Context: 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.

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.

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.

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.

Nicotine blood levels and short-term smoking reduction with an electronic nicotine delivery system.

Abstract:
To evaluate nicotine delivery from the NJOY® King Bold Electronic Nicotine Delivery System (ENDS) and its short-term potential for smoking reduction or cessation.

One 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.

After 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.

The NJOY® King Bold ENDS delivers nicotine and led to short-term smoking reduction.

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).

RCT with three arms.

Participants (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.

From 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.

In a series of controlled lab sessions with e-cig naïve 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.


Context: Vitamin B

To evaluate the benefits and harms of oral vitamin B

Randomised controlled trials (RCTs), quasi-RCTs, or cluster-RCTs evaluating the effects of oral vitamin B

Vitamin D3 and B12 supplementation in pregnancy.

Abstract:
To assess the efficacy of vitamin D3 or B12 supplementation during pregnancy.

Pregnant women at 6-14 weeks 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.

The 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 nmol/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.

In 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.

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.

In 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 μg 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.

800 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 -0·57 (SD 1·03) in the B12 group and -0·55 (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 -0·02 (95% CI -0·16 to 0·13). The mean cognitive composite scores were 97·7 (SD 10·5) in the B12 group and 97·1 (10·2) in the placebo group, with a mean difference of 0·5 (95% CI -0·6 to 1·7) 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.

Although 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.

Research Council of Norway.

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

The 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 µg of vitamin B

National 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.

Universal Trial Number: U1111-1183-4093.

clinicaltrials.gov: NCT03071666. Protocol date: version 1.2, 1 June 2017.

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.

Association of antenatal vitamin B complex supplementation with neonatal vitamin B

Abstract:
#PURPOSE: Evidence about the effect of maternal vitamin B
#METHODS: In an ongoing cluster randomized controlled trial conducted in three rural counties in northwest China, pregnant women < 20 weeks 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
#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
#CONCLUSIONS: Maternal vitamin B complex supplementation during pregnancy was associated with better neonatal vitamin B

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.

A 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 μg/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.

At baseline, 48% of women tested as insufficient or deficient in serum B12 (<222 pmol/l) and 51% as insufficient or deficient in holoTC (<45 pmol/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 μg/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%).

The 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 μg/day) was associated with improved B12 biomarkers, with a potential to improve preconception B12 status in South Asian women.

Efficacy of maternal B

Abstract:
Vitamin B

This 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

The 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.


Context: 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.

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.

We included randomised controlled trials comparing any surgical technique with any non-surgical therapies for CTS.

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.

Patients 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.

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.

To compare the short-term and long-term efficacy of splinting and surgery for relieving the symptoms of CTS.

A 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.

General improvement, number of nights waking up due to symptoms, and severity of symptoms.

In 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.

Treatment with open carpal tunnel release surgery resulted in better outcomes than treatment with wrist splinting for patients with CTS.

SURGICAL TREATMENT FOR THE CARPAL TUNNEL SYNDROME.

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.

Two 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.

We 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.

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.

In 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.

Both 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.

Over 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.

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.

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.

Clinical inquiries. Does surgery for carpal tunnel syndrome improve outcomes?

A randomized trial of splinting vs. surgery for carpal tunnel syndrome.

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.

The 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.

Seventy 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.

In 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.


Context: 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.

To evaluate the efficacy and safety of disulfiram for the treatment of cocaine dependence.

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.

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.

Randomized double-blind, placebo-controlled trial.

Urban methadone maintenance clinic.

Sixty-seven cocaine-dependent, methadone-maintained, opioid-dependent subjects (52% female; 51% Caucasian).

Study medication, either disulfiram or placebo, was placed directly in the methadone to ensure compliance for 12 weeks.

Primary outcome measures included weekly assessments of the frequency and quantity of drug and alcohol use, weekly urine toxicology screens and breathalyzer readings.

Disulfiram 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.

Disulfiram 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.

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.

Opioid 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.

Groups 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.

This preliminary study suggests the potential efficacy of disulfiram versus placebo for treatment of cocaine dependence in buprenorphine-maintained patients.

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.

To 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.

Randomized, 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.

A community-based outpatient substance abuse treatment program.

A total of 121 individuals meeting the criteria for current cocaine dependence.

Patients 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.

Random regression analyses of self-reported frequency of cocaine use and results of urine toxicology screens.

Participants 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.

Disulfiram 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.

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.

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.

208 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.

Few 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.

There 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.

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.

Randomized controlled trial.

Urban substance abuse treatment center.

Ninety-six of 122 subjects randomized to treatment.

One 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.

Percentage of days of cocaine and alcohol use during follow-up, verified by urine toxicology screens and breathalyzer tests.

First, 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.

These 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.

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.

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.

Data 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).

Few 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.

The 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.


Context: 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).

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.

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 ≥ 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.

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.

The 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.

Acceptance 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.

Acceptance 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.

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.

[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.

To reduce the number of falls and their complications in the population >= 70 years old of a health district through a multifactorial community intervention programme.

Multi-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.

Possible 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.

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.

In 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.

Eighty-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.

Tai 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.

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.

To evaluate the impact of two exercise promotion programmes on PA in people aged ≥ 65 years.

The 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 ≥ 65 years) in primary care.

Forty-three UK-based general practices in London and Nottingham/Derby.

A total of 1256 people ≥ 65 years were recruited through their general practices to take part in the trial.

The 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.

The 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.

In 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 = 0.02]. There was no significant difference in MVPA between OEP and usual care (AOR 1.17, 95% CI 0.72 to 1.92; p = 0.52). 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 = 0.042). 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 (£269 vs. £88 per participant in London; £218 vs. £117 in Nottingham). The cost per extra person exercising at, or above, target was £1919.64 in London and £1560.21 in Nottingham (mean £1739.93).

The 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.

This trial is registered as ISRCTN43453770.

This 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.

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.

We 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.

Compared 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.

Population-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.

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.

ASPREE 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 19 000 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 16 500 ASPREE participants aged ≥70 years recruited in Australia. The intervention is a once daily dose of enteric-coated aspirin (100 mg) 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.

This 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.

The protocol for this substudy is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000347561).

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.

A 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.

The 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.

ISRCTN 71002650; Pre-results.

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.

This 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.

Older 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.

This 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.

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.

The objective of this work is to determine whether 2000 IU/day of supplemental vitamin D3 decreases fall risk.

VITamin 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).

This is a nationwide study.

Men 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.

Interventions included vitamin D3 (cholecalciferol; 2000 IU/day) and/or omega-3 fatty acids (1 g/day) or respective placebos in a 2 × 2 factorial design.

Main outcome measures include 2 or more falls and falls resulting in a doctor or hospital visit.

Baseline 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.

Daily 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.


Context: 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.

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).

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.

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.

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.

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.

This 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).

The 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.

This study provides evidence to support the combination of ibuprofen (but not rofecoxib) with paracetamol for perioperative analgesia in children.

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.

160 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).

Total 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).

We 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.

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)

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.

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.

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.

Two 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.

There 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.

This 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.

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.

The 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.

Pain 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.

Acetaminophen and ibuprofen produced no significant differences in pain after separator placement.

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.

A 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.

Mean 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.

A combination of preoperative and postoperative ibuprofen is more effective than paracetamol in the control of orthodontic pain.