Context: 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.

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.

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.

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.

A randomized pretest and posttest control group, followed by a single-group pretest and posttest design.

Thirteen community-dwelling stroke survivors of at least 9 months.

A 10-week (3 days/week) program consisting of a warm-up, aerobic exercises, lower extremity muscle strengthening, and a cool-down.

Peak 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.

Significant 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.

The 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.

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.

Randomized, controlled pilot study with 2-month follow-up.

Rehabilitation center.

A 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.

Both 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.

Lower-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.

The 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.

The pilot study provides evidence for the efficacy of a task-related circuit class at improving locomotor function in chronic stroke.

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.

A 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.

The Motor Assessment Scale (MAS), the Sødring 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.

Patients 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.

The present study indicates that physiotherapy treatment using the MRP is preferable to that using the Bobath programme in the acute rehabilitation of stroke patients.

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.

We 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.

Follow-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.

Community 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.

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.

Fifty-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.

Comfortable 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.

With 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.

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.

Randomized controlled trial, using blocked randomization procedure with 2:1 ratio.

Inpatients 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.

A four-week regime of independent practice aimed at improving aspects of balance, as an addition to standard physiotherapy treatment based on the Bobath Approach.

Proportion of patients achieving 'normal' symmetry of weight distribution during sitting, standing, rising to stand, sitting down, and reaching.

Nineteen subjects were randomized to the control group; nine to the intervention group. There were no clinically significant differences in measured outcome between the groups.

The regime of independent practice had no measured beneficial effect on the balance ability of patients with recently acquired stroke.

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.

Inpatient rehabilitation unit.

Forty 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.

In 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.

Results 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.

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?

Randomised placebo-controlled trial with concealed allocation, assessor blinding and intention-to-treat analysis.

Twelve individuals who had a stroke less than three months previously and were able to sit unsupported.

The 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.

The 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.

After 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.

The sitting training protocol was both feasible and effective in improving sitting and standing up early after stroke and somewhat effective six months later.

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.

To examine the effect of additional trunk exercises on trunk performance after stroke.

An 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.

No 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).

Our 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.


Context: 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.

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.

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.

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.

In 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.

Sustained 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.

The use of e-Cigarette substantially decreased cigarette consumption without causing significant side effects in smokers not intending to quit (http://ClinicalTrials.gov number NCT01195597).

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.

In 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.

Sustained 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.

We 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.

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.

Parallel group, 3-arm, randomised controlled trial.

People aged ≥18 years resident in Auckland, New Zealand (NZ) who want to quit smoking.

Stratified blocked randomisation to allocate participants to either Elusion™ 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.

Biochemically verified (exhaled carbon monoxide) continuous abstinence at six months after quit day.

657 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.

This 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.

Australian NZ Clinical Trials Registry (ACTRN12610000866000).

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 = 100) received 7.2 mg nicotine cartridges for 12 weeks; GroupB (n = 100), a 6-week 7.2 mg nicotine cartridges followed by a further 6-week 5.4 mg nicotine cartridges; GroupC (n = 100) 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.

Declines 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.

In 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.

ClinicalTrials.gov NCT01164072 NCT01164072.

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) ≥50% reduction in the number of cig/day from baseline, defined as self-reported reduction in the number of cig/day (≥50%) compared to baseline; (b) ≥80% reduction in the number of cig/day from baseline, defined as self-reported reduction in the number of cig/day (≥80%) compared to baseline; (c) abstinence from smoking, defined as complete self-reported abstinence from tobacco smoking (together with an eCO concentration of ≤10 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 ).

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.

We did this pragmatic randomised-controlled superiority trial in Auckland, New Zealand, between Sept 6, 2011, and July 5, 2013. Adult (≥18 years) smokers wanting to quit were randomised (with computerised block randomisation, block size nine, stratified by ethnicity [Māori; Pacific; or non-Māori, non-Pacific], sex [men or women], and level of nicotine dependence [>5 or ≤5 Fagerström 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.

657 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 7·3% (21 of 289) with nicotine e-cigarettes, 5·8% (17 of 295) with patches, and 4·1% (three of 73) with placebo e-cigarettes (risk difference for nicotine e-cigarette vs patches 1·51 [95% CI -2·49 to 5·51]; for nicotine e-cigarettes vs placebo e-cigarettes 3·16 [95% CI -2·29 to 8·61]). 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.

E-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.

Health Research Council of New Zealand.

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.

To 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.

A 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.

Thirteen 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 ± standard deviation (SD) arterial COHb before 4.66±1.99 v. after 2.46±1.35; p=0.014 and mean ±SD venous COHb before 4.37±2.1 v. after 2.50±1.23; 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.

Smoking the Twisp e-cigarette may be a healthier and more acceptable alternative to smoking tobacco cigarettes.

Electronic cigarettes and smoking cessation: a quandary? - Authors' reply.

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.

We 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.

In the online survey, 40.2% (95% confidence interval [CI] = 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.

Awareness 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.

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.

Data 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.

Data 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).

Overall, 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 (≥20 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.

Awareness 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.


Context: 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.

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.

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.

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.

To test the hypothesis that cognitive stimulation therapy (CST) for older people with dementia would benefit cognition and quality of life.

A 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.

One 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.

The results compare favourably with trials of drugs for dementia. CST groups may have worthwhile benefits for many people with dementia.

The role of reality orientation therapy in restorative care of elderly patients with dementia plus stroke in the subacute nursing home setting.

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.

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.

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.

Using 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.

The 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.

The 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.

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.

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.

Reality orientation, a therapy for psychogeriatric patient: a controlled study.

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.

The 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).

Data on income and wealth were derived from official tax records. The characteristics of the different groups were compared by chi2 or t tests.

As 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.

The lower socioeconomic strata are clearly underrepresented in psychosocial interventions.

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).

Patients 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.

Patients 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).

A long-term CMI in ChEI-treated early Alzheimer disease patients produced additional mood and cognitive benefits.


Context: 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.

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.

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.

Comparison of Copan ESwab and FLOQSwab for COVID-19 Diagnosis: Working around a Supply Shortage.

Nasal Swab Sampling for SARS-CoV-2: a Convenient Alternative in Times of Nasopharyngeal Swab Shortage.

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.

We reviewed the medical record of 353 patients who received tests with both specimens simultaneously, and compared the performance between nasopharyngeal and oropharyngeal swabs.

Of 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).

In conclusion, our study suggests that nasopharyngeal swabs may be more suitable than oropharyngeal swab at this stage of COVID-19 outbreak.

Saliva as a Noninvasive Specimen for Detection of SARS-CoV-2.

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).

In 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 (κ) and Cycle threshold (Ct) values were recorded for all positive results as a surrogate measure for viral load.

Of 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 (κ = 0.890) for all viruses including SARS-CoV-2 and more concordant than HC to positive results by any method (κ = 0.959 vs 0.933). Mean SARS-CoV-2 E-gene and N-gene, rhinovirus and parainfluenza Ct values did not differ between HC and SCNT.

Self-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.

Saliva as an Alternate Specimen Source for Detection of SARS-CoV-2 in Symptomatic Patients Using Cepheid Xpert Xpress SARS-CoV-2.

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.

From 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.

Two-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 (κ coefficient 0.851, 95% CI 0.723-0.979; p < 0.001).

Saliva 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.

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).

We 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.

The 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.

Based 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.

Swabs Collected by Patients or Health Care Workers for SARS-CoV-2 Testing.


Context: 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.

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

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.

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).

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.

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.

We 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.

We 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.

A 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.

Treatment with AZA and cyclic MP for 6 months has little or no effect on IFN-beta bioactivity in NAb-positive patients with MS.

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.

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.

Therapeutic trial of Imuran (azathioprine) in multiple sclerosis.

Intensive immunosuppression in the treatment of multiple sclerosis.

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.

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.

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.


Context: 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.

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.

We included randomised controlled trials that enroled people at risk of developing a pressure ulcer.

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.

The 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.

A 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.

Mepentol is an effective measure for pressure ulcer prevention. It was more effective than a greasy placebo product, and was found to be cost-effective.

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.

Shear 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.

An 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.

The 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).

This safe and effective dressing can be used for patients with highly prominent bones and dry skin to prevent pressure ulcers.

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 = 6·1%) were detected in the intervention group versus seven (incidence = 7·4%) in the placebo group. Differences were not statistically significant (z = 0·08; P = 0·94), relative risk = 0·82 (95% confidence interval = 0·29–2·36). 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.

[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.

Prospective 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.

Of 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 ≤30; 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).

No 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.

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(®) Border Sacrum and Mepilex(®) 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 = 0·001). This represented a 10% difference in incidence between the groups (3·1% versus 13·1%) and a number needed to treat of ten patients to prevent one pressure ulcer. Overall there were fewer sacral (2 versus 8, P = 0·05) and heel pressure ulcers (5 versus 19, P = 0·002) and pressure injuries overall (7 versus 27, P = 0·002) in interventions than in controls. The time to injury survival analysis indicated that intervention group patients had a hazard ratio of 0·19 (P = 0·002) 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.

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).

The purpose of this study was to examine the effectiveness of different variations of massage in preventing pressure ulcers.

A 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'.

The results of three interventions did not differ significantly. DMSO did not fulfil the expectations raised by literature and a previous pilot-study.

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.

Four 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.

The 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.

We 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.

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.

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.

Patients 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.

In 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 £63,000 per 100 at risk patients).

The 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.

The 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).

A major contributor. Evaluation of Comfeel Pressure Relieving Dressing.