland dysfunction.", "PMID": "35383732"}, {"title": "A Comparison of TearCare and Lipiflow Systems in Reducing Dry Eye Disease Symptoms Associated with Meibomian Gland Disease.", "abstract": "To compare TearCare and Lipiflow systems in the ability to reduce the symptoms of dry eye disease (DED) associated with meibomian gland dysfunction (MGD).\n\nIn this multicenter, masked, randomized-controlled trial, 235 subjects received a single TearCare treatment (n = 115) or a single LipiFlow treatment (n = 120) and were followed for 1-month post-treatment. DED symptoms were assessed using the Ocular Surface Disease Index (OSDI), Symptom Assessment in Dry Eye (SANDE), and Eye Dryness (ED) questionnaires at baseline and at 1 month. Post-hoc subgroup analysis was conducted on subjects with less severe and more severe gland obstruction determined by baseline meibomian gland secretion score (MGSS).\n\nTearCare system significantly improved total OSDI, SANDE, and ED scores from baseline (\n\nTearCare provides significant DED symptom relief at 1 month after a single treatment. Outcomes were consistent in OSDI, SANDE, and ED assessments. In subjects with more severe gland dysfunction, TearCare performed significantly better than LipiFlow in improving quality of vision and overall DED symptom frequency determined by OSDI and SANDE.\n\nNCT03857919.", "PMID": "36065356"}, {"title": "Efficacy and Safety evaluation of a single thermal pulsation system treatment (Lipiflow", "abstract": "#PURPOSE: Evaluate the efficacy and safety of LipiFlow\n#METHODS: Patients (n\u2009=\u2009100 eyes, 50 subjects) diagnosed with MGD were recruited for this prospective, randomized, 3-month clinical trial. In Lipiflow group, patients (n\u2009=\u200950 eyes) received a single LipiFlow\n#RESULTS: Baseline parameters in both groups were comparable (p\u2009>\u20090.05). SPEED score and TBUT improved in two groups from baseline to 3\u00a0months. MGYLS number, MGS score, LLT improved in LipiFlow group and these improvements were maintained with no significant regression at 3\u00a0months. CFS showed significant improvement in warm compress group at 1\u00a0month compared with LipiFlow group. Moreover, the correlation analysis indicated LLT was positively correlated with TBUT, MGS score, and MGYLS number.\n#CONCLUSION: A single 12-min LipiFlow treatment is an effective therapy for MGD patients and can achieve improvements in symptoms alleviation and meibomian gland lipid secretion function lasting for at least 3\u00a0months.", "PMID": "36112256"}], "labels": [{"PMID": "24656693", "label": "included"}, {"PMID": "29398903", "label": "included"}, {"PMID": "31895884", "label": "included"}, {"PMID": "32103887", "label": "included"}, {"PMID": "33061275", "label": "included"}, {"PMID": "34581297", "label": "included"}, {"PMID": "34822140", "label": "included"}, {"PMID": "35383732", "label": "included"}, {"PMID": "36065356", "label": "included"}, {"PMID": "36112256", "label": "included"}]}
{"metadata": {"review_pmid": "38299639"}, "inputs": {"background": "IgA nephropathy (IgAN) is the most common primary glomerular disease, with approximately 20% to 40% of patients progressing to kidney failure within 25 years. Non-immunosuppressive treatment has become a mainstay in the management of IgAN by improving blood pressure (BP) management, decreasing proteinuria, and avoiding the risks of long-term immunosuppressive management. Due to the slowly progressive nature of the disease, clinical trials are often underpowered, and conflicting information about management with non-immunosuppressive treatment is common. This is an update of a Cochrane review, first published in 2011.", "objectives": "To assess the benefits and harms of non-immunosuppressive treatment for treating IgAN in adults and children. We aimed to examine all non-immunosuppressive therapies (e.g. anticoagulants, antihypertensives, dietary restriction and supplementation, tonsillectomy, and herbal medicines) in the management of IgAN.", "selection criteria": "Randomised controlled trials (RCTs) and quasi-RCTs of non-immunosuppressive agents in adults and children with biopsy-proven IgAN were included."}, "context": [{"title": "Combined therapy with prednisolone, azathioprine, heparin-warfarin, and dipyridamole for paediatric patients with severe IgA nephropathy--is it relevant for adult patients?", "abstract": "", "PMID": "10344344"}, {"title": "Short-term effect of vitamin K administration on prednisolone-induced loss of bone mineral density in patients with chronic glomerulonephritis.", "abstract": "Glucocorticoid-induced osteoporosis has been reported to be caused by enhanced bone resorption and suppressed bone formation. To clarify whether administration of vitamin K, which enhances bone formation, prevents prednisolone-induced loss of bone mineral density (BMD), a randomized, prospective, controlled study was conducted on 20 patients with chronic glomerulonephritis scheduled for treatment with prednisolone. All patients were initially treated with 0.8 mg/kg body weight/day of prednisolone (maximum of 40 mg) for 4 weeks, tapering to 20 mg/day over approximately 6 weeks. Ten patients received prednisolone alone (Group 1), and the other 10 patients received prednisolone plus 15 mg of menatetrenone, vitamin K, three times per day (Group 2). BMD of the lumbar spine measured by dual-energy X-ray absorptiometry (DXA) and biochemical markers of bone metabolism in blood and urine were evaluated before and 10 weeks after administration of prednisolone alone or with menatetrenone. In Group 1, treatment with prednisolone significantly reduced BMD of the lumbar spine from 1.14 +/- 0.12 to 1.10 +/- 0.11 g/cm2 (P = 0.0029). Serum intact osteocalcin and procollagen type I C-peptide (PICP) concentrations, biochemical markers of bone formation, were markedly reduced. A biochemical marker of bone resorption, urinary excretion of deoxypyridinoline, was significantly reduced. In Group 2, prednisolone-induced reduction of BMD was prevented by menatetrenone administration (1.09 +/- 0.09 to 1.07 +/- 0.07 g/cm2, P = 0.153). Menatetrenone prevented reduction of PICP concentration by prednisolone but not in serum intact osteocalcin concentration and urinary excretion of deoxypyridinoline. Thus, treatment with prednisolone resulted in loss of BMD of the lumbar spine associated with suppression of both bone formation and bone resorption. Menatetrenone is a useful agent in preventing prednisolone-induced loss of BMD.", "PMID": "10652960"}, {"title": "Sodium sensitivity of blood pressure appearing before hypertension and related to histological damage in immunoglobulin a nephropathy.", "abstract": "Patients with renal parenchymal disease exhibit sodium-sensitive hypertension. We examined patients with immunoglobulin A (IgA) nephropathy to determine whether this sensitivity appears before hypertension begins and whether this sensitivity is related to histological damage. Thirty-eight patients with IgA nephropathy followed a diet with an ordinary sodium level for 1 week and a sodium-restricted diet for 1 week, in random order, and were divided into 3 groups by their systemic blood pressure on the diet with an ordinary sodium level (optimal, <120/<80 mm Hg, n=15; normal to high-normal, 120 to 139/80 to 89 mm Hg, n=18; hypertensive, >/=140/>/=90 mm Hg, n=5). The sodium sensitivity index was calculated as the reciprocal of the slope of the pressure-natriuresis curve drawn by linkage of 2 datum points obtained during the different diets. The scores for glomerulosclerosis and tubulointerstitial damage were evaluated semiquantitatively. The sensitivity index, glomerulosclerosis score, and score for tubulointerstitial damage were higher in patients with normal to high-normal blood pressure or hypertension than in patients with optimal pressure. The sensitivity index was significantly correlated with glomerulosclerosis (P=0.001) and tubulointerstitial damage (P=0.002). In patients with normal to high-normal pressure, sodium restriction lowered blood pressure to the optimal range and decreased proteinuria. In patients with IgA nephropathy, sodium sensitivity of blood pressure related to renal histological damage appears before hypertension.", "PMID": "11463764"}, {"title": "Prospective randomized controlled multicenter trial on steroids plus ramipril in proteinuric IgA nephropathy.", "abstract": "Recent studies have shown that steroids improve renal survival and reduce proteinuria in IgA nephropathy (IgAN) patients with moderate urinary protein excretion and normal renal function. However, this effect seems to diminish over time. Moreover, it has been demonstrated that long-term use of ramipril reduces the risk of end-stage renal disease in proteinuric diabetic and non-diabetic chronic nephropathies. We have planned a long-term unblinded, prospective, centrally randomized, controlled, multicentric trial to assess whether combined treatment of steroids and ramipril is superior to ramipril alone in patients with progressive IgAN disease. A minimum of 134 patients with biopsy-proven IgAN, grade G3 or G4, daily proteinuria > 1.0 g and creatinine clearance > 50 mL/min will be enrolled during a 2-year recruitment period. The patients will be allocated randomly to receive a six-month course of oral prednisone (1.0 mg/Kg/day for 2 months, tapered by 0.2 mg/Kg/day every month) plus ramipril (2.5 mg/day for one month, increased by 1.25 mg/day every month to achieve and maintain a blood pressure less than 120-80 mm Hg and/or to reduce daily proteinuria to 1.0 g or less or by at least 50%) in the experimental group or ramipril alone in the control group. Ramipril will be administered during the whole 5-year follow-up period in both groups. The primary endpoint will be renal survival estimated by 50% increase in baseline serum creatinine; the secondary endpoints will be urinary protein and cytokine excretion and side-effects. Analyses will be done by intention to treat. A p <0.05 will be taken as significant.", "PMID": "11506246"}, {"title": "Additive antiproteinuric effect of combined ACE inhibition and angiotensin II receptor blockade.", "abstract": "Limitation of systemic and glomerular hypertension reduces urinary protein excretion and prevents renal function deterioration.\n\nTo investigate whether, in hypertensive patients with glomerulonephritis, a combination of an angiotensin converting enzyme inhibitor (ACEI, fosinopril 20 mg/day) with an angiotensin receptor blocker (ARB, irbesartan 150 mg/day) produces a more profound antiproteinuric effect than either drug alone.\n\nTen non-diabetic patients with glomerulonephritis, normal or slightly reduced but stable renal function (creatinine clearance 40-106 ml/min) without immunosuppression were studied. Clinical evaluations, 24 h blood pressure measurements and laboratory tests were performed as follows: (1) without medication (baseline) and in random sequence; (2) ACEI alone; (3) ARB alone; and (4) combination of ACEI + ARB. Each period lasted for 6 weeks, separated by three washout periods of 4 weeks each without therapy.\n\nACEI and ARB alone reduced proteinuria from 7.9 +/- 7.1 to 5.3 +/- 5.2 and 5.0 +/- 4.9 g/24 h (mean +/- SD), respectively. The combination of ACEI + ARB induced a more remarkable reduction of proteinuria in every patient (to 3.3 +/- 3.7 g/24 h) than either drug alone (P = 0.039 by ANOVA). The enhanced antiproteinuric effect of the combined therapy could not be attributed to a more pronounced reduction of 24 h mean arterial pressure (basal, 106 +/- 8; ACEI, 97 +/- 5; ARB, 98 +/- 5; ACEI+ARB, 95 +/- 5 mmHg) or creatinine clearance (basal, 77 +/- 27; ACEI, 73 +/- 31; ARB 80 +/- 30; ACEI + ARB, 73 +/- 32 ml/min).\n\nA combination of ACEI and ARB in patients with glomerulonephritis produces a more profound decrease in proteinuria than either drug alone. This additive antiproteinuric effect is not dependent on changes in blood pressure or creatinine clearance. A long-term controlled study is required to confirm the positive effect of this treatment on the progression of renal function loss.", "PMID": "11791035"}, {"title": "Additive antiproteinuric effect of combined ACE inhibition and angiotensin II receptor blockade.", "abstract": "Limitation of systemic and glomerular hypertension reduces urinary protein excretion and prevents renal function deterioration.\n\nTo investigate whether, in hypertensive patients with glomerulonephritis, a combination of an angiotensin converting enzyme inhibitor (ACEI, fosinopril 20 mg/day) with an angiotensin receptor blocker (ARB, irbesartan 150 mg/day) produces a more profound antiproteinuric effect than either drug alone.\n\nTen non-diabetic patients with glomerulonephritis, normal or slightly reduced but stable renal function (creatinine clearance 40-106 ml/min) without immunosuppression were studied. Clinical evaluations, 24 h blood pressure measurements and laboratory tests were performed as follows: (1) without medication (baseline) and in random sequence; (2) ACEI alone; (3) ARB alone; and (4) combination of ACEI + ARB. Each period lasted for 6 weeks, separated by three washout periods of 4 weeks each without therapy.\n\nACEI and ARB alone reduced proteinuria from 7.9 +/- 7.1 to 5.3 +/- 5.2 and 5.0 +/- 4.9 g/24 h (mean +/- SD), respectively. The combination of ACEI + ARB induced a more remarkable reduction of proteinuria in every patient (to 3.3 +/- 3.7 g/24 h) than either drug alone (P = 0.039 by ANOVA). The enhanced antiproteinuric effect of the combined therapy could not be attributed to a more pronounced reduction of 24 h mean arterial pressure (basal, 106 +/- 8; ACEI, 97 +/- 5; ARB, 98 +/- 5; ACEI+ARB, 95 +/- 5 mmHg) or creatinine clearance (basal, 77 +/- 27; ACEI, 73 +/- 31; ARB 80 +/- 30; ACEI + ARB, 73 +/- 32 ml/min).\n\nA combination of ACEI and ARB in patients with glomerulonephritis produces a more profound decrease in proteinuria than either drug alone. This additive antiproteinuric effect is not dependent on changes in blood pressure or creatinine clearance. A long-term controlled study is required to confirm the positive effect of this treatment on the progression of renal function loss.", "PMID": "11791035"}, {"title": "Effects of combined ACE inhibitor and angiotensin II antagonist treatment in human chronic nephropathies.", "abstract": "Proteinuria predicts renal disease progression, and its reduction by angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor antagonists (ARA) is renoprotective.\n\nIn this prospective, randomized, cross-over study of 24 patients with nondiabetic, chronic nephropathies, we compared the effects on proteinuria, renal hemodynamics, and glomerular permselectivity of 8 weeks with comparable blood pressure control achieved by benazepril (10 mg/day) and valsartan (80 mg/day) combined therapy with those achieved by benazepril (20 mg/day) or valsartan (160 mg/day) alone.\n\nDespite comparable changes in blood pressure and glomerular filtration rate (GFR), combined therapy decreased proteinuria more than benazepril (-56% vs. -45.9%, P=0.02) and valsartan (-41.5%, P=0.002). Changes in urinary protein to creatinine ratio followed the same trend. Filtration fraction and renal vascular resistances (RVR) decreased more with combined (-14.7%,-23.7%) or benazepril (-12.4%, -20.5%) than with valsartan (-2.7%, -12.5%, P < 0.05 vs. both). RVR changes, adjusted for GFR changes, were associated with those in proteinuria (P < 0.05). Changes in glomerular permeability were comparable and did not predict different changes in proteinuria in the three groups.\n\nAt comparable blood pressure, combined ACEi and ARA decreased proteinuria better than ACEi and ARA. The greater antiproteinuric effect most likely depended on an ACEi-related hemodynamic effect, in addition to glomerular size selectivity amelioration. Long-term combined ACEi and ARA therapy may be more renoprotective than treatment with each agent alone.", "PMID": "12631093"}, {"title": "A comparison of corticosteroid and warfarin therapy in IgA nephropathy with crescent formation: preliminary trial.", "abstract": "No satisfactory treatment exists for IgA nephropathy (IgAN), especially in patients with severe histologic damage. Several trials using steroids combined with other therapies such as warfarin have demonstrated unremarkable results. We investigated the renoprotective effects of warfarin and steroids in IgAN patients with crescent formation.\n\nFifteen Japanese patients with IgAN were followed for up to 3 years. Crescent formation was recognized in over half of their glomeruli from renal biopsy specimens. Treatments consisted of either 0.5 mg/kg per day of prednisolone, or warfarin monotherapy. Blood pressure was controlled with long-acting calcium channel blockers and alpha-beta blockers. Serum creatinine and urinary protein excretion were evaluated at least every 2 months for 36 months.\n\nTen of the 15 patients completed the study. The serum creatinine levels had increased in both groups by 3 years, but significantly more so in the group treated with warfarin. However, they were not significantly different between the two groups as measured at the beginning and end of the study. Blood pressure for all patients in the study was maintained below 130/85 mmHg. Excluded from the study were 5 patients who experienced either peptic ulcers (n = 2, steroid group) or bleeding problems (n = 3, warfarin group).\n\nThese results suggest that corticosteroid therapy may assist in preventing deterioration of renal function in patients with IgAN accompanied by crescent formation. However, further study would be required to decide its usefulness.", "PMID": "14586743"}, {"title": "A randomized controlled trial of mycophenolate mofetil in patients with IgA nephropathy [ISRCTN62574616].", "abstract": "IgAN is the most common type of glomerulonephritis in the world. Between 15 and 40 percent of adults and children diagnosed with IgAN eventually progress to ESRD. Despite the need for effective treatment strategies, very few RCTs for IgAN have been performed. The most effective therapies for IgAN appear to be corticosteroids, ACEi, and FOS that contain a high concentration of omega 3 fatty acids. While ACEi and FOS are generally well tolerated with minimal side effects, the use of high dose steroids over a long course of therapy is often associated with significant morbidity.\n\nThe objective of the study is to test the hypothesis that treatment with the immunosuppressive agent, MMF, will lead to significant and sustained improvement in urinary protein excretion in patients with IgAN who have been pre-treated (and continue to be treated) with ACEi and FOS compared to a placebo control group of patients receiving comparable doses of ACEi and FOS without MMF.\n\nAfter a three month treatment period with the ACEi, lisinopril and the FOS, Omacor, 100 (2 x 50) patients with IgAN and a urinary P/C ratio > or = 0.6 (males) and > or = 0.8 (females) and an estGFR > or = 40 ml/min/1.73 m2 will be randomized to treatment with either MMF or placebo for one year. All patients will be followed off study drug for a second year, but will continue treatment with lisinopril and Omacor for the two year duration of the study. The primary outcome measure of change in urine P/C ratio will be assessed at the end of years one and two.", "PMID": "15043759"}, {"title": "A randomized controlled trial of mycophenolate mofetil in patients with IgA nephropathy [ISRCTN62574616].", "abstract": "IgAN is the most common type of glomerulonephritis in the world. Between 15 and 40 percent of adults and children diagnosed with IgAN eventually progress to ESRD. Despite the need for effective treatment strategies, very few RCTs for IgAN have been performed. The most effective therapies for IgAN appear to be corticosteroids, ACEi, and FOS that contain a high concentration of omega 3 fatty acids. While ACEi and FOS are generally well tolerated with minimal side effects, the use of high dose steroids over a long course of therapy is often associated with significant morbidity.\n\nThe objective of the study is to test the hypothesis that treatment with the immunosuppressive agent, MMF, will lead to significant and sustained improvement in urinary protein excretion in patients with IgAN who have been pre-treated (and continue to be treated) with ACEi and FOS compared to a placebo control group of patients receiving comparable doses of ACEi and FOS without MMF.\n\nAfter a three month treatment period with the ACEi, lisinopril and the FOS, Omacor, 100 (2 x 50) patients with IgAN and a urinary P/C ratio > or = 0.6 (males) and > or = 0.8 (females) and an estGFR > or = 40 ml/min/1.73 m2 will be randomized to treatment with either MMF or placebo for one year. All patients will be followed off study drug for a second year, but will continue treatment with lisinopril and Omacor for the two year duration of the study. The primary outcome measure of change in urine P/C ratio will be assessed at the end of years one and two.", "PMID": "15043759"}], "labels": [{"PMID": "10344344", "label": "excluded"}, {"PMID": "10652960", "label": "excluded"}, {"PMID": "11463764", "label": "excluded"}, {"PMID": "11506246", "label": "excluded"}, {"PMID": "11791035", "label": "excluded"}, {"PMID": "11791035", "label": "excluded"}, {"PMID": "12631093", "label": "excluded"}, {"PMID": "14586743", "label": "excluded"}, {"PMID": "15043759", "label": "excluded"}, {"PMID": "15043759", "label": "excluded"}]}
{"metadata": {"review_pmid": "38288876"}, "inputs": {"background": "Laparoscopic surgery is the preferred option for many procedures. To properly perform laparoscopic surgery, it is essential that sudden movements and abdominal contractions in patients are prevented, as it limits the surgeon's view. There has been a growing interest in the potential beneficial effect of deep neuromuscular blockade (NMB) in laparoscopic surgery. Deep NMB improves the surgical field by preventing abdominal contractions, and it is thought to decrease postoperative pain. However, it is uncertain if deep NMB improves intraoperative safety and thereby improves clinical outcomes.", "objectives": "To evaluate the benefits and harms of deep neuromuscular blockade versus no, shallow, or moderate neuromuscular blockade during laparoscopic intra- or transperitoneal procedures in adults.", "selection criteria": "We included randomised clinical trials (irrespective of language, blinding, or publication status) in adults undergoing laparoscopic intra- or transperitoneal procedures comparing deep NMB to moderate, shallow, or no NMB. We excluded trials that did not report any of the primary or secondary outcomes of our review."}, "context": [{"title": "Evaluation of surgical conditions during laparoscopic surgery in patients with moderate vs deep neuromuscular block.", "abstract": "The routine use of neuromuscular blocking agents reduces the occurrence of unacceptable surgical conditions. In some surgeries, such as retroperitoneal laparoscopies, deep neuromuscular block (NMB) may further improve surgical conditions compared with moderate NMB. In this study, the effect of deep NMB on surgical conditions was assessed.\n\nTwenty-four patients undergoing elective laparoscopic surgery for prostatectomy or nephrectomy were randomized to receive moderate NMB (train-of-four 1-2) using the combination of atracurium/mivacurium, or deep NMB (post-tetanic count 1-2) using high-dose rocuronium. After surgery, NMB was antagonized with neostigmine (moderate NMB), or sugammadex (deep NMB). During all surgeries, one surgeon scored the quality of surgical conditions using a five-point surgical rating scale (SRS) ranging from 1 (extremely poor conditions) to 5 (optimal conditions). Video images were obtained and 12 anaesthetists rated a random selection of images.\n\nMean (standard deviation) SRS was 4.0 (0.4) during moderate and 4.7 (0.4) during deep NMB (P<0.001). Moderate block resulted in 18% of scores at the low end of the scale (Scores 1-3); deep block resulted in 99% of scores at the high end of the scale (Scores 4 and 5). Cardiorespiratory conditions were similar during and after surgery in both groups. Between anaesthetists and surgeon, there was poor agreement between scores of individual images (average \u03ba statistic 0.05).\n\nApplication of the five-point SRS showed that deep NMB results in an improved quality of surgical conditions compared with moderate block in retroperitoneal laparoscopies, without compromise to the patients' peri- and postoperative cardiorespiratory conditions. Trial registration The study was registered at clinicaltrials.gov under number NCT01361149.", "PMID": "24240315"}, {"title": "Deep neuromuscular block improves surgical conditions during laparoscopic hysterectomy: a randomised controlled trial.", "abstract": "The benefit of inducing deep neuromuscular block to improve laparoscopic surgical conditions is controversial.\n\nThe goal of this study was to determine the depth of neuromuscular block needed to guarantee excellent operating conditions during laparoscopic hysterectomy.\n\nA randomised controlled trial.\n\nA single-centre study performed between February 2011 and May 2012.\n\nOne hundred and two women of ASA physical status 1 or 2 gave consent to participate and were allocated randomly to one of two groups.\n\nUnder desflurane general anaesthesia, patients in Group S (shallow block), neuromuscular blockade was induced by administration of rocuronium 0.45\u200amg\u200a kg-1 followed by spontaneous recovery or a rescue bolus dose of 5 \u200amg if surgical conditions were unacceptable. In Group D (deep block), neuromuscular block was induced by administration of rocuronium 0.6\u200amg \u200akg-1 and maintained by bolus doses of 5 \u200amg if the train-of-four count exceeded two, using adductor pollicis electromyography.\n\nWith a stable pneumoperitoneum (13\u200ammHg), the surgeon scored the quality of the surgical field every 10\u200a min as excellent (1), good but not optimal (2), poor but acceptable (3) or unacceptable (4). The groups were compared using the Cochran-Armitage trend test. The level of neuromuscular blockade was recorded each time the surgical field score exceeded 1.\n\nFor groups S and D, respectively, the maximum surgical field scores were 1 in 21 and 34 patients, 2 in 11 and 11 patients, 3 in 4 and 5 patients and 4 in 14 and 0 patients. A trend towards higher scores was demonstrated in group S (P\u200a<\u200a0.001). Surgical field scores of 2, 3 and 4 occurred only when the train-of-four count was at least 1, 2 and 3, respectively.\n\nInducing deep neuromuscular block (train-of-four count <1) significantly improved surgical field scores and made it possible to completely prevent unacceptable surgical conditions.", "PMID": "24809482"}, {"title": "Surgical space conditions during low-pressure laparoscopic cholecystectomy with deep versus moderate neuromuscular blockade: a randomized clinical study.", "abstract": "Laparoscopic cholecystectomy performed during low intraabdominal pressure (<12 mm Hg) is associated with significantly less postoperative pain than standard pressure (\u226512 mm Hg). The impact on surgical space conditions and safety of operating at lower pressures has not been adequately described, but deep neuromuscular blockade may be beneficial. We investigated if deep muscle relaxation would be associated with a higher proportion of procedures with \"optimal\" surgical space conditions compared with moderate relaxation during low-pressure (8 mm Hg) laparoscopic cholecystectomy.\n\nIn this assessor-blinded study, 48 patients undergoing elective laparoscopic cholecystectomy were administered rocuronium for neuromuscular blockade and randomized to either deep neuromuscular blockade (rocuronium bolus plus infusion maintaining a posttetanic count 0-1) or moderate neuromuscular blockade (rocuronium repeat bolus only for inadequate surgical conditions with spontaneous recovery of neuromuscular function). Patients received anesthesia with propofol, remifentanil, and rocuronium. The primary outcome was the proportion of procedures with optimal surgical space conditions (assessed by the surgeon as 1 on a 4-point scale). Secondary outcomes included the proportion of procedures completed at pneumoperitoneum 8 mm Hg and surgical space conditions on dissection of the gallbladder (numeric rating scale 0-100; 0 = optimal surgical space conditions; 100 = unacceptable surgical space conditions).\n\nOptimal surgical space conditions during the entire procedure were observed in 7 of 25 patients allocated to deep neuromuscular blockade and in 1 of 23 patients allocated to moderate blockade (P = 0.05) with an absolute difference of 24% between the groups (95% confidence interval, 4%-43%). Laparoscopic cholecystectomy was completed at pneumoperitoneum 8 mm Hg in 15 of 25 and 8 of 23 patients in the deep and moderate group, respectively (95% confidence interval, -2% to 53%; P = 0.08). Surgical space conditions during dissection of the gallbladder assessed by use of the numeric rating scale were 20 (10-50) (median [25%-75% range]) in the deep neuromuscular blockade group and 30 (10-50) in the moderate group (P = 0.58; Wilcoxon-Mann-Whitney odds, 1.2; 95% confidence interval, 0.6-2.5). No operations were converted to laparotomy.\n\nDeep neuromuscular blockade was associated with surgical space conditions that were marginally better than with moderate muscle relaxation during low-pressure laparoscopic cholecystectomy.", "PMID": "24977638"}, {"title": "Neuromuscular blockade improves surgical conditions (NISCO).", "abstract": "We examined the impact of muscle relaxation on surgical conditions and patients' postoperative outcome during elective laparoscopic cholecystectomy under balanced anaesthesia.\n\nAfter approval and consent, 57 anaesthetized patients were randomly assigned to group no neuromuscular blockade (No NMB) and deep neuromuscular blockade (Deep NMB), i.e. no twitch response to train-of-four nerve stimulation. Laparoscopic cholecystectomy was performed using the 4-trocar technique with a CO2-pneumoperitoneum. Surgical conditions were assessed using a Visual Analogue Scale. Movement of diaphragm or abdominal muscles, inadequate visibility, or breathing and coughing against the ventilator were documented as events reflecting inadequate muscle relaxation. Independently, surgeons could request 0.3 mg/kg rocuronium to improve surgical conditions. Workflow variables were obtained as a surrogate of surgical conditions. Data are presented as mean (95 % confidence interval). The trial is registered at ClinicalTrials.gov (NCT00895778).\n\nWhile in 12 of 25 patients of group \"No NMB\" one or more adverse events impaired the surgical procedure (p < 0.001), only 1 of 25 patients of group \"Deep NMB\" showed an adverse event. Deep NMB resulted in an absolute risk reduction of 0.44 (0.23-0.65) and a number needed to treat of 2.3 (1.5-4.4), respectively. Surgeons requested 0.3 mg/kg rocuronium in 10 of 25 cases (40 %) of group \"No NMB\" only. This dose significantly improved surgical conditions by an average 62 of 100 possible points. All further variables did not differ between groups.\n\nDeep NMB ameliorates surgical conditions for laparoscopic cholecystectomy by improved visibility and reduction of involuntary movements.", "PMID": "25125097"}, {"title": "The Intraocular Pressure under Deep versus Moderate Neuromuscular Blockade during Low-Pressure Robot Assisted Laparoscopic Radical Prostatectomy in a Randomized Trial.", "abstract": "This study aimed to determine whether continuous deep neuromuscular blockade (NMB) improves the surgical conditions and facilitates robotic-assisted laparoscopic radical prostatectomy (RALRP) under low intra-abdominal pressure (IAP) to attenuate the increase in intraocular pressure (IOP) during CO2 pneumoperitoneum in the steep Trendelenburg (ST) position.\n\nSixty-seven patients undergoing RALRP were randomly assigned to a moderate NMB group (Group M), including patients who received atracurium infusion until the end of the ST position, maintaining a train of four count of 1-2; and the deep NMB group (Group D), including patients who received rocuronium infusion, maintaining a post-tetanic count of 1-2. IOP was measured in all patients at nine separate time points. All RALRPs were performed by one surgeon, who rated the overall and worst surgical conditions at the end of the ST position.\n\nThe highest IOP value was observed at T4 (60 min after the ST position) in both Group M (23.3 \u00b1 2.7 mmHg) and Group D (19.8 \u00b1 2.1 mmHg). RALRP was accomplished at an IAP of 8 mmHg in 88% Group D patients and 25% Group M patients. The overall surgical condition grade was 4.0 (3.0-5.0) in Group D and 3.0 (2.0-5.0) in Group M (P < 0.001).\n\nThe current study demonstrated that continuous deep NMB may improve surgical conditions and facilitate RALRP at a low IAP, resulting in significant attenuation of the increase on IOP. Moreover, low-pressure pneumoperitoneum, facilitated by deep NMB still provided acceptable surgical conditions.\n\nClinicalTrials.gov NCT02109133.", "PMID": "26317357"}, {"title": "No supplemental muscle relaxants are required during propofol and remifentanil total intravenous anesthesia for laparoscopic pelvic surgery.", "abstract": "No administration of supplemental muscle relaxants may be beneficial to the recovery of the ambulatory laparoscopic surgery. For this study, we compared the cardiorespiratory factors during propofol and remifentanil anesthesia for laparoscopic pelvic surgery (LPS) with or without supplemental muscle relaxants.\n\nIn total, 56 healthy female patients scheduled to undergo laparoscopic pelvic surgeries were randomly assigned to two groups (A and B). Anesthesia was induced with lidocaine 30 mg, propofol target organ concentration 5.0 microg/mL, remifentanil 3.0 ng/mL, and rocuronium 0.6 mg/kg intravenously (i.v.). After tracheal intubation, anesthesia was maintained with 2.0-5.0 microg/mL of propofol and 1-4 ng/mL of remifentanil i.v. All the patients' lungs were mechanically ventilated in both groups and intermittent bolus doses of rocuronium (0.15 mg/kg i.v.) were administered in group A-however, not in group B. Heart rate (HR) and systolic arterial pressure (SAP), diastolic arterial pressure (DAP), end-tidal carbon-dioxide concentration (EtCO(2)), peak inspiratory pressure (PIP), expired minute ventilation (MV), intra-abdominal pressure (IAP), and temperature were measured during the pneumoperitoneum.\n\nThere were no group differences in HR, SAP, DAP, EtCO(2), PIP, IAP, MV, PaO(2), PaCO(2), and temperature between groups A and B.\n\nNo supplemental muscle relaxants are required during propofol and remifentanil total i.v. anesthesia for LPS.", "PMID": "19226229"}, {"title": "Deep neuromuscular block reduces intra-abdominal pressure requirements during laparoscopic cholecystectomy: a prospective observational study.", "abstract": "Laparoscopic surgery causes specific post-operative discomfort and intraoperative cardiovascular, pulmonary, and splanchnic changes. The CO2 pneumoperitoneum-related intra-abdominal pressure (IAP) remains one of the main drivers of these changes. We investigated the influence of deep neuromuscular blockade (NMB) on IAP and surgical conditions.\n\nThis is an open prospective single-subject design study in 20 patients (14 female/6 male) undergoing laparoscopic cholecystectomy. Inclusion criteria were 18 years or older, and American Society of Anesthesiologists classification 1 to 3. Under a standardised anaesthesia, lowest IAP providing adequate surgical conditions was assessed without NMB and with deep NMB [post-tetanic count (PTC)<2] with rocuronium. The differences between IAP allowing for an adequate surgical field before and after administration of rocuronium were determined, as were effects of patient gender, age, and body mass index.\n\nMean IAP without NMB was 12.75 (standard deviation 4.49)\u2009mmHg. Immediately after achieving a deep NMB, this was 7.20 (2.51). This pressure difference of 5.55\u2009mmHg (5.08, P<0.001) dropped to 3.00\u2009mmHg (4.30, P<0.01) after 15\u2009min. Higher IAP differences were found in women compared with men. A modest inverse relationship was found between pressure difference and age.\n\nWe found an almost 25% lower IAP after a deep NMB compared with no block in laparoscopic cholecystectomy. Younger and female patients appear to benefit more from deep neuromuscular blockade to reduce IAP.", "PMID": "25684372"}, {"title": "Safety and Efficacy of Rocuronium With Sugammadex Reversal Versus Succinylcholine in Outpatient Surgery-A Multicenter, Randomized, Safety Assessor-Blinded Trial.", "abstract": "Complex surgical procedures are increasingly performed in an outpatient setting, with emphasis on rapid recovery and case turnover. In this study, the combination of rocuronium for neuromuscular blockade (NMB) reversed by single-dose sugammadex was compared with succinylcholine followed by spontaneous recovery in outpatient surgery. This multicenter, randomized, safety assessor-blinded study enrolled adults undergoing a short elective outpatient surgical procedure requiring NMB and tracheal intubation. Patients were randomized to NMB with either rocuronium 0.6 mg/kg for tracheal intubation with incremental doses of rocuronium 0.15 mg/kg and subsequent reversal with sugammadex 4.0 mg/kg at 1-2 posttetanic counts or succinylcholine 1.0 mg/kg for intubation with spontaneous recovery. The primary efficacy end point was the time from sugammadex administration to recovery of the train-of-four ratio to 0.9; for succinylcholine, time from administration to recovery of the first twitch (T1) to 90% was assessed. From 167 patients enrolled, 150 received treatment. The all-subjects-treated population comprised 70 patients in the rocuronium-sugammadex group and 80 in the succinylcholine group. Geometric mean (95% confidence interval) time from the start of sugammadex administration to recovery of the train-of-four ratio to 0.9 was 1.8 (1.6-2.0) minutes. Geometric mean (95% confidence interval) time from succinylcholine administration to recovery of T1 to 90% was 10.8 (10.1-11.5) minutes. Health outcome variables were similar between the groups. Adverse events were reported in 87.1% and 93.8% of patients for rocuronium-sugammadex and succinylcholine, respectively. In conclusion, rocuronium for intubation followed by sugammadex for reversal of NMB offers a viable treatment option in outpatient surgery without prolonging recovery duration or jeopardizing safety.", "PMID": "25768376"}, {"title": "Optimising abdominal space with deep neuromuscular blockade in gynaecologic laparoscopy--a randomised, blinded crossover study.", "abstract": "Insufflation of the abdomen during laparoscopy improves surgical space, but may cause post-operative shoulder pain. The incidence of shoulder pain is reduced using a lower insufflation pressure, but this may, however, compromise the surgical space. We aimed at investigating whether deep neuromuscular blockade (NMB) would enlarge surgical space, measured as the distance from the sacral promontory to the trocar in patients undergoing gynaecologic laparoscopy.\n\nFourteen patients were randomised in an assessor-blinded crossover design. The distance from the sacral promontory to the trocar was measured during deep NMB and without NMB at pneumoperitoneum 8 and 12\u2009mmHg both. Additionally, we assessed surgical conditions while suturing the abdominal fascia using a 4-point subjective rating scale. Deep NMB was established with rocuronium and reversed with sugammadex.\n\nAt 12\u2009mmHg pneumoperitoneum, deep NMB improved surgical space with a mean of 0.33 cm (95% confidence interval 0.07-0.59) (P=0.01, paired t-test) compared with no NMB. At 8\u2009mmHg pneumoperitoneum deep NMB improved surgical space with a mean of 0.3\u2009cm (95% confidence interval, 0.06-0.54) (P=0.005) compared with no NMB. Deep NMB resulted in significantly better ratings of surgical conditions during suturing of the fascia (P=0.03, Mann-Whitney U-test).\n\nDeep NMB enlarged surgical space measured as the distance from the sacral promontory to the trocar. The enlargement, however, was minor and the clinical significance is unknown. Moreover, deep NMB improved surgical conditions when suturing the abdominal fascia.", "PMID": "25789421"}, {"title": "Neuromuscular blockade during laparoscopic ventral herniotomy: protocol for a randomised controlled trial.", "abstract": "Laparoscopic herniotomy is the preferred technique for some ventral hernias. Several factors may influence the surgical conditions, one being the depth of neuromuscular blockade (NMB) applied. We hypothesised that deep neuromuscular blockade defined as a post-tetanic count below eight would provide a better surgical workspace.\n\nThis was an investigator-initiated, assessor- and patient-blinded randomised cross-over study. A total of 34 patients with planned laparoscopic umbilical, incisional and linea alba herniotomy were studied. Patients would be randomised to receive deep NMB followed by no NMB, or no NMB followed by deep NMB. Our primary outcome was improvement of the surgical workspace (rated on a five-point scale) estimated as the difference between the workspace during deep NMB and the workspace without NMB. Secondary outcomes included, among others, surgeon's rating of surgical conditions during suturing, duration of surgery and duration of the suturing of the hernia.\n\nThis randomised cross-over study investigated a potential effect on the surgical workspace in laparoscopic ventral herniotomy using deep NMB compared with no NMB. The study may provide knowledge relevant to other laparoscopic techniques.\n\nThe study is funded by a research grant from the Investigator Initiated Studies Program of Merck Sharp & Dohme Corp.\n\nNCT02247466.", "PMID": "26239595"}], "labels": [{"PMID": "24240315", "label": "included"}, {"PMID": "24809482", "label": "included"}, {"PMID": "24977638", "label": "included"}, {"PMID": "25125097", "label": "included"}, {"PMID": "26317357", "label": "included"}, {"PMID": "19226229", "label": "excluded"}, {"PMID": "25684372", "label": "excluded"}, {"PMID": "25768376", "label": "excluded"}, {"PMID": "25789421", "label": "excluded"}, {"PMID": "26239595", "label": "excluded"}]}
{"metadata": {"review_pmid": "38284415"}, "inputs": {"background": "Patient decision aids are interventions designed to support people making health decisions. At a minimum, patient decision aids make the decision explicit, provide evidence-based information about the options and associated benefits/harms, and help clarify personal values for features of options. This is an update of a Cochrane review that was first published in 2003 and last updated in 2017.", "objectives": "To assess the effects of patient decision aids in adults considering treatment or screening decisions using an integrated knowledge translation approach.", "selection criteria": "We included published randomized controlled trials comparing patient decision aids to usual care. Usual care was defined as general information, risk assessment, clinical practice guideline summaries for health consumers, placebo intervention (e.g. information on another topic), or no intervention."}, "context": [{"title": "A randomized controlled trial of shared decision making for prostate cancer screening.", "abstract": "To evaluate a patient-educational approach to shared decision making for prostate cancer screening.\n\nRandomized controlled trial with preoffice visit assessment and 2-week follow-up.\n\nUniversity-based family practice center.\n\nMen aged 45 through 70 years with no history of prostate cancer or treatment for prostate disease (N = 160). Two patients were unavailable for follow-up.\n\nTwenty-minute educational videotape on advantages and disadvantages of prostate-specific antigen (PSA) screening for prostate cancer.\n\nA measure of patients' core knowledge of prostate cancer developed for this study, reported preferences for PSA testing, and ratings of the videotape.\n\nPatients' core knowledge at baseline was poor. At 2-week follow-up, subjects undergoing videotape intervention showed a 78% improvement in the number of knowledge questions answered correctly (P = .001), and knowledge increased about mortality due to early-stage prostate cancer, PSA screening performance, treatment-related complications, and disadvantages of screening. No overall change was observed for control subjects. At follow-up, 48 (62%) of 78 intervention patients planned to have the PSA test compared with 64 (80%) of 80 control patients (18.5% absolute reduction; 95% confidence interval, 4.6%-32.4%; P = .009). Intervention subjects rated favorably the amount of information provided and the clarity, balance, and length of the videotape and would recommend the videotape to others.\n\nPatient education regarding the potential benefits and harms of early detection of prostate cancer can lead to more informed decision making. Incorporating the PSA videotape into the periodic health examination for asymptomatic men aged 50 years and older is recommended.", "PMID": "10418541"}, {"title": "A patient decision aid regarding antithrombotic therapy for stroke prevention in atrial fibrillation: a randomized controlled trial.", "abstract": "Decision aids are tools designed to help patients participate in the clinical decision-making process.\n\nTo determine whether use of an audiobooklet (AB) decision aid explaining the results of a clinical trial affected the decision-making process of study participants.\n\nRandomized controlled trial conducted from May 1997 to April 1998.\n\nFourteen centers that participated in the Stroke Prevention in Atrial Fibrillation (SPAF) III trial.\n\nA total of 287 patients from the SPAF III aspirin cohort study, in which patients with atrial fibrillation and a relatively low risk of stroke received 325 mg/d of aspirin and were followed up for a mean of 2 years.\n\nAt the end of SPAF III, participants were randomized to be informed of the study results with usual care plus use of an AB (AB group) vs usual care alone (control group). The AB included pertinent information to help patients decide whether to continue taking aspirin or switch to warfarin.\n\nPatients' ability to make choices regarding antithrombotic therapy, and 6-month adherence to these decisions. Their knowledge, expectations, decisional conflict (the amount of uncertainty about the course of action to take), and satisfaction with the decision-making process were also measured.\n\nMore patients in the AB group made a choice about antithrombotic therapy than in the control group (99% vs 94%; P = .02). Patients in the AB group were more knowledgeable and had more realistic expectations about the risk of stroke and hemorrhage (in the AB group, 53%-80% correctly estimated different risks; in the control group, 16%-28% gave correct estimates). Decisional conflict and satisfaction were similar for the 2 groups. After 6 months, a similar percentage of patients were still taking their initial choice of antithrombotic therapy (95% vs 93%; P = .44).\n\nFor patients with atrial fibrillation who had participated in a major clinical trial, the use of an AB decision aid improved their understanding of the benefits and risks associated with different treatment options and helped them make definitive choices about which therapy to take. Further studies are necessary to evaluate the acceptability and impact of decision aids in other clinical settings.", "PMID": "10463708"}, {"title": "Does informed consent alter elderly patients' preferences for colorectal cancer screening? Results of a randomized trial.", "abstract": "To assess the impact of informed consent on elderly patients' colorectal cancer (CRC) screening preferences.\n\nRandomized, controlled trial.\n\nFour general internal medicine practices.\n\nWe studied 399 elderly patients visiting their primary care provider for routine office visits.\n\nPatients were randomized to receive either a scripted control message briefly describing CRC screening methods or one of two informational interventions simulating an informed consent presentation about CRC screening. One intervention described CRC mortality risk reduction in relative terms; the other, in absolute terms.\n\nThe main outcome measure was intent to begin or continue fecal occult blood testing (FOBT), flexible sigmoidoscopy, or both. There was no difference in screening interest between the control group and the two information groups (p =.8). The majority (63%) of patients intended to begin or continue CRC screening. Informed patients were able to gauge more accurately the positive predictive value of screening (p =.0009). Control patients rated the efficacy of screening higher than did patients receiving relative risk reduction information, who rated it higher than did patients receiving absolute risk reduction information (p =.0002).\n\nElderly patients appeared to understand CRC screening information and use it to gauge the efficacy of screening, but provision of information had no impact on their preferences for screening. In view of the large proportion who preferred not to be screened, we conclude that elderly patients should be involved in the screening decision. However, factors other than provision of information must determine their CRC screening preferences.", "PMID": "10632830"}, {"title": "Videotape-based decision aid for colon cancer screening. A randomized, controlled trial.", "abstract": "Rates of colon cancer screening in the United States are low, in part because of poor communication between patients and providers about the availability of effective screening options.\n\nTo test whether a decision aid consisting of an educational video, targeted brochure, and chart marker increased performance of colon cancer screening in primary care practices.\n\nRandomized, controlled trial.\n\nThree community primary care practices in central North Carolina.\n\n1657 consecutive adult patients 50 to 75 years of age were contacted. Of these, 651 (39%) agreed to participate; 249 of the 651 participants (38%) were eligible. Eligible patients had no personal or family history of colon cancer and had not had fecal occult blood testing in the past year or flexible sigmoidoscopy, colonoscopy, or barium enema in the past 5 years.\n\nThe 249 participants were randomly assigned to view an 11-minute video about colon cancer screening (intervention group) or a video about automobile safety (control group). After viewing the video, intervention group participants chose a color-coded educational brochure (based on stages of change) to indicate their degree of interest in screening. A chart marker of the same color was attached to their charts. Controls received a generic brochure on automobile safety, and no chart marker was attached.\n\nFrequency of screening test ordering as reported by participants and frequency of completion of screening tests as verified by chart review.\n\nFecal occult blood testing or flexible sigmoidoscopy was ordered for 47.2% of intervention participants and 26.4% of controls (difference, 20.8 percentage points [95% CI, 8.6 to 32.9 percentage points]). Screening tests were completed by 36.8% of the intervention group and 22.6% of the control group (difference, 14.2 percentage points [CI, 3.0 to 25.4 percentage points]).\n\nA decision aid consisting of an educational video, brochure, and chart marker increased ordering and performance of colon cancer screening tests.", "PMID": "11085838"}, {"title": "Randomized, controlled trial of an interactive videodisc decision aid for patients with ischemic heart disease.", "abstract": "To determine the effect of the Ischemic Heart Disease Shared Decision-Making Program (IHD SDP) an interactive videodisc designed to assist patients in the decision-making process involving treatment choices for ischemic heart disease, on patient decision-making.\n\nRandomized, controlled trial.\n\nThe Toronto Hospital, University of Toronto, Toronto, Ontario, Canada.\n\nTwo hundred forty ambulatory patients with\n\nThe primary outcome was patient satisfaction with the decision-making process. This was measured using the 12-item Decision-Making Process Questionnaire that was developed and validated in a randomized trial of the benign prostatic hyperplasia SDP. Secondary outcomes included patient knowledge (measured using 20 questions about knowledge deemed necessary for an informed treatment decision), treatment decision, patient-angiographer agreement on decision, and general health scores. Outcomes were measured at the time of treatment decision and/or at 6 months follow-up. Shared decision-making program scores were similar for the intervention and control group (71% and 70%, respectively; 95% confidence interval [CI] for 1% difference, -3% to 7%). The intervention group had higher knowledge scores (75% vs 62%; 95% CI for 13% difference, 8% to 18%). The intervention group chose to pursue revascularization less often (58% vs 75% for the controls; 95% CI for 17% difference, 4% to 31%). At 6 months, 52% of the intervention group and 66% of the controls had undergone revascularization (95% CI for 14% difference, 0% to 28%). General health and angina scores were not different between the groups at 6 months. Exposure to the IHD SDP resulted in more patient-angiographer disagreement about treatment decisions.\n\nThere was no significant difference in satisfaction with decision-making process scores between the IHD SDP and usual practice groups. The IHD SDP patients were more knowledgeable, underwent less revascularization (interventional therapies), and demonstrated increased patient decision-making autonomy without apparent impact on quality of life.", "PMID": "11089711"}, {"title": "A randomized controlled trial of information-giving to patients referred for coronary angiography: effects on outcomes of care.", "abstract": "OBJECTIVE: To assess the impact of providing an educational videotape, 'Treatment Choices for Ischaemic Heart Disease: a Shared Decision-Making Program Videotape,' to patients referred for coronary angiography compared with standard patient-physician decision making (usual care). STUDY DESIGN: Randomized controlled clinical trial. SETTING: University Hospital and Veterans Affairs Hospital. PATIENTS: A consecutive sample of 217 patients referred for coronary angiography were randomized to receive 'usual care' or to receive the videotape in addition to standard patient physician decision making (videotape): 109 completed the study (50% completion rate). MAIN OUTCOME MEASURES: Knowledge of coronary artery disease, satisfaction, self-reported physical and mental health functioning, and the proportion of patients who were referred for coronary revascularization. RESULTS: Compared with patients who received 'usual care,' those who received the videotape were more knowledgeable (mean score 83 vs. 58%; P < 0.0001) but less satisfied with their treatment (79 vs. 88%; P = 0.038). There were no significant differences between the videotape and 'usual care' groups with respect to satisfaction with the decision making process (mean score 73 vs. 77%; P = 0.37), satisfaction with the decision made (mean score 73 vs. 78%; P = 0.28), physical functioning (38 vs. 38%; P = 0.76), mental health functioning (49 vs. 49%; P = 0.94), or in referral for coronary revascularization (OR 0.60; 95% CI 0.22-1.65; P = 0.33). CONCLUSION: Although the educational videotape increased patients' knowledge level, it was associated with a decrease in their level of satisfaction with treatment. Before there is wide-spread dissemination of this technology, advocates should demonstrate its effectiveness in everyday practice.", "PMID": "11281861"}, {"title": "Randomised controlled trial of an interactive multimedia decision aid on hormone replacement therapy in primary care.", "abstract": "To determine whether a decision aid on hormone replacement therapy influences decision making and health outcomes.\n\nRandomised controlled trial.\n\n26 general practices in the United Kingdom.\n\n205 women considering hormone replacement therapy.\n\nPatients' decision aid consisting of an interactive multimedia programme with booklet and printed summary.\n\nPatients' and general practitioners' perceptions of who made the decision, decisional conflict, treatment choice, menopausal symptoms, costs, anxiety, and general health status.\n\nBoth patients and general practitioners found the decision aid acceptable. At three months, mean scores for decisional conflict were significantly lower in the intervention group than in the control group (2.5 v 2.8; mean difference -0.3, 95% confidence interval -0.5 to -0.2); this difference was maintained during follow up. A higher proportion of general practitioners perceived that treatment decisions had been made \"mainly or only\" by the patient in the intervention group than in the control group (55% v 31%; 24%, 8% to 40%). At three months a lower proportion of women in the intervention group than in the control group were undecided about treatment (14% v 26%; -12%, -23% to -0.4%), and a higher proportion had decided against hormone replacement therapy (46% v 32%; 14%, 1% to 28%); these differences were no longer apparent by nine months. No differences were found between the groups for anxiety, use of health service resources, general health status, or utility. The higher costs of the intervention were largely due to the video disc technology used.\n\nAn interactive multimedia decision aid in the NHS would be popular with patients, reduce decisional conflict, and let patients play a more active part in decision making without increasing anxiety. The use of web based technology would reduce the cost of the intervention.", "PMID": "11532844"}, {"title": "Patient decision support intervention: increased consistency with decision analytic models.", "abstract": "Patient Decision Support (PDS) tools assist patients in using medical evidence to make choices consistent that are with their values and in using evidence about consequences of medical alternatives.\n\nTo evaluate a PDS intervention for perimenopausal hormone replacement therapy. We assessed the impact of the PDS on (1) consistency between the decision to take estrogen replacement therapy (ERT) or progesterone/estrogen replacement therapy (PERT) and the expected utility of treatment and (2) likelihood to take ERT and PERT pre- and postintervention.\n\nContent of the PDS was standardized. Randomized trial of three intensities of intervention: (1) brochure; (2) lecture/discussion; and (3) active decision support.\n\nParticipants were perimenopausal community volunteers between the ages of 40 and 65 (n = 248).\n\n(1) Consistent with values (correlation between expected utility (EU) and likelihood of taking hormones); and (2) Likelihood to take hormone replacement therapy.\n\n(1) The brochure group was less consistent with the decision analytic model than the lecture/discussion and active decision support groups. (2) Influence on decisions: PDS tools increased the number of women certain about whether or not to take hormones. There were no differences among experimental groups. Of 99 women uncertain about ERT pre-PDS, 65% changed. Twenty-one (32%) decided against ERT and 44 (68%) decided for ERT. (3) More intensive interventions produced modest gains in a normative direction.\n\nPDSs using any of 3 formats reduce uncertainty and assist women to make informed decisions. Increased consistency with decision analytic models appears to be driven by better estimates of likelihood of outcomes.", "PMID": "10098571"}, {"title": "Randomised controlled trial comparing effectiveness of touch screen system with leaflet for providing women with information on prenatal tests.", "abstract": "To compare the effectiveness of touch screen system with information leaflet for providing women with information on prenatal tests.\n\nRandomised controlled trial; participants allocated to intervention group (given access to touch screen and leaflet information) or control group (leaflet information only).\n\nAntenatal clinic in university teaching hospital.\n\n875 women booking antenatal care.\n\nAll participants received a leaflet providing information on prenatal tests. Women in the intervention arm also had access to touch screen information system in antenatal clinic.\n\nWomen's informed decision making on prenatal testing as measured by their uptake of and understanding of the purpose of specific tests; their satisfaction with information provided; and their levels of anxiety.\n\nAll women in the trial had a good baseline knowledge of prenatal tests. Women in the intervention group did not show any greater understanding of the purpose of the tests than control women. However, uptake of detailed anomaly scans was significantly higher in intervention group than the control group (94% (351/375) v 87% (310/358), P=0.0014). Levels of anxiety among nulliparous women in intervention group declined significantly over time (P<0.001).\n\nThe touch screen seemed to convey no benefit over well prepared leaflets in improving understanding of prenatal tests among the pregnant women. It did, however, seem to reduce levels of anxiety and may be most effective for providing information to selected women who have a relevant adverse history or abnormal results from tests in their current pregnancy.", "PMID": "10634736"}, {"title": "Effects of ZDV-based patient education on intentions toward ZDV use, HIV testing and reproduction among a US cohort of women.", "abstract": "This study examined the immediate effects of exposure to a patient education brochure concerning the risks and benefits of zidovudine (ZDV) therapy during pregnancy to reduce perinatal HIV transmission (protocol ACTG 076) on related knowledge, behavioural intentions and attitudes of women with and at-risk for HIV-infection. Self-reports were collected from 653 women of childbearing age from community family planning clinics and hospital-based HIV centres in 19 sites from nine US cities between May and November 1995. The intervention was a nine-page patient education brochure in Spanish, Creole and English versions, evently presenting the pros and cons of ZDV therapy to reduce perinatal HIV-transmission. Brochure exposure increased knowledge (p < 0.001) for all but one scale concerning ZDV resistance and increased the likelihood of women reporting intentions to take ZDV during pregnancy (p < 0.001) and to believe ZDV reduced transmission (p < 0.001). Brochure exposure had differential effects for some subpopulations. Intentions to have or terminate current or future pregnancies, knowledge about ZDV and attitudes toward ZDV varied mostly by ethnicity/race, language preference and HIV status. Pregnancy status, age, education and having an HIV-positive child had less impact on the brochure's effect, while income had no impact.", "PMID": "10716008"}], "labels": [{"PMID": "10418541", "label": "included"}, {"PMID": "10463708", "label": "included"}, {"PMID": "10632830", "label": "included"}, {"PMID": "11085838", "label": "included"}, {"PMID": "11089711", "label": "included"}, {"PMID": "11281861", "label": "included"}, {"PMID": "11532844", "label": "included"}, {"PMID": "10098571", "label": "excluded"}, {"PMID": "10634736", "label": "excluded"}, {"PMID": "10716008", "label": "excluded"}]}
{"metadata": {"review_pmid": "38275741"}, "inputs": {"background": "Diabetic macular oedema (DMO) is a common complication of diabetic retinopathy. Antiangiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) can reduce oedema, improve vision, and prevent further visual loss. These drugs have replaced laser photocoagulation as the standard of care for people with DMO. In the previous update of this review, we found moderate-quality evidence that, at 12 months, aflibercept was slightly more effective than ranibizumab and bevacizumab for improving vision in people with DMO, although the difference may have been clinically insignificant (less than 0.1 logarithm of the minimum angle of resolution (logMAR), or five Early Treatment Diabetic Retinopathy Study (ETDRS) letters, or one ETDRS line).", "objectives": "The objective of this updated review was to compare the effectiveness and safety of the different anti-VEGF drugs in RCTs at longer followup (24 months).", "selection criteria": "We included randomised controlled trials (RCTs) that compared any anti-angiogenic drug with an anti-VEGF mechanism of action versus another anti-VEGF drug, another treatment, sham, or no treatment in people with DMO."}, "context": [{"title": "Intravitreal bevacizumab (avastin) injection alone or combined with triamcinolone versus macular photocoagulation as primary treatment of diabetic macular edema.", "abstract": "To report the efficacy of a single intravitreal bevacizumab injection alone or in combination with intravitreal triamcinolone acetonide versus macular laser photocoagulation (MPC) as primary treatment of diabetic macular edema (DME).\n\nIn this randomized, three-arm clinical trial, 103 eyes of 97 patients with clinically significant DME and no previous treatment were enrolled. The eyes were randomly assigned to one of three study arms: the intravitreal bevacizumab (IVB) group, patients who received 1.25 mg of intravitreal bevacizumab (37 eyes); the IVB/IVT group, patients who received 1.25 mg of intravitreal bevacizumab and 2 mg of intravitreal triamcinolone (33 eyes); and the MPC group, patients who underwent focal or modified grid laser (33 eyes). Primary outcome measure was change in visual acuity.\n\nVisual acuity changes +/- SD at 12 weeks were -0.22 +/- 0.23, -0.13 +/- 0.31, and + 0.08 +/- 0.31 logarithm of the minimal angle of resolution in the IVB, IVB/IVT, and MPC groups, respectively. The marginal regression model based on generalized estimating equation analysis demonstrated that the visual acuity changes in the groups were statistically significant at both 6 weeks (P < 0.0001) and 12 weeks (P = 0.024). The significant treatment effect was demonstrated at both 6 weeks and 12 weeks in the IVB group and only at 6 weeks in the IVB/IVT group. Significant central macular thickness (CMT) reduction was observed in eyes in the IVB and IVB/IVT groups only up to 6 weeks; however, CMT changes were not significant in the groups.\n\nUp to 12 weeks, intravitreal bevacizumab treatment of patients with DME yielded better visual outcome than laser photocoagulation, although it was not associated with a significant decrease in CMT. No further beneficial effect of intravitreal triamcinolone could be demonstrated. Further clinical trials with longer follow-up are required to evaluate the long-term visual outcomes and complication profiles after primary treatment with such medications.", "PMID": "18046223"}, {"title": "Randomized trial of intravitreal bevacizumab alone or combined with triamcinolone versus macular photocoagulation in diabetic macular edema.", "abstract": "To compare the results of intravitreal bevacizumab (IVB) injection alone or in combination with intravitreal triamcinolone acetonide (IVT) versus macular laser photocoagulation (MPC) as a primary treatment of diabetic macular edema (DME).\n\nRandomized 3-arm clinical trial.\n\nA total of 150 eyes of 129 patients with clinically significant DME and no previous treatment.\n\nThe eyes were randomly assigned to 1 of the 3 study arms: the IVB group, patients who received 1.25 mg IVB (50 eyes); the IVB/IVT group, patients who received 1.25 mg of IVB and 2 mg of IVT (50 eyes); and the MPC group, patients who underwent focal or modified grid laser (50 eyes). Retreatment was performed at 12-week intervals whenever indicated.\n\nChange in best-corrected visual acuity (VA) at week 24.\n\nVA changes among the groups were statistically significant at 6 (P<0.001) and 24 (P = 0.012) weeks. The significant treatment effect was demonstrated in the IVB group at all follow-up visits and in the IVB/IVT group at 6 and 12 weeks. VA changes +/- standard deviation at 36 weeks were -0.28+/-0.25, -0.04+/-0.33, and +0.01+/-0.27 logarithm of minimum angle of resolution in the IVB, IVB/IVT, and MPC groups, respectively (P = 0.053). Significant central macular thickness (CMT) reduction was observed in all groups only up to 6 weeks; however, CMT changes were not significant among the groups in all visits. Overall, retreatment was required for 27 eyes up to 36 weeks (14 in the IVB group, 10 in the IVB/IVT group, and 3 in the MPC group). In the IVB group, in which a greater VA improvement was observed, only 1 injection was required in 72% of the cases. VA improvement >2 Snellen lines at 36 weeks was detected in 37%, 25%, and 14.8% of patients in the IVB, IVB/IVT, and MPC groups, respectively.\n\nIntravitreal bevacizumab injection in patients with DME yielded a better visual outcome at 24 weeks compared with macular photocoagulation. A change in CMT beyond the 6-week time point that corresponded to the vision change was not detected. No adjunctive effect of IVT was demonstrated.\n\nThe author(s) have no proprietary or commercial interest in any materials discussed in this article.", "PMID": "19376585"}, {"title": "Primary End Point (Six Months) Results of the Ranibizumab for Edema of the mAcula in diabetes (READ-2) study.", "abstract": "To compare ranibizumab with focal/grid laser or a combination of both in diabetic macular edema (DME).\n\nProspective, randomized, interventional, multicenter clinical trial.\n\nA total of 126 patients with DME.\n\nSubjects were randomized 1:1:1 to receive 0.5 mg of ranibizumab at baseline and months 1, 3, and 5 (group 1, 42 patients), focal/grid laser photocoagulation at baseline and month 3 if needed (group 2, 42 patients), or a combination of 0.5 mg of ranibizumab and focal/grid laser at baseline and month 3 (group 3, 42 patients).\n\nThe primary end point was the change from baseline in best-corrected visual acuity (BCVA) at month 6.\n\nAt month 6, the mean gain in BCVA was significantly greater in group 1 (+7.24 letters, P = 0.01, analysis of variance) compared with group 2 (-0.43 letters), and group 3 (+3.80 letters) was not statistically different from groups 1 or 2. For patients with data available at 6 months, improvement of 3 lines or more occurred in 8 of 37 (22%) in group 1 compared with 0 of 38 (0%) in group 2 (P = 0.002, Fisher exact test) and 3 of 40 (8%) in group 3. Excess foveal thickness was reduced by 50%, 33%, and 45% in groups 1, 2, and 3, respectively.\n\nDuring a span of 6 months, ranibizumab injections by the current protocol had a significantly better visual outcome than focal/grid laser treatment in patients with DME.", "PMID": "19700194"}, {"title": "A phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema.", "abstract": "To evaluate the safety and efficacy of pegaptanib sodium injection (pegaptanib) in the treatment of diabetic macular edema (DME).\n\nRandomized, double-masked, multicenter, dose-ranging, controlled trial.\n\nIndividuals with a best-corrected visual acuity (VA) between 20/50 and 20/320 in the study eye and DME involving the center of the macula for whom the investigator judged photocoagulation could be safely withheld for 16 weeks.\n\nIntravitreous pegaptanib (0.3 mg, 1 mg, 3 mg) or sham injections at study entry, week 6, and week 12 with additional injections and/or focal photocoagulation as needed for another 18 weeks. Final assessments were conducted at week 36.\n\nBest-corrected VA, central retinal thickness at the center point of the central subfield as assessed by optical coherence tomography measurement, and additional therapy with photocoagulation between weeks 12 and 36.\n\nOne hundred seventy-two patients appeared balanced for baseline demographic and ocular characteristics. Median VA was better at week 36 with 0.3 mg (20/50), as compared with sham (20/63) (P = 0.04). A larger proportion of those receiving 0.3 mg gained VAs of > or =10 letters (approximately 2 lines) (34% vs. 10%, P = 0.003) and > or =15 letters (18% vs. 7%, P = 0.12). Mean central retinal thickness decreased by 68 microm with 0.3 mg, versus an increase of 4 microm with sham (P = 0.02). Larger proportions of those receiving 0.3 mg had an absolute decrease of both > or =100 microm (42% vs. 16%, P = 0.02) and > or =75 microm (49% vs. 19%, P = 0.008). Photocoagulation was deemed necessary in fewer subjects in each pegaptanib arm (0.3 mg vs. sham, 25% vs. 48%; P = 0.04). All pegaptanib doses were well tolerated. Endophthalmitis occurred in 1 of 652 injections (0.15%/injection; i.e., 1/130 [0.8%] pegaptanib subjects) and was not associated with severe visual loss.\n\nIn this phase II trial, subjects assigned to pegaptanib had better VA outcomes, were more likely to show reduction in central retinal thickness, and were deemed less likely to need additional therapy with photocoagulation at follow-up.", "PMID": "16154196"}, {"title": "A phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema.", "abstract": "To provide data on the short-term effect of intravitreal bevacizumab for diabetic macular edema (DME).\n\nRandomized phase II clinical trial.\n\nOne hundred twenty-one eyes of 121 subjects (109 eligible for analysis) with DME and Snellen acuity equivalent ranging from 20/32 to 20/320.\n\nRandom assignment to 1 of 5 groups: (A) focal photocoagulation at baseline (n = 19), (B) intravitreal injection of 1.25 mg of bevacizumab at baseline and 6 weeks (n = 22), (C) intravitreal injection of 2.5 mg of bevacizumab at baseline and 6 weeks (n = 24), (D) intravitreal injection of 1.25 mg of bevacizumab at baseline and sham injection at 6 weeks (n = 22), or (E) intravitreal injection of 1.25 mg of bevacizumab at baseline and 6 weeks with photocoagulation at 3 weeks (n = 22).\n\nCentral subfield thickness (CST) on optical coherence tomography and best-corrected visual acuity (VA) were measured at baseline and after 3, 6, 9, 12, 18, and 24 weeks.\n\nAt baseline, median CST was 411 mum and median Snellen VA equivalent was 20/50. Compared with group A, groups B and C had a greater reduction in CST at 3 weeks and about 1 line better median VA over 12 weeks. There were no meaningful differences between groups B and C in CST reduction or VA improvement. A CST reduction > 11% (reliability limit) was present at 3 weeks in 36 of 84 (43%) bevacizumab-treated eyes and 5 of 18 (28%) eyes treated with laser alone, and at 6 weeks in 31 of 84 (37%) and 9 of 18 (50%) eyes, respectively. Combining focal photocoagulation with bevacizumab resulted in no apparent short-term benefit or adverse outcomes. Endophthalmitis developed in 1 eye. The following events occurred during the first 24 weeks in subjects treated with bevacizumab without attributing cause to the drug: myocardial infarction (n = 2), congestive heart failure (n = 1), elevated blood pressure (n = 3), and worsened renal function (n = 3).\n\nThese results demonstrate that intravitreal bevacizumab can reduce DME in some eyes, but the study was not designed to determine whether treatment is beneficial. A phase III trial would be needed for that purpose.", "PMID": "17698196"}, {"title": "Intravitreal bevacizumab with or without triamcinolone for refractory diabetic macular edema; a placebo-controlled, randomized clinical trial.", "abstract": "To evaluate the effect of three intravitreal injections of bevacizumab (IVB) alone or combined with triamcinolone (IVT) in the first injection for treatment of refractory diabetic macular edema (DME).\n\nIn this prospective, placebo-controlled, randomized clinical trial, 115 eyes of 101 patients with refractory DME were included. Subjects were randomly assigned to one of the three study arms: 1) three injections of IVB (1.25 mg/0.05 ml) at 6-week intervals, 2) combined IVB and IVT (1.25 mg/0.05 ml and 2 mg/0.05 ml respectively) followed by two injections of IVB at 6-week intervals, and 3) sham injection (control group). The primary outcome measure was change in central macular thickness (CMT). Secondary outcome measures were change in best-corrected logMAR visual acuity (BCVA ) and incidence of potential adverse events.\n\nCentral macular thickness was reduced significantly in both the IVB and IVB/IVT groups. At week 24, CMT change compared to the baseline was -95.7 microm (95% CI, -172.2 to -19.26) in the IVB group, -92.1 microm (95% CI, -154.4 to -29.7) in the IVB/IVT group, and 34.9 microm (95% CI, 7.9 to 61.9) in the control group. There was a significant difference between the IVB and control groups (P = 0.012) and between the IVB/IVT and control groups (P = 0.022). Improvement of BCVA was initiated at weeks 6 and 12 in the IVB/IVT and IVB groups respectively. In terms of BCVA change compared to the baseline at 24 weeks, the differences between the IVB and control groups (P = 0.01) and also between the IVB/IVT and control groups (P = 0.006) were significant. No significant differences were detected in the changes of CMT and BCVA between the IVB and IVB/IVT groups (P = 0.99). Anterior chamber reaction was noticed in eight (19.5%) and seven (18.9%) eyes respectively in the IVB and IVB/IVT groups the day after injection, and it resolved with no sequel. Elevation of IOP occurred in three eyes (8.1%) in the IVB/IVT group.\n\nThree consecutive intravitreal injections of bevacizumab had a beneficial effect on refractory DME in terms of CMT reduction and BCVA improvement. Addition of triamcinolone in the first injection seemed to induce earlier visual improvement; however, it did not show any significant additive effect later during follow-up.", "PMID": "17917738"}, {"title": "Intravitreal triamcinolone versus bevacizumab for treatment of refractory diabetic macular oedema (IBEME study).", "abstract": "The aim of this study was to compare the morphological and visual acuity outcomes associated with a single intravitreal injection of triamcinolone acetonide versus bevacizumab for the treatment of refractory diffuse diabetic macular oedema.\n\nTwenty-eight patients were randomly assigned to receive a single intravitreal injection of either 4 mg/0.1 ml triamcinolone acetonide or 1.5 mg/0.06 ml bevacizumab. Comprehensive ophthalmic evaluation was performed at baseline and at weeks 1, 4, 8 (+/-1), 12 (+/-2) and 24 (+/-2) after treatment. Main outcome measures included central macular thickness measured with optical coherence tomography (OCT) and best corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity.\n\nTwenty-six patients (26 eyes) completed all study visits (two patients missed two consecutive study visits). Central macular thickness was significantly reduced in the intravitreal triamcinolone group compared with the bevacizumab group at weeks 4, 8, 12 and 24 (p<0.05). Logarithm of the minimum angle of resolution (LogMAR) best-corrected visual acuity was significantly higher at weeks 8 (0.69; approximately 20/100(+1)) and 12 (0.74; 20/100(-2)) in the intravitreal triamcinolone group compared with the bevacizumab group (weeks 8 (0.83; approximately 20/125(-1)) and 12 (0.86; 20/160(+2))) (p<0.05). Significant change from baseline in mean intraocular pressure (mmHg) was seen at week 4 (+2.25) only in the intravitreal triamcinolone group (p<0.0001). No patient had observed cataract progression during the study.\n\nOne single intravitreal injection of triamcinolone may offer certain advantages over bevacizumab in the short-term management of refractory diabetic macular oedema, specifically with regard to changes in central macular thickness. The actual clinical relevance of our preliminary findings, however, remains to be determined in future larger studies.", "PMID": "17965109"}, {"title": "Intravitreal bevacizumab versus combined bevacizumab-triamcinolone versus macular laser photocoagulation in diabetic macular edema.", "abstract": "To evaluate the additive effect of triamcinolone to bevacizumab in comparison to standard macular laser photocoagulation versus bevacizumab in the management of diabetic macular edema (DME).\n\nIn a prospective, randomized clinical trial, 130 eyes of 110 patients with type 2 diabetes with DME were included. Eligible eyes were randomly assigned to 1.25 mg intravitreal bevacizumab (42 eyes) (IVB group) or combination of 1.25 mg bevacizumab and 2 mg triamcinolone acetonide (41 eyes) (IVB+IVT group) or macular laser photocoagulation (47 eyes) (MPC). Central macular thickness (CMT) and visual acuity changes at week 6 and 16 were assessed.\n\nThe mean age of the patients was 57 -/+7 years. Patients were followed 16 weeks. At week 6, all the three groups showed significant reduction in CMT but the reductions for IVB and IVB+IVT were significantly more than MPC (p<0.001). At week 16, the response was not stable for IVB (p<0.001), but IVB+IVT maintained its superior status to MPC (p<0.001). At week 16, visual acuities were essentially unchanged for the two groups of MPC and IVB and improvement for IVB+IVT was marginal and at most was 0.1 log MAR. No patient developed uveitis, endophthalmitis, or thromboembolic event.\n\nSingle intravitreal bevacizumab or triamcinolone plus bevacizumab injection brought about significantly greater macular thickness reduction in diabetic patients in comparison to standard laser treatment. However, the response for bevacizumab alone was short-lived. Reduction in macular thickness was only marginally associated with visual acuity improvement in the triamcinolone plus bevacizumab injection group.", "PMID": "18988166"}, {"title": "Intravitreal bevacizumab and/or macular photocoagulation as a primary treatment for diffuse diabetic macular edema.", "abstract": "To evaluate the efficacy of intravitreal injection of bevacizumab (IVB) followed by modified grid laser photocoagulation (MGP) versus each alone as a primary treatment of diffuse diabetic macular edema.\n\nA randomized 3-arm clinical trial in which 62 eyes of 48 patients with diffuse diabetic macular edema were enrolled. Eyes were randomly distributed to 1 of 3 study groups: 19 eyes underwent MGP (MGP group), 21 eyes received 1.25 mg of IVB (IVB group), and 22 eyes received IVB followed by MGP (combined group). All eyes underwent a complete ophthalmic examination including fluorescein angiography and optical coherence tomography at baseline and at 1, 3, and 6 months, after treatment. Fluorescein angiography was performed at the 3 and 6 months follow up visits. The outcome measures were the change compared with baseline in central macular thickness (CMT), changes in best-corrected visual acuity (BCVA), changes in fluorescein angiography leakage, and any reported complication. A P value less than 0.05 was considered statistically significant.\n\nOne month after treatment, the reduction in the mean CMT versus baseline was 49.88 \u03bcm (10.45%) in MGP group, 150.92 \u03bcm (31.30%) in IVB group, and 110.30 \u03bcm (23.77%) in the combined group, with a corresponding improvement in the mean BCVA. At 1 month, the improvement in CMT was better than baseline in all groups, yet only significant in the IVB group (P < 0.05) and the combined group (P < 0.05). The improvement in mean BCVA was significant in the IVB (P < 0.05) and the combined groups at 1 month (P < 0.05). At 3 months, the mean CMT was still better than baseline in all groups but this improvement was significant only in the combined group (P < 0.05). The improvement in the mean BCVA was significant only in the IVB and the combined groups (P < 0.05). Six months after treatment, the reduction in the mean CMT was significant in the combined group only (P < 0.05) and there was no significant improvement in the mean BCVA in all groups (P > 0.05). The BCVA did not deteriorate below baseline in all eyes included in the study, except three eyes in the MGP group. No complication related to the intravitreal injection was reported in the injected eyes.\n\nCombined therapy with IVB and sequential MGP 3 weeks later appeared to be superior to MGP or IVB alone in reducing macular thickening and improving visual acuity. However, no significant improvement in BCVA occurs 6 months after treatment. A combination of IVB and sequential MGP could be used as an initial treatment of diffuse diabetic macular edema.", "PMID": "20838357"}, {"title": "Randomized trial evaluating short-term effects of intravitreal ranibizumab or triamcinolone acetonide on macular edema after focal/grid laser for diabetic macular edema in eyes also receiving panretinal photocoagulation.", "abstract": "To evaluate 14-week effects of intravitreal ranibizumab or triamcinolone in eyes receiving focal/grid laser for diabetic macular edema and panretinal photocoagulation.\n\nThree hundred and forty-five eyes with a visual acuity of 20/320 or better, center-involved diabetic macular edema receiving focal/grid laser, and diabetic retinopathy receiving prompt panretinal photocoagulation were randomly assigned to sham (n = 123), 0.5-mg ranibizumab (n = 113) at baseline and 4 weeks, and 4-mg triamcinolone at baseline and sham at 4 weeks (n = 109). Treatment was at investigator discretion from 14 weeks to 56 weeks.\n\nMean changes (\u00b1SD) in visual acuity letter score from baseline were significantly better in the ranibizumab (+1 \u00b1 11; P < 0.001) and triamcinolone (+2 \u00b1 11; P < 0.001) groups compared with those in the sham group (-4 \u00b1 14) at the 14-week visit, mirroring retinal thickening results. These differences were not maintained when study participants were followed for 56 weeks for safety outcomes. One eye (0.9%; 95% confidence interval, 0.02%-4.7%) developed endophthalmitis after receiving ranibizumab. Cerebrovascular/cardiovascular events occurred in 4%, 7%, and 3% of the sham, ranibizumab, and triamcinolone groups, respectively.\n\nThe addition of 1 intravitreal triamcinolone injection or 2 intravitreal ranibizumab injections in eyes receiving focal/grid laser for diabetic macular edema and panretinal photocoagulation is associated with better visual acuity and decreased macular edema by 14 weeks. Whether continued long-term intravitreal treatment is beneficial cannot be determined from this study.", "PMID": "21394052"}], "labels": [{"PMID": "18046223", "label": "included"}, {"PMID": "19376585", "label": "included"}, {"PMID": "19700194", "label": "included"}, {"PMID": "16154196", "label": "excluded"}, {"PMID": "17698196", "label": "excluded"}, {"PMID": "17917738", "label": "excluded"}, {"PMID": "17965109", "label": "excluded"}, {"PMID": "18988166", "label": "excluded"}, {"PMID": "20838357", "label": "excluded"}, {"PMID": "21394052", "label": "excluded"}]}
{"metadata": {"review_pmid": "38275196"}, "inputs": {"background": "Observational studies in preterm newborns suggest that delay in administering amino acids (AA) could result in a protein catabolic state and impact on growth and development.", "objectives": "The objective of this review was to compare the efficacy and safety of early versus late administration of intravenous AA in neonates born at < 37 weeks of gestation.", "selection criteria": "We included randomised controlled trials (RCTs) comparing early administration of AA with late administration in premature newborn infants. We defined early administration of AA solution as the administration of AA in isolation or with total parenteral nutrition within the first 24 hours of birth, and late administration as the administration of AA in isolation or with total parenteral nutrition after the first 24 hours of birth."}, "context": [{"title": "Metabolic responses to early and high protein supplementation in a randomized trial evaluating the prevention of hyperkalemia in extremely low birth weight infants.", "abstract": "To determine whether early and higher intravenous amino acid (EHAA) supplementation decreases hyperkalemia in extremely low birth weight (ELBW) infants (<1000 g).\n\nInfants were enrolled at birth in a randomized, double-masked, prospective fashion and treated for 7 days. The standard group (SAA) infants received intravenous amino acid (AA) starting at 0.5 g x kg(-1) x d(-1) and increased by 0.5 g x kg(-1) every day to a maximum of 3 g x kg(-1) x d(-1). EHAA group infants received 2 g x kg(-1) x d(-1) of AA soon after birth and advanced by 1 g x kg(-1) every day to 4 g x kg(-1) x d(-1). Data analysis was by SPSS 11.5, with statistical significance at alpha = 0.05 and 90% power to determine a difference in mean K(+) level of 2.\n\nSixty-two patients, mean gestational age of 26.0 +/- 2.0 weeks and birth weight of 775 +/- 136 g, were enrolled. Hyperkalemia (K(+) > or =6.5 mEq/L) occurred in 13% of the studied population; no difference in incidence of hyperkalemia was found between the SAA and EHAA groups (16% vs 10%, respectively, P = .70). Serum blood urea nitrogen was higher in the EHAA group. AA infusion was stopped early in 6 patients for high blood urea nitrogen or elevated ammonia level.\n\nDuring the study period, hyperkalemia decreased significantly and was not affected by EHAA supplementation in the first week of life.", "PMID": "18589451"}, {"title": "The effects of early parenteral amino acids on sick premature infants.", "abstract": "To study the effects of early parenteral amino acid administration on body weight, fluid compartments and metabolic parameters during the first week of life in sick premature infants.\n\nAppropriate for gestational age, sick premature infants were randomized into two groups. Group A infants (n=8, birth weight 1258\u00b1339 g) were supplemented with amino acids starting within 24 h of birth and advanced to 2.5 g/kg per day by day 3. Group G infants (n=9, birth weight 1182\u00b1214 g) received amino acids starting on day 4 of life. Energy intake was comparable in the 2 groups. Amino acid concentrations and nitrogen balance studies were performed on day 3 of life. Total body water and extracellular water were measured on day 1 and 8 and change in intracellular volume was calculated.\n\nThere was no significant difference between the 2 groups in terms of weight, intracellular volume change from day 1 to day 8 of life, despite a significant (P<0.01) difference in protein intake. Plasma ammonia levels were comparable in the 2 groups, but plasma urea levels were significantly higher in group A vs. group G infants (7.2\u00b13.4 mmol/L vs. 3.2\u00b11.2 mmol/L respectively, P<0.01). Nitrogen balance was positive in all group A infants and negative in group G infants. Nitrogen loss was inversely correlated with energy intake in group G infants (P<0.05). The mean plasma amino acid concentrations in group A infants (compared to those of group G) were within previously reported ranges in older premature infants.\n\nThere was no significant effect on body weight and redistribution of body fluid compartments in infants receiving amino acids early during the first week of life. Serum urea concentrations were significantly higher in infants receiving early amino acids. Nitrogen losses in infants who did not receive amino acids were inversely correlated with energy intake during the first 3 days of life.", "PMID": "20830534"}, {"title": "Low birthweight infants and total parenteral nutrition immediately after birth. II. Randomised study of biochemical tolerance of intravenous glucose, amino acids, and lipid.", "abstract": "This randomised study aimed to compare the biochemical tolerance of three parenteral regimens administered during the first 48 hours of life. Twenty nine infants were randomised to either: (a) glucose 10%; (b) glucose 10%/amino acids; (c) glucose 10%/amino acids/lipid. Blood samples for plasma amino acid profiles, cholesterol, and triglyceride concentrations were taken on arrival in the neonatal unit and again between 36 and 48 hours of life. Arterial or capillary blood gas analysis and blood glucose estimates were performed routinely during the first 48 hours of life. There was a sharp decline in plasma amino acid concentrations in the group following (a) compared with the two groups following (b) and (c) regimens. In all groups plasma triglyceride and cholesterol were not significantly different before and after 48 hours of lipid infusion. Peak mean (SE) bilirubin concentrations (203 (12) v 181 (19) v 220 (20) mumol/l) and the need for phototherapy (nine v eight v five infants) were similar for each of the groups. Hypoglycaemia occurred most frequently during the (b) regimen and least commonly in the (c) group. There are potential health gains from giving parenteral nutrition to low birthweight infants immediately after birth, and this study indicates that restriction of nutritional intake immediately after birth in preterm infants may cause significant metabolic disturbance. This can be prevented by starting a regimen of intravenous amino acids and lipid immediately after birth.", "PMID": "7552604"}, {"title": "Effect of intravenous amino acids on protein metabolism of preterm infants during the first three days of life.", "abstract": "Twenty-three preterm infants with respiratory distress syndrome (mean birth weight 1.07 kg, SD 0.24 kg) were randomly assigned to receive glucose alone or glucose with amino acids (1.5 g.kg-1.d-1) i.v. beginning on the 1st d of life. Blood ammonia and serum urea, CO2 content, sodium, potassium, chloride, and ionized calcium concentrations were normal and did not differ between treatment groups. Nitrogen balance was significantly greater in the group that received amino acids [88 (SD 54) versus -135 (SD 45) mg.kg-1.d-1]. In 12 infants (seven, glucose-only; five, glucose and amino acids), leucine kinetic studies were also performed on the 3rd d of life. These 12 infants received a 4-h primed constant infusion of L-[1-13C]leucine. Blood and breath were collected and analyzed for [1-13C]ketoisocaproate and 13CO2, respectively. Leucine turnover and oxidation were calculated. Both leucine turnover and oxidation were significantly higher in the group receiving amino acids than in the glucose-only group [241 (SD 38) versus 164 (SD 25) mumol.kg-1.h-1 and 71 (SD 22) versus 40 (SD 17) mumol.kg-1.h-1, respectively]. In addition, the calculated rate of protein synthesis was higher in the group receiving amino acids [6.9 (SD 1.1) versus 5.0 (SD 1.2) g.kg-1.d-1]. These data indicate that the i.v. administration of amino acids (1.5 g.kg-1.d-1) to ill preterm infants beginning on the 1st d of life improves whole-body protein balance as a result of increased protein synthesis.", "PMID": "8433884"}, {"title": "Early parenteral feeding of amino acids.", "abstract": "Serial 24 hour balance studies of nitrogen and energy were carried out over 10 days in two groups of ventilator dependent preterm infants, of comparable weight and gestational age. In one group (n = 10) a parenteral amino acid source (Vamin 9) was started within 24 hours of birth, and in the other group (n = 11) it was not started until 72 hours. The feeding protocol was otherwise identical. The nitrogen intake (286 compared with 21 mg/kg/day), energy intake (188 compared with 151 kJ), and nitrogen retention (120 compared with -133 mg/kg/day), were all significantly higher during the first three days of life in the group in which the amino acid solution was started early. There were no differences by 7-10 days. The early introduction of amino acids improves the early nutritional state of sick preterm infants.", "PMID": "2511809"}, {"title": "[Intensive early amino acid supplementation is efficacious and safe in the management of preterm infants].", "abstract": "To evaluate the efficacy and safety of the parenteral administration of various quantities of amino acid in preterm infants.\n\nPreterm infants (birth weight 1000-2000 g) recruited into the study were randomized into three groups. High amino acid group (HP): 2.4 g/(kg.d) of amino acid IV within 24 hours after birth increasing by increments of 1.2 g/(kg.d) to a maximum of 3.6 g/(kg. d); medium amino acid group (MP): 1.0 g/(kg.d) of amino acid IV 24 hours after birth, increasing by increments of 0.5 g/(kg.d) until a maximum of 3.0 g/(kg.d); and low amino acid group (LP): 0.5 g/(kg.d) of amino acid on D3, increasing by increments of 0.5 g/(kg.d) until a maximum of 3.0 g/(kg.d) as the final dose.\n\nTotally 96 preterm infants were recruited: HP 34, MP 32 and LP 30. There were no significant differences in demographic or clinical characteristics among the 3 groups. HP group showed lower postnatal weight loss (43.4 g, 95% CI 74.3, 12.6) and weight loss% (2.84%, 95% CI 4.79%, 0.71%) than LP group. HP group showed shorter length of stay in NICU (5.25 d), days to reach 2000 g (7.03 d) and days to tolerate 100 kcal/(kg.d) enteral nutrition (4.52 d) than LP group. Cost of hospitalization was significantly lower in HP group than in LP group (-6275 RMB, 1 US$=8 RMB) and MP group (-5715 RMB). Mean serum RBP (D4), threonine and tyrosine levels were significantly higher in HP group than in LP group. Serum insulin levels were similar; mean serum glucose level was lower in HP group than in LP group. HP infants had lower incidence of sepsis than LP infants (21.9% vs 40.0%). There were no significant differences in the levels of blood ammonia, acid-base balance (as determined by pH and NaHCO3-), BUN, Cr, AST, and ALT.\n\nIntensive and early administration of intravenous amino acid [2.4 g/(kg.d)] improves preterm infants' growth and the tolerance of enteral feeding. It also reduces the cost of hospitalization, and the incidence of sepsis.", "PMID": "19573436"}, {"title": "Amino acid administration to premature infants directly after birth.", "abstract": "To test the hypothesis that the administration of 2.4 g amino acids (AA)/(kg.d) to very low birth weight infants is safe and results in a positive nitrogen balance.\n\nWe conducted a randomized, clinical trial. Preterm infants with birth weights <1500 g received either glucose and 2.4 g AA/(kg.d) from birth onward (n=66) or solely glucose during the first day with a stepwise increase in AA intake to 2.4 g AA/(kg.d) on day 3 (n=69). Blood gas analysis was performed daily during the first 6 postnatal days; blood urea nitrogen levels were determined on days 2, 4, and 6; AA plasma concentrations and nitrogen balances were determined on days 2 and 4. Student t tests, Mann-Whitney tests, and chi2 tests were performed to compare groups.\n\nInfants supplemented with AA had no major adverse side effects. Their blood urea nitrogen levels were higher, nitrogen balance turned positive upon AA administration, and more AA concentrations were within reference ranges.\n\nHigh-dose AA administration to very low birth weight infants can be introduced safely from birth onward and results in an anabolic state.", "PMID": "16227030"}, {"title": "Effects of early amino acid administration on leucine and glucose kinetics in premature infants.", "abstract": "We previously showed that, in prematurely born infants, an anabolic state without metabolic acidosis can be achieved upon intravenous amino acid (AA) administration in the immediate postnatal phase, despite a low energy intake. We hypothesized that the anabolic state resulted from an increased protein synthesis and not a decreased proteolysis. Furthermore, we hypothesized that the energy needed for the higher protein synthesis rate would be derived from an increased glucose oxidation. To test our hypotheses, 32 ventilated premature infants (<1500 g) received intravenously either solely glucose or glucose and 2.4 g AA/kg/d immediately postnatally. On postnatal d 2, each group received primed continuous infusions of either [1-13C]leucine or [U-13C6]glucose. 13CO2 enrichments in expiratory air and plasma [1-13C]alpha-KICA (as an intracellular leucine precursor) and [U-13C6]glucose enrichments were measured by mass spectrometry techniques. The AA administration resulted in an increased incorporation of leucine into body protein and a higher leucine oxidation rate, whereas leucine release from proteolysis was not affected. Glucose oxidation rate did not increase upon AA administration. In conclusion, the anabolic state resulting from AA administration in the immediate postnatal period resulted from increased protein synthesis and not decreased proteolysis. The energy needed for the additional protein synthesis was not derived from an increased glucose oxidation.", "PMID": "16627891"}, {"title": "Observational outcome results following a randomized controlled trial of early amino acid administration in preterm infants.", "abstract": "Several reports have investigated amino acid administration in premature infants during the early postnatal phase. Most of these previous studies, however, have only evaluated short-term in-hospital outcomes. Our aim was to describe long-term outcomes in premature infants previously subjected to different nutritional regimens in a randomized controlled trial. The primary outcome was survival without major disabilities, and the secondary outcomes included anthropometry and mental development.\n\nInfants born <32 weeks' gestation and <1500 g were randomized to receive glucose (n = 69) or glucose with 2.4 g \u00b7 kg(-1) \u00b7 day(-1 amino acids) (n = 63) from birth. From postnatal day 3 onward, the nutritional intake was similar. At 2 years of corrected age, the surviving infants were assessed for neurodevelopmental outcome and anthropometry.\n\nNinety-seven percent of the surviving infants were examined at follow-up, with no overall effect on survival without major disabilities. Boys, however, had a normal outcome significantly more often if amino acids were administered from birth onward (crude odds ratio 3.8, 95% confidence interval 1.3-11.4) and following adjustment for confounders (odds ratio 6.2, 95% confidence interval 1.0-38.0). The secondary outcomes exhibited no differences in anthropometric data. The mental developmental index was lower in the small number of girls who survived without major disabilities following the early administration of amino acids.\n\nIn this hypothesis-generating outcome study, premature boys, but not girls, benefited from amino acid administration directly following birth. The observed lower mental developmental index in a subgroup of girls, however, warrants further studies.", "PMID": "25187104"}], "labels": [{"PMID": "18589451", "label": "included"}, {"PMID": "20830534", "label": "included"}, {"PMID": "7552604", "label": "included"}, {"PMID": "8433884", "label": "included"}, {"PMID": "2511809", "label": "included"}, {"PMID": "19573436", "label": "included"}, {"PMID": "16227030", "label": "included"}, {"PMID": "16627891", "label": "included"}, {"PMID": "25187104", "label": "included"}]}
{"metadata": {"review_pmid": "38270182"}, "inputs": {"background": "Laryngeal mask airway surfactant administration (S-LMA) has the potential benefit of surfactant administration whilst avoiding endotracheal intubation and ventilation, ventilator-induced lung injury and bronchopulmonary dysplasia (BPD).", "objectives": "To evaluate the benefits and harms of S-LMA either as prophylaxis or treatment (rescue) compared to placebo, no treatment, or intratracheal surfactant administration via an endotracheal tube (ETT) with the intent to rapidly extubate (InSurE) or extubate at standard criteria (S-ETT) or via other less-invasive surfactant administration (LISA) methods on morbidity and mortality in preterm infants with or at risk of respiratory distress syndrome (RDS).", "selection criteria": "Randomised controlled trials (RCTs), cluster- or quasi-RCTs of S-LMA compared to placebo, no treatment, or other routes of administration (nebulised, pharyngeal instillation of surfactant before the first breath, thin endotracheal catheter surfactant administration or intratracheal surfactant instillation) on morbidity and mortality in preterm infants at risk of RDS. We considered published, unpublished and ongoing trials."}, "context": [{"title": "Implementation of Surfactant Administration through Laryngeal or Supraglottic Airways (SALSA): A Jordanian NICU's Journey to Improve Surfactant Administration.", "abstract": "Administration of liquid surfactant through an endotracheal tube for the treatment of respiratory distress syndrome has been the standard of care for decades. Surfactant administration through laryngeal or supraglottic airways (SALSA) is a simplified procedure for delivery of surfactant that is less invasive and better tolerated. The Al Bashir Maternity and Children\u2019s Hospital NICU in Amman, Jordan, implemented SALSA as a potentially better practice in 2019 with the objective to effectively and efficiently deliver surfactant in a minimally invasive way and to decrease the adverse events associated with intubation\u2212surfactant\u2212extubation (InSurE) and laryngoscopy. The quality improvement initiative was conducted from March 2019 to December 2019. All infants who weighed 750 g or more who required surfactant were eligible. As physicians were trained in the technique and use expanded, we were able to use plan\u2212do\u2212study\u2212act cycles to observe differences between SALSA and InSurE. The primary aim was the optimization of non-invasive ventilation by the effective and efficient delivery of surfactant. Balancing measures included episodes of bradycardia while receiving surfactant or the need for a second dose of surfactant. We evaluated 220 infants who received surfactant by SALSA or InSurE with a mean gestational age of 32 weeks and a mean birth weight of 1.8 kg. The Respiratory Severity Score (RSS) prior to surfactant administration was 2.7 in the SALSA group compared to 2.9 in the InSurE group (p = 0.024). Those in the InSurE group had a lower mean heart rate during the procedure (p =< 0.0001) and were more likely to need a second dose of surfactant (p = 0.026) or require intubation for mechanical ventilation (p = 0.022). Both groups were effectively delivered surfactant as evidenced by improvement in their RSS over an 8 h period. SALSA was a more time efficient surfactant delivery method (93 vs. 111 secs, p =< 0.0001). Implementation of SALSA into the Al Bashir NICU was successful. We found that it was equally effective to InSurE, but was a more efficient method of delivery. Infants who received surfactant by this method tolerated it well.", "PMID": "36010038"}, {"title": "ProSealTM laryngeal mask airway for surfactant administration in the treatment of respiratory distress syndrome in a premature infant.", "abstract": "The administration of surfactant via tracheal cannula with mechanical ventilation is the conventional treatment for infant respiratory distress syndrome. Hemodynamic and respiratory changes due to tracheal intubation and the need for premedication justify the search for less invasive alternatives of surfactant administration. The objective of this study was to describe the use of the ProSealTM laryngeal mask airway as an option for the treatment of respiratory distress syndrome in a premature infant born at 31 weeks of gestation, at 1335 g, with respiratory difficulty after the first hour of life and exhibiting the clinical and radiologic features of respiratory distress syndrome. The surfactant was administered with the use of the ProSealTM laryngeal mask airway at 3.5 hours of life. It was well tolerated, with no need for tracheal intubation. Normal gasometry and radiologic improvement were observed after three and six hours of administration. Oxygen administration was suspended after eight days, with no comorbidities at discharge. The laryngeal mask airway seems to be a painless and less invasive alternative to treat respiratory distress syndrome and may reduce the need for tracheal intubation and mechanical ventilation. The efficacy and advantages of this route of treatment should be confirmed in a study of an adequate sample. ", "PMID": "23917771"}, {"title": "The laryngeal mask airway for administration of surfactant in two neonates with respiratory distress syndrome.", "abstract": "We report the successful use of the Classic laryngeal mask airway to provide brief access to the intratracheal space for the administration of surfactant in two neonates with respiratory distress syndrome.", "PMID": "14962337"}, {"title": "Surfactant Administration Through Laryngeal or Supraglottic Airways.", "abstract": "Noninvasive ventilation is frequently used in the treatment of infants with respiratory distress syndrome. This practice is often effective in higher gestational age neonates, but can be difficult in those with lower gestational ages as surfactant deficiency can be severe. While noninvasive ventilation avoids the negative effects of intubation and ventilator-induced lung injury, failure of this mode of support does occur with relative frequency and is primarily caused by the poorly compliant, surfactant-deficient lung. Because of the potential problems associated with laryngoscopy and intubation, neonatologists have developed various methods to deliver surfactant in minimally invasive ways with the aim of improving the success of noninvasive ventilation. Methods of minimally invasive surfactant administration include various thin catheter techniques, aerosolization/nebulization, and the use of a laryngeal mask airway/supraglottic airway device. The clinician should recognize that currently the only US Food and Drug Administration-approved device to deliver surfactant is an endotracheal tube and all methods reviewed here are considered off-label use. This review will focus primarily on surfactant administration through laryngeal or supraglottic airways, providing a review of the history of this technique, animal and human trials, and comparison with other minimally invasive techniques. In addition, this review provides a step-by-step instruction guide on how to perform this procedure, including a multimedia tutorial to facilitate learning.", "PMID": "34599065"}, {"title": "ProSeal LMA for surfactant administration.", "abstract": "", "PMID": "18095983"}, {"title": "Laryngeal mask airway for surfactant administration in a newborn animal model.", "abstract": "Premature infants are subjected to adverse effects of intubation to benefit from surfactant. We hypothesized that administration of surfactant through a laryngeal mask airway (LMA) is as effective as administration through an endotracheal tube (ETT) and that time and physiologic changes during instrumentation will be less in the LMA group. This study is a randomized, controlled trial using newborn pigs. Lung injury was induced via surfactant washout. Animals were randomized into groups: 1) LMA placed, no surfactant administered (control; n = 8); 2) surfactant via an LMA (LMA group; n = 8); and 3) surfactant via an ETT (ETT group; n = 8). We demonstrated that partial pressure of oxygen in arterial blood (Pao2) levels of the LMA and ETT groups were not statistically different. Time for successful placement of LMA was 19 \u00b1 1 s versus ETT 123 \u00b1 35 s (mean \u00b1 SEM); number of attempts for successful LMA placement was 1.1 (1-2) versus ETT 1.9 (1-7) [mean (range)]. Administration of surfactant via an LMA compared with an ETT resulted in similar improvements in oxygenation. Placement of the device required less time and fewer attempts. These data suggest that further study in human neonates is justified. If proven effective, some infants with respiratory distress may be able to receive surfactant while avoiding intubation.", "PMID": "20613684"}, {"title": "Laryngeal mask airway used as a delivery conduit for the administration of surfactant to preterm infants with respiratory distress syndrome.", "abstract": "The laryngeal mask airway (LMA(TM), Laryngeal Mask Co. Ltd, Jersey, UK) is a supraglottic device used to administer positive pressure ventilation (PPV) in adults, pediatric and neonatal patients.\n\nTo avoid endotracheal intubation, we evaluated the feasibility and practicality of administering surfactant via the LMA(TM) in preterm infants with respiratory distress syndrome (RDS).\n\nInfants less than 72 h old with a gestational age of < or =35 weeks and a birth weight of >800 g, treated with nasal continuous positive airway pressure (CPAP, 5 cm H2O) for RDS were eligible for inclusion in the study if the arterial-to-alveolar oxygen tension ratio (a/APO2) was <0.20 over a period of >60 min.\n\nEight preterm infants, median gestational age 31 (range 28-35) weeks; birth weight 1,700 (880-2,520) g, treated with nasal CPAP for RDS were enrolled. Three hours after surfactant instillation, the mean a/APO2 was significantly increased (0.13 +/- 0.04 to 0.34 +/- 0.11; p < 0.01) without complications.\n\nThe LMA may be a useful and noninvasive conduit for the administration of surfactant therapy. A large randomized comparative clinical trial will be required to confirm the efficacy of this technique.", "PMID": "15650304"}, {"title": "Catheter and Laryngeal Mask Endotracheal Surfactant Therapy: the CALMEST approach as a novel MIST technique.", "abstract": "Neonatal respiratory distress syndrome (RDS) is a major cause of mortality and morbidity among preterm infants. Although the INSURE (INtubation, SURfactant administration, Estubation) technique for surfactant replacement therapy is so far the gold standard method, over the last years new approaches have been studied, i.e. less invasive surfactant administration (LISA) or minimally invasive surfactant therapy (MIST). Here we propose an originally modified MIST, called CALMEST (Catheter And Laryngeal Mask Endotracheal Surfactant Therapy), using a particular laryngeal mask as a guide for a thin catheter to deliver surfactant directly in the trachea.\n\nWe performed a preliminary study on a mannequin and a subsequent in vivo pilot trial.\n\nThis novel procedure is quick, effective and well tolerated and might represent an improvement in reducing neonatal stress. Ultimately, CALMEST offers an alternative approach that could be extremely useful for medical staff with low expertise in laryngoscopy and intubation.", "PMID": "27780385"}, {"title": "Surfactant Administration Through Laryngeal or Supraglottic Airways (SALSA): A Viable Method for Low-Income and Middle-Income Countries.", "abstract": "Administration of liquid surfactant through an endotracheal tube for the treatment of respiratory distress syndrome has been the standard of care for decades. A skilled health care provider is needed to perform this procedure. In lower-income and middle-income countries (LMICs), healthcare resources are often limited, leading to increased mortality of premature infants, many of whom would benefit from surfactant administration. Therefore, having a simplified procedure for delivery of surfactant without the need for advanced skills could be life-saving, potentially diminish gaps in care, and help ensure more equitable global neonatal survival rates. Modifications to the standard approach of surfactant administration have been put into practice and these include: INtubation-SURfactant-Extubation (INSURE), thin catheter surfactant administration (TCA), aerosolized surfactant, and surfactant administration through laryngeal or supraglottic airways (SALSA). Although there is a need for larger studies to evaluate the comparative effectiveness of these newer methods, these methods are being embraced by the global community and being implemented in various settings throughout the world. Because the SALSA technique does not require laryngoscopy, a provider skilled in laryngoscopy is not required for the procedure. Therefore, because of the ease of use and safety profile, the SALSA technique should be strongly considered as a viable method of delivering surfactant in LMICs.", "PMID": "35372140"}], "labels": [{"PMID": "36010038", "label": "excluded"}, {"PMID": "23917771", "label": "excluded"}, {"PMID": "14962337", "label": "excluded"}, {"PMID": "34599065", "label": "excluded"}, {"PMID": "18095983", "label": "excluded"}, {"PMID": "20613684", "label": "excluded"}, {"PMID": "15650304", "label": "excluded"}, {"PMID": "27780385", "label": "excluded"}, {"PMID": "35372140", "label": "excluded"}]}
{"metadata": {"review_pmid": "38269441"}, "inputs": {"background": "This is an updated version of a Cochrane Review first published in 2014. Phimosis is a condition in which the prepuce (foreskin) cannot be fully retracted past the head of the penis (glans). Phimosis is often treated surgically by circumcision or prepuce plasty; however, reports of non-invasive treatment using topical corticosteroids applied for four to eight weeks have suggested favorable outcomes.", "objectives": "To assess the effects of topical corticosteroids applied to the stenotic portion of the prepuce for the treatment of phimosis in boys compared with placebo or no treatment.", "selection criteria": "We included all randomized controlled trials (RCTs) that compared the use of any topical corticosteroid with placebo or no treatment for boys with any type or degree of phimosis."}, "context": [{"title": "Effect of topical steroid on non-retractile prepubertal foreskin by a prospective, randomized, double-blind study.", "abstract": "The present study, conducted in Hong Kong, aimed to evaluate the effect of topical steroid in non-retractile prepubertal foreskin by a prospective, randomized, double-blind design.\n\n137 boys with non-retractile foreskin were randomized to betamethasone (n = 66) or placebo (n = 71 ) for 4 weeks with application of the cream twice daily. Non-responders to treatment were offered steroid treatment for a further 4 weeks.\n\nThe mean pretreatment grade of the foreskin in the steroid and control groups was 5.08 +/- 0.66 and 4.97 +/- 0.70, respectively. At the 4-week follow-up, 49 of the former (74%) had a retractile foreskin (grade less than or equal to 3, mean 2.38 +/- 1.41). In contrast, only 31 of the control group (44%) had a retractile foreskin (less than or equal to 3, mean 3.55 +/- 1.55) (p < 0.001). Only 14 boys were circumcised because 43 of the remaining 57 boys had a retractile foreskin after 4 weeks of treatment.\n\nwhen treatment is necessary, application of topical steroid as a first line of treatment may avoid surgery in almost 90% of cases.", "PMID": "11095086"}, {"title": "The response of balanitis xerotica obliterans to local steroid application compared with placebo in children.", "abstract": "We evaluated the clinical effectiveness of topical steroid application for balanitis xerotica obliterans in children and analyzed the association of any clinical response with histological findings.\n\nOur double-blind, placebo controlled, randomized study included 40 boys in whom balanitis xerotica obliterans was diagnosed clinically by cicatricial phimosis. The severity of phimosis was graded into 4 groups. Patients were randomized to receive the topical application of 0.05% mometasone furoate or placebo. After 5 weeks phimosis severity was reevaluated and all patients underwent circumcision. Surgical specimens were histologically typed as an early, intermediate or late form of balanitis xerotica obliterans.\n\nSeven patients were withdrawn from the study. In the steroid group 7 boys had clinical improvement and 10 had no change. Histological study showed an early, intermediate and late form of balanitis xerotica obliterans in 5, 5 and 7 cases, respectively. Of cases with clinical improvement 5 were the early and 2 the intermediate type. In the placebo group 5 cases worsened clinically and 11 did not change. Histological evaluation revealed an early, intermediate and late form of balanitis xerotica obliterans in 3, 7 and 6 boys, respectively. Of the 5 cases with histological worsening, disease was the early, intermediate and late type in 2, 2 and 1, respectively.\n\nApplying a potent topical steroid affects improvement in balanitis xerotica obliterans in the histologically early and intermediate stages of disease, and may inhibit further worsening in the late stage.", "PMID": "11125410"}, {"title": "Psychological trauma of circumcision in the phallic period could be avoided by using topical steroids.", "abstract": "The objective of our study was to assess the efficacy of topical steroids in the treatment of phimosis and evaluate patients using the Diagnostic and Statistical Manual-III-Revised (DSM-III-R) test with the aim of eliminating castration anxiety of circumcision in the phallic period.\n\nOne hundred and forty-nine children with phimosis who required circumcision were included the study. The average age of the children was 4.47 years. All children underwent the DSM-III-R test and their parents were questioned. Patients were separated randomly into three groups. Group I comprised 51 children who would undergo circumcision; group II comprised 50 children who would be treated with a topical corticosteroid (0.05% bethamethasone cream) twice daily for 1 month; and group III comprised 48 children who would be treated with a topical placebo cream. On the 5th day of treatment, parents were told to retract the prepuce and were given hygiene routine instructions. Patients were seen immediately after treatment and again 2 months later.\n\nIn group II, 16 of the 50 children had non-retractable prepuce. Forty-two cases of phimosis were corrected after treatment. Eight patients received further monthly treatment and five benefited from the second course of treatment. In group III, 17 of the 48 patients had non-retractable prepuce and four had satisfactory results. Forty-four patients received placebo treatment for another month and eventually, 40 children underwent circumcision in this group. DSM-III-R test results showed a significant shift to anxiety in the circumcision group. The were no significant differences in the other groups.\n\nTopical steroids for the treatment of phimosis is a highly effective treatment alternative to surgery. It avoids or delays circumcision and can be practised during the phallic period to decrease castration anxiety. The treatment is suitable for patients from any religious or cultural background.", "PMID": "14633068"}, {"title": "An 18-month follow-up study after randomized treatment of phimosis in boys with topical steroid versus placebo.", "abstract": "To evaluate the treatment of phimosis using topical steroid.\n\nThis was a follow-up study after a prospective, randomized, double-blind study. A total of 137 boys with phimosis were randomly assigned to either betamethasone treatment or placebo for 4 weeks, with application of the cream twice daily. Non-responders to treatment were offered steroid treatment for a further 4 weeks. All patients were invited to a follow-up examination after 18 months.\n\nThe mean pre-treatment phimosis grades in the steroid and control groups were 5.08+/-0.66 and 4.97+/-0.70, respectively. At the 4-week follow-up, 49 boys (74%) in the steroid group were cured, compared to only 31 (44%) in the control group. Fourteen boys were circumcised after another 4 weeks of treatment; 43 of the remaining 57 boys (17 in the steroid group; 40 in the control group) had been cured. After a total of 92 boys took part in the 18-month follow-up study: 79 had been cured and 13 had suffered a relapse. Twenty-six patients did not took part in the follow-up investigation. No side-effects were noted.\n\nWhen treatment is necessary for phimosis, we recommend application of topical steroid as first-line treatment because surgery can then be avoided in 85% of cases. This first randomized, double-blind, follow-up study shows that the treatment effect persists for at least 18 months.", "PMID": "15764277"}, {"title": "Topical hydrocortisone and physiotherapy for nonretractile physiologic phimosis in infants.", "abstract": "The effect of hydrocortisone (HC), the steroid of lowest potency, and physiotherapy (PT) on non-retractile physiologic phimosis (PP) and the reduction of subsequent recurrent UTI was evaluated in male infants with UTI. Seventy-eight male infants with febrile UTI and nonretractile PP were prospectively randomized into HC (Plancol, n=39) and control (Vaseline, n=39) groups. Topical application of HC as a thin film around the preputial margin twice a day for four weeks with PT was instructed. The response rate in the HC group was 89.7% (35/39), which was significantly higher than the rate (20.5%; 8/39) in the control group (P<0.05). In the HC group, the response rate was much higher (96.1%) in the subgroup with PT than in the group without PT. Most of the response (88.5%) was observed within two weeks. During the following year, the recurrent rate of UTI was 7.1% (2/28) in the infants with retractile prepuces, which was significantly less than than the rate (29.6%; 8/27) in infants with nonretractile prepuces (P<0.05). In conclusion, topical HC and PT for 2-4 weeks proved to be a simple, safe and effective treatment for nonretractile PP in infants with UTI, and this procedure was beneficial in reducing recurrent UTI.", "PMID": "16791612"}, {"title": "Topical steroid treatment of phimosis in boys.", "abstract": "We evaluate whether steroid application alone or retraction and hygiene are responsible for successful results in boys treated with topical steroids for phimosis.\n\nA prospective study was performed, which included a control group of 42 patients with phimosis seen at our outpatient department from January to June 1997. During that time we trained the parent to retract and clean the foreskin only. From July 1997 to June 1998 topical steroid cream was prescribed in addition to retraction and hygiene in 276 boys with phimosis. All cases were divided into 3 subgroups of asymptomatic, symptomatic and buried penis.\n\nThe response rate was greater than 95% in patients who received topical steroid treatment in addition to improved hygiene. Only 13 boys (less than 5%) had no response to steroid treatment. Of the control patients 23 (55%) had no response to gentle retraction and personal hygiene. There was a significant difference (p<0.001) in response rate between the study and control groups. However, the subgroup with a buried penis responded poorly to steroid, retraction and hygiene treatment. There was significant difference (p<0.001) in response rate between the buried penis and other steroid groups but no significant difference (p>0.05) in the control group.\n\nPhimosis is a physiological condition in neonates due to natural adhesion between the foreskin and the glans. Chronic infection due to poor hygiene is responsible for most cases of childhood phimosis. Circumcision is the traditional treatment of choice for phimosis or unretractable foreskin, although it is not always desired by parents or surgeons. Topical steroid cream is an easy, safe and nonsurgical alternative for phimosis. However, boys with a buried penis are not good candidates for steroid treatment.", "PMID": "10458396"}, {"title": "Highly potent and moderately potent topical steroids are effective in treating phimosis: a prospective randomized study.", "abstract": "We report a prospective randomized study comparing the effects of highly potent and moderately potent topical steroids in treating pediatric phimosis.\n\nA total of 70 boys 1 to 12 years old with phimosis were randomly assigned to receive topical application of either betamethasone valerate 0.06% (a highly potent steroid) or clobetasone butyrate 0.05% (a moderately potent steroid). Parents of the boys were instructed to retract the foreskin gently without causing pain, and to apply the topical steroids over the stenotic opening of the prepuce twice daily for 4 weeks, then for another 4 weeks if no improvement was achieved. Retractibility of the prepuce was graded from 0 to 5. Response to treatment was arbitrarily defined as improvement in the retractibility score of more than 2 points.\n\nMean treatment and followup periods were 4.3 and 19.1 weeks, respectively. The response rates in boys treated with betamethasone valerate and clobetasone butyrate were 81.3% and 77.4%, respectively (p = 0.63). Mean retractibility score decreased from 3.9 +/- 1.0 to 1.7 +/- 1.1, and 4.2 +/- 1.0 to 1.9 +/- 1.0 in the betamethasone and clobetasone groups, respectively. Both steroids were effective in all age groups. Pretreatment retractibility score did not affect treatment outcomes. No adverse effect was encountered.\n\nHighly potent and moderately potent topical steroids are of comparable effectiveness in treating phimosis. A less potent steroid may be considered first to decrease the risk of the potential adverse effects.", "PMID": "15758802"}, {"title": "Phimosis: stretching methods with or without application of topical steroids?", "abstract": "Phimosis has been defined as unretractable foreskin without adherences or a circular band of tight prepuce preventing full retraction. We suggested a new treatment protocol combining betamethasone with stretching exercises to reduce the number of patients requiring surgery for phimosis. Between January 2003 and September 2004, 247 boys aged 4 to 14 years (mean 7.6) were included in this consecutive, prospective, open study. Patients were treated with 0.05% betamethasone cream applied to the distal aspect of the prepuce twice daily for the first 15 days, then once daily for 15 more days. Preputial gymnastics started 1 week after topical application of betamethasone. Ninety-six percent of patients receiving 1 or more cycles of betamethasone showed complete resolution of phimosis. There was a significant difference (P < .001) in response rate between the study and control groups. Only 10 boys in the study group had no response to steroid and stretching. Treatment with topical steroids, combined with stretching exercises, is a suitable alternative to surgical correction (preputial plasty/circumcision).", "PMID": "16291369"}, {"title": "[Comparative effectiveness of 0.1% metilprednisolone aceponate and 0.05% betamethasone dipropionate among children with nonretractable prepuce].", "abstract": "To compare clinical improvement between treatment with metilprednisolone aceponate vs. betamethasone dipropionate among children with nonretractable prepuce.\n\nBetween August 2001 and November 2002, we carried out a double blind and controlled clinical trial in 34 children with a diagnosis of nonretracable prepuce. Children were randomly assigned to one of the following groups and topical treatment was administered: Group A; metilprednisolone aceponate 0. I 1% and Group B; betamethasone dipropionate 0.05%.\n\nImprovement was noted in 88.2% of our sample studied; (n= 15) children from group A and 76.4% (n= 13) childrenfrom group B; however, we did not observe a significant difference when comparing percentages between the two groups (chi2 = 0.2; p = 0.6).\n\nThe percentage of clinical improvement was similar between the two groups of topical steroid treatment administered.", "PMID": "16711546"}, {"title": "Phimosis and topical steroids: new clinical findings.", "abstract": "Phimosis has been defined as unretractable foreskin without adherences and/or a circular band of tight prepuce preventing full retraction. The aim of this study is to evaluate the efficacy (response rate) of topical steroids for the treatment of tight phimosis at different age stages. After using the same medication with different dosage schemes, a retrospective analysis was carried out to assess the efficacy of topical steroids in the treatment of tight phimosis. Patients were divided into three groups: group A (betamethasone scheme A), group B (betamethasone scheme B) and group C (control group). Remission of phimosis, with a complete exposure and without a narrowing behind the glans, was considered a complete response to treatment. The outcomes were then related to dosage scheme and patient's age. The dosage for group A was more effective than the dosage for groups B and C (control group). Phimosis resolved in 90% (group A), 72% (group B) and 56% (group C) of cases. A successful treatment was closely related to the age of patients at the beginning of steroid application. The results showed that treatment with topical steroids, which in general gives good results, proved to be much more successful in patients aged between 4 and 8 years, suggesting the efficacy of an early beginning of the treatment.", "PMID": "17308904"}], "labels": [{"PMID": "11095086", "label": "included"}, {"PMID": "11125410", "label": "included"}, {"PMID": "14633068", "label": "included"}, {"PMID": "15764277", "label": "included"}, {"PMID": "16791612", "label": "included"}, {"PMID": "10458396", "label": "excluded"}, {"PMID": "15758802", "label": "excluded"}, {"PMID": "16291369", "label": "excluded"}, {"PMID": "16711546", "label": "excluded"}, {"PMID": "17308904", "label": "excluded"}]}
{"metadata": {"review_pmid": "38264795"}, "inputs": {"background": "Balancing the risk of bleeding and thrombosis after acute myocardial infarction (AMI) is challenging, and the optimal antithrombotic therapy remains uncertain. The potential of non-vitamin K antagonist oral anticoagulants (NOACs) to prevent ischaemic cardiovascular events is promising, but the evidence remains limited.", "objectives": "To evaluate the efficacy and safety of non-vitamin-K-antagonist oral anticoagulants (NOACs) in addition to background antiplatelet therapy, compared with placebo, antiplatelet therapy, or both, after acute myocardial infarction (AMI) in people without an indication for anticoagulation (i.e. atrial fibrillation or venous thromboembolism).", "selection criteria": "We searched for randomised controlled trials (RCTs) that evaluated NOACs plus antiplatelet therapy versus placebo, antiplatelet therapy, or both, in people without an indication for anticoagulation after an AMI."}, "context": [{"title": "Apixaban, an oral, direct, selective factor Xa inhibitor, in combination with antiplatelet therapy after acute coronary syndrome: results of the Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) trial.", "abstract": "After an acute coronary syndrome, patients remain at risk of recurrent events. Apixaban, an oral direct factor Xa inhibitor, is a novel anticoagulant that may reduce these events but also poses a risk of bleeding.\n\nApixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) was a phase 2, double-blind, placebo-controlled, dose-ranging study. Patients (n=1715) with recent ST-elevation or non-ST-elevation acute coronary syndrome were randomized to 6 months of placebo (n=611) or 1 of 4 doses of apixaban: 2.5 mg twice daily (n=317), 10 mg once daily (n=318), 10 mg twice daily (n=248), or 20 mg once daily (n=221). Nearly all patients received aspirin; 76% received clopidogrel. The primary outcome was International Society of Thrombosis and Hemostasis major or clinically relevant nonmajor bleeding. A secondary outcome was cardiovascular death, myocardial infarction, severe recurrent ischemia, or ischemic stroke. At the recommendation of the Data Monitoring Committee, the 2 higher-dose apixaban arms were discontinued because of excess total bleeding. Compared with placebo, apixaban 2.5 mg twice daily (hazard ratio, 1.78; 95% confidence interval, 0.91 to 3.48; P=0.09) and 10 mg once daily (hazard ratio, 2.45; 95% confidence interval, 1.31 to 4.61; P=0.005) resulted in a dose-dependent increase in major or clinically relevant nonmajor bleeding. Apixaban 2.5 mg twice daily (hazard ratio, 0.73; 95% confidence interval, 0.44 to 1.19; P=0.21) and 10 mg once daily (hazard ratio, 0.61; 95% confidence interval, 0.35 to 1.04; P=0.07) resulted in lower rates of ischemic events compared with placebo. The increase in bleeding was more pronounced and the reduction in ischemic events was less evident in patients taking aspirin plus clopidogrel than in those taking aspirin alone.\n\nWe observed a dose-related increase in bleeding and a trend toward a reduction in ischemic events with the addition of apixaban to antiplatelet therapy in patients with recent acute coronary syndrome. The safety and efficacy of apixaban may vary depending on background antiplatelet therapy. Further testing of apixaban in patients at risk of recurrent ischemic events is warranted.", "PMID": "19470889"}, {"title": "Rivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): a randomised, double-blind, phase II trial.", "abstract": "Rivaroxaban is an oral direct factor Xa inhibitor that has been effective in prevention of venous thromboembolism in patients undergoing elective orthopaedic surgery. However, its use after acute coronary syndromes has not been investigated. In this setting, we assessed the safety and efficacy of rivaroxaban and aimed to select the most favourable dose and dosing regimen.\n\nIn this double-blind, dose-escalation, phase II study, undertaken at 297 sites in 27 countries, 3491 patients stabilised after an acute coronary syndrome were stratified on the basis of investigator decision to use aspirin only (stratum 1, n=761) or aspirin plus a thienopyridine (stratum 2, n=2730). Participants were randomised within each strata and dose tier with a block randomisation method at 1:1:1 to receive either placebo or rivaroxaban (at doses 5-20 mg) given once daily or the same total daily dose given twice daily. The primary safety endpoint was clinically significant bleeding (TIMI major, TIMI minor, or requiring medical attention); the primary efficacy endpoint was death, myocardial infarction, stroke, or severe recurrent ischaemia requiring revascularisation during 6 months. Safety analyses included all participants who received at least one dose of study drug; efficacy analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00402597.\n\nThree patients in stratum 1 and 26 in stratum 2 never received the study drug. The risk of clinically significant bleeding with rivaroxaban versus placebo increased in a dose-dependent manner (hazard ratios [HRs] 2.21 [95% CI 1.25-3.91] for 5 mg, 3.35 [2.31-4.87] for 10 mg, 3.60 [2.32-5.58] for 15 mg, and 5.06 [3.45-7.42] for 20 mg doses; p<0.0001). Rates of the primary efficacy endpoint were 5.6% (126/2331) for rivaroxaban versus 7.0% (79/1160) for placebo (HR 0.79 [0.60-1.05], p=0.10). Rivaroxaban reduced the main secondary efficacy endpoint of death, myocardial infarction, or stroke compared with placebo (87/2331 [3.9%] vs 62/1160 [5.5%]; HR 0.69, [95% CI 0.50-0.96], p=0.0270). The most common adverse event in both groups was chest pain (248/2309 [10.7%] vs 118/1153 [10.2%]).\n\nThe use of an oral factor Xa inhibitor in patients stabilised after an acute coronary syndrome increases bleeding in a dose-dependent manner and might reduce major ischaemic outcomes. On the basis of these observations, a phase III study of low-dose rivaroxaban as adjunctive therapy in these patients is underway.\n\nJohnson & Johnson Pharmaceutical Research & Development and Bayer Healthcare AG.", "PMID": "19539361"}, {"title": "Dabigatran vs. placebo in patients with acute coronary syndromes on dual antiplatelet therapy: a randomized, double-blind, phase II trial.", "abstract": "After an acute coronary syndrome, patients remain at risk of recurrent ischaemic events, despite contemporary treatment, including aspirin and clopidogrel. We evaluated the safety and indicators of efficacy of the novel oral direct thrombin inhibitor dabigatran.\n\nIn this double-blind, placebo-controlled, dose-escalation trial, 1861 patients (99.2% on dual antiplatelet treatment) in 161 centres were enrolled at mean 7.5 days (SD 3.8) after an ST-elevation (60%) or non-ST-elevation (40%) myocardial infarction and randomized to twice daily treatment with dabigatran 50 mg (n = 369), 75 mg (n = 368), 110 mg (n = 406), 150 mg (n = 347), or placebo (n = 371). Primary outcome was the composite of major or clinically relevant minor bleeding during the 6-month treatment period. There were 96 primary outcome events and, compared with placebo, a dose-dependent increase with dabigatran, hazard ratio (HR) 1.77 (95% confidence intervals 0.70, 4.50) for 50 mg; HR 2.17 (0.88, 5.31) for 75 mg; HR 3.92 (1.72, 8.95) for 110 mg; and HR 4.27 (1.86, 9.81) for 150 mg. Compared with placebo, D-dimer concentrations were reduced in all dabigatran dose groups by an average of 37 and 45% at weeks 1 and 4, respectively (P< 0.001). Fourteen (3.8%) patients died, had a myocardial infarction or stroke in the placebo group compared with 17 (4.6%) in 50 mg, 18 (4.9%) in 75 mg, 12 (3.0%) in 110 mg, and 12 (3.5%) in the 150 mg dabigatran groups.\n\nDabigatran, in addition to dual antiplatelet therapy, was associated with a dose-dependent increase in bleeding events and significantly reduced coagulation activity in patients with a recent myocardial infarction.", "PMID": "21551462"}, {"title": "Rationale and design of the Anti-Xa therapy to lower cardiovascular events in addition to standard therapy in subjects with acute coronary syndrome-thrombolysis in myocardial infarction 51 (ATLAS-ACS 2 TIMI 51) trial: a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of rivaroxaban in subjects with acute coronary syndrome.", "abstract": "Although therapy with aspirin or aspirin plus a thienopyridine reduces the incidence of long-term adverse cardiovascular events among patients with acute coronary syndrome (ACS), there remains a significant residual risk of cardiovascular death, recurrent myocardial infarction (MI), and stroke. In a phase 2 trial (ClinicalTrials.gov NCT00402597) in which the addition of the factor Xa inhibitor rivaroxaban was compared with placebo, among ACS patients receiving either aspirin alone or dual-antiplatelet therapy with aspirin and a thienopyridine, the end point of death, MI, or stroke compared with placebo was reduced (87/2331 [3.9%] vs 62/1160 [5.5%]; hazard ratio 0.69, [95% CI 0.50-0.96], P = .027). Two candidate doses of rivaroxaban were selected for further evaluation in a pivotal phase 3.\n\nThe second ATLAS-ACS 2 TIMI 51 Trial is an international, randomized, double-blind, event-driven (n = 983) phase 3 trial involving more than 15,570 patients hospitalized with ACS (ClinicalTrials.gov NCT00809965). All patients are treated with a background of standard therapy including low-dose aspirin, and patients are stratified by the administration of a thienopyridine (clopidogrel or ticlopidine; stratum 2) or not (stratum 1). Within each stratum, patients are randomly assigned in a 1:1:1 ratio to receive rivaroxaban 2.5 mg twice daily, or rivaroxaban 5 mg twice daily, or placebo twice daily. The primary efficacy end point is the composite of cardiovascular death, MI, or stroke. The primary safety end point is thrombolysis in MI major bleeding not associated with coronary artery bypass graft surgery.\n\nThe ATLAS-ACS 2 TIMI 51 is testing the hypothesis that anticoagulation with the oral factor Xa inhibitor rivaroxaban reduces cardiovascular death, MI, and stroke among patients with ACS treated with guideline-based therapies for ACS.", "PMID": "21570509"}, {"title": "Rationale and design of the Anti-Xa therapy to lower cardiovascular events in addition to standard therapy in subjects with acute coronary syndrome-thrombolysis in myocardial infarction 51 (ATLAS-ACS 2 TIMI 51) trial: a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of rivaroxaban in subjects with acute coronary syndrome.", "abstract": "Although therapy with aspirin or aspirin plus a thienopyridine reduces the incidence of long-term adverse cardiovascular events among patients with acute coronary syndrome (ACS), there remains a significant residual risk of cardiovascular death, recurrent myocardial infarction (MI), and stroke. In a phase 2 trial (ClinicalTrials.gov NCT00402597) in which the addition of the factor Xa inhibitor rivaroxaban was compared with placebo, among ACS patients receiving either aspirin alone or dual-antiplatelet therapy with aspirin and a thienopyridine, the end point of death, MI, or stroke compared with placebo was reduced (87/2331 [3.9%] vs 62/1160 [5.5%]; hazard ratio 0.69, [95% CI 0.50-0.96], P = .027). Two candidate doses of rivaroxaban were selected for further evaluation in a pivotal phase 3.\n\nThe second ATLAS-ACS 2 TIMI 51 Trial is an international, randomized, double-blind, event-driven (n = 983) phase 3 trial involving more than 15,570 patients hospitalized with ACS (ClinicalTrials.gov NCT00809965). All patients are treated with a background of standard therapy including low-dose aspirin, and patients are stratified by the administration of a thienopyridine (clopidogrel or ticlopidine; stratum 2) or not (stratum 1). Within each stratum, patients are randomly assigned in a 1:1:1 ratio to receive rivaroxaban 2.5 mg twice daily, or rivaroxaban 5 mg twice daily, or placebo twice daily. The primary efficacy end point is the composite of cardiovascular death, MI, or stroke. The primary safety end point is thrombolysis in MI major bleeding not associated with coronary artery bypass graft surgery.\n\nThe ATLAS-ACS 2 TIMI 51 is testing the hypothesis that anticoagulation with the oral factor Xa inhibitor rivaroxaban reduces cardiovascular death, MI, and stroke among patients with ACS treated with guideline-based therapies for ACS.", "PMID": "21570509"}, {"title": "Rationale and design of the Anti-Xa therapy to lower cardiovascular events in addition to standard therapy in subjects with acute coronary syndrome-thrombolysis in myocardial infarction 51 (ATLAS-ACS 2 TIMI 51) trial: a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of rivaroxaban in subjects with acute coronary syndrome.", "abstract": "Although therapy with aspirin or aspirin plus a thienopyridine reduces the incidence of long-term adverse cardiovascular events among patients with acute coronary syndrome (ACS), there remains a significant residual risk of cardiovascular death, recurrent myocardial infarction (MI), and stroke. In a phase 2 trial (ClinicalTrials.gov NCT00402597) in which the addition of the factor Xa inhibitor rivaroxaban was compared with placebo, among ACS patients receiving either aspirin alone or dual-antiplatelet therapy with aspirin and a thienopyridine, the end point of death, MI, or stroke compared with placebo was reduced (87/2331 [3.9%] vs 62/1160 [5.5%]; hazard ratio 0.69, [95% CI 0.50-0.96], P = .027). Two candidate doses of rivaroxaban were selected for further evaluation in a pivotal phase 3.\n\nThe second ATLAS-ACS 2 TIMI 51 Trial is an international, randomized, double-blind, event-driven (n = 983) phase 3 trial involving more than 15,570 patients hospitalized with ACS (ClinicalTrials.gov NCT00809965). All patients are treated with a background of standard therapy including low-dose aspirin, and patients are stratified by the administration of a thienopyridine (clopidogrel or ticlopidine; stratum 2) or not (stratum 1). Within each stratum, patients are randomly assigned in a 1:1:1 ratio to receive rivaroxaban 2.5 mg twice daily, or rivaroxaban 5 mg twice daily, or placebo twice daily. The primary efficacy end point is the composite of cardiovascular death, MI, or stroke. The primary safety end point is thrombolysis in MI major bleeding not associated with coronary artery bypass graft surgery.\n\nThe ATLAS-ACS 2 TIMI 51 is testing the hypothesis that anticoagulation with the oral factor Xa inhibitor rivaroxaban reduces cardiovascular death, MI, and stroke among patients with ACS treated with guideline-based therapies for ACS.", "PMID": "21570509"}, {"title": "Apixaban with antiplatelet therapy after acute coronary syndrome.", "abstract": "Apixaban, an oral, direct factor Xa inhibitor, may reduce the risk of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome.\n\nWe conducted a randomized, double-blind, placebo-controlled clinical trial comparing apixaban, at a dose of 5 mg twice daily, with placebo, in addition to standard antiplatelet therapy, in patients with a recent acute coronary syndrome and at least two additional risk factors for recurrent ischemic events.\n\nThe trial was terminated prematurely after recruitment of 7392 patients because of an increase in major bleeding events with apixaban in the absence of a counterbalancing reduction in recurrent ischemic events. With a median follow-up of 241 days, the primary outcome of cardiovascular death, myocardial infarction, or ischemic stroke occurred in 279 of the 3705 patients (7.5%) assigned to apixaban (13.2 events per 100 patient-years) and in 293 of the 3687 patients (7.9%) assigned to placebo (14.0 events per 100 patient-years) (hazard ratio with apixaban, 0.95; 95% confidence interval [CI], 0.80 to 1.11; P=0.51). The primary safety outcome of major bleeding according to the Thrombolysis in Myocardial Infarction (TIMI) definition occurred in 46 of the 3673 patients (1.3%) who received at least one dose of apixaban (2.4 events per 100 patient-years) and in 18 of the 3642 patients (0.5%) who received at least one dose of placebo (0.9 events per 100 patient-years) (hazard ratio with apixaban, 2.59; 95% CI, 1.50 to 4.46; P=0.001). A greater number of intracranial and fatal bleeding events occurred with apixaban than with placebo.\n\nThe addition of apixaban, at a dose of 5 mg twice daily, to antiplatelet therapy in high-risk patients after an acute coronary syndrome increased the number of major bleeding events without a significant reduction in recurrent ischemic events. (Funded by Bristol-Myers Squibb and Pfizer; APPRAISE-2 ClinicalTrials.gov number, NCT00831441.).", "PMID": "21780946"}, {"title": "Rivaroxaban in patients with a recent acute coronary syndrome.", "abstract": "Acute coronary syndromes arise from coronary atherosclerosis with superimposed thrombosis. Since factor Xa plays a central role in thrombosis, the inhibition of factor Xa with low-dose rivaroxaban might improve cardiovascular outcomes in patients with a recent acute coronary syndrome.\n\nIn this double-blind, placebo-controlled trial, we randomly assigned 15,526 patients with a recent acute coronary syndrome to receive twice-daily doses of either 2.5 mg or 5 mg of rivaroxaban or placebo for a mean of 13 months and up to 31 months. The primary efficacy end point was a composite of death from cardiovascular causes, myocardial infarction, or stroke.\n\nRivaroxaban significantly reduced the primary efficacy end point, as compared with placebo, with respective rates of 8.9% and 10.7% (hazard ratio in the rivaroxaban group, 0.84; 95% confidence interval [CI], 0.74 to 0.96; P=0.008), with significant improvement for both the twice-daily 2.5-mg dose (9.1% vs. 10.7%, P=0.02) and the twice-daily 5-mg dose (8.8% vs. 10.7%, P=0.03). The twice-daily 2.5-mg dose of rivaroxaban reduced the rates of death from cardiovascular causes (2.7% vs. 4.1%, P=0.002) and from any cause (2.9% vs. 4.5%, P=0.002), a survival benefit that was not seen with the twice-daily 5-mg dose. As compared with placebo, rivaroxaban increased the rates of major bleeding not related to coronary-artery bypass grafting (2.1% vs. 0.6%, P<0.001) and intracranial hemorrhage (0.6% vs. 0.2%, P=0.009), without a significant increase in fatal bleeding (0.3% vs. 0.2%, P=0.66) or other adverse events. The twice-daily 2.5-mg dose resulted in fewer fatal bleeding events than the twice-daily 5-mg dose (0.1% vs. 0.4%, P=0.04).\n\nIn patients with a recent acute coronary syndrome, rivaroxaban reduced the risk of the composite end point of death from cardiovascular causes, myocardial infarction, or stroke. Rivaroxaban increased the risk of major bleeding and intracranial hemorrhage but not the risk of fatal bleeding. (Funded by Johnson & Johnson and Bayer Healthcare; ATLAS ACS 2-TIMI 51 ClinicalTrials.gov number, NCT00809965.).", "PMID": "22077192"}, {"title": "Rationale and design of a randomized, double-blind, event-driven, multicentre study comparing the efficacy and safety of oral rivaroxaban with placebo for reducing the risk of death, myocardial infarction or stroke in subjects with heart failure and significant coronary artery disease following an exacerbation of heart failure: the COMMANDER HF trial.", "abstract": "Thrombin is a critical element of crosstalk between pathways contributing to worsening of established heart failure (HF). The aim of this study is to explore the efficacy and safety of rivaroxaban 2.5\u2009mg bid compared with placebo (with standard care) after an exacerbation of HF in patients with reduced ejection fraction (HF-rEF) and documented coronary artery disease.\n\nThis is an international prospective, multicentre, randomized, double-blind, placebo-controlled, event-driven study of approximately 5000 patients for a targeted 984 events. Patients must have a recent symptomatic exacerbation of HF, increased plasma concentrations of natriuretic peptides (B-type natriuretic peptide \u2265200\u2009pg/mL or N-terminal pro-B-type natriuretic peptide \u2265800\u2009pg/mL), with left ventricular ejection fraction \u226440% and coronary artery disease. Patients requiring anticoagulation for atrial fibrillation or other conditions will be excluded. After an index event (overnight hospitalization, emergency department or observation unit admission, or unscheduled outpatient parenteral treatment for worsening HF), patients will be randomized 1:1 to rivaroxaban or placebo (with standard of care). The primary efficacy outcome event is a composite of all-cause mortality, myocardial infarction or stroke. The principal safety outcome events are the composite of fatal bleeding or bleeding into a critical space with potential permanent disability, bleeding events requiring hospitalization and major bleeding events according to International Society on Thrombosis and Haemostasis bleeding criteria.\n\nCOMMANDER HF is the first prospective study of a target-specific oral antithrombotic agent in HF. It will provide important information regarding rivaroxaban use following an HF event in an HF-rEF patient population with coronary artery disease.", "PMID": "25919061"}, {"title": "Design of a Randomized Placebo-Controlled Trial to Assess Dabigatran and Omeprazole in Patients with Myocardial Injury after Noncardiac Surgery (MANAGE).", "abstract": "Worldwide approximately 200 million adults undergo major surgery annually, of whom 8 million are estimated to suffer a myocardial injury after noncardiac surgery (MINS). There is currently no trial data informing the management of MINS. Antithrombotic agents such as direct oral anticoagulants might prevent major vascular complications in patients with MINS.\n\nThe Management of Myocardial Injury After Noncardiac Surgery (MANAGE) trial is a large international blinded randomized controlled trial of dabigatran vs placebo in patients who suffered MINS. We used a partial factorial design to also determine the effect of omeprazole vs placebo in reducing upper gastrointestinal bleeding and complications. Both study drugs were initiated in eligible patients within 35 days of suffering MINS and continued for a maximum of 2 years. The primary outcome is a composite of major vascular complications for the dabigatran trial and a composite of upper gastrointestinal complications for the omeprazole trial. We present the rationale and design of the trial and baseline characteristics of enrolled patients.\n\nThe trial randomized 1754 patients between January 2013 and July 2017. Patients' mean age was 69.9 years, 51.1% were male, 14.3% had a history of peripheral artery disease, 6.6% had a history of stroke or transient ischemic attack, 12.9% had a previous myocardial infarction, and 26.0% had diabetes. The diagnosis of MINS was on the basis of an isolated ischemic troponin elevation in 80.4% of participants.\n\nMANAGE is the first randomized controlled trial to evaluate a potential treatment of patients who suffered MINS.", "PMID": "29398173"}], "labels": [{"PMID": "19470889", "label": "included"}, {"PMID": "19539361", "label": "included"}, {"PMID": "21551462", "label": "included"}, {"PMID": "21570509", "label": "included"}, {"PMID": "21570509", "label": "included"}, {"PMID": "21570509", "label": "included"}, {"PMID": "21780946", "label": "included"}, {"PMID": "22077192", "label": "included"}, {"PMID": "25919061", "label": "excluded"}, {"PMID": "29398173", "label": "excluded"}]}
{"metadata": {"review_pmid": "38235907"}, "inputs": {"background": "Hepatorenal syndrome is a condition that occurs in people with chronic liver disease (such as alcoholic hepatitis, advanced cirrhosis, or fulminant liver failure) and portal hypertension. The prognosis is dismal, often with a survival of weeks to months. Hepatorenal syndrome is characterised by the development of intense splanchnic vasodilation favouring ascites and hypotension leading to renal vasoconstriction and acute renal failure. Therefore, treatment attempts focus on improving arterial pressure through the use of vasopressors, paracentesis, and increasing renal perfusion pressure. Several authors have reported that the placement of transjugular intrahepatic portosystemic shunts (TIPS) may be a therapeutic option because it decreases portal pressure and improves arterial and renal pressures. However, the evidence is not clearly documented and TIPS may cause adverse events. Accordingly, it is necessary to evaluate the evidence of the benefits and harms of TIPS to assess its value in people with hepatorenal syndrome.", "objectives": "To evaluate the benefits and harms of transjugular intrahepatic portosystemic shunts (TIPS) in adults with hepatorenal syndrome compared with sham, no intervention, conventional treatment, or other treatments.", "selection criteria": "We included only randomised clinical trials with a parallel-group design, which compared the TIPS placement with sham, no intervention, conventional therapy, or other therapies, in adults aged 18 years or older, regardless of sex or ethnicity, diagnosed with chronic liver disease and hepatorenal syndrome. We excluded trials of adults with kidney failure due to causes not related to hepatorenal syndrome, and we also excluded data from quasi-randomised, cross-over, and observational study designs as we did not design a separate search for such studies."}, "context": [{"title": "Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis.", "abstract": "The transjugular intrahepatic portosystemic shunt (TIPS) has been shown to be more effective than repeated paracentesis plus albumin in the control of refractory ascites. However, its effect on survival and healthcare costs is still uncertain.\n\nSeventy patients with cirrhosis and refractory ascites were randomly assigned to TIPS (35 patients) or repeated paracentesis plus intravenous albumin (35 patients). The primary endpoint was survival without liver transplantation. Secondary endpoints were complications of cirrhosis and costs.\n\nTwenty patients treated with TIPS and 18 treated with paracentesis died during the study period, whereas 7 patients in each group underwent liver transplantation (mean follow-up 282 +/- 43 vs. 325 +/- 61 days, respectively). The probability of survival without liver transplantation was 41% at 1 year and 26% at 2 years in the TIPS group, as compared with 35% and 30% in the paracentesis group (P = 0.51). In a multivariate analysis, only baseline blood urea nitrogen levels and Child-Pugh score were independently associated with survival. Recurrence of ascites and development of hepatorenal syndrome were lower in the TIPS group compared with the paracentesis group, whereas the frequency of severe hepatic encephalopathy was greater in the TIPS group. The calculated costs were higher in the TIPS group than in the paracentesis group.\n\nIn patients with refractory ascites, TIPS lowers the rate of ascites recurrence and the risk of developing hepatorenal syndrome. However, TIPS does not improve survival and is associated with an increased frequency of severe encephalopathy and higher costs compared with repeated paracentesis plus albumin.", "PMID": "12454841"}, {"title": "A comparison of paracentesis and transjugular intrahepatic portosystemic shunting in patients with ascites.", "abstract": "In patients with cirrhosis and ascites, creation of a transjugular intrahepatic portosystemic shunt may reduce the ascites and improve renal function. However, the benefit of this procedure as compared with that of large-volume paracentesis is uncertain.\n\nWe randomly assigned 60 patients with cirrhosis and refractory or recurrent ascites (Child-Pugh class B in 42 patients and class C in 18 patients) to treatment with a transjugular shunt (29 patients) or large-volume paracentesis (31 patients). The mean (+/-SD) duration of follow-up was 45+/-16 months among those assigned to shunting and 44+/-18 months among those assigned to paracentesis. The primary outcome was survival without liver transplantation.\n\nAmong the patients in the shunt group, 15 died and 1 underwent liver transplantation during the study period, as compared with 23 patients and 2 patients, respectively, in the paracentesis group. The probability of survival without liver transplantation was 69 percent at one year and 58 percent at two years in the shunt group, as compared with 52 percent and 32 percent in the paracentesis group (P=0.11 for the overall comparison, by the log-rank test). In a multivariate analysis, treatment with transjugular shunting was independently associated with survival without the need for transplantation (P=0.02). At three months, 61 percent of the patients in the shunt group and 18 percent of those in the paracentesis group had no ascites (P=0.006). The frequency of hepatic encephalopathy was similar in the two groups. Of the patients assigned to paracentesis in whom this procedure was unsuccessful, 10 received a transjugular shunt a mean of 5.5+/-4 months after randomization; 4 had a response to this rescue treatment.\n\nIn comparison with large-volume paracentesis, the creation of a transjugular intrahepatic portosystemic shunt can improve the chance of survival without liver transplantation in patients with refractory or recurrent ascites.", "PMID": "10841872"}, {"title": "Degree of hepatic dysfunction and improvement of renal function predict survival in patients with HRS type I: a retrospective analysis.", "abstract": "Hepatorenal syndrome (HRS) is a frequent complication of end-stage liver cirrhosis. HRS type I has a very poor prognosis. From which of the more or less established therapies, such as use of vasoconstrictors together with albumin or placement of a Transjugular Intrahepatic Portosystemic Shunt patients might profit remains elusive. Therefore, it is important to define parameters that predict an improved outcome in respect to kidney function and survival.\n\nThe clinical charts of 91 patients with cirrhosis and HRS type I were studied. The parameters associated with response to therapy, defined as a decrease in serum creatinine of more than 1.5 mg/dl on day 14 after diagnosis of HRS, and those associated with survival were assessed by multivariate analysis.\n\nThe median survival was 2.7 (1.5-3.8) months. Three independent predictive factors for survival were identified: Child-Pugh score (P = 0.05), Model of End-Stage Liver Disease (MELD) score less than 20 (P = 0.01), and response to therapy (P = 0.02). The Child-Pugh score (P = 0.00) and MELD score less than 20 (P = 0.02) were the parameters independently associated with the response to therapy, which occurred in 26% of the patients.\n\nOur data of this large monocentric series with HRS type I confirm the poor prognosis in these patients, especially in those with high Child-Pugh and MELD scores, and in those in whom kidney function does not improve within 2 weeks.", "PMID": "19794309"}, {"title": "Transjugular intrahepatic portosystemic stent-shunt for hepatorenal syndrome.", "abstract": "", "PMID": "9078203"}, {"title": "Long term outcome after transjugular intrahepatic portosystemic stent-shunt in non-transplant cirrhotics with hepatorenal syndrome: a phase II study.", "abstract": "Recent small studies on hepatorenal syndrome (HRS) indicate some clinical benefit after transjugular intrahepatic portosystemic stent-shunt (TIPS) but sufficient long term data are lacking.\n\nWe studied prospectively feasibility, safety, and long term survival after TIPS in 41 non-transplantable cirrhotics with HRS (phase II study).\n\nHRS was diagnosed using current criteria (severe (type I) HRS, n=21; moderate (type II) HRS, n=20). Thirty one patients (14 type I, 17 type II) received TIPS (8-10 mm) while advanced liver failure excluded shunting in 10. During follow up (median 24 months) we analysed renal function and survival (Kaplan-Meier).\n\nTIPS markedly reduced the portal pressure gradient (21 (5) to 13 (4) mm Hg (mean (SD)); p<0.001) with one procedure related death (3.2%). Renal function deteriorated without TIPS but improved (p<0.001) within two weeks after TIPS (creatinine clearance 18 (15) to 48 (42) ml/min; sodium excretion 9 (16) to 77 (78) mmol/24 hours) and stabilised thereafter. Following TIPS, three, six, 12, and 18 month survival rates were 81%, 71%, 48%, and 35%, respectively. As only 10% of non-shunted patients survived three months, total survival rates were 63%, 56%, 39%, and 29%, respectively. Multivariate Cox regression analysis revealed bilirubin (p<0.001) and HRS type (p<0.05) as independent survival predictors after TIPS.\n\nTIPS provides long term renal function and probably survival benefits in the majority of non-transplantable cirrhotics with HRS. These data warrant controlled trials evaluating TIPS in the management of HRS.", "PMID": "10896924"}, {"title": "Inpatient Mortality Benefit with Transjugular Intrahepatic Portosystemic Shunt for Hospitalized Hepatorenal Syndrome Patients.", "abstract": "It has been reported that transjugular intrahepatic portosystemic shunting (TIPS) might be utilized as a salvage option for hepatorenal syndrome (HRS), while randomized controlled trials are pending and real-world contemporary data on inpatient mortality is lacking.\n\nWe conducted an observational retrospective cohort study from the National Inpatient Sample from 2005 to 2014. We included all adult patients admitted with HRS and cirrhosis, using ICD 9-CM codes. We excluded cases with variceal bleeding, Budd-Chiari, end-stage renal disease, liver transplant and transfers to acute-care facilities. TIPS' association with inpatient mortality was assessed using\u00a0multivariable mixed-effects logistic regression,\u00a0as well as exact-matching,\u00a0thus mitigating for TIPS selection bias. The exact-matched analysis was repeated\u00a0among TIPS-only versus dialysis-only patients.\n\nA total of 79,354 patients were included. Nine hundred eighteen (1.2%) underwent TIPS. Between TIPS and non-TIPS groups, mean age (58\u00a0years) and gender (65% males) were similar. Overall mortality was 18% in TIPS and 48% in dialysis-only cases (n\u2009=\u200910,379; 13.1%). Ninety six (10.5%) TIPS patients underwent dialysis. In-hospital mortality in TIPS patients was twice less likely than in non-TIPS patients (adjusted odds ratio [aOR]\u2009=\u20090.43, 95% CI 0.30-0.62; p\u2009<\u20090.001), with similar results in matched analysis [exact-matched (em) OR\u2009=\u20090.39, 95% CI 0.17-0.89; p\u2009<\u20090.024; groups\u2009=\u200996; unweighted n\u2009=\u2009463]. Head-to-head comparison showed that TIPS-only patients were 3.3 times less likely to succumb inpatient versus dialysis-only patients (contrast aOR\u2009=\u20090.31, 95% CI 0.20-0.46; p\u2009<\u20090.001), with similar findings post-matching (emOR\u2009=\u20090.22, 95% CI 0.15-0.33; p\u2009<\u20090.001; groups\u2009=\u200954, unweighted n\u2009=\u20091457).\n\nContemporary, real-world data reveal that TIPS on its own, and when compared to dialysis, is associated with decreased inpatient mortality when utilized in non-bleeders-HRS patients. Further randomized studies are needed to establish the long-term benefit of TIPS in these patients.", "PMID": "32062714"}, {"title": "Transjugular intrahepatic portosystemic shunt for cirrhosis and ascites: Effects in patients with organic or functional renal failure.", "abstract": "A transjugular intrahepatic portosystemic shunt (TIPS) is increasingly being used for treatment of patients with refractory ascites and functional renal failure. In contrast, organic renal disease is commonly considered a relative contraindication for TIPS placement. The aim of this pilot study was to investigate the effects of TIPS in patients with refractory ascites and organic or functional renal impairment.\n\nA TIPS was placed for refractory or intractable ascites in 10 consecutive patients with liver cirrhosis and impaired renal function (serum creatinine > 1.5 mg/100 ml). Four of them had organic kidney disorders. Of these patients, three had moderate renal impairment, and one had end-stage renal disease and needed hemodialysis every other day. The other six patients had functional renal impairment due to the underlying liver disease.\n\nTIPS was effective in reducing ascites in 8 of 10 patients, including all patients with organic renal disease. Furthermore, after TIPS the renal function improved in all patients. Serum creatinine and serum urea levels decreased significantly from 1.8 +/- 0.1 to 1.5 +/- 0.1 mg/100 ml (P < 0.05) and from 107 +/- 13 to 78 +/- 14 mg/100 ml (P < 0.05), respectively. The renal function of the three patients with organic renal failure improved similarly, as observed in the six patients with functional renal failure. In the patient on hemodialysis, TIPS was effective in reducing the frequency of paracenteses.\n\nTIPS may be useful in patients with functional and in patients with organic renal disease, resulting in improvement of ascites and renal function.", "PMID": "10912668"}, {"title": "Gender Disparity in Inpatient Mortality After Transjugular Intrahepatic Portosystemic Shunt Creation in Patients Admitted With Hepatorenal Syndrome: A Nationwide Study.", "abstract": "The aim of this study was to evaluate inpatient mortality after transjugular intrahepatic portosystemic shunt (TIPS) creation compared with medical management (MM) in patients with hepatorenal syndrome (HRS).\n\nPatients with cirrhosis admitted with HRS between 2005 and 2014 were identified using associated International Classification of Diseases, Ninth Revision, codes in the National Inpatient Sample (n\u00a0= 153,112). Non-TIPS candidates and patients with parenchymal renal disease were excluded (n\u00a0= 73,454). The remaining admissions were assigned to groups of TIPS (International Classification of Diseases, Ninth Revision, code 39.1; n\u00a0= 971) or MM (n\u00a0= 78,687). Inpatient mortality was analyzed by treatment type and patient gender using \u03c7\n\nBaseline patient demographics were similar. Patients treated medically had higher baseline disease severity (median mortality risk score, 8.3 with MM versus 6.1 with TIPS; P < .01). Inpatient mortality was strongly modified by patient gender. TIPS creation conferred inpatient mortality benefit in men (28% of the MM group versus 10% of the TIPS group, P < .01) independent of all covariates (odds ratio, 0.4; 95% confidence interval, 0.17-0.78; P < .01). Women treated with TIPS creation experienced no mortality benefit (29% MM versus 32% TIPS; odds ratio, 1.5; 95% confidence interval, 0.75-3.23; P\u00a0= .23).\n\nTIPS creation is associated with reduced inpatient mortality in men, but not women, admitted with HRS. Drivers of this gender-based disparity are currently unclear and warrant focused investigation.", "PMID": "31541656"}, {"title": "Midodrine, octreotide, albumin, and TIPS in selected patients with cirrhosis and type 1 hepatorenal syndrome.", "abstract": "Hepatorenal syndrome (HRS) is a functional renal disorder complicating decompensated cirrhosis. Treatments to date, except liver transplantation, have been able to improve but not normalize renal function. The aim of this study was to determine the efficacy of transjugular intrahepatic portosystemic stent shunt (TIPS) as a treatment for type 1 HRS in ascitic cirrhotic patients, following improvement in systemic hemodynamics with a combination of midodrine, octreotide, and albumin (medical treatment). Fourteen ascitic cirrhotic patients with type 1 HRS received medical therapy until their serum creatinine reached below 135 micromol/L for at least 3 days, followed by a TIPS if there were no contraindications. Patients were assessed before and after medical treatment, as well as at 1 week and 1, 3, 6, and 12 months post-TIPS with measurements of renal function, sodium handling, systemic hemodynamics, central blood volume, and hormonal markers. Medical therapy for 14 +/- 3 days improved renal function (serum creatinine: 233 +/- 29 micromol/L vs. 112 +/- 8 micromol/L, P =.001) and renal sodium excretion (5 +/- 2 mmol/d vs. 9 +/- 2 mmol/d, P =.002) in 10 of the 14 patients. TIPS insertion in five of the responders further improved renal function and sodium excretion, so that by 12 months post-TIPS, glomerular filtration rate (96 +/- 20 mL/min, P <.01 vs. pre-TIPS) and urinary sodium excretion (119 +/- 15 mmol/d, P <.01 vs. pre-TIPS) were normal, associated with normalization of plasma renin and aldosterone levels and elimination of ascites. In conclusion, TIPS is an effective treatment for type 1 HRS in suitable patients with cirrhosis and ascites, following the improvement of renal function with combination therapy of midodrine, octreotide, and albumin.", "PMID": "15239086"}], "labels": [{"PMID": "12454841", "label": "included"}, {"PMID": "10841872", "label": "included"}, {"PMID": "19794309", "label": "excluded"}, {"PMID": "9078203", "label": "excluded"}, {"PMID": "10896924", "label": "excluded"}, {"PMID": "32062714", "label": "excluded"}, {"PMID": "10912668", "label": "excluded"}, {"PMID": "31541656", "label": "excluded"}, {"PMID": "15239086", "label": "excluded"}]}
{"metadata": {"review_pmid": "38235838"}, "inputs": {"background": "Pain, when treated inadequately, puts preterm infants at a greater risk of developing clinical and behavioural sequelae because of their immature pain system. Preterm infants in need of intensive care are repeatedly and persistently exposed to noxious stimuli, and this happens during a critical window of their brain development with peak rates of brain growth, exuberant synaptogenesis and the developmental regulation of specific receptor populations. Nearly two-thirds of infants born at less than 29 weeks' gestation require mechanical ventilation for some duration during the newborn period. These neonates are endotracheally intubated and require repeated endotracheal suctioning. Endotracheal suctioning is identified as one of the most frequent and most painful procedures in premature infants, causing moderate to severe pain. Even with improved nursing performance and standard procedures based on neonatal needs, endotracheal suctioning remains associated with mild pain.", "objectives": "To evaluate the benefits and harms of non-pharmacological interventions for the prevention of pain during endotracheal suctioning in mechanically ventilated neonates. Non-pharmacological interventions were compared to no intervention, standard care or another non-pharmacological intervention.", "selection criteria": "We included randomised controlled trials (RCTs), quasi-RCTs and cluster-RCTs that included term and preterm neonates who were mechanically ventilated via endotracheal tube or via tracheostomy tube and required endotracheal suctioning performed by doctors, nurses, physiotherapists or other healthcare professionals."}, "context": [{"title": "The effect of facilitated tucking during endotracheal suctioning on procedural pain in preterm neonates: a randomized controlled crossover study.", "abstract": "Premature infants not only feel and understand the pain, but also respond more intensively compared with term infants. Non-pharmacological methods of pain control are suitable to relieve pain in painful procedures. The facilitated tucking position is considered as a non-pharmacological method of pain control in infants; however, its impact on frequent and repeated procedural pain such as endotracheal suctioning remains to be studied.\n\nThis paper is the report of a study that examined the impact of facilitated tucking position on behavioral pain during suctioning in premature neonates.\n\nThis was a clinical trial study with a crossover design.\n\nThe study was conducted in a level II Neonatal Intensive Care Unit, located in a teaching hospital, affiliated to Tehran University of Medical Sciences, Tehran, Iran.\n\nThirty four infants were enrolled in this study based on the following inclusion criteria: age between 29 to 37 weeks of gestational age, birth weight 1200 grams or more, having an endotracheal tube, no congenital anomalies, no seizures diagnosis, no chest tubes, no intracranial hemorrhage higher than degree II, not receiving opiates and sedatives four hours before intervention and not receiving any painful procedure at least half an hour before the intervention.\n\nThe samples were randomly received a sequence of suctioning with/without or suctioning without/with facilitated tucking. Preterm Infant Pain Profile (PIPP) was used to collect the data. SPSS version 16.0 for Windows (SPSS Inc., Chicago, IL, USA) was used for statistical analysis.\n\nWhile 38.2% of infants experienced severe pain during suctioning without intervention, only 8.8% of them experienced severe pain during suctioning with intervention. The results of the paired t-test show that there is a statistically significant difference in the mean scores of pain between non-intervention and intervention cases (p < 0.001), and the mean pain score substantially reduced in cases with intervention.\n\nGiven the multiplicity of endotracheal suctioning frequency and the impossibility of frequent use of pharmacological methods of pain relief, the facilitated tucking position can be used as a safe non-pharmacological method for procedural pain management.\u00a0", "PMID": "24999148"}, {"title": "The effect of facilitated tucking position during endotracheal suctioning on physiological responses and coping with stress in premature infants: a randomized controlled crossover study.", "abstract": "Premature infants respond more intensively to pain compared with term infants. Facilitated tucking position as a non-pharmacological method of pain in infants has been suggested; however, its effect on acute procedural pain such as endotracheal suctioning remains to be studied. This study examined the effect of facilitated tucking position during suctioning on physiological responses and coping with stress in premature infants.\n\nThis was a randomized controlled crossover study. Thirty-four premature infants received an order of either suctioning with intervention - suctioning without intervention, or suctioning without intervention - suctioning with intervention. Neonatal Infant Pain Scale (NIPS) was used to collect the data.\n\nNo statistical significant difference was seen between intervention and non-intervention cases in terms of the average time duration to reach the pain score to one or zero, and also, in the average of changes in oxygen saturation. However, changes in heart rate were less in intervention cases.\n\nThe effect of facilitated tucking position on coping with stress was not found in this study. This non-pharmacological strategy can be suggested because of its effect on reducing changes in heart rate during painful procedure. It is suggested to replicate the study with larger number of samples.", "PMID": "24266524"}, {"title": "'Facilitated tucking by parents' in pain management of preterm infants-a randomized crossover trial.", "abstract": "There is a need for a safe and effective non-pharmacological pain management method for preterm infants. The parents could be given an active role in the pain management which may help the parents to cope with the stress related to painful situations of the infant.\n\nTo examine the effectiveness of a method called 'facilitated tucking by parents' (a parent holds the infant in a flexed position) in pain management during endotracheal/pharyngeal suctioning of preterm infants. In addition, the parental perception of the method was studied.\n\nA randomized crossover trial.\n\nTwenty preterm infants with one of their parents participated in the study. Infants' gestational age ranged from 24 to 33 (median 28) weeks and postnatal age from 6 to 37 days (median 15 days).\n\nThe primary outcome was the Neonatal Infant Pain Scale (NIPS) score. Heart rate and oxygen saturation were recorded. Parents completed a questionnaire about their perception of the procedure.\n\nThe highest NIPS score was median 3 (range from 2 to 6) using 'facilitated tucking by parents' and median 5 (range from 2 to 7) without tucking during suctioning (p < 0.001). The infants calmed down more quickly after 'facilitated tucking by parents' (5 s vs. 17 s, p = 0.024). Nineteen out of twenty parents preferred facilitated tucking during suctioning compared to control care.\n\nFacilitated tucking by parents is an effective and safe pain management method during suctioning of preterm infants. This study shows that parents can be given an active role in the pain care of their preterm infants.", "PMID": "16410042"}, {"title": "Endotracheal suctioning in preterm infants using four-handed versus routine care.", "abstract": "To evaluate the effect of four-handed care on preterm infants' physiologic and behavioral responses to and recovery from endotracheal suctioning versus routine endotracheal (ETT) suctioning.\n\nRandomized crossover design with infants as their own controls.\n\nSingle-family-room newborn intensive care unit in an academic health center.\n\nTen intubated infants on conventional ventilation with inline suctioning who were fewer than 37 weeks gestation at birth, and less than one week of age.\n\nEach infant was observed twice on a single day. One observation involved routine ETT suctioning and one involved four-handed care. Physiologic and behavioral response data were collected.\n\nNo differences were noted when comparing baseline heart rate (HR) or oxygen saturation (SpO(2)) data to those obtained during and after suctioning while in the routine care condition. In the four-handed care condition, mean SpO(2) increased from preobservation 95.49 to during observation saturation 97.75 (p = .001). Salivary cortisol levels did not differ between groups at baseline or postsuctioning. No significant difference in behavior state was observed between the two conditions. More stress and defense behaviors occurred postsuctioning when infants received routine care as opposed to four-handed care (p = .001) and more self-regulatory behaviors were exhibited by infants during (p = .019) and after suctioning (p = .016) when receiving four-handed care. No statistical difference was found in the number of monitor call-backs postsuctioning.\n\nFour-handed care during suctioning was associated with a decrease in stress and defense behaviors and an increase in self-regulatory behaviors.", "PMID": "23316894"}, {"title": "Effect of Expressed Breast Milk versus Swaddling versus Oral Sucrose Administration on Pain Associated with Suctioning in Preterm Neonates on Assisted Ventilation: A Randomized Controlled Trial.", "abstract": "The objective of our study was to assess the pain associated with suctioning in preterm neonates on assisted ventilation and comparing the use of expressed breast milk (EBM), sucrose, and swaddling to alleviate pain.\n\nStudy design: A randomized controlled clinical trial.\n\nPreterm neonates on assisted ventilation.\n\nMajor congenital anomalies and severe encephalopathy.\n\n6 months in level III neonatal Intensive Care Unit. In the first phase, we used premature infant pain profile (PIPP) score to assess pain associated with suctioning in preterm neonates on assisted ventilation. In the second phase, the effect of EBM, swaddling, and sucrose on pain relief during suctioning in neonates on assisted ventilation was assessed.\n\nThere was a significant increase in pain associated with suctioning in preterm neonates on assisted ventilation (preprocedure PIPP score 7.90 \u00b1 2.50; procedural PIPP score 13.63 \u00b1 2.57; \n\nSuctioning is painful for preterm neonates on assisted ventilation. There was no difference between EBM, swaddling, and sucrose in relieving pain associated with suctioning.", "PMID": "29123341"}, {"title": "The effect of gentle human touch during endotracheal suctioning on procedural pain response in preterm infant admitted to neonatal intensive care units: a randomized controlled crossover study.", "abstract": "Neonates in the neonatal intensive care unit are frequently subjected to painful procedures. Non-pharmacological pain control techniques are useful for reducing procedural pain. Touch as one of the aspects of developmental care used to reduce neonatal pain. The purpose of this study was to determine the effect of gentle human touch during endotracheal suctioning on procedural pain response in preterm neonates.\n\nThis was a clinical trial study with a crossover design. The study was conducted in a level III NICU in a hospital, affiliated to Iran University of Medical Sciences. Thirty-four neonates were enrolled in this study based on inclusion criteria. The samples were randomly received a sequence of suctioning with/without or suctioning without/with gentle human touch. Preterm Infant Pain Profile (PIPP) was used to collect the data. SPSS version 22 for Windows (SPSS Inc., Chicago, IL, USA) was used for statistical analysis.\n\n85.3% of neonates experienced moderate and 8.8% severe pain during suctioning without intervention, and only 64.7% of them experienced moderate and 2.9% severe pain during suctioning with intervention. The results of the paired \n\nResults from this study showed that the pain due to suctioning procedure is considerably reduced by applying Gentle Human Touch. And nurses can use this method as one of the non-pharmacological methods of pain management.", "PMID": "32316790"}, {"title": "The Effect of Endotracheal Suctioning Using the Four-handed Care on Physiological Criteria and Behavioral Responses of the Preterm Infants: Randomized Crossover Clinical Trial.", "abstract": "", "PMID": "35603088"}, {"title": "Comparison the Effect of Breast Milk Smell, White Noise and Facilitated Tucking Applied to Turkish Preterm Infants During Endotracheal Suctioning on Pain and Physiological Parameters.", "abstract": "This study aimed to determine the effect of the breast milk smell, white noise and facilitated tucking during endotracheal suctioning (ES) on pain and physiological findings.\n\nThe present study was conducted as a randomized, controlled experimental trial study. The sample of the study was composed of a total of 80 preterm infants. Pain was measured with PIPP-R pain scale. rMANOVA and bonferroni tests were used in the comparison of the pain scores of the groups.\n\nIt was determined that white noise and facilitated tucking were more effective in relieving infants before ES procedure (p\u00a0<\u00a0.05). No statistically significant difference was found between the groups in reducing the pain during ES procedure (p\u00a0>\u00a0.05). After the procedure, facilitated tucking was determined more effective in the recovery of preterm infants (p\u00a0<\u00a0.05).\n\nIt is recommended to use facilitated tucking and white noise for decreasing pain of ventilated preterm infants during the ES procedure.\n\nWhite noise and facilitated tucking were effective in relieving pain before procedure and facilitated tucking recovery in preterm infants after the ES procedure.", "PMID": "32690406"}, {"title": "The efficacy of facilitated tucking for relieving procedural pain of endotracheal suctioning in very low birthweight infants.", "abstract": "This study compared the efficacy of a behavioral pain reducing intervention (facilitated tucking) with standard neonatal intensive care unit (NICU) care for decreasing procedural pain (endotracheal suctioning) in very low birthweight (VLBW) infants.\n\nA prospective randomized crossover design with infants as their own controls were used. The sample consisted of 40 VLBW infants, 23-32 weeks gestation, and weighing 560-1498 g with tracheal intubation. The infants were observed twice during each endotracheal suctioning experience; one suctioning was done according to normal nursery routine; another was done using facilitated tucking (the caregiver \"hand-swaddling\" the infant by placing a hand on the infant's head and feet while providing flexion and containment). The Premature Infant Pain Profile (PIPP) measured the infant's pain response, and severity of illness of each infant was measured by the Score for Neonatal Acute Physiology (SNAP) and the NTISS (Neonatal Therapeutic Intervention Scoring System). Repeated measures analysis of variance (RMANOVA) determined the efficacy of facilitated tucking for reducing procedural pain (PIPP) and the effects of order of intervention vs. control. Regression analyses examined the relationship of gestational age, severity of illness, and number of painful procedures to the pain response.\n\nThere was a significant difference between the PIPP scores for tucking and nontucking positions (p = 0.001) and a nonsignificant interaction with order (p = 0.64) as well as a nonsignificant main effect for order (p = 0.46). In the regression analyses, all predictors taken together did not significantly predict PIPP scores in the tucked position (p = 0.11) or nontucked position (p = 0.57).\n\nFacilitated tucking is a developmentally sensitive, nonpharmacological comfort measure that can relieve procedural pain in VLBW infants. Nurses need to be increasingly aware of infant pain during daily care taking, and to use validated pain assessment instruments. Further clinical research on individual pain assessment is needed for better understanding of the quality and significance of pain for each infant, and the factors that affect pain expression.", "PMID": "15123970"}], "labels": [{"PMID": "24999148", "label": "included"}, {"PMID": "24266524", "label": "included"}, {"PMID": "16410042", "label": "included"}, {"PMID": "23316894", "label": "included"}, {"PMID": "29123341", "label": "included"}, {"PMID": "32316790", "label": "included"}, {"PMID": "35603088", "label": "included"}, {"PMID": "32690406", "label": "included"}, {"PMID": "15123970", "label": "included"}]}
{"metadata": {"review_pmid": "38226724"}, "inputs": {"background": "Hip and knee replacement surgery is a well-established means of improving quality of life, but is associated with a significant risk of bleeding. One-third of people are estimated to be anaemic before hip or knee replacement surgery; coupled with the blood lost during surgery, up to 90% of individuals are anaemic postoperatively. As a result, people undergoing orthopaedic surgery receive 3.9% of all packed red blood cell transfusions in the UK. Bleeding and the need for allogeneic blood transfusions has been shown to increase the risk of surgical site infection and mortality, and is associated with an increased duration of hospital stay and costs associated with surgery. Reducing blood loss during surgery may reduce the risk of allogeneic blood transfusion, reduce costs and improve outcomes following surgery. Several pharmacological interventions are available and currently employed as part of routine clinical care.", "objectives": "To determine the relative efficacy of pharmacological interventions for preventing blood loss in elective primary or revision hip or knee replacement, and to identify optimal administration of interventions regarding timing, dose and route, using network meta-analysis (NMA) methodology.", "selection criteria": "We included RCTs of people undergoing elective hip or knee surgery only. We excluded non-elective or emergency procedures, and studies published since 2010 that had not been prospectively registered (Cochrane Injuries policy). There were no restrictions on gender, ethnicity or age (adults only). We excluded studies that used standard of care as the comparator. Eligible interventions included: antifibrinolytics (tranexamic acid (TXA), aprotinin, epsilon-aminocaproic acid (EACA)), desmopressin, factor VIIa and XIII, fibrinogen, fibrin sealants and non-fibrin sealants."}, "context": [{"title": "Use of fibrin sealant to reduce bloody drainage and hemoglobin loss after total knee arthroplasty: a brief note on a randomized prospective trial.", "abstract": "A phase-III trial that included fifty-three patients undergoing unilateral primary total knee arthroplasty with cement was conducted to investigate the hemostatic efficacy of fibrin sealant.\n\nFollowing cementing of the joint, 10 mL of fibrin sealant was sprayed onto the wound before tourniquet deflation and wound closure. No placebo was used in the control group. All patients received drains.\n\nWithin twelve hours after the surgery, the amount of bloody drainage was 184.5 +/- 28.9 mL (mean and standard error) in the fibrin-sealant group (information available for twenty-three patients) and 408.3 +/- 54.6 mL in the control group (information available for twenty-three patients) (p = 0.002, after adjustment for variance in the time that the drainage was measured). On the first postoperative day, the hemoglobin level had decreased by 20.1 +/- 2.1 g/L in the fibrin-sealant group (information available for twenty-two patients) and by 27.3 +/- 2.1 g/L in the control group (information available for twenty-four patients). After adjustment for baseline values, the decrease in the hemoglobin level was 28.9% less in the fibrin-sealant group than in the control group (p = 0.005, 95% confidence limits = 10.2, 43.7). There were no seroconversions in the fibrin-sealant group.\n\nThese results suggest that fibrin sealant can safely reduce bloody drainage following total knee arthroplasty while maintaining higher hemoglobin levels.", "PMID": "11679600"}, {"title": "[Aprotinin (Antilysin Spofa)--its effect on decreasing hemorrhage in the postoperative period in hip arthroplasty].", "abstract": "Aprotinin is a non-specific inhibitor of serine proteases with hemostyptic and hemostatic properties. The effect covers suppression of fibrinolysis and support of the role of thrombocytes in coagulation. In a prospective randomized study we verified whether the application of aprotinin (Antilysin Spofa, Czech Republic) in the dosage effective in cardiosurgical patients reduces blood loss and the need for blood transfusion for orthopaedic patients.\n\n42 patients indicated to the primary THA were randomly selected into the study and control groups. Excluded were allergic patients and those who used aprotinin before.\n\nAdministration of 2.10(6) KIU of aprotinin was started preoperatively and is continued in the course of the first hour of surgery. In the operated on patients we recorded prior to operation and in the first post-operative morning the level of hemoglobin in blood and hematocrit, the number of infusions and blood transfusion units administered in the course of the surgery and in the post-operative period until the first post-operative morning. We recorded blood loss in the period between the surgery and the first post-operative morning. Data acquired in the patients of the studied and control groups were compared by means of ANOVA test for repeated measuring and with the use of Mann-Whitney and chi 2-test, the level of significance p < or = 0.05. During the hospitalization we the patients were checked for symptoms of deep venous trombosis and tromboembolic or other adverse events.\n\nHemoglobinemia and hematocrit in both groups significantly decreased after the operation (p < 0.0005), the differences between the studied and control groups were not significant. The number of administered blood units did not differ in the examined and control groups. The frequency of blood transfusions was postoperatively higher in the control group (59.1% as compared to 30%), however, the difference was not statistically significant (p = 0.059). Blood loss in the post-operative period was higher in the control group (p = 0.048). Patients from the control group got in total blood transfusion more frequently (p = 0.032). Differences in the total frequency of blood transfusion and in the amount of post-operative blood loss were statistically significant. In the course of hospitalisation no signs of deep phlebothrombosis or thromboembolic condition were encountered in either group of patients. Complications were not recorded.\n\nOur results correspond with most of the published data. Blood loss of the operated on patients who were administered prior to and at the beginning of the operation in total 2.10(6) KIU of aprotinin (Antilysin Spofa) in infusion was on average by 33% less in the post-operative period and in the whole peropetive period they required less frequently blood transfusion (40% vs 73%).\n\nInfusion of aprotinin (Antilysin Spofa) in the dosage of the order of 106 KIU significantly reduces post-operative blood loss and frequency of transfusion in the peroperative period in patients undergoing THA.", "PMID": "11759474"}, {"title": "Aprotinin versus placebo in major orthopedic surgery: a randomized, double-blinded, dose-ranging study.", "abstract": "We conducted a prospective, multicenter, double-blinded, dose-ranging study to compare the risk/benefit ratio of large- and small-dose aprotinin with placebo after major orthopedic surgery. Fifty-eight patients were randomized into three groups: Large-Dose Aprotinin (4 M kallikrein inactivator unit [KIU] bolus before surgery followed by a continuous infusion of 1 M KIU/h until the end of surgery), Small-Dose Aprotinin (2 M KIU bolus plus 0.5 M KIU/h), and Placebo. Bleeding was measured and calculated. Bilateral ascending venography was systematically performed on the third postoperative day. Measured and calculated blood loss decreased in the Large-Dose Aprotinin group (calculated bleeding, whole blood, hematocrit 30%, median [range], 2,023 mL [633-4,113] as compared with placebo, 3,577 mL [1,670-21,758 mL]). The total number of homologous and autologous units was also significantly decreased in the Large-Dose Aprotinin group (2 U [0-5 U] as compared with placebo, 4 U [0-42 U]). No increase in deep vein thrombosis or pulmonary embolism was observed in the aprotinin groups. Large-dose aprotinin was safe and effective in dramatically reducing the measured and calculated bleeding and the amount of transfused red blood cell units after major orthopedic surgery.\n\nLarge doses of aprotinin decrease blood loss and transfusion amount in major orthopedic surgery.", "PMID": "12145035"}, {"title": "Antifibrinolytic therapy and perioperative blood loss in cancer patients undergoing major orthopedic surgery.", "abstract": "Aprotinin has been reported to reduce blood loss and transfusion requirements in patients having major orthopedic operations. Data on whether epsilon amino-caproic acid (EACA) is effective in this population are sparse.\n\nSixty-nine adults with malignancy scheduled for either pelvic, extremity or spine surgery during general anesthesia entered this randomized, double-blind, placebo-controlled trial, and received either intravenous aprotinin (n = 23), bolus of 2 x 10(6) kallikrein inactivator units (KIU), followed by an infusion of 5 x 10(5) KIU/h, or EACA (n = 22), bolus of 150 mg/kg, followed by a 15 mg/kg/h infusion or saline placebo (n = 24) during surgery. Our goal was to determine whether prophylactic EACA or aprotinin therapy would reduce perioperative blood loss (intraoperative + first 48h) >30% when compared to placebo.\n\nThe mean age of the study population was 52 +/- 17 yr. The groups did not differ in age, duration of surgery, perioperative blood loss or number of packed erythrocyte units transfused. When compared to the placebo group, the two treated groups had a significantly lower D-Dimer level immediately after surgery, P < 0.01.\n\nUnder the conditions of this study, we were unable to find a clinical benefit to using aprotinin or EACA to reduce perioperative blood loss or transfusion requirements during major orthopedic surgery in cancer patients.", "PMID": "12552190"}, {"title": "Experience improves successful use of fibrin sealant in total knee arthroplasty: implications for surgical education.", "abstract": "This study evaluating fibrin sealant application in total knee arthroplasty (TKA) found significant differences in the decline in adjusted hemoglobin loss at 48 hours postoperatively in the treatment group (FS) relative to the control group (C) when the groups were segregated into early and late subgroups. The decline between the late C, 3.53 +/- 0.22 g/dL, and the late FS, 3.01 +/- 0.20 g/dL, was 0.52 g/dL (p = 0.04). The decline between the early C, 3.51 +/- 0.21 g/dL, and the early FS, 3.25 +/- 0.22 g/dL, was 0.26 g/dL (p = 0.34). This study demonstrates the importance of experience and education in successful application of tissue adhesives.", "PMID": "14649577"}, {"title": "A pilot study of the effects of Vivostat patient-derived fibrin sealant in reducing blood loss in primary hip arthroplasty.", "abstract": "A pilot study evaluated the effectiveness of Vivostat patient-derived fibrin sealant in reducing blood loss in patients who underwent primary hip arthroplasty. Eighty adult patients undergoing elective surgery were randomized to receive either Vivostat sealant or control (no additional hemostatic treatment). Patients allocated Vivostat sealant donated 120 mL of blood, which was then processed perioperatively to produce a fibrin sealant that was applied to the bleeding wound surfaces just before closure. Transfusion requirements, blood loss during surgery, drain volumes, and daily hematocrit and hemoglobin levels were measured. Hospitalization times, adverse events, and postoperative wound complications were also monitored. Blood loss during surgery and wound drainage volume was lower in the Vivostat group than in the control group, although the differences were not significantly different. Transfusion requirements (median, 270 mL of packed red blood cells) and hospitalization times (both median 7 days) were the same for both groups. No adverse events related to the use of Vivostat occurred. There were indications of a possible reduction in the incidence of postoperative wound oozing (15% vs 25%) and hematomas (6% vs 11%) with the use of Vivostat compared with the control group, although differences were not statistically significant. In conclusion, in this pilot study, use of Vivostat patient-derived fibrin in hip arthroplasty was not associated with a significant reduction in blood loss. Further studies, with larger numbers of patients, may be warranted to investigate a possible benefit of Vivostat in reducing postoperative wound complications.", "PMID": "16959690"}, {"title": "[Does aprotinin lessen intraoperative blood loss?].", "abstract": "", "PMID": "1716471"}, {"title": "The effect of an intravenous bolus of tranexamic acid on blood loss in total hip replacement.", "abstract": "Tranexamic acid is a fibrinolytic inhibitor which reduces blood loss in total knee replacement. We examined the effect on blood loss of a standardised intravenous bolus dose of 1 g of tranexamic acid, given at the induction of anaesthesia in patients undergoing total hip replacement and tested the potential prothrombotic effect by undertaking routine venography. In all, 36 patients received 1 g of tranexamic acid, and 37 no tranexamic acid. Blood loss was measured directly per-operatively and indirectly post-operatively. Tranexamic acid reduced the early post-operative blood loss and total blood loss (p = 0.03 and p = 0.008, respectively) but not the intraoperative blood loss. The tranexamic acid group required fewer transfusions (p = 0.03) and had no increased incidence of deep-vein thrombosis. The reduction in early post-operative blood loss was more marked in women (p = 0.05), in whom this effect was dose-related (r = -0.793). Our study showed that the administration of a standardised pre-operative bolus of 1 g of tranexamic acid was cost-effective in reducing the blood loss and transfusion requirements after total hip replacement, especially in women.", "PMID": "19483232"}, {"title": "The effect of desmopressin on blood loss in patients with rheumatoid arthritis undergoing hip arthroplasty.", "abstract": "Blood loss is an important issue for patients with rheumatoid arthritis undergoing hip surgery. We hypothesised that intraoperative desmopressin treatment would result in a reduction in blood loss in rheumatoid patients undergoing total hip arthroplasty.\n\nSeventy-five patients scheduled for elective total hip arthroplasty were randomised to three groups to receive 0.4 microg/kg desmopressin (D 0.4), 0.2 microg/kg desmopressin (D 0.2) or placebo intraoperatively in a double-blind fashion. Blood transfusions were based on calculated safe allowable blood loss and haemoglobin measurements (trigger 90 g/l, 5.59 mmol/l). The primary endpoint was the total blood loss measured till the end of the fourth post-operative day. Secondary endpoints included red cell transfusion requirements and haemoglobin.\n\nTotal blood loss during the study period was not significantly different between the groups (D 0.4 1829 +/- 1068; D 0.2 2240 +/- 843 and placebo 2254 +/- 1040 ml; P= 0.50). The total amount of red cell transfusions was fewer in group D 0.4 (3.6 +/- 1.6 U) when compared with D 0.2 (4.4 +/- 1.7 U; P=0.009) and placebo (4.5 +/- 2.0 U; P= 0.011) groups. Haemoglobin concentration was lower in the placebo group in the first (5.42 +/- 1.16 vs. 5.98 +/- 0.47 mmol/l; P=0.033) and the second (6.28 +/- 0.66 vs. 6.69 +/- 0.47 mmol/l; P=0.033) post-operative mornings compared with group D 0.4.\n\nDespite a lack of difference in the primary outcome, total blood loss, intraoperative administration of 0.4 microg/kg desmopressin resulted in fewer total red cell transfusion requirements in rheumatoid patients undergoing total hip arthroplasty when compared with 0.2 microg/kg treatment and placebo.", "PMID": "20546209"}, {"title": "Topical application of tranexamic acid reduces postoperative blood loss in total knee arthroplasty: a randomized, controlled trial.", "abstract": "Topical application of tranexamic acid to bleeding wound surfaces reduces blood loss in patients undergoing some major surgeries, without systemic complications. The objective of the present trial was to assess the efficacy and safety of the topical application of tranexamic acid on postoperative blood loss in patients undergoing primary unilateral total knee arthroplasty with cement.\n\nIn a prospective, double-blind, placebo-controlled trial, 124 patients were randomized to receive 1.5 or 3.0 g of tranexamic acid in 100 mL of normal saline solution or an equivalent volume of placebo (normal saline solution) applied into the joint for five minutes at the end of surgery. The primary outcome was blood loss calculated from the difference between the preoperative hemoglobin level and the corresponding lowest postoperative value or hemoglobin level prior to transfusion. The safety outcomes included Doppler ultrasound in all patients and measurement of plasma levels of tranexamic acid one hour after release of the tourniquet.\n\nTwenty-five patients were withdrawn for various reasons; therefore, ninety-nine patients were included in the intention-to-treat analysis. The postoperative blood loss was reduced in the 1.5 and 3-g tranexamic acid groups (1295 mL [95% confidence interval, 1167 to 1422 mL] and 1208 mL [95% confidence interval, 1078 to 1339 mL], respectively) in comparison with the placebo group (1610 mL [95% confidence interval, 1480 to 1738 mL]) (p < 0.017). The postoperative hemoglobin levels were higher in the 1.5 and 3.0-g tranexamic acid groups (10.0 g/dL [95% confidence interval, 9.5 to 10.4 g/dL] and 10.1 g/dL [95% confidence interval, 9.8 to 10.5 g/dL], respectively) in comparison with the placebo group (8.6 g/dL [95% confidence interval, 8.2 to 9 g/dL]) (p < 0.017). With the numbers studied, there was no difference in the rates of deep-vein thrombosis or pulmonary embolism between the three groups. Minimal systemic absorption of tranexamic acid was observed.\n\nAt the conclusion of a total knee arthroplasty with cement, topical application of tranexamic acid directly into the surgical wound reduced postoperative bleeding by 20% to 25%, or 300 to 400 mL, resulting in 16% to 17% higher postoperative hemoglobin levels compared with placebo, with no clinically important increase in complications being identified in the treatment groups.", "PMID": "21048170"}], "labels": [{"PMID": "11679600", "label": "excluded"}, {"PMID": "11759474", "label": "excluded"}, {"PMID": "12145035", "label": "excluded"}, {"PMID": "12552190", "label": "excluded"}, {"PMID": "14649577", "label": "excluded"}, {"PMID": "16959690", "label": "excluded"}, {"PMID": "1716471", "label": "excluded"}, {"PMID": "19483232", "label": "excluded"}, {"PMID": "20546209", "label": "excluded"}, {"PMID": "21048170", "label": "excluded"}]}
{"metadata": {"review_pmid": "38226663"}, "inputs": {"background": "Pilonidal sinus disease is a common and debilitating condition. Surgical treatment remains the mainstay for managing chronic disease, with options including midline and off-midline wound closure methods. However, the optimal approach remains uncertain. Recent developments in tension-free midline techniques require further exploration.", "objectives": "To assess the effects of midline and off-midline wound closure methods for pilonidal sinus, and to determine the optimal off-midline flap procedures.", "selection criteria": "We included parallel RCTs involving participants undergoing midline closure without flap techniques and off-midline closure for pilonidal sinus treatment. We excluded quasi-experimental studies and studies that enroled participants presenting with an abscess."}, "context": [{"title": "Treatment of pilonidal sinus by primary closure with a transposed rhomboid flap compared with deep suturing: a prospective randomised clinical trial.", "abstract": "To assess two techniques of primary closure after excision of pilonidal sinus.\n\nProspective randomised study.\n\nUniversity department of surgery, United Arab Emirates.\n\n46 patients with chronic pilonidal sinus disease, 24 treated by rhomboid flap transposition, and 22 by deep suturing technique.\n\nEarly mobility and recurrence.\n\nAll patients in the rhomboid flap transposition group healed their wounds primarily compared with 17 in the primary deep suturing group (77%). (P = 0.02). Five patients wounds broke down as a result of haematoma and infection (23%). The mean hospital stay for the rhomboid flap technique was 6 days compared with 9 days after deep suturing, and the mean follow up for both groups was 18 months, the rhomboid flap group returned to work a mean of nine days earlier than the deep suturing group (23 days). No recurrence has been identified yet in the rhomboid flap group, while 2 recurrences have developed in the deep suturing group (9%).\n\nPrimary closure after excision of pilonidal sinus with a transposed rhomboid flap is successful in the management of pilonidal sinus and is superior to primary closure by deep suturing.", "PMID": "10391165"}, {"title": "Randomized clinical trial comparing primary closure with the Limberg flap in the treatment of primary sacrococcygeal pilonidal disease.", "abstract": "The purpose of the study was to compare the outcome of excision and primary closure with that of rhomboid excision and the Limberg flap procedure in patients with primary sacrococcygeal pilonidal disease (SPD).\n\nTwo hundred consecutive patients with SPD were randomly allocated to undergo either excision and primary closure (group 1, n = 100) or rhomboid excision and the Limberg flap procedure (group 2, n = 100). Duration of operation, postoperative pain, time to first mobilization, length of hospital stay, postoperative complications, time to resumption of work, recurrence and time to recurrence were recorded for all patients.\n\n: Duration of operation was longer in group 2 than in group 1 (P = 0.001). However, postoperative pain was less (P < 0.001), mobilization earlier (P < 0.001), duration of hospital stay shorter (P < 0.001), time to resumption of work shorter (P < 0.001) and postoperative complications fewer (P < 0.001) in group 2. During a median follow-up of 28 months, no recurrence was detected in patients in group 2 versus 11 patients in group 1 (P = 0.001).\n\nBecause of its low complication rate and acceptable long-term results, rhomboid excision and the Limberg flap procedure is preferable to simple excision and primary closure in the treatment of SPD.", "PMID": "16078300"}, {"title": "Does technique alter quality of life after pilonidal sinus surgery?", "abstract": "Pilonidal sinus is a common disease in young adults that carries high postoperative morbidity and patient discomfort. Controversy still exists about the best surgical technique for the treatment of the disease in terms of recurrence rate and patient discomfort.\n\nFrom January 2000 to November 2003, 100 consecutive age- and sex-matched patients with chronic pilonidal sinus disease were randomized to receive surgical treatment in the forms of either excision and primary closure or rhomboid excision and Limberg flap. Time to return to work and to complete healing were recorded. To evaluate quality of life and patient comfort, all patients were asked to complete a questionnaire including short form 36, Visual Analogue Scale, time to sitting on toilet without pain, and time to walking without pain 3 months after surgery.\n\nEach group was composed of 50 patients. Mean follow-up was 19 months. There was a significant difference between the groups in terms of length of hospital stay (P=.005), time to complete healing (P<.001), time off work (P<.001), and wound infection rate (P=.03). Statistically significant differences were noted between the groups in items of general health perception (71.1+/-11.7 vs 78.2+/-14.1; P=.008), social functioning (87.3+/-32.8 vs 110.4+/-33.8; P=.001), and pain (54.5+/-14.0 vs 67.5+/-18.4; P<.001). Times to sitting on toilet and walking without pain showed significant differences between the groups (P=.006 and P<.001, respectively). The mean postoperative Visual Analogue Scale scores were 6.5+or= 1.7 and 7.4+/- 1.4, respectively (P<.001).\n\nShorter hospital stay, earlier healing, shorter time off work, lower ratio of complications, lower pain perception, and improved general health perception are the main advantages of te Limberg flap technique in pilonidal sinus surgery. All together, these parameters add to patient comfort and satisfaction after surgical treatment.", "PMID": "16105524"}, {"title": "Multicenter prospective randomized trial comparing modified Limberg flap transposition and Karydakis flap reconstruction in patients with sacrococcygeal pilonidal disease.", "abstract": "There is still no consensus as to the optimal treatment for sacrococcygeal pilonidal disease (SPD). Many recommend off-midline closure, if any excisional procedure is to be selected.\n\nThe authors prospectively studied 145 patients with SPD who presented at 3 hospitals. Patients were randomly assigned to undergo either modified Limberg flap (MLF) transposition (n = 72) or Karydakis flap reconstruction (n = 73). Surgical findings, complications, recurrence rates, and degree of patient satisfaction, evaluated via a standardized telephone interview, were compared.\n\nOperation time was longer in the MLF group. There were no significant differences between the two groups in terms of complication rate, length of stay, or recurrence rate. Patients in the Karydakis group reported feeling completely healed more quickly postoperatively. The two groups reported similar rates of satisfaction. Mandatory patient withdrawal from a given study arm because of the orifice straying from the midline occurred more frequently in the Karydakis group.\n\nThe MLF technique and the Karydakis procedure appear to generate comparable outcomes. With laterally situated orifices, however, the applicability of the Karydakis method may be limited.", "PMID": "20122682"}, {"title": "Randomized comparison of Limberg flap versus modified primary closure for the treatment of pilonidal disease.", "abstract": "The best surgical technique for sacrococcygeal pilonidal disease is still controversial. The aim of this randomized prospective trial was to compare both the results of Limberg flap procedure and primary closure.\n\nA total of 260 patients with sacrococcygeal pilonidal disease were assigned randomly to undergo Limberg flap procedure or tension-free primary closure.\n\nSuccess of surgery was achieved in 84.62% of Limberg flap patients versus 77.69% of primary closure (P = .0793). Surgical time for primary closure was shorter. Wound infection was more frequent in the primary closure group (P = .0254), which experienced less postoperative pain (P < .0001). No significant difference was found in time off from work (P = .672) and wound dehiscence. Recurrence was observed in 3.84% versus 0% in the primary closure versus Limberg flap group (P = .153).\n\nOur results do not show a clear benefit for surgical management by Limberg flap or primary closure. Limberg flap showed less convalescence and wound infection; our technique of tension-free primary closure was a day case procedure, less painful, and shorter than Limberg flap.", "PMID": "20637332"}, {"title": "Superiority of asymmetric modified Limberg flap for surgical treatment of pilonidal disease.", "abstract": "Cases treated surgically using wide excision plus classic Limberg flap or wide excision plus asymmetric modified Limberg flap were compared with respect to complications and patient comfort in the postoperative period.\n\nIn this prospective, randomized study, 68 of 70 patients were followed for a mean of 29.22 (range, 6-44) months after wide excision plus classic Limberg flap (Group 1, n=35) and after asymmetric modified Limberg flap closure (Group 2, n=33).\n\nThere were significantly more macerations in Group 1 (P<0.001). All macerations were detected on the lower part of the incision left on the intergluteal sulcus, and infections occurred subsequent to maceration. The infection rate was statistically higher in Group 1 than in Group 2 (P=0.028). We noted that as a result of these complications, time to suture removal (P=0.001), discharge from hospital (P=0.001), and time off from work (P=0.001) were significantly longer for Group 1 than for Group 2. There were two recurrences in the inferior part of the suture line in Group 1 and none in Group 2, which showed no statistical difference (P=0.493).\n\nThe deep intergluteal sulcus and midline gap were slightly flattened over the anococcygeal region. The vacuum effect was decreased, and there were less macerations and fewer infections. Time off from work and discharge time from hospital were shortened by eliminating the moisture effect and reducing complications by lateralizing the lower part of the suture line.", "PMID": "16322964"}, {"title": "Comparison of the short-term results after Limberg and Karydakis procedures for pilonidal disease: randomized prospective analysis of 100 patients.", "abstract": "The study was designed to compare the early postoperative results of the commonly used two surgical flap procedures in pilonidal disease: Karydakis and Limberg.\n\nOne hundred patients were randomized into two groups and standard Limberg or Karydakis procedures were performed. All had primary sinus orifices. Infected cases and the ones with secondary orifices over 2 cm distant from primary were excluded. Data were recorded concerning complications, need for analgesia and wound dressing, periods of time off work and off driving. Patients were asked to classify their first defecation manner after the operation and also pain according to a Visual Analogue Scale with range of 1-10.\n\nThere was a significantly higher wound infection rate in the Karydakis group than in the Limberg group (13/50 and 4/50 respectively). This also resulted in significantly higher values for wound dressings and need for analgesia. The time off work and off driving and also the Visual Analogue Scale scores were not significantly different between the two groups.\n\nBoth procedures can be safely performed in pilonidal disease with a standard length of stay in hospital and a similar loss of productive power. However, the Karydakis flap seems to have a significant higher infection rate and this probably increases the cost.", "PMID": "18637924"}, {"title": "Short and long-term results of the Karydakis flap versus the Limberg flap for treating pilonidal sinus disease: a prospective randomized study.", "abstract": "Pilonidal sinus is a common disease that mostly affects young people. Although various surgical techniques have been described for treating sacrococcygeal pilonidal disease (SPD), controversy still exists as to the best surgical technique. The purpose of this study was to compare the efficiency and short-term and long-term results of the Karydakis flap with that of the Limberg flap for treating SPD.\n\nIn this prospective randomized study, 269 patients with SPD were recruited to undergo either the Karydakis flap (n = 135) or the Limberg flap (n = 134) procedure between September 2004 and September 2008.\n\nThe mean operative time for the Karydakis group (42.32 \u00b1 8.64 minutes) was shorter than that for the Limberg group (50.14 \u00b1 6.96 minutes) (P = .01). The complication rate for the Karydakis group (n = 15 [11.1%]) was lower than that for the Limberg group (n = 28 [20.8%]) (P = .029). The visual analogue scale score for postoperative pain at the operation site on the 30th day was lower in the Karydakis group than in the Limberg group (2.22 \u00b1 1.01 vs 3.23 \u00b1 1.14, P = .01). The visual analogue scale score for satisfaction with the cosmetic appearance of the scars in the Karydakis group was 7.08 \u00b1 1.75, whereas it was 3.16 \u00b1 1.40 in the Limberg group at the 3rd month (P = .01). Length of hospital stay was significantly shorter in the Karydakis group than in the Limberg group (3.40 \u00b1 .94 vs 3.8 \u00b1 1.19 days, P = .03). Only 4 patients in the Karydakis group developed recurrence (3%), whereas 9 patients (6.9%) did so in the Limberg group (P = .151).\n\nThe Karydakis flap procedure should be chosen instead of the Limberg flap for treating uncomplicated SPD because of its lower postoperative complication rate, lower pain scores, shorter operation time and length of hospital stay, and good cosmetic satisfaction. However, no differences existed between the 2 surgical procedures in terms of recurrence prevention.", "PMID": "21788003"}, {"title": "Comparison of modified Limberg flap and Karydakis flap operations in pilonidal sinus surgery: prospective randomized study.", "abstract": "The best surgical technique for pilonidal sinus disease (PSD) is still disputed. The objective of this prospective randomized study is to compare the short and long-term results of modified Limberg flap and Karydakis flap surgeries that have been widely used in recent years. Ninety one patients were included in the study. The patients were divided into two groups: modified Limberg flap (MLF; n = 46) and Karydakis flap (KF; n = 45). Preoperative findings of the patients, their surgical findings, and short and long-term postoperative findings were recorded and statistically compared. While no significant difference was discovered between the groups in terms of postoperative analgesic need, hospital stay, postoperative infection rate, drain stay time, painless sitting time, painless toilet-sitting time, and painless walking time, return to work or school time was shorter in the MLF group compared with the KF group (20.61 \u00b1 7.89 days, 23.29 \u00b1 6.42, respectively; P < 0.05). Cosmetically, the visual analog scale (VAS) of the KF group was significantly higher than that of the MLF group (VAS score 7.12 \u00b1 1.28, 5.45 \u00b1 1.77, respectively; P < 0.05). Considering recurrence rates, no statistically significant difference was found between the groups. Our study found out that short and long-term results of the MLF and KF procedures are similar. We believe both methods can be safely used in surgical PSD treatment given that in the MLF procedure, shorter return-to-work time is achieved, while the procedure provides better cosmetic results. ", "PMID": "26011208"}, {"title": "Early results with the Mutaf technique: a novel off-midline approach in pilonidal sinus surgery.", "abstract": "The objective of the present study was to compare different off-midline techniques in terms of their advantages and disadvantages.\n\nA total of 81 patients were included in this prospective, controlled, randomized study. Patients in group 1 were treated with the Limberg flap, and patients in group 2 were treated with Mutaf technique. Patients were followed up for 9 months postsurgically and assessed at regular intervals.\n\nA total of 41 and 40 patients received surgical treatment with Limberg or Mutaf techniques, respectively. The 2 groups were similar in terms of age, gender, body mass index, and Tezel pilonidal sinus classification. Also, the 2 groups were comparable with regard to the frequency of preoperative discharge from the wound site, history of abscess formation, and the resultant antibiotic use. Early results showed similar recurrence rates and surgical-site complications between the 2 groups. Although a lower visual analogue scale score was found in group 2 at postoperative day 1, seroma persistence, time to withdrawal of surgical drains, and wound healing were more prolonged.\n\nIn this study, Mutaf technique was comparable to Limberg flap in the treatment of pilonidal sinus. Therefore, Mutaf technique may be offered as a viable surgical therapeutic option among off-midline closure approaches.", "PMID": "27186571"}], "labels": [{"PMID": "10391165", "label": "included"}, {"PMID": "16078300", "label": "included"}, {"PMID": "16105524", "label": "included"}, {"PMID": "20122682", "label": "included"}, {"PMID": "20637332", "label": "included"}, {"PMID": "16322964", "label": "excluded"}, {"PMID": "18637924", "label": "excluded"}, {"PMID": "21788003", "label": "excluded"}, {"PMID": "26011208", "label": "excluded"}, {"PMID": "27186571", "label": "excluded"}]}
{"metadata": {"review_pmid": "38224135"}, "inputs": {"background": "Clinical practice guidelines recommend testosterone replacement therapy (TRT) for men with sexual dysfunction and testosterone deficiency. However, TRT is commonly promoted in men without testosterone deficiency and existing trials often do not clearly report participants' testosterone levels or testosterone-related symptoms. This review assesses the potential benefits and harms of TRT in men presenting with complaints of sexual dysfunction.", "objectives": "To assess the effects of testosterone replacement therapy compared to placebo or other medical treatments in men with sexual dysfunction.", "selection criteria": "We included randomized controlled trials (RCTs) in men (40 years or over) with sexual dysfunction. We excluded men with primary or secondary hypogonadism. We compared testosterone or testosterone with phosphodiesterase-5 inhibitors (PDEI5I) to placebo or PDE5I alone."}, "context": [{"title": "Dehydroepiandrosterone in the treatment of erectile dysfunction: a prospective, double-blind, randomized, placebo-controlled study.", "abstract": "In 1994, the Massachusetts Male Aging Study presented an inverse correlation of the serum levels of dehydroepiandrosterone (DHEA) and the incidence of erectile dysfunction (ED). We evaluated the efficacy of DHEA replacement in the treatment of ED in a prospective, double-blind, randomized, placebo-controlled study.\n\nThe inclusion criteria included ED, normal physical and neurologic examinations, serum levels of testosterone, dihydrotestosterone, prolactin, and prostate-specific antigen (PSA) within the normal range, and a serum DHEA sulfate level below 1.5 micromol/L. Also all patients had a full erection after a pharmacologic erection test with 10O microg prostaglandin E1; pharmacocavernosography showed no visualization in corporeal venous structures. Forty patients from our impotence clinic were recruited and randomly divided into two groups of 20 patients each. Group 1 was treated with an oral dose of 50 mg DHEA and group 2 with a placebo one time a day for 6 months. The International Index of Erectile Function (IIEF), a 15-item questionnaire, was used to rate the success of this therapy.\n\nTherapy response was defined as the ability to achieve or maintain an erection sufficient for satisfactory sexual performance according to the National Institutes of Health Consensus Development Panel on Impotence. DHEA treatment was associated with higher mean scores for all five domains of the IIEF. There was no impact of DHEA treatment on the mean serum levels of PSA, prolactin, testosterone, the mean prostate volume, and the mean postvoid residual urine volume.\n\nOur results suggest that oral DHEA treatment may be of benefit in the treatment of ED. Although our patient data base is too small to do relevant statistical analysis, we believe that our data show a biologically obvious trend that justifies further extended studies.", "PMID": "10096389"}, {"title": "The effects of transdermal dihydrotestosterone in the aging male: a prospective, randomized, double blind study.", "abstract": "The objective of the study was to investigate the effects of dihydrotestosterone (DHT) gel on general well-being, sexual function, and the prostate in aging men. A total of 120 men participated in this randomized, placebo-controlled study (60 DHT and 60 placebo). All subjects had nocturnal penile tumescence once per week or less, andropause symptoms, and a serum T level of 15 nmol/liter or less and/or a serum SHBG level greater than 30 nmol/liter. The mean age was 58 yr (range, 50-70 yr). Of these subjects, 114 men completed the study. DHT was administered transdermally for 6 months, and the dose varied from 125-250 mg/d. General well-being symptoms and sexual function were evaluated using a questionnaire, and prostate symptoms were evaluated using the International Prostate Symptoms Score, transrectal ultrasonography, and assay of serum prostate-specific antigen. Early morning erections improved transiently in the DHT group at 3 months of treatment (P < 0.003), and the ability to maintain erection improved in the DHT group compared with the placebo group (P < 0.04). No significant changes were observed in general well-being between the placebo and the DHT group. Serum concentrations of LH, FSH, E2, T, and SHBG decreased significantly during DHT treatment. Treatment with DHT did not affect liver function or the lipid profile. Hemoglobin concentrations increased from 146.0 +/- 8.2 to 154.8 +/- 11.4 g/liter, and hematocrit from 43.5 +/- 2.5% to 45.8 +/- 3.4% (P < 0.001). Prostate weight and prostate-specific antigen levels did not change during the treatment. No major adverse events were observed. Transdermal administration of DHT improves sexual function and may be a useful alternative for androgen replacement. As estrogens are thought to play a role in the pathogenesis of prostate hyperplasia, DHT may be beneficial, compared with aromatizing androgens, in the treatment of aging men.", "PMID": "11932266"}, {"title": "AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function.", "abstract": "Testosterone replacement in hypogonadal men improves body composition, mood, and sexual functioning. In this 90-d study, we compared the pharmacokinetics and treatment effectiveness of a topical testosterone gel (AA2500) at two concentrations, 50 mg/d and 100 mg/d, to a testosterone patch and placebo gel in 406 hypogonadal men. Pharmacokinetic profiles were obtained, body composition was measured, and mood and sexual function were monitored. AA2500 treatments resulted in dose-dependent improvements in all pharmacokinetic parameters, compared with testosterone patch and placebo. Mean average concentrations at d 90 T were 13.8, 17.1, 11.9, and 7.3 nmol/liter for 50 mg/d AA2500, 100 mg/d AA2500, testosterone patch, and placebo, respectively. At d 90, the 100 mg/d AA2500 treatment improved lean body mass by 1.7 kg and percentage of body fat by 1.2% to a significantly greater degree than either control treatment. Significant improvements in spontaneous erections, sexual desire, and sexual motivation were also evidenced with the 100 mg/d AA2500 dose in comparison with placebo. Testosterone gel was well tolerated; however, the testosterone patch resulted in a high rate of application site reactions. Overall, AA2500 is an effective, well tolerated treatment for hypogonadism.", "PMID": "12788872"}, {"title": "Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency.", "abstract": "The objective of this study was to assess the effects of oral testosterone supplementation therapy on glucose homeostasis, obesity and sexual function in middle-aged men with type 2 diabetes and mild androgen deficiency. Forty-eight middle-aged men, with type 2 diabetes, (visceral) obesity and symptoms of androgen deficiency, were included in this open-label study. Twenty-four subjects received testosterone undecanoate (TU; 120 mg daily, for 3 months); 24 subjects received no treatment. Body composition was analyzed by bio-impedance. Parameters of metabolic control were determined. Symptoms of androgen deficiency and erectile dysfunction were scored by self-administered questionnaires. TU had a positive effect on (visceral) obesity: statistically significant reduction in body weight (2.66%), waist-hip ratio (-3.96%) and body fat (-5.65%); negligible changes were found in the control group. TU significantly improved metabolic control: decrease in blood glucose values and mean glycated hemoglobin (HbA1c) (from 10.4 to 8.6%). TU treatment significantly improved symptoms of androgen deficiency (including erectile dysfunction), with virtually no change in the control group. There were no adverse effects on blood pressure or hematological, biochemical and lipid parameters, and no adverse events. Oral TU treatment of type 2 diabetic men with androgen deficiency improves glucose homeostasis and body composition (decrease in visceral obesity), and improves symptoms of androgen deficiency (including erectile dysfunction). In these men, the benefit of testosterone supplementation therapy exceeds the correction of symptoms of androgen deficiency and also includes glucose homeostasis and metabolic control.", "PMID": "12809074"}, {"title": "Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone.", "abstract": "We compare the efficacy of testosterone gel (T-gel) versus placebo as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone.\n\nA randomized, placebo controlled, double-blind, parallel group, multicenter study was performed. A total of 75 hypogonadal men (18 to 80 years old, morning serum total testosterone 400 ng/dl or less) with confirmed lack of response to sildenafil monotherapy were randomized (1:1) to receive a daily dose of 1% T-gel or 5 gm placebo gel as adjunctive therapy to 100 mg sildenafil during a 12-week period. Subjects were evaluated for sexual function, primarily based on the International Index of Erectile Function (IIEF), quality of life and serum testosterone levels at baseline and weeks 4, 8 and 12.\n\nTestosterone treated subjects had greater improvement in erectile function compared to those who received placebo, reaching statistical significance at week 4 (4.4 vs 2.1, p = 0.029, 95.1% CI 0.3, 4.7). Similar trends were observed for improvements in orgasmic function, overall satisfaction, total IIEF score and percentage of IIEF responders. T-gel significantly (p < or =0.004) increased total and free testosterone levels throughout the study, although no significant correlations were made between testosterone levels and the IIEF at end point.\n\nT-gel taken with sildenafil may be beneficial in improving erectile function in hypogonadal men with erectile dysfunction who are unresponsive to sildenafil alone.", "PMID": "15247755"}, {"title": "Restorative increases in serum testosterone levels are significantly correlated to improvements in sexual functioning.", "abstract": "It is recognized that testosterone (T) levels decrease in men with age, as does sexual function. We hypothesize that T supplementation in hypogonadal men with sexual dysfunction will restore certain elements of sexual function. Hypogonadal male subjects (total T < or = 300 ng/dL, n = 406, mean age 58 years) reporting one or more symptoms of low testosterone were randomized to T gel (50 mg/d and 100 mg/d), T patch, or placebo. Twenty-four-hour pharmacokinetic profiles for T were obtained. The 3 primary end points evaluated at 30 and 90 days posttreatment included a significant change in the frequency of intercourse and nighttime erections per 7-day week as well as a change in sexual desire measured on a Likert-type scale and calculated as a mean daily score. At day 30, a significant increase from baseline in sexual desire was noted for those on 100 mg/d T gel compared with those on 50 mg/d T gel, T patch, or placebo (1.2 vs 0.4, 0.7, and 0.4, respectively). A significant increase from baseline in the frequency of nighttime erections was also noted for those on 100 mg/d T gel compared with those on 50 mg/d T gel or placebo (51% of subjects in the 100 mg/d T gel group had an increase in frequency vs 30% for the 50 mg/d T gel group and 26% in the placebo group). Finally, a significant increase from baseline in the frequency of intercourse was evidenced for those on 100 mg/d T gel compared with those on T patch or placebo (39% of subjects in the 100 mg/d T gel group had an increase in frequency vs 21% for the T patch group and 24% in the placebo group). Similar results were seen for 100 mg/d T gel at day 90 for sexual desire and nighttime erections vs placebo. These data demonstrate a clear relationship between restoring serum T concentrations and improvement in certain parameters of sexual function. We propose that threshold T levels are needed in order to significantly affect improvements in sexual functioning.", "PMID": "15477371"}, {"title": "Effect of 12 month oral testosterone on testosterone deficiency symptoms in symptomatic elderly males with low-normal gonadal status.", "abstract": "Relative androgen deficiency in ageing males is assumed to have adverse health effects. This study assessed the effect of 12 months' standard dose, oral testosterone, on symptoms attributed to testosterone deficiency in older men with plasma testosterone levels in the low-normal range for young men.\n\nTestosterone undecanoate (TU, 80 mg bid) or placebo was administered for one year to 76 healthy men, 60 years or older, with a free testosterone index (FTI) of 0.3-0.5 and significant symptoms on a questionnaire designed to evaluate androgen deficiency (ADAM). The ADAM was completed at baseline, 6 and 12 months. Hormone and safety data were collected at baseline, 1, 3, 6 and 12 months.\n\nAfter 12 months, plasma total testosterone was unchanged in both groups and sex hormone binding globulin decreased in the testosterone group (P = 0.01). FTI and calculated bioavailable testosterone (cBT) were greater in the testosterone group as compared with the placebo group (P = 0.021 and 0.025, respectively). There was no significant difference in total symptom score between testosterone and placebo groups after 12 months of oral TU. However, there were trends toward improvements in sadness/grumpiness (P = 0.063), reduced erection strength (P = 0.059) and decreased work performance symptoms (P = 0.077), particularly in men with baseline cBT levels below 3.1 nmol/l.\n\nThis study concludes that 80 mg bid oral TU does not improve overall ADAM questionnaire scores in older men with low-normal gonadal status. Oral TU may preserve mood and erectile function, as assessed by this questionnaire, particularly in men with the lowest testosterone levels.", "PMID": "15596419"}, {"title": "Difficulties in measuring the effect of testosterone replacement therapy on muscle function in older men.", "abstract": "Muscle wasting in older men may be related to androgen deficiency. We have assessed the effect of testosterone replacement therapy on muscle function in the upper and lower limbs of older (age > 60 years) men with blood testosterone levels < 14 nmol/L. Subjects (n = 7 per group) received testosterone enanthate 200 mg i.m. or placebo every 2 weeks in a double blind study over a 12-week period and underwent muscle testing every 4 weeks. A significant increase in blood levels of testosterone and a reduction in levels of sex hormone binding globulin occurred in the treatment group. Total body mass, haemoglobin and packed cell volume also increased significantly (p < 0.05). No improvements in handgrip strength, isometric strength of knee flexors and extensors or leg extensor power were seen in either group. Wide variability in all measures of muscle function were observed in these elderly men suggesting that very large study groups would be required to determine potential treatment benefits on muscle function.", "PMID": "10442299"}, {"title": "Testosterone improves rehabilitation outcomes in ill older men.", "abstract": "To determine whether testosterone supplementation improves rehabilitation outcomes in ill older men.\n\nA randomized, placebo-controlled, double-blind study.\n\nA Geriatric Evaluation and Management (GEM) unit based at a university- affiliated Veterans Affairs Medical Center.\n\nFifteen men aged 65 to 90 years admitted to the GEM for rehabilitation.\n\nSubjects were randomized to receive weekly intramuscular injections with testosterone enanthate 100 mg or placebo.\n\nTask-specific performance using the Functional Independence Measure (FIM) and grip strength was measured at the onset of the study and at the time of discharge from the GEM.\n\nAt baseline, FIM scores were similar between the placebo and the testosterone group (73.7 vs 70.7, P = .637), as was grip strength (49.7 vs 55.3 pounds, P = .555). At discharge from the GEM, testosterone-treated patients had improved FIM scores compared with baseline (93.6 vs 70.7; P = .012) and grip strength (68.7 vs 55.3 pounds; P = .033). In the placebo group there was no significant improvement of FIM scores compared with baseline (78.0 versus 73.7; P = .686) or of grip strength (48.9 vs 49.7 pounds; P = .686).\n\nTestosterone supplementation may improve rehabilitation outcomes in ill older men.", "PMID": "10811549"}, {"title": "Effects of anabolic precursors on serum testosterone concentrations and adaptations to resistance training in young men.", "abstract": "The effects of androgen precursors, combined with herbal extracts designed to enhance testosterone formation and reduce conversion of androgens to estrogens was studied in young men. Subjects performed 3 days of resistance training per week for 8 weeks. Each day during Weeks 1, 2, 4, 5, 7, and 8, subjects consumed either placebo (PL; n = 10) or a supplement (ANDRO-6; n = 10), which contained daily doses of 300 mg androstenedione, 150 mg DHEA, 750 mg Tribulus terrestris, 625 mg Chrysin, 300 mg Indole-3-carbinol, and 540 mg Saw palmetto. Serum androstenedione concentrations were higher in ANDRO-6 after 2, 5, and 8 weeks (p <.05), while serum concentrations of free and total testosterone were unchanged in both groups. Serum estradiol was elevated at Weeks 2, 5, and 8 in ANDRO-6 (p <.05), and serum estrone was elevated at Weeks 5 and 8 (p <.05). Muscle strength increased (p <.05) similarly from Weeks 0 to 4, and again from Weeks 4 to 8 in both treatment groups. The acute effect of one third of the daily dose of ANDRO-6 and PL was studied in 10 men (23 +/- 4 years). Serum androstenedione concentrations were elevated (p <.05) in ANDRO-6 from 150 to 360 min after ingestion, while serum free or total testosterone concentrations were unchanged. These data provide evidence that the addition of these herbal extracts to androstenedione does not result in increased serum testosterone concentrations, reduce the estrogenic effect of androstenedione, and does not augment the adaptations to resistance training.", "PMID": "10997957"}], "labels": [{"PMID": "10096389", "label": "included"}, {"PMID": "11932266", "label": "included"}, {"PMID": "12788872", "label": "included"}, {"PMID": "12809074", "label": "included"}, {"PMID": "15247755", "label": "included"}, {"PMID": "15477371", "label": "included"}, {"PMID": "15596419", "label": "included"}, {"PMID": "10442299", "label": "excluded"}, {"PMID": "10811549", "label": "excluded"}, {"PMID": "10997957", "label": "excluded"}]}
{"metadata": {"review_pmid": "38205864"}, "inputs": {"background": "Rates of asthma are high in children and adolescents, and young people with asthma generally report poorer health outcomes than those without asthma. Young people with asthma experience a range of challenges that may contribute to psychological distress. This is compounded by the social, psychological, and developmental challenges experienced by all people during this life stage. Psychological interventions (such as behavioural therapies or cognitive therapies) have the potential to reduce psychological distress and thus improve behavioural outcomes such as self-efficacy and medication adherence. In turn, this may reduce medical contacts and asthma attacks.", "objectives": "To determine the efficacy of psychological interventions for modifying health and behavioural outcomes in children with asthma, compared with usual treatment, treatment with no psychological component, or no treatment.", "selection criteria": "We included randomised controlled trials (RCTs) comparing psychological interventions of any duration with usual care, active controls, or a waiting-list control in male and female children and adolescents (aged five to 18 years) with asthma."}, "context": [{"title": "Health effects of written emotional disclosure in adolescents with asthma: a randomized, controlled trial.", "abstract": "To test the effects of written emotional disclosure on the health of adolescents with asthma and to examine how language in disclosures predicts outcomes.\n\nWe randomized 50 adolescents with asthma to write for 3 days at home about stressful events (disclosure) or control topics. At baseline and 2 months after writing, we assessed symptoms, affect, disability, internalizing behavior problems, and lung function; parents independently rated internalizing behavior and disability.\n\nCompared with control writing, disclosure writing led to improved positive affect and internalizing problems. Disclosure also decreased asthma symptoms and functional disability among adolescents with baseline elevations of these difficulties. Lung function was not changed. Disclosures with more negative emotion, insight, and causal words--and increased causal or insight words over days--predicted improved health.\n\nWritten emotional disclosure improves emotional and behavioral functioning among adolescents with asthma, particularly those whose writings suggest emotional processing and cognitive restructuring.", "PMID": "16014820"}, {"title": "Feasibility and impact of a school-based intervention for families of urban adolescents with asthma: results from a randomized pilot trial.", "abstract": "The purpose of this study was to test the feasibility and short-term outcomes of Asthma: It's a Family Affair!, a school-based intervention for adolescents with asthma and their caregivers. Twenty-four ethnic minority families with a middle school student with asthma were randomized to immediate intervention or no-treatment control. Intervention students received six group sessions on prevention and management of asthma. Caregivers received five group sessions teaching child-rearing skills to support the youth's autonomy and asthma self-management. All students attended all sessions; caregivers attended an average of three. Two months post-intervention, relative to controls, intervention caregivers reported better problem-solving with children. Intervention students were more responsible for carrying medication, took more prevention steps, and woke fewer nights from asthma. The intervention resulted in positive short-term changes in family relations, asthma management by students, and health status.", "PMID": "18411832"}, {"title": "Effect of relaxation-breathing training on anxiety and asthma signs/symptoms of children with moderate-to-severe asthma: a randomized controlled trial.", "abstract": "Emotional stress triggers and exacerbates asthma in children. Reducing anxiety in adults by relaxation-breathing techniques has been shown in clinical trials to produce good asthma outcomes. However, more evidence is needed on using this intervention with asthmatic children.\n\nTo evaluate the effectiveness of combined self-management and relaxation-breathing training for children with moderate-to-severe asthma compared to self-management-only training.\n\nTwo-group experimental design.\n\nPediatric outpatient clinic of a medical center in central Taiwan. Participants were 48 children, ages 6-14 years, with moderate-to-severe asthma and their parents.\n\nParticipants were randomly assigned to an experimental or comparison group and matched by gender, age, and asthma severity. Both groups participated in an asthma self-management program. Children in the experimental group were also given 30 min of training in a relaxation-breathing technique and a CD for home practice. Data on anxiety levels, self-perceived health status, asthma signs/symptoms, peak expiratory flow rate, and medication use were collected at baseline and at the end of the 12-week intervention. Effects of group, time, and group-time interaction were analyzed using the Mixed Model in SPSS (12.0).\n\nAnxiety (especially state anxiety) was significantly lower for children in the experimental group than in the comparison group. Differences in the other four physiological variables were also noted between pre- and post-intervention, but these changes did not differ significantly between groups.\n\nA combination of self-management and relaxation-breathing training can reduce anxiety, thus improving asthmatic children's health. These results can serve as an evidence base for psychological nursing practice with asthmatic children.", "PMID": "19246041"}, {"title": "Hypnosis for asthma--a controlled trial. A report to the Research Committee of the British Tuberculosis Association.", "abstract": "An investigation of hypnosis in asthma was made among patients aged 10 to 60 years with paroxysmal attacks of wheezing or tight chest capable of relief by bronchodilators. One group of patients was given hypnosis monthly and used autohypnosis daily for one year. Comparisons were made with a control group prescribed a specially devised set of breathing exercises aimed at progressive relaxation. Treatment was randomly allocated and patients were treated by physicians in nine centres. Results were assessed by daily diary recordings of wheezing and the use of bronchodilators, and by monthly recordings of F.E.V.(1) and vital capacity. At the end of the year independent clinical assessments were made by physicians unaware of the patients' treatment.There were 252 patients (127 hypnosis and 125 controls) accepted for analysis, but a number of them did not continue the prescribed treatment for the whole year: 28 hypnosis and 22 control patients failed to co-operate, left the district, or had family problems; one hypnosis and one control patient died. Seven hypnosis and 17 control patients were withdrawn as treatment failures, the difference between the two groups being statistically significant.As judged by analyses based on the daily \"score\" of wheezing recorded in patients' diaries, by the number of times bronchodilators were used, and by independent clinical assessors, both treatment groups showed some improvement Among men the assessments of wheezing score and use of bronchodilators showed similar improvement in the two treatment groups; among women, however, those treated by hypnosis showed improvement similar to that observed in the men, but those given breathing exercises made much less progress, the difference between the two treatment groups reaching statistical significance. Changes in F.E.V.(1) and V.C. between the control and hypnosis groups were closely similar.Independent clinical assessors considered the asthma to be \"much better\" in 59% of the hypnosis group and in 43% of the control group, the difference being significant There was little difference between the sexes. Physicians with previous experience of hypnosis obtained significantly better results than did those without such experience.", "PMID": "4880259"}, {"title": "A randomized, controlled trial of a community-based support program for families of children with chronic illness: pediatric outcomes.", "abstract": "Children with chronic illnesses have a heightened risk for mental health problems.\n\nTo develop, implement, and evaluate child outcomes of a 15-month, community-based, family-support intervention designed to reduce risk for poor adjustment and mental health problems in children with 1 of 4 chronic illnesses (diabetes mellitus, sickle cell anemia, cystic fibrosis, or moderate to severe asthma) and their mothers.\n\nRandomized, controlled clinical trial design with multiple measures of mental health based on both child and parent reports taken 1 year apart.\n\nCommunity-based intervention linked to subspecialty and general pediatric clinics and practices in Baltimore, Md.\n\nOne hundred thirty-six mothers and children aged 7 to 11 years with diabetes mellitus, sickle cell anemia, cystic fibrosis, or moderate to severe asthma.\n\nThe program, provided by \"experienced mothers\" and child life specialists, included telephone contacts, face-to-face visits, and special family events.\n\nOutcomes were measured using the following instruments: the Personal Adjustment and Role Skills Scale III, the Children's Depression Inventory, the Revised Children's Manifest Anxiety Scale, and the Self-Perception Profile for Children.\n\nThe experimental group's mean adjustment score increased over the intervention period while the control group's mean adjustment score decreased. Analysis of variance demonstrated that the intervention had a significant main effect on postintervention adjustment controlling for baseline scores (P =.01). Using a cutoff score indicating maladjustment, the percentage of experimental group children in the maladjustment range fell from 19% at baseline to 10% after the intervention; the percentage of control group children in the maladjustment range rose from 15% at baseline to 21% after the intervention. The effect of the intervention was more pronounced for children who had low physical self-esteem than for those who had moderate to high physical self-esteem at the beginning of the program.\n\nOur results demonstrate modest positive effects of a family support intervention in promoting the adjustment of children with selective chronic health conditions. Including child life specialists in a community-based intervention may be especially salient for children with chronic illnesses who have low physical self-esteem. The intervention had a similar outcome for all diagnostic groups, suggesting that it could be effective for children with any chronic illness and implemented in a variety of pediatric settings.", "PMID": "12038883"}, {"title": "Children with asthma have improved pulmonary functions after massage therapy.", "abstract": "Thirty-two children with asthma (16 4- to 8-year-olds and 16 9- to 14-year-olds) were randomly assigned to receive either massage therapy or relaxation therapy. The children's parents were taught to provide one therapy or the other for 20 minutes before bedtime each night for 30 days. The younger children who received massage therapy showed an immediate decrease in behavioral anxiety and cortisol levels after massage. Also, their attitude toward asthma and their peak air flow and other pulmonary functions improved over the course of the study. The older children who received massage therapy reported lower anxiety after the massage. Their attitude toward asthma also improved over the study, but only one measure of pulmonary function (forced expiratory flow 25% to 75%) improved. The reason for the smaller therapeutic benefit in the older children is unknown; however, it appears that daily massage improves airway caliber and control of asthma.", "PMID": "9602199"}, {"title": "Asthma severity, psychophysiological indicators of arousal, and immune function in asthma patients undergoing biofeedback-assisted relaxation.", "abstract": "Asthma is characterized by airway hyper-responsiveness, inflammation, and reversible obstruction. Respiratory tract infection, allergies, air pollution, and psychosocial factors impact the severity and frequency of asthma symptoms. Pharmacotherapy and self-care are the major components in the management of asthma, but behavioral interventions also have the potential to affect asthma morbidity. We conducted a small, randomized controlled study, examining the effects of biofeedback-assisted relaxation in 16 nonsmokers with nonsteroid-dependent mild asthma. Data were collected on asthma symptoms, pulmonary function, indicators of arousal, and cellular immune factors. The trained group evidenced a decrease in forehead muscle tension in comparison to the controls, but no changes in peripheral skin temperature. Decreases in asthma severity and bronchodilator medication usage for the experimental group were observed. Pulmonary function testing revealed a significant difference between groups in FEV1/FVC at posttest, with the E group having a higher ratio than the controls. The cellular immune data showed no significant group differences in total white blood cell or lymphocyte counts, but decreases over time were observed. Significant differences were observed in the numbers of neutrophils and basophils in the trained group compared to controls, which supports the concept of decreased inflammation. Results of delayed-type hypersensitivity skin testing suggested enhanced function, but they were not conclusive. These findings, though limited by size of population, suggest a positive effect of biofeedback-assisted relaxation in young, nonsteroid-dependent asthmatics. The mechanisms underlying linkages between psychological, behavioral, and immune responses in asthma require further study.", "PMID": "10932333"}, {"title": "Controlled trial of hypnosis in the symptomatic treatment of asthma.", "abstract": "", "PMID": "14468430"}, {"title": "Behaviour therapy in bronchial asthma: a controlled study.", "abstract": "", "PMID": "5849893"}, {"title": "Excessive breathlessness through emotional imagery in asthma.", "abstract": "Breathlessness and negative emotions during asthma attacks interact in complex patterns. This study tested the influence of emotional imagery on breathlessness during voluntary breath holding. Adolescents with and without asthma (n = 36 + 36) were assigned to positive imagery, negative imagery, or no imagery. There were four trials with close to thresholds for breath holding combined with imagery. Breathlessness and quality of imagery were measured by the end of breath holding. Additional measures were lung function and anxiety. The results showed that positive and negative imagery were only influencing breathlessness in participants with asthma. Although threshold duration for the groups were not significantly different, participants with asthma reported more breathlessness. The intensity of imagery enhanced breathlessness but diminished the accuracy of symptom perception. Positive imagery diminished breathlessness in participants with asthma, but also the difference in breathlessness between 75% and 95% of threshold duration. Breathlessness did not correlate with lung function, anxiety or other variables. It was concluded that emotional imagery during asthma attacks distracts from accurate introspection or enhances breathlessness, irrespective of anxiety.", "PMID": "11004739"}], "labels": [{"PMID": "16014820", "label": "included"}, {"PMID": "18411832", "label": "included"}, {"PMID": "19246041", "label": "included"}, {"PMID": "4880259", "label": "excluded"}, {"PMID": "12038883", "label": "excluded"}, {"PMID": "9602199", "label": "excluded"}, {"PMID": "10932333", "label": "excluded"}, {"PMID": "14468430", "label": "excluded"}, {"PMID": "5849893", "label": "excluded"}, {"PMID": "11004739", "label": "excluded"}]}
{"metadata": {"review_pmid": "38197546"}, "inputs": {"background": "Cholera causes acute watery diarrhoea and death if not properly treated. Outbreaks occur in areas with poor sanitation, including refugee camps. Several vaccines have been developed and tested over the last 50 years. This is an update of a Cochrane review, originally published in 1998, which explored the effects of all vaccines for preventing cholera. This review examines oral vaccines made from killed bacteria.", "objectives": "To assess the effectiveness and safety of the available World Health Organization (WHO)-prequalified oral killed cholera vaccines among children and adults.", "selection criteria": "We included randomized controlled trials (RCTs), including cluster-RCTs. There were no restrictions on the age and sex of the participants or the setting of the study. We considered any available WHO-prequalified oral killed cholera vaccine as an intervention. The control group was given a placebo, another vaccine, or no vaccine. The outcomes were related to vaccine effectiveness and safety. We included articles published in English only."}, "context": [{"title": "Two-year study of the protective efficacy of the oral whole cell plus recombinant B subunit cholera vaccine in Peru.", "abstract": "The protective efficacy of an oral inactivated whole cell Vibrio cholerae plus recombinant B subunit cholera vaccine was determined against El Tor cholera among Peruvian children and adults (2-65 years old) in a randomized, double-blind manner. Study subjects received 2 doses of vaccine or placebo 2 weeks apart, followed by a booster dose 10 months later. Surveillance for cholera was performed actively, with 2 visits per week to each household, and passively, at a local hospital. Stool samples were collected during diarrhea episodes and were cultured for V. cholerae. A total of 17,799 persons received 2 doses of vaccine or placebo, and 14,997 of these persons received the booster dose. After 2 doses (first surveillance period), V. cholerae biotype O1 was isolated from 17 vaccinees and 16 placebo recipients, demonstrating vaccine efficacy (VE) of -4%. After 3 doses (second surveillance period), V. cholerae O1 was isolated from 13 vaccinees and 32 placebo recipients, demonstrating VE of 61% (95% confidence interval \u00bfCI, 28%-79%). In the second surveillance period, the VE for illness requiring hospitalization was 82% (95% CI, 27%-96%). VE was also higher for persons >15 years old (VE, 72%; 95% CI, 28%-89%).", "PMID": "10823767"}, {"title": "Efficacy and safety of a modified killed-whole-cell oral cholera vaccine in India: an interim analysis of a cluster-randomised, double-blind, placebo-controlled trial.", "abstract": "Oral cholera vaccines consisting of killed whole cells have been available for many years, but they have not been used extensively in populations with endemic disease. An inexpensive, locally produced oral killed-whole-cell vaccine has been used in high-risk areas in Vietnam. To expand the use of this vaccine, it was modified to comply with WHO standards. We assessed the efficacy and safety of this modified vaccine in a population with endemic cholera.\n\nIn this double-blind trial, 107 774 non-pregnant residents of Kolkata, India, aged 1 year or older, were cluster-randomised by dwelling to receive two doses of either modified killed-whole-cell cholera vaccine (n=52 212; 1966 clusters) or heat-killed Escherichia coli K12 placebo (n=55 562; 1967 clusters), both delivered orally. Randomisation was done by computer-generated sequence in blocks of four. The primary endpoint was prevention of episodes of culture-confirmed Vibrio cholerae O1 diarrhoea severe enough for the patient to seek treatment in a health-care facility. We undertook an interim, per-protocol analysis at 2 years of follow-up that included individuals who received two completely ingested doses of vaccine or placebo. We assessed first episodes of cholera that occurred between 14 days and 730 days after receipt of the second dose. This study is registered with ClinicalTrials.gov, number NCT00289224.\n\n31 932 participants assigned to vaccine (1721 clusters) and 34 968 assigned to placebo (1757 clusters) received two doses of study treatment. There were 20 episodes of cholera in the vaccine group and 68 episodes in the placebo group (protective efficacy 67%; one-tailed 99% CI, lower bound 35%, p<0.0001). The vaccine protected individuals in age-groups 1.0-4.9 years, 5.0-14.9 years, and 15 years and older, and protective efficacy did not differ significantly between age-groups (p=0.28). We recorded no vaccine-related serious adverse events.\n\nThis modified killed-whole-cell oral vaccine, compliant with WHO standards, is safe, provides protection against clinically significant cholera in an endemic setting, and can be used in children aged 1.0-4.9 years, who are at highest risk of developing cholera in endemic settings.\n\nBill & Melinda Gates Foundation, Swedish International Development Cooperation Agency, Governments of South Korea, Sweden, and Kuwait.", "PMID": "19819004"}, {"title": "Efficacy of a low-cost, inactivated whole-cell oral cholera vaccine: results from 3 years of follow-up of a randomized, controlled trial.", "abstract": "Killed oral cholera vaccines (OCVs) have been licensed for use in developing countries, but protection conferred by licensed OCVs beyond two years of follow-up has not been demonstrated in randomized, clinical trials.\n\nWe conducted a cluster-randomized, placebo-controlled trial of a two-dose regimen of a low-cost killed whole cell OCV in residents 1 year of age and older living in 3,933 clusters in Kolkata, India. The primary endpoint was culture-proven Vibrio cholerae O1 diarrhea episodes severe enough to require treatment in a health care facility. Of the 66,900 fully dosed individuals (31,932 vaccinees and 34,968 placebo recipients), 38 vaccinees and 128 placebo-recipients developed cholera during three years of follow-up (protective efficacy 66%; one-sided 95%CI lower bound\u200a=\u200a53%, p<0.001). Vaccine protection during the third year of follow-up was 65% (one-sided 95%CI lower bound\u200a=\u200a44%, p<0.001). Significant protection was evident in the second year of follow-up in children vaccinated at ages 1-4 years and in the third year in older age groups.\n\nThe killed whole-cell OCV conferred significant protection that was evident in the second year of follow-up in young children and was sustained for at least three years in older age groups. Continued follow-up will be important to establish the vaccine's duration of protection.\n\nClinicalTrials.gov NCT00289224.", "PMID": "22028938"}, {"title": "5 year efficacy of a bivalent killed whole-cell oral cholera vaccine in Kolkata, India: a cluster-randomised, double-blind, placebo-controlled trial.", "abstract": "Efficacy and safety of a two-dose regimen of bivalent killed whole-cell oral cholera vaccine (Shantha Biotechnics, Hyderabad, India) to 3 years is established, but long-term efficacy is not. We aimed to assess protective efficacy up to 5 years in a slum area of Kolkata, India.\n\nIn our double-blind, cluster-randomised, placebo-controlled trial, we assessed incidence of cholera in non-pregnant individuals older than 1 year residing in 3933 dwellings (clusters) in Kolkata, India. We randomly allocated participants, by dwelling, to receive two oral doses of modified killed bivalent whole-cell cholera vaccine or heat-killed Escherichia coli K12 placebo, 14 days apart. Randomisation was done by use of a computer-generated sequence in blocks of four. The primary endpoint was prevention of episodes of culture-confirmed Vibrio cholerae O1 diarrhoea severe enough for patients to seek treatment in a health-care facility. We identified culture-confirmed cholera cases among participants seeking treatment for diarrhoea at a study clinic or government hospital between 14 days and 1825 days after receipt of the second dose. We assessed vaccine protection in a per-protocol population of participants who had completely ingested two doses of assigned study treatment.\n\n69 of 31\u2008932 recipients of vaccine and 219 of 34\u2008968 recipients of placebo developed cholera during 5 year follow-up (incidence 2\u00b72 per 1000 in the vaccine group and 6\u00b73 per 1000 in the placebo group). Cumulative protective efficacy of the vaccine at 5 years was 65% (95% CI 52-74; p<0\u00b70001), and point estimates by year of follow-up suggested no evidence of decline in protective efficacy.\n\nSustained protection for 5 years at the level we reported has not been noted previously with other oral cholera vaccines. Established long-term efficacy of this vaccine could assist policy makers formulate rational vaccination strategies to reduce overall cholera burden in endemic settings.\n\nBill & Melinda Gates Foundation and the governments of South Korea and Sweden.", "PMID": "24140390"}, {"title": "Feasibility and effectiveness of oral cholera vaccine in an urban endemic setting in Bangladesh: a cluster randomised open-label trial.", "abstract": "Cholera is endemic in Bangladesh with epidemics occurring each year. The decision to use a cheap oral killed whole-cell cholera vaccine to control the disease depends on the feasibility and effectiveness of vaccination when delivered in a public health setting. We therefore assessed the feasibility and protective effect of delivering such a vaccine through routine government services in urban Bangladesh and evaluated the benefit of adding behavioural interventions to encourage safe drinking water and hand washing to vaccination in this setting.\n\nWe did this cluster-randomised open-label trial in Dhaka, Bangladesh. We randomly assigned 90 clusters (1:1:1) to vaccination only, vaccination and behavioural change, or no intervention. The primary outcome was overall protective effectiveness, assessed as the risk of severely dehydrating cholera during 2 years after vaccination for all individuals present at time of the second dose. This study is registered with ClinicalTrials.gov, number NCT01339845.\n\nOf 268,896 people present at baseline, we analysed 267,270: 94,675 assigned to vaccination only, 92,539 assigned to vaccination and behavioural change, and 80,056 assigned to non-intervention. Vaccine coverage was 65% in the vaccination only group and 66% in the vaccination and behavioural change group. Overall protective effectiveness was 37% (95% CI lower bound 18%; p=0\u00b7002) in the vaccination group and 45% (95% CI lower bound 24%; p=0\u00b7001) in the vaccination and behavioural change group. We recorded no vaccine-related serious adverse events.\n\nOur findings provide the first indication of the effect of delivering an oral killed whole-cell cholera vaccine to poor urban populations with endemic cholera using routine government services and will help policy makers to formulate vaccination strategies to reduce the burden of severely dehydrating cholera in such populations.\n\nBill & Melinda Gates Foundation.", "PMID": "26164097"}, {"title": "Efficacy of a Single-Dose, Inactivated Oral Cholera Vaccine in Bangladesh.", "abstract": "A single-dose regimen of the current killed oral cholera vaccines that have been prequalified by the World Health Organization would make them more attractive for use against endemic and epidemic cholera. We conducted an efficacy trial of a single dose of the killed oral cholera vaccine Shanchol, which is currently given in a two-dose schedule, in an urban area in which cholera is highly endemic.\n\nNonpregnant residents of Dhaka, Bangladesh, who were 1 year of age or older were randomly assigned to receive a single dose of oral cholera vaccine or oral placebo. The primary outcome was vaccine protective efficacy against culture-confirmed cholera occurring 7 to 180 days after dosing. Prespecified secondary outcomes included protective efficacy against severely dehydrating culture-confirmed cholera during the same interval, against cholera and severe cholera occurring 7 to 90 versus 91 to 180 days after dosing, and against cholera and severe cholera according to age at baseline.\n\nA total of 101 episodes of cholera, 37 associated with severe dehydration, were detected among the 204,700 persons who received one dose of vaccine or placebo. The vaccine protective efficacy was 40% (95% confidence interval [CI], 11 to 60%; 0.37 cases per 1000 vaccine recipients vs. 0.62 cases per 1000 placebo recipients) against all cholera episodes, 63% (95% CI, 24 to 82%; 0.10 vs. 0.26 cases per 1000 recipients) against severely dehydrating cholera episodes, and 63% (95% CI, -39 to 90%), 56% (95% CI, 16 to 77%), and 16% (95% CI, -49% to 53%) against all cholera episodes among persons vaccinated at the age of 5 to 14 years, 15 or more years, and 1 to 4 years, respectively, although the differences according to age were not significant (P=0.25). Adverse events occurred at similar frequencies in the two groups.\n\nA single dose of the oral cholera vaccine was efficacious in older children (\u22655 years of age) and in adults in a setting with a high level of cholera endemicity. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02027207.).", "PMID": "27144848"}, {"title": "Safety of the oral cholera vaccine in pregnancy: Retrospective findings from a subgroup following mass vaccination campaign in Dhaka, Bangladesh.", "abstract": "Pregnant women are vulnerable to complications of cholera. Killed oral cholera vaccines (OCV) are not recommended for pregnant women though there is no evidence of harmful effects during pregnancy. We evaluated the effect of a killed OCV, Shanchol\u2122, on pregnancy outcomes during an effectiveness trial of the vaccine in urban Bangladesh.\n\nIndividuals \u2a7e1year were invited to participate in the trial, conducted in 2011 in Dhaka, Bangladesh. Pregnancy by history was an exclusion criterion and all women of reproductive age (15-49years) were verbally questioned about pregnancy at enrollment and prior to vaccination. Out of 48,414 women of reproductive age 286 women received the OCV unknowingly while pregnant. Out of these, we could recruit 69 women defined as exposed to OCV. Accordingly, we selected 69 pregnant women randomly from those who did not take the OCV (non-exposed to OCV). We evaluated adverse pregnancy outcome (spontaneous miscarriages, still births, or congenital malformations) between those who were exposed to OCV and those who were not exposed to OCV.\n\nAbout 16% of pregnant women exposed to OCV had pregnancy loss, as compared to 12% of unvaccinated pregnant women (P=0.38). One congenital anomaly was observed and occurred in women non-exposed to OCV group. Models that adjusted for baseline characteristics that were unbalanced between the exposed and non-exposed groups, revealed a no elevation of risk of adverse pregnancy outcomes in vaccinees versus non-vaccinees (Adj. OR (95% CI): 0.45 (0.11-1.88).\n\nNo excess of adverse fetal outcomes associated with receipt of OCV was observed in this study.\n\nClinical Trials.gov number NCT01339845.", "PMID": "28196715"}, {"title": "Efficacy of a bivalent killed whole-cell cholera vaccine over five years: a re-analysis of a cluster-randomized trial.", "abstract": "Oral cholera vaccine (OCV) is a feasible tool to prevent or mitigate cholera outbreaks. A better understanding of the vaccine's efficacy among different age groups and how rapidly its protection wanes could help guide vaccination policy.\n\nTo estimate the level and duration of OCV efficacy, we re-analyzed data from a previously published cluster-randomized, double-blind, placebo controlled trial with five years of follow-up. We used a Cox proportional hazards model and modeled the potentially time-dependent effect of age categories on both vaccine efficacy and risk of infection in the placebo group. In addition, we investigated the impact of an outbreak period on model estimation.\n\nVaccine efficacy was 38% (95% CI: -2%,62%) for those vaccinated from ages 1 to under 5 years old, 85% (95% CI: 67%,93%) for those 5 to under 15 years, and 69% (95% CI: 49%,81%) for those vaccinated at ages 15 years and older. Among adult vaccinees, efficacy did not appear to wane during the trial, but there was insufficient data to assess the waning of efficacy among child vaccinees.\n\nThrough this re-analysis we were able to detect a statistically significant difference in OCV efficacy when the vaccine was administered to children under 5 years old vs. children 5 years and older. The estimated efficacies are more similar to the previously published analysis based on the first two years of follow-up than the analysis based on all five years.\n\nClinicalTrials.gov identifier NCT00289224.", "PMID": "29463233"}, {"title": "Efficacy of a single-dose regimen of inactivated whole-cell oral cholera vaccine: results from 2 years of follow-up of a randomised trial.", "abstract": "A single-dose regimen of inactivated whole-cell oral cholera vaccine (OCV) is attractive because it reduces logistical challenges for vaccination and could enable more people to be vaccinated. Previously, we reported the efficacy of a single dose of an OCV vaccine during the 6 months following dosing. Herein, we report the results of 2 years of follow-up.\n\nIn this placebo-controlled, double-blind trial done in Dhaka, Bangladesh, individuals aged 1 year or older with no history of receipt of OCV were randomly assigned to receive a single dose of inactivated OCV or oral placebo. The primary endpoint was a confirmed episode of non-bloody diarrhoea for which the onset was at least 7 days after dosing and a faecal culture was positive for Vibrio cholerae O1 or O139. Passive surveillance for diarrhoea was done in 13 hospitals or major clinics located in or near the study area for 2 years after the last administered dose. We assessed the protective efficacy of the OCV against culture-confirmed cholera occurring 7-730 days after dosing with both crude and multivariable per-protocol analyses. This trial is registered at ClinicalTrials.gov, number NCT02027207.\n\nBetween Jan 10, 2014, and Feb 4, 2014, 205\u2008513 people were randomly assigned to receive either vaccine or placebo, of whom 204\u2008700 (102\u2008552 vaccine recipients and 102\u2008148 placebo recipients) were included in the per-protocol analysis. 287 first episodes of cholera (109 among vaccine recipients and 178 among placebo recipients) were detected during the 2-year follow-up; 138 of these episodes (46 in vaccine recipients and 92 in placebo recipients) were associated with severe dehydration. The overall incidence rates of initial cholera episodes were 0\u00b722 (95% CI 0\u00b718 to 0\u00b727) per 100\u2008000 person-days in vaccine recipients versus 0\u00b736 (0\u00b731 to 0\u00b742) per 100\u2008000 person-days in placebo recipients (adjusted protective efficacy 39%, 95% CI 23 to 52). The overall incidence of severe cholera was 0\u00b709 (0\u00b707 to 0\u00b712) per 100\u2008000 person-days versus 0\u00b719 (0\u00b715 to 0\u00b723; adjusted protective efficacy 50%, 29 to 65). Vaccine protective efficacy was 52% (8 to 75) against all cholera episodes and 71% (27 to 88) against severe cholera episodes in participants aged 5 years to younger than 15 years. For participants aged 15 years or older, vaccine protective efficacy was 59% (42 to 71) against all cholera episodes and 59% (35 to 74) against severe cholera. The protection in the older age groups was sustained throughout the 2-year follow-up. In participants younger than 5 years, the vaccine did not show protection against either all cholera episodes (protective efficacy -13%, -68 to 25) or severe cholera episodes (-44%, -220 to 35).\n\nA single dose of the inactivated whole-cell OCV offered protection to older children and adults that was sustained for at least 2 years. The absence of protection of young children might reflect a lesser degree of pre-existing natural immunity in this age group.\n\nBill & Melinda Gates Foundation to the International Vaccine Institute.", "PMID": "29550406"}, {"title": "Safety of a bivalent, killed, whole-cell oral cholera vaccine in pregnant women in Bangladesh: evidence from a randomized placebo-controlled trial.", "abstract": "Cholera increases the risk of harmful effects on foetuses. We prospectively followed pregnant women unaware of their pregnancy status who received a study agent in a clinical trial evaluating the association between exposure to an oral cholera vaccine (OCV) and foetal survival.\n\nStudy participants were selected from a randomized placebo-controlled trial conducted in Dhaka, Bangladesh. The vaccination campaign was conducted between January 10 and February 4, 2014. We enrolled women who were exposed to an OCV or placebo during pregnancy (Cohort 1) and women who were pregnant after the vaccination was completed (Cohort 2). Our primary endpoint was pregnancy loss (spontaneous miscarriage or stillbirth), and the secondary endpoints were preterm delivery and low birth weight. We employed a log-binomial regression to calculate the relative risk of having adverse outcomes among OCV recipients compared to that among placebo recipients.\n\nThere were 231 OCV and 234 placebo recipients in Cohort 1 and 277 OCV and 299 placebo recipients in Cohort 2. In Cohort 1, the incidence of pregnancy loss was 113/1000 and 115/1000 among OCV and placebo recipients, respectively. The adjusted relative risk for pregnancy loss was 0.97 (95% CI: 0.58-1.61; p\u2009=\u20090.91) in Cohort 1. We did not observe any variation in the risk of pregnancy loss between the two cohorts. The risks for preterm delivery and low birth weight were not significantly different between the groups in both cohorts.\n\nOur study provides additional evidence that exposure to an OCV during pregnancy does not increase the risk of pregnancy loss, preterm delivery, or low birth weight, suggesting that pregnant women in cholera-affected regions should not be excluded in a mass vaccination campaign.\n\nThe study is registered at ( http://clinicaltrials.gov ). Identifier: NCT02027207 .", "PMID": "31092224"}], "labels": [{"PMID": "10823767", "label": "included"}, {"PMID": "19819004", "label": "included"}, {"PMID": "22028938", "label": "included"}, {"PMID": "24140390", "label": "included"}, {"PMID": "26164097", "label": "included"}, {"PMID": "27144848", "label": "included"}, {"PMID": "28196715", "label": "included"}, {"PMID": "29463233", "label": "included"}, {"PMID": "29550406", "label": "included"}, {"PMID": "31092224", "label": "included"}]}
{"metadata": {"review_pmid": "38197528"}, "inputs": {"background": "Over 1.3 million people die each year as a result of traffic collisions and hundreds of thousands of others are permanently and seriously injured. Most of these deaths occur in low- and middle-income countries, where mortality rates can be up to 10 times higher than those of some high-income countries. Seat belts are designed to accomplish two key functions - to prevent the occupant from being ejected from the vehicle by the force of impact, and to extend the time that the decelerating force is applied to a person. Seat belts also spread the area of impact both to larger and less vulnerable parts of the body. Since the 1950s, seat belts have been factory-fitted to most vehicles, and today around 90% of high-income countries have adopted seat belt legislation that makes it mandatory for some, if not all, vehicle occupants to wear seat belts. However, the simple passing of laws is not sufficient to ensure seat belt use, and, while the enforcement of seat belt laws does increase seat belt use, other interventions have been developed to encourage voluntary - and hence sustainable - behaviour change.", "objectives": "To evaluate the benefits of behavioural-change interventions (educational-based, incentive-based, engineering-based, or a combination, but not enforcement-based) that promote the use of seat belts, and to determine which types of interventions are most effective.", "selection criteria": "We included randomised controlled trials (RCTs), both individually randomised and cluster-randomised, that evaluated education, engineering, incentive-based interventions (or combinations) that promoted seat belt use."}, "context": [{"title": "A statewide intervention to increase safety belt use: adding to the impact of a belt use law.", "abstract": "", "PMID": "10146854"}, {"title": "Effectiveness of a comprehensive multisector campaign to increase seat belt use in the greater Athens area, Greece. Hellenic Road Traffic Police Department.", "abstract": "This study assessed the effectiveness of a comprehensive campaign to increase seat belt use in Athens.\n\nIn 1996 a survey focusing on seat belt use was undertaken among occupants of 1400 passenger cars. From October 1997 to June 1998 the campaign was implemented; during the campaign, seat belt law enforcement was not intensified. In 1998 another inspection survey of 2250 cars was undertaken.\n\nThe program brought only a 6% increase in compliance, but there was an estimated gain of about 50 averted deaths and 1500 averted injuries.\n\nAn intensive campaign to increase seat belt use, conducted in the absence of increased law enforcement, resulted in moderate gains.", "PMID": "10589318"}, {"title": "Evaluation of a brief intervention for increasing seat belt use on a college campus.", "abstract": "The authors evaluated a brief intervention for increasing seat belt use among the front seat occupants of cars at a junior college, in a jurisdiction with a mandatory belt use law. The intervention included public posting of performance feedback and distribution of an informational flyer to cars in target parking lot. Feedback was the display of the proportion of drivers observed wearing seat belts on the previous observation day. Seat belt use among drivers increased from 64% during the baseline phase to 71% during the intervention phase. Seat belt use among front passengers increased from 49% during the baseline phase to 67% during the intervention phase. In both cases, seat belt use at follow-up was comparable to seat belt use during the intervention phase, although a trend toward decreasing belt use was noted. Also found was higher seat belt use among females as compared with males irrespective of their front seat occupant status (driver or passenger). Effects of the intervention are discussed in the context of increasing seat belt use in a hardcore nonuser population of predominantly young adults.", "PMID": "11428249"}, {"title": "A program to increase seat belt use along the Texas-Mexico border.", "abstract": "A school-based, bilingual intervention was developed to increase seat belt use among families living along the Texas-Mexico border. The intervention sought to increase seat belt use by changing perceived norms within the community (i.e., making the nonuse of seat belts less socially acceptable). The intervention was implemented in more than 110 classrooms and involved more than 2100 children. Blind coding, validity checks, and reliability estimates contributed to a rigorous program evaluation. Seat belt use increased by 10% among children riding in the front seat of motor vehicles in the intervention community, as compared with a small but nonsignificant decline in use among control community children. Seat belt use among drivers did not increase.", "PMID": "12453809"}, {"title": "Increasing the screening and counseling of adolescents for risky health behaviors: a primary care intervention.", "abstract": "To determine whether a systems intervention for primary care providers resulted in increased preventive screening and counseling of adolescent patients, compared with the usual standard of care.\n\nThe intervention was conducted in 2 outpatient pediatric clinics; 2 other pediatric clinics in the same health maintenance organization served as comparison sites. The intervention was implemented in 2 phases: first, pediatric primary care providers attended a training workshop (N = 37) to increase screening and counseling of adolescents in the areas of tobacco, alcohol, drugs, sexual behavior, and safety (seatbelt and helmet use). Second, screening and charting tools were integrated into the intervention clinics. Providers in the comparison sites (N = 39) continued to provide the usual standard of care to their adolescent patients. Adolescent reports were used to assess changes in provider behavior. After a well visit, 13- to 17-year olds (N = 2628) completed surveys reporting on whether their provider screened and counseled them for risky behavior.\n\nScreening and counseling rates increased significantly in each of the 6 areas in the intervention sites, compared with rates of delivery using the usual standard of care. Across the 6 areas combined, the average screening rate increased from 58% to 83%; counseling rates increased from 52% to 78%. There were no significant increases in the comparison sites during the same period. The training component seems to account for most of this increase, with the tools sustaining the effects of the training.\n\nThe study offers strong support for an intervention to increase clinicians' delivery of preventive services to a wide age range of adolescent patients.", "PMID": "15805371"}, {"title": "Cost effectiveness of a dealer's intervention in retrofitting rollover protective structures.", "abstract": "To evaluate the cost effectiveness of a 4.5 year education campaign that promoted farmers' adoption of rollover protective structures (ROPS) to prevent tractor overturn injuries.\n\nRandomized controlled trial, decision analysis, and cost effectiveness analysis.\n\nOne treatment county and one control county in the State of Kentucky.\n\nA campaign by a local tractor and equipment dealership to encourage farmers to purchase and install ROPS and seatbelt retrofit kits for older tractors.\n\nNumber of injuries averted and cost per injury averted.\n\nThe dealership's 4.5 year intervention was shown to potentially reduce both fatal (0.26) and non-fatal (1.50) injuries by 2.6% in its county over the intervention period using a 20 year analytic horizon. When extrapolated statewide, 6.7 lives would be saved and 39 non-fatal injuries would be averted over the combined 24.5 year combined intervention period and analytic horizon. The intervention for this period was cost effective with a \"savings\" of 35,713 dollars per injury (fatal plus non-fatal) averted at a 4% discount rate.\n\nTractor manufacturer promotions can influence their dealerships to promote ROPS retrofits by their customers. A manufacturer backed dealer ROPS retrofit campaign was cost effective in reducing overturn related injuries.", "PMID": "15933410"}, {"title": "Safety halls--an evaluation.", "abstract": "In most countries, drivers licensing systems usually include teaching some aspects of using safety equipment (e.g., airbags and seat belts). However, there is now evidence worldwide that such education is inadequate, as indicated by, for example, the overrepresentation of young drivers who do not use seat belts.\n\nA randomized controlled study was conducted in Sweden to evaluate the effects of visiting a facility known as a \"safety hall\" in combination with the mandatory skid training. The results were assessed to determine the effects of the knowledge and attitudes of learner drivers in the following subjects: airbags, securing loads, seat belts, sitting posture, speed, and tires. An experimental group and a control group comprising 658 and 668 learners, respectively, answered identical questionnaires on three different occasions (pretest, posttest 1, and posttest 2).\n\nThe results show that, for most of the topics considered, knowledge and attitudes in both groups were better at posttest 2 than at the pretest, and in general, the best knowledge and attitudes were found in the experimental group. The combined safety/skid training seems to have had the greatest effect on seat belts and loads. The findings also indicate that the safety halls can be further improved to achieve an even better effect.\n\nThe use of safety halls has improved the knowledge and attitudes of learner drivers concerning several important areas related to traffic safety. Since knowledge and attitudes are important predictors of behavior, implementing safety halls can be expected to lead to improvements, especially regarding the use of safety belts and securing loads.", "PMID": "16309707"}, {"title": "An emergency department intervention to increase booster seat use for lower socioeconomic families.", "abstract": "To evaluate the effectiveness of booster seat education within an emergency department (ED) setting for families residing in lower socioeconomic neighborhoods.\n\nThis was a prospective, randomized study of families with children aged 4 to 7 years and weighing 40 to 80 lb who presented to a pediatric ED without a booster seat and resided in lower socioeconomic communities. Subjects were randomly assigned to one of three groups: 1) received standard discharge instructions, 2) received five-minute booster seat training, and 3) received five-minute booster seat training and free booster seat with installation. Automobile restraint practices were obtained initially and by telephone at one month.\n\nA total of 225 children were enrolled. Before randomization in the study, 79.6% of parents reported that their child was usually positioned in the car with a lap/shoulder belt and 13.3% with a lap belt alone. Some parents (16.4%) had never heard of a booster seat, and 44.9% believed a lap belt was sufficient restraint. A total of 147 parents (65.3%) were contacted for follow-up at one month. Only one parent (1.3%) in the control group and four parents (5.3%) in the education group purchased and used a booster seat after their ED visit, while 55 parents (98.2%) in the education and installation group reported using the booster seat; 42 (75.0%) of these parents reported using the seat 100% of the time.\n\nEducation in a pediatric ED did not convince parents to purchase and use booster seats; however, the combination of education with installation significantly increased booster seat use in this population.", "PMID": "16531596"}, {"title": "Reducing the burden of road traffic injury: translating high-income country interventions to middle-income and low-income countries.", "abstract": "To increase seat belt restraint use in Guangzhou City, People's Republic of China.\n\nComparison group pre-test, post-test design.\n\nGuangzhou City.\n\nInterventions to increase the prevalence of seat belt use in high-income countries (enhanced training and enforcement practices along with raising of public awareness) were adapted and implemented in Guangzhou. The prevalence of seat belt use was determined before and after the introduction of the 12-month intervention. Seat belt prevalence was also examined over the same time period in the neighboring city of Nanning, and an incremental cost-effectiveness analysis of the intervention was undertaken.\n\nPrevalence rates and incremental cost effectiveness ratios.\n\nA 12% increase in seat belt use was observed in Guangzhou over the study period, increasing from a prevalence of 50% before (error range 30-62%) to 62% after (error range 60-67%) (p<0.001) the intervention; an absolute change difference between the intervention and reference city of 20% was achieved. The incremental cost-effectiveness ratio of the intervention was yen 3246 (US dollars 418) per disability-adjusted life year saved.\n\nThis city-wide intervention demonstrates that it is possible to increase the prevalence of seat belt use using similar methods to those used in high-income countries and, importantly, that such an approach is cost-effective.", "PMID": "18836043"}, {"title": "Encouraging the installation of rollover protective structures in New York State: the design of a social marketing intervention.", "abstract": "Increasing the percentage of rollover protective structure (ROPS) equipped tractors has been the focus of many agricultural safety campaigns. Traditionally efforts have attempted to persuade farmers through education or community awareness interventions. These efforts have lead to marginal change. In response, a social marketing approach was tested as a means for increasing interest in ROPS retrofitting in New York.\n\nAn initial phone survey was conducted with a random sample of New York farmers to identify a potential target population. Following target selection, in-depth interviews were conducted to isolate barriers and motivators to retrofitting. This information was used to develop message prototypes which were tested in small focus group discussions. Selected and revised messages, as well as various other incentives developed in response to feedback from interviews, were then tested in a prospective, quasi-randomized controlled trial.\n\nSmall crop and livestock farms were selected as the intervention target since they represent 86% of New York farms with none or only one ROPS protected tractor. Barriers to retrofitting which were identified in interviews were: 1) constant exposures normalize risk, 2) risk is modeled by significant others and 3) safety in general and retrofitting in particular requires too much time and money. The piloting of ROPS incentives led to a marked increase in ROPS sales in New York.\n\nSocial Marketing provides a promising framework for the design of agricultural injury prevention programs. The potential implications for other health initiatives seeking to promote behaviour change are also discussed.", "PMID": "19004904"}], "labels": [{"PMID": "10146854", "label": "excluded"}, {"PMID": "10589318", "label": "excluded"}, {"PMID": "11428249", "label": "excluded"}, {"PMID": "12453809", "label": "excluded"}, {"PMID": "15805371", "label": "excluded"}, {"PMID": "15933410", "label": "excluded"}, {"PMID": "16309707", "label": "excluded"}, {"PMID": "16531596", "label": "excluded"}, {"PMID": "18836043", "label": "excluded"}, {"PMID": "19004904", "label": "excluded"}]}
{"metadata": {"review_pmid": "38197473"}, "inputs": {"background": "Emotional and behavioural difficulties (EBD) in children are common, characterised by externalising or internalising behaviours that can be highly stable over time. EBD are an important cause of functional disability in childhood, and predictive of poorer psychosocial, academic, and occupational functioning into adolescence and adulthood. The prevalence, stability, and long-term consequences of EBD highlight the importance of intervening in childhood when behavioural patterns are more easily modified. Multiple factors contribute to the aetiology of EBD in children, and parenting plays an important role. The relationship between parenting and EBD has been described as bidirectional, with parents and children shaping one another's behaviour. One consequence of bidirectionality is that parents with insufficient parenting skills may become involved in increasingly negative behaviours when dealing with non-compliance in children. This can have a cyclical effect, exacerbating child behavioural difficulties and further increasing parental distress. Behavioural or skills-based parenting training can be highly effective in addressing EBD in children. However, emotional dysregulation may intercept some parents' ability to implement parenting skills, and there is recognition that skills-based interventions may benefit from adjunct components that better target parental emotional responses. Mindful parenting interventions have demonstrated some efficacy in improving child outcomes via improvements in parental emotion regulation, and there is potential for mindfulness training to enhance the effectiveness of standard parent training programmes.", "objectives": "To assess the effectiveness of mindfulness-enhanced parent training programmes on the psychosocial functioning of children (aged 0 to 18 years) and their parents.", "selection criteria": "We included randomised and quasi-randomised trials. Participants were parents or caregivers of children under the age of 18. The intervention was mindfulness-enhanced parent training programmes compared with a no-intervention, waitlist, or attentional control, or a parent training programme with no mindfulness component. The intervention must have combined mindfulness parent training with behavioural or skills-based parent training. We defined parent training programmes in terms of the delivery of a standardised and manualised intervention over a specified and limited period, on a one-to-one or group-basis, with a well-defined mindfulness component. The mindfulness component must have included mindfulness training (breath, visualisation, listening, or other sensory focus) and an explicit focus on present-focused attention and non-judgemental acceptance."}, "context": [{"title": "Reducing potential for child abuse among methadone-maintained parents: results from a randomized controlled trial.", "abstract": "High rates of child abuse and neglect occur in many families in which either or both parents abuse illicit drugs. This study reports on the results of a randomized controlled trial with families having a parent on methadone maintenance (N = 64), in which an intensive, home-based intervention, the Parents Under Pressure (PUP) program, was compared to standard care. A second brief intervention control group of families received a two-session parenting education intervention. The PUP intervention draws from the ecological model of child development by targeting multiple domains of family functioning including the psychological functioning of individuals in the family, parent-child relationships, and social contextual factors. Mindfulness skills were included to address parental affect regulation, a significant problem for this group of parents. At 3- and 6-month follow-up, PUP families showed significant reductions in problems across multiple domains of family functioning, including a reduction in child abuse potential, rigid parenting attitudes, and child behavior problems. Families in the brief intervention group showed a modest reduction in child abuse potential but no other changes in family function. There were no improvements found in the standard care group and some significant worsening was observed. Results are discussed in terms of their implications for improved treatment.", "PMID": "17481461"}, {"title": "Pilot study to gauge acceptability of a mindfulness-based, family-focused preventive intervention.", "abstract": "The purpose of the present study was to conduct a test of acceptability of a new model for family-focused drug prevention programs for families of early adolescents. An existing evidence-based behavioral intervention, the Strengthening Families Program: For Parents and Youth 10-14 (SFP), was adapted to include concepts and activities related to mindfulness and mindful parenting (an extension of mindfulness to the interpersonal domain of parent-child relationships). The foundation for this innovative intervention approach stems from research on the effects of mind-body treatments involving mindfulness meditation and the function of stress and coping in relation to parenting and parent well-being. One group of families participated in a seven-week pilot of this mindfulness-enhanced version of SFP. Results of a mixed-method implementation evaluation suggest that the new intervention activities were generally feasible to deliver, acceptable to participants, and perceived to yield positive benefits for family functioning and parent psychological well-being. The next phase of this research will involve curriculum refinement based upon results of this initial study, and a larger pilot efficacy trial will be conducted.", "PMID": "19680815"}, {"title": "Changing Parent's Mindfulness, Child Management Skills and Relationship Quality With Their Youth: Results From a Randomized Pilot Intervention Trial.", "abstract": "We evaluated the efficacy of a mindful parenting program for changing parents' mindfulness, child management practices, and relationships with their early adolescent youth and tested whether changes in parents' mindfulness mediated changes in other domains. We conducted a pilot randomized trial with 65 families and tested an adapted version of the ", "PMID": "24013587"}, {"title": "Interventions to reduce behavioral problems in children with cerebral palsy: an RCT.", "abstract": "To test Stepping Stones Triple P (SSTP) and Acceptance and Commitment Therapy (ACT) in a trial targeting behavioral problems in children with cerebral palsy (CP).\n\nSixty-seven parents (97.0% mothers; mean age 38.7 \u00b1 7.1 years) of children (64.2% boys; mean age 5.3 \u00b1 3.0 years) with CP (Gross Motor Function Classification System = 15, 22%; II = 18, 27%; III =12, 18%; IV = 18, 27%; V = 4, 6%) participated and were randomly assigned to SSTP, SSTP + ACT, or waitlist. Primary outcomes were behavioral and emotional problems (Eyberg Child Behavior Inventory [ECBI], Strengths and Difficulties Questionnaire [SDQ]) and parenting style (Parenting Scale [PS]) at postintervention and 6-month follow-up.\n\nSSTP with ACT was associated with decreased behavioral problems (ECBI Intensity mean difference [MD] = 24.12, confidence interval [CI] 10.22 to 38.03, P = .003; ECBI problem MD = 8.30, CI 4.63 to 11.97, P < .0001) including hyperactivity (SDQ MD = 1.66, CI 0.55 to 2.77, P = .004), as well as decreased parental overreactivity (PS MD = 0.60, CI 0.16 to 1.04, P = .008) and verbosity (PS MD = 0.68, CI 0.17 to 1.20, P = .01). SSTP alone was associated with decreased behavioral problems (ECBI problems MD = 6.04, CI 2.20 to 9.89, P = .003) and emotional symptoms (SDQ MD = 1.33, CI 0.45 to 2.21, P = .004). Decreases in behavioral and emotional problems were maintained at follow-up.\n\nSSTP is an effective intervention for behavioral problems in children with CP. ACT delivers additive benefits.", "PMID": "24709926"}, {"title": "Integrating mindfulness with parent training: effects of the Mindfulness-Enhanced Strengthening Families Program.", "abstract": "There is growing support for the efficacy of mindfulness training with parents as an intervention technique to improve parenting skills and reduce risk for youth problem behaviors. The evidence, however, has been limited to small scale studies, many with methodological shortcomings. This study sought to integrate mindfulness training with parents into the Strengthening Families Program: For Parents and Youth 10-14 (SFP 10-14), an empirically-validated family-based preventive intervention. It used a randomized-controlled comparative effectiveness study design (N = 432 families, 31% racial/ethnic minority) to test the efficacy of the Mindfulness-Enhanced Strengthening Families Program (MSFP), compared to standard SFP 10-14 and a minimal-treatment home study control condition. Results indicated that, in general, MSFP was as effective as SFP 10-14 in improving multiple dimensions of parenting, including interpersonal mindfulness in parenting, parent-youth relationship quality, youth behavior management, and parent well-being, according to both parent and youth reports at both postintervention and 1-year follow-up. This study also found that in some areas MSFP boosted and better sustained the effects of SFP 10-14, especially for fathers. Although the pattern of effects was not as uniform as hypothesized, this study provides intriguing evidence for the unique contribution of mindfulness activities to standard parent training.", "PMID": "25365122"}, {"title": "Mindfulness training effects for parents and educators of children with special needs.", "abstract": "Parents and teachers of children with special needs face unique social-emotional challenges in carrying out their caregiving roles. Stress associated with these roles impacts parents' and special educators' health and well-being, as well as the quality of their parenting and teaching. No rigorous studies have assessed whether mindfulness training (MT) might be an effective strategy to reduce stress and cultivate well-being and positive caregiving in these adults. This randomized controlled study assessed the efficacy of a 5-week MT program for parents and educators of children with special needs. Participants receiving MT showed significant reductions in stress and anxiety and increased mindfulness, self-compassion, and personal growth at program completion and at 2 months follow-up in contrast to waiting-list controls. Relational competence also showed significant positive changes, with medium-to-large effect sizes noted on measures of empathic concern and forgiveness. MT significantly influenced caregiving competence specific to teaching. Mindfulness changes at program completion mediated outcomes at follow-up, suggesting its importance in maintaining emotional balance and facilitating well-being in parents and teachers of children with developmental challenges.", "PMID": "22409766"}, {"title": "Mindfulness-based stress reduction for parents of young children with developmental delays: implications for parental mental health and child behavior problems.", "abstract": "Parents of children with developmental delays (DD) typically report elevated levels of parental stress compared with parents of typically developing children. Children with DD are also at high risk for exhibiting significant behaviour problems. Parental stress has been shown to impact the development of these behaviour problems; however, it is rarely addressed in interventions aimed at reducing child behaviour problems. The current study examined the efficacy of mindfulness-based stress reduction (MBSR) for parents of children with DD by investigating whether this intervention is effective in reducing parenting stress and whether decreases in parenting stress lead to reductions in behaviour problems among children with DD.\n\nForty six parents of children with DD were randomly assigned to an immediate treatment or wait list-control group. Participants completed questionnaires assessing parental stress and child behaviour problems at intake and at a second assessment, which took place after only the immediate treatment group had received the MBSR.\n\nParents who participated in MBSR reported significantly less stress and depression as well as greater life satisfaction compared with wait list-control parents. Regarding child outcomes, children whose parents participated in MBSR were reported to have fewer behaviour problems following the intervention, specifically in the areas of attention problems and ADHD symptomatology.\n\nResults indicated that MBSR may be an effective intervention for ameliorating parental stress and mental health problems among parents of children with DD. Additionally, these benefits may 'spill over' and improve behaviour challenges among these children.", "PMID": "23813562"}, {"title": "The effect of a family-based mindfulness intervention on children with attention deficit and hyperactivity symptoms and their parents: design and rationale for a randomized, controlled clinical trial (Study protocol).", "abstract": "About 4 % of children in Hong Kong have attention deficit hyperactivity disorder (ADHD). The parents of children with ADHD report higher levels of stress and show more negative parenting behavior. Medication and behavior training are evidence-based treatments, but both show significant limitations. In short, medical treatment is not suitable for preschool children and would suppress growth, whereas parents under stress may not be capable of consistently applying behavior management skills. Mindfulness training can improve attention and facilitate cognitive development and overall functioning. It has been widely adopted as a treatment option in health care, but its application in a family context is limited. In this context, a family-based mindfulness intervention (FBMI) has been developed to promote the attention and mental health of children with attention symptoms and to reduce the stress experienced by their parents. This article describes the design and conduct of the trial.\n\nA multicenter, 8-week, waitlist, randomized controlled trial of FBMI is currently being conducted in Hong Kong (from mid-2015 to mid-2016). Its effectiveness will be examined by comparing the participants who receive treatment to those in a waitlist control group. The study population consists of one hundred twenty children with ADHD, or with symptoms of inattention and hyperactivity, between 5 and 7 years of age and their parents. To be included in the study, the children are required to meet or exceed the borderline cutoff score of the Chinese version of the Strengths and Weaknesses of ADHD Symptoms and Normal Behaviors Rating Scale (SWAN-C). The primary outcome measures are the children's ADHD symptoms and behavior and the parents' stress. The secondary outcome measures include the children's overall behavioral problems and performance on the Attention Network Test, the parents' ADHD symptoms, the parents' mindful parenting scores, and heart rate variability of parents.\n\nThis study is probably the first randomized controlled trial of FBMI for young children and their caregivers. A rigorous design and multiple outcome measures are used to examine the effectiveness of FBMI. If the hypotheses are confirmed, FBMI may serve as an additional treatment option for children with ADHD.\n\nThis study is registered with the Chinese Clinical Trial Registry (reference number: ChiCTR-IOR-15007292 ). Registered 28 October 2015.", "PMID": "26980323"}, {"title": "Effectiveness of mindfulness-based interventions on quality of life and positive reappraisal coping among parents of children with autism spectrum disorder.", "abstract": "Previous research has supported mindfulness-based interventions (MBIs) to enhance quality of life (QOL) in different populations, but no studies have been found to examine the effectiveness of MBIs on QOL among parents of children with ASD.\n\nThe purpose of the current study was to examine the effectiveness of brief MBI on perceived QOL and positive stress reappraisal (PSR) among parents of children with ASD.\n\nA quasi-experimental, with nonequivalent control group design was used. One hundred and four parents of children with ASD were equally assigned to the intervention and control groups. The study groups were matched on measures of their gender and age, and level of severity of ASD in children. The intervention group participated in MBI program for 5 weeks, while the control group had not attended the program.\n\nAfter the intervention program, results of paired samples t-test indicated that parents in the intervention group demonstrated significant improvements in measures of psychological health domain of QOL, social health domain of QOL, mindfulness, and positive stress reappraisal with medium to large effect size (P<0.01). The control group demonstrated improvement in measures of the dependent variables with small effect size.\n\nMBI is culturally adaptable, acceptable, and effective method to improve QOL and PSR in parents of children with ASD.", "PMID": "27107368"}, {"title": "Manual Development and Pilot Randomised Controlled Trial of Mindfulness-Based Cognitive Therapy Versus Usual Care for Parents with a History of Depression.", "abstract": "Parental depression can adversely affect parenting and children's development. We adapted mindfulness-based cognitive therapy (MBCT) for parents (MBCT-P) with a history of depression and describe its development, feasibility, acceptability and preliminary estimates of efficacy. Manual development involved interviews with 12 parents who participated in MBCT groups or pilot MBCT-P groups. We subsequently randomised 38 parents of children aged between 2 and 6\u00a0years to MBCT-P plus usual care (", "PMID": "27642371"}], "labels": [{"PMID": "17481461", "label": "included"}, {"PMID": "19680815", "label": "included"}, {"PMID": "24013587", "label": "included"}, {"PMID": "24709926", "label": "included"}, {"PMID": "25365122", "label": "included"}, {"PMID": "22409766", "label": "excluded"}, {"PMID": "23813562", "label": "excluded"}, {"PMID": "26980323", "label": "excluded"}, {"PMID": "27107368", "label": "excluded"}, {"PMID": "27642371", "label": "excluded"}]}
{"metadata": {"review_pmid": "38193637"}, "inputs": {"background": "The prevalence of peripheral artery disease (PAD) in the general population is about 12% to 14% and it increases with age. PAD increased from 164 million people in 2000 to 202 million people in 2010. More than two-thirds of people with PAD are based in low- or middle-income countries. Critical limb ischaemia (CLI) occurs in 1% to 2% of people with intermittent claudication over five years. One third of people with CLI have isolated below the knee (BTK) lesions. CLI and isolated BTK lesions are associated with a higher incidence of limb loss when compared with people with multilevel arterial disease. Endovascular procedures such as angioplasty (with or without stenting) are widely used to treat isolated BTK lesions, aiming to improve blood flow and limb salvage. The technical success of any angioplasty procedure depends on the ability to cross the target lesion. Failed attempts are underestimated in the literature and failures in the real world appear to be higher than reported. People with isolated BTK lesions undergoing angioplasty by conventional femoral access present a high failure rate to cross these lesions. Retrograde distal access may provide some advantages that can lead to successful crossing of the target lesion.", "objectives": "To evaluate the benefits and harms of retrograde distal access versus conventional femoral access for people undergoing below the knee angioplasty.", "selection criteria": "We planned to include randomised or quasi-randomised controlled trials comparing people undergoing retrograde distal access versus people undergoing conventional femoral access (ipsilateral antegrade or contralateral retrograde) for BTK angioplasty."}, "context": [{"title": "Percutaneous transluminal angioplasty of infrapopliteal arteries in patients with intermittent claudication: acute and one-year results.", "abstract": "In advanced stages of infrapopliteal peripheral arterial occlusive disease with critical ischemia of the lower limb, the efficacy of percutaneous transluminal angioplasty (PTA) is well established. In contrast, PTA is currently not the therapy of choice in intermittent claudication (IC). In this prospective study, patients with IC were treated percutaneously. Technical aspects and long-term results are presented. In 78 patients (61 males, or 78.2%; age, 71 +/- 11 years) with IC (Rutherford grade 2 or 3), 104 interventions were performed. At baseline, the initial/absolute walking distance (IWD/AWD) was 49 +/- 34/102 +/- 88 m; the ankle-brachial index (ABI) was 0.61 +/- 0.2 before and 0.49 +/- 0.2 after exercise. A crossover approach was used in 74% and an antegrade access in 26% of the cases. In 19 interventions (18.3%), the excimer laser technique was used, and in 26 interventions (25%) a total of 39 stents were implanted. Procedural success rate was 89.4%. IWD and AWD improved to 107 +/- 67 m and 167 +/- 74 m (P < 0.0001 vs. baseline each), respectively, and the ABI at rest and after exercise increased to 0.88 +/- 0.13 and 0.72 +/- 0.19 (P < 0.0001 vs. baseline each). Six complications occurred (5.8%). One embolic occlusion, two minor groin hematoma, one arteriovenous fistula, one compartment syndrome, and one perforation. All were treated conservatively. After 12 months, the primary patency rate was 66.3%, cumulative primary assisted patency rate was 81.9%, and secondary patency rate was 91.5%. Percutaneous revascularization of infrapopliteal arteries in patients with IC is feasible and associated with good acute clinical results and an encouraging long-term patency rate. The complication rate is low.", "PMID": "15619276"}, {"title": "Sirolimus-eluting versus bare stents after suboptimal infrapopliteal angioplasty for critical limb ischemia: enduring 1-year angiographic and clinical benefit.", "abstract": "To report the 1-year angiographic and clinical outcome from a prospective single-center study investigating the infrapopliteal application of sirolimus-eluting versus bare metal stents in patients with critical limb ischemia (CLI) who underwent below-the-knee endovascular revascularization.\n\nStenting was performed as a bailout procedure for suboptimal angioplasty results (flow-limiting dissection, elastic recoil, or postangioplasty residual stenosis >30%). In the first 29 patients, infrapopliteal stenting was performed with bare metal stents (group B) and with sirolimus-eluting stents in the other 29 patients (group S).\n\nBelow-the-knee angioplasty and stenting involved 65 lesions in 40 infrapopliteal arteries of 29 limbs in group B and 66 lesions in 41 infrapopliteal arteries of 29 limbs in group S. Baseline comorbidities (hyperlipidemia and symptomatic cardiac and carotid disease) were more pronounced in group S (p<0.05). At 6 months, sirolimus-eluting stents demonstrated significantly higher primary patency (OR 5.625, 95% CI 1.711 to 18.493, p = 0.004) and decreased in-stent binary restenosis (OR 0.067, 95% CI 0.021 to 0.017, p<0.001) and in-segment binary restenosis (OR 0.229, 95% CI 0.099 to 0.533, p = 0.001). After 1 year, sirolimus-eluting stents were steadily associated with increased primary patency (OR 10.401, 95% CI 3.425 to 31.589, p<0.001) and significantly less in-stent (OR 0.156, 95% CI 0.060 to 0.407, p<0.001) and in-segment (OR 0.089, 95% CI 0.023 to 0.349, p = 0.001) binary restenosis. In addition, sirolimus-eluting stents were associated with significantly fewer cumulative target lesion reinterventions at 6 months (OR 0.057, 95% CI 0.008 to 0.426, p = 0.005) and 1 year (OR 0.238, 95% CI 0.067 to 0.841, p = 0.026). No significant differences between groups B and S were noted at 1 year with respect to mortality (10.3% versus 13.8%, respectively), minor amputation (17.2% versus 10.3%), or limb salvage (100% versus 96%).\n\nThe application of sirolimus-eluting stents reduces the restenosis rate in the infrapopliteal arteries and the rate of repeat endovascular procedures the first year after treatment.", "PMID": "17484536"}, {"title": "Clinical results of below-the knee intervention using pedal-plantar loop technique for the revascularization of foot arteries.", "abstract": "Recent registries and randomized trials support the role of percutaneous revascularization in patients with critical limb ischemia (CLI) due to below-the-knee (BTK) atherosclerotic disease, as percutaneous transluminal angioplasty (PTA) for BTK disease has shown to be feasible and safe in this setting. Nonetheless, succes rates remain suboptimal with current techniques. The authors aimed to appraise clinical results following PTA of foot vessels exploiting a novel technique, based on the recanalization of both pedal and plantar arteries and their anatomical anastomosis in order to restore direct arterial in-flow from both anterior and posterior tibial vessels, defined as the pedal-plantar loop technique.\n\nBaseline, procedural and mid-term outcome data of all consecutive patients with CLI due to BTK disease in which PTA was attempted using the pedal-plantar loop technique were prospectively collected between January 2007 and September 2008. The primary end-point was acute success (i.e. the composite of technical, angiographic and procedural success). Secondary end-points included limb salvage rate, major (above the ankle) and minor (below the ankle) amputation, change in Rutherford class and transcutaneous oxygen tension, reocclusion/restenosis, rehospitalization, and repeat revascularization after 12 months.\n\nA total of 1331 consecutive patients with CLI were treated using BTK PTA and 135 (10.1%) were approached with the pedal-plantar loop technique in order to recanalize the foot arteries. Target lesions were mostly occlusive and diffusely diseased, involving in most cases the tibial arteries as well as the in-flow and out-flow vessels. Acute success was achieved for tibial PTA in 100% of the cases, with ability to position and inflate the balloon and achieve adequate angiographic results without peri-procedural complications in all, whereas acute success for the pedal-plantar loop technique was 85%. Clinical improvement in functional status was obtained and maintained after an average of 12 months, with a significant improvement of transcutaneous oxygen tension after 15 days, 59+/-16 mmHg in the group of patients in which the foot arteries revascularization was successfully feasible, versus 42+/-12 mmHg in patients achieving patency of two BTK vessels at the ankle level with partial out-flow in the foot (P<0.001).\n\nPercutaneous revascularization of foot arteries in patients with CLI is feasible and safe, and appears to provide positive clinical results at both acute and mid-term follow-up.", "PMID": "19543193"}, {"title": "Alternative techniques for treatment of complex below-the knee arterial occlusions in diabetic patients with critical limb ischemia.", "abstract": "The purpose of this study was to describe alternative endovascular (EV) techniques and assess their feasibility and efficacy in minimizing failure rates in limb salvage for the treatment of complex below-the knee (BTK) occlusions that could not be crossed with a conventional antegrade access.\n\nBetween December 2007 and November 2010, 1,035 patients (557 male) underwent EV treatment for critical limb ischemia in our institution. In 124 (12% [83 male], mean age 68.2\u00a0\u00b1\u00a00.5\u00a0years) patients, transfemoral antegrade revascularization attempt failed, and an alternative approach was used. Follow-up was performed at 1 and 6\u00a0months. Results were compared with 56 patients treated between November 2002 and November 2007, in whom conventional technique was unsuccessful and unconventional techniques were not adopted.\n\nTechnical success was achieved in 119 (96%) patients. The limb-salvage rates were 96.8% and 83% at 1- and 6-month follow-up, respectively. Sixteen (12.9%) and 33 (26.6%) patients underwent reintervention at 1- and 6-month follow-up, respectively. Transcutaneous oxygen tension increased at 1\u00a0month (44.7\u00a0\u00b1\u00a01.1 vs. 15.7\u00a0\u00b1\u00a00.8\u00a0mmHg; p\u00a0<\u00a00.001) and remained stable at follow-up. Twenty (16.1%) patients required major amputation. Thirteen (10.4%) patients died during follow-up. In our previous experience, percutaneous transluminal angioplasty failure, amputation, and death rates were 10.9, 39.2, and 23.2%, respectively. Alternative techniques allowed a significant decrease of major amputation and death rates (p\u00a0=\u00a00.0001 and p\u00a0=\u00a00.02, respectively).\n\nThe use of alternative techniques seems feasible in case of a failed antegrade BTK revascularization attempt and could minimize failure rates in the treatment of complex occlusions while providing satisfying clinical success rates at 6\u00a0months.", "PMID": "22278664"}, {"title": "Incidence and risk factors of vascular complications following endovascular treatment of peripheral arterial disease via the popliteal artery.", "abstract": "To evaluate vascular complications associated with endovascular treatment (EVT) of peripheral arterial disease (PAD) through the popliteal artery and to identify the risk factors for these complications. Between November 2005 and January 2009, 63 patients with PAD received EVT via the popliteal artery. Retrograde (n\u00a0=\u00a058) and antegrade (n\u00a0=\u00a05) transpopliteal procedures were performed to target 77 lesions, including 12 distal to the trifurcation. Thirty-five punctures were performed under ultrasound guidance and 7 under angiographic guidance; 21 punctures were performed without any guidance. Vascular complications were evaluated by physical examination and duplex ultrasonography. Vascular complications at the popliteal puncture site occurred in 8 patients (12.7%): 6 hematomas and 2 arteriovenous fistulas (AVF). Seven of 24 patients receiving hemodialysis (HD) (29%) had significantly higher complications (P\u00a0=\u00a00.004) compared with 1 of 39 patients not receiving hemodialysis (non-HD) (2.6%). HD alone was also a significant risk factor for hematoma (P\u00a0=\u00a00.010). Both AVF occurred in HD patients (P\u00a0=\u00a00.141), and one occurred despite ultrasound-guided puncture. Ultrasound-guided puncture showed no significant improvement in reducing both complications. The combination of antiplatelet and anticoagulant therapy showed no statistical significance in overall complications. In non-HD patients, the transpopliteal approach in the EVT of PAD seems to be safe. More attention should be paid to HD patients when using the transpopliteal approach due to a higher complication rate. ", "PMID": "24122587"}, {"title": "Retrograde transplantar arch angioplasty of below-the-knee arterial occlusions: outcomes compared to anterograde recanalization.", "abstract": "To compare the clinical outcomes of retrograde transplantar arch angioplasty and conventional below-the-knee (BTK) anterograde recanalization.\n\nOne hundred twelve limbs in 96 patients underwent attempt at antegrade tibial angioplasty. Among 27 technical failures, retrograde trans-dorsal or -planter percutaneous transluminal angioplasty was attempted in 22 limbs. Ankle-brachial index (ABI), thrombolysis in myocardial infarction (TIMI) flow grade, and dorsal/plantar arterial pulse score improvement were compared immediately after the procedures between patients received successful anterograde angioplasty (anterograde angioplasty group [AAG], 85 limbs in 71 patients) and retrograde angioplasty (retrograde angioplasty group [RAG], 22 limbs in 20 patients). Target vessel restenosis and limb salvage were observed during follow-up.\n\nPrimary technical success rate was 75.9% in the RAG (vs. 74.0% AAG, P > .05). ABI improved from 0.55 \u00b1 0.21 to 0.93 \u00b1 0.19 in the RAG (vs. 0.56 \u00b1 0.14 to 0.89 \u00b1 0.18 AAG, P > .05). TIMI flow grade demonstrated greater reperfusion of distal foot tissue in the RAG (2.3 \u00b1 0.8 vs. 1.0 \u00b1 0.8, P < .05). Primary patency rates at 12 and 24 months were 63.6% (14 of 22) and 45.5% (10 of 22) in the RAG and 52.9% (45 of 85) and 37.6% (32 of 85) in the AAG, respectively (P > .05). Kaplan-Meier analysis after 24 months found limb salvage rates of 93.8% in the RAG and 96.5% in the AAG (P > .05).\n\nRetrograde transplantar arch angioplasty achieved better immediate blood flow and similar ABI improvement, primary patency rate, and limb salvage rate compared to conventional transtibial angioplasty for BTK occlusions. This could become a supplementary technique when anterograde angioplasty fails.", "PMID": "25088835"}, {"title": "Use of Tapered Balloons to Recanalize Occluded Below-the-Knee Arteries in Diabetic Patients with Critical Limb Ischemia.", "abstract": "The aim of this study was to evaluate the outcome of tapered balloon use in recanalization of long occlusions of below-the-knee (BTK) arteries in diabetic patients with critical limb ischemia (CLI).\n\nForty-nine occluded BTK arteries in 35 diabetic patients with CLI were revascularized in our Diabetic Foot Center between January and September 2014 using tapered balloons. Twelve-month outcomes were evaluated in terms of healing of the lesions, survival, limb salvage, primary patency, primary assisted patency, and secondary patency.\n\nThe patients were predominantly male (27/35, 77.1%) with a mean age of 70.9\u00a0years (\u00b110.3 standard deviation [SD]). During the follow-up (mean duration 12.4\u00a0months\u00a0\u00b1\u00a04 SD), healing of the lesions was obtained in 27 of the 35 cases (77.1%). Estimated 12-month survival and limb salvage were 85.7% and 91.1%, respectively. Estimated 12-month primary patency, primary assisted patency, and secondary patency were 78.3%, 79%, and 88.9%, respectively. Univariate analysis demonstrated that the presence of chronic renal failure affected survival (P\u00a0=\u00a00.005), and assignment to Rutherford class 6 affected limb salvage (P\u00a0=\u00a00.005), primary patency (P\u00a0<\u00a00.001), and primary assisted patency (P\u00a0<\u00a00.001). Furthermore, the presence of coronary artery disease affected primary patency (P\u00a0=\u00a00.001) and primary assisted patency (P\u00a0=\u00a00.05).\n\nTapered balloons are a safe and effective means to recanalize long occlusions of BTK arteries in diabetic patients with CLI. Outcomes are poorer in patients with major tissue loss and with a history of coronary artery disease. Further experience with larger groups is needed to validate these outcomes.", "PMID": "26616502"}, {"title": "Outcomes of Endovascular Therapy With the Controlled Antegrade Retrograde Subintimal Tracking (CART) or Reverse CART Technique for Long Infrainguinal Occlusions.", "abstract": "To compare the safety, efficacy, and clinical outcomes associated with the controlled antegrade retrograde subintimal tracking (CART) or reverse CART (r-CART) technique to the conventional retrograde approach in the treatment of patients with long infrainguinal occlusions.\n\nFrom May 2008 to April 2014, 121 patients failed antegrade recanalization and underwent a retrograde approach to recanalize long infrainguinal occlusions. Patients who underwent successful endovascular therapy (EVT) by the conventional retrograde approach (CRA group) were compared to patients who had successful EVT using the CART/r-CART technique (CART group) after failure of a bidirectional approach. The efficacy, safety, vessel patency, and other clinical outcomes were compared between the groups.\n\nFifty-eight patients (mean age 71.6 \u00b1 12.2 years; 32 men) underwent successful EVT (47.9%, 58/121) using the conventional retrograde approach (CRA group), while 44 patients (mean age 70.8 \u00b1 11.1 years; 31 men) among the 50 patients who underwent the CART/r-CART technique were successfully treated (88.0%, 44/50). Both groups had similar average occlusion lengths and gained 100% immediate hemodynamic success after EVT. There was no significant difference between the groups regarding procedure-related complications. During follow-up, 28 patients died (p=0.380), but there were no differences in the rates of major (p=0.279) or minor amputation (p=0.417) between the groups. There was no difference in the 2-year primary patency (31% vs 24%, p=0.686), assisted primary patency (66% vs 76%, p=0.251), target vessel revascularization (65% vs 54%, p=0.845), or sustained clinical success (52% vs 46%, p=0.995) rates between the CRA and CART groups, respectively.\n\nBased on acceptable safety, efficacy, and follow-up results in this study, the CART/r-CART technique can salvage patients with long peripheral occlusions after failure of the conventional antegrade or retrograde approach.", "PMID": "26862146"}, {"title": "Outcome of a drug-eluting stent in longer below-the-knee lesions in patients with critical limb ischemia.", "abstract": "The superiority of drug eluting stents versus bare metal stents or balloon angioplasty in the treatment of patients with critical limb ischemia and infrapopliteal lesions has been established. However, only shorter lesions were evaluated. This study was designed to evaluate the immediate and long-term (up to 12 months) outcome of the Xience Prime\u2122 Everolimus-Eluting Coronary Stent System (Abbott Vascular) in a controlled, prospective, multi-center investigation for long lesions up to 10 cm.\n\nAll patients with critical limb ischemia and long infrapopliteal lesions between 30 and 100 mm, who met the inclusion criteria, were included in this study. The primary endpoint was primary patency at 12 months, defined as absence of restenosis (\u226550% stenosis) or occlusion based on quantitative analysis of contrast angiography.\n\nBetween August 2011 and October 2013, 60 patients were enrolled in this study with a mean lesion length of 47.40\u00b125.06 mm (range 2-100 mm). The primary patency rate at 12 months was 75.4%. Freedom from target lesion revascularization was 84.9%. The amputation rate was rare (94.4% freedom from amputation). At the 12-month follow-up time point, a total of 36 out of 42 (85.7%) patients improved in their Rutherford classification by at least 1 class.\n\nThe use of everolimus-eluting stents in longer infrapopliteal lesions in the treatment of critical limb ischemia is safe and effective with a comparable primary patency, freedom from target lesion revascularization and amputation free survival as in short lesions.", "PMID": "27455888"}, {"title": "Tibiopedal Access for Crossing of Infrainguinal Artery Occlusions: A Prospective Multicenter Observational Study.", "abstract": "To report a prospective, multicenter, observational study (ClinicalTrials.gov identifier NCT01609621) of the safety and effectiveness of tibiopedal access and retrograde crossing in the treatment of infrainguinal chronic total occlusions (CTOs).\n\nTwelve sites around the world prospectively enrolled 197 patients (mean age 71\u00b111 years, range 41-93; 129 men) from May 2012 to July 2013 who met the inclusion criterion of at least one CTO for which a retrograde crossing procedure was planned or became necessary. The population consisted of 64 (32.5%) claudicants (Rutherford categories 2/3) and 133 (67.5%) patients with critical limb ischemia (Rutherford category \u22654). A primary antegrade attempt to cross had been made prior to the tibiopedal attempt in 132 (67.0%) cases. Techniques used for access, retrograde lesion crossing, and treatment were at the operator's discretion. Follow-up data were obtained 30 days after the procedure.\n\nTechnical tibiopedal access success was achieved in 184 (93.4%) of 197 patients and technical occlusion crossing success in 157 (85.3%) of the 184 successful tibial accesses. Failed access attempts were more common in women (9 of 13 failures). The rate of successful crossing was roughly equivalent between sexes [84.7% (50/59) women compared to 85.6% (107/125) men]. Technical success did not differ significantly based on a prior failed antegrade attempt: the access success rate was 92.4% (122/132) after a failed antegrade access vs 95.4% (62/65) in those with a primary tibiopedal attempt (p=0.55). Similarly, crossing success was achieved in 82.8% (101/122) after a failed antegrade access vs 90.3% (56/62) for patients with no prior antegrade attempt (p=0.19). Minor complications related to the access site occurred in 11 (5.6%) cases; no patient had access vessel thrombosis, compartment syndrome, or surgical revascularization.\n\nTibiopedal access appears to be safe and can be used effectively for the crossing of infrainguinal lesions in patients with severe lower limb ischemia.", "PMID": "27558463"}], "labels": [{"PMID": "15619276", "label": "excluded"}, {"PMID": "17484536", "label": "excluded"}, {"PMID": "19543193", "label": "excluded"}, {"PMID": "22278664", "label": "excluded"}, {"PMID": "24122587", "label": "excluded"}, {"PMID": "25088835", "label": "excluded"}, {"PMID": "26616502", "label": "excluded"}, {"PMID": "26862146", "label": "excluded"}, {"PMID": "27455888", "label": "excluded"}, {"PMID": "27558463", "label": "excluded"}]}
{"metadata": {"review_pmid": "38189593"}, "inputs": {"background": "Haemodialysis (HD) requires safe and effective anticoagulation to prevent clot formation within the extracorporeal circuit during dialysis treatments to enable adequate dialysis and minimise adverse events, including major bleeding. Low molecular weight heparin (LMWH) may provide a more predictable dose, reliable anticoagulant effects and be simpler to administer than unfractionated heparin (UFH) for HD anticoagulation, but may accumulate in the kidneys and lead to bleeding.", "objectives": "To assess the efficacy and safety of anticoagulation strategies (including both heparin and non-heparin drugs) for long-term HD in people with kidney failure. Any intervention preventing clotting within the extracorporeal circuit without establishing anticoagulation within the patient, such as regional citrate, citrate enriched dialysate, heparin-coated dialysers, pre-dilution haemodiafiltration (HDF), and saline flushes were also included.", "selection criteria": "Randomised controlled trials (RCTs) and quasi-randomised controlled studies (quasi-RCTs) evaluating anticoagulant agents administered during HD treatment in adults and children with kidney failure."}, "context": [{"title": "Comparison of low-molecular-weight heparin (enoxaparin sodium) and standard unfractionated heparin for haemodialysis anticoagulation.", "abstract": "Low-molecular-weight heparin (LMWH) has been suggested as providing safe, efficient, convenient and possibly more cost-effective anticoagulation for haemodialysis (HD) than unfractionated heparin, with fewer side-effects and possible benefits on uraemic dyslipidaemia.\n\nIn this prospective, randomized, cross-over study we compared the safety, clinical efficacy and cost effectiveness of Clexane (enoxaparin sodium; Rh\u00f4ne-Poulenc Rorer) with unfractionated heparin in 36 chronic HD patients. They were randomly assigned to either Clexane (1 mg/kg body weight, equivalent to 100 IU) or standard heparin, and followed prospectively for 12 weeks (36 dialyses) before crossing over to the alternate therapy for a further 12 weeks. Heparin anticoagulation was monitored using activated coagulation times.\n\nDialysis with Clexane resulted in less frequent minor fibrin/clot formation in the dialyser and lines than with heparin (P<0.001), but was accompanied by increased frequency of minor haemorrhage between dialyses (P<0.001). Clexane dose reduction (to a mean of 0.69 mg/kg) eliminated excess minor haemorrhage without increasing clotting frequencies. Mean vascular compression times were similar in both groups. Over 24 weeks, no changes in standard serum lipid profiles were observed.\n\nThis study suggests that a single-dose protocol of Clexane is an effective and very convenient alternative to sodium heparin, but currently direct costs are about 16% more. We recommend an initial dose of 0.70 mg/kg.", "PMID": "10534515"}, {"title": "Comparison of low-molecular-weight heparin (enoxaparin sodium) and standard unfractionated heparin for haemodialysis anticoagulation.", "abstract": "Low-molecular-weight heparin (LMWH) has been suggested as providing safe, efficient, convenient and possibly more cost-effective anticoagulation for haemodialysis (HD) than unfractionated heparin, with fewer side-effects and possible benefits on uraemic dyslipidaemia.\n\nIn this prospective, randomized, cross-over study we compared the safety, clinical efficacy and cost effectiveness of Clexane (enoxaparin sodium; Rh\u00f4ne-Poulenc Rorer) with unfractionated heparin in 36 chronic HD patients. They were randomly assigned to either Clexane (1 mg/kg body weight, equivalent to 100 IU) or standard heparin, and followed prospectively for 12 weeks (36 dialyses) before crossing over to the alternate therapy for a further 12 weeks. Heparin anticoagulation was monitored using activated coagulation times.\n\nDialysis with Clexane resulted in less frequent minor fibrin/clot formation in the dialyser and lines than with heparin (P<0.001), but was accompanied by increased frequency of minor haemorrhage between dialyses (P<0.001). Clexane dose reduction (to a mean of 0.69 mg/kg) eliminated excess minor haemorrhage without increasing clotting frequencies. Mean vascular compression times were similar in both groups. Over 24 weeks, no changes in standard serum lipid profiles were observed.\n\nThis study suggests that a single-dose protocol of Clexane is an effective and very convenient alternative to sodium heparin, but currently direct costs are about 16% more. We recommend an initial dose of 0.70 mg/kg.", "PMID": "10534515"}, {"title": "Comparison of different routes of administration of nadroparin in hemodialysis.", "abstract": "In an open, crossover, randomized study in hemodialysis patients, we investigated possible differences of the effect of the low molecular weight heparin (LMWH) nadroparin/fraxiparine in relation to the route of administration.\n\nThe effect of nadroparin, administered by the venous line or by the arterial line after priming of the extracorporeal circuit with a part of the total dose administered, was compared with administration of the same dose by the arterial line as recommended by the manufacturer. Twelve stable, chronic hemodialysis patients were studied during 3 dialysis sessions for each treatment option. Concomitant medication was kept constant.\n\nResults obtained after administration of nadroparin by the venous line were comparable to those obtained after administration by the arterial line. When a part of the dose was added to the priming solution, the anti-Xa activity, measured after 2 hours of dialysis, was somewhat lower (p = 0.09). There was also a tendency towards longer manual compression time in this group. There was no difference in hemoglobin, serum urea and creatinine before the study and at the end of each treatment option.\n\nWe therefore conclude that the safety and efficacy of administration of LMWH by the arterial and by the venous route are identical. There is no need for addition of a small dose of LMWH to the priming fluid.", "PMID": "10584996"}, {"title": "Effect of anticoagulation on blood membrane interactions during hemodialysis.", "abstract": "Adequate anticoagulation is a precondition to prevent extracorporeal blood clotting and to improve biocompatibility during hemodialysis. In this study, we performed a morphologic analysis by using scanning electron microscopy to compare three modes of anticoagulation-conventional unfractionated heparin (UFH), low molecular weight heparin (LMWH; dalteparin sodium), or sodium citrate during hemodialysis-on membrane-associated coagulation activation.\n\nFifteen patients on regular hemodialysis therapy were investigated. Five patients received UFH, five patients LMWH, and five patients sodium citrate as an anticoagulant during a standardized hemodialysis protocol using a single-use polysulfone capillary dialyzer. Membrane-associated clotting was evaluated using a scanning electron microscope. A dialyzer clotting score was used for quantitative description of coagulation activation on membrane segments.\n\nUsing UFH as an anticoagulant revealed the most pronounced cell adhesion and thrombus formation and the highest dialyzer clotting score (11.5 +/- 1.3 of a maximal 20 points). LMWH had a lower dialyzer clotting score than UFH (10.4 +/- 1.2 of 20 points). During the use of sodium citrate, a negligible thrombus formation and the lowest dialyzer clotting score (1.6 +/- 0.6 of 20 points, P < 0.05) were observed.\n\nThe results of this investigation indicate that using sodium citrate as an anticoagulant during hemodialysis induces a lower activation of coagulation than both conventional and fractionated heparin, which might contribute to an improvement of biocompatibility of hemodialysis extracorporeal circulation.", "PMID": "10504511"}, {"title": "A randomized trial of minidose warfarin for the prevention of late malfunction in tunneled, cuffed hemodialysis catheters.", "abstract": "Minidose warfarin (1 mg/day) has been associated with a 74% reduction in the thrombosis rate of central venous catheters used in oncology patients. To determine the efficacy of minidose warfarin on late malfunction caused by thrombosis or fibrin sheath formation in tunneled, cuffed catheters (TCC) used for hemodialysis (HD), we performed a randomized, placebo-controlled trial.\n\nOne hundred five chronic HD patients with TCCs were initially randomized. Of these, 85 (warfarin 41 and placebo 44) completed the first two weeks of the protocol and were followed for the first year of TCC life or until TCC removal.\n\nSixteen TCCs failed with late TCC malfunction, eight in each group. In a multivariate analysis, there was no significant effect of warfarin on thrombosis-free TCC survival or time to the first urokinase (UK) instillation for incipient thrombosis. The presence of a low hemoglobin (Hgb; <10.5 g/dL) or a low international normalized ratio (INR; <1.00) was significantly associated with a higher risk of late TCC malfunction (RR 5.2 and 4.0, respectively), a higher risk of incipient TCC thrombosis requiring UK (RR 2.0 and 2.8, respectively), and higher rates of UK dosing. Diabetics had a 3.6-fold higher risk of late TCC malfunction and a twofold higher risk of incipient thrombosis requiring UK, although these findings were not statistically significant. Aspirin use, race, age, number of hospitalizations, erythropoietin dose, intradialytic heparin dose, serum albumin, and the number of episodes of TCC-associated infection were not significantly associated with late TCC malfunction.\n\nThrombosis prophylaxis using fixed minidose warfarin is not efficacious in TCCs used for HD. However, the present data suggest improved TCC survival in patients with an INR> 1.00. Patients with diabetes and those with a low Hgb or INR have a higher risk of late TCC malfunction.", "PMID": "11318966"}, {"title": "Low-intensity warfarin is ineffective for the prevention of PTFE graft failure in patients on hemodialysis: a randomized controlled trial.", "abstract": "Polytetrafluoroethylene (PTFE) dialysis grafts in patients with end-stage renal disease (ESRD) are prone to thrombotic failure. The objective of this multicenter, randomized, double-blind, placebo-controlled clinical trial was to determine if warfarin reduces the risk of failure of PTFE dialysis grafts. Patients with ESRD and newly placed PTFE grafts were studied at community and academic dialysis centers in Southwestern Ontario. Patients were allocated to receive warfarin or matching placebo, with the warfarin administered to achieve a target INR of 1.4 to 1.9. Time to graft failure was the main outcome measure. A total of 107 patients (56 allocated to warfarin) were randomized. The time-to-event analysis revealed no significant difference in the likelihood of graft survival between the two groups (odds ratio, 1.76 in favor of placebo; 95% confidence interval, 0.72 to 4.34). Six major bleeds occurred in five patients allocated to warfarin compared with none in the patients who received placebo (P = 0.03). In conclusion, low-dose warfarin was associated with an excess of clinically important major bleeding in patients with ESRD enrolled in this study. Furthermore, low-intensity, monitored-dose warfarin does not appear to prolong PTFE graft survival.", "PMID": "12191977"}, {"title": "Dermatan sulphate in haemodialysis.", "abstract": "Experimental work suggests that dermatan sulphate has potential as an antithrombotic agent: it can inhibit venous thrombi yet has less effect upon bleeding than heparin. While heparin functions as an anticoagulant primarily by its ability to accelerate the action of the plasma protein inhibitor antithrombin III, dermatan sulphate acts selectively through a structurally related inhibitor, heparin co-factor II, to inhibit thrombin. We have done a series of dose-finding studies of the use of dermatan sulphate as an anticoagulant/antithrombotic agent in patients on maintenance haemodialysis. Dermatan sulphate proved to be an effective anticoagulant in this setting.", "PMID": "1346414"}, {"title": "Antithrombotic properties of dermatan sulphate (MF 701) in haemodialysis for chronic renal failure.", "abstract": "The therapeutic potential of the glycosaminoglycan (GAG), dermatan sulphate (DS), as an antithrombotic agent in humans has yet to be established. We have performed dose ranging studies of DS to determine its effectiveness as an antithrombotic agent in patients (n = 6-8) undergoing haemodialysis for chronic renal failure. In an initial study, Study 1, i.v. bolus doses of 2-4 mg/kg and 5-6 mg/kg DS were given to patients dialysing with polyacrylonitrile hollow fibre (PAN HF) membranes. In a second crossover study, Study 2, performed using cuprophane hollow fibre (CHF) membranes, i.v. bolus doses of 3 mg/kg and 6 mg/kg DS were compared to a standard unfractionated heparin (UFH) regime that has been shown previously to inhibit fibrin formation. Further infusion studies, Study 3 and Study 4 evaluated the antithrombotic efficacy of an i.v. DS bolus of 3 mg/kg plus an i.v. infusion of DS 0.6 mg kg-1 h-1 and a DS bolus of 5 mg/kg plus an infusion of 1 mg kg-1 h-1 over 5 h, respectively. These studies were compared to standard UFH regimes in a randomised crossover design. Plasma levels of fibrinopeptide A (FPA) and thrombin-antithrombin (TAT) were used as markers of fibrin formation and thrombin generation during dialysis using both membranes. The changes in DS concentration following administration of the different doses were similar in Studies 1 and 2. However, the effectiveness of DS as an anticoagulant appeared to depend markedly on the different dialyser types used in the two studies.(ABSTRACT TRUNCATED AT 250 WORDS)", "PMID": "1455403"}, {"title": "The effect of oral anticoagulation on clotting during hemodialysis.", "abstract": "Between 5% and 10% of hemodialysis patients are treated with oral anticoagulants. It is currently unknown whether additional anticoagulation with heparin or low-molecular-weight heparin (LMWH) is needed to prevent clotting during hemodialysis.\n\nIn this prospective, randomized, cross-over study 10 patients treated with oral anticoagulants (phenprocoumon) received either no additional anticoagulation or low dose dalteparin (bolus of 40 IU/kg body weight) before dialysis. Efficacy of hemodialysis was measured by normalized weekly Kt/V and urea reduction rate (URR). Thrombus formation was evaluated by measurement of D-dimer and inspection of air traps and dialyser.\n\nThe median international normalized ratio (INR) did not differ between both observation periods (phenprocoumon 2.2(2 to 3) vs. dalteparin 2.1(2 to 2.9). The anti-Xa level in dalteparin patients was 0.33 (0.27 to 0.38) IU/mL after 2 hours and 0.16 (0.03 to 0.23) IU/mL after 4 hours of hemodialysis. The median increase of D-dimer was significantly higher in patients without additional dalteparin therapy during hemodialysis (DeltaD-dimer 0.23 microg/mL vs. 0.03 mug/mL) (P= 0.0004). Complete thrombosis of the dialyser membrane occurred in one patient in the phenprocoumon group but in none with combined treatment. The extent of thrombosis in the arterial and venous air trap and dialyser was significantly less in patients with additional dalteparin therapy (P= 0.0014, P= 0.0002, and P= 0.0005, respectively). Weekly Kt/V and URR was similar in both groups.\n\nStandard oral anticoagulation with an INR between 2 and 3 is insufficient to prevent clotting during hemodialysis. Additional low dose anticoagulation with a LMWH or heparin is necessary to facilitate treatment.", "PMID": "16014067"}, {"title": "Assessment of the heparin-binding AN69 ST hemodialysis membrane: II. Clinical studies without heparin administration.", "abstract": "Binding polyanionic unfractionated heparin over the modified AN69 polyacrylonitrile membrane, the surface electronegativity of which has been neutralized by polyethyleneimine (AN69-ST), renders the membrane more hemocompatible. This property was tested in two groups of long-term hemodialysis patients. Results were rated as massive or partial clotting of a dialyzer at the end of the session. Group I patients were included in a prospective, cross-over study comparing standard dialysis with hemodialysis without systemic administration of unfractionated heparin (n = 12, 123 sessions). In all instances, priming was made with 2 I saline containing 5,000 IU/l heparin. Only patchy or partial clotting was observed in 11% and 39% of the sessions with standard and heparin-free administration, respectively. Group II patients were included in an open, observational pilot study testing the effects of the heparin-coated membrane, without systemic administration of heparin, in patients at high risk of bleeding (n = 68, 331 sessions). Massive clotting was observed in six sessions only (less than 2%) and normal or slightly patchy dialyzers were found in 88% of the sessions. It is concluded that the dialysis AN69 ST membrane, after adequate priming at bedside, can be used without systemic administration of heparin for hemodialysis in patients at high risk of bleeding.", "PMID": "16156297"}], "labels": [{"PMID": "10534515", "label": "included"}, {"PMID": "10534515", "label": "included"}, {"PMID": "10584996", "label": "included"}, {"PMID": "10504511", "label": "excluded"}, {"PMID": "11318966", "label": "excluded"}, {"PMID": "12191977", "label": "excluded"}, {"PMID": "1346414", "label": "excluded"}, {"PMID": "1455403", "label": "excluded"}, {"PMID": "16014067", "label": "excluded"}, {"PMID": "16156297", "label": "excluded"}]}
{"metadata": {"review_pmid": "38189560"}, "inputs": {"background": "Electronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol by heating an e-liquid. People who smoke, healthcare providers and regulators want to know if ECs can help people quit smoking, and if they are safe to use for this purpose. This is a review update conducted as part of a living systematic review.", "objectives": "To examine the safety, tolerability and effectiveness of using electronic cigarettes (ECs) to help people who smoke tobacco achieve long-term smoking abstinence, in comparison to non-nicotine EC, other smoking cessation treatments and no treatment.", "selection criteria": "We included trials in which people who smoke were randomized to an EC or control condition. We also included uncontrolled intervention studies in which all participants received an EC intervention as these studies have the potential to provide further information on harms and longer-term use. Studies had to report an eligible outcome."}, "context": [{"title": "Effect of an electronic nicotine delivery device (e-Cigarette) on smoking reduction and cessation: a prospective 6-month pilot study.", "abstract": "Cigarette smoking is a tough addiction to break. Therefore, improved approaches to smoking cessation are necessary. The electronic-cigarette (e-Cigarette), a battery-powered electronic nicotine delivery device (ENDD) resembling a cigarette, may help smokers to remain abstinent during their quit attempt or to reduce cigarette consumption. Efficacy and safety of these devices in long-term smoking cessation and/or smoking reduction studies have never been investigated.\n\nIn this prospective proof-of-concept study we monitored possible modifications in smoking habits of 40 regular smokers (unwilling to quit) experimenting the 'Categoria' e-Cigarette with a focus on smoking reduction and smoking abstinence. Study participants were invited to attend a total of five study visits: at baseline, week-4, week-8, week-12 and week-24. Product use, number of cigarettes smoked, and exhaled carbon monoxide (eCO) levels were measured at each visit. Smoking reduction and abstinence rates were calculated. Adverse events and product preferences were also reviewed.\n\nSustained 50% reduction in the number of cig/day at week-24 was shown in 13/40(32.5%) participants; their median of 25 cigs/day decreasing to 6 cigs/day (p < 0.001). Sustained 80% reduction was shown in 5/40(12.5%) participants; their median of 30 cigs/day decreasing to 3 cigs/day (p = 0.043). Sustained smoking abstinence at week-24 was observed in 9/40(22.5%) participants, with 6/9 still using the e-Cigarette by the end of the study. Combined sustained 50% reduction and smoking abstinence was shown in 22/40 (55%) participants, with an overall 88% fall in cigs/day. Mouth (20.6%) and throat (32.4%) irritation, and dry cough (32.4%) were common, but diminished substantially by week-24. Overall, 2 to 3 cartridges/day were used throughout the study. Participants' perception and acceptance of the product was good.\n\nThe use of e-Cigarette substantially decreased cigarette consumption without causing significant side effects in smokers not intending to quit (http://ClinicalTrials.gov number NCT01195597).", "PMID": "21989407"}, {"title": "Impact of an electronic cigarette on smoking reduction and cessation in schizophrenic smokers: a prospective 12-month pilot study.", "abstract": "Cigarette smoking is a tough addiction to break. This dependence is the most common dual diagnosis for individuals with schizophrenia. Currently three effective drugs are approved for smoking cessation: nicotine replacement therapy (NRT), varenicline and bupropion. However, some serious side effects of varenicline have been reported, including depression, suicidal thoughts, and suicide. The use of bupropion also has side effects. It should not be used by people who have epilepsy or any condition that lowers the seizure threshold, nor by people who take a specific class of drugs called monoamine oxidase inhibitors. Hence, there are pharmacodynamic reason to believe they could precipitate or exacerbate psychosis. For its capacity to deliver nicotine and provide a coping mechanism for conditioned smoking cues by replacing some of the rituals associated with smoking gestures, electronic-cigarettes may reduce nicotine withdrawal symptoms without serious side effects. Our recent work with ECs in healthy smokers not intending to quit consistently show surprisingly high success rates. We hypothesised that these positive findings could be replicated in difficult patients with schizophrenia This tool may help smokers with schizophrenia remain abstinent during their quitting attempts or to reduce cigarette consumption. Efficacy and safety of these devices in long-term smoking cessation and/or smoking reduction studies have never been investigated for this special population.\n\nIn this study we monitored possible modifications in smoking habits of 14 smokers (not intending to quit) with schizophrenia experimenting with the \"Categoria\" e-Cigarette with a focus on smoking reduction and smoking abstinence. Study participants were invited to attend six study visits: at baseline, week-4, week-8, week-12 week-24 and week 52. Product use, number of cigarettes smoked, carbon monoxide in exhaled breath (eCO) and positive and negative symptoms of schizophrenia levels were measured at each visit. Smoking reduction and abstinence rates were calculated. Adverse events were also reviewed.\n\nSustained 50% reduction in the number of cig/day at week-52 was shown in 7/14 (50%) participants; their median of 30 cig/day decreasing significantly to 15 cig/day (p = 0.018). Sustained smoking abstinence at week-52 was observed in 2/14 (14.3%) participants. Combined sustained 50% reduction and smoking abstinence was shown in 9/14 (64.3%) participants. Nausea was observed in 2/14 (14.4%) of participants, throat irritation in 2/14 (14.4%) of participants, headache in 2/14 (14.4%) of participants , and dry cough in 4/14 (28.6%) of participants. However, these adverse events diminished substantially by week-24. Overall, one to two cartridges/day were used throughout the study. Positive and negative symptoms of schizophrenia are not increased after smoking reduction/cessation in patients using e-cigarettes.\n\nWe have shown for the first time that the use of e-cigarette substantially decreased cigarette consumption without causing significant side effects in chronic schizophrenic patients who smoke not intending to quit. This was achieved without negative impacts on the symptoms of schizophrenia as assessed by SAPS and SANS symptoms scales.", "PMID": "23358230"}, {"title": "Study protocol for a randomised controlled trial of electronic cigarettes versus nicotine patch for smoking cessation.", "abstract": "Electronic cigarettes (e-cigarettes or electronic nicotine delivery systems [ENDS]) are electrically powered devices generally similar in appearance to a cigarette that deliver a propylene glycol and/or glycerol mist to the airway of users when drawing on the mouthpiece. Nicotine and other substances such as flavourings may be included in the fluid vaporised by the device. People report using e-cigarettes to help quit smoking and studies of their effects on tobacco withdrawal and craving suggest good potential as smoking cessation aids. However, to date there have been no adequately powered randomised trials investigating their cessation efficacy or safety. This paper outlines the protocol for this study.\n\nParallel group, 3-arm, randomised controlled trial.\n\nPeople aged \u226518 years resident in Auckland, New Zealand (NZ) who want to quit smoking.\n\nStratified blocked randomisation to allocate participants to either Elusion\u2122 e-cigarettes with nicotine cartridges (16 mg) or with placebo cartridges (i.e. no nicotine), or to nicotine patch (21 mg) alone. PARTICIPANTS randomised to the e-cigarette groups will be told to use them ad libitum for one week before and 12 weeks after quit day, while participants randomised to patches will be told to use them daily for the same period. All participants will be offered behavioural support to quit from the NZ Quitline.\n\nBiochemically verified (exhaled carbon monoxide) continuous abstinence at six months after quit day.\n\n657 people (292 in both the nicotine e-cigarette and nicotine patch groups and 73 in the placebo e-cigarettes group) will provide 80% power at p = 0.05 to detect an absolute difference of 10% in abstinence between the nicotine e-cigarette and nicotine patch groups, and 15% between the nicotine and placebo e-cigarette groups.\n\nThis trial will inform international debate and policy on the regulation and availability of e-cigarettes. If shown to be efficacious and safe, these devices could help many smokers as an alternative smoking cessation aid to standard nicotine products.\n\nAustralian NZ Clinical Trials Registry (ACTRN12610000866000).", "PMID": "23496861"}, {"title": "EffiCiency and Safety of an eLectronic cigAreTte (ECLAT) as tobacco cigarettes substitute: a prospective 12-month randomized control design study.", "abstract": "Electronic cigarettes (e-cigarettes) are becoming increasingly popular with smokers worldwide. Users report buying them to help quit smoking, to reduce cigarette consumption, to relieve tobacco withdrawal symptoms, and to continue having a 'smoking' experience, but with reduced health risks. Research on e-cigarettes is urgently needed in order to ensure that the decisions of regulators, healthcare providers and consumers are based on science. Methods ECLAT is a prospective 12-month randomized, controlled trial that evaluates smoking reduction/abstinence in 300 smokers not intending to quit experimenting two different nicotine strengths of a popular e-cigarette model ('Categoria'; Arbi Group Srl, Italy) compared to its non-nicotine choice. GroupA (n\u200a=\u200a100) received 7.2 mg nicotine cartridges for 12 weeks; GroupB (n\u200a=\u200a100), a 6-week 7.2 mg nicotine cartridges followed by a further 6-week 5.4 mg nicotine cartridges; GroupC (n\u200a=\u200a100) received no-nicotine cartridges for 12 weeks. The study consisted of nine visits during which cig/day use and exhaled carbon monoxide (eCO) levels were measured. Smoking reduction and abstinence rates were calculated. Adverse events and product preferences were also reviewed.\n\nDeclines in cig/day use and eCO levels were observed at each study visits in all three study groups (p<0.001 vs baseline), with no consistent differences among study groups. Smoking reduction was documented in 22.3% and 10.3% at week-12 and week-52 respectively. Complete abstinence from tobacco smoking was documented in 10.7% and 8.7% at week-12 and week-52 respectively. A substantial decrease in adverse events from baseline was observed and withdrawal symptoms were infrequently reported during the study. Participants' perception and acceptance of the product under investigation was satisfactory.\n\nIn smokers not intending to quit, the use of e-cigarettes, with or without nicotine, decreased cigarette consumption and elicited enduring tobacco abstinence without causing significant side effects.\n\nClinicalTrials.gov NCT01164072 NCT01164072.", "PMID": "23826093"}, {"title": "Effectiveness and tolerability of electronic cigarette in real-life: a 24-month prospective observational study.", "abstract": "Electronic cigarettes (e-Cigarette) are battery-operated devices designed to vaporise nicotine that may aid smokers to quit or reduce their cigarette consumption. Research on e-Cigarettes is urgently needed to ensure that the decisions of regulators, healthcare providers and consumers are evidence based. Here we assessed long-term effectiveness and tolerability of e-Cigarette used in a 'naturalistic' setting. This prospective observational study evaluated smoking reduction/abstinence in smokers not intending to quit using an e-Cigarette ('Categoria'; Arbi Group, Italy). After an intervention phase of 6 months, during which e-Cigarette use was provided on a regular basis, cigarettes per day (cig/day) and exhaled carbon monoxide (eCO) levels were followed up in an observation phase at 18 and 24 months. Efficacy measures included: (a) \u226550% reduction in the number of cig/day from baseline, defined as self-reported reduction in the number of cig/day (\u226550%) compared to baseline; (b) \u226580% reduction in the number of cig/day from baseline, defined as self-reported reduction in the number of cig/day (\u226580%) compared to baseline; (c) abstinence from smoking, defined as complete self-reported abstinence from tobacco smoking (together with an eCO concentration of \u226410 ppm). Smoking reduction and abstinence rates were computed, and adverse events reviewed. Of the 40 subjects, 17 were lost to follow-up at 24 months. A >50% reduction in the number of cig/day at 24 months was shown in 11/40 (27.5%) participants with a median of 24 cig/day use at baseline decreasing significantly to 4 cig/day (p = 0.003). Smoking abstinence was reported in 5/40 (12.5%) participants while combined >50% reduction and smoking abstinence was observed in 16/40 (40%) participants at 24 months. Five subjects stopped e-Cigarette use (and stayed quit), three relapsed back to tobacco smoking and four upgraded to more performing products by 24 months. Only some mouth irritation, throat irritation, and dry cough were reported. Withdrawal symptoms were uncommon. Long-term e-Cigarette use can substantially decrease cigarette consumption in smokers not willing to quit and is well tolerated. ( http://ClinicalTrials.govnumberNCT01195597 ).", "PMID": "23873169"}, {"title": "Electronic cigarettes for smoking cessation: a randomised controlled trial.", "abstract": "Electronic cigarettes (e-cigarettes) can deliver nicotine and mitigate tobacco withdrawal and are used by many smokers to assist quit attempts. We investigated whether e-cigarettes are more effective than nicotine patches at helping smokers to quit.\n\nWe did this pragmatic randomised-controlled superiority trial in Auckland, New Zealand, between Sept 6, 2011, and July 5, 2013. Adult (\u226518 years) smokers wanting to quit were randomised (with computerised block randomisation, block size nine, stratified by ethnicity [M\u0101ori; Pacific; or non-M\u0101ori, non-Pacific], sex [men or women], and level of nicotine dependence [>5 or \u22645 Fagerstr\u00f6m test for nicotine dependence]) in a 4:4:1 ratio to 16 mg nicotine e-cigarettes, nicotine patches (21 mg patch, one daily), or placebo e-cigarettes (no nicotine), from 1 week before until 12 weeks after quit day, with low intensity behavioural support via voluntary telephone counselling. The primary outcome was biochemically verified continuous abstinence at 6 months (exhaled breath carbon monoxide measurement <10 ppm). Primary analysis was by intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12610000866000.\n\n657 people were randomised (289 to nicotine e-cigarettes, 295 to patches, and 73 to placebo e-cigarettes) and were included in the intention-to-treat analysis. At 6 months, verified abstinence was 7\u00b73% (21 of 289) with nicotine e-cigarettes, 5\u00b78% (17 of 295) with patches, and 4\u00b71% (three of 73) with placebo e-cigarettes (risk difference for nicotine e-cigarette vs patches 1\u00b751 [95% CI -2\u00b749 to 5\u00b751]; for nicotine e-cigarettes vs placebo e-cigarettes 3\u00b716 [95% CI -2\u00b729 to 8\u00b761]). Achievement of abstinence was substantially lower than we anticipated for the power calculation, thus we had insufficient statistical power to conclude superiority of nicotine e-cigarettes to patches or to placebo e-cigarettes. We identified no significant differences in adverse events, with 137 events in the nicotine e-cigarettes group, 119 events in the patches group, and 36 events in the placebo e-cigarettes group. We noted no evidence of an association between adverse events and study product.\n\nE-cigarettes, with or without nicotine, were modestly effective at helping smokers to quit, with similar achievement of abstinence as with nicotine patches, and few adverse events. Uncertainty exists about the place of e-cigarettes in tobacco control, and more research is urgently needed to clearly establish their overall benefits and harms at both individual and population levels.\n\nHealth Research Council of New Zealand.", "PMID": "24029165"}, {"title": "Carboxyhaemoglobin levels, health and lifestyle perceptions in smokers converting from tobacco cigarettes to electronic cigarettes.", "abstract": "Chronic obstructive pulmonary disease and lung cancer are diseases associated with smoking tobacco cigarettes. Smokers find cessation difficult.\n\nTo determine whether smoking the Twisp electronic cigarette (e-cigarette), containing nicotine in a vegetable-based glycerine substance, would reduce carboxyhaemoglobin (COHb) levels in regular cigarette smokers by (i) comparing arterial and venous COHb levels before and after smoking the Twisp e-cigarette for 2 weeks; and (ii) evaluating changes in participants' perception of their health and lifestyle following the use of Twisp e-cigarettes.\n\nA single group within-subject design was used where tobacco cigarette smokers converted to Twisp e-cigarettes for 2 weeks. Prior to using the Twisp e-cigarette and after using this device for 2 weeks, arterial COHb, venous COHb and venous cotinine levels were determined. Additionally, the participants were asked to complete a questionnaire outlining their perceptions on health and lifestyle.\n\nThirteen participants of median age 38 years (range 23 - 46) with a smoking median of 20 cigarettes/day (range 12 - 30) completed the study. COHb levels (%) were significantly reduced after smoking Twisp e-cigarettes for 2 weeks (mean \u00b1 standard deviation (SD) arterial COHb before 4.66\u00b11.99 v. after 2.46\u00b11.35; p=0.014 and mean \u00b1SD venous COHb before 4.37\u00b12.1 v. after 2.50\u00b11.23; p=0.018). There was excellent agreement between arterial and venous COHb levels (intraclass correlation coefficient 0.916). A decrease in cotinine levels (p=0.001) and an increase in oxygen saturation (p=0.002) were also observed. The majority of participants perceived improvements in their health and lifestyle parameters.\n\nSmoking the Twisp e-cigarette may be a healthier and more acceptable alternative to smoking tobacco cigarettes.", "PMID": "24148175"}, {"title": "Electronic cigarettes and smoking cessation: a quandary? - Authors' reply.", "abstract": "", "PMID": "24485579"}, {"title": "Nicotine blood levels and short-term smoking reduction with an electronic nicotine delivery system.", "abstract": "To evaluate nicotine delivery from the NJOY\u00ae King Bold Electronic Nicotine Delivery System (ENDS) and its short-term potential for smoking reduction or cessation.\n\nOne week of ad libitum use was followed by measurements of plasma nicotine, heart rate, and craving and withdrawal after 12 hours of nicotine abstinence in 25 adult smokers not interested in quitting.\n\nAfter 5 minutes of use, blood nicotine levels increased by a mean of 3.5 ng/mL (p < .001), heart rate increased, and craving was reduced by 55%. Cigarettes per day were reduced by 39% during the test week, and perceptions of use for reduction or cessation were positive.\n\nThe NJOY\u00ae King Bold ENDS delivers nicotine and led to short-term smoking reduction.", "PMID": "24629555"}, {"title": "Effectiveness of the electronic cigarette: An eight-week Flemish study with six-month follow-up on smoking reduction, craving and experienced benefits and complaints.", "abstract": "Smoking reduction remains a pivotal issue in public health policy, but quit rates obtained with traditional quit-smoking therapies remain disappointingly low. Tobacco Harm Reduction (THR), aiming at less harmful ways of consuming nicotine, may provide a more effective alternative. One promising candidate for THR are electronic cigarettes (e-cigs). The aim of this study was to investigate the efficacy of second-generation e-cigs both in terms of acute craving-reduction in the lab and in terms of smoking reduction and experienced benefits/complaints in an eight-month Randomized Controlled Trial (RCT).\n\nRCT with three arms.\n\nParticipants (N = 48) unwilling to quit smoking were randomized into two e-cig groups and one control group. During three lab sessions (over two months) participants, who had been abstinent for four hours, vaped/smoked for five minutes, after which we monitored the effect on craving and withdrawal symptoms. eCO and saliva cotinine levels were also measured. In between lab sessions, participants in the e-cig groups could use e-cigs or smoke ad libitum, whereas the control group could only smoke. After the lab sessions, the control group also received an e-cig. The RCT included several questionnaires, which repeatedly monitored the effect of ad libitum e-cig use on the use of tobacco cigarettes and the experienced benefits/complaints up to six months after the last lab session.\n\nFrom the first lab session on, e-cig use after four hours of abstinence resulted in a reduction in cigarette craving which was of the same magnitude as when a cigarette was smoked, while eCO was unaffected. After two months, we observed that 34% of the e-cig groups had stopped smoking tobacco cigarettes, versus 0% of the control group. After five months, the e-cig groups demonstrated a total quit-rate of 37%, whereas the control group showed a quit rate of 38% three months after initiating e-cig use. At the end of the eight-month study, 19% of the e-cig groups and 25% of the control group were totally abstinent from smoking, while an overall reduction of 60% in the number of cigarettes smoked per day was observed (compared to intake). eCO levels decreased, whereas cotinine levels were the same in all groups at each moment of measurement. Reported benefits far outweighed the reported complaints.\n\nIn a series of controlled lab sessions with e-cig na\u00efve tobacco smokers, second generation e-cigs were shown to be immediately and highly effective in reducing abstinence induced cigarette craving and withdrawal symptoms, while not resulting in increases in eCO. Remarkable (>50 pc) eight-month reductions in, or complete abstinence from tobacco smoking was achieved with the e-cig in almost half (44%) of the participants.", "PMID": "25358095"}], "labels": [{"PMID": "21989407", "label": "included"}, {"PMID": "23358230", "label": "included"}, {"PMID": "23496861", "label": "included"}, {"PMID": "23826093", "label": "included"}, {"PMID": "23873169", "label": "included"}, {"PMID": "24029165", "label": "included"}, {"PMID": "24148175", "label": "included"}, {"PMID": "24485579", "label": "included"}, {"PMID": "24629555", "label": "included"}, {"PMID": "25358095", "label": "included"}]}
{"metadata": {"review_pmid": "38189492"}, "inputs": {"background": "Vitamin B", "objectives": "To evaluate the benefits and harms of oral vitamin B", "selection criteria": "Randomised controlled trials (RCTs), quasi-RCTs, or cluster-RCTs evaluating the effects of oral vitamin B"}, "context": [{"title": "Vitamin D3 and B12 supplementation in pregnancy.", "abstract": "To assess the efficacy of vitamin D3 or B12 supplementation during pregnancy.\n\nPregnant women at 6-14\u00a0weeks in the intervention arm received oral high dose intermittent vitamin D3 and/or low dose B12 supplementation if they had vitamin D or vitamin B12 deficiency. The control arm received prescribed dietary instruction only. An additional observational arm for those mothers at booking with normal vitamin D and vitamin B12 level was also recruited. All groups received standard care during pregnancy.\n\nThe primary endpoint of either vitamin D or B12 at term was not met. At baseline 25% participants in both the interventional and control arms had severe D deficiency (<30\u00a0nmol/l), reducing to under 3.4% in both groups. No maternal differences in vitamin D or B12 levels were found at delivery between the intervention, control, or observational groups. No significant difference in any of the pregnancy or birth outcomes was observed between three groups.\n\nIn this study, oral supplementation of high dose intermittent vitamin D or low dose vitamin B12 regime failed to correct the relevant nutritional deficiencies in Bangladeshi pregnant women as per protocol. Both dietary supplementation and high dose vitamin D corrected severe vitamin deficiency.", "PMID": "33662489"}, {"title": "The effect of vitamin B12 supplementation during pregnancy on infant growth and development in Nepal: a community-based, double-blind, randomised, placebo-controlled trial.", "abstract": "Vitamin B12 is required for healthy infant growth and development, but low and marginal vitamin B12 status is endemic in low-income and middle-income countries. We aimed to measure the effect of vitamin B12 supplementation from early pregnancy until 6 months post partum on infant growth and neurodevelopment.\n\nIn this community-based, double-blind, placebo-controlled trial, we randomly assigned (1:1) 800 pregnant women (aged 20-40 years) who were up to 15 weeks pregnant-recruited from home visits and outpatient departments at three hospitals in Nepal-to daily supplementation with 50 \u03bcg oral vitamin B12 or placebo until 6 months postpartum. Independent scientists generated the list that linked allocation to participants' study identification number. Participants were masked to group assignment and all investigators were masked until data cleaning was completed. The primary outcomes were length-for-age Z score (LAZ) at age 12 months and the cognitive composite score of the Bayley Scales of Infant and Toddler Development (3rd edition) at age 6 months and 12 months. The primary and secondary outcomes, including adverse events, were assessed in the intention-to-treat population, for all participants with available outcome data. This trial is registered with ClinicalTrials.gov, NCT03071666.\n\n800 eligible pregnant women were enrolled in the trial between March 28, 2017, and Oct 15, 2020, with 400 women randomly assigned to each group. Follow-up was completed on May 18, 2022. At baseline, 569 (71%) of 800 women had plasma vitamin B12 indicating low or marginal status (<221 pmol/L). We found no effect of vitamin B12 on the primary outcomes. The mean LAZ at age 12 months were -0\u00b757 (SD 1\u00b703) in the B12 group and -0\u00b755 (1.03) in the placebo group (366 infants in the vitamin B12 group vs 363 infants in the placebo group) with a mean difference of -0\u00b702 (95% CI -0\u00b716 to 0\u00b713). The mean cognitive composite scores were 97\u00b77 (SD 10\u00b75) in the B12 group and 97\u00b71 (10\u00b72) in the placebo group, with a mean difference of 0\u00b75 (95% CI -0\u00b76 to 1\u00b77) measured in 364 and 361 infants. Stillbirths or infant deaths occurred in three (1%) of 374 women in the vitamin B12 group and nine (2%) of 379 women in the placebo group.\n\nAlthough vitamin B12 deficiency was prevalent in our study population and vitamin B12 supplementation from early pregnancy substantially improved vitamin B12 status, supplementation did not improve infant growth or neurodevelopment. Our findings support the current WHO recommendations of no routine vitamin B12 supplementation during pregnancy.\n\nResearch Council of Norway.", "PMID": "37031691"}, {"title": "The effects of vitamin B12 supplementation in pregnancy and postpartum on growth and neurodevelopment in early childhood: Study Protocol for a Randomized Placebo Controlled Trial.", "abstract": "Vitamin B\n\nThe study is an individually randomised double-blind placebo controlled trial in 800 pregnant Nepalese women randomised in a 1:1 ratio. A daily dose of 50\u2009\u00b5g of vitamin B\n\nNational Health and Research Council, Nepal (NHRC 253/2016) and Regional Committee for Medical and Health Research Ethics of Western Norway (2016/1620/REK vest) have approved the study. Investigators who have contributed to the conceptualising, conducting, as well as being involved in the data analyses and manuscript writing will be eligible for authorship and be responsible to share outcomes with different stakeholders through publications and workshops. The results from this study may support new dietary guidelines for Nepalese and possibly South Asian pregnant women that can lead to improved pregnancy outcomes, neurodevelopment and cognitive functioning in children.\n\nUniversal Trial Number: U1111-1183-4093.\n\nclinicaltrials.gov: NCT03071666. Protocol date: version 1.2, 1 June 2017.", "PMID": "28851784"}, {"title": "Combined Vitamin B-12 and Balanced Protein-Energy Supplementation Affect Homocysteine Remethylation in the Methionine Cycle in Pregnant South Indian Women of Low Vitamin B-12 Status.", "abstract": "", "PMID": "28446631"}, {"title": "Association of antenatal vitamin B complex supplementation with neonatal vitamin B", "abstract": "#PURPOSE: Evidence about the effect of maternal vitamin B\n#METHODS: In an ongoing cluster randomized controlled trial conducted in three rural counties in northwest China, pregnant women\u2009<\u200920\u00a0weeks of gestation were randomized to three treatment groups: blank control, iron supplements, or vitamin B complex supplements. All women were administered folic acid supplements during the periconceptional period. In a sub-study, we collected cord blood samples of 331 participants from the control or vitamin B complex groups in the Xunyi county from January 2017 to December 2017. Plasma concentrations of folate, vitamin B\n#RESULTS: Compared with newborns whose mothers were in the control group, newborns of the vitamin B complex-supplemented women had significantly higher cord plasma vitamin B\n#CONCLUSIONS: Maternal vitamin B complex supplementation during pregnancy was associated with better neonatal vitamin B", "PMID": "32577886"}, {"title": "Preventing vitamin B12 deficiency in South Asian women of childbearing age: a randomised controlled trial comparing an oral vitamin B12 supplement with B12 dietary advice.", "abstract": "To examine the effectiveness, acceptability and sustainability of interventions to reduce vitamin B12 (B12) deficiency in South Asian women before conception.\n\nA 6-month randomised controlled trial conducted in Auckland, New Zealand. Participants (62 South Asian women, 18-50 years old) were stratified by dietary practices, then randomised to three treatment groups: B12 Supplement (oral cyanocobalamin 6\u2009\u03bcg/day) (n=21), Placebo (n=21), or B12 Dietary Advice (n=20). Primary outcome measures were changes in B12 biomarkers (serum B12 and holotranscobalamin (holoTC)) at 6 months. Dietary B12 intake was estimated from a B12 food-specific frequency questionnaire (B12FFQ). Intention-to-treat analysis was applied using 'last observation carried forward' method. Changes in B12 biomarkers by treatment were compared using analysis of variance. Pearson's correlations tested relationships between dietary B12 intake and B12 biomarkers.\n\nAt baseline, 48% of women tested as insufficient or deficient in serum B12 (<222\u2009pmol/l) and 51% as insufficient or deficient in holoTC (<45\u2009pmol/l). B12 status was moderately correlated with dietary B12 intake (r=0.5, 95% confidence interval (CI) (0.3-0.7)) and 44% of women reported insufficient dietary intake (<2.4\u2009\u03bcg/day). B12 Supplement was the only treatment group to record a significant increase in B12 biomarkers over 6 months: serum B12 by 30% (95% CI (11-48%)) and holoTC by 42% (12-72%).\n\nThe prevalence of B12 insufficiency among Auckland South Asian women is high and moderately correlated with inadequate intake of foods that contain B12. Cyanocobalamin supplementation (6\u2009\u03bcg/day) was associated with improved B12 biomarkers, with a potential to improve preconception B12 status in South Asian women.", "PMID": "24736677"}, {"title": "Efficacy of maternal B", "abstract": "Vitamin B\n\nThis double-blind, multicentre, randomised controlled trial will enrol 720 vegetarian pregnant women in their first trimester from antenatal clinics at two hospitals (one in India and one in Nepal). Eligible mothers who give written consent will be randomised to receive either 250 mcg methylcobalamin or 50 mcg (quasi control), from enrolment to 6 months post-partum, given as an oral daily capsule. All mothers and their infants will continue to receive standard clinical care. The primary trial outcome is the offspring's neurodevelopment status at 9 months of age, assessed using the Development Assessment Scale of Indian Infants. Secondary outcomes include the infant's biochemical B\n\nThe study protocol has been approved by ethical committees at each study site (India and Nepal) and at University College London, UK. The study results will be disseminated to healthcare professionals and academics globally via conferences, presentations and publications. Researchers at each study site will share results with participants during their follow-up visits.", "PMID": "32457078"}], "labels": [{"PMID": "33662489", "label": "excluded"}, {"PMID": "37031691", "label": "excluded"}, {"PMID": "28851784", "label": "excluded"}, {"PMID": "28446631", "label": "excluded"}, {"PMID": "32577886", "label": "excluded"}, {"PMID": "24736677", "label": "excluded"}, {"PMID": "32457078", "label": "excluded"}]}
{"metadata": {"review_pmid": "38189479"}, "inputs": {"background": "Carpal tunnel syndrome (CTS) is a compression neuropathy of the median nerve at the wrist. Surgery is considered when symptoms persist despite the use of non-surgical treatments. It is unclear whether surgery produces a better outcome than non-surgical therapy. This is an update of a Cochrane review published in 2008.", "objectives": "To assess the evidence regarding the benefits and harms of carpal tunnel release compared with non-surgical treatment in the short (< 3 months) and long (> 3 months) term.", "selection criteria": "We included randomised controlled trials comparing any surgical technique with any non-surgical therapies for CTS."}, "context": [{"title": "Splinting or surgery for carpal tunnel syndrome? Design of a randomized controlled trial [ISRCTN18853827].", "abstract": "Carpal tunnel syndrome is a common disorder, which can be treated with surgery or conservative options. However, there is insufficient evidence and no consensus among physicians with regard to the preferred treatment for carpal tunnel syndrome. Therefore, a randomized controlled trial is conducted to compare the short- and long-term efficacy of surgery and splinting in patients with carpal tunnel syndrome. An attempt is also made to avoid the (methodological) limitations encountered in earlier trials on the efficacy of various treatment options for carpal tunnel syndrome.\n\nPatients of 18 years and older, with clinically and electrophysiologically confirmed idiopathic carpal tunnel syndrome, are recruited by neurologists in 13 hospitals. Patients included in the study are randomly allocated to either open carpal tunnel release or wrist splinting during the night for at least 6 weeks. The primary outcomes are general improvement, waking up at night and severity of symptoms (main complaint, night and daytime pain, paraesthesia and hypoesthesia). Outcomes are assessed up to 18 months after randomization.", "PMID": "11801195"}, {"title": "Splinting vs surgery in the treatment of carpal tunnel syndrome: a randomized controlled trial.", "abstract": "Carpal tunnel syndrome (CTS) can be treated with nonsurgical or surgical options. However, there is no consensus on the most effective method of treatment.\n\nTo compare the short-term and long-term efficacy of splinting and surgery for relieving the symptoms of CTS.\n\nA randomized controlled trial conducted from October 1998 to April 2000 at 13 neurological outpatient clinics in the Netherlands. A total of 176 patients with clinically and electrophysiologically confirmed idiopathic CTS were assigned to wrist splinting during the night for at least 6 weeks (89 patients) or open carpal tunnel release (87 patients); 147 patients (84%) completed the final follow-up assessment 18 months after randomization.\n\nGeneral improvement, number of nights waking up due to symptoms, and severity of symptoms.\n\nIn the intention-to-treat analyses, surgery was more effective than splinting on all outcome measures. The success rates (based on general improvement) after 3 months were 80% for the surgery group (62/78 patients) vs 54% for the splinting group (46/86 patients), which is a difference of 26% (95% confidence interval [CI], 12%-40%; P<.001). After 18 months, the success rates increased to 90% for the surgery group (61/68 patients) vs 75% for the splinting group (59/79 patients), which is a difference of 15% (95% CI, 3%-27%; P =.02). However, by that time 41% of patients (32/79) in the splint group had also received the surgery treatment.\n\nTreatment with open carpal tunnel release surgery resulted in better outcomes than treatment with wrist splinting for patients with CTS.", "PMID": "12215131"}, {"title": "SURGICAL TREATMENT FOR THE CARPAL TUNNEL SYNDROME.", "abstract": "", "PMID": "14132628"}, {"title": "Randomized clinical trial of surgery versus conservative therapy for carpal tunnel syndrome [ISRCTN84286481].", "abstract": "Conservative treatment remains the standard of care for treating mild to moderate carpal tunnel syndrome despite a small number of well-controlled studies and limited objective evidence to support current treatment options. There is an increasing interest in the usefulness of wrist magnetic resonance imaging could play in predicting who will benefit for various treatments.\n\nTwo hundred patients with mild to moderate symptoms will be recruited over 3 1/2 years from neurological surgery, primary care, electrodiagnostic clinics. We will exclude patients with clinical or electrodiagnostic evidence of denervation or thenar muscle atrophy. We will randomly assign patients to either a well-defined conservative care protocol or surgery. The conservative care treatment will include visits with a hand therapist, exercises, a self-care booklet, work modification/ activity restriction, B6 therapy, ultrasound and possible steroid injections. The surgical care would be left up to the surgeon (endoscopic vs. open) with usual and customary follow-up. All patients will receive a wrist MRI at baseline. Patients will be contacted at 3, 6, 9 and 12 months after randomization to complete the Carpal Tunnel Syndrome Assessment Questionnaire (CTSAQ). In addition, we will compare disability (activity and work days lost) and general well being as measured by the SF-36 version II. We will control for demographics and use psychological measures (SCL-90 somatization and depression scales) as well as EDS and MRI predictors of outcomes.\n\nWe have designed a randomized controlled trial which will assess the effectiveness of surgery for patients with mild to moderate carpal tunnel syndrome. An important secondary goal is to study the ability of MRI to predict patient outcomes.", "PMID": "15656907"}, {"title": "Surgical decompression versus local steroid injection in carpal tunnel syndrome: a one-year, prospective, randomized, open, controlled clinical trial.", "abstract": "Optimal treatment of carpal tunnel syndrome (CTS) has not been established. This study compared the effects of local steroid injection versus surgical decompression in new-onset CTS of at least 3 months' duration.\n\nIn a 1-year, prospective, randomized, open, controlled clinical trial, we studied the effects of surgical decompression versus local steroid injection in 163 wrists with a clinical and neurophysiologic diagnosis of CTS. Clinical assessments were done at baseline and at 3, 6, and 12 months after treatment. The primary end point was the percentage of wrists that reached a >or=20% improvement in the visual analog scale score for nocturnal paresthesias at 3 months of followup. Statistical analysis was done by Student's t-test for continuous variables and by chi-square test for categorical variables. Analyses were performed on an intent-to-treat basis. P values less than 0.05 were considered statistically significant.\n\nBoth treatment groups had comparable severity of CTS at baseline. Eighty wrists were randomly assigned to the surgery group and 83 wrists to the local steroid injection group. In the intent-to-treat analysis, at 3 months of followup, 94.0% of the wrists in the steroid injection group versus 75.0% in the surgery group reached a 20% response for nocturnal paresthesias (P = 0.001). At 6 and 12 months, the percentages of responders were 85.5% versus 76.3% (P = 0.163) and 69.9% versus 75.0% (P = 0.488), for local steroid injection and surgical decompression, respectively.\n\nOver the short term, local steroid injection is better than surgical decompression for the symptomatic relief of CTS. At 1 year, local steroid injection is as effective as surgical decompression for the symptomatic relief of CTS.", "PMID": "15692981"}, {"title": "Carpal tunnel syndrome despite negative neurophysiological studies.", "abstract": "The purpose of the present study was to compare the results of conservative and operative treatment for patients with carpal tunnel syndrome having normal neurophysiological studies. We studied 125 patients with normal neurophysiological studies and analysed eight symptoms and signs as \"prognostic factors\". Ninety-six patients were treated conservatively (splintage, steroid injection, antiinflammatory medications, activity modification) and 29 were treated surgically (open decompression). One year after initiation of treatment we assessed the outcome and statistically analysed (chi-square test) the differences between the two groups. We did not find any statistically significant correlation between \"prognostic factors\" and outcome. Twenty four percent of the group treated non-operatively had a good or excellent outcome, whereas 90% of the group treated operatively had a good or excellent outcome. This difference was statistically significant (p < 0.0001). Our study supports the view that the diagnosis of carpal tunnel syndrome is clinical and not neurophysiological. We now recommend operative treatment for these patients.", "PMID": "12050998"}, {"title": "Comparison of open carpal tunnel release and local steroid treatment outcomes in idiopathic carpal tunnel syndrome.", "abstract": "To compare the efficacy of local steroid injection and open carpal tunnel release, a symptom and functional status questionnaire (Boston Questionnaire) and sensory and motor nerve conduction studies were performed in 90 patients with electrophysiologically proven idiopathic carpal tunnel syndrome, of whom 44 were treated surgically and 46 by two-dose steroid injection. Electrophysiologic studies and the Boston Questionnaire were applied before and at the 3rd and 6th months after treatment. Both groups showed significant improvement at first follow-up. The surgically treated group showed a significant and further improvement of symptoms and conduction values between the 3rd- and 6th-month evaluations, whereas no significant change was observed in the patient group treated by steroid injection. By the end of follow-up, 5% of the hands in the open carpal tunnel release (OCTR) group and 13% of the hands in the local steroid injection (LSIG) group showed electrophysiological worsening, and 5% of the hands in the OCTR group and 22% of the hands in the LSIG group showed symptomatic worsening. Our results show that steroid injection provides an improvement comparable with that from surgical release of the median nerve at a 3-month interval. However, this improvement is not long-lasting.", "PMID": "12120909"}, {"title": "Clinical inquiries. Does surgery for carpal tunnel syndrome improve outcomes?", "abstract": "", "PMID": "12540318"}, {"title": "A randomized trial of splinting vs. surgery for carpal tunnel syndrome.", "abstract": "", "PMID": "12638558"}, {"title": "Surgery versus conservative therapy in carpal tunnel syndrome in people aged 70 years and older.", "abstract": "Carpal tunnel syndrome is common in the general population, with a prevalence that increases with age. Although good satisfaction has been described after carpal tunnel release, little is known about the long-term outcome of treatment in elderly individuals with carpal tunnel syndrome.\n\nThe authors reviewed data from a population-based sample of 102 patients aged 70 years and older with carpal tunnel syndrome. They used valid and sensitive mailed follow-up outcome [Boston Carpal Tunnel, satisfaction (American Academy of Orthopaedic Surgeons), and health status (Short Form-36) questionnaires to assess symptoms, functional status, expectations of treatment, and satisfaction with the results at a minimum of 2 years after initial diagnosis.\n\nSeventy patients with a mean age of 77.0 years (range, 70.2 to 88.5 years) responded to the survey, with a mean follow-up of 4.8 years. Patients who had surgery were more likely to have had more severe disease than those treated nonoperatively (Mantel-Haentzel test, p < 0.001). Satisfaction was 93 percent after surgical treatment and 54 percent after nonsurgical treatment. Patients who had surgery had significantly better relief of symptoms (t test, p < 0.01), functional status (t test, p < 0.05), satisfaction (t test, p < 0.001), and expectations with treatment (t test, p < 0.05) scores as compared with those who had nonsurgical treatment.\n\nIn patients over the age of 70, surgery appears to be associated with better symptom relief, functional status, satisfaction, and expectations with treatment than nonoperative therapy does. Age should not be considered a contraindication for carpal tunnel surgery, nor should nonoperative therapy be favored in this age group.", "PMID": "16980856"}], "labels": [{"PMID": "11801195", "label": "included"}, {"PMID": "12215131", "label": "included"}, {"PMID": "14132628", "label": "included"}, {"PMID": "15656907", "label": "included"}, {"PMID": "15692981", "label": "included"}, {"PMID": "12050998", "label": "excluded"}, {"PMID": "12120909", "label": "excluded"}, {"PMID": "12540318", "label": "excluded"}, {"PMID": "12638558", "label": "excluded"}, {"PMID": "16980856", "label": "excluded"}]}
{"metadata": {"review_pmid": "38180268"}, "inputs": {"background": "Cocaine is a psychostimulant used by approximately 0.4% of the general population worldwide. Cocaine dependence is a chronic mental disorder characterised by the inability to control cocaine use and a host of severe medical and psychosocial complications. There is current no approved pharmacological treatment for cocaine dependence. Some researchers have proposed disulfiram, a medication approved to treat alcohol use disorder. This is an update of a Cochrane review first published in 2010.", "objectives": "To evaluate the efficacy and safety of disulfiram for the treatment of cocaine dependence.", "selection criteria": "We included randomised controlled trials that evaluated disulfiram alone or associated with psychosocial interventions versus placebo, no intervention, other pharmacological interventions, or any psychosocial intervention for the treatment of cocaine dependence."}, "context": [{"title": "Disulfiram treatment for cocaine dependence in methadone-maintained opioid addicts.", "abstract": "Cocaine use by patients on methadone maintenance treatment is a widespread problem and is associated with a poorer prognosis. Recent studies have evaluated disulfiram as a treatment for individuals with comorbid alcohol and cocaine abuse. We evaluated the efficacy of disulfiram for cocaine dependence, both with and without co-morbid alcohol abuse, in a group of methadone-maintained opioid addicts.\n\nRandomized double-blind, placebo-controlled trial.\n\nUrban methadone maintenance clinic.\n\nSixty-seven cocaine-dependent, methadone-maintained, opioid-dependent subjects (52% female; 51% Caucasian).\n\nStudy medication, either disulfiram or placebo, was placed directly in the methadone to ensure compliance for 12 weeks.\n\nPrimary outcome measures included weekly assessments of the frequency and quantity of drug and alcohol use, weekly urine toxicology screens and breathalyzer readings.\n\nDisulfiram treated subjects decreased the quantity and frequency of cocaine use significantly more than those treated with placebo. Alcohol use was minimal for all subjects regardless of the medication.\n\nDisulfiram may be an effective pharmacotherapy for cocaine abuse among methadone-maintained opioid addicts, even in those individuals without co-morbid alcohol abuse. Disulfiram inhibits dopamine beta-hydroxylase resulting in an excess of dopamine and decreased synthesis of norepinephrine. Since cocaine is a potent catecholamine re-uptake inhibitor, disulfiram may blunt cocaine craving or alter the \"high\", resulting in a decreased desire to use cocaine.", "PMID": "10723850"}, {"title": "Disulfiram versus placebo for cocaine dependence in buprenorphine-maintained subjects: a preliminary trial.", "abstract": "We examined the effects of disulfiram versus placebo on cocaine dependence in buprenorphine-maintained subjects.\n\nOpioid and cocaine dependent subjects (n = 20) were induced onto buprenorphine maintenance, then randomized to disulfiram (250 mg q.d. ; n = 11) or placebo (n = 9) treatment for 12 weeks.\n\nGroups were comparable at baseline on demographic measures and on baseline measures of drug-use severity. Fifteen subjects completed the study, including 8 subjects randomized to disulfiram (72.7%) and 7 subjects randomized to placebo (77.8%). The total number of weeks abstinent from cocaine was significantly greater on disulfiram versus placebo (mean +/- SD: 7.8 +/- 2.6 vs. 3.3 +/- 0.5, p <.05) and the number of days to achieving 3 weeks (24.6 +/- 15.1 vs. 57.8 +/- 7.7, p <.01) of continuous cocaine abstinence was significantly lower in disulfiram compared with placebo. The number of cocaine-negative urine tests during the trial were also higher on disulfiram (14.7) than on placebo (8.6); furthermore, subjects in the disulfiram group achieved consistently higher rates of cocaine-negative urine tests in each 3-week interval and the increase over time was faster in the disulfiram compared with placebo.\n\nThis preliminary study suggests the potential efficacy of disulfiram versus placebo for treatment of cocaine dependence in buprenorphine-maintained patients.", "PMID": "10862808"}, {"title": "Efficacy of disulfiram and cognitive behavior therapy in cocaine-dependent outpatients: a randomized placebo-controlled trial.", "abstract": "Disulfiram has emerged as a promising treatment for cocaine dependence, but it has not yet been evaluated in general populations of cocaine users.\n\nTo compare the effectiveness of disulfiram therapy with that of a placebo condition in reducing cocaine use and to compare the effectiveness of 2 active behavioral therapies-cognitive behavior therapy (CBT) and interpersonal psychotherapy (IPT)-in reducing cocaine use.\n\nRandomized, placebo-controlled, double-masked (for medication condition), factorial (2 x 2) trial with 4 treatment conditions: disulfiram plus CBT, disulfiram plus IPT, placebo plus CBT, and placebo plus IPT.\n\nA community-based outpatient substance abuse treatment program.\n\nA total of 121 individuals meeting the criteria for current cocaine dependence.\n\nPatients received either disulfiram (250 mg/d) or placebo in identical capsules. Medication compliance was monitored using a riboflavin marker procedure. Both behavioral therapies (CBT and IPT) were manual guided and were delivered in individual sessions for 12 weeks.\n\nRandom regression analyses of self-reported frequency of cocaine use and results of urine toxicology screens.\n\nParticipants assigned to disulfiram reduced their cocaine use significantly more than those assigned to placebo, and those assigned to CBT reduced their cocaine use significantly more than those assigned to IPT (P<.01 for both). Findings were consistent across all study samples (eg, intention to treat, treatment initiators, and treatment completers). Benefits of disulfiram use and CBT were most pronounced for participants who were not alcohol dependent at baseline or who fully abstained from drinking alcohol during treatment. Adverse effects experienced by participants who received disulfiram were mild and were not considerably different from those experienced by participants who received placebo.\n\nDisulfiram and CBT are effective therapies for general populations of cocaine-dependent individuals. Disulfiram seems to exert a direct effect on cocaine use rather than through reducing concurrent alcohol use.", "PMID": "14993114"}, {"title": "Efficacy of disulfiram and cognitive behavior therapy in cocaine-dependent outpatients: a randomized placebo-controlled trial.", "abstract": "Disulfiram has emerged as a promising treatment for cocaine dependence, but it has not yet been evaluated in general populations of cocaine users.\n\nTo compare the effectiveness of disulfiram therapy with that of a placebo condition in reducing cocaine use and to compare the effectiveness of 2 active behavioral therapies-cognitive behavior therapy (CBT) and interpersonal psychotherapy (IPT)-in reducing cocaine use.\n\nRandomized, placebo-controlled, double-masked (for medication condition), factorial (2 x 2) trial with 4 treatment conditions: disulfiram plus CBT, disulfiram plus IPT, placebo plus CBT, and placebo plus IPT.\n\nA community-based outpatient substance abuse treatment program.\n\nA total of 121 individuals meeting the criteria for current cocaine dependence.\n\nPatients received either disulfiram (250 mg/d) or placebo in identical capsules. Medication compliance was monitored using a riboflavin marker procedure. Both behavioral therapies (CBT and IPT) were manual guided and were delivered in individual sessions for 12 weeks.\n\nRandom regression analyses of self-reported frequency of cocaine use and results of urine toxicology screens.\n\nParticipants assigned to disulfiram reduced their cocaine use significantly more than those assigned to placebo, and those assigned to CBT reduced their cocaine use significantly more than those assigned to IPT (P<.01 for both). Findings were consistent across all study samples (eg, intention to treat, treatment initiators, and treatment completers). Benefits of disulfiram use and CBT were most pronounced for participants who were not alcohol dependent at baseline or who fully abstained from drinking alcohol during treatment. Adverse effects experienced by participants who received disulfiram were mild and were not considerably different from those experienced by participants who received placebo.\n\nDisulfiram and CBT are effective therapies for general populations of cocaine-dependent individuals. Disulfiram seems to exert a direct effect on cocaine use rather than through reducing concurrent alcohol use.", "PMID": "14993114"}, {"title": "Short-term efficacy of Disulfiram or Naltrexone in reducing positive urinalysis for both cocaine and cocaethylene in cocaine abusers: a pilot study.", "abstract": "Cocaine abusers frequently report taking the drug in association with alcohol. This combined intake leads to the synthesis of cocaethylene, an active metabolite with effects similar to those of cocaine, but more prolonged. Since pharmacological effects of cocaethylene may partially account for the habit of cocaine abusers to take the drug in combination with ethanol, a main therapeutic goal in these patients should be making body fluids negative for cocaethylene. This randomized controlled open study conducted on 12 subjects co-abusers of cocaine and alcohol, evaluates the efficacy of a 12-week pharmacological treatment with Disulfiram (DIS) 400mg daily or Naltrexone (NTX) 50mg daily associated with Cognitive Behaviour Therapy (CBT), as compared to CBT alone, in terms of: (i) stay in treatment; (ii) drug-free urinalyses for cocaine and cocaethylene; (iii) reduction of alcohol and cocaine craving. Data presented in this study are restricted to the first 4 weeks of treatment when all the enrolled subjects were still available for examination. In fact, of the 12 subjects enrolled in the study only 4 (33%) completed the 12-week treatment. Of these, three were in the CBT group and one in the NTX/CBT group. Results show that CBT treated subjects remained in treatment longer than those assigned to either DIS/CBT or NTX/CBT therapies. However, during the first 4 weeks of treatment, CBT-group urine tested positive almost always for both cocaine and cocaethylene. In contrast, both DIS/CBT and NTX/CBT treatments were associated to a statistically significant reduction, of positive urinalysis for both cocaine and cocaethylene, with respect to CBT alone. Moreover, across the first 4 weeks of treatment DIS/CBT and NTX/CBT treated subjects maintained lower scores at Visual Analogue Scales (VAS) for both cocaine and alcohol craving than subjects receiving CBT alone. This pilot study suggests that the transient efficacy of pharmacological treatments in maintaining subjects drug free, does not add to the capability of CBT to retain them in treatment.", "PMID": "17174102"}, {"title": "Short-term efficacy of Disulfiram or Naltrexone in reducing positive urinalysis for both cocaine and cocaethylene in cocaine abusers: a pilot study.", "abstract": "Cocaine abusers frequently report taking the drug in association with alcohol. This combined intake leads to the synthesis of cocaethylene, an active metabolite with effects similar to those of cocaine, but more prolonged. Since pharmacological effects of cocaethylene may partially account for the habit of cocaine abusers to take the drug in combination with ethanol, a main therapeutic goal in these patients should be making body fluids negative for cocaethylene. This randomized controlled open study conducted on 12 subjects co-abusers of cocaine and alcohol, evaluates the efficacy of a 12-week pharmacological treatment with Disulfiram (DIS) 400mg daily or Naltrexone (NTX) 50mg daily associated with Cognitive Behaviour Therapy (CBT), as compared to CBT alone, in terms of: (i) stay in treatment; (ii) drug-free urinalyses for cocaine and cocaethylene; (iii) reduction of alcohol and cocaine craving. Data presented in this study are restricted to the first 4 weeks of treatment when all the enrolled subjects were still available for examination. In fact, of the 12 subjects enrolled in the study only 4 (33%) completed the 12-week treatment. Of these, three were in the CBT group and one in the NTX/CBT group. Results show that CBT treated subjects remained in treatment longer than those assigned to either DIS/CBT or NTX/CBT therapies. However, during the first 4 weeks of treatment, CBT-group urine tested positive almost always for both cocaine and cocaethylene. In contrast, both DIS/CBT and NTX/CBT treatments were associated to a statistically significant reduction, of positive urinalysis for both cocaine and cocaethylene, with respect to CBT alone. Moreover, across the first 4 weeks of treatment DIS/CBT and NTX/CBT treated subjects maintained lower scores at Visual Analogue Scales (VAS) for both cocaine and alcohol craving than subjects receiving CBT alone. This pilot study suggests that the transient efficacy of pharmacological treatments in maintaining subjects drug free, does not add to the capability of CBT to retain them in treatment.", "PMID": "17174102"}, {"title": "A double blind, placebo-controlled trial that combines disulfiram and naltrexone for treating co-occurring cocaine and alcohol dependence.", "abstract": "This is a double blind, placebo-controlled trial that evaluated the efficacy of disulfiram, naltrexone and their combination in patients with co-occurring cocaine and alcohol dependence.\n\n208 patients were randomized to disulfiram (250 mg/day), naltrexone (100 mg/day), the combination, or placebo for 11 weeks. Outcomes were in-trial abstinence from cocaine and/or alcohol.\n\nFew safety concerns were reported, although medication adherence was low in a number of patients for both medications, alone or in combination. In the primary analyses (GEE modeling), abstinence from cocaine as measured by cocaine-negative urines and days of self-reported abstinence from cocaine or alcohol did not differ between placebo and any of the medication groups. However, patients taking disulfiram (alone or in combination) were most likely to achieve combined abstinence from cocaine and alcohol. Secondary analyses revealed that patients taking the disulfiram-naltrexone combination were most likely to achieve 3 consecutive weeks of abstinence from cocaine and alcohol.\n\nThere was an association between disulfiram treatment and abstinence from cocaine and alcohol. More patients taking the disulfiram-naltrexone combination achieved 3 consecutive weeks of abstinence in treatment than placebo-treated patients.", "PMID": "18079068"}, {"title": "One-year follow-up of disulfiram and psychotherapy for cocaine-alcohol users: sustained effects of treatment.", "abstract": "To evaluate outcomes 1 year after cessation of treatment for cocaine- and alcohol-dependent individuals.\n\nRandomized controlled trial.\n\nUrban substance abuse treatment center.\n\nNinety-six of 122 subjects randomized to treatment.\n\nOne of five treatments delivered over 12 weeks. Cognitive-behavioral treatment (CBT) plus disulfiram; Twelve-Step facilitation (TSF) plus disulfiram; clinical management (CM) plus disulfiram; CBT without disulfiram; TSF without disulfiram.\n\nPercentage of days of cocaine and alcohol use during follow-up, verified by urine toxicology screens and breathalyzer tests.\n\nFirst, as a group, participants reported significant decreases in frequency of cocaine, but not alcohol, use after the end of treatment. Secondly, the main effects of disulfiram on cocaine and alcohol use were sustained during follow-up. Finally, initiation of abstinence for even brief periods of time within treatment was associated with significantly better outcome during follow-up.\n\nThese findings support the efficacy of disulfiram with this challenging population and suggest that comparatively brief treatments that facilitate the initiation of abstinence may have long-term benefits.", "PMID": "11048353"}, {"title": "The URICA as a measure of motivation to change among treatment-seeking individuals with concurrent alcohol and cocaine problems.", "abstract": "The original 4-factor structure of the University of Rhode Island Change Assessment (URICA; C. C. DiClemente & S. O. Hughes, 1990) was replicated, and the scale's internal consistency was found to be acceptable in a sample of 106 cocaine- and alcohol-dependent participants receiving either disulfiram or no medication in a psychotherapy trial. In addition, participants categorized as having high Committed Action (CA), a new URICA composite, had a significantly greater percentage of days abstinent from both alcohol and cocaine (85.6%) than low-CA participants (72.7%, p < .01). Furthermore, a significant Treatment x CA interaction emerged, suggesting that low-CA participants had better outcomes than those with high CA when assigned to medication, whereas high-CA participants fared equally well with or without medication.", "PMID": "12503902"}, {"title": "Ethnic differences in substance abuse treatment retention, compliance, and outcome from two clinical trials.", "abstract": "This study examined the results of two previous studies that evaluated African Americans and whites who were undergoing treatment for cocaine dependence to determine whether the groups differed in pretreatment characteristics, treatment retention, compliance, and cocaine use outcome.\n\nData were taken from two trials (N=111 in each), in which patients were randomly assigned to groups that used different behavioral treatments (cognitive-behavioral treatment and 12-step facilitation) and pharmacotherapies (desipramine and disulfiram).\n\nFew differences between African Americans and whites were found in terms of demographic characteristics, reasons for seeking treatment, or expectations of treatment. In both studies African Americans and whites did not differ significantly with respect to cocaine use outcomes, but African-American participants completed significantly fewer days of treatment than white participants. In study 2, which was not placebo controlled, African Americans who received disulfiram remained in treatment significantly longer than African Americans who did not receive disulfiram. However, in study 1, in which patients took either desipramine or a placebo, no interactions of ethnicity by medication were found. Among patients who expected improvement to take a month or longer in study 1, African Americans remained in treatment for fewer days than whites.\n\nThe behavioral therapies evaluated did not significantly differ in effectiveness for African Americans and whites, suggesting that they are broadly applicable across these ethnic groups. Findings also suggest possible strategies for improving retention of African Americans in treatment. Such strategies might include offering treatment with a medication component and better addressing participants' treatment expectations.", "PMID": "14762242"}], "labels": [{"PMID": "10723850", "label": "included"}, {"PMID": "10862808", "label": "included"}, {"PMID": "14993114", "label": "included"}, {"PMID": "14993114", "label": "included"}, {"PMID": "17174102", "label": "included"}, {"PMID": "17174102", "label": "included"}, {"PMID": "18079068", "label": "included"}, {"PMID": "11048353", "label": "excluded"}, {"PMID": "12503902", "label": "excluded"}, {"PMID": "14762242", "label": "excluded"}]}
{"metadata": {"review_pmid": "38180112"}, "inputs": {"background": "Around one-third of older adults aged 65 years or older who live in the community fall each year. Interventions to prevent falls can be designed to target the whole community, rather than selected individuals. These population-level interventions may be facilitated by different healthcare, social care, and community-level agencies. They aim to tackle the determinants that lead to risk of falling in older people, and include components such as community-wide polices for vitamin D supplementation for older adults, reducing fall hazards in the community or people's homes, or providing public health information or implementation of public health programmes that reduce fall risk (e.g. low-cost or free gym membership for older adults to encourage increased physical activity).", "objectives": "To review and synthesise the current evidence on the effects of population-based interventions for preventing falls and fall-related injuries in older people. We defined population-based interventions as community-wide initiatives to change the underlying societal, cultural, or environmental conditions increasing the risk of falling.", "selection criteria": "We included randomised controlled trials (RCTs), cluster RCTs, trials with stepped-wedge designs, and controlled non-randomised studies evaluating population-level interventions for preventing falls and fall-related injuries in adults \u2265 60 years of age. Population-based interventions target entire communities. We excluded studies only targeting people at high risk of falling or with specific comorbidities, or residents living in institutionalised settings."}, "context": [{"title": "Determinants of acceptance of a community-based program for the prevention of falls and fractures among the elderly.", "abstract": "Low-energy fractures among the elderly may be prevented by measures aimed at reducing the risk of falling or increasing the strength of the skeleton. Acceptance of these interventions in the target population is necessary for their success.\n\nThe total elderly population in a Danish municipality 7,543 community-dwelling persons aged 66+ years, were offered participation in one of three intervention programs: 2,550 persons were offered a home safety inspection, evaluation of prescribed medicine, and identification of possible health and food problems (Program I); 2,445 persons were offered 1000 mg of elemental calcium and 400 IU (10 microg) of vitamin D(3) per day in combination with evaluation of prescribed medicine (Program II); and 2,548 persons were offered a combination of the two programs (Program III). Acceptance was defined as willingness to receive an introductory visit by a nurse.\n\nAcceptance of Program I was 50%; of Program II, 56% (P < 0.00005 as contrasted with Program I); and of Program III, 46% (P < 0.005). Acceptance was associated with gender (females, 53%; males, 47%) and did not change from ages 66 to 84 but decreased significantly after the age of 85. Widows aged 66-84 had the highest acceptance (57%) and never married males aged 66-84 the lowest (30%). An important determinant, however, was the individual social service center that communicated the specific program. Acceptance varied from 39 to 66% between the social centers.\n\nAcceptance of a fall and fracture prevention program varies with intervention type; with gender, age, and social status of the target population; and with the motivation and attitude of the health workers involved in the implementation of the program.", "PMID": "11493044"}, {"title": "Evaluation of an inter-organizational prevention program against injuries among the elderly in a WHO Safe Community.", "abstract": "The aim of the study was to evaluate the outcome of a participatory community-based prevention program against injuries among the elderly. A population-based quasi-experimental design was used with pre- and post-implementation measurements in an intervention and a control area. The program was based on cross-sectoral participation in detecting and taking action against injuries among the elderly. Change in the relative risk of injury was estimated by the odds ratio. Morbidity in moderately (AIS 2) severe injury in the study area was reduced from 46 per 1000 population years to 25 per 1000 population years (odds ratio 0.55; 95% confidence interval 0.46-0.65), while the minor (AIS 1) injuries increased (odds ratio 1.55; 95% confidence interval 1.21-1.91). The risk of severe or fatal (AIS 3-6) injuries remained constant. In the study area, only a slight decrease in the total morbidity rate was observed (odds ratio 0.87; 95% confidence interval 0.77-0.99). In the control area, there was no evident change in the total morbidity rates. Falls decreased or showed a tendency to decrease in the age groups 65 to 79-y-old in the study area, while they increased in the older age group. The results indicate that no sharp boundaries should be drawn between safety education, physical conditioning, environmental adjustments and secondary prevention measures when planning safety promotion among the elderly. Future studies should address these issues along with the methodological complexity associated with assessment of participatory community-based safety promotion programs.", "PMID": "11593439"}, {"title": "[Effectiveness of a multifactorial intervention to prevent falls among elderly people in a community].", "abstract": "The falls of old people are a common problem that will increase as the population ages and which are accompanied by high morbidity and mortality. Multifactorial intervention has proved effective in reducing the number of falls.\n\nTo reduce the number of falls and their complications in the population >= 70 years old of a health district through a multifactorial community intervention programme.\n\nMulti-centred community intervention quasi-experimental study with no randomised allocation. It will be run in two communities, viz Salt and Girona-4, both of which are health districts in the province of Girona. In both an initial study will seek to establish the prevalence of falls and their consequences in people >= 70 years old. Data will be obtained from several randomised samples, using a questionnaire drawn up for the purpose. A multifactorial community intervention lasting two years (intervention group) will be made in the Salt Health District. There will be no specific intervention in the other community (control group). Later, effectiveness will be evaluated through randomised samples given the same questionnaire.\n\nPossible limitations of the study are the effect of contamination between the two communities, the existence of factors external to the intervention programme, losses due to people moving and deaths, and difficulty in assessing community activity. This programme can be applied to other communities as part of care and health education activities undertaken by primary care teams.", "PMID": "11602125"}, {"title": "Community-based tai chi and its effect on injurious falls, balance, gait, and fear of falling in older people.", "abstract": "It is important to determine the effect of adherence to a tai chi program on falls and related functional outcomes in older people. This study examined the effect of a community-based tai chi program on injurious falls, balance, gait, and fear of falling among people aged 65 years and older in Taiwan.\n\nIn 6 rural villages in Taichung County, 1,200 subjects participated in the initial assessment. During a 1-year intervention period, all study villages were provided with education on fall prevention. Two villages had been provided tai chi exercise (n=472 participants or \"tai chi villagers\"), and 4 villages served as control villages (n=728 participants or \"control villagers\"). Injurious falls were ascertained by telephone interviews every 3 months over a 2-year study period; additionally, balance, gait, and fear of falling were assessed in 2 follow-up assessments.\n\nEighty-eight subjects, 83 from the tai chi villages and 5 from the control villages, participated and practiced in the tai chi program (the group labeled \"tai chi practitioners\"). After the tai chi program, injurious falls among the control villagers significantly declined by 44% (adjusted rate ratio [RR]=0.56; 95% confidence interval [CI]=0.36-0.92). Compared with the results for the control villagers, the decline was 31% greater (RR=0.69; 95% CI=0.30-1.56) among the tai chi villagers and 50% greater (RR=0.5; 95% CI=0.11-2.17) among the tai chi practitioners; the results did not reach statistical significance. Furthermore, compared with the scores for the control villagers, the scores for the tai chi practitioners increased by 1.8 points (95% CI=0.2-3.4) on the Tinetti Balance Scale and increased by 0.9 point (95% CI=0.1-1.8) on the Tinetti Gait Scale. No significant changes in the fear of falling were detected among the tai chi practitioners, tai chi villagers, and control villagers.\n\nTai chi can prevent a decline in functional balance and gait among older people. However, the reduction in injurious falls attained with tai chi did not reach statistical significance; the statistical inefficiency may have resulted partly from the large decline in injurious falls in control villagers. Finally, the unexpected effect of educational intervention on reducing injurious falls in different settings needs to be further examined.", "PMID": "16959668"}, {"title": "Multicentre cluster randomised trial comparing a community group exercise programme and home-based exercise with usual care for people aged 65 years and over in primary care.", "abstract": "Regular physical activity (PA) reduces the risk of falls and hip fractures, and mortality from all causes. However, PA levels are low in the older population and previous intervention studies have demonstrated only modest, short-term improvements.\n\nTo evaluate the impact of two exercise promotion programmes on PA in people aged \u2265\u200965 years.\n\nThe ProAct65+ study was a pragmatic, three-arm parallel design, cluster randomised controlled trial of class-based exercise [Falls Management Exercise (FaME) programme], home-based exercise [Otago Exercise Programme (OEP)] and usual care among older people (aged \u2265\u200965 years) in primary care.\n\nForty-three UK-based general practices in London and Nottingham/Derby.\n\nA total of 1256 people \u2265\u200965 years were recruited through their general practices to take part in the trial.\n\nThe FaME programme and OEP. FaME included weekly classes plus home exercises for 24 weeks and encouraged walking. OEP included home exercises supported by peer mentors (PMs) for 24 weeks, and encouraged walking.\n\nThe primary outcome was the proportion that reported reaching the recommended PA target of 150 minutes of moderate to vigorous physical activity (MVPA) per week, 12 months after cessation of the intervention. Secondary outcomes included functional assessments of balance and falls risk, the incidence of falls, fear of falling, quality of life, social networks and self-efficacy. An economic evaluation including participant and NHS costs was embedded in the clinical trial.\n\nIn total, 20,507 patients from 43 general practices were invited to participate. Expressions of interest were received from 2752 (13%) and 1256 (6%) consented to join the trial; 387 were allocated to the FaME arm, 411 to the OEP arm and 458 to usual care. Primary outcome data were available at 12 months after the end of the intervention period for 830 (66%) of the study participants. The proportions reporting at least 150 minutes of MVPA per week rose between baseline and 12 months after the intervention from 40% to 49% in the FaME arm, from 41% to 43% in the OEP arm and from 37.5% to 38.0% in the usual-care arm. A significantly higher proportion in the FaME arm than in the usual-care arm reported at least 150 minutes of MVPA per week at 12 months after the intervention [adjusted odds ratio (AOR) 1.78, 95% confidence interval (CI) 1.11 to 2.87; p\u2009=\u20090.02]. There was no significant difference in MVPA between OEP and usual care (AOR 1.17, 95% CI 0.72 to 1.92; p\u2009=\u20090.52). Participants in the FaME arm added around 15 minutes of MVPA per day to their baseline physical activity level. In the 12 months after the close of the intervention phase, there was a statistically significant reduction in falls rate in the FaME arm compared with the usual-care arm (incidence rate ratio 0.74, 95% CI 0.55 to 0.99; p\u2009=\u20090.042). Scores on the Physical Activity Scale for the Elderly showed a small but statistically significant benefit for FaME compared with usual care, as did perceptions of benefits from exercise. Balance confidence was significantly improved at 12 months post intervention in both arms compared with the usual-care arm. There were no statistically significant differences between intervention arms and the usual-care arm in other secondary outcomes, including quality-adjusted life-years. FaME is more expensive than OEP delivered with PMs (\u00a3269 vs. \u00a388 per participant in London; \u00a3218 vs. \u00a3117 in Nottingham). The cost per extra person exercising at, or above, target was \u00a31919.64 in London and \u00a31560.21 in Nottingham (mean \u00a31739.93).\n\nThe FaME intervention increased self-reported PA levels among community-dwelling older adults 12 months after the intervention, and significantly reduced falls. Both the FaME and OEP interventions appeared to be safe, with no significant differences in adverse reactions between study arms.\n\nThis trial is registered as ISRCTN43453770.\n\nThis project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 49. See the NIHR Journals Library website for further project information.", "PMID": "25098959"}, {"title": "Translating a Fall Prevention Intervention Into Practice: A Randomized Community Trial.", "abstract": "We examined whether community translation of an effective evidence-based fall prevention program via standard monetary support can produce a community-wide reduction in fall injuries in older adults and evaluated whether an enhanced version with added technical support and capacity building amplified the fall reduction effect.\n\nWe completed a randomized controlled community trial among adults aged 65 and older in (1) 10 control communities receiving no special resources or guidance on fall prevention, (2) 5 standard support communities receiving modest funding to implement Stepping On, and (3) 5 enhanced support communities receiving funding and technical support. The primary outcome was hospital inpatient and emergency department discharges for falls, examined with Poisson regression.\n\nCompared with control communities, standard and enhanced support communities showed significantly higher community-wide reductions (9% and 8%, respectively) in fall injuries from baseline (2007-2008) to follow-up (2010-2011). No significant difference was found between enhanced and standard support communities.\n\nPopulation-based fall prevention interventions can be effective when implemented in community settings. More research is needed to identify the barriers and facilitators that influence the successful adoption and implementation of fall prevention interventions into broad community practice.", "PMID": "25602891"}, {"title": "A randomised controlled trial of low-dose aspirin for the prevention of fractures in healthy older people: protocol for the ASPREE-Fracture substudy.", "abstract": "Disability, mortality and healthcare burden from fractures in older people is a growing problem worldwide. Observational studies suggest that aspirin may reduce fracture risk. While these studies provide room for optimism, randomised controlled trials are needed. This paper describes the rationale and design of the ASPirin in Reducing Events in the Elderly (ASPREE)-Fracture substudy, which aims to determine whether daily low-dose aspirin decreases fracture risk in healthy older people.\n\nASPREE is a double-blind, randomised, placebo-controlled primary prevention trial designed to assess whether daily active treatment using low-dose aspirin extends the duration of disability-free and dementia-free life in 19\u2005000 healthy older people recruited from Australian and US community settings. This substudy extends the ASPREE trial data collection to determine the effect of daily low-dose aspirin on fracture and fall-related hospital presentation risk in the 16\u2005500 ASPREE participants aged \u226570\u2005years recruited in Australia. The intervention is a once daily dose of enteric-coated aspirin (100\u2005mg) versus a matching placebo, randomised on a 1:1 basis. The primary outcome for this substudy is the occurrence of any fracture-vertebral, hip and non-vert-non-hip-occurring post randomisation. Fall-related hospital presentations are a secondary outcome.\n\nThis substudy will determine whether a widely available, simple and inexpensive health intervention-aspirin-reduces the risk of fractures in older Australians. If it is demonstrated to safely reduce the risk of fractures and serious falls, it is possible that aspirin might provide a means of fracture prevention.\n\nThe protocol for this substudy is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000347561).", "PMID": "26002770"}, {"title": "A cluster randomised controlled trial of advice, exercise or multifactorial assessment to prevent falls and fractures in community-dwelling older adults: protocol for the prevention of falls injury trial (PreFIT).", "abstract": "Falls are the leading cause of accident-related mortality in older adults. Injurious falls are associated with functional decline, disability, healthcare utilisation and significant National Health Service (NHS)-related costs. The evidence base for multifactorial or exercise interventions reducing fractures in the general population is weak. This protocol describes a large-scale UK trial investigating the clinical and cost-effectiveness of alternative falls prevention interventions targeted at community dwelling older adults.\n\nA three-arm, pragmatic, cluster randomised controlled trial, conducted within primary care in England, UK. Sixty-three general practices will be randomised to deliver one of three falls prevention interventions: (1) advice only; (2) advice with exercise; or (3) advice with multifactorial falls prevention (MFFP). We aim to recruit over 9000 community-dwelling adults aged 70 and above. Practices randomised to deliver advice will mail out advice booklets. Practices randomised to deliver 'active' interventions, either exercise or MFFP, send all trial participants the advice booklet and a screening survey to identify participants with a history of falling or balance problems. Onward referral to 'active' intervention will be based on falls risk determined from balance screen. The primary outcome is peripheral fracture; secondary outcomes include number with at least one fracture, falls, mortality, quality of life and health service resource use at 18 months, captured using self-report and routine healthcare activity data.\n\nThe study protocol has approval from the National Research Ethics Service (REC reference 10/H0401/36; Protocol V.3.1, 21/May/2013). User groups and patient representatives were consulted to inform trial design. Results will be reported at conferences and in peer-reviewed publications. A patient-friendly summary of trial findings will be published on the prevention of falls injury trial (PreFIT) website. This protocol adheres to the recommended SPIRIT Checklist. Amendments will be reported to relevant regulatory parties.\n\nISRCTN 71002650; Pre-results.", "PMID": "26781504"}, {"title": "Implementation of the Stopping Elderly Accidents, Deaths, and Injuries Initiative in Primary Care: An Outcome Evaluation.", "abstract": "Older adult falls pose a growing burden on the U.S. health care system. The Centers for Disease Control and Prevention's Stopping Elderly Accidents, Deaths, and Injuries (STEADI) initiative was developed as a multifactorial approach to fall prevention that includes screening for fall risk, assessing for modifiable risk factors, and prescribing evidence-based interventions to reduce fall risk. The purpose of this study was to determine the impact of a STEADI initiative on medically treated falls within a large health care system in Upstate New York.\n\nThis cohort study classified older adults who were screened for fall risk into 3 groups: (a) At-risk and no Fall Plan of Care (FPOC), (b) At-risk with a FPOC, and (c) Not-at-risk. Poisson regression examined the group's effect on medically treated falls when controlling for other variables. The sample consisted of 12,346 adults age 65 or older who had a primary care visit at one of 14 outpatient clinics between September 11, 2012, and October 30, 2015. A medically treated fall was defined as a fall-related treat-and-release emergency department visit or hospitalization.\n\nOlder adults at risk for fall with a FPOC were 0.6 times less likely to have a fall-related hospitalization than those without a FPOC (p = .041), and their postintervention odds were similar to those who were not at risk.\n\nThis study demonstrated that implementation of STEADI fall risk screening and prevention strategies among older adults in the primary care setting can reduce fall-related hospitalizations and may lower associated health care expenditures.", "PMID": "30239774"}, {"title": "VITamin D and OmegA-3 TriaL (VITAL): Effects of Vitamin D Supplements on Risk of Falls in the US Population.", "abstract": "It is unclear whether vitamin D supplementation reduces risk of falls, and results from randomized controlled trials (RCTs) are conflicting.\n\nThe objective of this work is to determine whether 2000 IU/day of supplemental vitamin D3 decreases fall risk.\n\nVITamin D and OmegA-3 TriaL (VITAL) is a double-blind, placebo-controlled RCT including 25 871 adults, randomly assigned November 2011 to March 2014 and treated for 5.3 years (median).\n\nThis is a nationwide study.\n\nMen 50 years or older and women 55 years or older (mean age, 67.1 years) without cancer or cardiovascular disease at baseline participated in this study.\n\nInterventions included vitamin D3 (cholecalciferol; 2000 IU/day) and/or omega-3 fatty acids (1 g/day) or respective placebos in a 2\u2005\u00d7\u20052 factorial design.\n\nMain outcome measures include 2 or more falls and falls resulting in a doctor or hospital visit.\n\nBaseline serum total 25-hydroxyvitamin D (25[OH]D) level was 77 nmol/L; characteristics were well-balanced between groups. Numbers of participants with 2 or more falls were similar between active and placebo groups (9.8% vs 9.4%). Over 5 years, there were no differences in the proportion having 2 or more falls (odds ratio [OR] = 0.97; 95% CI, 0.90-1.05, P = .50), falls resulting in a doctor visit (OR = 1.03; 95% CI, 0.94-1.13, P = .46), or resulting in a hospital visit (OR = 1.04; 95% CI, 0.90-1.19, P = .61) between groups. Results did not differ between those with baseline 25(OH)D less than 50 vs 50 nmol/L or greater or other cut points.\n\nDaily supplemental vitamin D3 vs placebo did not decrease fall risk in generally healthy adults not selected for vitamin D insufficiency. This large RCT does not indicate that supplemental vitamin D should be used for primary prevention of falls in the US population.", "PMID": "32492153"}], "labels": [{"PMID": "11493044", "label": "included"}, {"PMID": "11593439", "label": "included"}, {"PMID": "11602125", "label": "included"}, {"PMID": "16959668", "label": "excluded"}, {"PMID": "25098959", "label": "excluded"}, {"PMID": "25602891", "label": "excluded"}, {"PMID": "26002770", "label": "excluded"}, {"PMID": "26781504", "label": "excluded"}, {"PMID": "30239774", "label": "excluded"}, {"PMID": "32492153", "label": "excluded"}]}
{"metadata": {"review_pmid": "38180091"}, "inputs": {"background": "Children often require pain management following surgery to avoid suffering. Effective pain management has consequences for healing time and quality of life. Ibuprofen, a frequently used non-steroidal anti-inflammatory drug (NSAID) administered to children, is used to treat pain and inflammation in the postoperative period.", "objectives": "1) To assess the efficacy and safety of ibuprofen (any dose) for acute postoperative pain management in children compared with placebo or other active comparators. 2) To compare ibuprofen administered at different doses, routes (e.g. oral, intravenous, etc.), or strategies (e.g. as needed versus as scheduled).", "selection criteria": "We included randomised controlled trials (RCTs) in children aged 17 years and younger, treated for acute postoperative or postprocedural pain, that compared ibuprofen to placebo or any active comparator. We included RCTs that compared different administration routes, doses of ibuprofen and schedules."}, "context": [{"title": "An evaluation of preoperative ibuprofen for treatment of pain associated with orthodontic separator placement.", "abstract": "Patients undergoing orthodontic treatment can experience significant levels of pain. This study assessed the effectiveness of preoperative ibuprofen in reducing the incidence and the severity of pain after orthodontic separator placement. Sixty-three adolescent patients (mean age, 13 years) were included in this randomized, double-blind, placebo-controlled, prospective study. Patients were randomly assigned to 1 of 3 experimental conditions: (1) 400 mg of ibuprofen taken orally 1 hour before separator placement and a lactose placebo taken orally immediately after the appointment, (2) a lactose placebo taken orally 1 hour before separator placement and 400 mg of ibuprofen taken orally immediately after the appointment, or (3) a lactose placebo taken orally 1 hour before separator placement and again immediately after the appointment. The patient's level of discomfort was assessed with a visual analog scale at 2, 6, and 24 hours, as well as at 2, 3, and 7 days after placement of the orthodontic separators. An analysis of variance and Duncan's multiple range test revealed that 2 hours after their orthodontic appointment the patients who had taken ibuprofen 1 hour before separator placement had significantly less pain with chewing than did the patients who received either ibuprofen postoperatively or a placebo. Additional measures suggest a trend for less pain for this group of patients. These results support the use of pretreatment ibuprofen for patients requiring analgesics for orthodontic discomfort. Future study of the use of preemptive analgesics in orthodontics is warranted.", "PMID": "11113797"}, {"title": "The effect of preemptive and/or postoperative ibuprofen therapy for orthodontic pain.", "abstract": "The control of pain during orthodontic treatment is of vital interest to both clinicians and patients. Surprisingly, there has been limited research into the control of orthodontic pain, and there is no standard of care for controlling this discomfort. The purpose of this study was to compare the effectiveness of preemptive ibuprofen therapy, postoperative ibuprofen therapy, and a combination of the 2 therapies. Forty-one orthodontic patients aged 9 years 3 months to 16 years 11 months who were to undergo separator placement were enrolled in this prospective study. Patients were randomly assigned to 1 of 3 experimental conditions: (1) 400 mg ibuprofen taken orally 1 hour before separator placement and 400 mg ibuprofen taken orally 6 hours after the initial dose, (2) 400 mg ibuprofen taken orally 1 hour before separator placement and a lactose capsule taken orally 6 hours after the initial dose, or (3) a lactose capsule taken orally 1 hour before separator placement and 400 mg ibuprofen taken 6 hours after the initial placebo. The results revealed that preemptive ibuprofen therapy significantly decreased pain that was experienced 2 hours after separator placement and at bedtime. Beginning on day 2, there was a trend for patients who had taken both preemptive and postoperative ibuprofen doses to have lower pain scores compared with the other 2 groups. In conclusion, these data indicate that ibuprofen taken 60 minutes before separator placement alleviates pain at 2 hours and at bedtime after treatment. Further study with the use of additional postoperative doses is warranted.", "PMID": "11455373"}, {"title": "Double-blind, placebo-controlled analgesic study of ibuprofen or rofecoxib in combination with paracetamol for tonsillectomy in children.", "abstract": "The analgesics used for paediatric tonsillectomy may be associated with side-effects such as sedation, respiratory depression and vomiting (opioids) or increased bleeding [non-steroidal anti-inflammatory drugs (NSAIDs)]. In our institution, we employ a combination of paracetamol, NSAID and opioid, although there is no published evidence of analgesic benefit from adding NSAIDs to paracetamol in children.\n\nThis randomized, double-blinded clinical study examined the analgesic effectiveness of combining paracetamol (20 mg kg(-1)) with rofecoxib (0.625 mg kg(-1)), ibuprofen (5 mg kg(-1)) or placebo as premedication for (adeno)tonsillectomy (n=98) in children aged 3-15 yr. Intravenous fentanyl 1-2 microg kg(-1) was given intraoperatively. Regular oral paracetamol (15 mg kg(-1), 4 hourly) was given after operation and could be supplemented on request from the child with oral ibuprofen 5 mg kg(-1) or oral codeine 1 mg kg(-1). The primary outcome variable was need for early supplementary analgesia (within 2 h after surgery).\n\nThe addition of ibuprofen to paracetamol reduced the need for early analgesia from 72% to 38% of children (difference 34%; 95% confidence interval 4-64%). The addition of rofecoxib to paracetamol did not significantly alter the need for early analgesia (68 vs 72%). Pain scores were higher in those children who required early analgesia. There were no differences between the groups in operative blood loss or complications, total 24-h analgesic consumption, pain scores at 4 and 8 h, vomiting or antiemetic use.\n\nThis study provides evidence to support the combination of ibuprofen (but not rofecoxib) with paracetamol for perioperative analgesia in children.", "PMID": "11881888"}, {"title": "Analgesic efficacy of rectal acetaminophen and ibuprofen alone or in combination for paediatric day-case adenoidectomy.", "abstract": "Acetaminophen and non-steroidal anti-inflammatory drugs have different mechanisms of action. We investigated if combining rectal acetaminophen with ibuprofen would provide better postoperative analgesia compared with either drug alone after adenoidectomy in children.\n\n160 children, aged 1-6 yr, undergoing day-case adenoidectomy, were randomized to receive either acetaminophen 40 mg kg(-1), ibuprofen 15 mg kg(-1), their combination, or placebo rectally immediately after anaesthetic induction. A standard anaesthetic method was used and all children received alfentanil 10 micro g kg(-1) i.v. during induction. Meperidine 5-10 mg i.v. was used for rescue analgesia for a pain score (Objective Pain Scale) over 3. Recovery times, sedation scores and the need for rescue analgesia and adverse events during the first 24 h after anaesthesia were recorded. Rescue analgesic at home was ibuprofen 10 mg kg(-1).\n\nTotal meperidine requirements were significantly less in the groups receiving acetaminophen, ibuprofen, or their combination compared with the group receiving placebo indicating an opioid-sparing effect of 19-28% (P<0.05). Children given acetaminophen were more sedated than those given ibuprofen (P<0.05). Discharge criteria were fulfilled earlier in the ibuprofen group than in all the other groups (P<0.05). At home, less children (49%) needed rescue analgesia in the combination group compared with the other groups (74-77%) (P<0.02).\n\nWe conclude that prophylactically administered rectal acetaminophen combined with ibuprofen does not improve analgesia after adenoidectomy in the immediate postoperative period compared with either drug alone but does decrease the need for analgesia at home. Ibuprofen results in lesser sedation and faster discharge than when acetaminophen is used.", "PMID": "12925475"}, {"title": "Efficacy of rectal ibuprofen in controlling postoperative pain in children.", "abstract": "The efficacy of ibuprofen with scheduled administration, starting preoperatively, for postoperative pain was studied in 128 boys and girls, 4 to 12 yr old, having elective surgery. In a double blind placebo-controlled study, rectal ibuprofen (40 mg.kg-1.day-1 in divided doses) or placebo was given for up to three days. For two hours after surgery heart rate, blood pressure and respiratory rate were recorded every 15 min together with sedation scores and pain scores, as assessed by an observer and the patient. Morphine was given to all children, 0.1 mg.kg-1 iv or 0.15 mg.kg-1 im according to clinical needs. Every morning on the ward the patients were interviewed about the efficacy of the analgesic treatment. All unwanted effects were registered. In the recovery room the heart rate was lower (P less than 0.05) and the patient's pain scores were less (P less than 0.05) in the ibuprofen group. After orthopaedic operations children needed more opioid than after ophthalmic or general surgical procedures (P less than 0.001). However, after all operations the need for additional morphine was less in the recovery room (P less than 0.05), during the day of operation (P less than 0.01) and during the three-day study period (P less than 0.01) in children receiving ibuprofen. On the day of operation the analgesic therapy was considered to be good or very good by 44/53 and 32/49 of the children in ibuprofen and placebo groups, respectively (P less than 0.05). Later, their assessments did not differ.(ABSTRACT TRUNCATED AT 250 WORDS)", "PMID": "1551152"}, {"title": "Pain control during fixed orthodontic appliance therapy.", "abstract": "The control of pain during orthodontic treatment is of great interest to both clinicians and patients. However, there has been limited research into the control of this pain, and there is no standard of care for controlling this discomfort. This prospective study determines the pain sequelae in fixed orthodontic treatment and evaluates comparatively the analgesic effects of nonsteroidal anti-inflammatory drugs for the control of this pain. One hundred and fifty orthodontic patients who were to have teeth bonded in at least one arch were randomly assigned to one of six groups: (1) placebo/placebo, (2) ibuprofen/ibuprofen, (3) flurbiprofen/flurbiprofen, (4) acetaminophen/acetaminophen, (5) naproxen sodium/naproxen sodium, and (6) aspirin/aspirin. The pain evaluations were made during chewing, biting, fitting the front teeth, and fitting the back teeth using a 100-mm visual analogue scale (VAS) for seven days. All the analgesics succeeded in decreasing the pain levels compared with the placebo group. However, naproxen sodium and aspirin groups showed the lowest pain values, and the acetaminophen group showed VAS results similar to those of the two analgesics.", "PMID": "15825785"}, {"title": "Effects of preoperative ibuprofen and naproxen sodium on orthodontic pain.", "abstract": "Three experimental groups of 20 patients each, all of whom were to undergo fixed orthodontic treatment, were enrolled in this prospective study. Group 1 was given a placebo, group 2 was given 400 mg ibuprofen, and group 3 was given 550 mg naproxen sodium. All the patients received only one dose that was given one hour before archwire placement. All patients were asked to complete a questionnaire concerning the pain perceived after archwire placement. The questionnaire was in the form of a seven-page booklet that contained 100-mm horizontal Visual Analogue Scale on which the patient marked the degree of discomfort at the indicated time periods. The patients were instructed to make a check on the scale at each time interval to represent the perceived severity of pain during each of four activities, ie, chewing, biting, fitting back teeth together, and fitting front teeth together. Incidence and severity of pain were recorded by the patient at two hours, six hours, nighttime on the day of appointment, 24 hours after the appointment, and two days, three days, and seven days after bonding. The results revealed that patients taking 550 mg naproxen sodium one hour before archwire placement had significantly lower levels of pain at two hours, six hours, and nighttime after adjustment than patients taking placebo or ibuprofen. However, the use of additional postoperative doses was recommended to control orthodontic pain completely.", "PMID": "16279825"}, {"title": "A comparison of paracetamol, ibuprofen or their combination for pain relief following extractions in children under general anaesthesia: a randomized controlled trial.", "abstract": "This study was designed to compare the effectiveness of different oral analgesics for relieving pain and distress in children following the extraction of teeth under general anaesthesia (GA). The analgesics included paracetamol alone, ibuprofen alone, and paracetamol and ibuprofen in combination.\n\nTwo hundred and one subjects were randomly allocated to one of four groups. Forty-seven children were included in the ibuprofen alone (5 mg kg(-1)) group, 51 in the paracetamol/ibuprofen combination (15/5 mg kg(-1)) group, 48 in the high-dose paracetamol (20 mg kg(-1)) group, and 55 children were included in the usual-dose paracetamol (15 mg kg(-1)) group (control group). Evaluation of distress for children was made immediately pre-operatively, on recovery from anaesthesia and again after 15 min by using a five-point face scale. Furthermore, each child was observed immediately postoperatively and 15 min postoperatively for signs of pain using the Children's Hospital of Eastern Ontario Pain Scale.\n\nThere were significant decreases in the mean pain and distress scores for both the ibuprofen alone and paracetamol/ibuprofen combination groups compared to the control group (usual-dose paracetamol) at 15 min postoperatively.\n\nThis study provides evidence to support the oral administration of ibuprofen alone or in combination with paracetamol for postoperative analgesia in children who are having teeth extracted under GA.", "PMID": "17397460"}, {"title": "Preoperative acetaminophen vs ibuprofen for control of pain after orthodontic separator placement.", "abstract": "Pain control during orthodontics is an important aspect of patient compliance. The aim of this prospective, randomized, double-blind clinical trial was to compare the pain control effectiveness of acetaminophen (650 mg) with ibuprofen (400 mg) taken 1 hour before separator placement in adolescents.\n\nThe patients recorded their discomfort on a 100-mm visual analog scale during several activities (teeth not touching, chewing, and fitting back teeth together) and by selecting words adapted from the McGill Pain Questionnaire at 5 time intervals: immediately before separator placement, immediately after separator placement, 2 to 3 hours later, at bedtime, and on awakening the next morning. The patients (n = 33) were randomly assigned to the ibuprofen group or the acetaminophen group. A repeated-measures ANOVA was performed as a function of time and treatment group.\n\nPain increased immediately after separator placement, lessened, and then increased to a peak the next morning. The most commonly selected words to describe pain were \"annoying,\" \"sore,\" and \"tight.\" There was no significant difference in pain at any time after separator placement regardless of the medication taken.\n\nAcetaminophen and ibuprofen produced no significant differences in pain after separator placement.", "PMID": "17920504"}, {"title": "A randomized clinical trial comparing the efficacy of ibuprofen and paracetamol in the control of orthodontic pain.", "abstract": "Previous research has shown that ibuprofen provides effective relief from orthodontic pain. The aim of this study was to ascertain whether paracetamol (also known as acetaminophen) provided pain relief of equivalent or greater magnitude.\n\nA multicenter, noninferiority, randomized clinical trial was conducted in 3 orthodontic clinics; 159 patients aged 12 to 16 years attending for routine orthodontic treatment were randomly allocated to receive either 400 mg of oral ibuprofen or 1 g of oral paracetamol an hour before and again 6 hours after separator placement. Pain scores were recorded on 7 visual analog scales (10 cm) over a week. The margin of equivalence was defined as 10 mm.\n\nMean orthodontic pain from 2 hours after separation to bedtime was 8.5 mm (90% CI: lower, 3.7; upper,13.2) higher in the paracetamol group. This confidence interval lies partly outside the margin of equivalence, suggesting that paracetamol is not equivalent, and excludes the value 0, suggesting that ibuprofen is superior. From day 1 onward, there was a trend for patients who had taken ibuprofen to experience less pain at most time intervals compared with the paracetamol group. Two doses of ibuprofen, taken on the day of separator placement, were insufficient to control orthodontic pain on day 1 after placement.\n\nA combination of preoperative and postoperative ibuprofen is more effective than paracetamol in the control of orthodontic pain.", "PMID": "17920505"}], "labels": [{"PMID": "11113797", "label": "included"}, {"PMID": "11455373", "label": "included"}, {"PMID": "11881888", "label": "included"}, {"PMID": "12925475", "label": "included"}, {"PMID": "1551152", "label": "included"}, {"PMID": "15825785", "label": "included"}, {"PMID": "16279825", "label": "included"}, {"PMID": "17397460", "label": "included"}, {"PMID": "17920504", "label": "included"}, {"PMID": "17920505", "label": "included"}]}
{"metadata": {"review_pmid": "38174816"}, "inputs": {"background": "During a stimulated cycle of in vitro fertilisation or intracytoplasmic sperm injection (IVF/ICSI), women receive daily doses of gonadotropin follicle-stimulating hormone (FSH) to induce multifollicular development in the ovaries. A normal response to stimulation (e.g. retrieval of 5 to 15 oocytes) is considered desirable. Generally, the number of eggs retrieved is associated with the dose of FSH. Both hyper-response and poor response are associated with an increased chance of cycle cancellation. In hyper-response, this is due to increased risk of ovarian hyperstimulation syndrome (OHSS), while poor response cycles are cancelled because the quantity and quality of oocytes is expected to be low. Clinicians often individualise the FSH dose using patient characteristics predictive of ovarian response. Traditionally, this meant women's age, but increasingly, clinicians use various ovarian reserve tests (ORTs). These include basal FSH (bFSH), antral follicle count (AFC), and anti-M\u00fcllerian hormone (AMH). It is unclear whether individualising FSH dose improves clinical outcomes. This review updates the 2018 version.", "objectives": "To assess the effects of individualised gonadotropin dose selection using markers of ovarian reserve in women undergoing IVF/ICSI.", "selection criteria": "We included randomised controlled trials (RCTs) that compared (a) different doses of FSH in women with a defined ORT profile (i.e. predicted low, normal, or high responders based on AMH, AFC, and/or bFSH) or (b) an individualised dosing strategy (based on at least one ORT measure) versus uniform dosing or a different individualised dosing algorithm."}, "context": [{"title": "A prospective, randomized, double-blind clinical trial to study the efficacy and efficiency of a fixed dose of recombinant follicle stimulating hormone (Puregon) in women undergoing ovarian stimulation.", "abstract": "A prospective, randomized, double-blind, multicentre (n = 5) study was conducted to compare the influence of either a 100 or 200 IU daily fixed-dose regimen of recombinant follicle stimulating hormone (FSH) on the number of oocytes retrieved and the total dose used in down-regulated women undergoing ovarian stimulation. Fertilization was done by intracytoplasmic sperm injection or conventional in-vitro fertilization. A total of 199 women were treated with FSH, 101 subjects with 100 IU and 98 subjects with 200 IU. In subjects of the 200 IU treatment group, significantly more oocytes were retrieved compared to the 100 IU group (10.6 versus 6.2 oocytes, P < 0.001). The total dose needed to develop at least three follicles with a diameter of > or = 17 mm was significantly lower in the 100 IU treatment group (1114 IU versus 1931 IU, P < 0.001). In the low-dose group, significantly lower serum concentrations of oestradiol, progesterone and FSH were observed at the day of human chorionic gonadotrophin administration. Although more cycle cancellations due to low response were seen in the 100 IU group (n = 24 versus n = 3), the clinical pregnancy rate per started cycle was similar (24.7% in the 100 IU group versus 23.3% in the 200 IU group). In the high-dose group, more side-effects, in particular more cases of ovarian hyperstimulation syndrome, were noted. It is concluded that compared to 200 IU, the use of a 100 IU fixed dose is less efficacious in terms of the number of oocytes retrieved, but more efficient as indicated by a lower total dose.", "PMID": "10221686"}, {"title": "Increasing the daily dose of recombinant follicle stimulating hormone (Puregon) does not compensate for the age-related decline in retrievable oocytes after ovarian stimulation.", "abstract": "A prospective, randomized, double-blind, multicentre (n = 6) study was conducted to compare the influence of either a 150 or 250 IU daily fixed-dose regimen of recombinant follicle stimulating hormone (FSH, Puregon) on the number of oocytes retrieved and the total dose used in down-regulated women between 30 and 39 years of age undergoing ovarian stimulation. In all, 138 women were treated with recombinant FSH, 67 with 150 IU and 71 with 250 IU. The number of oocytes retrieved in the low-dose group was 9.1 compared to 10.6 in the high-dose group (not significant). In the 30-33 years of age class receiving the 250 IU dose, a surplus of 4.2 oocytes (14.8 versus 10.6) was found, whereas in the 37-39 age class nearly one oocyte more was retrieved in the 150 IU group (8.1 versus 7.4). The total dose used to reach the criterion for human chorionic gonadotrophin (HCG) administration was 1727 IU for the women treated with 150 IU daily and 2701 IU for the 250 IU treated women (P < 0. 001). No significant relationships were found between serum FSH concentrations as obtained in the early follicular phase and the number of oocytes collected, or the total dose. It is concluded that in women between 30 and 39 years of age, the decline in number of oocytes retrieved with increasing age cannot be overcome by augmenting the daily dose of recombinant FSH from 150 to 250 IU.", "PMID": "10611184"}, {"title": "A pilot study involving minimal ovarian stimulation for in vitro fertilization: extending the \"follicle-stimulating hormone window\" combined with the gonadotropin-releasing hormone antagonist cetrorelix.", "abstract": "To study whether minimal interference in the process of selection of the single dominant follicle may serve as the basis for a simplified ovarian stimulation regimen for IVF.\n\nSingle-center randomized pilot study.\n\nTertiary referral fertility center.\n\nFifteen normo-ovulatory patients with a regular indication for IVF.\n\nOvarian stimulation for IVF was begun with 100 or 150 IU/d recombinant FSH starting on cycle day 5. From cycle day 8 or later, cotreatment was begun with 0.25 mg/d GnRH antagonist. No luteal support was provided.\n\nTotal number of dominant follicles and characteristics of the endocrine cycle.\n\nMultiple follicle development occurred in five of eight patients in the 100-IU group and in all seven women in the 150-IU group. Follicular phase and luteal phase lengths were normal, but the endocrine profile was abnormal.\n\nA fixed daily dose of 150 IU recombinant FSH starting in the midfollicular phase resulted in ongoing growth of a restricted number of dominant follicles and sufficient oocytes retrieved to lead to ET. A marked reduction in the total amount of gonadotropins administered compared with standard treatment was achieved. Withholding luteal support did not exclude pregnancies.", "PMID": "10785238"}, {"title": "A randomized, double-blind clinical trial using fixed daily doses of 100 or 200 IU of recombinant FSH in ICSI cycles.", "abstract": "The effect of 100 and 200 IU per day recombinant FSH (rFSH) on numbers of oocytes retrieved and the total dose used in ovarian stimulation before intracytoplasmic sperm injection was investigated in a double-blind, randomized multicentre trial. A total of 91 women was treated with a low-dose protocol and 88 with a high-dose regimen at five centres. For each started cycle, significantly more oocytes were retrieved in the 200 IU group than in 100 IU group (12.0 versus 5.7, P < 0.001); total rFSH consumption was 1121 and 1875 IU in the low- and high-dose groups respectively. Significant variations were noted between centres with regard to numbers of oocytes collected per started cycle, ranging from 2.8 to 7.2 in the 100 IU group and from 9.0 to 19.1 in the high-dose group. Exploratory analyses of secondary outcomes suggested there were no differences in vital pregnancy rates per started cycle (19.2 versus 16.9%) and per embryo transfer (26.2 versus 19.3%) in the low- and high dose groups respectively. There were four hospitalizations due to ovarian hyperstimulation syndrome, all in the 200 IU group.", "PMID": "11387277"}, {"title": "A prospective, randomized comparison of two starting doses of recombinant FSH in combination with cetrorelix in women undergoing ovarian stimulation for IVF/ICSI.", "abstract": "A prospective randomized study was carried out in two centres to compare the number of oocytes retrieved after two different starting doses of recombinant human FSH (rhFSH) (Gonal-F) in women undergoing ovarian stimulation for IVF/intracytoplasmic sperm injection (ICSI) cycles using the multiple dose regimen of the gonadotrophin-releasing hormone (GnRH) antagonist cetrorelix (Cetrotide) to prevent induction of the premature LH surge.\n\nSixty women were randomized to receive rhFSH 150 IU ('low'), and 60 women to receive rhFSH 225 IU ('high') as the starting dose for the first 5 days of stimulation. From stimulation day 6 and onwards, including the day of human chorionic gonadotrophin (HCG) administration, the women received 0.25 mg of cetrorelix as a daily dose. The primary endpoint was the number of oocytes retrieved.\n\nThe mean number (+/- SD) of oocytes was 9.1 +/- 4.4 and 11.0 +/- 4.6 in the 'low' and 'high' groups respectively (P = 0.024). The mean number of 75 IU ampoules of rhFSH was significantly lower in the 'low' group (23.0 +/- 6.3 versus 30.5 +/- 5.6, P < 0.0001). The ongoing pregnancy rate per started cycle and per embryo transfer were 25.9 and 28.8% versus 25.4 and 26.8% respectively in the 'low' and 'high' rhFSH groups (P = NS).\n\nWhen using a starting dose of 225 IU rhFSH combined with the multiple dose of 0.25 mg cetrorelix from stimulation day 6, significantly more oocytes were obtained than with a starting dose of 150 IU rhFSH.", "PMID": "11473962"}, {"title": "A double-blind clinical trial comparing a fixed daily dose of 150 and 250 IU of recombinant follicle-stimulating hormone in women undergoing in vitro fertilization.", "abstract": "To determine the efficacy and efficiency of two fixed doses of recombinant follicle-stimulating hormone (FSH) in controlled ovarian hyperstimulation.\n\nRandomized, double-blind clinical trial.\n\nFifteen IVF clinics in Argentina, Brazil, Chile, Colombia, Mexico, and Venezuela.\n\nWomen between 30 and 39 years of age undergoing IVF or intracytoplasmic sperm injection (ICSI).\n\nDaily doses of either 150 IU or 250 IU of recombinant FSH (Puregon) until at least two follicles >or=20 mm were seen on ultrasound.\n\nNumber of cumulus-oocyte complexes retrieved and total dose of recombinant FSH used.\n\nTwo hundred one women received 150 IU and 203 used 250 IU. In the low-dose group 8.9 oocytes were retrieved compared to 10.2 in the high-dose group (not significant). The 150 IU-treated women received a total of 1,589 IU and the total dose used in 250 IU treated women was 2,492 IU. Implantation rates were 10.0% in the 150 IU group and 10.9% in the 250 IU group. The vital pregnancy rates per started cycle in the low-dose and high-dose groups were 17.1% and 16.7%, respectively. Two women, both in the 250 IU group, were hospitalized because of the ovarian hyperstimulation syndrome (OHSS).\n\nAn increase from 150 IU to 250 IU daily dose of recombinant FSH in women between 30 and 39 years of age has only limited value in augmenting ovarian response.", "PMID": "11704116"}, {"title": "Comparison of two different fixed doses of follitropin-beta in controlled ovarian hyperstimulation: A prospective randomized, double blind clinical trial.", "abstract": "A prospective randomized, double blind, single centre study was conducted to compare the efficacy, efficiency and clinical side effects of daily fixed dose regimen of either 100 IU or 200 IU of recombinant follicle stimulating hormone(rFSH) Follitropin beta in down-regulated women undergoing controlled ovarian hyperstimulation(COH) for either conventional in vitro fertilization(IVF) or intracytoplasmic sperm injection(ICSI). A total of sixty women were randomly allocated according to the criteria for the treatment by either 100 IU(n = 30) or 200 IU (n = 30) of FSH. Although more cycle cancellations due to low response were observed in the 100 IU group (n = 9 vs n = 2), two cases of mild and moderate ovarian hyperstimulation syndrome were noted in the higher dose group. Subjects in the group treated with 200 IU appeared to yield more follicles > 17 mm (4.4 vs 3.3, p = 0.05) and more oocytes compared to the group treated with 100 IU (9.2 versus 6.0 oocytes, NS). The total dosage required to develop at least three follicles according to the protocol was significantly lower in the group treated with 100 IU (1203.33 versus 2106. 67, P < 0.0001). In conclusion, a fixed daily dose of 200 IU of rFSH Follitropin beta compared to a fixed daily dose of 100 IU is more effective in terms of follicles > 17 mm development and the number of oocytes retrieved along with a lower cancellation rate, but less efficient as indicated by a higher total rFSH dose needed", "PMID": "15560689"}, {"title": "[Results of application of high daily doses of recombinant follicle stimulating hormone in different age groups of women in IVF program].", "abstract": "A prospective, randomized, comparative study has been carried out to investigate the effectiveness of administration of recombinant FSH (rFSH, Gonal-F) in doses 150 and 225 IU in different age groups of women. 63 patients started a long gonadotrophin-releasing hormone agonist protocol (GnRHa, Diphereline, 0,1 mg): 31 received rFSH 150 IU/day and 32 - 225 IU/day. The objective was to assess the impact of these dosing regimens in down-regulated women. Duration of treatment for reaching administered criteria for human chorionic gonadotropin (HCG, Profazi) showed that the results in low-dose group and high-dose group were similar (11,8+/-0,2 days versus 11,2+/-0,4 days). Though, the total dose used per cycle of stimulation for group of patients receiving 225 IU was 2493+/-56 IU and 1762+/-37 IU in the 150 IU group (p<0,001). Average number of retrieved oocytes in low-dose group was 7,4+/-0,5 and 8,9+/-0,7 in high-dose group (no significant difference). In the group of women 31-33 years of age receiving 225 IU more oocytes were retrieved (13,1+/-1,1 versus 9,3+/-0,7 in 150 IU treatment group). Thus the patients of the age 37-39 years receiving 150 IU dose a slightly higher number of oocytes were found (6,1+/-0,3 versus 5,3+/-0,4). No significant relationships were found between serum FSH concentrations as obtained in the early follicular phase and the number of oocytes collected, or the total dose. The rates of obtained transferable embryos (1 and 2 degree) were 67% in low-dose group and 54% in high-dose group. There was better quality of retrieved oocytes than in the stimulation protocol with rFSH. According to the clinical pregnancy and delivery rates per cycles (respectively 26 and 23% in 150 IU group, 19 and 16% in the 225 IU group) and embryo transfer per cycle (29 and 25% in 150 IU group, 21 and 18% in 225 IU group) no significant difference has been found. Our study has shown that in women between 31-39 years of age, the decline in number of oocytes retrieved with increasing age cannot be overcome by augmenting the daily dose of recombinant FSH from 150 to 225 IU.", "PMID": "16052045"}, {"title": "What is the optimum maximal gonadotropin dosage used in microdose flare-up cycles in poor responders?", "abstract": "To find out the optimum maximal dosage of recombinant follicle stimulating hormone (rFSH) in microdose gonadotropin-releasing hormone analog (GnRH-a) flare cycles in poor responders.\n\nProspective randomized study.\n\nPrivate infertility clinic.\n\nA total of 119 women were taken into the study.\n\nThe study group underwent a microdose protocol with a GnRH-agonist followed by rFSH administration. On the third day of GnRH-a administration, 119 patients were randomized in three groups to receive daily fixed doses of 300 IU of rFSH (group A, n = 38), or 450 IU of rFSH (group B, n = 39), or 600 IU of rFSH (group C, n = 42).\n\nPeak E(2) levels, days of stimulation with rFSH, total rFSH dosage, total number of oocytes retrieved, M2 oocytes retrieved, total number of embryos, number of embryos transferred, number of Grade-1 embryos transferred, clinical pregnancy rate (positive fetal cardiac activity), and cancellation rates of stimulation and embryo transfer.\n\nClinical pregnancy rates were 13.1%, 15.3%, and 16.1% for group A, group B, and group C, respectively. There were no significant differences in the age, peak serum E(2) concentration, days of stimulation with rFSH, total number of M2 oocytes retrieved, number of embryos transferred, clinical pregnancy rates, and cancellation rates of stimulation and embryo transfer between the three groups except for total rFSH dosage.\n\nThere is no need to use doses above 300 IU of rFSH to increase the pregnancy rate in microdose cycles. In addition, because the duration of stimulation does not differ between the groups, the usage of 300 IU rFSH in microdose cycles results in less total amount of rFSH consumed in a cycle compared with higher dosages, and this would obviously cost less money to the patients.", "PMID": "19368912"}, {"title": "Individual versus standard dose of rFSH in a mild stimulation protocol for intrauterine insemination: a randomized study.", "abstract": "Controlled ovarian stimulation (COS) and intrauterine insemination (IUI) are often used as the first-line treatment for subfertile couples. To minimize the variability in ovarian response in patients' first treatment cycle, we recently developed a recombinant follicle-stimulating hormone (rFSH) dosage nomogram. The nomogram has now been tested.\n\nMulticentre randomized controlled trial (RCT) including 228 ovulatory patients scheduled for COS and IUI. Patients were randomized to 'individual' (50-100 IU rFSH/day, n = 113) or 'standard' (75 IU rFSH/day, n = 115) dose. 'Individual' dose was prescribed according to the nomogram, which was based on patients' body weight and antral follicle count. The primary end-point was the proportion of patients with two to three follicles > or = 14 mm (maximum two follicles > or = 18 mm) on the day of hCG (leading follicle = 18 mm). Primary analysis was made by intention-to-treat.\n\nIn the 'individual' group, 79/113 (70%) of the patients developed two to three follicles versus 64/115 (56%) in the 'standard' group [absolute difference = 14.3 percentage points; 95% confidence interval (CI) 2-26, P = 0.03; absolute difference = 14.4; 95% CI 2-27, P = 0.02, when adjusting for centre]. Among patients with two to three follicles, the proportion of patients with two follicles was 46/79 (58%) in the 'individual' group versus 34/64 (53%) in the 'standard' group, P = 0.54. Ongoing pregnancy rate was 23/113 (20%) in the 'individual' group and 21/115 (18%) in the 'standard' group and the rate of multiple gestations was 1/113 (1%) versus 5/115 (4%), P = 0.21.\n\nThis RCT is the first to clinically test a dosage nomogram in ovulatory IUI patients' first rFSH treatment cycle. Dosing according to the nomogram was superior to standard dosing.\n\nClinicalTrials.gov Identifier NCT00374634.", "PMID": "19602518"}], "labels": [{"PMID": "10221686", "label": "excluded"}, {"PMID": "10611184", "label": "excluded"}, {"PMID": "10785238", "label": "excluded"}, {"PMID": "11387277", "label": "excluded"}, {"PMID": "11473962", "label": "excluded"}, {"PMID": "11704116", "label": "excluded"}, {"PMID": "15560689", "label": "excluded"}, {"PMID": "16052045", "label": "excluded"}, {"PMID": "19368912", "label": "excluded"}, {"PMID": "19602518", "label": "excluded"}]}
{"metadata": {"review_pmid": "38174814"}, "inputs": {"background": "Chronic lymphocytic leukaemia (CLL) is the most common lymphoproliferative disease in adults and currently remains incurable. As the progression-free period shortens after each successive treatment, strategies such as maintenance therapy are needed to improve the degree and duration of response to previous therapies. Monoclonal antibodies, immunomodulatory agents, and targeted therapies are among the available options for maintenance therapy. People with CLL who achieve remission after previous therapy may choose to undergo medical observation or maintenance therapy to deepen the response. Even though there is widespread use of therapeutic maintenance agents, the benefits and harms of these treatments are still uncertain.", "objectives": "To assess the effects and safety of maintenance therapy, including anti-CD20 monoclonal antibody, immunomodulatory drug therapy, anti-CD52 monoclonal antibody, Bruton tyrosine kinase inhibitor, and B-cell lymphoma-2 tyrosine kinase inhibitor, for individuals with CLL.", "selection criteria": "We included RCTs with prospective identification of participants. We excluded cluster-randomised trials, cross-over trial designs, and non-randomised studies. We included studies comparing maintenance therapies with placebo/observation or head-to-head comparisons."}, "context": [{"title": "Consolidation with alemtuzumab in patients with chronic lymphocytic leukemia (CLL) in first remission--experience on safety and efficacy within a randomized multicenter phase III trial of the German CLL Study Group (GCLLSG).", "abstract": "Patients with CLL responding to initial chemotherapy with fludarabine alone (F) or in combination with cyclophosphamide (FC) were randomized for treatment with alemtuzumab (30 mg i.v. TIW, 12 weeks) or observation. Of 21 evaluable patients, 11 were randomized to alemtuzumab before the study was stopped due to severe infections in seven of 11 patients. These infections (one life-threatening pulmonary aspergillosis IV; four CMV reactivations III requiring i.v. ganciclovir; one pulmonary tuberculosis III; one herpes zoster III) were successfully treated and not associated with cumulative dose of alemtuzumab. In the observation arm, one herpes zoster infection II and one sinusitis I were documented. At 6 months after randomization, two patients in the alemtuzumab arm converted to CR, while three patients in the observation arm progressed. After alemtuzumab treatment, five of six patients achieved a molecular remission in peripheral blood while all patients in the observation arm remained MRD-positive (P=0.048). At 21.4 months median follow-up, patients receiving alemtuzumab showed a significant longer progression-free survival (no progression vs mean 24.7 months; P=0.036). In conclusion, a consolidation therapy with alemtuzumab is able to achieve molecular remissions and longer survival in CLL, but a safe treatment regimen needs to be determined.", "PMID": "15071604"}, {"title": "Consolidation with alemtuzumab improves progression-free survival in patients with chronic lymphocytic leukaemia (CLL) in first remission: long-term follow-up of a randomized phase III trial of the German CLL Study Group (GCLLSG).", "abstract": "Alemtuzumab has shown considerable activity in untreated and relapsed chronic lymphocytic leukaemia. We report our long-term experience in 21 patients within a randomized phase III trial investigating the role of alemtuzumab for consolidation therapy after first-line fludarabine +/- cyclophosphamide, which was stopped prematurely due to severe infections. However, after a median follow-up of 48 months, progression-free survival was significantly prolonged for patients receiving alemtuzumab consolidation compared to those with no further treatment (P = 0.004). Minimal residual disease (MRD) levels were persistently reduced after consolidation. Therefore, despite toxicity, MRD reduction by alemtuzumab consolidation translates into a significantly improved long-term clinical outcome.", "PMID": "19016732"}, {"title": "Chlorambucil plus rituximab with or without maintenance rituximab as first-line treatment for elderly chronic lymphocytic leukemia patients.", "abstract": "In a phase II trial, we evaluated chlorambucil and rituximab (CLB-R) as first-line induction treatment with or without R as maintenance for elderly chronic lymphocytic leukemia (CLL) patients. Treatment consisted of eight 28-day cycles of CLB (8 mg/m(2) /day, days 1-7) and R (day 1 of cycle 3, 375 mg/m(2) ; cycles 4-8, 500 mg/m(2) ). Responders were randomized to 12 8-week doses of R (375 mg/m(2) ) or observation. As per intention-to-treat analysis, 82.4% (95% CI, 74.25-90.46%) of 85 patients achieved an overall response (OR), 16.5% a complete response (CR), 2.4% a CR with incomplete bone marrow recovery. The OR was similar across Binet stages (A 86.4%, B 81.6%, and C 78.6%) and age categories (60-64 years, 92.3%; 65-69, 85.2%; 70-74, 75.0%; \u226575, 81.0%). CLB-R was well tolerated. After a median follow-up of 34.2 months, the median progression-free survival (PFS) was 34.7 months (95% CI, 33.1-39.5). TP53 abnormalities, complex karyotype, and low CD20 gene expression predicted lack of response; SF3B1 mutation and BIRC3 disruption low CR rates. IGHV mutations significantly predicted PFS. R maintenance tended towards a better PFS than observation and was safe and most beneficial for patients in partial response and for unmutated IGHV cases. CLB-R represents a promising option for elderly CLL patients.", "PMID": "24415640"}, {"title": "Ofatumumab maintenance versus observation in relapsed chronic lymphocytic leukaemia (PROLONG): an open-label, multicentre, randomised phase 3 study.", "abstract": "Ofatumumab is a human anti-CD20 monoclonal antibody that has proven efficacy as monotherapy in refractory chronic lymphocytic leukaemia. We assessed the efficacy and safety of ofatumumab maintenance treatment versus observation for patients in remission after re-induction treatment for relapsed chronic lymphocytic leukaemia.\n\nThis open-label, multicentre, randomised phase 3 study enrolled patients aged 18 years or older from 130 centres in 24 countries who had chronic lymphocytic leukaemia in complete or partial remission after second-line or third-line treatment. Eligible patients had a WHO performance status of 0-2, had a response assessment within the previous 3 months, did not have refractory disease, autoimmune haemolytic anaemia requiring treatment, chronic or active infection requiring treatment, and had not previously received maintenance treatment or autologous or allogeneic stem-cell transplant. Using a randomisation list generated by a central computerised system and an interactive voice recognition system, we randomly assigned (1:1) patients to receive ofatumumab (300 mg followed by 1000 mg 1 week later and every 8 weeks for up to 2 years) or undergo observation. Randomisation was stratified by number and type of previous treatment and remission status after induction treatment (block size of four). Treatment assignment was open label. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. We report the results of a prespecified interim analysis after two-thirds of the planned study events (disease progression or death) had happened. This trial is closed to accrual but follow-up is ongoing. This trial is registered with ClinicalTrials.gov, number NCT00802737.\n\nBetween May 6, 2010, and June 19, 2014, we enrolled 474 patients: 238 patients were randomly assigned to receive ofatumumab maintenance treatment and 236 to undergo observation. One (<1%) patient in the ofatumumab group did not receive the allocated intervention (withdrawal of consent). The median follow-up was 19\u00b71 months (IQR 10\u00b73-28\u00b78). Progression-free survival was improved in patients assigned to the ofatumumab group (29\u00b74 months, 95% CI 26\u00b72-34\u00b72) compared with those assigned to observation (15\u00b72 months, 11\u00b78-18\u00b78; hazard ratio 0\u00b750, 95% CI 0\u00b738-0\u00b766; p<0\u00b70001). The most common grade 3 or higher adverse events up to 60 days after last treatment were neutropenia (56 [24%] of 237 patients in the ofatumumab group vs 23 [10%] of 237 in the observation group) and infections (31 [13%] vs 20 [8%]). 20 (8%) of 237 patients in the ofatumumab group and three (1%) of 237 patients in the observation group had adverse events that led to permanent discontinuation of treatment. Up to 60 days after last treatment, two deaths related to adverse events occurred in the ofatumumab treatment group and five deaths related to adverse events occurred in the observation group; no deaths were attributed to the study drug.\n\nThese data are important for the development of optimum maintenance strategies in patients with relapsed chronic lymphocytic leukaemia, notably in the present era of targeted drugs, many of which are to be used until progression.", "PMID": "26377300"}, {"title": "Phase III, randomized study of ofatumumab versus physicians' choice of therapy and standard versus extended-length ofatumumab in patients with bulky fludarabine-refractory chronic lymphocytic leukemia.", "abstract": "We report results of a randomized, phase III study of ofatumumab versus physicians' choice treatment in patients with bulky fludarabine-refractory chronic lymphocytic leukemia and explore extended versus standard-length ofatumumab treatment. Patients (79 ofatumumab, 43 physicians' choice) completed a median 6 (ofatumumab) or 3 (physicians' choice) months' therapy. Ofatumumab-treated patients with stable disease or better were randomized (2:1) to 6 months' extended ofatumumab treatment or observation. Although the study did not meet the primary endpoint of progression-free survival (PFS) by independent review committee (ofatumumab: 5.4 months, physicians' choice: 3.6 months; p\u2009=\u20090.27), median PFS by investigators was significantly longer for ofatumumab versus physicians' choice (7.0 versus 4.5 months; p\u2009=\u20090.003) as was time to next therapy (median 11.5 versus 6.5 months; p\u2009=\u20090.0004). PFS and time to next therapy were significantly longer with ofatumumab extended treatment than observation (p\u2009=\u20090.026 and p\u2009=\u20090.002, respectively; n\u2009=\u200937). The adverse-event profile of long-term ofatumumab administration showed no unexpected findings (Clinicaltrials.gov identifier: NCT01313689).", "PMID": "26784000"}, {"title": "Dose intensification and molecular responses in patients with chronic lymphocytic leukaemia: a phase II single centre study.", "abstract": "Chronic lymphocytic leukaemia is a condition which has a median age of 65 years but approximately 10% of patients are younger than 50. Fludarabine has been shown to produce better response rates than conventional single agent or combination chemotherapy but as yet no improved survival. We have treated a series of 10 patients presenting with de novo (six) or relapsed (four) chronic lymphocytic leukaemia (CLL) with fludarabine as cytoreduction treatment and consolidation of the response with CD34 selected peripheral blood stem cell transplantation using cyclophosphamide and total body irradiation (TBI) as conditioning therapy. We report here on the progenitor cell harvest characteristics and clinical and molecular responses to both fludarabine and high-dose consolidation. Our results indicate that at 3 months post transplant clinical remissions were induced in 10/10 patients and molecular responses in 7/8 (88%) evaluable patients. Molecular relapses occurred on long-term follow-up at 6, 9, 12 and 24 months post transplant but patients continued in clinical and haematological remission. Two patients have died from progressive disease and a third patient from aggressive high grade lymphoma. Median survival from the time of transplantation for the group overall was 22 months (range 6-45). There was no procedure-related mortality in the first 100 days.", "PMID": "10556958"}, {"title": "Consolidation therapy with high-dose cyclophosphamide improves the quality of response in patients with chronic lymphocytic leukemia treated with fludarabine as induction therapy.", "abstract": "Fludarabine is the most active agent in the treatment of chronic lymphocytic leukemia (CLL). Despite this activity only a minority of patients treated with fludarabine achieve a complete response. We evaluated a new treatment program of sequential therapy with fludarabine followed by high-dose cyclophosphamide in previously untreated patients with CLL. This report details the results in 25 patients with previously untreated CLL. Patients received fludarabine (25 mg/m2/day x 5 days every 4 weeks for six cycles) as induction followed by consolidation with high-dose cyclophosphamide at one of three dose levels 1.5 g/m2, 2.25 g/m2, or 3 g/m2 administered every 2 weeks for three doses. High-dose cyclophosphamide was given with G-CSF support (5 microg/kg/day days 3-12). Complete response (CR) required a normal physical examination, normal CBC, a normal bone marrow evaluation including no residual lymphoid nodules on biopsy. A nodular response was defined as a complete response with the exception of an occasional residual nodule seen on bone marrow biopsy. Flow cytometric analysis for CD5:CD19 dual staining and kappa/lambda clonal excess was performed in all patients as a sensitive measure of minimal residual disease (MRD). Selected patients had patient/tumor-specific oligonucleotides generated that were subsequently used in a polymerase chain reaction as an extremely sensitive measure of MRD. There were no treatment-related deaths and no patient encountered unacceptable toxicity. After completion of this sequential regimen 76% (95% confidence interval: 59-93%) of patients had a major response: eight (32%) achieved a CR, four (16%) a nodular response, seven (28%) a PR, and six patients (24%) failed. Four patients withdrew from study during induction with fludarabine and did not receive at least one cycle of cyclophosphamide. Of the 21 patients who received consolidation with cyclophosphamide 10 (48%) had an improved quality of response when compared to that achieved with fludarabine. Two patients (8%) had no disease detectable by flow cytometry ('flow cytometric' CR) after six cycles of fludarabine. This improved to nine patients (36%) after high-dose cyclophosphamide. Following consolidation with high-dose cyclophosphamide three patients (12%) tested negative by PCR. All of these patients had morphologic evidence of residual disease after six cycles of fludarabine. Consolidation with high-dose cyclophosphamide increased the fraction of patients achieving a nodular response or CR three-fold (16% to 48%). This appears to be clinically relevant because with a median follow-up of 52 (range 34-78) months the projected 6-year survival for patients achieving a CR or NR is 91% compared to 41% for all others (P = 0.012). We conclude that sequential therapy with fludarabine followed by high-dose cyclophosphamide in previously untreated patients with CLL is safe and can improve the quality of response in a large proportion of patients compared to therapy with fludarabine alone.", "PMID": "10995003"}, {"title": "Clonotypic polymerase chain reaction confirms minimal residual disease in CLL nodular PR: results from a sequential treatment CLL protocol.", "abstract": "Patient-tumor-specific oligonucleotides were generated for the detection of minimal residual disease (MRD) in a highly specific and sensitive clonotypic polymerase chain reaction (cPCR). The clone-specific region of highest diversity, CDR-III, was PCR amplified and sequenced. Nested CDR-III clonotypic primers were used in a semi-nested cPCR with a sensitivity of at least 1 in 10(5) cells. Patients with protocol-eligible Rai intermediate or high-risk chronic lymphocytic leukemia (CLL) received induction with fludarabine 25 mg/m(2) per day for 5 days every 4 weeks for 6 cycles, followed by consolidative high-dose cyclophosphamide (1.5, 2.25, or 3g/m(2)). cPCR was performed on peripheral blood and bone marrow mononuclear cells. All 5 patients achieving a clinical partial remission (PR) studied by cPCR were positive. Five patients achieved nodular PR (nPR) (residual nodules or suspicious lymphocytic infiltrates in a bone marrow biopsy as the sole suggestion of residual disease). Five of 5 patients with nPR were cPCR positive. In contrast, flow cytometry for CD5-CD19 dual staining and kappa--lambda clonal excess detected MRD in only 3 of the same 5 nPR patients, all of whom were cPCR positive, and immunohistochemistry detected MRD in only 1 of 4 assessable patients. Three of 7 CR patients evaluable by cPCR had MRD. Only 1 CR patient had MRD by flow cytometry; that patient was also cPCR positive. These data support the conclusions that nodular PR in CLL represents MRD and that clonotypic PCR detects MRD in CLL more frequently than flow cytometry or immunohistochemistry. (Blood. 2001;97:1929-1936)", "PMID": "11264154"}, {"title": "Safety and efficacy of subcutaneous Campath-1H for treating residual disease in patients with chronic lymphocytic leukemia responding to fludarabine.", "abstract": "Recent observations suggested that targeted monoclonal antibodies might be best employed in lymphoid malignancies under conditions of minimal residual disease. This prompted us to investigate the role of Campath-1H as treatment for patients with chronic lymphocytic leukemia (CLL) in whom fludarabine (FAMP) had produced a marked disease debulking with persistence of bone marrow (BM) infiltration or a complete remission (CR) without the disappearance of the molecular aberration (IgH monoclonal expression). As intravenous Campath-1H is almost invariably associated with reactions, sometimes of WHO grade 3-4, we adopted the subcutaneous route of administration, which proved to induce rare and mild adverse reactions but had comparable efficacy. DESIGN AND METHODS. Nine patients (7 males, 2 females) with a median age of 55 years (range 41-61) who responded to FAMP (1 had a CR, 5 a nodular partial remission [PRN], and 3 a partial remission [PR]), according to NCI Working Group Criteria, received subcutaneous Campath-1H, three times a week for 6 weeks in escalating doses up to 10 mg. Monoclonal rearrangement of IgH was present in all patients before immunotherapy. Patients received acyclovir and cotrimoxazole as infection prophylaxis. Granulocyte colony-stimulating factor (G-CSF), at the dosage of 5-10 microg/kg/die, or intermediate-dose Ara-C (800 mg/m(2)/q 12h x 6 doses), was administered to obtain peripheral blood stem cell (PBSC) mobilization.\n\nAll patients were evaluable for response. Five patients, 2 in PR and 3 in PRN after FAMP treatment, reached a CR. Three patients, one in PR, one in PRN and one in CR, converted to a molecular remission. In four out of seven patients PBSC harvesting was successful; more than 2.5 x 10(6) cells/kg were collected from all these patients. Collection was polyclonal for IgH gene rearrangement in three cases. One patient has been transplanted after cyclophosphamide and total body irradiation as conditioning regimen, without complications and with rapid hemopoietic engraftment. All patients were evaluable for toxicity. A WHO grade 1-2 skin reaction was observed in 5 patients at the site of injection. No infectious episodes were recorded. Two out of three patients presenting cytomegalovirus reactivation, without pneumonia, were successfully treated with oral gancyclovir.\n\nSubcutaneous Campath-1H administered to CLL patients with residual BM disease after FAMP proved to be safe and effective. Of nine patients, three obtained a molecular CR and five converted into a morphologic and immunophenotypic CR. In four of seven patients submitted to PBSC mobilization, this treatment also allowed a harvest uncontaminated by CD5/CD19 double-positive CLL cells, which was polyclonal for IgH gene rearrangement in three cases.", "PMID": "12091119"}, {"title": "Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine.", "abstract": "This phase II pilot study determined the efficacy and safety of alemtuzumab (Campath-1H; Burroughs Wellcome, United Kingdom) in patients with chronic lymphocytic leukemia (CLL), all of whom had previously received fludarabine and other chemotherapy regimens.\n\nTwenty-four patients were treated with intravenous alemtuzumab at six centers in the United States. The target dose of 30 mg over 2 hours, three times weekly, was administered for up to 16 weeks. Responses were evaluated by an independent panel of experts using 1996 National Cancer Institute-sponsored Working Group criteria. Safety assessments included analysis of lymphocyte subpopulations. Antimicrobial prophylaxis was not mandatory.\n\nEight patients (33%) achieved a major response (all partial remissions), with a median time to response of 3.9 months (range, 1.6 to 5.3 months). The median duration of response was 15.4 months (range, 4.6 to >or= 38.0 months), the median time to disease progression was 19.6 months (range, 7.7 to >or= 42.0 months), and the median survival time was 35.8 months (range, 8.8 to >or= 47.1 months). Acute infusion-related events, mainly grades 1 and 2, were most common and most severe in the first week. Ten patients (eight nonresponders and two responders) experienced major infections on-study. Pneumocystis carinii pneumonia was reported in two patients on-study; neither had received prophylaxis. Median CD4+ and CD8+ counts decreased and then began to increase by the end of the study, with further recovery by 1-month follow-up. One of 53 samples obtained from 10 patients had a low titer of alemtuzumab antibodies.\n\nAlemtuzumab has significant activity in poor-prognosis, fludarabine-treated CLL patients. However, because of a relatively high incidence of opportunistic infections accompanying profound lymphopenia, future protocols should include mandatory prophylaxis.", "PMID": "12228210"}], "labels": [{"PMID": "15071604", "label": "included"}, {"PMID": "19016732", "label": "included"}, {"PMID": "24415640", "label": "included"}, {"PMID": "26377300", "label": "included"}, {"PMID": "26784000", "label": "included"}, {"PMID": "10556958", "label": "excluded"}, {"PMID": "10995003", "label": "excluded"}, {"PMID": "11264154", "label": "excluded"}, {"PMID": "12091119", "label": "excluded"}, {"PMID": "12228210", "label": "excluded"}]}
{"metadata": {"review_pmid": "38174786"}, "inputs": {"background": "Researchers and decision-makers often use evidence from randomised controlled trials (RCTs) to determine the efficacy or effectiveness of a treatment or intervention. Studies with observational designs are often used to measure the effectiveness of an intervention in 'real world' scenarios. Numerous study designs and their modifications (including both randomised and observational designs) are used for comparative effectiveness research in an attempt to give an unbiased estimate of whether one treatment is more effective or safer than another for a particular population. An up-to-date systematic analysis is needed to identify differences in effect estimates from RCTs and observational studies. This updated review summarises the results of methodological reviews that compared the effect estimates of observational studies with RCTs from evidence syntheses that addressed the same health research question.", "objectives": "To assess and compare synthesised effect estimates by study type, contrasting RCTs with observational studies. To explore factors that might explain differences in synthesised effect estimates from RCTs versus observational studies (e.g. heterogeneity, type of observational study design, type of intervention, and use of propensity score adjustment). To identify gaps in the existing research comparing effect estimates across different study types.", "selection criteria": "We included systematic methodological reviews that compared quantitative effect estimates measuring the efficacy or effectiveness of interventions tested in RCTs versus in observational studies. The included reviews compared RCTs to observational studies (including retrospective and prospective cohort, case-control and cross-sectional designs). Reviews were not eligible if they compared RCTs with studies that had used some form of concurrent allocation."}, "context": [{"title": "Randomized trials versus observational studies in adolescent pregnancy prevention.", "abstract": "The objective of this study is to compare the results of randomized trials and observational studies of interventions to prevent adolescent pregnancy. We identified published and unpublished reports through computerized searches of CATLINE, CINAHL, CONFERENCE PAPERS INDEX, DISSERTATION ABSTRACTS ONLINE, EMBASE, ERIC, MEDLINE, NTIS, POPLINE, PsycINFO, and SOCIOLOGICAL ABSTRACTS; manual searches of eight relevant journals; reference lists from primary articles; and contact with content experts. We included randomized trials and observational studies that evaluated the impact of primary prevention interventions including sex education classes, school-based clinics, free-standing clinics, physician/nurse practitioner practice-based service, improved access, and community-based programs on four outcomes: sexual intercourse, birth control use, responsible sexual behavior, or pregnancy in adolescents. One investigator abstracted the data and a second conducted a detailed review of the abstraction. We identified 13 randomized trials and 17 observational studies. We generated estimates of the impact of the interventions separately for males and females for all four outcomes for both observational studies and randomized trials. For six of the eight outcomes the summary odds ratios for the observational studies showed a significant intervention benefit (P<0.05) while the randomized trials did not show a benefit for any outcome in either females or males. The difference between the results of the observational studies and randomized trials was statistically significant in two of the eight outcomes (P<0.05 for initiation of intercourse and pregnancy in females). Observational studies yield systematically greater estimates of treatment effects than randomized trials of adolescent pregnancy prevention interventions. Public policy or individual patient treatment decisions should be based on observational studies only when randomized trials are unavailable and only with careful consideration of possible biases.", "PMID": "10729689"}, {"title": "A comparison of observational studies and randomized, controlled trials.", "abstract": "For many years it has been claimed that observational studies find stronger treatment effects than randomized, controlled trials. We compared the results of observational studies with those of randomized, controlled trials.\n\nWe searched the Abridged Index Medicus and Cochrane data bases to identify observational studies reported between 1985 and 1998 that compared two or more treatments or interventions for the same condition. We then searched the Medline and Cochrane data bases to identify all the randomized, controlled trials and observational studies comparing the same treatments for these conditions. For each treatment, the magnitudes of the effects in the various observational studies were combined by the Mantel-Haenszel or weighted analysis-of-variance procedure and then compared with the combined magnitude of the effects in the randomized, controlled trials that evaluated the same treatment.\n\nThere were 136 reports about 19 diverse treatments, such as calcium-channel-blocker therapy for coronary artery disease, appendectomy, and interventions for subfertility. In most cases, the estimates of the treatment effects from observational studies and randomized, controlled trials were similar. In only 2 of the 19 analyses of treatment effects did the combined magnitude of the effect in observational studies lie outside the 95 percent confidence interval for the combined magnitude in the randomized, controlled trials.\n\nWe found little evidence that estimates of treatment effects in observational studies reported after 1984 are either consistently larger than or qualitatively different from those obtained in randomized, controlled trials.", "PMID": "10861324"}, {"title": "A systematic review of comparisons of effect sizes derived from randomised and non-randomised studies.", "abstract": "There is controversy about the value of evidence about the effectiveness of healthcare interventions from non-randomised study designs. Advocates for quasi-experimental and observational (QEO) studies argue that evidence from randomised controlled trials (RCTs) is often difficult or impossible to obtain, or is inadequate to answer the question of interest. Advocates for RCTs point out that QEO studies are more susceptible to bias and refer to published comparisons that suggest QEO estimates tend to find a greater benefit than RCT estimates. However, comparisons from the literature are often cited selectively, may be unsystematic and may have failed to distinguish between different explanations for any discrepancies observed.\n\nThe aim was to investigate the association between methodological quality and the magnitude of estimates of effectiveness by comparing systematically estimates of effectiveness derived from RCTs and QEO studies. Quantifying any such association should help healthcare decision-makers to judge the strength of evidence from non-randomised studies. Two strategies were used to minimise the influence of differences in external validity between RCTs and QEO studies: a comparison of the RCT and QEO study estimates of effectiveness of any intervention, where both estimates were reported in a single paper a comparison of the RCT and QEO study estimates of effectiveness for specified interventions, where the estimates were reported in different papers. The authors also sought to identify study designs that have been proposed to address one or more of the problems often found with conventional RCTs.\n\nRelevant literature was identified from: The Cochrane Library, MEDLINE, EMBASE, DARE, and the Science Citation Index. References of relevant papers already identified experts. Electronic searches were very difficult to design and yielded few papers for the first strategy and when identifying study designs. CHOICE OF INTERVENTIONS TO REVIEW FOR STRATEGIES 1 AND 2: For strategy 1, any intervention was eligible. For strategy 2, interventions for which the population, intervention and outcome investigated were anticipated to be homogeneous across studies were selected for review: Mammographic screening (MSBC) of women to reduce mortality from breast cancer. Folic acid supplementation (FAS) to prevent neural tube defects in women trying to conceive. DATA EXTRACTION AND QUALITY ASSESSMENT: Data were extracted by the first author and checked by the second author. Disagreements were negotiated with reference to the paper concerned. For strategy 1, study quality was scored using a checklist to assess whether the RCT and QEO study estimates were derived from the same populations, whether the assessment of outcomes was 'blinded', and the extent to which the QEO study estimate took account of possible confounding. For strategy 2, a more detailed instrument was used to assess study quality on four dimensions: the quality of reporting, the generalisability of the results, and the extent to which estimates of effectiveness may have been subject to bias or confounding. All quality assessments were carried out by three people. DATA SYNTHESIS AND ANALYSIS: For strategy 1, pairs of comparisons between RCT and QEO study estimates were classified as high or low quality. Seven indices of the size of discrepancies between estimates of effect size and outcome frequency were calculated, where possible, for each comparison. Distributions of the size and direction of discrepancies were compared for high- and low-quality comparisons. FOR STRATEGY 2, THREE ANALYSES WERE CARRIED OUT: Attributes of the instrument were described by k statistics, percentage agreement, and Cronbach's a values. Regression analyses were used to investigate -variations in study quality. (ABSTRACT TRUNCATED)", "PMID": "11134917"}, {"title": "Comparison of evidence of treatment effects in randomized and nonrandomized studies.", "abstract": "There is substantial debate about whether the results of nonrandomized studies are consistent with the results of randomized controlled trials on the same topic.\n\nTo compare results of randomized and nonrandomized studies that evaluated medical interventions and to examine characteristics that may explain discrepancies between randomized and nonrandomized studies.\n\nMEDLINE (1966-March 2000), the Cochrane Library (Issue 3, 2000), and major journals were searched.\n\nForty-five diverse topics were identified for which both randomized trials (n = 240) and nonrandomized studies (n = 168) had been performed and had been considered in meta-analyses of binary outcomes.\n\nData on events per patient in each study arm and design and characteristics of each study considered in each meta-analysis were extracted and synthesized separately for randomized and nonrandomized studies.\n\nVery good correlation was observed between the summary odds ratios of randomized and nonrandomized studies (r = 0.75; P<.001); however, nonrandomized studies tended to show larger treatment effects (28 vs 11; P =.009). Between-study heterogeneity was frequent among randomized trials alone (23%) and very frequent among nonrandomized studies alone (41%). The summary results of the 2 types of designs differed beyond chance in 7 cases (16%). Discrepancies beyond chance were less common when only prospective studies were considered (8%). Occasional differences in sample size and timing of publication were also noted between discrepant randomized and nonrandomized studies. In 28 cases (62%), the natural logarithm of the odds ratio differed by at least 50%, and in 15 cases (33%), the odds ratio varied at least 2-fold between nonrandomized studies and randomized trials.\n\nDespite good correlation between randomized trials and nonrandomized studies-in particular, prospective studies-discrepancies beyond chance do occur and differences in estimated magnitude of treatment effect are very common.", "PMID": "11497536"}, {"title": "Hierarchy of evidence: differences in results between non-randomized studies and randomized trials in patients with femoral neck fractures.", "abstract": "There have been a number of non-randomized studies comparing arthroplasty with internal fixation in patients with femoral neck fractures. However, there remains considerable debate about whether the results of non-randomized studies are consistent with the results of randomized, controlled trials. Given the economic burden of hip fractures, it remains essential to identify therapies to improve outcomes; however, whether data from non-randomized studies of an intervention should be used to guide patient care remains unclear. We aimed to determine whether the pooled results of mortality and revision surgery among non-randomized studies were similar to those of randomized trials in studies comparing arthroplasty with internal fixation in patients with femoral neck fractures.\n\nWe conducted a Medline search from 1969 to June 2002, identifying both randomized and non-randomized studies comparing internal fixation with arthroplasty in patients with femoral neck fractures. Additional strategies to identify relevant articles included Cochrane database, SCISEARCH, textbooks, annual meeting programs, and content experts. We abstracted information on mortality and revision rates in each study and compared the pooled results between non-randomized and randomized studies. In addition, we explored potential reasons for dissimilar results between the two study designs.\n\nWe identified 140 citations that addressed the general topic of comparison of arthroplasty and internal fixation for hip fracture. Of these, 27 studies met the eligibility criteria, 13 of which were non-randomized studies and 14 of which were randomized trials. Mortality data was available in all 13 non-randomized studies ( n=3108 patients) and in 12 randomized studies ( n=1767 patients). Non-randomized studies overestimated the risk of mortality by 40% when compared with the results of randomized trials (relative risk 1.44 vs 1.04, respectively). Information on revision risk was available in 9 non-randomized studies ( n=2764 patients) and all 14 randomized studies ( n=1901 patients). Both estimates from non-randomized and randomized studies revealed a significant reduction in the risk of revision surgery with arthroplasty compared with internal fixation (relative risk 0.38 vs 0.23, respectively). The reduction in the risk of revision surgery with arthroplasty compared with internal fixation was 62% for non-randomized studies and 77% for randomized trials. Thus, non-randomized studies underestimated the relative benefit of arthroplasty by 19.5%. Non-randomized studies with point estimates of relative risk similar to the pooled estimate for randomized trials all controlled for patient age, gender, and fracture displacement in their comparisons of mortality. We were unable to identify reasons for differences in the revision rate results between the study designs.\n\nSimilar to other reports in medical subspecialties, non-randomized studies provided results dissimilar to randomized trials of arthroplasty vs internal fixation for mortality and revision rates in patients with femoral neck fractures. Investigators should be aware of these discrepancies when evaluating the merits of alternative surgical interventions, especially when both randomized trials and non-randomized comparative studies are available.", "PMID": "14576955"}, {"title": "Comparison of evidence on harms of medical interventions in randomized and nonrandomized studies.", "abstract": "Information on major harms of medical interventions comes primarily from epidemiologic studies performed after licensing and marketing. Comparison with data from large-scale randomized trials is occasionally feasible. We compared evidence from randomized trials with that from epidemiologic studies to determine whether they give different estimates of risk for important harms of medical interventions.\n\nWe targeted well-defined, specific harms of various medical interventions for which data were already available from large-scale randomized trials (> 4000 subjects). Nonrandomized studies involving at least 4000 subjects addressing these same harms were retrieved through a search of MEDLINE. We compared the relative risks and absolute risk differences for specific harms in the randomized and nonrandomized studies.\n\nEligible nonrandomized studies were found for 15 harms for which data were available from randomized trials addressing the same harms. Comparisons of relative risks between the study types were feasible for 13 of the 15 topics, and of absolute risk differences for 8 topics. The estimated increase in relative risk differed more than 2-fold between the randomized and nonrandomized studies for 7 (54%) of the 13 topics; the estimated increase in absolute risk differed more than 2-fold for 5 (62%) of the 8 topics. There was no clear predilection for randomized or nonrandomized studies to estimate greater relative risks, but usually (75% [6/8]) the randomized trials estimated larger absolute excess risks of harm than the nonrandomized studies did.\n\nNonrandomized studies are often conservative in estimating absolute risks of harms. It would be useful to compare and scrutinize the evidence on harms obtained from both randomized and nonrandomized studies.", "PMID": "16505459"}, {"title": "Examining heterogeneity in meta-analysis: comparing results of randomized trials and nonrandomized studies of interventions for low back pain.", "abstract": "Literature review.\n\nTo assess the influence of various factors in statistical heterogeneity of meta-analyses of interventions for low back pain. One of these factors was study design: randomized controlled trial (RCT) versus nonrandomized study (NRS).\n\nThe presence of statistical heterogeneity poses a challenge to the conduct and interpretation of meta-analyses.\n\nWe searched MEDLINE, EMBASE, and The Cochrane Library up to May 2005 for comparative studies of interventions for low back pain. The interventions with the highest number of NRSs were selected. All NRSs and RCTs of the same interventions were combined using meta-analysis. Subgroup analyses and meta-regression were performed according to study design and other factors that were selected by a panel of 20 experts.\n\nNRSs frequently either agree with RCTs or underestimate the effects compared with RCTs. The interventions and the respective factors that explained statistical heterogeneity were a) surgery versus conservative treatments (17 NRSs and 8 RCTs): study design (odds ratio, OR: 1.56 and 4.69 for nonrandomized and randomized studies, respectively), pain duration (OR: 1.75 and 3.55 for chronic and acute, respectively), and involvement of workers' compensation (OR: 1.85 and 5.07, with and without, respectively); b) surgery with fusion versus surgery without fusion (17 NRSs and 3 RCTs): spondylolisthesis (OR: 2.15 and 1.22, with and without, respectively); c) Instrumented fusion versus noninstrumented fusion (15 NRSs and 8 RCTs): previous surgery (OR: 2.89 and 1.36, with and without, respectively) and levels fused (OR: 1.50 and 2.98, single and multilevel, respectively).\n\nComparisons between RCTs and NRSs may be influenced by various factors, including study design. However, other factors were more powerful explanatory variables than study design. These factors included pain duration, involvement of workers' compensation, presence of spondylolisthesis, previous surgery, and levels fused.", "PMID": "18303468"}, {"title": "Methods in health services research. Interpreting the evidence: choosing between randomised and non-randomised studies.", "abstract": "", "PMID": "10426754"}, {"title": "Use of observational databases to evaluate the effectiveness of antiretroviral therapy for HIV infection: comparison of cohort studies with randomized trials. EuroSIDA, the French Hospital Database on HIV and the Swiss HIV Cohort Study Groups.", "abstract": "It is important to assess the extent of bias when comparing the clinical efficacy of antiretroviral regimens in observational databases because, with the current lack of planned large trials, such analyses may represent the only means of assessing the risk of serious clinical events associated with new regimens. We aimed to compare the results from observational databases with those from randomized trials.\n\nThree treatment comparisons from randomized trials [Delta, AIDS Clinical Trials Group (ACTG) 175, Community Programs for Clinical Research on AIDS (CPCRA) 007 and ACTC 320] were mimicked in cohorts: (i) zidovudine monotherapy versus combination regimens of two nucleoside analogues; (ii) zidovudine combined with either didanosine or zalcitabine; and (iii) a dual combination versus a triple regimen including a protease inhibitor. Data for over 10 000 patients from the French Hospital Database on HIV, the EuroSIDA study and the Swiss HIV cohort study were analysed for each of the comparisons. Progression to AIDS disease or death was analysed in Cox models, adjusting for baseline differences, and results compared with randomized trials.\n\nFor comparison (i) the adjusted relative risk estimates from cohorts were between 0.61 and 0.84, favouring combinations over monotherapy, compared with 0.57 to 0.63 for trials. For comparison (ii) relative risk estimates from cohorts ranged from 0.81 to 1.01 compared with 0.77 to 0.92 for trials. For comparison (iii), two of the cohorts showed similar results to the ACTG 320 trial but one indicated a higher risk of progression on triple therapy [relative risk 1.20, 95% confidence interval (CI) 1.01-1.441, in direct contrast to the trial result (relative risk 0.50, 95% CI 0.33-0.76).\n\nSerious biases can be present when comparing outcomes from the use of antiretroviral regimens in observational studies. However, such bias is not inevitable and careful interpretation of the results from several observational studies considered together is likely to be informative, guiding the design of new trials.", "PMID": "10546860"}, {"title": "Randomized, controlled trials, observational studies, and the hierarchy of research designs.", "abstract": "In the hierarchy of research designs, the results of randomized, controlled trials are considered to be evidence of the highest grade, whereas observational studies are viewed as having less validity because they reportedly overestimate treatment effects. We used published meta-analyses to identify randomized clinical trials and observational studies that examined the same clinical topics. We then compared the results of the original reports according to the type of research design.\n\nA search of the Medline data base for articles published in five major medical journals from 1991 to 1995 identified meta-analyses of randomized, controlled trials and meta-analyses of either cohort or case-control studies that assessed the same intervention. For each of five topics, summary estimates and 95 percent confidence intervals were calculated on the basis of data from the individual randomized, controlled trials and the individual observational studies.\n\nFor the five clinical topics and 99 reports evaluated, the average results of the observational studies were remarkably similar to those of the randomized, controlled trials. For example, analysis of 13 randomized, controlled trials of the effectiveness of bacille Calmette-Gu\u00e9rin vaccine in preventing active tuberculosis yielded a relative risk of 0.49 (95 percent confidence interval, 0.34 to 0.70) among vaccinated patients, as compared with an odds ratio of 0.50 (95 percent confidence interval, 0.39 to 0.65) from 10 case-control studies. In addition, the range of the point estimates for the effect of vaccination was wider for the randomized, controlled trials (0.20 to 1.56) than for the observational studies (0.17 to 0.84).\n\nThe results of well-designed observational studies (with either a cohort or a case-control design) do not systematically overestimate the magnitude of the effects of treatment as compared with those in randomized, controlled trials on the same topic.", "PMID": "10861325"}], "labels": [{"PMID": "10729689", "label": "included"}, {"PMID": "10861324", "label": "included"}, {"PMID": "11134917", "label": "included"}, {"PMID": "11497536", "label": "included"}, {"PMID": "14576955", "label": "included"}, {"PMID": "16505459", "label": "included"}, {"PMID": "18303468", "label": "included"}, {"PMID": "10426754", "label": "excluded"}, {"PMID": "10546860", "label": "excluded"}, {"PMID": "10861325", "label": "excluded"}]}
{"metadata": {"review_pmid": "38174776"}, "inputs": {"background": "Different therapeutic strategies are available for the treatment of people with relapsing-remitting multiple sclerosis (RRMS), including immunomodulators, immunosuppressants and biological agents. Although each one of these therapies reduces relapse frequency and slows disability accumulation compared to no treatment, their relative benefit remains unclear. This is an update of a Cochrane review published in 2015.", "objectives": "To compare the efficacy and safety, through network meta-analysis, of interferon beta-1b, interferon beta-1a, glatiramer acetate, natalizumab, mitoxantrone, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, pegylated interferon beta-1a, daclizumab, laquinimod, azathioprine, immunoglobulins, cladribine, cyclophosphamide, diroximel fumarate, fludarabine, interferon beta 1-a and beta 1-b, leflunomide, methotrexate, minocycline, mycophenolate mofetil, ofatumumab, ozanimod, ponesimod, rituximab, siponimod and steroids for the treatment of people with RRMS.", "selection criteria": "Randomised controlled trials (RCTs) that studied one or more of the available immunomodulators and immunosuppressants as monotherapy in comparison to placebo or to another active agent, in adults with RRMS."}, "context": [{"title": "Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis: results of a 2-year prospective randomised multicentre study (INCOMIN).", "abstract": "The three interferon beta preparations approved for treatment of relapsing-remitting multiple sclerosis (MS) differ in dose and frequency of administration. Interferon beta-1a 30 microg is administered once a week, interferon beta-1a 22 microg or 44 microg is given three times a week, and interferon beta-1b 250 microg is administered on alternate days. No clinical study directly comparing the different regimens has been published. The INCOMIN study was designed to compare the clinical and magnetic resonance imaging (MRI) benefits of on-alternate-day interferon beta-1b 250 microg with once-weekly interferon beta-1a 30 microg.\n\nINCOMIN was a 2-year, prospective, randomised, multicentre study. 188 patients with relapsing-remitting MS were assigned to interferon beta-1b (n=96) or interferon beta-1a (n=92). Primary outcome measures were the proportion of patients free from relapses and that of patients free from new proton density/T2 lesions at MRI assessment. Several secondary outcome measures were also assessed. Analysis was by intention to treat.\n\nOver 2 years, 49 (51%) individuals administered interferon beta-1b remained relapse-free compared with 33 (36%) given interferon beta-1a relative risk of relapse 0.76; 95% CI 0.59-0.9; p=0.03); and 42 (55%) compared with 19 (26%), respectively, remained free from new T2 lesions at MRI (relative risk of new T2 lesion 0.6; 0.45-0.8; p<0.0003). In both groups, the differences between the two treatments increased during the second year. There were also significant differences in favour of interferon beta-1b in most of the secondary outcome measures, including delay of confirmed disease progression.\n\nHigh-dose interferon beta-1b administered every other day is more effective than interferon beta-1a given once a week.", "PMID": "11988242"}, {"title": "No difference in efficacy of two different doses of intravenous immunoglobulins in MS: clinical and MRI assessment.", "abstract": "We performed a double-blind, placebo-controlled study to evaluate the efficacy of low and high dose of intravenous immunoglobulins (IVIG) in relapsing/remitting (RR) multiple sclerosis (MS). Patients (n = 49) with clinical definite RR MS were randomly allocated to three groups and treated with 0.2 g/kg (n = 17) or 0.4 g/kg (n = 15) once a month of IVIG and placebo (n = 17) for 12 months. Clinical data were assessed monthly and magnetic resonance imaging (MRI) was performed every 3 months during the study period. Annual relapse rate (ARR) and change of the mean Expanded Disability Status Scale (EDSS) and Neurological Rating Scale Score (NRSS) from baseline to study conclusion were used as the clinical end-points. For MRI activity total lesion volume on T2-weighted image (T2WI), new lesions and gadolinium (Gd)-enhanced lesions on T1WI were analysed. ARR in both IVIG groups (0.88 for 0.2 g/kg and 0.86 for 0.4 g/kg) was reduced compared with placebo (1.24) during treatment period. Neurological disability measured with EDSS decreased slightly in both the IVIG groups (0.029 and 0.066, respectively) and increased by 0.29 in placebo (P = 0.0117). The neurologic impairment measured by NRSS showed similar trend. The total lesion volume on T2WI increased by 13.56% in placebo whereas in the 0.4 g/kg IVIG group decreased by -3.95% and in the 0.2 g/kg IVIG group increased by 3.6%. The cumulative numbers of Gd-enhancing lesions and new T2WI lesions in the IVIG groups were reduced in comparison with the placebo group. Our findings suggest that the dose 0.2 g/kg of IVIG is equally effective as 0.4 g/kg in reducing MS activity.", "PMID": "12453070"}, {"title": "A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis.", "abstract": "Natalizumab is the first alpha4 integrin antagonist in a new class of selective adhesion-molecule inhibitors. We report the results of a two-year phase 3 trial of natalizumab in patients with relapsing multiple sclerosis.\n\nOf a total of 942 patients, 627 were randomly assigned to receive natalizumab (at a dose of 300 mg) and 315 to receive placebo by intravenous infusion every four weeks for more than two years. The primary end points were the rate of clinical relapse at one year and the rate of sustained progression of disability, as measured by the Expanded Disability Status Scale, at two years.\n\nNatalizumab reduced the risk of sustained progression of disability by 42 percent over two years (hazard ratio, 0.58; 95 percent confidence interval, 0.43 to 0.77; P<0.001). The cumulative probability of progression (on the basis of Kaplan-Meier analysis) was 17 percent in the natalizumab group and 29 percent in the placebo group. Natalizumab reduced the rate of clinical relapse at one year by 68 percent (P<0.001) and led to an 83 percent reduction in the accumulation of new or enlarging hyperintense lesions, as detected by T2-weighted magnetic resonance imaging (MRI), over two years (mean numbers of lesions, 1.9 with natalizumab and 11.0 with placebo; P<0.001). There were 92 percent fewer lesions (as detected by gadolinium-enhanced MRI) in the natalizumab group than in the placebo group at both one and two years (P<0.001). The adverse events that were significantly more frequent in the natalizumab group than in the placebo group were fatigue (27 percent vs. 21 percent, P=0.048) and allergic reaction (9 percent vs. 4 percent, P=0.012). Hypersensitivity reactions of any kind occurred in 25 patients receiving natalizumab (4 percent), and serious hypersensitivity reactions occurred in 8 patients (1 percent).\n\nNatalizumab reduced the risk of the sustained progression of disability and the rate of clinical relapse in patients with relapsing multiple sclerosis. Adhesion-molecule inhibitors hold promise as an effective treatment for relapsing multiple sclerosis. (ClinicalTrials.gov number, NCT00027300.).", "PMID": "16510744"}, {"title": "Evidence of interferon beta-1a dose response in relapsing-remitting MS: the OWIMS Study. The Once Weekly Interferon for MS Study Group.", "abstract": "To compare efficacy of interferon beta-1a, 22 microg or 44 microg weekly, with placebo in relapsing MS.\n\nUncertainty exists concerning the optimal dose regimen for interferon beta in relapsing-remitting MS. Many patients and physicians prefer the convenience and lesser side effects of an injection given once weekly (qw) as opposed to three times weekly. Pharmacokinetic data and information on biologic markers suggest that this frequency may be suboptimal.\n\nRandomized, double-blind study of interferon beta-1a 22 microg, 44 microg, or placebo administered by weekly subcutaneous injection for 48 weeks. Proton density (PD)/T2-weighted and T1-weighted-gadolinium MRI scans during 24 weeks of therapy were analyzed for the number of combined unique (CU) lesions (primary outcome). Biannual PD/T2 scans were analyzed for T2 activity and burden of disease (BOD).\n\nCU lesions at 24 weeks had a median of 0.71/scan with placebo, 0.5/scan with 22 microg (not significant), and 0.33/scan with 44 microg (p = 0.002). T2 new lesion count/scan (mean/median) at 48 weeks was 3.2/1.5 for placebo, 2.4/1.0 for 22 microg (p = 0.03), and 1.5/1.0 for 44 microg (p = 0.0005). BOD at 48 weeks showed a median increase of 5.9% for placebo compared with a decrease of 1.4% in the 44 microg group (p = 0.0058) and 2% in the 22 microg group (p = 0.0018). No clinical variable, apart from steroid use in the 44 microg qw group (p = 0.014), showed significance.\n\nThese data confirm an MRI benefit of interferon beta-1a at low dose in MS, but highlight the limited clinical effect. Taken together with other studies, the data demonstrate a dose-effect relationship for both clinical and MRI variables.", "PMID": "10489026"}, {"title": "European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging--measured disease activity and burden in patients with relapsing multiple sclerosis. European/Canadian Glatiramer Acetate Study Group.", "abstract": "Two prior double-blind, placebo-controlled, randomized trials demonstrated that glatiramer acetate (GA) reduces relapse rates in patients with relapsing remitting multiple sclerosis (RRMS). This study was designed to determine the effect, onset, and durability of any effect of GA on disease activity monitored with magnetic resonance imaging (MRI) in patients with RRMS. Two hundred thirty-nine eligible patients were randomized to receive either 20 mg GA (n = 119) or placebo (n = 120) by daily subcutaneous injection. Eligibility required one or more relapses in the 2 years before entry and at least one enhancing lesion on a screening MRI. The study was a randomized, double-blind, placebo-controlled phase during which all patients studied underwent monthly MRI scans and clinical assessments over 9 months. The primary outcome measure was the total number of enhancing lesions on T1-weighted images. Secondary outcome measures included the proportion of patients with enhancing lesions, the number of new enhancing lesions and change in their volume; the number of new lesions detected on T2-weighted images and change in their volume, and the change in volume of hypointense lesions seen on unenhanced T1-weighted images. Clinical measures of disease activity were also evaluated. The active treatment and placebo groups were comparable at entry for all demographic, clinical, and MRI variables. Treatment with GA showed a significant reduction in the total number of enhancing lesions compared with placebo (-10.8, 95% confidence interval -18.0 to -3.7; p = 0.003). Consistent differences favoring treatment with GA were seen for almost all secondary end points examined: number of new enhancing lesions (p < 0.003), monthly change in the volume of enhancing lesions (p = 0.01), and change in volume (p = 0.006) and number of new lesions seen on T2-weighted images (p < 0.003). The relapse rate was also significantly reduced by 33% for GA-treated patients (p = 0.012). All effects increased over time. Glatiramer acetate significantly reduced MRI-measured disease activity and burden.", "PMID": "11261502"}, {"title": "Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.", "abstract": "Interferon beta is used to modify the course of relapsing multiple sclerosis. Despite interferon beta therapy, many patients have relapses. Natalizumab, an alpha4 integrin antagonist, appeared to be safe and effective alone and when added to interferon beta-1a in preliminary studies.\n\nWe randomly assigned 1171 patients who, despite interferon beta-1a therapy, had had at least one relapse during the 12-month period before randomization to receive continued interferon beta-1a in combination with 300 mg of natalizumab (589 patients) or placebo (582 patients) intravenously every 4 weeks for up to 116 weeks. The primary end points were the rate of clinical relapse at 1 year and the cumulative probability of disability progression sustained for 12 weeks, as measured by the Expanded Disability Status Scale, at 2 years.\n\nCombination therapy resulted in a 24 percent reduction in the relative risk of sustained disability progression (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P=0.02). Kaplan-Meier estimates of the cumulative probability of progression at two years were 23 percent with combination therapy and 29 percent with interferon beta-1a alone. Combination therapy was associated with a lower annualized rate of relapse over a two-year period than was interferon beta-1a alone (0.34 vs. 0.75, P<0.001) and with fewer new or enlarging lesions on T(2)-weighted magnetic resonance imaging (0.9 vs. 5.4, P<0.001). Adverse events associated with combination therapy were anxiety, pharyngitis, sinus congestion, and peripheral edema. Two cases of progressive multifocal leukoencephalopathy, one of which was fatal, were diagnosed in natalizumab-treated patients.\n\nNatalizumab added to interferon beta-1a was significantly more effective than interferon beta-1a alone in patients with relapsing multiple sclerosis. Additional research is needed to elucidate the benefits and risks of this combination treatment. (ClinicalTrials.gov number, NCT00030966.).", "PMID": "16510745"}, {"title": "Oral fingolimod (FTY720) for relapsing multiple sclerosis.", "abstract": "Fingolimod (FTY720) is a new oral immunomodulating agent under evaluation for the treatment of relapsing multiple sclerosis.\n\nWe randomly assigned 281 patients to receive oral fingolimod, at a dose of 1.25 mg or 5.0 mg, or a placebo once daily, and we followed these patients for 6 months with magnetic resonance imaging (MRI) and clinical evaluations (core study, months 0 to 6). The primary end point was the total number of gadolinium-enhanced lesions recorded on T(1)-weighted MRI at monthly intervals for 6 months. In an extension study in which the investigators and patients remained unaware of the dose assignments (months 7 to 12), patients who received placebo underwent randomization again to one of the fingolimod doses.\n\nA total of 255 patients completed the core study. The median total number of gadolinium-enhanced lesions on MRI was lower with 1.25 mg of fingolimod (1 lesion, P<0.001) and 5.0 mg of fingolimod (3 lesions, P=0.006) than with placebo (5 lesions). The annualized relapse rate was 0.77 in the placebo group, as compared with 0.35 in the group given 1.25 mg of fingolimod (P=0.009) and 0.36 in the group given 5.0 mg of fingolimod (P=0.01). For the 227 patients who completed the extension study, the number of gadolinium-enhanced lesions and relapse rates remained low in the groups that received continuous fingolimod, and both measures decreased in patients who switched from placebo to fingolimod. Adverse events included nasopharyngitis, dyspnea, headache, diarrhea, and nausea. Clinically asymptomatic elevations of alanine aminotransferase levels were more frequent with fingolimod (10 to 12%, vs. 1% in the placebo group). One case of the posterior reversible encephalopathy syndrome occurred in the 5.0-mg group. Fingolimod was also associated with an initial reduction in the heart rate and a modest decrease in the forced expiratory volume in 1 second.\n\nIn this proof-of-concept study, fingolimod reduced the number of lesions detected on MRI and clinical disease activity in patients with multiple sclerosis. Evaluation in larger, longer-term studies is warranted. (Clinicaltrials.gov numbers, NCT00333138 [core study] and NCT00235430 [ClinicalTrials.gov] [extension].).", "PMID": "16971719"}, {"title": "Full results of the Evidence of Interferon Dose-Response-European North American Comparative Efficacy (EVIDENCE) study: a multicenter, randomized, assessor-blinded comparison of low-dose weekly versus high-dose, high-frequency interferon beta-1a for relapsing multiple sclerosis.", "abstract": "Interferon (IFN)-beta therapy represents an important advance in the management of relapsing multiple sclerosis (MS), but information about the relative benefits and risks of available preparations is limited.\n\nThis report describes the full results of the Evidence of Interferon Dose-response-European North American Comparative Efficacy (EVIDENCE) study, combining analyses that were previously reported in separate publications for different phases of the study.\n\nThe EVIDENCE study was a multicenter, randomized, assessor-blinded comparison of 2 IFN-beta dosing regimens. In the study, patients with relapsing MS were randomly assigned to SC IFN-beta1a 44 lag TIW (Rebif, Serono Inc., Geneva, Switzerland) or IM IFN-betala 30 mug QW (Avonex, Biogen Idec, Cambridge, Massachusetts) for 1 to 2 years. The primary clinical end point during the comparative phase was the proportion of patients who remained free from relapses; secondary and tertiary clinical end points included the annualized relapse rate and time to first relapse, re- spectively. All clinical and magnetic resonance imaging (MRI) evaluations were performed by blinded assessors. In the crossover phase of the study, patients who were originally randomized to low-dose QW treatment switched to the high-dose TIW treatment for an additional 8 months. Adverse events were determined by spontaneous reporting and monthly laboratory testing during the comparative phase.\n\nA total of 677 patients were enrolled in the study and evenly randomized to treatment; 605 patients completed the comparative phase and 439 completed the crossover phase. During the comparative phase, a significantly higher proportion of patients in the high-dose TIW treatment group remained free from relapses when compared with patients in the low-dose QW treatment group (adjusted odds ratio, 1.5; 95% CI, 1.1-2.0; P = 0.023). The high-dose TIW regimen was also associated with a significant reduction in the annualized relapse rate (-17%; P = 0.033) and a prolonged time to first relapse (hazard ratio, 0.70; P = 0.002). MRI measures of disease activity were significantly reduced in the high-dose TIW group compared with the low-dose QW treatment. During the crossover phase, a 50% reduction in mean relapse rates was observed in patients who converted from low-dose QW treatment to high-dose TIW treatment (P < 0.001), with significant concomitant reductions in MRI activity. Injection-site reactions were significantly more common with high-dose TIW treatment than with low-dose QW treatment (85% vs 33%; P < 0.001). Neutralizing antibody formation was more common with high-dose TIW treatment than with low-dose QW treatment (26% vs 3%; P < 0.001).\n\nThe comparative phase of the EVIDENCE study found that treatment of MS with SC IFN-beta1a 44 microg TIW was associated with a significant reduction in clinical and imaging measures of disease activity over 1 to 2 years, when compared with IM IFN-betala 30 microg QW treatment. The crossover phase found that patients who changed from low-dose QW treatment to high-dose TIW treatment experienced enhanced benefits of treatment without a substantial increase in adverse events.", "PMID": "18035202"}, {"title": "Intravenous immunoglobulin in relapsing-remitting multiple sclerosis: a dose-finding trial.", "abstract": "Several studies have reported a reduction of relapses after the long-term administration of IV immunoglobulin (IVIG) to patients with relapsing-remitting multiple sclerosis (RRMS), but they were mostly small and differed in terms of predefined outcome variables and treatment regimen. We therefore set out to test two different doses of a new formulation of immunoglobulin termed IGIV-C 10% for suppression of both clinical and MRI disease activity as well as safety.\n\nOne hundred twenty-seven patients with RRMS participated in this multicenter, randomized, double-blind, placebo-controlled trial. Forty-four and 42 patients received treatment with 0.2 and 0.4 g/kg of IGIV-C 10%, and 41 patients received an equal volume of placebo (0.1% albumin) every 4 weeks for 48 weeks. The primary endpoint was the proportion of relapse-free patients. The main secondary endpoint was lesion activity assessed by 6-weekly MRI.\n\nBaseline variables were similar in IVIG- and placebo-treated groups. After 1 year, the proportion of relapse-free patients did not differ statistically according to treatment (IVIG 0.2 g/kg: 57%; IVIG 0.4 g/kg: 60%; placebo: 68%), and there was no difference regarding the cumulative number of unique newly active MRI lesions (median numbers: IVIG 0.2 g/kg: 8.0; IVIG 0.4 g/kg: 5.0; placebo: 7.2) after 48 weeks. There were no significant between-group differences in the rates of adverse events.\n\nAlthough IV immunoglobulin (IVIG) treatment was well tolerated, this study did not substantiate a beneficial effect of IVIG in doses ranging from 0.2 to 0.4 g/kg. This result seriously questions the utility of IVIG for the treatment of relapsing-remitting multiple sclerosis.", "PMID": "18645164"}, {"title": "Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study.", "abstract": "Oral fumarate (BG00012) might have dual anti-inflammatory and neuroprotective effects. Our aim was to assess the efficacy and safety of BG00012 in patients with relapsing-remitting multiple sclerosis.\n\n257 patients, aged 18-55 years, with relapsing-remitting multiple sclerosis were randomly assigned to receive 120 mg once daily (n=64), 120 mg three times daily (n=64), or 240 mg three times daily (n=64) BG00012, or placebo (n=65) for 24 weeks. During an extension period of 24 weeks for safety assessment, patients treated with placebo received BG00012 240 mg three times daily. The primary endpoint was total number of new gadolinium enhancing (GdE) lesions on brain MRI scans at weeks 12, 16, 20, and 24. Additional endpoints included cumulative number of new GdE lesions (weeks 4-24), new or enlarging T2-hyperintense lesions, new T1-hypointense lesions at week 24, and annualised relapse rate. Analysis was done on the efficacy-evaluable population. Safety and tolerability were also assessed. This study is registered with ClinicalTrials.gov, number NCT00168701.\n\nTreatment with BG00012 240 mg three times daily reduced by 69% the mean total number of new GdE lesions from week 12 to 24 compared with placebo (1.4 vs 4.5, p<0.0001). It also reduced number of new or enlarging T2-hyperintense (p=0.0006) and new T1-hypointense (p=0.014) lesions compared with placebo. BG00012 reduced annualised relapse rate by 32% (0.44 vs 0.65 for placebo; p=0.272). Adverse events more common in patients given BG00012 than in those given placebo included abdominal pain, flushing, and hot flush. Dose-related adverse events in patients on BG00012 were headache, fatigue, and feeling hot.\n\nThe anti-inflammatory effects and favourable safety profile of BG00012 warrant further long-term phase III studies in large patient groups.", "PMID": "18970976"}], "labels": [{"PMID": "11988242", "label": "included"}, {"PMID": "12453070", "label": "included"}, {"PMID": "16510744", "label": "included"}, {"PMID": "10489026", "label": "excluded"}, {"PMID": "11261502", "label": "excluded"}, {"PMID": "16510745", "label": "excluded"}, {"PMID": "16971719", "label": "excluded"}, {"PMID": "18035202", "label": "excluded"}, {"PMID": "18645164", "label": "excluded"}, {"PMID": "18970976", "label": "excluded"}]}
{"metadata": {"review_pmid": "38096386"}, "inputs": {"background": "Lumbar puncture is a common invasive procedure performed in newborns for diagnostic and therapeutic purposes. Approximately one in two lumbar punctures fail, resulting in both short- and long-term negative consequences for the clinical management of patients. The most common positions used to perform lumbar puncture are the lateral decubitus and sitting position, and each can impact the success rate and safety of the procedure. However, it is uncertain which position best improves patient outcomes.", "objectives": "To assess the benefits and harms of the lateral decubitus, sitting, and prone positions for lumbar puncture in newborn infants.", "selection criteria": "We included randomized controlled trials (RCTs) and quasi-RCTs involving newborn infants of postmenstrual age up to 46 weeks and 0 days, undergoing lumbar puncture for any indication, comparing different positions (i.e. lateral decubitus, sitting, and prone position) during the procedure."}, "context": [{"title": "Lumbar Puncture in the prone position for Low Birth Weight Neonates.", "abstract": "Lumbar puncture in the lateral decubitus position will make the neonates uncomfortable and is likely to cause position change and unstable vital signs, and the application of sedative drugs will cause adverse effects. This study explored a novel method for lumbar puncture in the prone position for low weight neonates.\n\nThe neonates were randomly assigned into the standard position group receiving lumbar puncture in the lateral decubitus position; and the improved position group receiving lumbar puncture in the prone position. The success rate of first time attempts and the overall success rate of lumbar puncture, incidence of adverse effects, NIAPAS scores were collected and compared between these two groups. The difference in success rate and adverse effects incidence rate was analysed through Chi-square. Student's t-test was used for the test of NIAPAS rating.\n\nThe improved position group had a higher success rate of first attempt and overall success rate, significantly lower incidence of adverse effect and lower NIAPAS scores than those of the standard position group (P<0.05).\n\nThis lumbar puncture in the prone position is safer, more effective, and more comfortable for preterm neonates and those with low birth weight. Thus, this method is worth of further promotion.\n\nRegistration number, ChiCTR2100049923; Date of Registration, August 11, 2021; Retrospectively registered.", "PMID": "34980050"}, {"title": "A Randomized Controlled Trial of Positioning for Lumbar Puncture in Young Infants.", "abstract": "The lateral and sitting positions are those most widely used to perform lumbar puncture (LP) in infants. This study sought to compare LP success rates by position. Secondary outcomes were successful LP on the first attempt and rates of procedural complications.\n\nInfants aged 1 to 90 days undergoing LP in our pediatric emergency department between June 1, 2012 and October 31, 2013 were randomized to 1 position or the other. Successful LP was defined as collection of cerebrospinal fluid with a red blood cell count of less than 10,000 cells/mm on either of the first 2 attempts. Electronic medical records were reviewed for patient information, cerebrospinal fluid results, and procedural complications. Providers completed a questionnaire detailing their previous LP experience and technique. Primary results were analyzed using the intention-to-treat principle.\n\nWe enrolled 168 infants. Of 167 with data eligible for analysis, 82 (49%) were randomized to the lateral position. There was no statistically significant difference in LP success rate between the lateral (77%, 63/82) and sitting (72%, 61/85) positions (difference, 5.1%; 95% confidence interval, -8.2%-18.3%). There were no significant differences in success on the first LP attempt or the rates of procedural complications.\n\nAmong infants 1 to 90 days of age, this study found no difference in LP success between the lateral and sitting positions.", "PMID": "26417957"}, {"title": "Study protocol: NeoCLEAR: Neonatal Champagne Lumbar punctures Every time - An RCT: a multicentre, randomised controlled 2\u2009\u00d7\u20092 factorial trial to investigate techniques to increase lumbar puncture success.", "abstract": "The neonatal period carries the highest risk of bacterial meningitis (~\u20091 in 5000 births), bearing high mortality (~\u200910%) and morbidity (20-50%) rates. Lumbar puncture (LP) remains essential to the diagnosis of meningitis. Though LP is a common procedure in neonates, success rates are lower (50-60%) than in other patient populations. None of the currently-practised neonatal LP techniques are supported by evidence from adequately-powered, randomised controlled trials (RCTs). NeoCLEAR aims to compare two modifications to the traditional technique which are free, accessible, and commonly practised: sitting (as opposed to lying) position, and 'early' (as opposed to 'late') stylet removal.\n\nWritten parental informed consent permitting, infants in neonatal/maternity wards, of 27\n\nTwo modifications to the traditional LP technique (sitting vs lying position; and early vs late stylet removal) will be simultaneously investigated in an efficient and appropriately-powered 2\u2009\u00d7\u20092 factorial RCT design. Analysis will identify the optimal techniques (in terms of obtaining easily-interpretable cerebrospinal fluid), as well as the impact on infants, parents and healthcare systems whilst providing robust safety data. Using a pragmatic RCT design, all practitioners will be trained in all LP techniques, but there will inevitably be variation between unit practice guidelines and other aspects of individual care. An improved LP technique would result in: \u2022 Fewer uninterpretable samples, repeated attempts and procedures \u2022 Reduced distress for infants and families \u2022 Decreased antibiotic use and risk of antibiotic resistance \u2022 Reduced healthcare costs due to fewer procedures, reduced length of stay, shorter antibiotic courses, and minimised antibiotic-associated complications TRIAL REGISTRATION: ISRCTN14040914. Date assigned: 26/06/2018.", "PMID": "32295554"}, {"title": "Assessment of infant position and timing of stylet removal to improve lumbar puncture success in neonates (NeoCLEAR): an open-label, 2\u2009\u00d7\u20092 factorial, randomised, controlled trial.", "abstract": "Newborn infants are the highest-risk age group for bacterial meningitis. Lumbar punctures are therefore frequently performed in neonates, but success rates are low (50-60%). In Neonatal Champagne Lumbar punctures Every time-A Randomised Controlled Trial (NeoCLEAR), we sought to optimise infant lumbar puncture by evaluating two modifications to traditional technique: sitting position versus lying down and early stylet removal (stylet removal after transecting the subcutaneous tissue) versus late stylet removal.\n\nNeoCLEAR was an open-label, 2\u2009\u00d7\u20092 factorial, randomised, controlled trial, conducted in 21 UK neonatal and maternity units. Infants requiring lumbar puncture at 27\n\nBetween Aug 3, 2018, and Aug 31, 2020, 1082 infants were randomly assigned to sitting (n=546) or lying (n=536), and early (n=549) or late (n=533) stylet removal. 1076 infants were followed-up until discharge and included in the modified intention-to-treat analysis. 961 (89%) infants were term, and 936 (87%) were younger than 3 days. Successful first lumbar puncture was more frequently observed in sitting than in lying position (346 [63\u00b77%] of 543 vs 307 [57\u00b76%] of 533; adjusted risk ratio 1\u00b710 [95% CI 1\u00b701 to 1\u00b721], p=0\u00b7029; number needed to treat=16). Timing of stylet removal had no discernible effect on the primary outcome (338 [62\u00b70%] of 545 infants in the early stylet removal group and 315 [59\u00b73%] of 531 in the late stylet removal group had a successful first lumbar puncture; adjusted risk ratio 1\u00b704 [95% CI 0\u00b794-1\u00b715], p=0\u00b745). Sitting was associated with fewer desaturations than was lying (median lowest oxygen saturations during first lumbar puncture 93% [IQR 89-96] vs 90% [85-94]; median difference 3\u00b70% [2\u00b71-3\u00b79], p<0\u00b70001). One infant from the sitting plus late stylet removal group developed a scrotal haematoma 2 days after lumbar puncture, which was deemed to be possibly related to lumbar puncture.\n\nNeoCLEAR is the largest trial investigating paediatric lumbar puncture so far. Success rates were improved when sitting rather than lying. Sitting lumbar puncture is safe, cost neutral, and well tolerated. We predominantly recruited term neonates younger than 3 days; other populations warrant further study. Neonatal lumbar puncture is commonly performed worldwide; these results therefore strongly support the widespread adoption of sitting technique for neonatal lumbar puncture.\n\nUK National Institute for Health and Care Research.", "PMID": "36460015"}, {"title": "Spinal anaesthesia for inguinal herniotomy in preterm infants sedated with nitrous oxide: a comparison of lumbar puncture in the lateral or sitting position.", "abstract": "This study compares spinal anaesthesia for inguinal herniotomy in preterm infants in the lateral or sitting position. Thirty patients were randomly divided into two equal groups. One hour before spinal anaesthesia, a eutetic mixture of local anaesthetic cream was applied to the lower lumbar spine. Sedation with nitrous oxide 50% in oxygen was given to all patients before and during induction of spinal anaesthesia, and throughout surgery. Lumbar punctures were performed at the L4-5 interspace using a 2.5 cm 22 G needle. Isobaric bupivacaine 0.5% with epinephrine 1 : 200 000 at a bupivacaine dose of 1 mg.kg-1 was injected in the lateral or sitting position. Measurements included heart rate, blood pressure, oxygen saturation, maximum sensory block height and duration of motor block and analgesia. There were no statistically significant differences between the groups in any measured parameters. Median [range] maximum block height was T5[T4-T7] in the lateral group and T5[T4-T5] in the sitting group. The median [range] duration of motor blockade was 67 [50-85] min in the lateral group and 63 [50-80] min in the sitting group. Our results indicate that in preterm infants sedated with nitrous oxide, spinal anaesthesia for inguinal herniotomy performed with isobaric bupivacaine 0.5% at a dose 1.0 mg.kg-1 in the lateral or sitting position is equally effective and is associated with minimal side effects.", "PMID": "12437706"}, {"title": "The effect of lumbar puncture position in sick neonates.", "abstract": "Clinical deterioration has been observed in sick neonates during lumbar puncture. This study was done to determine if hypoxemia occurred during lumbar puncture, if hypoxemia was position dependent, if transcutaneous PO2 (TcPO2) monitoring effected hypoxemia, and what possible mechanisms were involved. Twenty-six neonates received lumbar punctures in either a standard lateral knee-chest position, sitting position, or modified lateral without knee-chest position. Care was taken not to extend or flex the neck. Mean TcPO2 was lower for standard lateral than sitting or modified lateral positions. The time TcPO2 was under 50 mm Hg was greater for standard lateral positions than sitting or modified lateral positions. Increased intraesophageal pressure, in the standard lateral position, suggests extrathoracic compression of the chest by the abdominal contents. We recommend lumbar punctures be done in the sitting or modified lateral position.", "PMID": "6637909"}], "labels": [{"PMID": "34980050", "label": "included"}, {"PMID": "26417957", "label": "included"}, {"PMID": "32295554", "label": "included"}, {"PMID": "36460015", "label": "included"}, {"PMID": "12437706", "label": "included"}, {"PMID": "6637909", "label": "included"}]}
{"metadata": {"review_pmid": "38096261"}, "inputs": {"background": "Cranberries (particularly in the form of cranberry juice) have been used widely for several decades for the prevention and treatment of urinary tract infections (UTIs). The aim of this review is to assess the effectiveness of cranberries in treating such infections.", "objectives": "To assess the effectiveness of cranberries for the treatment of UTIs.", "selection criteria": "All randomised controlled trials (RCTs) or quasi-RCTs of cranberry juice or cranberry products for the treatment of UTIs. Studies of men, women or children were to be included."}, "context": [{"title": "Does cranberry extract reduce antibiotic use for symptoms of acute uncomplicated urinary tract infections (CUTI)? Protocol for a feasibility study.", "abstract": "Consultations in primary care for symptoms of urinary tract infections (UTIs) are common and patients are frequently treated with antibiotics. Given increasing antimicrobial resistance, there has been interest in non-antibiotic treatment options for common infections. One such option is the use of cranberry extract to treat symptoms attributable to UTIs.\n\nA target of 45 women consulting in primary care, with symptoms suggestive of an uncomplicated UTI for whom the practitioner would normally prescribe antibiotics, will be randomised to receive one of three treatment approaches: (1) immediate prescription for antibiotics; (2) immediate prescription for antibiotics plus a 7-day course of cranberry capsules and (3) cranberry capsules plus a delayed prescription for antibiotics to be used in case their symptoms do not get better, or get worse. Follow-up will be by daily rating of symptoms and recording of treatments used for 2 weeks in an online symptom diary. Interviews will be conducted with around 10-15 study participants, as well as with around 10-15 women who have experienced a UTI but have not been approached to take part in the study. Both groups will be asked about their experience of having a UTI, their thoughts on non-antibiotic treatments for UTIs and their thoughts on, or experience of, the feasibility trial. The primary objective is to assess the feasibility of undertaking a full trial in primary care of the effectiveness of cranberry extract to reduce antibiotic use for symptoms of acute uncomplicated UTI. The secondary objective is to conduct a preliminary assessment of the extent to which cranberry might reduce antibiotic use and symptom burden.\n\nThis feasibility study with embedded interviews will inform the planning and sample size calculation of an adequately powered trial to definitively determine whether cranberry helps to alleviate the symptoms of acute uncomplicated UTIs in women and whether it can safely reduce antibiotic use.\n\nISRCTN registry, ID: 10399299. Registered on 24 January 2019.", "PMID": "31870413"}, {"title": "Does cranberry extract reduce antibiotic use for symptoms of acute uncomplicated urinary tract infections (CUTI)? A feasibility randomised trial.", "abstract": "To determine the feasibility of conducting a randomised trial of the effectiveness of cranberry extract in reducing antibiotic use by women with symptoms of acute, uncomplicated urinary tract infection (UTI).\n\nOpen-label feasibility randomised parallel group trial.\n\nFour general practices in Oxfordshire.\n\nWomen aged 18 years and above presenting to general practice with symptoms of acute, uncomplicated UTI.\n\nWomen were randomly assigned using Research Electronic Data Capture in a 1:1:1 ratio to: (1) immediate antibiotics alone (n=15); (2) immediate antibiotics and immediate cranberry capsules for up to 7 days (n=15); or (3) immediate cranberry capsules and delayed antibiotics for self-initiation in case of non-improvement or worsening of symptoms (n=16).\n\nThe primary outcome measures were: rate of recruitment of participants; numbers lost to follow-up; proportion of electronic diaries completed by participants; and acceptability of the intervention and study procedures to participants and recruiters. Secondary outcomes included an exploration of differences in symptom burden and antibiotic use between groups.\n\nFour general practitioner practices (100%) were opened and recruited participants between 1 July and 2 December 2019, with nine study participants recruited per month on average. 68.7% (46/67) of eligible participants were randomised (target 45) with a mean age of 48.4 years (SD 19.9, range 18-81). 89.1% (41/46) of diaries contained some participant entered data and 69.6% (32/46) were fully complete. Three participants (6.5%) were lost to follow-up and two (4.4%) withdrew. Of women randomly assigned to take antibiotics alone (controls), one-third of respondents reported consuming cranberry products (33.3%, 4/12). There were no serious adverse events.\n\nIt appears feasible to conduct a randomised trial of the use of cranberry extract in the treatment of acute, uncomplicated UTI in general practice.\n\nISRCTN Registry (ID: 10399299).", "PMID": "33619202"}, {"title": "Prevention and treatment of cystitis during menopause: efficacy of a nutraceutical containing D-mannose, inulin, cranberry, bearberry, ", "abstract": "To evaluate the efficacy of a nutraceutical compound containing Uticlin\u00ae (D-mannose, cranberry, bearberry, \n\nThis was a prospective cohort study of menopausal women recruited with a history of recurrent UTIs in the previous twelve months and who intended to treat their bladder problem without the use of antibiotics and/or anti-inflammatories. Women were proposed the use of an oral nutraceutical compound. The drug was taken for ten days, every month. Women were assigned to two parallel cohorts: patients using (group 1) or not using (group 2) this nutraceutical compound. The primary objective of the study was to evaluate the number of women with less than two infective episodes in the 6-month follow-up and less than three episodes in the 12-month follow-up. The secondary endpoints were to evaluate the reduction of related symptoms at 12-month follow-up, according to the Visual Analog Scale (VAS).\n\nAt 6 months of therapy, the reduction in the number of patients with \u2265 2 UTIs was statistically significant (\n\nIn menopausal women, the combination of D-mannose, inulin, cranberry, bearberry, ", "PMID": "33100948"}, {"title": "Effect of urinary acidifiers on formaldehyde concentration and efficacy with methenamine therapy.", "abstract": "Twenty-seven patients with indwelling urinary catheters and chronic bacteriuria were studied for methenamine efficacy. In a crossover fashion, each patient received methenamine mandelate granules 4 g/day alone, with ascorbic acid 4 g/day, and with ascorbic acid 4 g/day plus cranberry cocktail one 1/day. Proteus vulgaris, Pseudomonas aeruginosa, and E. coli were the common pathogens. Urinary acidifiers had no significant effect on mean urine pH, however, high urinary formaldehyde concentrations were associated with the use of ascorbic acid. Bacteriocidal formaldehyde levels were more frequently present in patients with acidic urine pH than those with alkaline pH. Although ascorbic acid increased formaldehyde levels, additional cranberry cocktail had no further effect. Despite higher formaldehyde levels, urine culture results were positive in most cases with or without urine acidification. Methenamine therapy may be of limited value in asymptomatic chronic bacteriuric patients with indwelling catheters.", "PMID": "7106162"}, {"title": "Predictability of methenamine efficacy based on type of urinary pathogen and pH.", "abstract": "This study involved 27 geriatric patients with asymptomatic chronic bacteriuria; all had indwelling Foley catheters. The treatment regimens (daily oral dosage) were: methenamine mandelate (MM) granules, 4 gm; MM, 4 gm, plus ascorbic acid, 4 gm; and MM, 4 gm, plus ascorbic acid, 4 gm, plus cranberry cocktail, 1 liter--administered according to a cross-over design. Proteus vulgaris, Pseudomonas aeruginosa and E. coli were the most common urinary organisms. Proteus organisms were more often found in alkaline than in acidic urines, but the type of pathogen had no influence on urinary pH. Urinary formaldehyde concentration [HCHO] was lower in patients with Proteus infection (17.7 micrograms/ml) than in those with Pseudomonas (21.9 micrograms/ml) or E. coli infection (21.8 micrograms/ml). However, for Proteus infection, [HCHO] was higher in patients receiving MM plus ascorbic acid than in those receiving MM alone. Addition of cranberry cocktail to ascorbic acid did not enhance urinary pH, [HCHO] or methenamine efficacy. Our data suggest that in Foley catheter patients with chronic asymptomatic bacteriuria secondary to Proteus, Pseudomonas or E. coli infection, the type of urinary pathogen or the urinary pH cannot be used to predict the efficacy of methenamine therapy either with or without urinary acidifying agents.", "PMID": "7014695"}, {"title": "Lack of effect of ascorbic acid, hippuric acid, and methenamine (urinary formaldehyde) on the copper-reduction glucose test in geriatric patients.", "abstract": "Ascorbic acid and hippuric acid (from cranberry juice) are commonly used to acidify the urine for the purpose of enhancing the degradation of therapeutic methenamine mandelate to urinary formaldehyde. A study was made of 27 nondiabetic geriatric patients with indwelling Foley catheters and chronic bacteriuria who were treated with methenamine mandelate (4 gm), ascorbic acid (4 gm), and cranberry cocktail (1 liter) daily. All of 972 urine samples showed formaldehyde in mean concentrations between 14 and 25 microgram/ml. No glucose was found when the urine was tested by the copper-reduction method. In vitro false positive reactions reported in the literature do not appear to be duplicated as an in vivo problem.", "PMID": "7365188"}, {"title": "Combination of cranberry extract and D-mannose - possible enhancer of uropathogen sensitivity to antibiotics in acute therapy of urinary tract infections: Results of a pilot study.", "abstract": "Uncomplicated lower urinary tract infections are extremely common in women. Antibiotic treatment for acute episodes and for recurrence prophylaxis has its drawbacks and alternative therapies are sought in order to reduce the antimicrobial resistance phenomenon and the intestinal dismicrobism expansion. There are few studies on the effect of combination of cranberry extract with D-mannose in acute urinary tract infection management. In a pilot, randomized study 93 non-pregnant, otherwise healthy women, were enrolled with mean age of 39.77\u00b110.36, diagnosed with uncomplicated lower urinary tract infection. Medical history, clinical examination, urine culture and a list of complaints were noted at the baseline visit. In a first phase of the study, treatment with either guideline recommended antibiotic alone or in association with the investigated product (cranberry extract plus D-mannose) was prescribed and all patients were clinically examined at day 7. All ameliorated and cured patients received in a second phase of the study, in a double-blind manner, prophylaxis with the investigated product or placebo for another 21 days, then a second clinical examination and a check of the list of complaints were performed. The cure rates were higher at day 7 when investigated product was added to antibiotic (91.6 vs. 84.4%). In resistant strains, a significantly higher cure rate was shown when the investigated product was added to antibiotic prescribed (88.8 vs. 37.5%, P<0.0001). The effect of cranberry extract plus D-mannose combination in acute urinary tract infection episodes seems to be promising. The significant cure rate registered in the patients with antibiotic-resistant urine cultures may be explained by a beneficial influence of the product on the antimicrobial sensitivity. Further studies are needed on this subject.", "PMID": "32905041"}, {"title": "Clinical evaluation of herbal coded formulation Cran-off to Urixin in the treatment of urinary tract infection.", "abstract": "Urinary Tract Infections are the largest group of infections after the respiratory tract infections. In 85% of the cases the causative organism is E. Coli. A clinical trial was conducted to evaluate the efficacy of coded herbal formulation \"Cranoff\" (Test drug) for the treatment of Urinary tract infection comparing with Urixin (Control). One hundred and thirty patients suffering from Urinary tract infection from both groups (Males: 45, mean age: 34\u00b114 and females: 85, mean age: 33\u00b113 year, range: 15-55) were enrolled in the trial and divided in to two groups according to treatment regimens. Cranoff (Test drug) 500mg two capsules and Urixin (Pipemidic Acid Trihydrate JP15) (Control) 400mg capsules twice daily were prescribed for 2-3 weeks. Urinary tract infection was improved in 23 (35.38%) patients out of 65 patients by the use of Cranoff (Test drug), and in 15 (23.07%) patients out of 65 by the use of Urixin (Control drug). Furthermore, there was a significant improvement in Urinary tract infection associated clinical features as compared to Urixin. It is concluded that Cranoff possesses a therapeutic value for the improvement of urinary tract infection and its associated symptoms as compared to Urixin. ", "PMID": "25730788"}], "labels": [{"PMID": "31870413", "label": "excluded"}, {"PMID": "33619202", "label": "excluded"}, {"PMID": "33100948", "label": "excluded"}, {"PMID": "7106162", "label": "excluded"}, {"PMID": "7014695", "label": "excluded"}, {"PMID": "7365188", "label": "excluded"}, {"PMID": "32905041", "label": "excluded"}, {"PMID": "25730788", "label": "excluded"}]}
{"metadata": {"review_pmid": "38095590"}, "inputs": {"background": "Many people receiving palliative care have reduced oral intake during their illness, and particularly at the end of their life. Management of this can include the provision of medically assisted hydration (MAH) with the aim of improving their quality of life (QoL), prolonging their life, or both. This is an updated version of the original Cochrane Review published in Issue 2, 2008, and updated in February 2011 and March 2014.", "objectives": "To determine the effectiveness of MAH compared with placebo and standard care, in adults receiving palliative care on their QoL and survival, and to assess for potential adverse events.", "selection criteria": "We included all relevant randomised controlled trials (RCTs) of studies of MAH in adults receiving palliative care aged 18 and above. The criteria for inclusion was the comparison of MAH to placebo or standard care."}, "context": [{"title": "Effects of parenteral hydration in terminally ill cancer patients: a preliminary study.", "abstract": "Most patients with cancer develop decreased oral intake and dehydration before death. This study aimed to determine the effect of parenteral hydration on overall symptom control in terminally ill cancer patients with dehydration.\n\nPatients with clinical evidence of mild to moderate dehydration and a liquid oral intake less than 1,000 mL/day were randomly assigned to receive either parenteral hydration with 1,000 mL (treatment group) or placebo with 100 mL normal saline administered over 4 hours for 2 days. Patients were evaluated for target symptoms (hallucinations, myoclonus, fatigue, and sedation), global well-being, and overall benefit.\n\nTwenty-seven patients randomly assigned to the treatment group had improvement in 53 (73%) of their 73 target symptoms versus 33 (49%) of 67 target symptoms in the placebo group (n=22; P = .005). Fifteen (83%) of 18 and 15 (83%) of 18 patients had improved myoclonus and sedation after hydration versus eight (47%) of 17 and five (33%) of 15 patients after placebo (P = .035 and P = .005, respectively). There were no significant differences of improvement in hallucinations or fatigue between groups. When blinded to treatment, patients (17 [63%] of 77) and investigators (20 [74%] of 27) perceived hydration as effective compared with placebo in nine (41%) of 22 patients (P = .78) and 12 (54%) of 22 investigators (P = .15), respectively. The intensity of pain and swelling at the injection site were not significantly different between groups.\n\nParenteral hydration decreased symptoms of dehydration in terminally ill cancer patients who had decreased fluid intake. Hydration was well tolerated, and a placebo effect was observed. Studies with larger samples and a longer follow-up period are justified.", "PMID": "15800328"}, {"title": "Parenteral hydration in patients with advanced cancer: a multicenter, double-blind, placebo-controlled randomized trial.", "abstract": "The vast majority of patients with cancer at the end of life receive parenteral hydration in hospitals and no hydration in hospice, with limited evidence supporting either practice. In this randomized controlled trial, we determined the effect of hydration on symptoms associated with dehydration, quality of life, and survival in patients with advanced cancer.\n\nWe randomly assigned 129 patients with cancer from six hospices to receive parenteral hydration (normal saline 1 L per day) or placebo (normal saline 100 mL per day) daily over 4 hours. The primary outcome was change in the sum of four dehydration symptoms (fatigue, myoclonus, sedation and hallucinations, 0 = best and 40 = worst possible) between day 4 and baseline. Secondary outcomes included Edmonton Symptom Assessment Scale (ESAS), Memorial Delirium Assessment Scale (MDAS), Nursing Delirium Screening Scale (NuDESC), Unified Myoclonus Rating Scale (UMRS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Dehydration Assessment Scale, creatinine, urea, and overall survival. Intention-to-treat analysis was conducted to examine the change by day 4 \u00b1 2 and day 7 \u00b1 2 between groups.\n\nThe hydration (n = 63) and placebo (n = 66) groups had similar baseline characteristics. We found no significant differences between the two groups for change in the sum of four dehydration symptoms (-3.3 v -2.8, P = .77), ESAS (all nonsignificant), MDAS (1 v 3.5, P = .084), NuDESC (0 v 0, P = .13), and UMRS (0 v 0, P = .54) by day 4. Results for day 7, including FACIT-F, were similar. Overall survival did not differ between the two groups (median, 21 v 15 days, P = .83).\n\nHydration at 1 L per day did not improve symptoms, quality of life, or survival compared with placebo.", "PMID": "23169523"}, {"title": "Hypodermoclysis for control of dehydration in terminal-stage cancer.", "abstract": "Many of those involved in palliative care have justifiable objections to the introduction of intravenous hydration in patients with dehydration-associated symptoms and advanced cancer. Researchers from the University of Buenos Aires carried out a randomized, comparative and prospective trail to determine the usefulness of hypodermoclysis in the control of thirst, chronic nausea and delirium. Forty-two patients were randomized into two groups. Both groups received drugs subcutaneously (haloperidol 2.5 mg every 4 hours to control delirium and/or metoclopramide 10 mg every 4 hours to control chronic nausea). The study group also received 1000 ml 5% dextrose in water infusion plus 140 milliequivalent per litre (mEq/L) sodium chloride, at a rate of 42 ml/hour per day. Both groups showed significant and equal improvements in relief of thirst and chronic nausea at 24 hours. After 48 hours, this improvement was maintained in the group that received hydration, but only for the relief of chronic nausea. Delirium did not improve significantly in either group during the 48-hour trial period. Current data suggest that decisions on rehydration of patients with terminal-phase cancer should be based more on the patient's comfort than on providing optimal hydration.", "PMID": "12411847"}, {"title": "A cluster randomised feasibility trial of clinically assisted hydration in cancer patients in the last days of life.", "abstract": "The provision of clinically assisted hydration at the end-of-life is one of the most contentious issues in medicine.\n\nThe aim of this feasibility study was to answer the question 'can a definitive (adequately powered) study be done?'\n\nThe study was a cluster randomised trial, with sites randomised on a one-to-one basis to intervention 'A' (regular mouth care and usual other care) or intervention 'B' (clinically assisted hydration, mouth care and usual other care). Participants were assessed every 4 h, and data collected on clinical problems, therapeutic interventions and overall survival.\n\nThe study was conducted at 12 sites/'clusters' with specialist palliative care teams (4 cancer centres and 8 hospices), and participants were cancer patients in the last week of life who were unable to maintain sufficient oral fluid intake.\n\nThe study achieved its pre-determined criteria for success. Two hundred patients were recruited to the study, and 199 participants completed the study, over a 1-year period. A total of 38.5% participants discontinued clinically assisted hydration due to adverse effects: none of these adverse events were rated as 'severe' or worse in intensity. The primary reasons for discontinuation were site problems ( n = 2), localised oedema ( n = 13), generalised oedema ( n = 5), respiratory secretions ( n = 6) and nausea and vomiting ( n = 1).\n\nThe results of this feasibility study suggest that a definitive study can be done, but that minor changes are needed to the protocol to standardise the administration of clinically assisted hydration (which may reduce the incidence of certain adverse effects).", "PMID": "29343167"}, {"title": "Fluid status of terminally ill cancer patients with intestinal obstruction: an exploratory observational study.", "abstract": "Although the dehydration-rehydration problem in end-of-life care is one of the most important issues, clinical indications of hydration therapy have not been clarified because the pathophysiology is poorly understood. To explore the physiological changes of fluid status in terminally ill cancer patients, a prospective observational study was performed. We obtained 9 pairs of blood samplings from hospice inpatients with irreversible bowel obstruction who underwent two or more laboratory examinations during the admission periods. The plasma renin activity (PRA) and brain natriuretic peptide (BNP) were measured, in addition to basic laboratory tests performed as clinically required. A chart review evaluated the degree of fluid retention symptoms. In 7 patients receiving intravenous rehydration of 700-2200 ml/day, the mean PRA level significantly increased from 3.5+/-2.5 ng ml(-1) h(-1) to 11+/-8.2 ng ml(-1) x h(-1) ( P=0.047), and the mean BNP level significantly decreased from 52+/-34 pg/ml to 22+/-14 pg/ml ( P=0.047). Edema, ascites, and pleural effusion/pulmonary edema deteriorated in 5, 3, and 5 patients, respectively. In 2 patients without rehydration therapy, peripheral edema deteriorated with increased PRA levels (0.5 to 20 ng ml(-1) x h(-1), 0.4 to 8.7 ng ml(-1) x h(-1), respectively). In conclusion, intravenous volume depletion with fluid retention symptoms was observed in terminally ill cancer patients with intestinal obstruction both receiving and not receiving intravenous hydration. The pathological mechanism hypothesized is the fluid shift from the intravascular compartment to the interstitial spaces.", "PMID": "12353126"}, {"title": "Association between hydration volume and symptoms in terminally ill cancer patients with abdominal malignancies.", "abstract": "To explore the association between hydration volume and symptoms during the last 3 weeks of life in terminally ill cancer patients.\n\nThis was a multicenter, prospective, observational study of 226 consecutive terminally ill patients with abdominal malignancies. Primary responsible physicians and nurses evaluated the severity of membranous dehydration (dehydration score calculated from three physical findings), peripheral edema (edema score calculated from seven physical findings), ascites and pleural effusion (rated as physically undetectable to symptomatic), bronchial secretion, hyperactive delirium (Memorial Delirium Assessment Scale), communication capacity (Communication Capacity Scale), agitation (Agitation Distress Scale), myoclonus and bedsores.\n\nPatients were classified into two groups: the hydration group (n=59) who received 1 l or more of artificial hydration per day, 1 and 3 weeks before death, and the non-hydration group (n=167). The percentage of patients with deterioration in dehydration score in the final 3 weeks was significantly higher in the non-hydration group than the hydration group (35% versus 14%; P=0.002), while the percentages of patients whose symptom scores for edema, ascites and pleural effusion increased were significantly higher in the hydration group than the non-hydration group (44% versus 29%, P=0.039; 29% versus 8.4%, P <0.001; 15% versus 5.4%, P=0.016; respectively). After controlling for multiple covariates and treatment settings, the association between hydration group and dehydration/ascites score was statistically significant. Subgroup analysis of patients with peritoneal metastases identified statistically significant interaction between hydration group and dehydration/pleural effusion score. There were no significant differences in the degree of bronchial secretion, hyperactive delirium, communication capacity, agitation, myoclonus or bedsores.\n\nArtificial hydration therapy could alleviate membranous dehydration signs, but could worsen peripheral edema, ascites and pleural effusions. It is suggested that the potential benefits of artificial hydration therapy should be balanced with the risk of worsening fluid retention symptoms. Further clinical studies are strongly needed to identify the effects of artificial hydration therapy on overall patient well-being, and an individualized treatment and close monitoring of dehydration and fluid retention symptoms is strongly recommended.", "PMID": "15684225"}, {"title": "Artificial hydration therapy, laboratory findings, and fluid balance in terminally ill patients with abdominal malignancies.", "abstract": "To explore the association between hydration volume and laboratory findings, and between calculated fluid balance and changes in clinical signs of dehydration and fluid retention in terminally ill cancer patients, a secondary analysis of a large multicenter, prospective, observational study was performed. The study enrolled 125 abdominal cancer patients who received laboratory examinations in the last week before death. Patients were classified into two groups: the hydration group (n = 44), who received 1L or more of artificial hydration per day both 1 and 3 weeks before death, and the nonhydration group (n = 81). The mean albumin level 1 week before death was significantly lower in the hydration group than in the nonhydration group, and the interaction between hydration group and decrease in the albumin level was statistically significant after adjusting multiple covariates (from 2.8 +/- 0.68 mg/dL 3 weeks before death to 2.4 +/- 0.56 mg/dL 24 hours before death in the hydration group vs. a decrease of 2.8 +/- 0.53 to 2.6+ /- 0.45 mg/dL in the nonhydration group, P = 0.015). There was no significant difference between the groups in the mean blood urea nitrogen/creatinine, sodium, or potassium levels 1 week before death. Among 53 patients who had oral fluid intake of less than 500 mL/day throughout the last 3 weeks and completed a fluid balance study, the median of calculated fluid balance was -400 mL/day 3 weeks before death, -521 mL/day 1 week before death, and -421 mL/day 24 hours before death. Calculated fluid balances did not significantly differ between the patients with deterioration of dehydration signs, edema, ascites, and pleural effusion during the final 3 weeks and those without. These data suggest that active artificial hydration might result in hypoalbuminemia, with no clear beneficial effects on normalizing blood urea nitrogen/creatinine, sodium, or potassium levels. Fluid balance did not significantly correlate with changes in dehydration-and fluid retention-signs. Calculated fluid balance is not an appropriate alternative to direct monitoring of patient symptoms. More studies are needed to determine the clinical efficacy of artificial hydration for terminally ill cancer patients.", "PMID": "16488346"}, {"title": "Effect of parenteral hydration therapy based on the Japanese national clinical guideline on quality of life, discomfort, and symptom intensity in patients with advanced cancer.", "abstract": "Although an evidence-based clinical guideline for parenteral hydration therapy was established in Japan, the efficacy of the guideline has not been assessed.\n\nOur purpose was to explore the effect of parenteral hydration therapy based on this clinical guideline on quality of life (QoL), discomfort, symptoms, and fluid retention signs in patients with advanced cancer.\n\nThis multicenter, prospective, observational study included 161 patients with advanced abdominal cancer who received guideline-based hydration therapy. We evaluated the longitudinal changes of the global QoL (Item 30 of European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-C30); the Discomfort Scale; the intensity of seven physical symptoms; and the severity of fluid retention signs. We also evaluated patient satisfaction and the feeling of benefit from hydration one week after the study commenced, and bronchial secretions, hyperactive delirium, communication capacity, and agitation 48 hours before a patient's death.\n\nThe global QoL, the Discomfort Scale, and the intensities of all physical symptoms, except for vomiting and drowsiness, were stable throughout the study period. More than 80% of patients maintained all fluid retention signs. Patient global satisfaction was 76.4 (0-100) and feeling of benefit was 5.43 (range 0-7).\n\nGuideline-based parenteral hydration therapy contributed to maintaining global QoL and provided satisfaction and a feeling of benefit without increasing discomfort and worsening symptoms and fluid retention signs in patients with advanced cancer.", "PMID": "22651946"}, {"title": "Parenteral hydration in patients with advanced cancer: a multicenter, double-blind, placebo-controlled randomized trial.", "abstract": "The vast majority of patients with cancer at the end of life receive parenteral hydration in hospitals and no hydration in hospice, with limited evidence supporting either practice. In this randomized controlled trial, we determined the effect of hydration on symptoms associated with dehydration, quality of life, and survival in patients with advanced cancer.\n\nWe randomly assigned 129 patients with cancer from six hospices to receive parenteral hydration (normal saline 1 L per day) or placebo (normal saline 100 mL per day) daily over 4 hours. The primary outcome was change in the sum of four dehydration symptoms (fatigue, myoclonus, sedation and hallucinations, 0 = best and 40 = worst possible) between day 4 and baseline. Secondary outcomes included Edmonton Symptom Assessment Scale (ESAS), Memorial Delirium Assessment Scale (MDAS), Nursing Delirium Screening Scale (NuDESC), Unified Myoclonus Rating Scale (UMRS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Dehydration Assessment Scale, creatinine, urea, and overall survival. Intention-to-treat analysis was conducted to examine the change by day 4 \u00b1 2 and day 7 \u00b1 2 between groups.\n\nThe hydration (n = 63) and placebo (n = 66) groups had similar baseline characteristics. We found no significant differences between the two groups for change in the sum of four dehydration symptoms (-3.3 v -2.8, P = .77), ESAS (all nonsignificant), MDAS (1 v 3.5, P = .084), NuDESC (0 v 0, P = .13), and UMRS (0 v 0, P = .54) by day 4. Results for day 7, including FACIT-F, were similar. Overall survival did not differ between the two groups (median, 21 v 15 days, P = .83).\n\nHydration at 1 L per day did not improve symptoms, quality of life, or survival compared with placebo.", "PMID": "23169523"}, {"title": "Hydration in advanced cancer: can bioelectrical impedance analysis improve the evidence base? A systematic review of the literature.", "abstract": "Decisions surrounding the administration of clinically assisted hydration to patients dying of cancer can be challenging because of the limited understanding of hydration in advanced cancer and a lack of evidence to guide health care professionals. Bioelectrical impedance analysis (BIA) has been used to assess hydration in various patient groupings, but evidence for its use in advanced cancer is limited.\n\nTo critically appraise existing methods of hydration status assessment in advanced cancer and review the potential for BIA to assess hydration in advanced cancer.\n\nSearches were carried out in four electronic databases. A hand search of selected peer-reviewed journals and conference abstracts also was conducted. Studies reporting (de)hydration assessment (physical examination, biochemical measures, symptom assessment, and BIA) in patients with advanced cancer were included.\n\nThe results highlight how clinical examination and biochemical tests are standard methods of assessing hydration, but limitations exist with these methods in advanced cancer. Furthermore, there is disagreement over the evidence for some commonly associated symptoms with dehydration in cancer. Although there are limitations with using BIA alone to assess hydration in advanced cancer, analysis of BIA raw measurements through the method of bioelectrical impedance vector analysis may have a role in this population.\n\nThe benefits and burdens of providing clinically assisted hydration to patients dying of cancer are unclear. Bioelectrical impedance vector analysis shows promise as a hydration assessment tool but requires further study in advanced cancer. Innovative methodologies for research are required to add to the evidence base and ultimately improve the care for the dying.", "PMID": "23200189"}], "labels": [{"PMID": "15800328", "label": "included"}, {"PMID": "23169523", "label": "included"}, {"PMID": "12411847", "label": "included"}, {"PMID": "29343167", "label": "included"}, {"PMID": "12353126", "label": "excluded"}, {"PMID": "15684225", "label": "excluded"}, {"PMID": "16488346", "label": "excluded"}, {"PMID": "22651946", "label": "excluded"}, {"PMID": "23169523", "label": "included"}, {"PMID": "23200189", "label": "excluded"}]}
{"metadata": {"review_pmid": "38088821"}, "inputs": {"background": "Otitis media with effusion (OME) is an accumulation of fluid in the middle ear cavity, common amongst young children. The fluid may cause hearing loss. Although most episodes of OME in children resolve spontaneously within a few months, when persistent it may lead to behavioural problems and a delay in expressive language skills. Management of OME includes watchful waiting, medical, surgical and other treatments, such as autoinflation. Oral or topical steroids are sometimes used to reduce inflammation in the middle ear.", "objectives": "To assess the effects (benefits and harms) of topical and oral steroids for OME in children.", "selection criteria": "We included randomised controlled trials (RCTs) and quasi-randomised trials in children aged 6 months to 12 years with unilateral or bilateral OME. We included studies that compared topical or oral steroids with either placebo or watchful waiting (no treatment)."}, "context": [{"title": "[The efficacy of combining antibiotic treatment with topical intranasal steroid administration in the treatment of chronic otitis media with effusion].", "abstract": "We evaluated the efficacy of antibiotic treatment with or without topical administration of intranasal budesonide in chronic otitis media with effusion (OME).\n\nThe study included 62 patients (age range 2 to 12 years) with chronic OME. The patients were randomly assigned to three groups, namely, antibiotic treatment (20 patients, ampicillin/sulbactam, 25 mg/kg/daily), antibiotic treatment combined with intranasal budesonide (20 patients, 200 mg/daily), and no treatment (22 patients). All patients and families were questioned regarding the presence of allergy, frequent upper respiratory tract infections, passive smoking, low birth weight, and pre-school nursery attendance. Otoscopic examination findings and the results of tympanograms obtained at the time of diagnosis, and at the end of four and eight weeks of treatment were evaluated.\n\nAt the end of eight weeks, significant improvement in tympanograms and otoscopic findings was obtained in both groups when compared with the control group (p<0.05). Resolution rates were 24% (9/37 ears), 39% (14/36), and 5% (2/40) with antibiotic, budesonide, and no treatment groups, respectively. Although budesonide treatment was associated with a higher rate of resolution of effusion compared to that of antibiotic alone, this did not reach significance (p>0.05).\n\nFurther studies with larger patient series are required to better evaluate the efficacy of antibiotic treatment and topical intranasal steroid administration in chronic OME.", "PMID": "12422079"}, {"title": "Systemic steroid for chronic otitis media with effusion in children.", "abstract": "To determine the efficacy of a short course of an adrenocorticosteroid agent (prednisolone) given with amoxicillin as compared with that of amoxicillin alone for the treatment of chronic middle ear effusion (MEE). The efficacy of 2 weeks versus 4 weeks of amoxicillin with and without steroid was also assessed.\n\nIn a double-blind, randomized trial, children who were 1 to 9 years of age and had MEE of at least 2 months' duration were assigned to 1 of 4 treatment arms: 1) steroid + amoxicillin for 14 days, then amoxicillin for 14 more days; 2) steroid + amoxicillin for 14 days, then placebo for amoxicillin for 14 more days; 3) placebo (for steroid) + amoxicillin for 14 days, then amoxicillin for 14 more days; or 4) placebo (for steroid) + amoxicillin for 14 days, then placebo for amoxicillin for 14 more days. Children were examined by otoscopy, tympanometry, and audiometry at entry and 2 and 4 weeks after entry; those without MEE at the 4-week visit returned monthly for up to 3 more visits or until recurrence of effusion. Serum immunoglobulin (Ig) G, IgM, IgA, and varicella titers were obtained at entry, and allergy skin testing was performed at the 4-week visit.\n\nA total of 144 children was entered; 135 children (94%) returned for the 2-week visit, and 132 (92%) were seen for the 4-week visit. At the 2-week visit, 33.3% of children in the steroid + amoxicillin group had no MEE compared with 16.7% in the placebo + amoxicillin group (95% confidence interval for the difference in proportions: 2.4%-31.0%). At the 4-week visit, the percentage of children with no MEE in the steroid-treated group was 32.8%, whereas that in the placebo group was 20.0% (95% confidence interval for the difference in proportions in the 2 groups: -2.0%-27.7%). Comparing change in middle ear status from the 2- to the 4-week visit, there were no significant differences in recurrence of MEE or additional clearance of MEE between those who were treated with amoxicillin for 2 weeks and those who were treated for 4 weeks. By the 4-month visit, 68.4% of children who were in the steroid group and had no MEE at the 4-week visit had recurrence of MEE as did 69.2% of such children in the placebo group. A total of 126 (87.5%) children underwent allergy skin testing. Of the 122 children who had a positive reaction to histamine, 51 (41.8%) had 1 or more positive reactions to the test allergens. There was no difference in response to treatment between those with positive allergy tests and those without.\n\nThere was a significant difference in the proportion of children who were effusion-free immediately after 14 days of treatment with steroid and amoxicillin compared with those who were treated only with amoxicillin for 14 days. Within 2 weeks of finishing treatment, there was no longer any significant difference between the 2 groups regardless of whether amoxicillin was continued or not. Therefore, we conclude that treatment with the dose and type of steroid used in this study should not be universally recommended for treatment of chronic otitis media with effusion, and treatment with amoxicillin, if used, should not continue beyond 14 days.", "PMID": "12456902"}, {"title": "The role of topical nasal steroids in the treatment of children with otitis media with effusion and/or adenoid hypertrophy.", "abstract": "Topical steroid treatment can be a powerful alternative to surgery in controlling adenoid hypertrophy and otitis media with effusion (OME).\n\nA prospective, controlled, randomized, clinical study in an academic tertiary care center. A total of 122 children (3-15-year-old) on the waiting list for an adenoidectomy and/or ventilation tube placement were enrolled into the study and control groups. The study group (67 patients with adenoid hypertrophy, 34 of them with otitis media with effusion) received intranasal mometasone furoate monohydrate 100 mcg/day, and the control group (55 patients with adenoid hypertrophy, 29 of them with otitis media with effusion) was followed up without any treatment. All patients were evaluated at 0 and 6 weeks. The assessment of each patient included history, a symptom questionnaire, a skin prick test, a tympanogram, if possible a pure tone audiogram, and otoscopic and endoscopic examinations. The size of adenoid tissue was graded as a percentage according to obliteration of the choanae. The adenoid/choana ratio (A/C) was recorded for each patient. Symptoms were scored as 0 (absent), 1 (intermittent/periodic), or 2 (continuous). The data were analyzed with the \"Statistical Package for the Social Sciences\" (SPSS 9.0) using the appropriate nonparametric tests for nominal and ordinal data.\n\nResolution of otitis media with effusion in the study group (42.2%) was significantly higher than that in the control group (14.5%) (p<0.001). Forty-five patients (67.2%) with adenoid hypertrophy in the study group showed a significant decrease in adenoid size according to the endoscopic evaluation compared to the control group (p<0.001). A significant improvement in obstructive symptoms was seen in the study group (p<0.001). The endoscopically measured adenoid/choana ratio and degree of obstructive symptoms showed a significant correlation (r=0.838 p<0.001, r=0.879 p<0.001, r=0.838 p<0.001, r=0.879 p<0.001). The adenoid/choana ratio improved significantly in atopic patients in the study group (p<0.05), whereas in atopic patients in the control group there was no change (p=0.221).\n\nNasal mometasone furoate monohydrate treatment can significantly reduce adenoid hypertrophy and eliminate obstructive symptoms. It is a useful alternative to surgery, at least in the short term, for otitis media with effusion.", "PMID": "16169093"}, {"title": "The role of topical nasal steroids in the treatment of children with otitis media with effusion and/or adenoid hypertrophy.", "abstract": "Topical steroid treatment can be a powerful alternative to surgery in controlling adenoid hypertrophy and otitis media with effusion (OME).\n\nA prospective, controlled, randomized, clinical study in an academic tertiary care center. A total of 122 children (3-15-year-old) on the waiting list for an adenoidectomy and/or ventilation tube placement were enrolled into the study and control groups. The study group (67 patients with adenoid hypertrophy, 34 of them with otitis media with effusion) received intranasal mometasone furoate monohydrate 100 mcg/day, and the control group (55 patients with adenoid hypertrophy, 29 of them with otitis media with effusion) was followed up without any treatment. All patients were evaluated at 0 and 6 weeks. The assessment of each patient included history, a symptom questionnaire, a skin prick test, a tympanogram, if possible a pure tone audiogram, and otoscopic and endoscopic examinations. The size of adenoid tissue was graded as a percentage according to obliteration of the choanae. The adenoid/choana ratio (A/C) was recorded for each patient. Symptoms were scored as 0 (absent), 1 (intermittent/periodic), or 2 (continuous). The data were analyzed with the \"Statistical Package for the Social Sciences\" (SPSS 9.0) using the appropriate nonparametric tests for nominal and ordinal data.\n\nResolution of otitis media with effusion in the study group (42.2%) was significantly higher than that in the control group (14.5%) (p<0.001). Forty-five patients (67.2%) with adenoid hypertrophy in the study group showed a significant decrease in adenoid size according to the endoscopic evaluation compared to the control group (p<0.001). A significant improvement in obstructive symptoms was seen in the study group (p<0.001). The endoscopically measured adenoid/choana ratio and degree of obstructive symptoms showed a significant correlation (r=0.838 p<0.001, r=0.879 p<0.001, r=0.838 p<0.001, r=0.879 p<0.001). The adenoid/choana ratio improved significantly in atopic patients in the study group (p<0.05), whereas in atopic patients in the control group there was no change (p=0.221).\n\nNasal mometasone furoate monohydrate treatment can significantly reduce adenoid hypertrophy and eliminate obstructive symptoms. It is a useful alternative to surgery, at least in the short term, for otitis media with effusion.", "PMID": "16169093"}, {"title": "Management for the children with otitis media with effusion in the tertiary hospital.", "abstract": "Recently, new evidence-based recommendations have been introduced for diagnosing and managing otitis media with effusion (OME) in children. However, there are some difficulties to follow the general guidelines in the tertiary hospitals. The purpose is to evaluate the efficiency of antibiotics or antihistamines for treatment of children with OME in the tertiary hospital with a randomized prospective clinical study.\n\nEighty-four children with OME who had been diagnosed in the tertiary hospital were randomized to receive 5 different medications for 2 weeks. We prescribed antibiotics (amoxicillin-clavulanate syrup) in Group I (n=16), antibiotics/steroids (prednisolone) in Group II (n=18), antibiotics/antihistamines (ebastine) in Group III (n=15), antibiotics/steroids/antihistamines in Group IV (n=17), and mucolytics (ivy leaf extract) in Group V (n=17) for control. We followed-up children every 2 weeks and evaluated the state of OME at 3 months.\n\nThirty six (42.9%) of 84 children were resolved within average 6.9 weeks after the treatments. Thirty-six (42.9%) were treated with ventilation tube insertion and 12 patients (14.3%) were observed. There was no difference in the resolution rates of OME among the five different protocols (P>0.05). There was no difference in the resolution rates among groups who used steroids, antihistamines, steroids and antihistamines, or other medications to manage 42 children with allergies (P>0.05).\n\nIn the tertiary hospital, the cure rate of children with OME was not as high as well-known, and antibiotics or anti-allergic medications were not more effective than control. We may, therefore, need any other guidelines which are different from the previous evidence-based recommendations, including early operation in the tertiary hospitals.", "PMID": "19434268"}, {"title": "A double-blind randomised placebo-controlled trial of topical intranasal corticosteroids in 4- to 11-year-old children with persistent bilateral otitis media with effusion in primary care.", "abstract": "To determine the clinical effectiveness and cost-effectiveness of topical mometasone in children with bilateral otitis media with effusion (OME).\n\nA double-blind randomised placebo-controlled trial with an intention to treat analysis; the 10.6% of patients lost to follow-up at 1 month were censored in the analysis.\n\n76 Medical Research Council General Practice Research Framework practices throughout the UK between 2004 and 2007.\n\nA sample of 217 children aged 4-11 years was selected from those presenting to their GP with one or more episodes of otitis media or ear-related problems in the previous 12 months whom the research nurse confirmed had bilateral glue ear using microtympanometry (B B or B C2 types using a modified Jerger classification) at randomisation.\n\nMometasone 50 micrograms in each nostril or placebo spray once daily for 3 months.\n\nThe primary outcome was the proportions of children cleared of OME assessed by tympanometry at 1 month. Secondary outcomes included clearance at 3 months and 9 months; adverse events; OM8-30 scores (a functional health status responsive disease-specific measure); hearing loss; days with otalgia; cost-effectiveness; and health utilities.\n\nOf the topical steroid group, 40.6% (39/96) demonstrated tympanometric clearance (C1 or A type) in one or both ears at 1 month, compared with 44.9% (44/98) of the placebo group. The absolute risk reduction at 1 month was -4.3% (95% CI -18.05% to 9.26%); the odds ratio (OR) was 0.84 (95% CI 0.48 to 1.48). Four covariates were pre-specified for inclusion in logistic regression analysis: age as a continuous variable (p = 0.94), season (p = 0.70), atopy (p = 0.61) and clinical severity (p = 0.006). The adjusted OR (AOR) at 1 month for the main outcome was 0.93 (95% CI 0.50 to 1.75). Secondary analysis at 3 months showed 58.1% of the steroid group had resolved and 52.3% of the placebo group, AOR 1.45 (95% CI 0.74 to 2.84). At 9 months 55.6% of the treated group remained clear in at least one ear and 65.3% of the placebo group, AOR 0.82 (95% CI 0.39 to 1.75). Adverse events (although relatively minor) occurred in 7-22% of children and included nasal stinging, epistaxis, dry throat and cough. The OM8-30 scores (p = 0.55) reported hearing difficulty (p = 0.08), and days with otalgia (p = 0.46) were not significantly different between groups at 3 months. The economic evaluation found the active treatment arm to be dominated by placebo, accruing slightly (but not significantly) higher costs and fewer quality-adjusted life-years (QALYs), with a 24.2% probability that topical steroids are a cost-effective use of NHS resources at a ceiling ratio of 20,000 pounds per QALY gained.\n\nUse of topical intranasal corticosteroids is very unlikely to be a clinically effective treatment for OME (glue ear) in the primary care setting.\n\nCurrent Controlled Trials ISRCTN38988331.", "PMID": "19671372"}, {"title": "Topical intranasal corticosteroids in 4-11 year old children with persistent bilateral otitis media with effusion in primary care: double blind randomised placebo controlled trial.", "abstract": "To determine the clinical effectiveness of topical intranasal corticosteroids in children with bilateral otitis media with effusion.\n\nDouble blind randomised placebo controlled trial.\n\n76 Medical Research Council General Practice Research Framework practices throughout the United Kingdom, between 2004 and 2007.\n\n217 children aged 4-11 years who had at least one practice recorded episode of otitis media or a related ear problem in the previous 12 months, and with bilateral otitis media with effusion confirmed by a research nurse using otoscopy plus micro-tympanometry (B/B or B/C2, modified Jerger types).\n\nMometasone furoate 50 microg or placebo spray given once daily into each nostril for three months.\n\nProportions of children cured of bilateral otitis media with effusion assessed with tympanometry (C1 or A type) at one month (primary end point), three months, and nine months; adverse events; three month diary symptoms. Results 41% (39/96) of the topical steroid group and 45% (44/98) of the placebo group were cured in one or both ears at one month (difference favouring placebo 4.3% (95% confidence interval -9.3% to 18.1%). Poisson regression was done with adjustment for four pre-specified covariates (clinical severity, P=0.003; atopy, P=0.67; age, P=0.92; season, P=0.71). The adjusted relative risk at one month was 0.97 (95% confidence interval 0.74 to 1.26). At three months, 58% of the topical steroid group and 52% of the placebo group were cured (relative risk 1.23, 0.84 to 1.80). Diary symptoms did not differ between the two groups, and no significant harms were reported.\n\nTopical steroids are unlikely to be an effective treatment for otitis media with effusion in general practice. High rates of natural resolution occurred by 1-3 months.\n\nCurrent Controlled Trials ISRCTN38988331; National Research Register NO575123823; MREC 03/11/073.", "PMID": "20015903"}, {"title": "Hearing thresholds and tympanic membrane sequelae in children managed medically or surgically for otitis media with effusion.", "abstract": "To determine the long-term effects of ventilation tube insertion on hearing thresholds and tympanic membrane pathologic abnormalities in children with otitis media with effusion.\n\nProspective cohort study.\n\nTertiary care children's hospital, otorhinolaryngology and audiology service.\n\nPatients aged 8 to 16 years who participated in a randomized controlled trial of medical vs surgical (ventilation tube [VT]) treatment for recurrent otitis media with effusion at ages 2.5 to 7 years.\n\nHearing thresholds and tympanic membrane sequelae.\n\nOne hundred thirteen of 125 children who had participated in the trial underwent blinded audiometric, tympanometric, otomicroscopic, and parental questionnaire evaluation 6 to 10 years following the trial. Thirty of 57 [corrected] medical subjects received ventilation tubes and 18 of 56 [corrected] VT subjects received more than 1 set of tubes. To evaluate sequelae risk associated with ventilation tubes independent of disease severity, we compared 27 medical subjects who never received ventilation tubes and 38 subjects randomized to VT who only received 1 set of tubes.\n\nTympanic membrane pathologic abnormalities were present in 81% of VT subjects and 19% of medical subjects (relative risk, 4.4; 95% confidence interval, 2.2-9.9). Hearing thresholds were 2.1 to 8.1 dB higher in subjects treated with tubes (P = .005).\n\nIn children who were candidates for ventilation tube insertion randomly assigned to receive medical or VT treatment for otitis media with effusion, elevated hearing thresholds and tympanic membrane pathologic abnormalities were more common in VT subjects 6 to 10 years after insertion.", "PMID": "16330739"}, {"title": "Resolution of otitis media with effusion with the use of a stepped treatment regimen of trimethoprim-sulfamethoxazole and prednisone.", "abstract": "This double blind, placebo-controlled trial was designed to determine whether intervention with a stepped regimen of trimethoprim-sulfamethoxazole (TMP-SMX) and prednisone would prevent high risk children from developing chronic otitis media with effusion (OME) and recurrent acute otitis media. Forty-two children were enrolled, assigned to treatment with active drug or placebo and then examined at 2-week intervals. They received TMP-SMX (or placebo) during the first 2 weeks, TMP-SMX and prednisone (or placebo) during Weeks 3 and 4 for persistent OME and TMP-SMX (or placebo) for Weeks 5 and 6 if OME was still unresolved. After treatment 48% of active drug and 14% of placebo subjects resolved OME bilaterally (P less than 0.05). Active drug subjects also had fewer acute otitis media episodes than placebo subjects while receiving study treatment (P less than 0.01). Although this treatment regimen produced short term OME resolution, long term benefits were not demonstrated.", "PMID": "1876465"}, {"title": "Topical intranasal corticosteroids for otitis media with effusion in primary care.", "abstract": "", "PMID": "20056694"}], "labels": [{"PMID": "12422079", "label": "included"}, {"PMID": "12456902", "label": "included"}, {"PMID": "16169093", "label": "included"}, {"PMID": "16169093", "label": "included"}, {"PMID": "19434268", "label": "included"}, {"PMID": "19671372", "label": "included"}, {"PMID": "20015903", "label": "included"}, {"PMID": "16330739", "label": "excluded"}, {"PMID": "1876465", "label": "excluded"}, {"PMID": "20056694", "label": "excluded"}]}
{"metadata": {"review_pmid": "38084817"}, "inputs": {"background": "Substance use is a global issue, with around 30 to 35 million individuals estimated to have a substance-use disorder. Motivational interviewing (MI) is a client-centred method that aims to strengthen a person's motivation and commitment to a specific goal by exploring their reasons for change and resolving ambivalence, in an atmosphere of acceptance and compassion. This review updates the 2011 version by Smedslund and colleagues.", "objectives": "To assess the effectiveness of motivational interviewing for substance use on the extent of substance use, readiness to change, and retention in treatment.", "selection criteria": "We included randomised controlled trials with individuals using drugs, alcohol, or both. Interventions were MI or motivational enhancement therapy (MET), delivered individually and face to face. Eligible control interventions were no intervention, treatment as usual, assessment and feedback, or other active intervention."}, "context": [{"title": "Maritally distressed women with alcohol problems: the impact of a short-term alcohol-focused intervention on drinking behaviour and marital satisfaction.", "abstract": "To evaluate the efficacy of a short-term alcohol-focused intervention for maritally distressed women, and to explore changes in relationship functioning.\n\nParticipants were assigned randomly to an alcohol-focused treatment or to a waiting-list control group. The waiting-list control group began the intervention at 1-month follow-up.\n\nThe intervention took place at a research and training centre offering outpatient psychology services to the community.\n\nA sample of 32 women with alcohol and marital problems were recruited through the media. Participants reported protracted alcohol problems, moderate to severe impact of alcohol on social and occupational functioning, and moderate to severe marital distress.\n\nMeasures of average alcohol consumption, marital distress, relational efficacy and depression were administered at pre- and post-therapy, and at 1, 6 and 12-month follow-up.\n\nThe intervention involved six 1-hour sessions, consisting of clinical assessment, motivational interviewing, cognitive-behavioural strategies and relapse prevention.\n\nAt 1-month follow-up, the intervention was associated with statistically significant improvements in alcohol consumption, marital satisfaction, relational efficacy and depression, and these effects were sustained at 12-month follow-up.\n\nAt 1-month follow-up the intervention was associated with decreased alcohol consumption and depression, and increased marital satisfaction and relational efficacy, with evidence of maintained effects at 12-month follow-up. However, it is unlikely that reduced problem drinking and improved confidence in resolving problems were the only factors producing low marital quality in these couples. Further research is needed to identify those individuals who might benefit from marital interventions.", "PMID": "11070529"}, {"title": "Clinical profile of participants in a brief intervention program for cannabis use disorder.", "abstract": "The increasing demand for cannabis dependence treatment has led to the identification of significant gaps in the knowledge of effective interventions. A randomized controlled trial of brief cognitive-behavioral interventions (CBT) for cannabis dependence was undertaken to address this issue. A total of 229 participants were assessed and allocated to either a 6-session CBT program, a single-session brief intervention, or a delayed-treatment control group. This paper demonstrates that individuals with cannabis use disorder will present for a brief intervention program. While they report similar patterns of cannabis use to nontreatment samples, they report a range of serious health and psychosocial consequences. While they appear relatively socially stable, they typically demonstrated severe cannabis dependence and significantly elevated levels of psychological distress, with the most commonly cited reason for cannabis use being stress relief. There were clinically relevant gender differences among the sample. This study provides more evidence of the demand for, and nature of issues relevant to, interventions for cannabis use disorders, and supports the need for further research into how best to assist individuals with these disorders.", "PMID": "11239727"}, {"title": "A randomized controlled trial of motivational enhancement therapy (MET) for mild to moderate alcohol dependence.", "abstract": "This study was designed to conduct a randomized controlled trial of motivational enhancement therapy (MET) with two control conditions: nondirective reflective listening (NDRL) and no further counseling (NFC); and to conduct this study in a sample of patients with a primary diagnosis of mild to moderate alcohol dependence, in a \"real-life\" clinical setting.\n\nPatients with mild to moderate alcohol dependence were recruited, assessed and treated at the Community Alcohol and Drug Service of Christchurch, New Zealand. All patients received a feedback/education session before randomization to either four sessions of MET, four sessions of NDRL, or NFC. Outcome data on 122 subjects (57.4% men) were obtained 6 months following the end of treatment, by an interviewer who was blind to the treatment condition. The primary drinking outcome was unequivocal heavy drinking, defined as drinking 10 or more standard drinks six or more times in the follow-up period. Global assessment scale (GAS) measured general personal/social functioning.\n\nOf patients treated with MET, 42.9% showed unequivocal heavy drinking compared with 62.5% of the NDRL and 65.0% of the NFC groups (p = .04). No significant differences were found for GAS score according to treatment condition.\n\nIn patients with mild to moderate alcohol dependence, MET is more effective for reducing unequivocal heavy drinking than either a feedback/education session alone or four sessions of NDRL. MET can be considered an effective \"value added\" counseling intervention in a real-life clinical setting. In patients with mild to moderate alcohol dependence, nondirective reflective listening provides no additional advantage over a feedback/education session alone.", "PMID": "11414349"}, {"title": "Findings of a pilot study of motivational interviewing with pregnant drinkers.", "abstract": "Cost-effective interventions are needed for counseling pregnant drinkers, in order to reduce risk of fetal alcohol effects.\n\n42 pregnant women who reported alcohol consumption participated in this pilot study of motivational interviewing. Following a comprehensive alcohol use assessment, the participants were randomly assigned to receive either written information about the risks related to drinking during pregnancy or a one-hour motivational interview. The motivational interview was an empathic, client-centered, but directive session focusing on the health of the participants' unborn babies.\n\nAt the end of a 2-month follow-up period, the 34 women (81%) who remained in the study showed a significant reduction in alcohol consumption and peak intoxication levels. Women who had reported the highest blood alcohol concentration (BAC) levels during early pregnancy showed a significantly greater reduction in their estimated BACs at follow-up (during later pregnancy) if assigned to the treatment rather than the control condition.\n\nMotivational interviewing shows promise as a specific intervention for initiating a reduction in drinking among pregnant women who are at greatest risk. Simpler assessment and advice may suffice for women with lower initial consumption levels.", "PMID": "10091968"}, {"title": "Motivational interviewing and treatment adherence among psychiatric and dually diagnosed patients.", "abstract": "The effect of motivational interviewing on outpatient treatment adherence among psychiatric and dually diagnosed inpatients was investigated. Subjects were 121 psychiatric inpatients, 93 (77%) of whom had concomitant substance abuse/dependence disorders, who were randomly assigned to: a) standard treatment (ST), including pharmacotherapy, individual and group psychotherapy, activities therapy, milieu treatment, and discharge planning; or b) ST plus motivational interviewing (ST+MI), which involved 15 minutes of feedback on the results of a motivational assessment early in the hospitalization, and a 1-hour motivational interview just before discharge. Interviewers utilized motivational techniques described in Miller and Rollnick (1991), such as reflective listening, discussion of treatment obstacles, and elicitation of motivational statements. Results indicated that the proportion of patients who attended their first outpatient appointment was significantly higher for the ST+MI group (47%) than for the ST group (21%; chi2 = 8.87, df = 1, p<.01) overall, and for dually diagnosed patients (42% for ST+MI vs. 16% for ST only; chi2 = 7.68, df = 1, p<.01). Therefore, brief motivational interventions show promise in improving outpatient treatment adherence among psychiatric and dually diagnosed patients.", "PMID": "10535657"}, {"title": "Brief intervention for harm reduction with alcohol-positive older adolescents in a hospital emergency department.", "abstract": "This study evaluated the use of a brief motivational interview (MI) to reduce alcohol-related consequences and use among adolescents treated in an emergency room (ER) following an alcohol-related event. Patients aged 18 to 19 years (N = 94) were randomly assigned to receive either MI or standard care (SC). Assessment and intervention were conducted in the ER during or after the patient's treatment. Follow-up assessments showed that patients who received the MI had a significantly lower incidence of drinking and driving, traffic violations, alcohol-related injuries, and alcohol-related problems than patients who received SC. Both conditions showed reduced alcohol consumption. The harm-reduction focus of the MI was evident in that MI reduced negative outcomes related to drinking, beyond what was produced by the precipitating event plus SC alone.", "PMID": "10596521"}, {"title": "Motivation to change substance use among offenders of domestic violence.", "abstract": "Substance use alone leads to increased rates of violence, reduction in adherence to treatment regimes, and other negative psychiatric sequelae. Given the high rates of co-occurring substance use and family violence-related problems, substance use was assessed among offenders of domestic violence who were mandated by court to attend anger management classes. Rates of substance dependence diagnoses ranged from 33 to 50%, while rates of substance abuse diagnoses ranged from 60 to 75%. This study evaluated the effectiveness of a motivational enhancement intervention on readiness to change substance use. Two anger management groups were targeted to assess substance use, violence, and motivation to change substance use behaviors. One group was randomly chosen to partake in a motivational enhancement intervention session. The comparison group was offered standard anger management classes. Forty-one clients were evaluated for substance abuse and dependence diagnosis using criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. A brief motivation to change survey, adapted from the Readiness to Change subscale of the Stages of Change Readiness and Treatment Eagerness Scale was administered pre- and postsession. Results indicate that a motivational enhancement intervention is feasible and effective in increasing readiness to change substance use among domestic violence offenders. The results illustrate the importance of assessing and treating substance use among offenders of domestic violence, as this may be an important indicator for higher dropout rates and reoffenses among this population.", "PMID": "10867294"}, {"title": "Motivational interviewing with psychiatrically ill substance abusing patients.", "abstract": "This pilot study reports the relative efficacy of a one-session preadmission motivational interview (n = 13) compared to a standard preadmission interview (n = 10) for psychiatrically ill substance abusing patients in a partial hospital program.", "PMID": "10914297"}, {"title": "Effects of a brief motivational intervention with college student drinkers.", "abstract": "This study consisted of a randomized controlled trial of a 1-session motivational intervention for college student binge drinkers. Sixty students who reported binge drinking 2 or more times in the past 30 days were randomly assigned to either a no-treatment control or a brief intervention group. The intervention provided students with feedback regarding personal consumption, perceived drinking norms, alcohol-related problems, situations associated with heavy drinking, and alcohol expectancies. At 6-week follow-up, the brief intervention group exhibited significant reductions on number of drinks consumed per week, number of times drinking alcohol in the past month, and frequency of binge drinking in the past month. Estimates of typical student drinking mediated these reductions. This study replicates earlier research on the efficacy of brief interventions with college students and extends previous work regarding potential mechanisms of change.", "PMID": "10965648"}, {"title": "Comparison of extended versus brief treatments for marijuana use.", "abstract": "Adult marijuana users (N = 291) seeking treatment were randomly assigned to an extended 14-session cognitive-behavioral group treatment (relapse prevention support group; RPSG), a brief 2-session individual treatment using motivational interviewing (individualized assessment and intervention; IAI), or a 4-month delayed treatment control (DTC) condition. Results indicated that marijuana use, dependence symptoms, and negative consequences were reduced significantly in relation to pretreatment levels at 1-, 4-, 7-, 13-, and 16-month follow-ups. Participants in the RPSG and IAI treatments showed significantly and substantially greater improvement than DTC participants at the 4-month follow-up. There were no significant differences between RPSG and IAI outcomes at any follow-up. The relative efficacy of brief versus extended interventions for chronic marijuana-using adults is discussed.", "PMID": "11068976"}], "labels": [{"PMID": "11070529", "label": "included"}, {"PMID": "11239727", "label": "included"}, {"PMID": "11414349", "label": "included"}, {"PMID": "10091968", "label": "excluded"}, {"PMID": "10535657", "label": "excluded"}, {"PMID": "10596521", "label": "excluded"}, {"PMID": "10867294", "label": "excluded"}, {"PMID": "10914297", "label": "excluded"}, {"PMID": "10965648", "label": "excluded"}, {"PMID": "11068976", "label": "excluded"}]}
{"metadata": {"review_pmid": "38084761"}, "inputs": {"background": "Pompe disease is caused by a deficiency of the enzyme acid alpha-glucosidase (GAA). People with infantile-onset disease have either a complete or a near-complete enzyme deficiency; people with late-onset Pompe disease (LOPD) retain some residual enzyme activity. GAA deficiency is treated with an intravenous infusion of recombinant human acid alglucosidase alfa, an enzyme replacement therapy (ERT). Alglucosidase alfa and avalglucosidase alfa are approved treatments, but cipaglucosidase alfa with miglustat is not yet approved.", "objectives": "To assess the effects of enzyme replacement therapies in people with late-onset Pompe disease.", "selection criteria": "We included randomised controlled trials (RCTs) of ERT in people with LOPD of any age."}, "context": [{"title": "Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial.", "abstract": "Pompe disease is a rare, progressive neuromuscular disorder caused by deficiency of acid \u03b1-glucosidase (GAA) and accumulation of lysosomal glycogen. We assessed the safety and efficacy of avalglucosidase alfa, a recombinant human GAA enzyme replacement therapy specifically designed for enhanced mannose-6-phosphate-receptor targeting and enzyme uptake aimed at increased glycogen clearance, compared with the current approved standard of care, alglucosidase alfa, in patients with late-onset Pompe disease.\n\nWe did a randomised, double-blind, phase 3 trial at 55 sites in 20 countries. We enrolled individuals (aged \u22653 years) with enzymatically confirmed late-onset Pompe disease who had never received treatment. We used a centralised treatment allocation system to randomly allocate participants to either avalglucosidase alfa or alglucosidase alfa. Participants and investigators were unaware of their treatment allocation. The primary outcome measure was change from baseline to week 49 in upright forced vital capacity percent (FVC%) predicted. We used a hierarchical fixed sequential testing strategy, whereby non-inferiority of avalglucosidase alfa compared with alglucosidase alfa was assessed first, with a non-inferiority margin of 1\u00b71. If non-inferiority was seen, then superiority was tested with a 5% significance level. The key secondary objective was effect on functional endurance, measured by the 6-minute walk test (6MWT). Safety was assessed, including treatment-emergent adverse events and infusion-associated reactions. The modified intent-to-treat population was the primary analysis population for all efficacy analyses. The safety population was the analysis population for safety analyses. This trial is registered with ClinicalTrials.gov, NCT02782741. We report results of the 49-week primary analysis period.\n\nBetween Nov 2, 2016, and March 29, 2019, 100 participants were randomly allocated avalglucosidase alfa (n=51) or alglucosidase alfa (n=49). Treatment with avalglucosidase alfa resulted in a least-squares mean improvement in upright FVC% predicted of 2\u00b789% (SE 0\u00b788) compared with 0\u00b746% (0\u00b793) with alglucosidase alfa at week 49 (difference 2\u00b743% [95% CI -0\u00b713 to 4\u00b799]). Non-inferiority was shown because the lower bound of the 95% CI for the difference far exceeded the predefined non-inferiority margin but did not exclude 0 (p=0\u00b70074). Superiority was not reached (p=0\u00b7063), so formal testing was stopped, as per the testing hierarchy. Improvements were also seen in the 6MWT with avalglucosidase alfa compared with alglucosidase alfa, with greater increases in distance covered (difference 30\u00b701 m [95% CI 1\u00b733 to 58\u00b769]) and percent predicted (4\u00b771% [0\u00b725 to 9\u00b717]). Treatment-emergent adverse events potentially related to treatment were reported in 23 (45%) of 51 participants in the avalglucosidase alfa group and in 24 (49%) of 49 in the alglucosidase alfa group, and infusion-associated reactions were reported in 13 (26%) participants in the avalglucosidase alfa group and 16 (33%) in the alglucosidase alfa group. Of the five trial withdrawals, all in the alglucosidase alfa group, four were due to adverse events, including two infusion-associated reactions. Serious treatment-emergent adverse events were reported in eight (16%) participants who received avalglucosidase alfa and in 12 (25%) who received alglucosidase alfa. One participant treated with alglucosidase alfa died because of acute myocardial infarction determined to be unrelated to treatment. Antidrug antibody responses were similar in both groups. High and persistent titres (\u226512\u2008800) and neutralising antibodies were more common with alglucosidase alfa (in 16 [33%] participants) than with avalglucosidase alfa (ten [20%]).\n\nWe consider that this study provides evidence of clinically meaningful improvement with avalglucosidase alfa therapy over alglucosidase alfa in respiratory function, ambulation, and functional endurance, with no new safety signals reported. An open-label extended-treatment period is ongoing to confirm the long-term safety and efficacy of avalglucosidase alfa, with the aim for this therapy to become the new standard treatment in late-onset Pompe disease.\n\nSanofi Genzyme.", "PMID": "34800399"}, {"title": "Correction to Lancet Neurol 2021; 20: 1012-16.", "abstract": "", "PMID": "35305341"}, {"title": "Correction of Biochemical Abnormalities and Improved Muscle Function in a Phase I/II Clinical Trial of Clenbuterol in Pompe Disease.", "abstract": "This 52-week, phase I/II double-blind, randomized, placebo-controlled study investigated the novel use of clenbuterol in late-onset Pompe disease (LOPD) stably treated with ERT. Eleven of thirteen participants completed the study. No serious adverse events were related to clenbuterol, and transient minor adverse events included mild elevations of creatine kinase, muscle spasms, and tremors. At week 52, the 6-min walk test distance increased by a mean of 16\u00a0m (p\u00a0= 0.08), or a mean of 3% of predicted performance (p\u00a0= 0.03), and the maximum inspiratory pressure increased 8% (p\u00a0= 0.003) for the clenbuterol group. The quick motor function test score improved by a mean of seven points (p\u00a0= 0.007); and the gait, stairs, gower, chair test improved by a mean of two points (p\u00a0= 0.004). Clenbuterol decreased glycogen content in the vastus lateralis by 50% at week 52. Transcriptome analysis revealed more normal muscle gene expression for 38 of 44 genes related to Pompe disease following clenbuterol. The placebo group demonstrated no significant changes over the course of the study. This study provides initial evidence for safety and efficacy of adjunctive clenbuterol in patients with LOPD (NCT01942590).", "PMID": "30025991"}, {"title": "Improved muscle function in a phase I/II clinical trial of albuterol in Pompe disease.", "abstract": "This 24-week, Phase I/II, double-blind, randomized, placebo-controlled study investigated the safety and efficacy of extended-release albuterol in late-onset Pompe disease stably treated with enzyme replacement therapy at the standard dose for 4.9 (1.0-9.4) years and with no contraindications to intake of albuterol. Twelve of 13 participants completed the study. No serious adverse events were related to albuterol, and transient minor drug-related adverse events included muscle spasms and tremors. For the albuterol group, forced vital capacity in the supine position increased by 10% (p\u00a0<\u00a0.005), and forced expiratory volume in one second increased by 8% (p\u00a0<\u00a0.05); the six-minute walk test increased 25\u00a0m (p\u00a0<\u00a0.05; excluding one participant unable to complete muscle function testing); the Gross Motor Function Measure increased by 8% (p\u00a0<\u00a0.005) with the greatest increases in the Standing (18%; p\u00a0<\u00a0.05) and Walking, Running, and Jumping (11%; p\u00a0<\u00a0.005) subtests. No significant improvements would be expected in patients with late-onset Pompe disease who were stably treated with enzyme replacement therapy. The placebo group demonstrated no significant increases in performance on any measure. These data support a potential benefit of extended-release albuterol as adjunctive therapy in carefully selected patients with late-onset Pompe disease based on ability to take albuterol on enzyme replacement therapy (NCT01885936).", "PMID": "31839530"}, {"title": "Safety and efficacy of cipaglucosidase alfa plus miglustat versus alglucosidase alfa plus placebo in late-onset Pompe disease (PROPEL): an international, randomised, double-blind, parallel-group, phase 3 trial.", "abstract": "Pompe disease is a rare disorder characterised by progressive loss of muscle and respiratory function due to acid \u03b1-glucosidase deficiency. Enzyme replacement therapy with recombinant human acid \u03b1-glucosidase, alglucosidase alfa, is the first approved treatment for the disease, but some patients do not respond, and many do not show a sustained benefit. We aimed to assess the safety and efficacy of an investigational two-component therapy (cipaglucosidase alfa, a novel recombinant human acid \u03b1-glucosidase, plus miglustat, an enzyme stabiliser) for late-onset Pompe disease.\n\nWe did a randomised, double-blind, parallel-group, phase 3 trial at 62 neuromuscular and metabolic medical centres in 24 countries in the Americas, Asia-Pacific, and Europe. Eligible participants were aged 18 years or older with late-onset Pompe disease, and had either been receiving alglucosidase alfa for at least 2 years or were enzyme replacement therapy-naive. Participants were randomly assigned (2:1) using interactive response technology software, stratified by 6-min walk distance and previous enzyme replacement therapy status, to intravenous cipaglucosidase alfa (20 mg/kg) plus oral miglustat or to intravenous alglucosidase alfa (20 mg/kg) plus oral placebo once every 2 weeks for 52 weeks. Patients, investigators, and outcome assessors were masked to treatment assignment. The primary endpoint was change from baseline to week 52 in 6-min walk distance, assessed using a mixed-effect model for repeated measures analysis for comparison of superiority in the intention-to-treat population (all patients who received at least one dose of study drug). This study is now complete and is registered with ClinicalTrials.gov, NCT03729362.\n\nBetween Dec 3, 2018, and Nov 26, 2019, 130 patients were screened for eligibility and 125 were enrolled and randomly assigned to receive cipaglucosidase alfa plus miglustat (n=85) or alglucosidase alfa plus placebo (n=40). Two patients in the alglucosidase alfa plus placebo group did not receive any dose due to absence of genotype confirmation of late-onset Pompe disease and were excluded from analysis. Six patients discontinued (one in the alglucosidase alfa plus placebo group, five in the cipaglucosidase alfa plus miglustat group), and 117 completed the study. At week 52, mean change from baseline in 6-min walk distance was 20\u00b78 m (SE 4\u00b76) in the cipaglucosidase alfa plus miglustat group versus 7\u00b72 m (6\u00b76) in the alglucosidase alfa plus placebo group using last observation carried forward (between-group difference 13\u00b76 m [95% CI -2\u00b78 to 29\u00b79]). 118 (96%) of 123 patients experienced at least one treatment-emergent adverse event during the study; the incidence was similar between the cipaglucosidase alfa plus miglustat group (n=81 [95%]) and the alglucosidase alfa plus placebo group (n=37 [97%]). The most frequently reported treatment-emergent adverse events were fall (25 [29%] patients in the cipaglucosidase alfa plus miglustat group vs 15 [39%] in the alglucosidase alfa plus placebo group), headache (20 [24%] vs 9 [24%]), nasopharyngitis (19 [22%] vs 3 [8%]), myalgia (14 [16%] vs 5 [13%]), and arthralgia (13 [15%]) vs 5 [13%]). 12 serious adverse events occurred in eight patients in the cipaglucosidase alfa plus miglustat group; only one event (anaphylaxis) was deemed related to study drug. One serious adverse event (stroke) occurred in the alglucosidase alfa plus placebo group, which was deemed unrelated to study drug. There were no deaths.\n\nCipaglucosidase alfa plus miglustat did not achieve statistical superiority to alglucosidase alfa plus placebo for improving 6-min walk distance in our overall population of patients with late-onset Pompe disease. Further studies should investigate the longer-term safety and efficacy of cipaglucosidase alfa plus miglustat and whether this investigational two-component therapy might provide benefits, particularly in respiratory function and in patients who have been receiving enzyme replacement therapy for more than 2 years, as suggested by our secondary and subgroup analyses.\n\nAmicus Therapeutics.", "PMID": "34800400"}, {"title": "Cardiovascular abnormalities in late-onset Pompe disease and response to enzyme replacement therapy.", "abstract": "We evaluated the prevalence of cardiovascular abnormalities and the efficacy and safety of enzyme replacement therapy in patients with late-onset Pompe disease.\n\nNinety patients were randomized 2:1 to enzyme replacement therapy or placebo in a double-blinded protocol. Electrocardiograms and echocardiograms were obtained at baseline and scheduled intervals during the 78-week study period. Baseline cardiovascular abnormalities, and efficacy and safety of enzyme replacement therapy were described. Three pediatric patients were excluded.\n\nEighty-seven patients were included. Median age was 44 years; 51% were men. At baseline, a short PR interval was present in 10%, 7% had decreased left ventricular systolic function, and 5% had elevated left ventricular mass on echocardiogram (all in mild range). There was no change in cardiovascular status associated with enzyme replacement therapy. No significant safety concerns related to enzyme replacement therapy were identified.\n\nAlthough some patients with late-onset Pompe disease had abnormalities on baseline electrocardiogram or echocardiogram, those classically seen in infantile Pompe disease, such as significant ventricular hypertrophy, were not noted. Cardiovascular parameters were not impacted by enzyme replacement therapy, and there were no cardiovascular safety concerns. The cardiovascular abnormalities identified may be related to Pompe disease or other comorbid conditions.", "PMID": "21543987"}, {"title": "A randomized study of alglucosidase alfa in late-onset Pompe's disease.", "abstract": "Pompe's disease is a metabolic myopathy caused by a deficiency of acid alpha glucosidase (GAA), an enzyme that degrades lysosomal glycogen. Late-onset Pompe's disease is characterized by progressive muscle weakness and loss of respiratory function, leading to early death. We conducted a randomized, placebo-controlled trial of alglucosidase alfa, a recombinant human GAA, for the treatment of late-onset Pompe's disease.\n\nNinety patients who were 8 years of age or older, ambulatory, and free of invasive ventilation were randomly assigned to receive biweekly intravenous alglucosidase alfa (20 mg per kilogram of body weight) or placebo for 78 weeks at eight centers in the United States and Europe. The two primary end points were distance walked during a 6-minute walk test and percentage of predicted forced vital capacity (FVC).\n\nAt 78 weeks, the estimated mean changes from baseline in the primary end points favored alglucosidase alfa (an increase of 28.1+/-13.1 m on the 6-minute walk test and an absolute increase of 3.4+/-1.2 percentage points in FVC; P=0.03 and P=0.006, respectively). Similar proportions of patients in the two groups had adverse events, serious adverse events, and infusion-associated reactions; events that occurred only in patients who received the active study drug included anaphylactic reactions and infusion-associated reactions of urticaria, flushing, hyperhidrosis, chest discomfort, vomiting, and increased blood pressure (each of which occurred in 5 to 8% of the patients).\n\nIn this study population, treatment with alglucosidase alfa was associated with improved walking distance and stabilization of pulmonary function over an 18-month period. (ClinicalTrials.gov number, NCT00158600.)", "PMID": "20393176"}], "labels": [{"PMID": "34800399", "label": "included"}, {"PMID": "35305341", "label": "included"}, {"PMID": "30025991", "label": "included"}, {"PMID": "31839530", "label": "included"}, {"PMID": "34800400", "label": "included"}, {"PMID": "21543987", "label": "included"}, {"PMID": "20393176", "label": "included"}]}
{"metadata": {"review_pmid": "38078559"}, "inputs": {"background": "Many children undergo various surgeries, which often lead to acute postoperative pain. This pain influences recovery and quality of life. Non-steroidal anti-inflammatory drugs (NSAIDs), specifically cyclo-oxygenase (COX) inhibitors such as diclofenac, can be used to treat pain and reduce inflammation. There is uncertainty regarding diclofenac's benefits and harms compared to placebo or other drugs for postoperative pain.", "objectives": "To assess the efficacy and safety of diclofenac (any dose) for acute postoperative pain management in children compared with placebo, other active comparators, or diclofenac administered by different routes (e.g. oral, rectal, etc.) or strategies (e.g. 'as needed' versus 'as scheduled').", "selection criteria": "We included randomised controlled trials (RCTs) in children under 18 years of age undergoing surgery that compared diclofenac (delivered in any dose and route) to placebo or any active pharmacological intervention. We included RCTs comparing different administration routes of diclofenac and different strategies."}, "context": [{"title": "Effect of pre-operative rectal diclofenac suppository on post-operative analgesic requirement in cleft palate repair: A randomised clinical trial.", "abstract": "Opioid analgesics used for analgesia are associated with sedation, respiratory depression and post-operative nausea and vomiting. Non-steroidal anti-inflammatory drugs such as diclofenac are a safe and effective alternative with opioid-sparing effect.\n\nTo evaluate the effectiveness of pre-operative rectal diclofenac suppository (1 mg/kg) in cleft palate repair for post-operative analgesia and reduction in post-operative opioid requirements.\n\nA randomized clinical trial.\n\nAfter obtaining approval from the institutional ethical committee, 60 children were allocated by a computer-generated randomisation into two groups of 30 each; group D (Diclofenac group) and group C (Conventional group). Children in group D and group C were similar in all aspects except for the fact that group D children received 1 mg/kg diclofenac suppository after induction. Pain was evaluated using modification of the objective pain scale by Hannallah and colleagues for 6 h post-operatively by an anaesthesiology resident or nursing staff who was blinded to the group. If the pain score was more than 3, rescue analgesic I.V. fentanyl 0.5 \u03bcgm/kg was administered. The pain scores at different intervals, number of doses and quantity of rescue analgesic required were noted.\n\nWe observed that pre-operative rectal diclofenac provided effective analgesia in the immediate post-operative period, as evidenced by reduced pain scores and reduced opioid requirement (P=0.00002). There was no evidence of any increased perioperative bleeding in the diclofenac group.\n\nPre-operative rectal diclofenac reduces opioid consumption and provides good post-operative analgesia.", "PMID": "22923826"}, {"title": "Comparison Between Efficacy of Transdermal Ketoprofen and Diclofenac Patch in Patients Undergoing Therapeutic Extraction-A Randomized Prospective Split Mouth Study.", "abstract": "Postoperative pain control is a significant aspect of patient treatment after an oral and maxillofacial surgical procedure. The use of a transdermal patch is one such method to provide postoperative analgesia. The present study was undertaken to investigate the efficacy of a single-dose transdermal patch of ketoprofen compared with that of diclofenac postoperatively after therapeutic extraction of first premolar teeth for patients undergoing orthodontic treatment.\n\nA split mouth randomized clinical trial was conducted of 40 patients aged 15 to 25\u00a0years who had required therapeutic extraction of both maxillary and mandibular first premolar teeth bilaterally. A single ketoprofen patch was applied for the first and fourth quadrant extraction, and diclofenac patch was applied for the second and third quadrant extraction after atraumatic therapeutic exodontia at 2 consecutive appointments with the patient under local anesthesia. The data were obtained and analyzed using the Student t test and Shapiro-Wilk test using SPSS software (IBM Corp, Armonk, NY).\n\nAll 40 patients who had received a single-dose ketoprofen patch had experienced less postoperative pain and did not require a rescue analgesic with a mean visual analog scale (VAS) score of 1.13\u00a0\u00b1\u00a00.335 (P\u00a0<\u00a0.00001). The patients who had received a diclofenac patch reported comparatively elevated pain scores in the initial 24\u00a0hours, with a mean VAS score of 2.0\u00a0\u00b1\u00a00.5064 postoperatively, and 20% of the diclofenac treatment arm had required a rescue analgesic. No complications were observed among the patients postoperatively in either treatment arm.\n\nBoth the ketoprofen and diclofenac transdermal patches were effective in achieving postoperative analgesia in patients after therapeutic extraction, with ketoprofen superior to diclofenac as a transdermal medicament.", "PMID": "31077671"}, {"title": "Tramadol vs. diclofenac for posttonsillectomy analgesia.", "abstract": "To compare the analgesic efficacy of oral tramadol hydrochloride and oral diclofenac sodium for posttonsillectomy pain management.\n\nSingle-blind (surgeon and research team members), prospective, randomized, controlled clinical trial.\n\nSixty-four patients 11 years and older undergoing bipolar electrocautery tonsillectomy were randomized to either the oral tramadol or the oral diclofenac postoperative pain group. Patients recorded pain levels twice daily for 14 days using a visual analogue scale.\n\nPain scores for the 14 days were not significantly different between the oral tramadol and oral diclofenac groups. There were no significant differences in the incidence of postoperative hemorrhage and hospital readmission for uncontrolled pain.\n\nOral tramadol can deliver the same analgesic efficacy as oral diclofenac for posttonsillectomy pain relief, which might be beneficial for avoiding the adverse effects of nonsteroidal anti-inflammatory drug therapy.", "PMID": "11296045"}, {"title": "Efficacy and safety of premedication with oral ketamine for day-case adenoidectomy compared with rectal diazepam/diclofenac and EMLA.", "abstract": "Because of its pain-attenuating and sedative properties oral ketamine has been used as premedication in children and adults. We wanted to compare in children scheduled for adenoidectomy safety and efficacy of oral ketamine with a premedication that causes similar preoperative sedation and relief of pain at the venepuncture site. We also evaluated the effect of i.v. glycopyrrolate added to these combinations.\n\nOne hundred children between 10 and 15 kg of body weight scheduled for day-case adenoidectomy were randomly assigned to one of four groups: groups DG and DS received diclofenac 12.5 mg and diazepam 0.5 mg/kg rectally, EMLA cream at the venepuncture site, and placebo orally; groups KG and KS received ketamine 6.0 mg/kg orally, placebo cream at the puncture site, and placebo rectally; additionally, groups DG and KG received glycopyrrolate 5 microg/kg, and groups DS and KS received placebo intravenously. We recorded perioperatively scores (open scale 1-9) for stridor, sedation, bleeding, nausea, pain, heart rate, the need for analgesics and registered psychotomimesis and well-being at home.\n\nThe children of the K-groups became more tearful during separation from their parents (P=0.0072). No other differences were found between the ketamine and diazepam/diclofenac groups before and after premedication until induction of anaesthesia. Oral ketamine produced unpleasant psychotomimesis in four out of 59 children. During the first 10 min postoperatively, the score for stridor was significantly higher in group KS than in the D-groups; stridor scores > or = 6 were seen in one child of the D-groups (DS) and in six children of the K-groups (n.s.), of whom three developed laryngospasm (one reintubation). Glycopyrrolate diminished salivation in all groups, but had no effect on stridor scores. Additionally, glycopyrrolate delayed the onset of eating at home.\n\nPremedication with racemic oral ketamine 6 mg/kg does not seem to be suitable for upper airway procedures. Addition of i.v. glycopyrrolate before the induction of anaesthesia significantly reduced the scores for salivation.", "PMID": "10669283"}, {"title": "The effect of a combination of rectal diclofenac and caudal bupivacaine on postoperative analgesia in children.", "abstract": "Both caudal anaesthesia and non-steroidal anti-inflammatory drugs have been used in the management of postoperative pain in children. The aim of the present study was to evaluate the combination of caudal analgesia and rectally administered diclofenac in the treatment of pain following minor surgery in children. Thirty-nine, ASA grade 1 or 2, children undergoing inguinal or penoscrotal surgery were randomly assigned to receive either a caudal block using 0.125% bupivacaine with adrenaline or a similar caudal block in combination with rectally administered diclofenac 1 mg.kg-1. Children given a caudal block alone were more likely to need analgesia in the first 24 h postoperatively. It would appear that the combination of a caudal block and rectal diclofenac in children undergoing minor lower abdominal surgery reduces the need for subsequent analgesia.", "PMID": "7573879"}, {"title": "Postoperative analgesia using diclofenac and acetaminophen in children.", "abstract": "Diclofenac dosing in children for analgesia is currently extrapolated from adult data. Oral diclofenac 1.0\u00a0mg\u00b7kg(-1) is recommended for children aged 1-12\u00a0years. Analgesic effect from combination diclofenac/acetaminophen is unknown.\n\nChildren (n\u00a0=\u00a0151) undergoing tonsillectomy (c. 1995) were randomized to receive acetaminophen elixir 40\u00a0mg\u00b7kg(-1) before surgery and 20\u00a0mg\u00b7kg(-1) rectally at the end of surgery with diclofenac suspension 0.1\u00a0mg\u00b7kg(-1) , 0.5\u00a0mg\u00b7kg(-1) , or 2.0\u00a0mg\u00b7kg(-1) before surgery or placebo. A further 93 children were randomized to receive diclofenac 0.1\u00a0mg\u00b7kg(-1) , 0.5\u00a0mg\u00b7kg(-1) , or 2.0\u00a0mg\u00b7kg(-1) only. Postoperative pain was assessed (visual analogue score, VAS 0-10) at half-hourly intervals from waking until discharge. Data were pooled with those from a further 222 children and 30 adults. One-compartment models with first-order absorption and elimination described the pharmacokinetics of both medicines. Combined drug effects were described using a modified EMAX model with an interaction term. An interval-censored model described the hazard of study dropout.\n\nAnalgesia onset had an equilibration half-time of 0.496\u00a0h for acetaminophen and 0.23\u00a0h for diclofenac. The maximum effect (EMAX ) was 4.9. The concentration resulting in 50% of EMAX (C50 ) was 1.23\u00a0mg\u00b7l(-1) for diclofenac and 13.3\u00a0mg\u00b7l(-1) for acetaminophen. A peak placebo effect of 6.8 occurred at 4\u00a0h. Drug effects were additive. The hazard of dropping out was related to pain (hazard ratio of 1.35 per unit change in pain). Diclofenac 1.0\u00a0mg\u00b7kg(-1) with acetaminophen 15\u00a0mg\u00b7kg(-1) achieves equivalent analgesia to acetaminophen 30\u00a0mg\u00b7kg(-1) .\n\nCombination therapy can be used to achieve similar analgesia with lower doses of both drugs.", "PMID": "24815417"}, {"title": "Oral dexamethasone decreases postoperative pain, swelling, and trismus more than diclofenac following third molar removal: a randomized controlled clinical trial.", "abstract": "The aim of this study was to compare the anti-inflammatory potential of two pharmacotherapy protocols based on the parameters of pain, trismus, and swelling, after extraction of third molars.\n\nThirty patients selected with symmetrical impaction of third molars were submitted to surgical procedures in both sides in different times. For one group, dexamethasone was used for 3\u00a0days, and for another group diclofenac sodium was also used for the same period. The main variables analyzed were the visual analogue pain scale (VAS), but others were also analyzed such as swelling and trismus, which were submitted to statistical analysis.\n\nThe results had no difference regarding the length of procedures (p\u00a0=\u00a00.986) and the pain in the immediate and 4-h postoperative period (p\u00a0=\u00a00.723 and 0.541). The rescue analgesic consumption was higher (p\u00a0<\u00a00.05) when using the protocol with diclofenac sodium. The variables mouth opening (p\u00a0<\u00a00.05) and swelling (p\u00a0<\u00a00.05) were significantly better when using the protocol with dexamethasone in the postoperative period.\n\nMedical protocol with the use of dexamethasone in the postoperative period was more effective in controlling pain, trismus, and swelling, after the extraction of third molars, when compared to diclofenac sodium.", "PMID": "28597117"}, {"title": "A randomised controlled trial of two analgesic techniques for paediatric tonsillectomy*.", "abstract": "Investigators from Bristol described a fentanyl- and diclofenac-based analgesic technique for tonsillectomy with low postoperative nausea and vomiting rates and low pain scores. This study compared the effectiveness of a modified Bristol technique with a codeine-based regimen with respect to PONV and analgesia. Sixty-five children, ASA 1-2, were randomly assigned to either the Bristol group (fentanyl 1-2 \u03bcg.kg(-1) and diclofenac 1-2 mg.kg(-1)) or codeine group (codeine 1.5 mg.kg(-1)). All children received paracetamol 15 mg.kg(-1) and dexamethasone 0.1 mg.kg(-1) . Postoperative nausea and vomiting and pain scores were recorded hourly, and fitness for discharge was assessed at 4 h. The overall incidence of postoperative nausea and vomiting was 21% with no difference between groups (Bristol group 8/30, codeine group 5/32, p = 0.29). Children in the Bristol group required analgesia earlier than those in the codeine group (p < 0.005), but maximum pain scores were not different (Bristol group median (IQR [range) 4.5 (3-5 [0-5]), codeine group 4.0 (2-5 [1-5]), p = 0.15). Twenty-three per cent of children were assessed as not fit for discharge at 4 h. The codeine-based regimen may have a small advantage over the Bristol regimen, but neither technique seems ideally suited for a day-case service without a longer period of observation. You can respond to this article at http://www.anaesthesiacorrespondence.com.", "PMID": "21883125"}, {"title": "Comparison of preoperative rectal paracetamol with paracetamol - diclofenac combination for postoperative analgesia in pediatric surgeries under general anesthesia.", "abstract": "Traditionally, pain in children is a topic that has received only minimal attention. However, in the recent times, considerable progress has been made in the field of neonatal and pediatric pharmacology. The concept of preemptive analgesia is important in combating postoperative pain in children. In this study, we sought to compare the effectiveness of preemptive analgesia provided by paracetamol alone and by its combination with diclofenac when administered per rectum.\n\nTo compare the efficacy of preoperative rectal paracetamol with paracetamol - diclofenac combination for postoperative analgesia in pediatric surgeries under general anesthesia.\n\nProspective randomized double-blind study.\n\nSixty children scheduled for various surgeries under general anesthesia were randomly allocated into two Groups A and B, with 30 in each. Children in Group A received paracetamol suppository 20 mg/kg and those in Group B received paracetamol 20 mg/kg + diclofenac 2 mg/kg as suppository immediately after tracheal intubation. All the children were assessed for 24 h from the time of extubation. The pain was measured using numerical rating scale in children above 7 years and face-legs-activity-cry-consolability scale in children below 7 years. The time interval between extubation and the administration of the first dose of rescue analgesic was taken as the duration of postoperative analgesia.\n\nDescriptive and inferential statistical methods were used to analyze the data.\n\nThe duration of postoperative analgesia was significantly longer in paracetamol + diclofenac group (21.13 \u00b1 2.68 h) as compared to paracetamol alone group (10.18 \u00b1 2.39 h).\n\nThe combination of paracetamol and diclofenac administered per rectum preoperatively is more effective than paracetamol alone in providing postoperative analgesia in children.", "PMID": "27212765"}], "labels": [{"PMID": "22923826", "label": "excluded"}, {"PMID": "31077671", "label": "excluded"}, {"PMID": "11296045", "label": "excluded"}, {"PMID": "10669283", "label": "excluded"}, {"PMID": "7573879", "label": "excluded"}, {"PMID": "24815417", "label": "excluded"}, {"PMID": "28597117", "label": "excluded"}, {"PMID": "21883125", "label": "excluded"}, {"PMID": "27212765", "label": "excluded"}]}
{"metadata": {"review_pmid": "38078494"}, "inputs": {"background": "This is an updated version of a Cochrane Review last updated in 2020. Epilepsy is a common neurological disorder, affecting 0.5% to 1% of the population. In nearly 30% of cases, epilepsy is resistant to currently available drugs. Pharmacological treatment remains the first choice to control epilepsy. Lamotrigine is a second-generation antiseizure medication. When used as an add-on (in combination with other antiseizure medications), lamotrigine can reduce seizures, but with some adverse effects.", "objectives": "To evaluate the benefits and harms of add-on lamotrigine, compared with add-on placebo or no add-on treatment in people with drug-resistant focal epilepsy.", "selection criteria": "We included randomised controlled trials (RCTs) that investigated add-on lamotrigine versus add-on placebo or no add-on treatment in people of any age with drug-resistant focal epilepsy. We used data from the first period of eligible cross-over trials."}, "context": [{"title": "A placebo-controlled trial of lamotrigine add-on therapy for partial seizures in children. Lamictal Pediatric Partial Seizure Study Group.", "abstract": "To compare the safety and efficacy of add-on lamotrigine and placebo in the treatment of children and adolescents with partial seizures.\n\nAdd-on and monotherapy lamotrigine is safe and effective in adults with partial seizures, and reports of preliminary uncontrolled trials suggest similar benefits in children.\n\nWe studied 201 children with diagnoses of partial seizures of any subtype currently receiving stable conventional regimens of antiepileptic therapy at 40 study sites in the United States and France. After a baseline observation period (to confirm that more than four seizures occurred in each of two consecutive 4-week periods), patients were randomized to add-on lamotrigine or placebo therapy. A 6-week dose-escalation period was followed by a 12-week maintenance period.\n\nCompared with placebo, lamotrigine significantly reduced the frequency of all partial seizures and the frequency of secondarily generalized partial seizures in these treatment-resistant patients. The most commonly reported adverse events in the lamotrigine-treated patients were vomiting, somnolence, and infection; the frequency of these and other adverse events was similar to that in the placebo-treated group, with the exception of ataxia, dizziness, tremor, and nausea, which were more frequent in the lamotrigine-treated group. The frequency of withdrawals for adverse events was similar between groups. Two patients were hospitalized for skin rash, which resolved after discontinuation of lamotrigine therapy.\n\nLamotrigine was effective for the adjunctive treatment of partial seizures in children and demonstrated an acceptable safety profile.", "PMID": "10563619"}, {"title": "Lamotrigine extended-release as adjunctive therapy for partial seizures.", "abstract": "To evaluate the efficacy and tolerability of once-daily adjunctive lamotrigine extended-release (XR) for partial seizures in epilepsy.\n\nPatients more than 12 years old diagnosed with epilepsy with partial seizures and taking one to two baseline antiepileptic drugs were randomized to adjunctive once-daily lamotrigine XR or placebo in a double-blind, parallel-group trial. The study comprised a baseline phase, a 7-week double-blind escalation phase, and a 12-week double-blind maintenance phase during which doses of study medication and concomitant antiepileptic drugs were maintained.\n\nOf the 243 randomized patients, 239 (118 lamotrigine XR, 121 placebo) entered the escalation phase and received study medication. Lamotrigine XR was more effective than placebo with respect to median percent reduction from baseline in weekly partial seizure frequency (primary endpoint-entire 19-week treatment phase: 46.6% vs 24.5%, p = 0.0001 [corrected] via Wilcoxon test; escalation phase: 29.8% vs 15.6%, p = 0.027; maintenance phase: 58.4% vs 26.8%, p [corrected] < 0.0001). The percentage of patients with >or=50% reduction in partial seizure frequency (44.0% vs 20.8%, p = 0.0002) [corrected] and time to >or=50% reduction in partial seizure frequency (p = 0.0001) [corrected] also favored lamotrigine XR over placebo. A similar pattern of results was observed for secondarily generalized seizures. The most common adverse events were headache (lamotrigine XR 16%, placebo 18%) [corrected] and dizziness (lamotrigine XR 19%, [corrected] placebo 5%). Differences between lamotrigine XR and placebo on health outcomes measures were not significant.\n\nOnce-daily adjunctive lamotrigine extended-release compared with placebo effectively reduced partial seizure frequency and was well tolerated in this double-blind study. Results support the clinical utility of this new once-daily formulation.", "PMID": "17938371"}, {"title": "Adjunctive lamotrigine for partial seizures in patients aged 1 to 24 months.", "abstract": "This randomized, double-blind, placebo-controlled trial was conducted to assess the efficacy and tolerability of adjunctive lamotrigine for the treatment of partial seizures in infants aged 1 to 24 months.\n\nThe study used a responder-enriched design in which all patients received adjunctive lamotrigine during an open-label phase (n = 177; maximum maintenance dose 5.1 mg/kg/day for those on non-enzyme-inducing antiepileptic drugs [AEDs] or valproate and 15.6 mg/kg/day for those on enzyme-inducing AEDs). Patients meeting response criteria were randomly assigned to double-blind treatment for up to 8 weeks with continued lamotrigine (n = 19) or to withdrawal from lamotrigine (placebo; n = 19) while background AEDs were maintained.\n\nThe proportion of treatment failures (patients who met escape criteria or withdrew before completing the double-blind phase) was lower with lamotrigine (58%) than with placebo (84%). This finding was not significant in the primary analysis (two-sided chi(2) test [primary endpoint]). A post hoc sensitivity analysis of the primary endpoint was also performed (p = 0.045 by one-sided, mid-p corrected Fisher exact test). The median time to meet escape criteria was longer with lamotrigine (42 days) than with placebo (22 days) (p = 0.059). During the last 28 days of the open-label phase, 53% of the patients had a >or=50% reduction in frequency of partial seizures with lamotrigine. Additional reduction in partial seizure frequency was observed during the double-blind phase compared with the last 4 weeks of the open-label phase among those randomly assigned to lamotrigine (32% with a >or=25% reduction) but not those randomly assigned to placebo (5% with a >or=25% reduction). Lamotrigine was well tolerated, with an adverse event profile comparable to that observed in older pediatric patients.\n\nLamotrigine was well tolerated, and the data indicate that it may be efficacious in the treatment of partial seizures in infants aged 1 to 24 months.", "PMID": "18077797"}, {"title": "A comparison of pregabalin, lamotrigine, and placebo as adjunctive therapy in patients with refractory partial-onset seizures.", "abstract": "This study assessed the comparative efficacy of pregabalin for refractory partial seizures.\n\nFour-hundred and thirty-four patients with partial seizures were randomized to pregabalin, lamotrigine, or placebo as adjunctive therapy for 17 weeks of double-blind treatment. In phase I (11 weeks), pregabalin was titrated over 1 week and lamotrigine over 5 weeks to fixed dosages of 300mg/day for both. In phase II (6 weeks), patients not yet seizure-free were increased to pregabalin 600mg/day or lamotrigine 400mg/day.\n\nDuring phase I, there was a nonsignificant trend toward a greater reduction in seizures with pregabalin versus placebo and lamotrigine. Across the 17 weeks of treatment, pregabalin showed a median percentage reduction from baseline in seizure frequency of -20.0% (p=.001) versus placebo, and -9.7% (p=.080) versus lamotrigine. The responder rate (> or =50% reduction in seizure frequency) for pregabalin exceeded that of placebo (36% vs 21%; p=.007) and lamotrigine (36% vs 24%; p=.04). Adverse events were consistent with the known safety profiles of pregabalin and lamotrigine.\n\nPregabalin was demonstrated to be noninferior to lamotrigine in the treatment of refractory partial seizures. Overall conclusions were complicated by an unusually large and heterogeneous placebo response.", "PMID": "20696552"}, {"title": "A randomised double-blind placebo-controlled crossover add-on trial of lamotrigine in patients with treatment-resistant partial seizures.", "abstract": "Efficacy and safety of lamotrigine (LTG) as add-on therapy was assessed in a randomised double-blind placebo-controlled trial of this drug in 23 adult patients with refractory partial seizures. Fifteen patients showed an improvement on LTG treatment, with a greater than 50% decrease in total seizure count in 7 patients. Fourteen patients experienced fewer simple and complex partial seizures, with 8 patients benefitting by more than a 50% decrease in seizure frequency. The drug was well tolerated over the 2 month treatment period. The plasma concentration of concomitant antiepileptic drugs remained unchanged. No haematological or chemical abnormalities were noted.", "PMID": "2127016"}, {"title": "Gabapentin and lamotrigine in Indian patients of partial epilepsy refractory to carbamazepine.", "abstract": "52 patients (25 males and 27 females) suffering from refrectory partial seizures, of not more than two years duration and on carbamazepine monotherapy were enrolled in this study. Patients were randomly put on gabapentin (19 males and 8 females) or lamotrigine (6 males and 19 females) as add on therapy. The efficacy of the drugs was assessed by the seizure frequency, pattern of seizures and seizure free interval. The safety was evaluated from the biochemical investigations and the adverse effects observed or reported by the patients during the course of the study. The average frequency of basal partial seizures was 6.26+3.86 and 5.04+2.47 which decreased significantly (p<. 001) after 12 weeks of add on therapy to 1.75+2.16. and 1.68+2.94 in the GBP and LTG group respectively. However, there was no significant difference between the two drugs after 12 weeks of add on therapy. The PCB (primary change in basal seizure frequency) values decreased to -72+34.92 and -76.22+29.68 in the GBP and LTG group respectively. The difference in these two groups was not significant. The responder rate was 77.7% and 92% respectively in GBP and LTG group respectively. GBP was found to be more effective in partial seizures with secondarily generalization while LTG was effective in all subtypes of partial seizures. The abnormal scalp EEG was recorded in 33.3% (9 of 27 patients) in GBP group and 40 %( 10 of 25 patients) in LTG group and it did not revert to normal in 33.3% and 40% of patients in either of groups (GBP/LTG). Minor side effects which were self limiting were noticed in 80% in groups I and 74% were groups II.", "PMID": "12391470"}, {"title": "Adjunctive lamotrigine XR for primary generalized tonic-clonic seizures in a randomized, placebo-controlled study.", "abstract": "Efficacy and tolerability of once-daily adjunctive lamotrigine extended-release (XR) for primary generalized tonic-clonic (PGTC) seizures in epilepsy were evaluated. Patients (n = 153) \u2265 13 years old diagnosed with epilepsy with PGTC seizures were randomized to once-daily adjunctive lamotrigine XR or placebo in a double-blind, parallel-group trial comprising a baseline phase, a 7-week double-blind escalation phase, and a 12-week double-blind maintenance phase. Lamotrigine XR was more effective than placebo with respect to median percentage reduction from baseline in weekly PGTC seizure frequency (primary endpoint-19-week treatment phase: 75.4% vs 32.1%, P<0.0001; escalation phase: 61.9% vs 30.6%, P = 0.0016; maintenance phase: 89.7% vs 33.3%, P<0.0001). Lamotrigine XR was more effective than placebo with respect to the percentage of patients with \u226550% reduction in PGTC seizure frequency. Significant separation from placebo for \u226550% reduction in PGTC seizures was observed beginning on treatment day 8. The most common adverse event was headache (lamotrigine XR 14%, placebo 16%).", "PMID": "20937567"}, {"title": "Cognitive effects of lamotrigine versus topiramate as adjunctive therapy in older adults with epilepsy.", "abstract": "Older individuals may be more susceptible to cognitive side effects of antiepileptic drugs than are younger adults. This randomized, double-blind study compared the cognitive effects of lamotrigine (median maintenance dosage, 500.0 mg/d) and topiramate (median maintenance dosage, 300.0 mg/d) as adjunctive therapy for 16 weeks in patients \u226550 years of age. Fifty-one patients (lamotrigine, n=25; topiramate, n=26) were enrolled, and 28 patients (lamotrigine, n=15; topiramate, n=13) completed the study. In a combined analysis of all cognitive tests performed, no significant differences between treatment groups were noted. However, analyses of individual cognitive test results revealed that lamotrigine-treated patients had significantly better results on the Controlled Oral Word Association Test and the Symbol-Digit Modalities Test, whereas topiramate-treated patients had significantly more favorable results on the Digit Cancellation Test and the Rey Auditory-Verbal Learning Test. Larger studies are needed to further clarify the differences in the cognitive effects of lamotrigine and topiramate in older patients.", "PMID": "21577364"}, {"title": "Influence of concomitant antiepileptic drugs on plasma lamotrigine concentration in adult Japanese epilepsy patients.", "abstract": "Lamotrigine (LTG) is an antiepileptic drug (AED) that was approved in Japan in 2008. We evaluated the influence of AEDs that induce hepatic enzymes (including phenytoin (PHT), phenobarbital (PB), carbamazepine (CBZ)), valproic acid (VPA), and various combinations of these drugs, on plasma LTG concentration in adult Japanese epilepsy patients. A total of 621 patients (mean age 34.4\u00b111.8 years) were evaluated retrospectively. We calculated the concentration to dose ratio (CD ratio) for LTG with different AED regimens, and employed multiple regression analysis to determine factors influencing the LTG concentration. There was a linear correlation between the dose and concentration of LTG in patients treated with LTG (group I), LTG+VPA (group II), LTG+inducers (group III), or LTG+VPA+inducers (group IV). The mean CD ratio of patients on LTG monotherapy was 1.43\u00b10.4 (\u03bcg/mL)/(mg/kg). When LTG was combined with VPA, the CD ratio increased about 2.2-fold, but there was no significant correlation between the CD ratio and VPA concentration. The mean CD ratios calculated in patients receiving LTG+PHT, LTG+PB, and LTG+CBZ were 0.56, 0.84, and 0.91, respectively. Addition of PHT significantly reduced the CD ratio in a concentration-dependent manner, in comparison with PB and CBZ (p<0.005 and p<0.001, respectively). Stepwise multiple regression analysis showed that the coefficient of determination of groups I, II, III, and IV were 0.94, 0.94, 0.90, and 0.91, respectively. In the clinical setting, these findings can help to estimate LTG concentrations and predict the inducing or inhibiting effects of concomitant AEDs.", "PMID": "22466551"}, {"title": "Analysis of three lamotrigine extended-release clinical trials: comparison of pragmatic ITT and LOCF methodologies.", "abstract": "Early withdrawal of patients from a clinical trial can compromise the robustness of the data by introducing bias into the analysis. This is most commonly addressed by using the \"intent to treat\" (ITT) population and \"last observation carried forward\" (LOCF) methodology, where a patient's last assessment is carried forward. This can lead to overstatement of treatment efficacy especially if events indicative of treatment failure are infrequent. An alternative methodology, labeled \"pragmatic ITT\" (P-ITT), requires patients to have a positive outcome and to complete the trial in order to be considered a treatment success by that outcome measure. Data from 3 randomized multicenter lamotrigine extended-release (LTG XR) trials were analyzed and response (proportions seizure-free and with 50% response) were compared using LOCF and P-ITT methodologies. In 2 of the 3 trials, a lower response for both seizure freedom and 50% response was seen during the Maintenance phase using the P-ITT methodology. In the trial that did not show a difference, only a small number of patients withdrew early, thus negating the benefit brought by the P-ITT method. Differences between methodologies were not noted when evaluation was applied to the entire treatment period, most likely a reflection of the fact that a therapeutic dose of lamotrigine is not rapidly achieved. We propose that the P-ITT may be a simpler, more informative method for evaluating the effectiveness of a drug, especially in comparison to another active drug(s).", "PMID": "22497754"}], "labels": [{"PMID": "10563619", "label": "included"}, {"PMID": "17938371", "label": "included"}, {"PMID": "18077797", "label": "included"}, {"PMID": "20696552", "label": "included"}, {"PMID": "2127016", "label": "included"}, {"PMID": "12391470", "label": "excluded"}, {"PMID": "20937567", "label": "excluded"}, {"PMID": "21577364", "label": "excluded"}, {"PMID": "22466551", "label": "excluded"}, {"PMID": "22497754", "label": "excluded"}]}
{"metadata": {"review_pmid": "38063254"}, "inputs": {"background": "Anticholinergics are medications that block the action of acetylcholine in the central or peripheral nervous system. Medications with anticholinergic properties are commonly prescribed to older adults. The cumulative anticholinergic effect of all the medications a person takes is referred to as the anticholinergic burden. A high anticholinergic burden may cause cognitive impairment in people who are otherwise cognitively healthy, or cause further cognitive decline in people with pre-existing cognitive problems. Reducing anticholinergic burden through deprescribing interventions may help to prevent onset of cognitive impairment or slow the rate of cognitive decline.", "objectives": "Primary objective \u2022 To assess the efficacy and safety of anticholinergic medication reduction interventions for improving cognitive outcomes in cognitively healthy older adults and older adults with pre-existing cognitive issues. Secondary Objectives \u2022 To compare the effectiveness of different types of reduction interventions (e.g. pharmacist-led versus general practitioner-led, educational versus audit and feedback) for reducing overall anticholinergic burden. \u2022 To establish optimal duration of anticholinergic reduction interventions, sustainability, and lessons learnt for upscaling \u2022 To compare results according to differing anticholinergic scales used in medication reduction intervention trials \u2022 To assess the efficacy of anticholinergic medication reduction interventions for improving other clinical outcomes, including mortality, quality of life, clinical global impression, physical function, institutionalisation, falls, cardiovascular diseases, and neurobehavioral outcomes.", "selection criteria": "We included randomised controlled trials (RCTs) of interventions that aimed to reduce anticholinergic burden in older people and that investigated cognitive outcomes."}, "context": [{"title": "Cognitive effects of reducing anticholinergic drug burden in a frail elderly population: a randomized controlled trial.", "abstract": "Observational studies report a relationship between anticholinergic drug scale (ADS) score and cognitive function. This study investigated whether a reduced ADS score improved cognitive function in a frail elderly population.\n\nThis randomized, controlled, single-blinded trial, recruited long-term residents with an ADS score of greater than or equal to 3 from 22 nursing homes in Norway. The participants were randomly allocated (1:1) to intervention or control. The intervention was a pharmacist-initiated reduction of ADS score after multidisciplinary drug reviews. Primary end point was Consortium to Establish a Registry for Alzheimer's Disease 10-wordlist test for immediate recall. Secondary end points were Mini-Mental Sate Examination, delayed recall and recognition of words, saliva flow, and serum anticholinergic activity (SAA).The participants were retested after 4 and 8 weeks, and the study groups were compared after adjusting for baseline differences.\n\nEighty-seven patients were included. The median ADS score was reduced by 2 units (p < .0001) in the intervention group and remained unchanged in the control group. After 8 weeks, the adjusted mean difference in immediate recall was 0.54 words between the intervention and control group (95% confidence interval [CI]: -0.91, 2.05; p = .48). The study groups did not differ significantly in any of the other cognitive end points, salvia flow, or SAA at either follow-up (p > .18).\n\nPharmacist-initiated drug changes significantly reduced ADS score but did not improve cognitive function in nursing home residents. Moreover, the drug changes did not reduce SAA or mouth dryness significantly, which might indicate limited applicability of the ADS score to prevent prescription risks in this population.", "PMID": "22982689"}, {"title": "The relationship of serum anticholinergic activity to mental status performance in an elderly nursing home population.", "abstract": "Adverse drug reactions among elderly patients pose a significant clinical problem. The authors used a serum radioreceptor assay [RRA] to quantify drug-induced muscarinic blockade in 34 randomly selected nursing home residents. A random intervention group and the nonintervention control subjects were then retested 4 weeks later. The reduction of serum antimuscarinic activity (as determined by RRA) did relate to changes on several measures of cognitive function. A calculated \"antimuscarinic index\" lost significance with the RRA following intervention and may have overestimated the impact of a dosage reduction.", "PMID": "1821247"}, {"title": "Reducing the anticholinergic and sedative load in older patients on polypharmacy by pharmacist-led medication review: a randomised controlled trial.", "abstract": "To evaluate if a pharmacist-led medication review is effective at reducing the anticholinergic/sedative load, as measured by the Drug Burden Index (DBI).\n\nRandomised controlled single blind trial.\n\n15 community pharmacies in the Northern Netherlands.\n\n157 community-dwelling patients aged \u226565 years who used \u22655 medicines for \u22653 months, including at least one psycholeptic/psychoanaleptic medication and who had a DBI\u22651.\n\nA medication review by the community pharmacist in collaboration with the patient's general practitioner and patient.\n\nThe primary outcome was the proportion of patients whose DBI decreased by at least 0.5. Secondary outcomes were the presence of anticholinergic/sedative side effects, falls, cognitive function, activities of daily living, quality of life, hospital admission and mortality. Data were collected at baseline and 3\u2009months follow-up.\n\nMean participant age was 75.7 (SD, 6.9) years in the intervention arm and 76.6 (SD, 6.7) years in the control arm, the majority were female (respectively 69.3% and 72.0%). Logistic regression analysis showed no difference in the proportion of patients with a\u22650.5\u2009decrease in DBI between intervention arm (17.3%) and control arm (15.9%), (OR 1.04, CI 0.47 to 2.64, p=0.927). Intervention patients scored higher on the Digit Symbol Substitution Test, measure of cognitive function (OR 2.02, CI 1.11 to 3.67, p=0.021) and reported fewer sedative side effects (OR 0.61, CI 0.40 to 0.94, p=0.024) at follow-up. No significant difference was found for other secondary outcomes.\n\nPharmacist-led medication review as currently performed in the Netherlands was not effective in reducing the anticholinergic/sedative load, measured with the DBI, within the time frame of 3 months. Preventive strategies, signalling a rising load and taking action before chronic use of anticholinergic/sedative medication is established may be more successful.\n\nNCT02317666.", "PMID": "30030308"}, {"title": "Different effects of dopaminergic and anticholinergic therapies on cognitive and motor function in Parkinson's disease. A follow-up study of untreated patients.", "abstract": "The cognitive performance of a group of 82 newly diagnosed patients with Parkinson's disease who had never been treated was reassessed approximately 4 mths after randomization to one of three monotherapies (levodopa, bromocriptine or anticholinergic drugs). Dopaminergic and anticholinergic treatments both led to improvement in motor control but their effects upon cognitive performance dissociated. Anticholinergic drugs produced impairment in processes underlying the immediate registration of information whilst dopaminergic therapy produced improvement on a task dependent on working memory and cognitive sequencing. Other cognitive measures showed no change on treatment. The deficits that were affected by cholinergic and dopaminergic modulation are those that were most compromised in the early, untreated state in Parkinson's disease. The data support the notion that cognitive impairment in Parkinson's disease is multifactorial in origin: short-term memory processes are served by both dopaminergic and cholinergic subcortico-frontal systems but much of the cognitive impairment of Parkinson's disease is independent of this subcortical neurochemical pathology and may be due to early neuronal dysfunction within the cerebral cortex.", "PMID": "1486457"}, {"title": "Effects of discontinuation of long-term anticholinergic treatment in elderly schizophrenia patients.", "abstract": "Anticholinergic medication (ACM) is frequently used in psychiatry to treat the side-effects of D2 blocking agents. However, ACM is not without adverse effects and, in the elderly, cognitive and memory impairments have been emphasized. The aim of this study was to evaluate the effects of discontinuation of ACM on cognitive functions in a group of elderly chronic schizophrenia patients. Twenty-seven elderly patients (age 60 years or older), who were diagnosed as suffering from schizophrenia (DSM-IV) and receiving ACM in addition to antipsychotic treatment, were enrolled. Before and after ACM was discontinued, the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) subscale was administered. Twenty-one patients completed the study. All were receiving Akineton (biperiden), 2-6 mg daily before the study. Significant improvement in the ADAS-Cog total score was demonstrated (P < 0.03), as well as in the ideational praxia and orientation subscales. Improvement was correlated with the previous dose of biperidin. No adverse events or emergent extrapyramidal symptoms were noted. Discontinuation of ACM may be warranted in chronic schizophrenia patients since it may improve cognitive functioning with no adverse effects.", "PMID": "15101567"}, {"title": "Do anticholinergics affect reaction time? A possible impact on the course of rehabilitation.", "abstract": "To assess if oxybutynin and tolterodine have an effect on simple reaction time in healthy volunteers.\n\nSimple reaction time was evaluated before and 90 minutes after the oral administration of oxybutynin and tolterodine in a cross-over design. Twenty seven healthy volunteers, aged 26 to 48 years, were included in the study. The electromyographic activity of the flexor digitorum superficialis muscle that was used for the response was recorded, and premotor time was measured.\n\nThe mean age of the study group was 33.1 \u00b1 7.4 years. Mean premotor times before oxybutynin and before tolterodine administration were statistically non-significant. Mean premotor times after the administration of oxybutynin and tolterodine were significantly longer than the initial premotor times (p = 0.003).\n\nThe results of the study showed that oxybutynin and tolterodine prolonged the simple reaction time. The prolonged simple reaction time may suggest a perceptive impairment. The potential for perceptive impairment as a side effect of oxybutynin and tolterodine might suggest a negative impact on the rehabilitation interventions and the activities of daily living because of central nervous system effects.", "PMID": "20871143"}, {"title": "Effect of anticholinergic use for the treatment of overactive bladder on cognitive function in postmenopausal women.", "abstract": "Overactive bladder (OAB) is a common condition affecting the elderly. The mainstay of treatment for OAB is medical therapy with anticholinergics. However, adverse events have been reported with this class of drugs, including cognitive changes.\n\nThe objective of this study was to investigate the effect of an anticholinergic medication, trospium chloride, on cognitive function in postmenopausal women being treated for OAB.\n\nThis was a prospective cohort study conducted at a urogynaecology clinic at one academic medical centre from January to December 2010, with 12-week follow-up after medication initiation. Women aged 55 years or older seeking treatment for OAB and opting for anticholinergic therapy were recruited. Baseline cognitive function was assessed via the Hopkins Verbal Learning Test-Revised Form (HVLT-R) [and its five subscales], the Orientation, Memory & Concentration (OMC) short form, and the Mini-Cog evaluation. After initiation of trospium chloride extended release, cognitive function was reassessed at Day 1, Week 1, Week 4 and Week 12. Bladder function was assessed via three condition-specific quality-of-life questionnaires. Secondary outcomes included change in bladder symptoms, correlation between cognitive and bladder symptoms, and overall medication compliance. The main outcome measure was change in HVLT-R score at Week 4 after medication initiation, compared with baseline (pre-medication) score.\n\nOf 50 women enrolled, 35 completed the assessment. The average age was 70.4 years and 77.1% had previously taken anticholinergic medication for OAB. At enrollment 65.7% had severe overactive bladder and 71.4% had severe urge incontinence. Cognitive function showed an initial decline on Day 1 in HVLT-R total score (p\u2009=\u20090.037), HVLT-R Delayed Recognition subscale (p\u2009=\u20090.011) and HVLT-R Recognition Bias subscale (p\u2009=\u20090.01). At Week 1 the HVLT-R Learning subscale declined from baseline (p\u2009=\u20090.029). All HVLT-R scores normalized by Week 4. OMC remained stable throughout. The Mini-Cog nadired at a 90.9% pass rate at Week 4. OAB symptoms did not improve until Week 4, based on questionnaire scores (p\u2009<\u20090.05).\n\nCognitive function exhibited early changes after initiation of trospium chloride but normalized within 4 weeks. Cognitive changes occurred weeks prior to OAB symptom improvement. Surveillance for cognitive changes with anticholinergic use should be part of OAB management.", "PMID": "22873491"}, {"title": "Potential benefits of reducing medication-related anticholinergic burden for demented older adults: a prospective cohort study.", "abstract": "Medication-related anticholinergic burden is a quality indicator for geriatric pharmacotherapy; however, little is known regarding the benefits of reducing anticholinergic burden for demented patients\n\nDemented residents in a Veteran Home were enrolled for this study and an educational program was held for primary care physicians providing services at the Veterans Home. Residents were assigned to the intervention group if the primary care team could adhere to the research protocol and the remaining residents were assigned to the reference group receiving conventional care. Anticholinergic burden was estimated by Clinician-Rated Anticholinergic Score (CR-ACHS). Healthcare outcomes; for example, hospitalizations, mortality, cognitive and physical function, were compared between groups.\n\nOverall, 53 of the 67 demented residents (mean age 83.4 \u00b1 4.4 years) completed this study. Anticholinergic exposure was found in 38 participants (56.7%) at baseline, in which antipsychotics (n=29, 76.3%) and antidepressants (n=19, 50%) were the most common agents. Compared with participants in the reference group, CR-ACHS was significantly reduced in the intervention group at 12-week follow up (intervention group vs reference group=0.5 \u00b1 1.1 vs 1.1 \u00b1 1.3, P=0.021), whereas the mean Mini-Mental State Examination and Barthel Index were similar between groups. In contrast, no clinical complication was observed regarding medication adjustments during the study period.\n\nAnticholinergic burden can be successfully and safely reduced through an educational program for primary care physicians, but the benefit of reducing anticholinergic burden remained unclear within the first 12 weeks. Further investigation is required to evaluate the long-term benefits of reducing anticholinergic burden for demented older adults.", "PMID": "23216534"}, {"title": "Effects of anticholinergic challenge on psychopathology and cognition in drug-free patients with schizophrenia and healthy volunteers.", "abstract": "Many aspects of the neurobiology of schizophrenia, especially the physiological basis of the negative symptoms and associated cognitive deficits, remain inadequately understood. Tandon and Greden (1989) postulated a central role of dopaminergic/cholinergic imbalance in schizophrenia.\n\nIn light of this hypothesis, we elected to investigate the effects of anticholinergic challenge on psychopathology, cognition and attention in 12 unmedicated patients with schizophrenia and 12 healthy controls. The first examination occurred before any pharmacological intervention; the second examination was carried out immediately following an intravenous infusion of 5 mg biperiden, a centrally acting antimuscarinergic agent.\n\nThe biperiden challenge provoked a considerable increase in PANSS scores in both groups which was significantly more pronounced in patients (repeated measures analysis of variance (ANOVA) (rmANOVA): F(df)\u2009=\u20096.4(1,22); p\u2009=\u20090.019). The increase in the PANSS scores showed a significant negative correlation with age in patients. Biperiden caused considerable cognitive impairments in both groups. A significant group difference (rmANOVA) could be observed for TMT-B (F(df)\u2009=\u200911.29(1,22); p\u2009=\u20090.003).\n\nThe anticholinergic intervention caused more pronounced psychopathological and cognitive deteriorating effects in patients suffering from schizophrenia than in healthy volunteers. This could be related to the disrupted cholinergic transmission in schizophrenia. Our findings speak on behalf of the need of a more restrictive use of anticholinergics in psychiatric patients. The age-related attenuation of PANSS score increases in patients could be related to the age-dependent changes in dopamine dynamics and also to the age-associated decline of the availability of muscarinic receptors. Our results emphasise the need for further investigation of cholinergic disturbances in schizophrenia.", "PMID": "25373869"}, {"title": "Effects of discontinuing anticholinergic treatment on movement disorders, cognition and psychopathology in patients with schizophrenia.", "abstract": "Physicians have prescribed anticholinergic agents such as benztropine, procyclidine, biperiden and trihexyphenidyl for treatment and prophylaxis of antipsychotic-induced extrapyramidal symptoms (EPS) for decades. Anticholinergic agents can however worsen tardive dyskinesia and cause many adverse effects, including cognitive impairment. Previous studies of anticholinergic discontinuation in patients with schizophrenia receiving antipsychotics have yielded a wide range of EPS relapse rates. Improvement in cognition after anticholinergic withdrawal was observed in some studies.\n\nThis study evaluated the effect of anticholinergic discontinuation on movement disorders, cognition and general psychopathology after a 4-week taper in 20 outpatients with schizophrenia or schizoaffective disorder treated with antipsychotics.\n\nEighteen of twenty patients successfully discontinued their anticholinergic medication; two did not because of akathisia. Repeated measures analysis of variance did not show a significant effect of anticholinergic discontinuation on total Extrapyramidal Symptoms Rating Scale score or on the Parkinsonism, Akathisia, Dystonia or Tardive Dyskinesia subscales. However, significant improvement was found on the Brief Assessment of Cognition in Schizophrenia composite z score at weeks 6, 8 and 12 compared with baseline. Significant improvements were seen on the motor and the symbol-coding tasks. No significant effects were observed on the Positive and Negative Syndrome Scale, Clinical Global Impression - Severity and Clinical Global Impression - Improvement scales.\n\nIn this 12-week study of anticholinergic discontinuation in 20 outpatients with schizophrenia or schizoaffective disorder, gradual decrease and discontinuation of anticholinergics led to a positive effect on cognition. There were no adverse consequences on general psychopathology and no significant differences for 18 of 20 subjects on movement disorders.", "PMID": "25489477"}], "labels": [{"PMID": "22982689", "label": "included"}, {"PMID": "1821247", "label": "included"}, {"PMID": "30030308", "label": "included"}, {"PMID": "1486457", "label": "excluded"}, {"PMID": "15101567", "label": "excluded"}, {"PMID": "20871143", "label": "excluded"}, {"PMID": "22873491", "label": "excluded"}, {"PMID": "23216534", "label": "excluded"}, {"PMID": "25373869", "label": "excluded"}, {"PMID": "25489477", "label": "excluded"}]}
{"metadata": {"review_pmid": "38054555"}, "inputs": {"background": "Aortic valve disease is a common condition easily treatable with cardiac surgery. This is conventionally performed by opening the sternum ('median sternotomy') and replacing the valve under cardiopulmonary bypass. Median sternotomy is well tolerated, but as less invasive options become available, the efficacy of limited incisions has been called into question. In particular, the effects of reducing the visibility and surgical access have raised safety concerns with regard to the placement of cannulae, venting of the heart, epicardial wire placement, and de-airing of the heart at the end of the procedure. These difficulties may increase operating times, affecting outcome. The benefits of smaller incisions are thought to include decreased pain; improved respiratory mechanics; reductions in wound infections, bleeding, and need for transfusion; shorter intensive care stay; better cosmesis; and a quicker return to normal activity. This is an update of a Cochrane review first published in 2017, with seven new studies.", "objectives": "To assess the effects of minimally invasive aortic valve replacement via a limited sternotomy versus conventional aortic valve replacement via median sternotomy in people with aortic valve disease requiring surgical replacement.", "selection criteria": "We included randomised controlled trials comparing aortic valve replacement via a median sternotomy versus aortic valve replacement via a limited sternotomy. We excluded trials that performed other minimally invasive incisions such as mini-thoracotomies, port access, transapical, transfemoral or robotic procedures. Although some well-conducted prospective and retrospective case-control and cohort studies exist, these were not included in this review."}, "context": [{"title": "Minimally invasive versus conventional aortic valve operations: a prospective study in 120 patients.", "abstract": "Risk evaluation comparing the minimally invasive and standard aortic valve operations has not been studied.\n\nFour surgeons were randomly assigned to perform the minimally invasive (L-shaped sternotomy) (group 1) or the conventional (group 2) operation in 120 patients exclusively.\n\nIn both groups (n = 60) a CarboMedics prothesis was implanted in 90% of patients. There was no significant difference in the cross-clamping period (group 1, 60 minutes; range, 35 to 116 minutes), in the duration of extracorporal circulation (group 1, 84 minutes; range, 51 to 179 minutes) or in the time from skin-to-skin (group 1, 195 minutes; range, 145 to 466 minutes). Patients in group 1 were extubated earlier (p<0.001), the postoperative blood loss was less (p<0.001), and the need for analgesics was reduced (p<0.05). In 5 patients in group 1 a redo operation was required for bleeding (p>0.05), 3 patients in group 1 required a redo operation because of paravalvular leakage or endocarditis (p>0.05), the 30-day mortality rate was 1.6%. Overall the survival rate was 95% in group 1 and 97% in group 2 (mean follow-up, 294 days; range, 30 to 745 days).\n\nThe advantages of minimally invasive aortic valve operation include reduced trauma from incision and duration of ventilation, decreased blood loss and postoperative pain, the avoidance of groin cannulation, and a cosmetically attractive result. Simple equipment is used with a high degree of effectiveness and with no sacrifice of safety. Our study demonstrated the practicability and reliability of this new method.", "PMID": "10320242"}, {"title": "Ministernotomy versus median sternotomy for aortic valve replacement: a prospective, randomized study.", "abstract": "Minimally invasive aortic valve replacement reduces surgical trauma and, supposedly, postoperative pain, blood loss, and length of stay. A prospective, randomized study was designed to prove these theoretical advantages.\n\nForty patients undergoing isolated, elective aortic valve replacement were randomized into two equal groups. Patients in group M underwent aortic valve replacement through a ministernotomy (reversed L or reversed C). In group S, a median sternotomy was used. The anesthetic and surgical protocol was identical for both groups. Pain was evaluated on a daily basis. Pulmonary function tests were performed preoperatively and before hospital discharge in all patients.\n\nThere were two deaths in each group. Cross-clamp time was longer in group M: 70 +/- 19 minutes versus 51 +/- 13 minutes in group S (p = 0.005). There were no statistically significant differences between groups M and S in pump time (95 +/- 20 minutes versus 83 +/- 19 minutes), extubation time (9.9 hours in both groups), chest drainage (479 +/- 274 mL/L 24 hours versus 355 +/- 159 mL/24 hours), transfusion requirements (27% in both groups), pain evaluation (1.34 +/- 1.3 versus 2.15 +/- 1.5), length of stay (6.2 +/- 2.3 days versus 6.3 +/- 2.5 days), and cosmetic appraisal. Forced vital capacity decreased 26% from preoperative reference values in group M and 33% in group S (p = not significant). Forced expiratory volume in 1 second decreased 22% and 35%, respectively (p = not significant).\n\nThis study has failed to prove the theoretical advantages of minimally invasive aortic valve replacement. With this technique, cross-clamp time is longer than with a median sternotomy.", "PMID": "10391259"}, {"title": "Does ministernotomy improve postoperative outcome in aortic valve operation? A prospective randomized study.", "abstract": "The aim of this study was to compare the postoperative outcome obtained in patients undergoing elective aortic valve operation, either through ministernotomy or conventional sternotomy.\n\nBetween January 1999 and July 2001, 80 consecutive patients undergoing elective aortic valve replacement were randomly divided into two groups: group I (n = 40 patients) undergoing a ministernotomy approach (reversed-C or reversed-L), and group II (n = 40 patients) undergoing conventional sternotomy.\n\nThe length of skin incision was significantly shorter in group I than in group II (8.2+/-1.3 cm versus 23.7+/-2.6 cm, p < 0.001). No significant differences were found in cardiopulmonary bypass duration, associated procedures, or aortic cross-clamping times. Total operating time was 3.7+/-0.46 hours in group I compared with 3.4+/-0.6 hours in group II (p = 0.014). A similar incidence of cardiac, neurologic, infective, and renal complications between groups was found. Mean mediastinal drainage and mean blood transfusions (amount of blood transfused) per patient were greater in group II (p < 0.004 and p < 0.001, respectively). Twenty-five (62.5%) patients in group II and 15 (37.5%) patients in group I required postoperative blood transfusion (p = 0.04). Mechanical ventilation time was significantly longer in group II (6.2+/-1.8 hours versus 4.4+/-0.9 hours, p = 0.006). Five days after the surgical procedure, spirometric data analysis demonstrated a significantly lower total lung capacity and maximum inspiratory and expiratory pressures in group II compared with group I (p = 0.003, p = 0.007, and p < 0.001, respectively).\n\nOur results showed that ministernotomy had not only important cosmetic advantages but also beneficial effects in blood loss and transfusion, postoperative pain, and probably in sternal stability. Ministernotomy also improved recovery of respiratory function and allowed earlier extubation and hospital discharge.", "PMID": "11845860"}, {"title": "Pain and quality of life after minimally invasive versus conventional cardiac surgery.", "abstract": "The aim of this study was to evaluate pain and quality of life after minimally invasive cardiac operations in comparison with conventional cardiac operations.\n\nFrom October 1996 to May 1997 a total of 338 patients were interviewed daily using standard scoring systems (myocardial revascularization, n = 160; mitral valve reconstruction or replacement, n = 58; aortic valve replacement, n = 120).\n\nRegarding ventricular function and intensive care and hospital stay, there were no significant differences between groups. Pain decreased until the seventh postoperative day in all patients. Patients with a lateral minithoracotomy (minimally invasive revascularization and mitral valve operations) had lower pain levels from the third postoperative day onward. There were no differences in quality of life, postoperative wound healing, or stability of the bony thorax.\n\nIn cardiac operations overall pain levels are relatively low. After minimally invasive procedures with lateral minithoracotomy, earlier mobilization is possible because of a better stability of the bony thorax, resulting in lower pain levels.", "PMID": "10391268"}, {"title": "\"I\" ministernotomy for aortic valve replacement.", "abstract": "Minimally invasive surgical approaches have been applied recently in the management of valvular heart disease. In this report, we reviewed our preliminary experience of minimally invasive aortic valve replacement.\n\nEighteen patients were operated on by means of an \"I\" ministernotomy, and 16 patients were operated on by means of a full median sternotomy during the same period. There was no difference between these two groups in term of age, sex, and preoperative left ventricular ejection fraction. In patients of the ministernotomy group, the operations were approached through an \"I\" median sternal split, from the second to the fifth intercostal space, 8 to 10 cm in length, with transverse division. Cardiopulmonary bypass was established through aorto-right atrial cannulation with aortic cross-clamping and antegrade or retrograde delivery of blood cardioplegia.\n\nUnder direct vision, aortic valve replacement was performed successfully in patients of both groups. The duration of cardiopulmonary bypass time and aortic cross-clamp time was significantly longer in the ministernotomy group than in the full sternotomy group. However, the length of incision, duration of endotracheal intubation, intensive care unit stay, pain score, postoperative length of stay, and return to normal activity interval were significantly shorter and lower in patients of the ministernotomy group than in those of the full sternotomy group. All patients recovered from the operation rapidly. Follow-up was complete in all patients with no late complications. Echocardiographic examination showed good function of aortic prostheses.\n\nOur experience demonstrates that the \"I\" ministernotomy provides good exposure, reduced wound pain, enhanced recovery, shortened hospital stay, and good cosmetic healing. It may be a good alternative for surgical correction of aortic valve lesions.", "PMID": "10421112"}, {"title": "Minimally invasive aortic valve replacement (AVR) compared to standard AVR.", "abstract": "Minimally invasive cardiac surgery has been developed to offer patients the benefits of open heart operations with decreased pain and limited skin incision. A limited superior median sternotomy has been shown to provide a good exposure for aortic valve replacement (AVR) and good results. In this study we report the results of minimally invasive AVR compared to standard sternotomy AVR performed in the same period.\n\nFrom May 1996 to January 1998, 86 patients received isolated aortic valve replacement by the limited superior median sternotomy(group 1). As a control group (group 2), 78 patients were enrolled who underwent isolated aortic valve replacements by standard sternotomy in the same period.\n\nMedian ischemic time and median bypass time between the two groups showed no significant difference (P > 0.05). Median entire operation time in group 1 was obviously shorter than that in group 2 (P < 0.01). Median postoperative drainage was 229 ml in group 1, 369 ml in group 2. The difference between the two groups (P < 0.05) was significant. Median postoperative respiratory support time was 7.43 h in group 1, 11.26 h in group 2, with significant difference (P < 0.05). Median duration of hospital stay were 6.2 days in group 1, 9.4 days in group 2, with significant difference (P < 0.01). Reoperations for bleeding were two in group 1, four in group 2, superficial wound infection and sternum disruption occurred once in group 1 and four times in group 2. There were two hospital deaths respectively in the two groups (not procedure related).\n\nThe limited superior median sternotomy provides good exposure to the left ventricular outflow tract, aortic valve, ascending aorta, and even to the mitral valve through the roof of the left atrium. Therefore it seems to be suitable for all kinds of aortic valve operations. Besides less pain, shorter skin incision, shorter respiratory support time and lower blood loss, it has more advantages as opening and closure of the sternum is faster; decreasing infection and disruption of the sternum, and finally decreasing the time required for hospitalization and recovery.", "PMID": "10613563"}, {"title": "Pulmonary function following aortic valve replacement: a comparison between ministernotomy and median sternotomy.", "abstract": "Minimally invasive aortic valve replacement (AVR) has several theoretical advantages over standard median sternotomy, but the effects of these techniques on postoperative pulmonary function have not been determined.\n\nTwenty-six patients undergoing AVR through either a ministernotomy (group M; n = 12) or a median sternotomy (group S; n = 14) underwent pulmonary function tests. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), PaO2 and PaCO2 were determined preoperatively and before hospital discharge (at a mean of five days). Data regarding time to extubation, degree of pain and opening of the pleura were collected prospectively. Both groups had similar preoperative characteristics.\n\nThere was a significant decrease in FVC, FEVJ, PaO2 and PaCO2 during the postoperative period in all patients, though differences between the groups were not significant. Patients in group M referred less pain than those in group S. In this group, the fall in FVC and FEV1 correlated with the degree of pain, while preoperative FVC correlated with early extubation. Pleurotomy did not affect pulmonary function or pain.\n\nFVC, FEV1, PaO2 and PaCO2 are reduced significantly following AVR, but a minimally invasive approach does not prevent postoperative pulmonary dysfunction.", "PMID": "10616235"}, {"title": "Aortic valve replacement via ministernotomy: early results of a two-center study.", "abstract": "The reversed T ministernotomy has been proposed by Gundry to perform different congenital and common acquired heart valve operations. In this study we assessed the technical aspects of this approach for aortic valve replacement before starting a prospective randomized study. We evaluated the results of a two-Center study on the technical feasibility of aortic valve replacement via the reversed T ministernotomy according to the Gundry's approach.\n\nFrom January to October 1998 aortic valve replacement via ministernotomy was successfully accomplished in 16 patients at the Catholic University of the Sacred Heart of Rome (Italy) and the Academisch Ziekenhuis of Groningen (The Netherlands).\n\nNo complications were reported, except for the damage to the internal mammary artery during the opening of the sternum. The mean postoperative stay was 5.1 days. The postoperative respiratory recovery was easy and fast.\n\nProspective randomized studies are needed to evaluate the effectiveness of the minimally invasive approach compared to standard sternotomy.", "PMID": "10630053"}, {"title": "Minimally-invasive versus conventional aortic valve replacement--perioperative course and mid-term results.", "abstract": "We performed a case-control-study to compare perioperative and mid-term results of minimally invasive with conventional aortic valve replacement.\n\nBetween 8/96 and 7/97, 113 patients underwent isolated aortic valve replacement (minimally invasive: 29, conventional: 84) in our Department. Diagnosis, ejection fraction, pressure gradient/regurgitation fraction, age, gender and body-mass-index were used as matching criteria for the case-control-study. For qualitative data correspondence was requested, for quantitative data deviations up to 10% were accepted. With these criteria 25 patients of the minimally invasive group were matched to 25 patients of conventional group. All patients were reexplored 1 year after aortic valve replacement. Statistical analysis was done by the Fisher's exact test for qualitative data and the Mann-Whitney test for quantitative data.\n\nWe implanted 15 (20) bioprosthesis' and 10 (five) mechanical prosthesis' in the minimally invasive, respectively, conventional group. There were no statistically significant differences between both groups with respect to the perioperative course, only duration of surgery (mean 201.6 vs. 143.9 min, P < 0.01) and extracorporeal circulation (mean 116.1 vs. 71.3 min, P < 0.01) as well as aortic-cross-clamp-time (mean 77.9 vs. 46.9 min, P < 0.01) were significantly longer in the minimally invasive group. Postoperative complications occurred in one patient of the minimally invasive group (dissection of the right coronary artery) and four patients of the conventional group (third degree AV block, pneumothorax, grand mal convulsion, cardiopulmonary resuscitation). Two patients, one of each group, died during follow-up for unknown reasons. Follow-up revealed no significant differences with respect to clinical and echocardiographic data, but the shorter skin incision was cosmetically more accepted by patients of the minimally invasive group. Minor paravalvular leaks occurred in four patients of the minimally invasive and three patients of the conventional group as diagnosed by transthoracic echocardiography.\n\nBoth surgical techniques may be performed with comparable perioperative and mid-term results, but the better cosmetic result in the minimally invasive group is paid by a longer duration of surgery.", "PMID": "10647835"}, {"title": "Stress caused by minimally invasive cardiac surgery versus conventional cardiac surgery: incidence of systemic inflammatory response syndrome.", "abstract": "The present study was conducted to evaluate the degree of stress in patients induced by minimally invasive cardiac surgery (MICS) in comparison with that caused by conventional cardiac surgery. We did this by assessing the incidence of systemic inflammatory response syndrome (SIRS). A total of 48 adult patients who underwent surgery for single valve disease were included in this study, 27 of whom underwent conventional surgery and 21 MICS. We evaluated the stress inflicted on the patients in these two groups by analyzing the duration and degree of SIRS and the level of C-reactive protein (CRP). SIRS was assessed by measuring body temperature, heart rate, respiratory rate, and white blood cell counts. There were no significant differences in the operating times, perfusion times, or aorta clamp times between the two groups; and the mean volume of blood transfusion did not differ significantly either. There was no significant difference in the incidence of SIRS or the mean duration of SIRS between the two groups. The CRP levels did not differ significantly between the two groups. Thus although MICS is superior to conventional cardiac surgery in that only a small skin incision is required, the stress experienced by the patient may be the same as that experienced by the patient undergoing conventional cardiac surgery.", "PMID": "11338008"}], "labels": [{"PMID": "10320242", "label": "included"}, {"PMID": "10391259", "label": "included"}, {"PMID": "11845860", "label": "included"}, {"PMID": "10391268", "label": "excluded"}, {"PMID": "10421112", "label": "excluded"}, {"PMID": "10613563", "label": "excluded"}, {"PMID": "10616235", "label": "excluded"}, {"PMID": "10630053", "label": "excluded"}, {"PMID": "10647835", "label": "excluded"}, {"PMID": "11338008", "label": "excluded"}]}
{"metadata": {"review_pmid": "38054551"}, "inputs": {"background": "Management of chronic obstructive pulmonary disease (COPD) commonly involves a combination of long-acting bronchodilators including beta2-agonists (LABA) and muscarinic antagonists (LAMA). LABA and LAMA bronchodilators are now available in single-combination inhalers. In individuals with persistent symptoms or frequent exacerbations, inhaled corticosteroids (ICS) are also used with combination LABA and LAMA inhalers. However, the benefits and risks of adding ICS to combination LABA/LAMA inhalers as a triple therapy remain unclear.", "objectives": "To assess the effects of adding an ICS to combination LABA/LAMA inhalers for the treatment of stable COPD.", "selection criteria": "We included parallel-group randomised controlled trials of three weeks' duration or longer that compared the treatment of stable COPD with ICS in addition to combination LABA/LAMA inhalers against combination LABA/LAMA inhalers alone."}, "context": [{"title": "Triple therapy with budesonide/glycopyrrolate/formoterol fumarate with co-suspension delivery technology versus dual therapies in chronic obstructive pulmonary disease (KRONOS): a double-blind, parallel-group, multicentre, phase 3 randomised controlled trial.", "abstract": "Inhaled corticosteroids have been used in patients with chronic obstructive pulmonary disease (COPD), but the potential benefits of their use in triple therapy are not well known. We aimed to compare the efficacy of a triple therapy with corresponding dual therapies in symptomatic patients with moderate to very severe COPD, without a requirement for a history of exacerbations.\n\nIn this double-blind, parallel-group, multicentre phase 3 randomised controlled trial, we recruited patients from hospitals and care centres in Canada, China, Japan, and the USA. Eligible patients were 40-80 years of age, were current or former smokers (with a smoking history of \u226510 pack-years), had an established clinical history of COPD, and were symptomatic for COPD, despite receiving two or more inhaled maintenance therapies for at least 6 weeks before screening. We randomly assigned patients (2:2:1:1) using an interactive web response system to receive budesonide/glycopyrrolate/formoterol fumarate metered-dose inhaler 320/18/9\u00b76 \u03bcg (BGF MDI), glycopyrrolate/ formoterol fumarate metered-dose inhaler 18/9\u00b76 \u03bcg (GFF MDI), budesonide/formoterol fumarate metered-dose inhaler 320/9\u00b76 \u03bcg (BFF MDI), or open-label budesonide/formoterol fumarate dry-powder inhaler 400/12 \u03bcg (BUD/ FORM DPI). Primary endpoints for the Europe/Canada statistical analysis approach were FEV\n\nBetween Aug 20, 2015, and Jan 5, 2018, 3047 patients were screened from 215 sites, and 1902 were randomly assigned to receive BGF MDI (n=640), GFF MDI (n=627), BFF MDI (n=316), or BUD/FORM DPI (n=319). Over 24 weeks, BGF MDI significantly improved FEV\n\nBGF MDI was efficacious, well tolerated, and could be a more appropriate treatment than the corresponding dual therapies for symptomatic patients with moderate to very severe COPD, irrespective of exacerbation history.\n\nPearl-a member of the AstraZeneca Group.", "PMID": "30232048"}, {"title": "Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD.", "abstract": "The benefits of triple therapy for chronic obstructive pulmonary disease (COPD) with an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting \u03b2\n\nIn this randomized trial involving 10,355 patients with COPD, we compared 52 weeks of a once-daily combination of fluticasone furoate (an inhaled glucocorticoid) at a dose of 100 \u03bcg, umeclidinium (a LAMA) at a dose of 62.5 \u03bcg, and vilanterol (a LABA) at a dose of 25 \u03bcg (triple therapy) with fluticasone furoate-vilanterol (at doses of 100 \u03bcg and 25 \u03bcg, respectively) and umeclidinium-vilanterol (at doses of 62.5 \u03bcg and 25 \u03bcg, respectively). Each regimen was administered in a single Ellipta inhaler. The primary outcome was the annual rate of moderate or severe COPD exacerbations during treatment.\n\nThe rate of moderate or severe exacerbations in the triple-therapy group was 0.91 per year, as compared with 1.07 per year in the fluticasone furoate-vilanterol group (rate ratio with triple therapy, 0.85; 95% confidence interval [CI], 0.80 to 0.90; 15% difference; P<0.001) and 1.21 per year in the umeclidinium-vilanterol group (rate ratio with triple therapy, 0.75; 95% CI, 0.70 to 0.81; 25% difference; P<0.001). The annual rate of severe exacerbations resulting in hospitalization in the triple-therapy group was 0.13, as compared with 0.19 in the umeclidinium-vilanterol group (rate ratio, 0.66; 95% CI, 0.56 to 0.78; 34% difference; P<0.001). There was a higher incidence of pneumonia in the inhaled-glucocorticoid groups than in the umeclidinium-vilanterol group, and the risk of clinician-diagnosed pneumonia was significantly higher with triple therapy than with umeclidinium-vilanterol, as assessed in a time-to-first-event analysis (hazard ratio, 1.53; 95% CI, 1.22 to 1.92; P<0.001).\n\nTriple therapy with fluticasone furoate, umeclidinium, and vilanterol resulted in a lower rate of moderate or severe COPD exacerbations than fluticasone furoate-vilanterol or umeclidinium-vilanterol in this population. Triple therapy also resulted in a lower rate of hospitalization due to COPD than umeclidinium-vilanterol. (Funded by GlaxoSmithKline; IMPACT ClinicalTrials.gov number, NCT02164513 .).", "PMID": "29668352"}, {"title": "A phase III randomised controlled trial of single-dose triple therapy in COPD: the IMPACT protocol.", "abstract": "Patients with symptomatic advanced chronic obstructive pulmonary disease (COPD) who experience recurrent exacerbations are particularly at risk of poor outcomes and present a significant burden on healthcare systems. The relative merits of treating with different inhaled combination therapies e.g. inhaled corticosteroids (ICS)/long-acting \u03b22-agonist (LABA), LABA/long-acting muscarinic antagonists (LAMA), ICS/LABA/LAMA, in this patient group are poorly understood, as is reflected in current guidelines. The InforMing the PAthway of COPD Treatment (IMPACT) study will evaluate the efficacy and safety of fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) versus FF/VI or UMEC/VI over a 52-week treatment period. The study has been designed with a focus on understanding the comparative merits of each treatment modality in different phenotypes/endotypes.This is a phase III, randomised, double-blind, three-arm, parallel-group, global multicentre study comparing the rate of moderate and severe exacerbations between FF/UMEC/VI and FF/VI or UMEC/VI over a 52-week treatment period. The study aims to recruit 10\u200a000 patients from approximately 1070 centres. Eligible patients are aged \u226540\u2005years, with symptomatic advanced COPD (Global initiative for chronic Obstructive Lung Disease (GOLD) group D) and an exacerbation in the previous 12\u2005months.The first patients were recruited to the IMPACT study (ClinicalTrials.gov: NCT02164513) in June 2014 and the anticipated completion date is July 2017.", "PMID": "27418551"}, {"title": "Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial.", "abstract": "Evidence is scarce on the relative risk-benefit of inhaled triple therapy, consisting of inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting \u03b2\n\nThis randomised, parallel-group, double-blind, double-dummy study was done at 187 sites across 17 countries. Eligible patients had symptomatic COPD, severe or very severe airflow limitation, at least one moderate or severe exacerbation in the previous year, and were receiving inhaled maintenance medication. After a 2 week run-in period with one inhalation per day of IND/GLY (85 \u03bcg/43 \u03bcg), patients were randomly assigned (1:1), via an interactive response technology system, to receive 52 weeks of treatment with two inhalations of extrafine BDP/FF/G (87 \u03bcg/5 \u03bcg/9 \u03bcg) twice per day or one inhalation of IND/GLY (85 \u03bcg/43 \u03bcg) per day. Randomisation was stratified by country and severity of airflow limitation. The primary endpoint was the rate of moderate-to-severe COPD exacerbations across 52 weeks of treatment in all randomised patients who received at least one dose of study drug and had at least one post-baseline efficacy assessment. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02579850.\n\nBetween May, 29 2015, and July 10, 2017, 1532 patients received BDP/FF/G (n=764) or IND/GLY (n=768). Moderate-to-severe exacerbation rates were 0\u00b750 per patient per year (95% CI 0\u00b745-0\u00b757) for BDP/FF/G and 0\u00b759 per patient per year (0\u00b753-0\u00b767) for IND/GLY, giving a rate ratio of 0\u00b7848 (0\u00b7723-0\u00b7995, p=0\u00b7043) in favour of BDP/FF/G. Adverse events were reported by 490 (64%) of 764 patients receiving BDP/FF/G and 516 (67%) of 768 patients receiving IND/GLY. Pneumonia occurred in 28 (4%) patients receiving BDP/FF/G versus 27 (4%) patients receiving IND/GLY. One treatment-related serious adverse event occurred in each group: dysuria in a patient receiving BDP/FF/G and atrial fibrillation in a patient receiving IND/GLY.\n\nIn patients with symptomatic COPD, severe or very severe airflow limitation, and an exacerbation history despite maintenance therapy, extrafine BDP/FF/G significantly reduced the rate of moderate-to-severe exacerbations compared with IND/GLY, without increasing the risk of pneumonia.\n\nChiesi Farmaceutici.", "PMID": "29429593"}, {"title": "A phase III study of triple therapy with budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler 320/18/9.6\u202f\u03bcg and 160/18/9.6\u202f\u03bcg using co-suspension delivery technology in moderate-to-very severe COPD: The ETHOS study protocol.", "abstract": "Single inhaler triple therapies providing an inhaled corticosteroid, a long-acting muscarinic antagonist, and a long-acting \u03b2\n\nETHOS is an ongoing, randomized, double-blind, multicenter, parallel-group, 52-week study in symptomatic patients with moderate-to-very severe COPD and a history of exacerbation(s) in the previous year. Two doses of single inhaler triple therapy with budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI 320/18/9.6\u202f\u03bcg and 160/18/9.6\u202f\u03bcg) will be compared to glycopyrrolate/formoterol fumarate (GFF) MDI 18/9.6\u202f\u03bcg and budesonide/formoterol fumarate (BFF) MDI 320/9.6\u202f\u03bcg, all formulated using co-suspension delivery technology. Outcomes include the rate of moderate/severe (primary endpoint) and severe COPD exacerbations, symptoms, quality of life, and all-cause mortality. Sub-studies will assess lung function and cardiovascular safety.\n\nFrom June 2015-July 2018, 16,044 patients were screened and 8572 were randomized. Preliminary baseline demographics show that 55.9% of patients had experienced \u22652 moderate/severe exacerbations in the previous year, 79.1% were receiving an ICS-containing treatment at study entry, and 59.9% had blood eosinophil counts \u2265150\u202fcells/mm\n\nETHOS will provide data on exacerbations, patient-reported outcomes, mortality, and safety in 8572 patients with moderate-to-very severe COPD receiving triple and dual fixed-dose combinations. For the first time, ICS/LAMA/LABA triple therapy with two different doses of ICS will be compared to dual ICS/LABA and LAMA/LABA therapies.\n\nNCT02465567.", "PMID": "31605923"}, {"title": "Triple Inhaled Therapy at Two Glucocorticoid Doses in Moderate-to-Very-Severe COPD.", "abstract": "#BACKGROUND: Triple fixed-dose regimens of an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting \u03b2\n#METHODS: In a 52-week, phase 3, randomized trial to evaluate the efficacy and safety of triple therapy at two dose levels of inhaled glucocorticoid in patients with moderate-to-very-severe COPD and at least one exacerbation in the past year, we assigned patients in a 1:1:1:1 ratio to receive twice-daily inhaled doses of triple therapy (inhaled glucocorticoid [320 \u03bcg or 160 \u03bcg of budesonide], a LAMA [18 \u03bcg of glycopyrrolate], and a LABA [9.6 \u03bcg of formoterol]) or one of two dual therapies (18 \u03bcg of glycopyrrolate plus 9.6 \u03bcg of formoterol or 320 \u03bcg of budesonide plus 9.6 \u03bcg of formoterol). The primary end point was the annual rate (the estimated mean number per patient per year) of moderate or severe COPD exacerbations, as analyzed in the modified intention-to-treat population with the use of on-treatment data only.\n#RESULTS: The modified intention-to-treat population comprised 8509 patients. The annual rates of moderate or severe exacerbations were 1.08 in the 320-\u03bcg-budesonide triple-therapy group (2137 patients), 1.07 in the 160-\u03bcg-budesonide triple-therapy group (2121 patients), 1.42 in the glycopyrrolate-formoterol group (2120 patients), and 1.24 in the budesonide-formoterol group (2131 patients). The rate was significantly lower with 320-\u03bcg-budesonide triple therapy than with glycopyrrolate-formoterol (24% lower: rate ratio, 0.76; 95% confidence interval [CI], 0.69 to 0.83; P<0.001) or budesonide-formoterol (13% lower: rate ratio, 0.87; 95% CI, 0.79 to 0.95; P\u2009=\u20090.003). Similarly, the rate was significantly lower with 160-\u03bcg-budesonide triple therapy than with glycopyrrolate-formoterol (25% lower: rate ratio, 0.75; 95% CI, 0.69 to 0.83; P<0.001) or budesonide-formoterol (14% lower: rate ratio, 0.86; 95% CI, 0.79 to 0.95; P\u2009=\u20090.002). The incidence of any adverse event was similar across the treatment groups (range, 61.7 to 64.5%); the incidence of confirmed pneumonia ranged from 3.5 to 4.5% in the groups that included inhaled glucocorticoid use and was 2.3% in the glycopyrrolate-formoterol group.\n#CONCLUSIONS: Triple therapy with twice-daily budesonide (at either the 160-\u03bcg or 320-\u03bcg dose), glycopyrrolate, and formoterol resulted in a lower rate of moderate or severe COPD exacerbations than glycopyrrolate-formoterol or budesonide-formoterol. (Funded by AstraZeneca, ETHOS ClinicalTrials.gov number, NCT02465567.).", "PMID": "32579807"}, {"title": "A phase III study of triple therapy with budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler 320/18/9.6\u202f\u03bcg and 160/18/9.6\u202f\u03bcg using co-suspension delivery technology in moderate-to-very severe COPD: The ETHOS study protocol.", "abstract": "Single inhaler triple therapies providing an inhaled corticosteroid, a long-acting muscarinic antagonist, and a long-acting \u03b2\n\nETHOS is an ongoing, randomized, double-blind, multicenter, parallel-group, 52-week study in symptomatic patients with moderate-to-very severe COPD and a history of exacerbation(s) in the previous year. Two doses of single inhaler triple therapy with budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI 320/18/9.6\u202f\u03bcg and 160/18/9.6\u202f\u03bcg) will be compared to glycopyrrolate/formoterol fumarate (GFF) MDI 18/9.6\u202f\u03bcg and budesonide/formoterol fumarate (BFF) MDI 320/9.6\u202f\u03bcg, all formulated using co-suspension delivery technology. Outcomes include the rate of moderate/severe (primary endpoint) and severe COPD exacerbations, symptoms, quality of life, and all-cause mortality. Sub-studies will assess lung function and cardiovascular safety.\n\nFrom June 2015-July 2018, 16,044 patients were screened and 8572 were randomized. Preliminary baseline demographics show that 55.9% of patients had experienced \u22652 moderate/severe exacerbations in the previous year, 79.1% were receiving an ICS-containing treatment at study entry, and 59.9% had blood eosinophil counts \u2265150\u202fcells/mm\n\nETHOS will provide data on exacerbations, patient-reported outcomes, mortality, and safety in 8572 patients with moderate-to-very severe COPD receiving triple and dual fixed-dose combinations. For the first time, ICS/LAMA/LABA triple therapy with two different doses of ICS will be compared to dual ICS/LABA and LAMA/LABA therapies.\n\nNCT02465567.", "PMID": "31605923"}, {"title": "Triple Inhaled Therapy at Two Glucocorticoid Doses in Moderate-to-Very-Severe COPD.", "abstract": "#BACKGROUND: Triple fixed-dose regimens of an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting \u03b2\n#METHODS: In a 52-week, phase 3, randomized trial to evaluate the efficacy and safety of triple therapy at two dose levels of inhaled glucocorticoid in patients with moderate-to-very-severe COPD and at least one exacerbation in the past year, we assigned patients in a 1:1:1:1 ratio to receive twice-daily inhaled doses of triple therapy (inhaled glucocorticoid [320 \u03bcg or 160 \u03bcg of budesonide], a LAMA [18 \u03bcg of glycopyrrolate], and a LABA [9.6 \u03bcg of formoterol]) or one of two dual therapies (18 \u03bcg of glycopyrrolate plus 9.6 \u03bcg of formoterol or 320 \u03bcg of budesonide plus 9.6 \u03bcg of formoterol). The primary end point was the annual rate (the estimated mean number per patient per year) of moderate or severe COPD exacerbations, as analyzed in the modified intention-to-treat population with the use of on-treatment data only.\n#RESULTS: The modified intention-to-treat population comprised 8509 patients. The annual rates of moderate or severe exacerbations were 1.08 in the 320-\u03bcg-budesonide triple-therapy group (2137 patients), 1.07 in the 160-\u03bcg-budesonide triple-therapy group (2121 patients), 1.42 in the glycopyrrolate-formoterol group (2120 patients), and 1.24 in the budesonide-formoterol group (2131 patients). The rate was significantly lower with 320-\u03bcg-budesonide triple therapy than with glycopyrrolate-formoterol (24% lower: rate ratio, 0.76; 95% confidence interval [CI], 0.69 to 0.83; P<0.001) or budesonide-formoterol (13% lower: rate ratio, 0.87; 95% CI, 0.79 to 0.95; P\u2009=\u20090.003). Similarly, the rate was significantly lower with 160-\u03bcg-budesonide triple therapy than with glycopyrrolate-formoterol (25% lower: rate ratio, 0.75; 95% CI, 0.69 to 0.83; P<0.001) or budesonide-formoterol (14% lower: rate ratio, 0.86; 95% CI, 0.79 to 0.95; P\u2009=\u20090.002). The incidence of any adverse event was similar across the treatment groups (range, 61.7 to 64.5%); the incidence of confirmed pneumonia ranged from 3.5 to 4.5% in the groups that included inhaled glucocorticoid use and was 2.3% in the glycopyrrolate-formoterol group.\n#CONCLUSIONS: Triple therapy with twice-daily budesonide (at either the 160-\u03bcg or 320-\u03bcg dose), glycopyrrolate, and formoterol resulted in a lower rate of moderate or severe COPD exacerbations than glycopyrrolate-formoterol or budesonide-formoterol. (Funded by AstraZeneca, ETHOS ClinicalTrials.gov number, NCT02465567.).", "PMID": "32579807"}, {"title": "A phase III study of triple therapy with budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler 320/18/9.6\u202f\u03bcg and 160/18/9.6\u202f\u03bcg using co-suspension delivery technology in moderate-to-very severe COPD: The ETHOS study protocol.", "abstract": "Single inhaler triple therapies providing an inhaled corticosteroid, a long-acting muscarinic antagonist, and a long-acting \u03b2\n\nETHOS is an ongoing, randomized, double-blind, multicenter, parallel-group, 52-week study in symptomatic patients with moderate-to-very severe COPD and a history of exacerbation(s) in the previous year. Two doses of single inhaler triple therapy with budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI 320/18/9.6\u202f\u03bcg and 160/18/9.6\u202f\u03bcg) will be compared to glycopyrrolate/formoterol fumarate (GFF) MDI 18/9.6\u202f\u03bcg and budesonide/formoterol fumarate (BFF) MDI 320/9.6\u202f\u03bcg, all formulated using co-suspension delivery technology. Outcomes include the rate of moderate/severe (primary endpoint) and severe COPD exacerbations, symptoms, quality of life, and all-cause mortality. Sub-studies will assess lung function and cardiovascular safety.\n\nFrom June 2015-July 2018, 16,044 patients were screened and 8572 were randomized. Preliminary baseline demographics show that 55.9% of patients had experienced \u22652 moderate/severe exacerbations in the previous year, 79.1% were receiving an ICS-containing treatment at study entry, and 59.9% had blood eosinophil counts \u2265150\u202fcells/mm\n\nETHOS will provide data on exacerbations, patient-reported outcomes, mortality, and safety in 8572 patients with moderate-to-very severe COPD receiving triple and dual fixed-dose combinations. For the first time, ICS/LAMA/LABA triple therapy with two different doses of ICS will be compared to dual ICS/LABA and LAMA/LABA therapies.\n\nNCT02465567.", "PMID": "31605923"}, {"title": "Triple Inhaled Therapy at Two Glucocorticoid Doses in Moderate-to-Very-Severe COPD.", "abstract": "#BACKGROUND: Triple fixed-dose regimens of an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting \u03b2\n#METHODS: In a 52-week, phase 3, randomized trial to evaluate the efficacy and safety of triple therapy at two dose levels of inhaled glucocorticoid in patients with moderate-to-very-severe COPD and at least one exacerbation in the past year, we assigned patients in a 1:1:1:1 ratio to receive twice-daily inhaled doses of triple therapy (inhaled glucocorticoid [320 \u03bcg or 160 \u03bcg of budesonide], a LAMA [18 \u03bcg of glycopyrrolate], and a LABA [9.6 \u03bcg of formoterol]) or one of two dual therapies (18 \u03bcg of glycopyrrolate plus 9.6 \u03bcg of formoterol or 320 \u03bcg of budesonide plus 9.6 \u03bcg of formoterol). The primary end point was the annual rate (the estimated mean number per patient per year) of moderate or severe COPD exacerbations, as analyzed in the modified intention-to-treat population with the use of on-treatment data only.\n#RESULTS: The modified intention-to-treat population comprised 8509 patients. The annual rates of moderate or severe exacerbations were 1.08 in the 320-\u03bcg-budesonide triple-therapy group (2137 patients), 1.07 in the 160-\u03bcg-budesonide triple-therapy group (2121 patients), 1.42 in the glycopyrrolate-formoterol group (2120 patients), and 1.24 in the budesonide-formoterol group (2131 patients). The rate was significantly lower with 320-\u03bcg-budesonide triple therapy than with glycopyrrolate-formoterol (24% lower: rate ratio, 0.76; 95% confidence interval [CI], 0.69 to 0.83; P<0.001) or budesonide-formoterol (13% lower: rate ratio, 0.87; 95% CI, 0.79 to 0.95; P\u2009=\u20090.003). Similarly, the rate was significantly lower with 160-\u03bcg-budesonide triple therapy than with glycopyrrolate-formoterol (25% lower: rate ratio, 0.75; 95% CI, 0.69 to 0.83; P<0.001) or budesonide-formoterol (14% lower: rate ratio, 0.86; 95% CI, 0.79 to 0.95; P\u2009=\u20090.002). The incidence of any adverse event was similar across the treatment groups (range, 61.7 to 64.5%); the incidence of confirmed pneumonia ranged from 3.5 to 4.5% in the groups that included inhaled glucocorticoid use and was 2.3% in the glycopyrrolate-formoterol group.\n#CONCLUSIONS: Triple therapy with twice-daily budesonide (at either the 160-\u03bcg or 320-\u03bcg dose), glycopyrrolate, and formoterol resulted in a lower rate of moderate or severe COPD exacerbations than glycopyrrolate-formoterol or budesonide-formoterol. (Funded by AstraZeneca, ETHOS ClinicalTrials.gov number, NCT02465567.).", "PMID": "32579807"}], "labels": [{"PMID": "30232048", "label": "included"}, {"PMID": "29668352", "label": "included"}, {"PMID": "27418551", "label": "included"}, {"PMID": "29429593", "label": "included"}, {"PMID": "31605923", "label": "included"}, {"PMID": "32579807", "label": "included"}, {"PMID": "31605923", "label": "included"}, {"PMID": "32579807", "label": "included"}, {"PMID": "31605923", "label": "included"}, {"PMID": "32579807", "label": "included"}]}
{"metadata": {"review_pmid": "38054505"}, "inputs": {"background": "Immunisation plays a major role in reducing childhood morbidity and mortality. Getting children immunised against potentially fatal and debilitating vaccine-preventable diseases remains a challenge despite the availability of efficacious vaccines, particularly in low- and middle-income countries. With the introduction of new vaccines, this becomes increasingly difficult. There is therefore a current need to synthesise the available evidence on the strategies used to bridge this gap. This is a second update of the Cochrane Review first published in 2011 and updated in 2016, and it focuses on interventions for improving childhood immunisation coverage in low- and middle-income countries.", "objectives": "To evaluate the effectiveness of intervention strategies to boost demand and supply of childhood vaccines, and sustain high childhood immunisation coverage in low- and middle-income countries.", "selection criteria": "Eligible studies were randomised controlled trials (RCTs), non-randomised RCTs (nRCTs), controlled before-after studies, and interrupted time series conducted in low- and middle-income countries involving children that were under five years of age, caregivers, and healthcare providers."}, "context": [{"title": "Home delivery of heat-stable vaccines in Indonesia: outreach immunization with a prefilled, single-use injection device.", "abstract": "Extending immunization coverage to underserved populations will require innovative immunization strategies. This study evaluated one such strategy: the use of a prefilled, single-use injection device for outreach immunization by village midwives. The device, UniJect, is designed to prevent refilling or reuse. Stored at ambient temperatures for up to 1 month in midwives' homes, vaccine-filled UniJect devices were immediately available for outreach. Between July 1995 and April 1996, 110 midwives on the Indonesia islands of Lombok and Bali visited the homes of newborn infants to deliver hepatitis B vaccine to the infants and tetanus toxoid to their mothers. Observations and interviews showed that the midwives used the device properly and safely to administer approximately 10,000 sterile injections in home settings. There were no problems with excessive heat exposure during the storage or delivery of vaccine. Injection recipients and midwives expressed a strong preference for the UniJect device over a standard syringe. Use of the prefilled device outside the cold chain simplified the logistics and facilitated the speed and efficiency of home visits, while the single-dose format minimized vaccine wastage.\n\nRecent studies have found that up to 30% of injections given for immunization are not sterile.  Disposable syringes are reused and reusable syringes are often improperly sterilized.  Findings are presented from an evaluation of the use of a prefilled, single-use injection device for outreach immunization by village midwives.  Such devices can reduce the transmission of bloodborne pathogens and diseases, and reduce vaccine wastage associated with multi-dose vials.  The device evaluated, UniJect, is designed to prevent refilling or reuse.  Stored at ambient temperatures for up to 1 month in midwives' homes, vaccine-filled UniJect devices were immediately available for use.  Between July 1995 and April 1996, 110 midwives on the Indonesian islands of Lombok and Bali visited the homes of newborn infants to deliver hepatitis B vaccine to infants and tetanus toxoid to their mothers.  Observations and interviews found that the midwives safely and properly used the device to administer approximately 10,000 sterile injections in home settings.  No problems were experienced with excessive heat exposure during the storage or delivery of vaccine.  Injection recipients and midwives strongly preferred the UniJect device over a standard syringe.  Furthermore, use of the prefilled device outside of the cold chain simplified the logistics and facilitated the speed and efficiency of home visits, while the single-dose format minimized vaccine wastage.", "PMID": "10083709"}, {"title": "The improvement of immunization coverage by early immunisation of children in Malaysia.", "abstract": "", "PMID": "1023007"}, {"title": "[Investigation on the effect and strategy of polio eradication in Hainan Province].", "abstract": "Hainan Province was a hyperendemic area of poliomyelitis, with an average incidence rate of 0.28 per hundred thousand before 1993. A series of strategy was developed for polio eradication in the whole province in July 1993.\n\nHealth education, regular and strenthening immunization programs, AFP surveillance.\n\n1. OPV vaccination rate increased to 97.93%, 2. incidence rate of polio had a 80.93% reduction, 3. seasonal peak of epidemic was cut down, 4. endemic cycle was broken and 5. the endemic area became smaller. The number of counties (cities) where polio cases occured reduced for 81.33% in 1993 than that in 1989. Four boosters had been implemented from 1993 to 1997, to eliminated blank spots of immunization. The average geometric antibody of titre increased to 1:400 and above. After the establishment of polio surveillance system in 1991, 1. the reporting rate of non-AFP increased from 0 to 1.27 per hundred thousand, 2. rate of double specimens collection increased from 0 to 87.10%, 3. positive rate of virus isolation from 23.07% to 34.80%, 4. the positive specimens were appraised by National Polio Surveillance Center and no wild strain was found. Health education has made remarkable impact and immunization knowledge among parents had a 75 percentage point increase.\n\nResults showed that strategy of polio eradication has made positive effects and provided valuable experiences for the control or elimination of diseases which can be prevented by vaccines.", "PMID": "10682537"}, {"title": "The hepatitis B prevention education programme in Poland.", "abstract": "The main objective of the hepatitis B prevention education programme in Poland is to promote education in the school setting. The programme stems from the national policy for the prevention of hepatitis B virus (HBV) infection and is an element of the national Health Prevention Programme. The main aims of the programme include reducing morbidity from HBV infection by increasing community awareness, facilitating access to vaccination, establishing local lobbies to support the programme, and encouraging cooperation with vaccine producers. The education programme has been implemented in three phases, starting with a pilot programme in 1996 that was extended to half of Poland in 1997 and to the whole country in 1998. The programme is divided into five stages, consisting of meetings at central, voivodship and local levels, vaccination of children and evaluation of the programme.", "PMID": "10683545"}, {"title": "Evaluation of the hepatitis B prevention education programme in Poland.", "abstract": "Evaluation of the hepatitis B prevention education programme was performed as a survey including all the coordinators in 25 regions (211 coordinators; half the country). The success of the programme was defined by an objective measure (the ratio of vaccinated children to the total number of children in a region) and a subjective measure (the need to introduce changes in current procedures). The best information was felt to be provided on the subjective area, with financial aspects raising the most doubts. There was a high level of participation in local training by school nurses, but insufficient participation by paediatric nurses and paediatricians. In one-third of the regions schools fulfilled the tasks set them, but in 19% of the regions only a few schools did. Information about vaccination was given in most public children's clinics in 65% of the regions, but there was no activity in 6% of the regions. Recruitment of sponsorship was successful, with only 12% of parents paying the full cost of vaccination. The most important factors contributing to the success of the education programme were the health education and the epidemiology departments of state sanitary inspection, the schools' medical services and paediatric services. The greatest perceived need for change in procedures was in the area of cooperation with local authorities. Only 56% of those surveyed felt the director of the local sanitary station participated to a significant extent, though the programme is very dependent on such participation. Overall, 12% of the regions achieved a ratio of 20 or more between vaccinated and non-vaccinated children, with another 52% reaching a ratio of 5-19.9. The perceived need for changes in cooperation with the Health Service was smaller in regions in which the ratio of vaccinated children was higher. The survey showed a connection between the results of the education programme and the incidence of hepatitis B virus infection.", "PMID": "10683546"}, {"title": "Awareness of pulse polio immunisation.", "abstract": "Mass polio immunisation campaign was launched in the national capital territory of Delhi with 2 doses of polio vaccine to be administered to children upto 3 years of age on October and December 4, 1994 respectively. Massive information, education & communication (IEC) efforts through mass media and interpersonal communication preceded the dates of the campaign. A study to assess the awareness of general population was carried out by interviewing 225 adult residents of Delhi using a structured questionnaire. These were drawn by two stage stratified random sampling. Zonewise assembly segments in the first stage and census enumeration blocks in the second stage formed the sampling frame. The study, carried out 3 days prior to date of administration of first dose of oral polio, revealed that 60.4% of population was aware of the programme being launched and 31.6% about aim of the programme. None of the respondents were aware of all the specific parameters put together correctly viz., objective, immunisation days, age group & immunisation status of children. The higher level of awareness was directly proportional to the level of education. The overwhelming success of the programme was indicated by immunisation of > 90% children upto 3 years of age all over Delhi in the first phase of the programme. The key to success of the programme despite low awareness is explained on the basis of unflinching efforts put in by vaccine centre level committees, integrated child development scheme (ICDS) and urban basic service (UBS) functionaries in mobilising people to reach various vaccination centres. Other states planning to launch such mass campaigns should pay attention to social mobilisation in addition to IEC efforts for successful completion of the programme.", "PMID": "10829972"}, {"title": "Evaluation of mass pulse immunization with oral polio vaccine in Delhi: is pre-registration of children necessary?", "abstract": "Delhi was the fourth State in India to conduct mass immunization of children (Pulse Polio Immunization) of the < 3 year age group with Oral Polio Vaccine (OPV) as a strategy towards the eradication of poliomyelitis. This study attempted to evaluate the immunization coverage achieved and the channels of communication which were effective in increasing coverage in three high risk areas of Delhi during October 1994. The overall immunization coverage was 89%. Information sources like enumeration visits, posters, television, radio and schools statistically correlated with the Pulse Polio Immunization (PPI) outcome. However, the cost of enumeration was high. Other less expensive channels of communication appeared to be equally effective. Only 11% of the children surveyed were not immunized with PPI OPV. The major reasons why some children did not receive OPV was that parents were \"not informed\" or they were \"too busy\".", "PMID": "10829979"}, {"title": "Improving immunization coverage in rural areas of Ecuador: a cost-effectiveness analysis.", "abstract": "This study describes the costs and outcomes of two different immunization strategies used by the district level of the Ministry of Health carried out between 1993 and 1995 in Low-Napo area, Napo, Ecuador. One was centrally planned and managed by the District Hospital (DH) and the other planned and implemented together with community health workers (CHW). Immunization costs were estimated directly from survey records and communication of the Ministry of Health. Outcomes information was abstracted from the vaccination statistics of the Napo Province Health Department for 1993/1995. Community health workers strategy immunized 113 children with an average cost of US $32 per child. District Hospital strategy had an average cost of US $777.6 per immunized child.Thus, CHWs strategy is more effective and less costly than the DH strategy. This study shows that in order to maximize the cost-effectiveness of immunization, it is important to involve community participation in both planning and implementation. Continuous follow-up and evaluation of the immunization programme and further research on vaccine efficacy are necessary in order to maintain these results.", "PMID": "11205594"}, {"title": "Low-cost on-the-job peer training of nurses improved immunization coverage in Indonesia.", "abstract": "In Indonesia responsibility for immunizations is placed on local government health centres and on the nurses who provide the immunizations at each centre. An on-the-job peer training programme for these nurses, which was designed to improve the immunization performance of poorly performing health centres in terms of coverage and practice in Maluku province, was evaluated. Experienced immunization nurses were sent to health centres where nurses were inexperienced or performing poorly; the experienced nurses spent 1-2 weeks providing on-the-job training for the less experienced ones. An evaluation of the 13 centres that participated in the programme and the 95 that did not found that the programme increased both immunization coverage and the quality of practice. Coverage of diphtheria/pertussis/tetanus (DPT), polio, and measles vaccinations rose by about 39% in all 13 participating centres when compared with non-participating centres, and by about 54% in the 11 centres that had a functioning transportation system during the year after training. These results reflect increases in the actual number of doses given and improvements in the accuracy of reports. Potential threats to the study's validity were examined and found not to be significant. The out-of-pocket cost of the training programme was about US$ 53 per trainee or about US$ 0.05 per additional vaccine reported to have been given. The marginal cost per additional fully immunized child was estimated to be US$ 0.50.", "PMID": "11242822"}, {"title": "Changes in Expanded Program for Immunization coverage for mother and child in Krakor, Cambodia 1996--1998.", "abstract": "We evaluated a training intervention aimed at enhancing the roles of health centre staff, Village Health Volunteers (VHVs) and Traditional Birth Attendants (TBAs) within the Expanded Program for Immunization (EPI) in the district of Krakor, Cambodia. We conducted population-based surveys to determine the coverage of the EPI at baseline (1996) and after the intervention (1998), using data from health cards for mothers and their children and history data. Statistically significant changes over the 2-year period were apparent for tetanus, BCG, polio and DTP, supporting the positive impact the training intervention had on immunization coverage in the district.", "PMID": "11469945"}], "labels": [{"PMID": "10083709", "label": "excluded"}, {"PMID": "1023007", "label": "excluded"}, {"PMID": "10682537", "label": "excluded"}, {"PMID": "10683545", "label": "excluded"}, {"PMID": "10683546", "label": "excluded"}, {"PMID": "10829972", "label": "excluded"}, {"PMID": "10829979", "label": "excluded"}, {"PMID": "11205594", "label": "excluded"}, {"PMID": "11242822", "label": "excluded"}, {"PMID": "11469945", "label": "excluded"}]}