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Focused psychosocial interventions for children in low-resource humanitarian settings: a systematic review and individual participant data meta-analysis.

Background: Results from studies evaluating the effectiveness of focused psychosocial support interventions in children exposed to traumatic events in humanitarian settings in low-income and middle-income countries have been inconsistent, showing varying results by setting and subgroup (eg, age or gender). We aimed to assess the effectiveness of these interventions, and to explore which children are likely to benefit most. Methods: We did a systematic review and meta-analysis of individual participant data (IPD) from 3143 children recruited to 11 randomised controlled trials of focused psychosocial support interventions versus waiting list. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, PsycArticles, Web of Science, and the main local low-income and middle-income countries (LMICs) databases according to the list of databases relevant to LMIC developed collaboratively by Cochrane and WHO Library, up to November, 2016. We included randomised controlled trials that assessed the effectiveness of focused psychosocial support interventions in children exposed to traumatic events in LMICs, compared with waiting lists (eg, inactive controls). We excluded quasi-randomised trials, studies that did not focus on psychosocial support interventions, and studies that compared two active interventions without control conditions. We requested anonymised data from each trial for each of the prespecified variables for each child who was randomly assigned. The main outcomes considered were continuous scores in post-traumatic stress disorder (PTSD) symptoms, depressive symptoms, and anxiety symptoms assessed with rating scales administered immediately (0-4 weeks) after the intervention. We harmonised all individual items from rating scales using item response theory methods. This study is registered with PROSPERO, number CRD42013006960. Findings: We identified a beneficial effect of focused psychosocial support interventions on PTSD symptoms (standardised mean difference [SMD] -0·33, 95% CI -0·52 to -0·14) that was maintained at follow-up (-0·21, -0·42 to -0·01). We also identified benefits at the endpoint for functional impairment (-0·29, -0·43 to -0·15) and for strengths: coping (-0·22, -0·43 to -0·02), hope (-0·29, -0·48 to -0·09), and social support (-0·27, -0·52 to -0·02). In IPD meta-analyses focused on age, gender, displacement status, region, and household size we found a stronger improvement in PTSD symptoms in children aged 15-18 years (-0·43, -0·63 to -0·23), in non-displaced children (-0·40, -0·52 to -0·27), and in children living in smaller households (<6 members; -0·27, -0·42 to -0·11). Interpretation: Overall, focused psychosocial interventions are effective in reducing PTSD and functional impairment, and in increasing hope, coping, and social support. Future studies should focus on strengthening interventions for younger children, displaced children, and children living in larger households. Funding: European Commission FP7th Framework Programme for Research (Marie Curie International Outgoing Fellowship) and the National Institute on Aging.

The Lancet. Global health · meta-analysis · 99 citationsread the source →

Nicotine receptor partial agonists for smoking cessation.

Background: Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting as an agonist) and reducing smoking satisfaction (acting as an antagonist). Objectives: To review the efficacy of nicotine receptor partial agonists, including varenicline and cytisine, for smoking cessation. Search methods: We searched the Cochrane Tobacco Addiction Group's specialised register for trials, using the terms ('cytisine' or 'Tabex' or 'dianicline' or 'varenicline' or 'nicotine receptor partial agonist') in the title or abstract, or as keywords. The register is compiled from searches of MEDLINE, EMBASE, and PsycINFO using MeSH terms and free text to identify controlled trials of interventions for smoking cessation and prevention. We contacted authors of trial reports for additional information where necessary. The latest update of the specialised register was in May 2015, although we have included a few key trials published after this date. We also searched online clinical trials registers. Selection criteria: We included randomised controlled trials which compared the treatment drug with placebo. We also included comparisons with bupropion and nicotine patches where available. We excluded trials which did not report a minimum follow-up period of six months from start of treatment. Data collection and analysis: We extracted data on the type of participants, the dose and duration of treatment, the outcome measures, the randomisation procedure, concealment of allocation, and completeness of follow-up. The main outcome measured was abstinence from smoking at longest follow-up. We used the most rigorous definition of abstinence, and preferred biochemically validated rates where they were reported. Where appropriate we pooled risk ratios (RRs), using the Mantel-Haenszel fixed-effect model. Main results: Two trials of cytisine (937 people) found that more participants taking cytisine stopped smoking compared with placebo at longest follow-up, with a pooled risk ratio (RR) of 3.98 (95% confidence interval (CI) 2.01 to 7.87; low-quality evidence). One recent trial comparing cytisine with NRT in 1310 people found a benefit for cytisine at six months (RR 1.43, 95% CI 1.13 to 1.80).One trial of dianicline (602 people) failed to find evidence that it was effective (RR 1.20, 95% CI 0.82 to 1.75). This drug is no longer in development. We identified 39 trials that tested varenicline, 27 of which contributed to the primary analysis (varenicline versus placebo). Five of these trials also included a bupropion treatment arm. Eight trials compared varenicline with nicotine replacement therapy (NRT). Nine studies tested variations in varenicline dosage, and 13 tested usage in disease-specific subgroups of patients. The included studies covered 25,290 participants, 11,801 of whom used varenicline. The pooled RR for continuous or sustained abstinence at six months or longer for varenicline at standard dosage versus placebo was 2.24 (95% CI 2.06 to 2.43; 27 trials, 12,625 people; high-quality evidence). Varenicline at lower or variable doses was also shown to be effective, with an RR of 2.08 (95% CI 1.56 to 2.78; 4 trials, 1266 people). The pooled RR for varenicline versus bupropion at six months was 1.39 (95% CI 1.25 to 1.54; 5 trials, 5877 people; high-quality evidence). The RR for varenicline versus NRT for abstinence at 24 weeks was 1.25 (95% CI 1.14 to 1.37; 8 trials, 6264 people; moderate-quality evidence). Four trials which tested the use of varenicline beyond the 12-week standard regimen found the drug to be well-tolerated during long-term use. The number needed to treat with varenicline for an additional beneficial outcome, based on the weighted mean control rate, is 11 (95% CI 9 to 13). The most commonly reported adverse effect of varenicline was nausea, which was mostly at mild to moderate levels and usually subsided over time. Our analysis of reported serious adverse events occurring during or after active treatment suggests there may be a 25% increase in the chance of SAEs among people using varenicline (RR 1.25; 95% CI 1.04 to 1.49; 29 trials, 15,370 people; high-quality evidence). These events include comorbidities such as infections, cancers and injuries, and most were considered by the trialists to be unrelated to the treatments. There is also evidence of higher losses to follow-up in the control groups compared with the intervention groups, leading to a likely underascertainment of the true rate of SAEs among the controls. Early concerns about a possible association between varenicline and depressed mood, agitation, and suicidal behaviour or ideation led to the addition of a boxed warning to the labelling in 2008. However, subsequent observational cohort studies and meta-analyses have not confirmed these fears, and the findings of the EAGLES trial do not support a causal link between varenicline and neuropsychiatric disorders, including suicidal ideation and suicidal behaviour. The evidence is not conclusive, however, in people with past or current psychiatric disorders. Concerns have also been raised that varenicline may slightly increase cardiovascular events in people already at increased risk of those illnesses. Current evidence neither supports nor refutes such an association, but we await the findings of the CATS trial, which should establish whether or not this is a valid concern. Authors' conclusions: Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and three-fold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion or with NRT. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The most frequently recorded adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Early reports of possible links to suicidal ideation and behaviour have not been confirmed by current research. Future trials of cytisine may test extended regimens and more intensive behavioural support.

The Cochrane database of systematic reviews · meta-analysis · 234 citationsread the source →

Efficacy and cost-effectiveness of therapist-guided internet cognitive behavioural therapy for paediatric anxiety disorders: a single-centre, single-blind, randomised controlled trial.

Background: Paediatric anxiety disorders are associated with substantial disability and long-term adverse consequences, but only a small proportion of affected children have access to evidence-based treatment. Internet-delivered cognitive behavioural therapy (ICBT) could help increase accessibility but needs further rigorous assessment. We aimed to assess the efficacy and cost-effectiveness of ICBT in the treatment of paediatric anxiety disorders. Methods: We did a single-blind randomised controlled trial in a clinical research unit within the Child and Adolescent Mental Health Services in Stockholm (Sweden). Eligible participants were children aged 8-12 years with a diagnosis of a principal anxiety disorder (seperation anxiety disorder, generalised anxiety disorder, specific phobia, social anxiety disorder, or panic disorder) of at least moderate severity. We randomly allocated participants (1:1) to ICBT or internet-delivered child-directed play, an active comparator aimed to improve parent-child relationships and increase a child's self-esteem without directly targeting anxiety. Block sizes for the randomisation varied between four and six and were generated using a computer random-number generator, and the allocation was concealed from the researchers by opaque sealed envelopes. Both treatment programmes comprised 12 modules presented over 12 weeks with weekly asynchronous online therapist support, and consisted of texts, films, illustrations, and exercises. The primary outcome was severity rating of the principal anxiety disorder 12-weeks post-treatment, via the Anxiety Disorder Interview Schedule for Diagnostic and Statistical Manual of Mental Disorders-IV (a rating of at least 4 corresponds to meeting the criteria for the principal diagnosis), assessed by clinicians masked to treatment allocation. All participants were included in the primary analysis (intention-to-treat). This trial is registered at ClinicalTrials.gov, number NCT02350257. Findings: Between March 11, 2015, and Oct 21, 2016, 131 participants were recruited and allocated to either ICBT (n=66) or internet-delivered child-directed play (n=65). The clinician-assessed severity rating of the principal anxiety disorder improved significantly after the 12-weeks treatment period for participants in both ICBT (within-group effect size 1·22, 95% CI 0·78-1·65) and the active control (0·72, 0·44-1·00) groups. However, greater improvement was seen with ICBT than with the active control (estimated mean difference 0·79, 95% CI 0·42-1·16, p=0·002; between-group effect size 0·77, 95% CI 0·40-1·15). 29 (48%) participants in the ICBT group no longer had their principal diagnosis, compared to nine (15%) in the active control group (odds ratio 5·41, 95% CI 2·26 to 12·90, p<0·0001); the number needed to treat for ICBT to gain one additional participant in remission was three (95% CI 2·85 to 3·15). ICBT resulted in an average societal-cost saving of €493·05 (95% CI 477·17 to 508·92) per participant. No severe adverse events were reported. Interpretation: ICBT is an efficacious and cost-effective treatment for paediatric anxiety disorders that should be considered for implementation in routine clinical care. Funding: The Swedish Research Council for Health, Working Life and Welfare, and Stockholm County Council.

The Lancet. Child & adolescent health · randomised controlled trial · 51 citationsread the source →

Non-specialist psychosocial interventions for children and adolescents with intellectual disability or lower-functioning autism spectrum disorders: a systematic review.

Background: The development of effective treatments for use by non-specialists is listed among the top research priorities for improving the lives of people with mental illness worldwide. The purpose of this review is to appraise which interventions for children with intellectual disabilities or lower-functioning autism spectrum disorders delivered by non-specialist care providers in community settings produce benefits when compared to either a no-treatment control group or treatment-as-usual comparator. Methods and findings: We systematically searched electronic databases through 24 June 2013 to locate prospective controlled studies of psychosocial interventions delivered by non-specialist providers to children with intellectual disabilities or lower-functioning autism spectrum disorders. We screened 234 full papers, of which 34 articles describing 29 studies involving 1,305 participants were included. A majority of the studies included children exclusively with a diagnosis of lower-functioning autism spectrum disorders (15 of 29, 52%). Fifteen of twenty-nine studies (52%) were randomized controlled trials and just under half of all effect sizes (29 of 59, 49%) were greater than 0.50, of which 18 (62%) were statistically significant. For behavior analytic interventions, the best outcomes were shown for development and daily skills; cognitive rehabilitation, training, and support interventions were found to be most effective for improving developmental outcomes, and parent training interventions to be most effective for improving developmental, behavioral, and family outcomes. We also conducted additional subgroup analyses using harvest plots. Limitations include the studies' potential for performance bias and that few were conducted in lower- and middle-income countries. Conclusions: The findings of this review support the delivery of psychosocial interventions by non-specialist providers to children who have intellectual disabilities or lower-functioning autism spectrum disorders. Given the scarcity of specialists in many low-resource settings, including many lower- and middle-income countries, these findings may provide guidance for scale-up efforts for improving outcomes for children with developmental disorders or lower-functioning autism spectrum disorders. Protocol registration: PROSPERO CRD42012002641

PLoS medicine · systematic review · 80 citationsread the source →

Change in non-abstinent WHO drinking risk levels and alcohol dependence: a 3 year follow-up study in the US general population.

Background: Alcohol dependence is often untreated. Although abstinence is often the aim of treatment, many drinkers prefer drinking reduction goals. Therefore, if supported by evidence of benefit, drinking reduction goals could broaden the appeal of treatment. Regulatory agencies are considering non-abstinent outcomes as efficacy indicators in clinical trials, including reduction in WHO drinking risk levels-very high, high, moderate, and low-defined in terms of mean ethanol consumption (in grams) per day. We aimed to study the relationship between reductions in WHO drinking risk levels and subsequent reduction in the risk of alcohol dependence. Methods: In this population-based cohort study, we included data from 22 005 drinkers who were interviewed in 2001-02 (Wave 1) and re-interviewed 3 years later (2004-05; Wave 2) in the US National Epidemiologic Survey on Alcohol and Related Conditions. Alcohol consumption (WHO drinking risk levels) and alcohol dependence (at least three of seven DSM-IV criteria in the previous 12 months) were assessed at both waves. We used logistic regression to test the relationship between change in WHO drinking risk levels between Waves 1 and 2, and alcohol dependence at Wave 2. Findings: At Wave 1, 2·5% (weighted proportion) of the respondents were very-high-risk drinkers, 2·5% were high-risk drinkers, 4·8% were moderate-risk drinkers, and most (90·2%) were low-risk drinkers. Reduction in WHO drinking risk level predicted significantly lower odds of alcohol dependence at Wave 2, particularly among very-high-risk drinkers (adjusted odds ratios 0·27 [95% CI 0·18-0·41] for reduction by one level, 0·17 [0·10-0·27] for two levels, and 0·07 [0·05-0·10] for three levels) and high-risk drinkers (0·64 [0·54-0·75] for one level and 0·12 [0·09-0·15] for two levels), and among those with alcohol dependence at Wave 1 (0·29 [0·15-0·57] for one level, 0·06 [0·04-0·10] for two levels, and 0·04 [0·03-0·06] for three levels in very-high-risk drinkers). Interpretation: Our results support the use of reductions in WHO drinking risk levels as an efficacy outcome in clinical trials. Because these risk levels can be readily translated into standard drink equivalents per day of different countries, the WHO risk levels could also be used internationally to guide treatment goals and clinical recommendations on drinking reduction. Funding: US National Institute on Alcohol Abuse and Alcoholism, New York State Psychiatric Institute, the Alcohol Clinical Trials Initiative.

The lancet. Psychiatry · cohort or longitudinal · 117 citationsread the source →

Effects of intranasal oxytocin on 'compassion focused imagery'.

This study explored the effects of oxytocin on Compassion Focused Imagery (CFI), that is, imagining another "mind" being deeply compassionate to oneself, and the interaction of these effects with self-criticism and feeling socially safe with others. Forty-four healthy participants (29 men and 15 women) completed self-report measures of self-criticism, attachment style, and social safeness before taking part in a double-blind randomized placebo controlled study. They attended two imagery sessions, receiving oxytocin in one and a placebo in the other. Positive affect was measured before and after each imagery session, and "imagery experience" was assessed after each session. Overall, oxytocin increased the ease of imagining compassionate qualities but there were important individual differences in how CFI was experienced. Participants higher in self-criticism, lower in self-reassurance, social safeness, and attachment security had less positive experiences of CFI under oxytocin than placebo, indicating that the effects of oxytocin on affiliation may depend on attachment and self-evaluative styles.

Emotion (Washington, D.C.) · randomised controlled trial · 80 citationsread the source →

Roles of Birth Mode and Infant Gut Microbiota in Intergenerational Transmission of Overweight and Obesity From Mother to Offspring.

Importance: Maternal overweight, which often results in cesarean delivery, is a strong risk factor for child overweight. Little is known about the joint contribution of birth mode and microbiota in the infant gut to the association between maternal prepregnancy overweight and child overweight. Objective: To investigate the association of birth mode with microbiota in the infant gut, and whether this mediates the association between maternal and child overweight. Design, setting, and participants: An observational study was conducted of 935 full-term infants born between January 1, 2009, and December 31, 2012, in the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Maternal prepregnancy body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared using height and weight data taken from medical records or maternal report. Infant gut microbiota were profiled with 16S ribosomal RNA sequencing in fecal samples collected at a mean (SD) age of 3.7 (1.0) months. At ages 1 and 3 years, BMI z scores adjusted for age and sex were generated according to World Health Organization criteria. Statistical analysis was conducted from January 29 to June 15, 2017. Exposures: Mothers of normal weight (BMI, 18.5-24.9) and overweight or obese (BMI, ≥25.0) mothers. Main outcome and measures: Risk of overweight and obesity (>97th percentile BMI z scores) among children at ages 1 and 3 years. Results: Of the 935 mother-infant pairs in the study (mean [SD] age, 32.5 [4.5] years) 382 (40.9%) were overweight, 69 of 926 infants (7.5%) were overweight at age 1 year, and 90 of 866 infants (10.4%) were overweight at age 3 years. Compared with being born vaginally to a mother of normal weight, infants born vaginally to overweight or obese mothers were 3 times more likely to become overweight at age 1 year (adjusted odds ratio [OR], 3.33; 95% CI, 1.49-7.41), while cesarean-delivered infants of overweight mothers had a 5-fold risk of overweight at age 1 year (adjusted OR, 5.02; 95% CI, 2.04-12.38). Similar risks were also observed at age 3 years. Multiple mediator path modeling revealed that birth mode and infant gut microbiota (Firmicutes species richness, especially of the Lachnospiraceae family) sequentially mediated the association between maternal prepregnancy overweight and childhood overweight at ages 1 and 3 years. Bacterial genera belonging to the Lachnospiraceae family were more abundant in infants of overweight mothers; however, the participating genera of Lachnospiraceae differed between infants delivered vaginally and those delivered via cesarean birth. Conclusions and relevance: This study found evidence of a novel sequential mediator pathway involving birth mode and Firmicutes species richness (especially higher abundance of Lachnospiraceae) for the intergenerational transmission of overweight.

JAMA pediatrics · cohort or longitudinal · 208 citationsread the source →

Substance use and abuse in first-episode psychosis: prevalence before and after early intervention.

Unlabelled: Despite the high prevalence of substance abuse among first-episode psychosis (FEP) populations, few studies examine whether early intervention (EI) improves substance abuse. Objective: To examine the prevalence and pattern of substance use and abuse among an FEP sample over 12 months. Methods: All the participants were diagnosed with a first episode of a schizophrenia spectrum disorder. The participants were followed prospectively. The prevalence rates of substance use and abuse from this sample were compared before and after 12 months of EI services and were compared with rates observed in a sample from the general population. Results: A total of 200 participants (80.0% males; mean age 24 years) entered the study: 183 participants completed all the assessments at baseline, 131 participants completed all the assessments at 12 months. At baseline, the findings showed similar prevalence rates between the FEP sample and the general sample for lifetime cannabis use (60% vs 55%, respectively) and hazardous alcohol use (26% vs 21%) but significantly different prevalence rates for lifetime hallucinogen (29% vs 15%; P < .001) and cocaine use (20% vs 14%; P < .001). At 12 months, the prevalence rates for drug abuse (P < .01), hazardous alcohol use (P < .01), and concurrent drug abuse and hazardous alcohol use (P < .05) were significantly lower than at baseline. Conclusion: Substance use and abuse decreased significantly after 12 months of EI services; EI services may be able to detect and to reduce substance use among FEP patients before it becomes a more serious disorder.

Schizophrenia bulletin · cohort or longitudinal · 74 citationsread the source →

Effect of Varenicline Combined With Medical Management on Alcohol Use Disorder With Comorbid Cigarette Smoking: A Randomized Clinical Trial.

Importance: Individuals with alcohol use disorder have high rates of cigarette smoking. Varenicline tartrate, an approved treatment for smoking cessation, may reduce both drinking and smoking. Objectives: To test the efficacy of varenicline with medical management for patients with alcohol use disorder and comorbid smoking seeking alcohol treatment, and to evaluate the secondary effects on smoking abstinence. Design, setting, and participants: This phase 2, randomized, double-blind, parallel group, placebo-controlled trial was conducted at 2 outpatient clinics from September 19, 2012, to August 31, 2015. Eligible participants met alcohol-dependence criteria and reported heavy drinking (≥5 drinks for men and ≥4 drinks for women) 2 or more times per week and smoking 2 or more times per week; 131 participants were randomized to either varenicline or placebo stratified by sex and site. All analyses were of the intention-to-treat type. Data analysis was conducted from February 5, 2016, to September 29, 2017. Interventions: Varenicline tartrate, 1 mg twice daily, and matching placebo pills for 16 weeks. Medical management emphasized medication adherence for 4 weeks followed by support for changing drinking. Main outcomes and measures: Percentage of heavy drinking days (PHDD) weeks 9 to 16, no heavy drinking days (NHDD) weeks 9 to 16, and prolonged smoking abstinence weeks 13 to 16. Results: Of 131 participants, 39 (29.8%) were women and 92 (70.2%) were men, the mean (SD) age was 42.7 (11.7) years, and the race/ethnicity self-identified by most respondents was black (69 [52.7%]). Sixty-four participants were randomized to receive varenicline, and 67 to receive placebo. Mean change in PHDD between varenicline and placebo across sex and site was not significantly different. However, a significant treatment by sex by time interaction for PHDD (F1,106 = 4.66; P = .03) revealed that varenicline compared with placebo resulted in a larger decrease in log-transformed PHDD in men (least square [LS] mean difference in change from baseline, 0.54; 95% CI, -0.09 to 1.18; P = .09; Cohen d = 0.45) but a smaller decrease in women (LS mean difference, -0.69; 95% CI, -1.63 to 0.25; P = .15; Cohen d = -0.53). Thirteen of 45 men (29%) had NHDD taking varenicline compared with 3 of 47 men (6%) taking placebo (Cohen h = 0.64; 95% CI, 0.22-1.03), whereas 1 of 19 women (5%) had NHDD compared with 5 of 20 women (25%) taking placebo (Cohen h = -0.60; 95% CI, -1.21 to 0.04). Taking varenicline, 8 of 64 participants (13%) achieved prolonged smoking abstinence; no one (0 of 67) quit smoking taking placebo (P = .003; Cohen h = 0.72; 95% CI, 0.38-1.07). Conclusions and relevance: Varenicline with medical management resulted in decreased heavy drinking among men and increased smoking abstinence in the overall sample. Varenicline could be considered to promote improvements in men with these dual behavioral health risks. Trial registration: clinicaltrials.gov Identifier: NCT01553136.

JAMA psychiatry · randomised controlled trial · 77 citationsread the source →

Cannabinoid facilitation of fear extinction memory recall in humans.

A first-line approach to treat anxiety disorders is exposure-based therapy, which relies on extinction processes such as repeatedly exposing the patient to stimuli (conditioned stimuli; CS) associated with the traumatic, fear-related memory. However, a significant number of patients fail to maintain their gains, partly attributed to the fact that this inhibitory learning and its maintenance is temporary and conditioned fear responses can return. Animal studies have shown that activation of the cannabinoid system during extinction learning enhances fear extinction and its retention. Specifically, CB1 receptor agonists, such as Δ9-tetrahydrocannibinol (THC), can facilitate extinction recall by preventing recovery of extinguished fear in rats. However, this phenomenon has not been investigated in humans. We conducted a study using a randomized, double-blind, placebo-controlled, between-subjects design, coupling a standard Pavlovian fear extinction paradigm and simultaneous skin conductance response (SCR) recording with an acute pharmacological challenge with oral dronabinol (synthetic THC) or placebo (PBO) 2 h prior to extinction learning in 29 healthy adult volunteers (THC = 14; PBO = 15) and tested extinction retention 24 h after extinction learning. Compared to subjects that received PBO, subjects that received THC showed low SCR to a previously extinguished CS when extinction memory recall was tested 24 h after extinction learning, suggesting that THC prevented the recovery of fear. These results provide the first evidence that pharmacological enhancement of extinction learning is feasible in humans using cannabinoid system modulators, which may thus warrant further development and clinical testing. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

Neuropharmacology · randomised controlled trial · 129 citationsread the source →

Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial.

Background: Obesity is associated with a reduction in life expectancy and an increase in mortality from cardiovascular diseases, cancer, and other causes. We therefore assessed the efficacy and safety of two doses of phentermine plus topiramate controlled-release combination as an adjunct to diet and lifestyle modification for weight loss and metabolic risk reduction in individuals who were overweight and obese, with two or more risk factors. Methods: In this 56-week phase 3 trial, we randomly assigned overweight or obese adults (aged 18-70 years), with a body-mass index of 27-45 kg/m(2) and two or more comorbidities (hypertension, dyslipidaemia, diabetes or prediabetes, or abdominal obesity) to placebo, once-daily phentermine 7·5 mg plus topiramate 46·0 mg, or once-daily phentermine 15·0 mg plus topiramate 92·0 mg in a 2:1:2 ratio in 93 centres in the USA. Drugs were administered orally. Patients were randomly assigned by use of a computer-generated algorithm that was implemented through an interactive voice response system, and were stratified by sex and diabetic status. Investigators, patients, and study sponsors were masked to treatment. Primary endpoints were the percentage change in bodyweight and the proportion of patients achieving at least 5% weight loss. Analysis was by intention to treat. This study is registered with Clinical Trials.gov, number NCT00553787. Findings: Of 2487 patients, 994 were assigned to placebo, 498 to phentermine 7·5 mg plus topiramate 46·0 mg, and 995 to phentermine 15·0 mg plus topiramate 92·0 mg; 979, 488, and 981 patients, respectively, were analysed. At 56 weeks, change in bodyweight was -1·4 kg (least-squares mean -1·2%, 95% CI -1·8 to -0·7), -8·1 kg (-7·8%, -8·5 to -7·1; p<0·0001), and -10·2 kg (-9·8%, -10·4 to -9·3; p<0·0001) in the patients assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus topiramate 92·0 mg, respectively. 204 (21%) patients achieved at least 5% weight loss with placebo, 303 (62%; odds ratio 6·3, 95% CI 4·9 to 8·0; p<0·0001) with phentermine 7·5 mg plus topiramate 46·0 mg, and 687 (70%; 9·0, 7·3 to 11·1; p<0·0001) with phentermine 15·0 mg plus topiramate 92·0 mg; for ≥10% weight loss, the corresponding numbers were 72 (7%), 182 (37%; 7·6, 5·6 to 10·2; p<0·0001), and 467 (48%; 11·7, 8·9 to 15·4; p<0·0001). The most common adverse events were dry mouth (24 [2%], 67 [13%], and 207 [21%] in the groups assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus topiramate 92·0 mg, respectively), paraesthesia (20 [2%], 68 [14%], and 204 [21%], respectively), constipation (59 [6%], 75 [15%], and 173 [17%], respectively), insomnia (47 [5%], 29 [6%], and 102 [10%], respectively), dizziness (31 [3%], 36 [7%], 99 [10%], respectively), and dysgeusia (11 [1%], 37 [7%], and 103 [10%], respectively). 38 (4%) patients assigned to placebo, 19 (4%) to phentermine 7·5 mg plus topiramate 46·0 mg, and 73 (7%) to phentermine 15·0 mg plus topiramate 92·0 mg had depression-related adverse events; and 28 (3%), 24 (5%), and 77 (8%), respectively, had anxiety-related adverse events. Interpretation: The combination of phentermine and topiramate, with office-based lifestyle interventions, might be a valuable treatment for obesity that can be provided by family doctors. Funding: Vivus.

Lancet (London, England) · randomised controlled trial · 667 citationsread the source →

Text Messaging-Based Interventions for Smoking Cessation: A Systematic Review and Meta-Analysis.

Background: Tobacco use is one of the leading preventable global health problems producing nearly 6 million smoking-related deaths per year. Interventions delivered via text messaging (short message service, SMS) may increase access to educational and support services that promote smoking cessation across diverse populations. Objective: The purpose of this meta-analysis is to (1) evaluate the efficacy of text messaging interventions on smoking outcomes, (2) determine the robustness of the evidence, and (3) identify moderators of intervention efficacy. Methods: Electronic bibliographic databases were searched for records with relevant key terms. Studies were included if they used a randomized controlled trial (RCT) to examine a text messaging intervention focusing on smoking cessation. Raters coded sample and design characteristics, and intervention content. Summary effect sizes, using random-effects models, were calculated and potential moderators were examined. Results: The meta-analysis included 20 manuscripts with 22 interventions (N=15,593; 8128 (54%) women; mean age=29) from 10 countries. Smokers who received a text messaging intervention were more likely to abstain from smoking relative to controls across a number of measures of smoking abstinence including 7-day point prevalence (odds ratio (OR)=1.38, 95% confidence interval (CI)=1.22, 1.55, k=16) and continuous abstinence (OR=1.63, 95% CI=1.19, 2.24, k=7). Text messaging interventions were also more successful in reducing cigarette consumption relative to controls (d+=0.14, 95% CI=0.05, 0.23, k=9). The effect size estimates were biased when participants who were lost to follow-up were excluded from the analyses. Cumulative meta-analysis using the 18 studies (k=19) measuring abstinence revealed that the benefits of using text message interventions were established only after only five RCTs (k=5) involving 8383 smokers (OR=1.39, 95% CI=1.15, 1.67, P<.001). The inclusion of the subsequent 13 RCTs (k=14) with 6870 smokers did not change the established efficacy of text message interventions for smoking abstinence (OR=1.37, 95% CI=1.25, 1.51, P<.001). Smoking abstinence rates were stronger when text messaging interventions (1) were conducted in Asia, North America, or Europe, (2) sampled fewer women, and (3) recruited participants via the Internet. Conclusions: The evidence for the efficacy of text messaging interventions to reduce smoking behavior is well-established. Using text messaging to support quitting behavior, and ultimately long-term smoking abstinence, should be a public health priority.

JMIR mHealth and uHealth · review · 169 citationsread the source →

Emotional responses and psychological health among young people amid climate change, Fukushima's radioactive water release, and wars in Ukraine and the Middle East, and the mediating roles of media exposure and nature connectedness: a cross-national analysis.

Background: New global crises are emerging, while existing global crises remain unabated. Coping with climate change, the radioactive water released into the Pacific Ocean subsequent to the Fukushima nuclear accident in Japan, and the wars in Ukraine and the Middle East (hereafter referred to as the wars) as individual crises can negatively affect the psychological health of young people, but little is known about the compounded impact of multiple crises. We aimed to examine: (1) the emotional responses of young people towards each individual crisis, (2) how aggregate levels of emotional engagement in global crises might pose different potential trajectories in psychological health, and (3) the protective or exacerbating role of media exposure and nature connectedness as mediators on psychological health outcomes of young people. Methods: We conducted a cross-national online survey among young people (aged 18-29 years) from China, Portugal, South Africa, the USA, and the UK. We adopted stratified purposive sampling and distributed the survey using online platforms (www.wenjuan.com and www.prolific.com). Individuals were eligible for inclusion in our analysis if they were literate in Chinese or English and had no mental disorders diagnosed within the past 12 months. Participants were asked questions on their demographic characteristics and time spent on social media, including proportion of time exposed to media pertaining to global crises of interest, and they completed surveys based on validated scales that measure depression, anxiety, stress, and wellbeing, as well as emotional responses to each global crisis and nature relatedness. We assessed the survey results using descriptive statistics, ANOVA tests, cluster analysis for individual emotional responses, and structural equation modelling for the aggregate measure of emotional engagement towards individual global crises. Findings: Between Oct 20 and Nov 3, 2023, 2579 individuals participated in the survey, of whom 400 participants from each country (200 male and 200 female participants) were included in our analysis (mean age 24·36 years [SD 2·86]). The mean emotional engagement varied between the global crises of interest (on a scale from 0 to 68, where 0 indicates no emotional response and 68 indicates strong emotional responses across 17 different emotions; wars: 32·42 [SD 14·57]; climate change: 28·79 [14·17]; radioactive water: 21·26 [16·08]), and emotional engagement also varied by country; for instance, for respondents from China, mean emotional engagement in radioactive water was relatively high (39·15 [10·72]) compared with the other countries, and for respondents from the USA, engagement with the wars was relatively low (29·45 [15·78]). We found significant variations in the level of emotional engagement between different crises, with distinct emotional profiles observed among individual countries. To assess the role of media exposure and nature connectedness on psychological outcomes, using structural equation modelling, we constructed a multi-country model comprising Portugal, South Africa, the USA, and the UK, and a standalone model for China. These models elucidated associations between emotional engagement and psychological distress and wellbeing, explaining substantial portions of the variance in both. Notably, while greater emotional engagement in the ecological crises (ie, climate change and radioactive water) generally predicted worse psychological health outcomes, we found the direction of effect for war crises to have positive outcomes for mental health in the standalone China model. Additionally, we found that media exposure mediated the negative effect of wars on psychological distress in the multi-country model, and positive psychological wellbeing in the standalone China model. Moreover, nature connectedness emerged as a potent mediator, effectively mitigating the adverse mental health effects of emotional engagement with some crises, such as radioactive water and climate change. Interpretation: Our findings offer valuable insights into the nuanced dynamics of emotional engagement in global crises and its implications for mental health outcomes among young people across diverse global contexts. Further research is needed to understand the contribution of ongoing and new global crises towards a compounded negative future outlook on young people's mental health to identify effective communication and intervention strategies that can mitigate the effect of this global challenge. Funding: Research Grants Council of Hong Kong, China.

The Lancet. Planetary health · 9 citationsread the source →

Association of Childhood Adversities With Suicide Ideation and Attempts in Puerto Rican Young Adults.

Importance: Racial/ethnic and sex disparities in suicide ideation and attempts are well established, with higher risk of suicide ideation and attempt among US racial/ethnic minority school-aged youths (than their White peers) and girls and women (than boys and men). The suicide-related risk of racial/ethnic minority young adults, especially young women, may be strongly influenced by adverse childhood experiences, known early determinants of suicide ideation and attempts. Objectives: To assess lifetime and past-year prevalence estimates of suicide ideation and suicide attempt and to examine sex differences in the role of adverse childhood experiences as a prospective risk factor for Puerto Rican young adults from 2 sociocultural contexts. Design, setting, and participants: Data in this longitudinal cohort study are from 4 waves of the Boricua Youth Study, a population-based cohort study of Puerto Rican children from San Juan and Caguas, Puerto Rico, and the South Bronx, New York, 5 to 17 years of age (N = 2491; waves 1-3: 2000-2004) and 15 to 29 years of age (wave 4: 2013-2017). Data analysis was performed from February 26, 2019, to October 16, 2020. Exposures: Adverse childhood experiences were assessed by interview in childhood and early adolescence (waves 1-3) and included child maltreatment (physical, sexual, and emotional abuse and neglect), exposure to violence, parental loss (separation, divorce, and death), and parental maladjustment (mental health problems, substance or alcohol abuse, intimate partner violence, and incarceration). Main outcomes and measures: Lifetime and past-year suicide ideation and attempt were assessed in young adulthood (wave 4) using the World Health Organization Composite International Diagnostic Interview. Results: Among 2004 Puerto Rican young adults (80.4% of the original cohort; mean [SD] age, 22.9 [2.8] years; 1019 [50.8%] male), young women compared with young men had a higher prevalence of lifetime suicide attempt (9.5% vs 3.6%) and lifetime suicide ideation (16.4% vs 11.5%), whereas past-year suicide ideation (4.4% vs 2.4%) was not statistically different. Logistic regression models, adjusting for demographics and lifetime psychiatric disorders, found that young women but not young men with more adverse childhood experiences had higher odds of suicide ideation (lifetime; odds ratio [OR], 2.44; 95% CI, 1.54-3.87; past year: OR, 2.56; 95% CI, 1.18-5.55). More adverse childhood experiences were also prospectively associated with lifetime suicide attempt (OR, 1.16; 95% CI, 1.04-1.29), irrespective of sex. Conclusions and relevance: The findings of this cohort study suggest that, among Puerto Rican young adults from 2 different sociocultural contexts, adverse childhood experiences were relevant to understanding suicide attempt and suicide ideation, the latter specifically among young women. The prevention of cumulative adverse childhood experiences could reduce later risk of suicide attempts and, among young women, for suicide ideation.

JAMA psychiatry · 36 citationsread the source →

Young Australians' use of pornography and associations with sexual risk behaviours.

Objectives: Amid public health concern that rising pornography use may have a negative impact on young people's health and wellbeing, we report prevalence of pornography viewing and explore factors associated with viewing frequency and age at first viewing. Methods: Cross-sectional online survey in a convenience sample of Victorians aged 15 to 29 years recruited via social media. Results: Ever viewing pornography was reported by 815 of 941 (87%) participants. The median age at first pornography viewing was 13 years for men and 16 years for women. More frequent pornography viewing was associated with male gender, younger age, higher education, non-heterosexual identity, ever having anal intercourse and recent mental health problems. Younger age at first pornography viewing was associated with male gender, younger current age, higher education, non-heterosexual identity, younger age at first sexual contact and recent mental health problems. Conclusions: Pornography use is common and associated with some health and behavioural outcomes. Longitudinal research is needed to determine the causal impact of pornography on these factors. Implications for public health: Viewing pornography is common and frequent among young people from a young age and this needs to be considered in sexuality education.

Australian and New Zealand journal of public health · 58 citationsread the source →

Communication About Prognosis With Adolescent and Young Adult Patients With Cancer: Information Needs, Prognostic Awareness, and Outcomes of Disclosure.

Purpose Communication about prognosis affects decisions patients and family members make about cancer care, and most patients say they want to know about their chances of cure. We sought to evaluate experiences with prognosis communication among adolescents and young adults (AYAs) with cancer. Patients and Methods We surveyed 203 AYAs with cancer age 15 to 29 years (response rate, 74%) treated at Dana-Farber Cancer Institute and their oncologists. Patients were approached within 6 weeks of diagnosis and asked to report on their prognosis communication preferences and experiences, their beliefs about likelihood of cure, and psychosocial outcomes of communication, such as trust (using an item from the Trust in Physician Scale), peace of mind (using select items from the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale), and anxiety and depression (using the Hospital Anxiety and Depression Scale). Oncologists were asked to report the patient's likelihood of cure. Results Most patients (83%, 167 of 203 patients) considered prognostic information to be extremely or very important. Patients who reported having received more extensive prognostic disclosure had higher odds of trust in the oncologist (odds ratio [OR], 1.30; 95% CI, 1.01 to 1.67; P = .05), peace of mind (OR, 2.13; 95% CI, 1.29 to 3.51; P = .002), and hope related to physician communication (OR, 1.27; 95% CI, 1.01 to 1.59; P = .04), after adjusting for patient sex, age, race or ethnicity, prognosis, and diagnosis. Disclosure was also associated with lower distress related to knowing about prognosis (OR, 0.65; 95% CI, 0.44 to 0.95; P = .03). However, a majority of patients (62%) reported prognostic estimates that exceeded those reported by physicians (McNemar P < .001). Conclusion Most AYAs with cancer value receiving prognostic information, which is positively associated with aspects of well-being. However, most overestimate chances of cure relative to oncologists, highlighting the importance of efforts to improve communication with this young population.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 93 citationsread the source →

Psychological treatments for depression and anxiety in dementia and mild cognitive impairment.

Background: Experiencing anxiety and depression is very common in people living with dementia and mild cognitive impairment (MCI). There is uncertainty about the best treatment approach. Drug treatments may be ineffective and associated with adverse effects. Guidelines recommend psychological treatments. In this updated systematic review, we investigated the effectiveness of different psychological treatment approaches. Objectives: Primary objective To assess the clinical effectiveness of psychological interventions in reducing depression and anxiety in people with dementia or MCI. Secondary objectives To determine whether psychological interventions improve individuals' quality of life, cognition, activities of daily living (ADL), and reduce behavioural and psychological symptoms of dementia, and whether they improve caregiver quality of life or reduce caregiver burden. Search methods: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE, Embase, four other databases, and three trials registers on 18 February 2021. Selection criteria: We included randomised controlled trials (RCTs) that compared a psychological intervention for depression or anxiety with treatment as usual (TAU) or another control intervention in people with dementia or MCI. Data collection and analysis: A minimum of two authors worked independently to select trials, extract data, and assess studies for risk of bias. We classified the included psychological interventions as cognitive behavioural therapies (cognitive behavioural therapy (CBT), behavioural activation (BA), problem-solving therapy (PST)); 'third-wave' therapies (such as mindfulness-based cognitive therapy (MBCT)); supportive and counselling therapies; and interpersonal therapies. We compared each class of intervention with control. We expressed treatment effects as standardised mean differences or risk ratios. Where possible, we pooled data using a fixed-effects model. We used GRADE methods to assess the certainty of the evidence behind each result. Main results: We included 29 studies with 2599 participants. They were all published between 1997 and 2020. There were 15 trials of cognitive behavioural therapies (4 CBT, 8 BA, 3 PST), 11 trials of supportive and counselling therapies, three trials of MBCT, and one of interpersonal therapy. The comparison groups received either usual care, attention-control education, or enhanced usual care incorporating an active control condition that was not a specific psychological treatment. There were 24 trials of people with a diagnosis of dementia, and five trials of people with MCI. Most studies were conducted in community settings. We considered none of the studies to be at low risk of bias in all domains.  Cognitive behavioural therapies (CBT, BA, PST) Cognitive behavioural therapies are probably slightly better than treatment as usual or active control conditions for reducing depressive symptoms (standardised mean difference (SMD) -0.23, 95% CI -0.37 to -0.10; 13 trials, 893 participants; moderate-certainty evidence). They may also increase rates of depression remission at the end of treatment (risk ratio (RR) 1.84, 95% CI 1.18 to 2.88; 2 studies, with one study contributing 2 independent comparisons, 146 participants; low-certainty evidence). We were very uncertain about the effect of cognitive behavioural therapies on anxiety at the end of treatment (SMD -0.03, 95% CI -0.36 to 0.30; 3 trials, 143 participants; very low-certainty evidence). Cognitive behavioural therapies probably improve patient quality of life (SMD 0.31, 95% CI 0.13 to 0.50; 7 trials, 459 participants; moderate-certainty evidence) and activities of daily living at end of treatment compared to treatment as usual or active control (SMD -0.25, 95% CI -0.40 to -0.09; 7 trials, 680 participants; moderate-certainty evidence). Supportive and counselling interventions Meta-analysis showed that supportive and counselling interventions may have little or no effect on depressive symptoms in people with dementia compared to usual care at end of treatment (SMD -0.05, 95% CI -0.18 to 0.07; 9 trials, 994 participants; low-certainty evidence). We were very uncertain about the effects of these treatments on anxiety, which was assessed only in one small pilot study. Other interventions There were very few data and very low-certainty evidence on MBCT and interpersonal therapy, so we were unable to draw any conclusions about the effectiveness of these interventions. Authors' conclusions: CBT-based treatments added to usual care probably slightly reduce symptoms of depression for people with dementia and MCI and may increase rates of remission of depression. There may be important effect modifiers (degree of baseline depression, cognitive diagnosis, or content of the intervention). CBT-based treatments probably also have a small positive effect on quality of life and activities of daily living. Supportive and counselling interventions may not improve symptoms of depression in people with dementia. Effects of both types of treatment on anxiety symptoms are very uncertain. We are also uncertain about the effects of other types of psychological treatments, and about persistence of effects over time. To inform clinical guidelines, future studies should assess detailed components of these interventions and their implementation in different patient populations and in different settings.

The Cochrane database of systematic reviews · meta-analysis · 57 citationsread the source →

Comparative analysis of obesity prevalence, antioxidant and oxidant status in children with Down syndrome - a sibling-controlled study.

Introduction: Down syndrome (DS), a common genetic disorder, leads to various physical, cognitive, and developmental challenges. The supplementary copy of chromosome 21 introduces an abundance of genes, which potentially can influence metabolic irregularities. The aim of the study is to conduct a comprehensive comparative assessment of oxidative stress indicators (TAS, TOS, OSI), BMI, fasting glucose, and insulin levels, HOMA-IR among children and adolescents with DS in contrast to their non-DS siblings. Material and methods: and the control group (CG) comprised 20 individuals, siblings of SG (mean age 15.92 years). Anthropometric measurements were conducted. TAS, TOS, fasting glucose, and insulin were assessed. BMI, BMI SDS, OSI and HOMA-IR were calculated. Results: SG vs. CG: BMI - overweight (29,19% vs. 15%), obese (19,05% vs. 5%); TAS (1.92 mmol/l vs. 1.79 mmol/l (p = 0.0015)); TOS (51.52 mmol/l vs. 33.05 mmol/l (p = 0.014)); OSI (2475.02 vs. 1949,75 (p = 0.038)); no significant differences in fasting glucose, insulin and HOMA-IR. Statistically significant correlations in SG: TOS and BMI, BMI SDS, HOMA-IR; OSI and BMI, BMI SDS, HOMA-IR; HOMA-IR and BMI SDS; fasting insulin and BMI PC; in CG: TAS and BMI; fasting glucose and fasting insulin. Conclusions: The research results indicate differences in metabolic processes between the group of individuals with DS compared to the CG, despite shared environmental conditions. The presence of an additional copy of chromosome 21 may contribute to the occurrence of metabolic disorders. These findings emphasize the need for further research that will lead to a better understanding of these relationships and contribute to the development of effective therapeutic strategies.

Pediatric endocrinology, diabetes, and metabolism · 1 citationsread the source →

Effect of Fractional Carbon Dioxide vs Sham Laser on Sexual Function in Survivors of Breast Cancer Receiving Aromatase Inhibitors for Genitourinary Syndrome of Menopause: The LIGHT Randomized Clinical Trial.

Importance: Survivors of breast cancer present more severe symptoms of genitourinary syndrome of menopause (GSM) than patients without history of breast cancer. Recently, new treatments, such as vaginal laser therapy, have appeared, but evidence of their efficacy remains scarce. Objective: To assess the safety and efficacy of carbon dioxide (CO2) vs sham vaginal laser therapy after 6 months of follow-up in survivors of breast cancer with GSM receiving aromatase inhibitors. Design, setting, and participants: This prospective double-blind sham-controlled randomized clinical trial with two parallel study groups was performed during October 2020 to March 2022 in a tertiary referral hospital. Survivors of breast cancer using aromatase inhibitors were assessed for eligibility, and eligible patients were randomized into the 2 treatment groups. Follow-up was conducted at 6 months. Data were analyzed in July 2022. Interventions: All patients from both groups were instructed to use the first-line treatment (FLT) based on nonhormonal moisturizers and vaginal vibrator stimulation. Patients for each group were allocated to 5 monthly sessions of fractional CO2 laser therapy (CLT) or sham laser therapy (SLT). Main outcomes and measures: The primary outcome was sexual function, evaluated through Female Sexual Function Index (FSFI) score. Other subjective measures of efficacy included a visual analog scale of dyspareunia, vaginal pH, a Vaginal Health Index, quality of life (assessed via Short-Form 12), and body image (assessed with the Spanish Body Image Scale). Objective measures of efficacy included vaginal maturation index, vaginal epithelial elasticity (measured in Pascals) and vaginal epithelial thickness (measured in millimeters). Measures were assessed before and after the intervention. Tolerance (measured on a Likert scale), adverse effects, and estradiol levels were recorded. Results: Among 211 survivors of breast cancer assessed, 84 women were deemed eligible and 72 women (mean [SD] age, 52.6 [8.3] years) were randomized to CLT (35 participants) or SLT (37 participants) and analyzed. There were no statistically significant differences between groups at baseline. At 6 months, both groups showed improvement in FSFI (mean [SD] score at baseline vs 6 months: CLT, 14.8 [8.8] points vs 20.0 [9.5] points; SLT, 15.6 [7.0] points vs 23.5 [6.5] points), but there was no significant difference between CLT and SLT groups in the improvement of sexual function evaluated through the FSFI test overall (mean [SD] difference, 5.2 [1.5] points vs 7.9 [1.2] points; P = .15) or after excluding women who were not sexually active (mean [SD] difference, 2.9 [1.4] points vs 5.5 [1.1] points; P = .15). There were also no differences between improvement of the 2 groups at 6 months of follow-up in the other assessed subjective outcomes, including dyspareunia (mean [SD] difference, -4.3 [3.4] vs -4.5 [2.3]; P = .73), Vaginal Health Index (mean [SD] difference, 3.3 [4.1] vs 5.0 [4.5]; P = .17), body image (mean [SD] difference, -3.7 [4.5] vs -2.7 [4.8]; P = .35), and quality of life (mean [SD] difference, -0.3 [3.6] vs -0.7 [3.2]; P = .39). Similarly, there were no differences in improvements in objective outcomes, including vaginal pH (mean [SD] difference, -0.6 [0.9] vs -0.8 [1.2]; P = .29), vaginal maturation index (mean [SD] difference, 10.2 [17.4] vs 14.4 [17.1]; P = .15), vaginal epithelial thickness (mean [SD] difference, 0.021 [0.014] mm vs 0.013 [0.012] mm; P = .30), vaginal epithelial elasticity (mean [SD] difference, -1373 [3197] Pascals vs -2103 [3771] Pascals; P = .64). There were significant improvements in the overall analysis regardless of group in many outcomes. The 2 interventions were well tolerated, but tolerance was significantly lower in the CLT group than the SLT group (mean [SD] Likert scale score, 3.3 [1.3] vs 4.1 [1.0]; P = .007). No differences were observed in complications or serum estradiol levels. Conclusions and relevance: In this randomized clinical trial, vaginal laser treatment was found to be safe after 6 months of follow-up, but no statistically significant differences in efficacy were observed between CLT and SLT. Trial registration: ClinicalTrials.gov identifier: NCT04619485.

JAMA network open · randomised controlled trial · 62 citationsread the source →

Predictors of treatment resistance in patients with schizophrenia: a population-based cohort study.

Background: Identification of patients at high risk of treatment-resistant schizophrenia at the time of schizophrenia diagnosis would be of great clinical benefit in minimising the delay to clozapine treatment in patients unlikely to respond to non-clozapine antipsychotics. However, little is known about predictors of treatment resistance in this patient population. We used a treatment-based proxy for treatment-resistant schizophrenia to identify candidate predictors of treatment resistance at first hospital contact with a schizophrenia diagnosis. Methods: In this population-based cohort study, we obtained Danish national registry data for all adult patients (≥18 years) with incident schizophrenia diagnosed between Jan 1, 1996, and Dec 31, 2006, and followed up until Dec 31, 2010. Our main proxy definition of treatment-resistant schizophrenia was the earliest instance of either clozapine initiation or hospital admission for schizophrenia after having had two periods of different antipsychotic monotherapy. We did multivariable Cox proportional hazards regression analysis to estimate the association between baseline candidate predictors and treatment resistance. Findings: 8624 patients fulfilled the criteria for inclusion. In multivariable complete-case analyses, 1703 (21%) of 8044 patients fulfilled the main proxy definition of treatment-resistant schizophrenia during a median follow-up of 9·1 years (IQR 6·3-11·9). Younger age (hazard ratio 0·96 [95% CI 0·95-0·97]), living in a less urban area (provincial 1·38 [1·23-1·56], rural 1·44 [1·25-1·65]), primary education level (0·88 [0·79-0·98]), more than 30 bed-days in psychiatric hospital in the year before first schizophrenia diagnosis (1·54 [1·35-1·75]), inpatient at first schizophrenia diagnosis (2·07 [1·87-2·29]), paranoid subtype (1·24 [1·13-1·37]), comorbid personality disorder (1·24 [1·11-1·39]), psychotropic drug use (antipsychotics 1·51 [1·35-1·69], antidepressants 1·15 [1·03-1·29], and benzodiazepines 1·22 [1·10-1·37]), and previous suicide attempt (1·21 [1·07-1·39]) were all significantly associated with treatment-resistant schizophrenia. Interpretation: Our study identifies several candidate predictors that could potentially be included in future prediction models for treatment-resistant schizophrenia. Notably, established risk factors for schizophrenia did not predict treatment resistance, suggesting that treatment-resistant disease might be a distinct subtype of schizophrenia and not merely a more severe form. Funding: European Community's Seventh Framework Programme.

The lancet. Psychiatry · 127 citationsread the source →

Severity, predictors and clinical correlates of Post-COVID syndrome (PCS) in Germany: A prospective, multi-centre, population-based cohort study.

Background: Post-COVID syndrome (PCS) is an important sequela of COVID-19, characterised by symptom persistence for >3 months, post-acute symptom development, and worsening of pre-existing comorbidities. The causes and public health impact of PCS are still unclear, not least for the lack of efficient means to assess the presence and severity of PCS. Methods: COVIDOM is a population-based cohort study of polymerase chain reaction (PCR) confirmed cases of SARS-CoV-2 infection, recruited through public health authorities in three German regions (Kiel, Berlin, Würzburg) between November 15, 2020 and September 29, 2021. Main inclusion criteria were (i) a PCR confirmed SARS-CoV-2 infection and (ii) a period of at least 6 months between the infection and the visit to the COVIDOM study site. Other inclusion criteria were written informed consent and age ≥18 years. Key exclusion criterion was an acute reinfection with SARS-CoV-2. Study site visits included standardised interviews, in-depth examination, and biomaterial procurement. In sub-cohort Kiel-I, a PCS (severity) score was developed based upon 12 long-term symptom complexes. Two validation sub-cohorts (Würzburg/Berlin, Kiel-II) were used for PCS score replication and identification of clinically meaningful predictors. This study is registered at clinicaltrials.gov (NCT04679584) and at the German Registry for Clinical Studies (DRKS, DRKS00023742). Findings: In Kiel-I (n = 667, 57% women), 90% of participants had received outpatient treatment for acute COVID-19. Neurological ailments (61·5%), fatigue (57·1%), and sleep disturbance (57·0%) were the most frequent persisting symptoms at 6-12 months after infection. Across sub-cohorts (Würzburg/Berlin, n = 316, 52% women; Kiel-II, n = 459, 56% women), higher PCS scores were associated with lower health-related quality of life (EQ-5D-5L-VAS/-index: r = -0·54/ -0·56, all p < 0·0001). Severe, moderate, and mild/no PCS according to the individual participant's PCS score occurred in 18·8%, 48·2%, and 32·9%, respectively, of the Kiel-I sub-cohort. In both validation sub-cohorts, statistically significant predictors of the PCS score included the intensity of acute phase symptoms and the level of personal resilience. Interpretation: PCS severity can be quantified by an easy-to-use symptom-based score reflecting acute phase disease burden and general psychological predisposition. The PCS score thus holds promise to facilitate the clinical diagnosis of PCS, scientific studies of its natural course, and the development of therapeutic interventions. Funding: The COVIDOM study is funded by the Network University Medicine (NUM) as part of the National Pandemic Cohort Network (NAPKON).

EClinicalMedicine · 132 citationsread the source →

Modifiable risk factors in the first 1000 days for subsequent risk of childhood overweight in an Asian cohort: significance of parental overweight status.

Background/objective: Many studies have identified early-life risk factors for subsequent childhood overweight/obesity, but few have evaluated how they combine to influence risk of childhood overweight/obesity. We examined associations, individually and in combination, of potentially modifiable risk factors in the first 1000 days after conception with childhood adiposity and risk of overweight/obesity in an Asian cohort. Methods: Six risk factors were examined: maternal pre-pregnancy overweight/obesity (body mass index (BMI) ⩾25 kg m-2), paternal overweight/obesity at 24 months post delivery, maternal excessive gestational weight gain, raised maternal fasting glucose during pregnancy (⩾5.1 mmol l-1), breastfeeding duration <4 months and early introduction of solid foods (<4 months). Associations between number of risk factors and adiposity measures (BMI, waist-to-height ratio (WHtR), sum of skinfolds (SSFs), fat mass index (FMI) and overweight/obesity) at 48 months were assessed using multivariable regression models. Results: Of 858 children followed up at 48 months, 172 (19%) had none, 274 (32%) had 1, 244 (29%) had 2, 126 (15%) had 3 and 42 (5%) had ⩾4 risk factors. Adjusting for confounders, significant graded positive associations were observed between number of risk factors and adiposity outcomes at 48 months. Compared with children with no risk factors, those with four or more risk factors had s.d. unit increases of 0.78 (95% confidence interval 0.41-1.15) for BMI, 0.79 (0.41-1.16) for WHtR, 0.46 (0.06-0.83) for SSF and 0.67 (0.07-1.27) for FMI. The adjusted relative risk of overweight/obesity in children with four or more risk factors was 11.1(2.5-49.1) compared with children with no risk factors. Children exposed to maternal pre-pregnancy (11.8(9.8-13.8)%) or paternal overweight status (10.6(9.6-11.6)%) had the largest individual predicted probability of child overweight/obesity. Conclusions: Early-life risk factors added cumulatively to increase childhood adiposity and risk of overweight/obesity. Early-life and preconception intervention programmes may be more effective in preventing overweight/obesity if they concurrently address these multiple modifiable risk factors.

International journal of obesity (2005) · 47 citationsread the source →

Longitudinal Changes in Posttraumatic Stress Disorder After Resettlement Among Yazidi Female Refugees Exposed to Violence.

Importance: Posttraumatic stress disorder (PTSD) is highly prevalent among refugees surviving mass atrocities, especially among women. Longitudinal studies investigating factors associated with PTSD course are essential to enable adequate treatment yet widely lacking. Objective: To identify longitudinal changes in PTSD severity and posttraumatic coping among severely traumatized female refugees as well as risk and protective factors for PTSD course. Design, setting, and participants: This prospective cohort study took place in 14 German cities in the context of a humanitarian admission program that resettled 1000 especially vulnerable women and children from northern Iraq to Germany. Approximately 400 adult beneficiaries of the humanitarian admission program were eligible for the study. At baseline, a total of 116 of the 400 beneficiaries (29.0%) participated, with 96 (82.8%) of these women participating in the follow-up assessment. The study included a baseline assessment conducted 2 years after resettlement (September 1, 2017, to January 12, 2018) and a 1-year follow-up (August 29, 2018, to January 15, 2019). Exposures: Violence and/or captivity during the 2014 genocide in northern Iraq by the so-called Islamic State. Main outcomes and measures: Posttraumatic stress disorder severity and coping strategies were assessed in interpreter-aided interviews using the Impact of Event Scale-Revised. Results: A total of 116 women (mean [SD] age, 32.2 [8.2] years; 115 [99.1%] Yazidi; 1 [0.9%] Christian) participated at baseline. According to the Impact of Event Scale-Revised, a high PTSD severity was found (mean [SD] raw sum score, 60.88 [15.75] of 88, with higher scores indicating greater distress), with no significant change over time. Helpful coping strategies included prayer, belief in collective strength, and belief in personal strength. Earlier symptoms of intrusions (β = 0.389, P = .007) and longer captivity (β = 0.218, P = .02) were identified as being associated with PTSD severity 1 year later. Longer captivity was associated with PTSD aggravation over time (β = 0.227, P = .04). Posttraumatic strengthening in faith (β = -0.206, P = .05) and in social relationships (β = -0.221, P = .03) were associated with a reduction in PTSD symptoms. Conclusions and relevance: These findings suggest that female refugee survivors of genocide are at high risk for severe and chronic PTSD beyond the initial years of resettlement. The findings provide suggestions for mental health care specialized for particularly vulnerable populations.

JAMA network open · 9 citationsread the source →

Nurturing Movement: Longitudinal Associations Between Caregiver Type, Adolescent Diet, and Young Adult Physical Activity in a National Cohort.

Background: Childhood obesity rates remain high in the United States, with long-term implications for physical and mental health. Emerging research suggests that caregiving arrangements, particularly those involving non-parental caregivers such as grandparents, may influence adolescent health behaviors, including diet and physical activity. This study examined whether caregiver type (parents-only, grandparents-only, or multi-generational households) during adolescence predicted dietary patterns and physical activity trajectories into young adulthood. Methods: Data were drawn from 6260 participants in the National Longitudinal Study of Adolescent to Adult Health (Add Health). Caregiver type was identified at baseline (Wave 1), and dietary intake and physical activity were assessed across four waves from adolescence (~age 15) to early adulthood (~age 29). We employed generalized linear models and linear mixed-effects models with multiply imputed data to examine changes in sedentary behavior, individual exercise, and team sport participation over time, controlling for age, sex, and race. Results: Overall dietary intake at baseline did not significantly differ by caregiver type (Wilks' Λ = 0.998, p = 0.389); however, an exploratory comparison indicated lower dairy consumption in homes with a grandparent present (t(6258) = 1.995, p = 0.046). Trajectories of individual exercise differed significantly by caregiver type over time (Time × Caregiver interaction: F(6, 10,395.601) = 2.795, p = 0.010), with adolescents in grandparent-only households reporting higher individual exercise at Wave 1. Sedentary behavior trajectories also significantly differed by caregiver group over time (Wave × Caregiver interaction: F(6, 18,951.310) = 23.026, p < 0.001). Baseline nutrition was positively associated with individual exercise trajectories into young adulthood (Time × Nutrition interaction: F(2.961, 13,096.103) = 3.974, p = 0.012). Conclusions: Caregiver structure during adolescence appears to shape long-term physical activity patterns, albeit modestly. These findings highlight the need to consider diverse family configurations-particularly grandparent-led households-when designing public health interventions to promote adolescent nutrition and physical activity.

Nutrientsread the source →

Parental education and inequalities in child mortality: a global systematic review and meta-analysis.

Background: The educational attainment of parents, particularly mothers, has been associated with lower levels of child mortality, yet there is no consensus on the magnitude of this relationship globally. We aimed to estimate the total reductions in under-5 mortality that are associated with increased maternal and paternal education, during distinct age intervals. Methods: This study is a comprehensive global systematic review and meta-analysis of all existing studies of the effects of parental education on neonatal, infant, and under-5 child mortality, combined with primary analyses of Demographic and Health Survey (DHS) data. The literature search of seven databases (CINAHL, Embase, MEDLINE, PsycINFO, PubMed, Scopus, and Web of Science) was done between Jan 23 and Feb 8, 2019, and updated on Jan 7, 2021, with no language or publication date restrictions. Teams of independent reviewers assessed each record for its inclusion of individual-level data on parental education and child mortality and excluded articles on the basis of study design and availability of relevant statistics. Full-text screening was done in 15 languages. Data extracted from these studies were combined with primary microdata from the DHS for meta-analyses relating maternal or paternal education with mortality at six age intervals: 0-27 days, 1-11 months, 1-4 years, 0-4 years, 0-11 months, and 1 month to 4 years. Novel mixed-effects meta-regression models were implemented to address heterogeneity in referent and exposure measures among the studies and to adjust for study-level covariates (wealth or income, partner's years of schooling, and sex of the child). This study was registered with PROSPERO (CRD42020141731). Findings: The systematic review returned 5339 unique records, yielding 186 included studies after exclusions. DHS data were compiled from 114 unique surveys, capturing 3 112 474 livebirths. Data extracted from the systematic review were synthesized together with primary DHS data, for meta-analysis on a total of 300 studies from 92 countries. Both increased maternal and paternal education showed a dose-response relationship linked to reduced under-5 mortality, with maternal education emerging as a stronger predictor. We observed a reduction in under-5 mortality of 31·0% (95% CI 29·0-32·6) for children born to mothers with 12 years of education (ie, completed secondary education) and 17·3% (15·0-18·8) for children born to fathers with 12 years of education, compared with those born to a parent with no education. We also showed that a single additional year of schooling was, on average, associated with a reduction in under-5 mortality of 3·04% (2·82-3·23) for maternal education and 1·57% (1·35-1·72) for paternal education. The association between higher parental education and lower child mortality was significant for both parents at all ages studied and was largest after the first month of life. The meta-analysis framework incorporated uncertainty associated with each individual effect size into the model fitting process, in an effort to decrease the risk of bias introduced by study design and quality. Interpretation: To our knowledge, this study is the first effort to systematically quantify the transgenerational importance of education for child survival at the global level. The results showed that lower maternal and paternal education are both risk factors for child mortality, even after controlling for other markers of family socioeconomic status. This study provides robust evidence for universal quality education as a mechanism to achieve the Sustainable Development Goal target 3.2 of reducing neonatal and child mortality. Funding: Research Council of Norway, Bill & Melinda Gates Foundation, and Rockefeller Foundation-Boston University Commission on Social Determinants, Data, and Decision Making (3-D Commission).

Lancet (London, England) · meta-analysis · 132 citationsread the source →

Practitioner Review: Therapist variability, patient-reported therapeutic alliance, and clinical outcomes in adolescents undergoing mental health treatment - a systematic review and meta-analysis.

Background: Previous meta-analyses have only found small correlations (r = .10 to r = .19) between therapeutic alliance and clinical outcomes in samples of adolescents receiving psychological therapy. Although study-level variables have been found to moderate this, little is known about the impact of therapist variability. The present meta-analysis aimed to address this gap by using patient-therapist ratio as a moderator variable. Methods: Contrary to previous reviews of adolescent alliance, individual effect sizes were extracted using a preregistered conceptual hierarchy. Controlling for treatment-level confounds, a random effects meta-analysis assessed the moderating effect of patient-therapist ratio on the alliance-outcome relationship in predefined single-predictor and multipredictor meta-regressions. Results: The alliance-outcome relationship was found to be larger than previously thought (k = 28, N = 2,911, r = .29, 95% Confidence Interval 0.21, 0.37; p < .0001, I2  = 80%). When study samples exceeding the adolescent 12-19 age range were removed, the correlation rose (k = 15, N = 1,797, r = .34, 95% Confidence Interval 0.23, 0.45; p < .0001, I2  = 83%). In contrast to research with adults, patient-therapist ratio did not moderate this relationship in either single-predictor (p = .26) or multi-predictor (p = .22) models. Conclusions: The alliance-outcome relationship for adolescents was larger than previously thought, and comparable to estimates in adult samples. The failure of patient-therapist ratio to moderate its strength, however, challenges the hypothesis that variability in therapist characteristics is an important determinant of the alliance-outcome effect in this age group.

Journal of child psychology and psychiatry, and allied disciplines · meta-analysis · 48 citationsread the source →

Self-determination theory interventions for health behavior change: Meta-analysis and meta-analytic structural equation modeling of randomized controlled trials.

Objective: We conducted a meta-analysis of randomized controlled trials (RCTs) to promote health behavior change based on self-determination theory (SDT). The review aimed to (a) quantify the impact of SDT interventions on health behaviors, (b) test mediation by theoretically specified variables (autonomous motivation and perceived competence), and (c) identify moderators of intervention effectiveness. Method: Computerized searches and additional strategies identified 56 articles that yielded 65 independent tests of SDT interventions. Random effects meta-analysis and metaregressions were conducted via STATA; meta-analytic structural equation modeling (MASEM) was used to test mediation. Results: The sample-weighted average effect size for SDT interventions was d+ = .23, and there were significant effects for physical activity, sedentary behavior, diet, alcohol consumption, and smoking cessation (.16 ≥ d+ ≥ .29). Effect sizes exhibited both publication bias and small sample bias but remained significantly different from zero, albeit of smaller magnitude, after correction for bias (d+ ≥ .15). MASEM indicated that autonomous motivation and perceived competence mediated intervention effects on behavior. Metaregression analyses indicated that features of the sample, intervention, or methodology generally did not moderate effect sizes. Conclusion: The present review indicates that SDT interventions have a significant but small effect on health behavior change and suggests several directions for future research. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Journal of consulting and clinical psychology · meta-analysis · 101 citationsread the source →

Adverse childhood experiences and related outcomes among adults experiencing homelessness: a systematic review and meta-analysis.

Background: Adverse childhood experiences (ACEs) are strong risk factors for homelessness and poor health and functioning. We aimed to evaluate the lifetime prevalence of ACEs and their associations with health-related and functioning-related outcomes among homeless adults. Methods: In this systematic review and meta-analysis, we searched from database inception to Nov 11, 2020, for original and peer-reviewed studies in English that documented lifetime prevalence of ACEs or associations between ACEs and health-related or functioning-related outcomes. We selected studies if they included a definable group of homeless adults and measured at least four ACE categories. We calculated pooled estimates of lifetime prevalence of one or more ACEs and four or more ACEs with random-effects models. We used the leave-one-out method in sensitivity analyses and studied meta-regressions to explore potential moderators of ACE prevalence. We also did a narrative summary of associations between ACEs and health-related and functioning-related outcomes, as there were too few studies on each outcome for quantitative meta-analysis. This study is registered with PROSPERO, CRD42020218741. Findings: We identified 2129 studies through systematic search, of which 29 studies (16 942 individuals) were included in the systematic review, 20 studies (10 034 individuals) were included in the meta-analysis for one or more ACEs, and 15 studies (5693 individuals) were included in the meta-analysis for four or more ACEs. Studies included samples of adults experiencing homelessness in the USA, Canada, and the UK; participants in the included studies were predominantly male (65·2%) and mean ages ranged between 18·3 and 58·1 years, but many studies did not report race, ethnicity, and sexual and gender minority data. Lifetime prevalence of one or more ACEs among homeless adults was 89·8% (95% CI 83·7-93·7) and the lifetime prevalence of four or more ACEs was 53·9% (45·9-61·7). Considerable heterogeneity was identified in both meta-analyses (I2>95%). Of the potential moderators analysed, the ACE measurement tool significantly moderated the estimated lifetime prevalence of one or more ACEs and four or more ACEs, and age also significantly moderated the estimated lifetime prevalence of four or more ACEs. In the narrative synthesis, ACEs were consistently positively associated with high suicidality (two studies), suicide attempt (three studies), major depressive disorder (two studies), substance misuse (two studies), and adult victimisation (two studies). Interpretation: The lifetime prevalence of ACEs is substantially higher among homeless adults than among the general population, and ACE exposure might be associated with prevalence of mental illness, substance misuse, and victimisation. Policy efforts and evidence-based interventions are urgently needed to prevent ACEs and address associated poor outcomes among this population. Funding: Rhodes Trust and Canadian Institutes of Health Research.

The Lancet. Public health · meta-analysis · 70 citationsread the source →

The Value of Mobile Health in Improving Breastfeeding Outcomes Among Perinatal or Postpartum Women: Systematic Review and Meta-analysis of Randomized Controlled Trials.

Background: Breastfeeding is essential for maintaining the health of mothers and babies. Breastfeeding can reduce the infection rate and mortality in newborns, and can reduce the chances of overweight and obesity in children and adolescents. For mothers, a longer duration of breastfeeding can reduce the risk of breast cancer, ovarian cancer, and type 2 diabetes. Although breastfeeding has many benefits, the global breastfeeding rate is low. With the progress of time, the popularity of mobile devices has increased rapidly, and interventions based on mobile health (mHealth) may have the potential to facilitate the improvement of the breastfeeding status. Objective: The main objective of this study was to analyze the existing evidence to determine whether mHealth-based interventions can improve the status of breastfeeding. Methods: We systematically searched multiple electronic databases (PubMed, Web of Science, The Cochrane Library, Embase, CNKI, WanFang, and Vip ) to identify eligible studies published from 1966 to October 29, 2020. Included studies were randomized controlled trials (RCTs) studying the influence of mHealth on breastfeeding. The Cochrane Collaboration Risk of Bias tool was used to examine the risk of publication bias. RevMan 5.3 was used to analyze the data. Results: A total of 15 RCTs with a total sample size of 4366 participates met the inclusion criteria. Compared with usual care, interventions based on mHealth significantly increased the postpartum exclusive breastfeeding rate (odds ratio [OR] 3.18, 95% CI 2.20-4.59; P<.001), enhanced breastfeeding self-efficacy (mean difference [MD] 8.15, 95% CI 3.79-12.51; P=.002; I2=88%), reduced health problems in infants (OR 0.62, 95% CI 0.43-0.90; P=.01; I2=0%), and improved participants' attitudes toward breastfeeding compared with usual care (MD 3.94, 95% CI 1.95-5.92; P<.001; I2=0%). There was no significant difference in the initiation of breastfeeding within an hour of birth between the intervention group and the usual care group (OR 1.26, 95% CI 0.55-2.90; P=.59). In addition, subgroup analysis was carried out according to different subjects and publication times. The results showed that the breastfeeding rate was not limited by the types of subjects. The breastfeeding rate based on mHealth at 1 month and 2 months after delivery did not change over the time of publication (2009 to 2020), and the breastfeeding rate based on mHealth at 3 months and 6 months after delivery gradually increased with time (2009 to 2020). Conclusions: Interventions based on mHealth can significantly improve the rate of postpartum exclusive breastfeeding, breastfeeding efficacy, and participants' attitudes toward breastfeeding, and reduce health problems in infants. Therefore, encouraging women to join the mHealth team is feasible, and breastfeeding-related information can be provided through simple measures, such as text messages, phone calls, and the internet, to improve the health of postpartum women and their babies.

JMIR mHealth and uHealth · meta-analysis · 49 citationsread the source →

Long working hours, socioeconomic status, and the risk of incident type 2 diabetes: a meta-analysis of published and unpublished data from 222 120 individuals.

Background: Working long hours might have adverse health effects, but whether this is true for all socioeconomic status groups is unclear. In this meta-analysis stratified by socioeconomic status, we investigated the role of long working hours as a risk factor for type 2 diabetes. Methods: We identified four published studies through a systematic literature search of PubMed and Embase up to April 30, 2014. Study inclusion criteria were English-language publication; prospective design (cohort study); investigation of the effect of working hours or overtime work; incident diabetes as an outcome; and relative risks, odds ratios, or hazard ratios (HRs) with 95% CIs, or sufficient information to calculate these estimates. Additionally, we used unpublished individual-level data from 19 cohort studies from the Individual-Participant-Data Meta-analysis in Working-Populations Consortium and international open-access data archives. Effect estimates from published and unpublished data from 222 120 men and women from the USA, Europe, Japan, and Australia were pooled with random-effects meta-analysis. Findings: During 1·7 million person-years at risk, 4963 individuals developed diabetes (incidence 29 per 10 000 person-years). The minimally adjusted summary risk ratio for long (≥55 h per week) compared with standard working hours (35-40 h) was 1·07 (95% CI 0·89-1·27, difference in incidence three cases per 10 000 person-years) with significant heterogeneity in study-specific estimates (I(2)=53%, p=0·0016). In an analysis stratified by socioeconomic status, the association between long working hours and diabetes was evident in the low socioeconomic status group (risk ratio 1·29, 95% CI 1·06-1·57, difference in incidence 13 per 10 000 person-years, I(2)=0%, p=0·4662), but was null in the high socioeconomic status group (1·00, 95% CI 0·80-1·25, incidence difference zero per 10 000 person-years, I(2)=15%, p=0·2464). The association in the low socioeconomic status group was robust to adjustment for age, sex, obesity, and physical activity, and remained after exclusion of shift workers. Interpretation: In this meta-analysis, the link between longer working hours and type 2 diabetes was apparent only in individuals in the low socioeconomic status groups. Funding: Medical Research Council, European Union New and Emerging Risks in Occupational Safety and Health research programme, Finnish Work Environment Fund, Swedish Research Council for Working Life and Social Research, German Social Accident Insurance, Danish National Research Centre for the Working Environment, Academy of Finland, Ministry of Social Affairs and Employment (Netherlands), Economic and Social Research Council, US National Institutes of Health, and British Heart Foundation.

The lancet. Diabetes & endocrinology · meta-analysis · 174 citationsread the source →

Cannabis-based medicines for chronic neuropathic pain in adults.

Background: This review is one of a series on drugs used to treat chronic neuropathic pain. Estimates of the population prevalence of chronic pain with neuropathic components range between 6% and 10%. Current pharmacological treatment options for neuropathic pain afford substantial benefit for only a few people, often with adverse effects that outweigh the benefits. There is a need to explore other treatment options, with different mechanisms of action for treatment of conditions with chronic neuropathic pain. Cannabis has been used for millennia to reduce pain. Herbal cannabis is currently strongly promoted by some patients and their advocates to treat any type of chronic pain. Objectives: To assess the efficacy, tolerability, and safety of cannabis-based medicines (herbal, plant-derived, synthetic) compared to placebo or conventional drugs for conditions with chronic neuropathic pain in adults. Search methods: In November 2017 we searched CENTRAL, MEDLINE, Embase, and two trials registries for published and ongoing trials, and examined the reference lists of reviewed articles. Selection criteria: We selected randomised, double-blind controlled trials of medical cannabis, plant-derived and synthetic cannabis-based medicines against placebo or any other active treatment of conditions with chronic neuropathic pain in adults, with a treatment duration of at least two weeks and at least 10 participants per treatment arm. Data collection and analysis: Three review authors independently extracted data of study characteristics and outcomes of efficacy, tolerability and safety, examined issues of study quality, and assessed risk of bias. We resolved discrepancies by discussion. For efficacy, we calculated the number needed to treat for an additional beneficial outcome (NNTB) for pain relief of 30% and 50% or greater, patient's global impression to be much or very much improved, dropout rates due to lack of efficacy, and the standardised mean differences for pain intensity, sleep problems, health-related quality of life (HRQoL), and psychological distress. For tolerability, we calculated number needed to treat for an additional harmful outcome (NNTH) for withdrawal due to adverse events and specific adverse events, nervous system disorders and psychiatric disorders. For safety, we calculated NNTH for serious adverse events. Meta-analysis was undertaken using a random-effects model. We assessed the quality of evidence using GRADE and created a 'Summary of findings' table. Main results: We included 16 studies with 1750 participants. The studies were 2 to 26 weeks long and compared an oromucosal spray with a plant-derived combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) (10 studies), a synthetic cannabinoid mimicking THC (nabilone) (two studies), inhaled herbal cannabis (two studies) and plant-derived THC (dronabinol) (two studies) against placebo (15 studies) and an analgesic (dihydrocodeine) (one study). We used the Cochrane 'Risk of bias' tool to assess study quality. We defined studies with zero to two unclear or high risks of bias judgements to be high-quality studies, with three to five unclear or high risks of bias to be moderate-quality studies, and with six to eight unclear or high risks of bias to be low-quality studies. Study quality was low in two studies, moderate in 12 studies and high in two studies. Nine studies were at high risk of bias for study size. We rated the quality of the evidence according to GRADE as very low to moderate. Primary outcomesCannabis-based medicines may increase the number of people achieving 50% or greater pain relief compared with placebo (21% versus 17%; risk difference (RD) 0.05 (95% confidence interval (CI) 0.00 to 0.09); NNTB 20 (95% CI 11 to 100); 1001 participants, eight studies, low-quality evidence). We rated the evidence for improvement in Patient Global Impression of Change (PGIC) with cannabis to be of very low quality (26% versus 21%;RD 0.09 (95% CI 0.01 to 0.17); NNTB 11 (95% CI 6 to 100); 1092 participants, six studies). More participants withdrew from the studies due to adverse events with cannabis-based medicines (10% of participants) than with placebo (5% of participants) (RD 0.04 (95% CI 0.02 to 0.07); NNTH 25 (95% CI 16 to 50); 1848 participants, 13 studies, moderate-quality evidence). We did not have enough evidence to determine if cannabis-based medicines increase the frequency of serious adverse events compared with placebo (RD 0.01 (95% CI -0.01 to 0.03); 1876 participants, 13 studies, low-quality evidence).Secondary outcomesCannabis-based medicines probably increase the number of people achieving pain relief of 30% or greater compared with placebo (39% versus 33%; RD 0.09 (95% CI 0.03 to 0.15); NNTB 11 (95% CI 7 to 33); 1586 participants, 10 studies, moderate quality evidence). Cannabis-based medicines may increase nervous system adverse events compared with placebo (61% versus 29%; RD 0.38 (95% CI 0.18 to 0.58); NNTH 3 (95% CI 2 to 6); 1304 participants, nine studies, low-quality evidence). Psychiatric disorders occurred in 17% of participants using cannabis-based medicines and in 5% using placebo (RD 0.10 (95% CI 0.06 to 0.15); NNTH 10 (95% CI 7 to 16); 1314 participants, nine studies, low-quality evidence).We found no information about long-term risks in the studies analysed. Subgroup analysesWe are uncertain whether herbal cannabis reduces mean pain intensity (very low-quality evidence). Herbal cannabis and placebo did not differ in tolerability (very low-quality evidence). Authors' conclusions: The potential benefits of cannabis-based medicine (herbal cannabis, plant-derived or synthetic THC, THC/CBD oromucosal spray) in chronic neuropathic pain might be outweighed by their potential harms. The quality of evidence for pain relief outcomes reflects the exclusion of participants with a history of substance abuse and other significant comorbidities from the studies, together with their small sample sizes.

The Cochrane database of systematic reviews · meta-analysis · 288 citationsread the source →

Yoga for improving health-related quality of life, mental health and cancer-related symptoms in women diagnosed with breast cancer.

Background: Breast cancer is the cancer most frequently diagnosed in women worldwide. Even though survival rates are continually increasing, breast cancer is often associated with long-term psychological distress, chronic pain, fatigue and impaired quality of life. Yoga comprises advice for an ethical lifestyle, spiritual practice, physical activity, breathing exercises and meditation. It is a complementary therapy that is commonly recommended for breast cancer-related impairments and has been shown to improve physical and mental health in people with different cancer types. Objectives: To assess effects of yoga on health-related quality of life, mental health and cancer-related symptoms among women with a diagnosis of breast cancer who are receiving active treatment or have completed treatment. Search methods: We searched the Cochrane Breast Cancer Specialised Register, MEDLINE (via PubMed), Embase, the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 1), Indexing of Indian Medical Journals (IndMED), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal and Clinicaltrials.gov on 29 January 2016. We also searched reference lists of identified relevant trials or reviews, as well as conference proceedings of the International Congress on Complementary Medicine Research (ICCMR), the European Congress for Integrative Medicine (ECIM) and the American Society of Clinical Oncology (ASCO). We applied no language restrictions. Selection criteria: Randomised controlled trials were eligible when they (1) compared yoga interventions versus no therapy or versus any other active therapy in women with a diagnosis of non-metastatic or metastatic breast cancer, and (2) assessed at least one of the primary outcomes on patient-reported instruments, including health-related quality of life, depression, anxiety, fatigue or sleep disturbances. Data collection and analysis: Two review authors independently collected data on methods and results. We expressed outcomes as standardised mean differences (SMDs) with 95% confidence intervals (CIs) and conducted random-effects model meta-analyses. We assessed potential risk of publication bias through visual analysis of funnel plot symmetry and heterogeneity between studies by using the Chi2 test and the I2 statistic. We conducted subgroup analyses for current treatment status, time since diagnosis, stage of cancer and type of yoga intervention. Main results: We included 24 studies with a total of 2166 participants, 23 of which provided data for meta-analysis. Thirteen studies had low risk of selection bias, five studies reported adequate blinding of outcome assessment and 15 studies had low risk of attrition bias. Seventeen studies that compared yoga versus no therapy provided moderate-quality evidence showing that yoga improved health-related quality of life (pooled SMD 0.22, 95% CI 0.04 to 0.40; 10 studies, 675 participants), reduced fatigue (pooled SMD -0.48, 95% CI -0.75 to -0.20; 11 studies, 883 participants) and reduced sleep disturbances in the short term (pooled SMD -0.25, 95% CI -0.40 to -0.09; six studies, 657 participants). The funnel plot for health-related quality of life was asymmetrical, favouring no therapy, and the funnel plot for fatigue was roughly symmetrical. This hints at overall low risk of publication bias. Yoga did not appear to reduce depression (pooled SMD -0.13, 95% CI -0.31 to 0.05; seven studies, 496 participants; low-quality evidence) or anxiety (pooled SMD -0.53, 95% CI -1.10 to 0.04; six studies, 346 participants; very low-quality evidence) in the short term and had no medium-term effects on health-related quality of life (pooled SMD 0.10, 95% CI -0.23 to 0.42; two studies, 146 participants; low-quality evidence) or fatigue (pooled SMD -0.04, 95% CI -0.36 to 0.29; two studies, 146 participants; low-quality evidence). Investigators reported no serious adverse events. Four studies that compared yoga versus psychosocial/educational interventions provided moderate-quality evidence indicating that yoga can reduce depression (pooled SMD -2.29, 95% CI -3.97 to -0.61; four studies, 226 participants), anxiety (pooled SMD -2.21, 95% CI -3.90 to -0.52; three studies, 195 participants) and fatigue (pooled SMD -0.90, 95% CI -1.31 to -0.50; two studies, 106 participants) in the short term. Very low-quality evidence showed no short-term effects on health-related quality of life (pooled SMD 0.81, 95% CI -0.50 to 2.12; two studies, 153 participants) or sleep disturbances (pooled SMD -0.21, 95% CI -0.76 to 0.34; two studies, 119 participants). No trial adequately reported safety-related data. Three studies that compared yoga versus exercise presented very low-quality evidence showing no short-term effects on health-related quality of life (pooled SMD -0.04, 95% CI -0.30 to 0.23; three studies, 233 participants) or fatigue (pooled SMD -0.21, 95% CI -0.66 to 0.25; three studies, 233 participants); no trial provided safety-related data. Authors' conclusions: Moderate-quality evidence supports the recommendation of yoga as a supportive intervention for improving health-related quality of life and reducing fatigue and sleep disturbances when compared with no therapy, as well as for reducing depression, anxiety and fatigue, when compared with psychosocial/educational interventions. Very low-quality evidence suggests that yoga might be as effective as other exercise interventions and might be used as an alternative to other exercise programmes.

The Cochrane database of systematic reviews · meta-analysis · 217 citationsread the source →

Health system and community level interventions for improving antenatal care coverage and health outcomes.

Background: The World Health Organization (WHO) recommends at least four antenatal care (ANC) visits for all pregnant women. Almost half of pregnant women worldwide, and especially in developing countries do not receive this amount of care. Poor attendance of ANC is associated with delivery of low birthweight babies and more neonatal deaths. ANC may include education on nutrition, potential problems with pregnancy or childbirth, child care and prevention or detection of disease during pregnancy. This review focused on community-based interventions and health systems-related interventions. Objectives: To assess the effects of health system and community interventions for improving coverage of antenatal care and other perinatal health outcomes. Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (7 June 2015) and reference lists of retrieved studies. Selection criteria: We included randomised controlled trials (RCTs), quasi-randomised trials and cluster-randomised trials. Trials of any interventions to improve ANC coverage were eligible for inclusion. Trials were also eligible if they targeted specific and related outcomes, such as maternal or perinatal death, but also reported ANC coverage. Data collection and analysis: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Main results: We included 34 trials involving approximately 400,000 women. Some trials tested community-based interventions to improve uptake of antenatal care (media campaigns, education or financial incentives for pregnant women), while other trials looked at health systems interventions (home visits for pregnant women or equipment for clinics). Most trials took place in low- and middle-income countries, and 29 of the 34 trials used a cluster-randomised design. We assessed 30 of the 34 trials as of low or unclear overall risk of bias. Comparison 1: One intervention versus no interventionWe found marginal improvements in ANC coverage of at least four visits (average odds ratio (OR) 1.11, 95% confidence interval (CI) 1.01 to 1.22; participants = 45,022; studies = 10; Heterogeneity: Tau² = 0.01; I² = 52%; high quality evidence). Sensitivity analysis with a more conservative intra-cluster correlation co-efficient (ICC) gave similar marginal results. Excluding one study at high risk of bias shifted the marginal pooled estimate towards no effect. There was no effect on pregnancy-related deaths (average OR 0.69, 95% CI 0.45 to 1.08; participants = 114,930; studies = 10; Heterogeneity: Tau² = 0.00; I² = 0%; low quality evidence), perinatal mortality (average OR 0.98, 95% CI 0.90 to 1.07; studies = 15; Heterogeneity: Tau² = 0.01; I² = 58%; moderate quality evidence) or low birthweight (average OR 0.94, 95% CI 0.82 to 1.06; studies = five; Heterogeneity: Tau² = 0.00; I² = 5%; high quality evidence). Single interventions led to marginal improvements in the number of women who delivered in health facilities (average OR 1.08, 95% CI 1.02 to 1.15; studies = 10; Heterogeneity: Tau² = 0.00; I² = 0%; high quality evidence), and in the proportion of women who had at least one ANC visit (average OR 1.68, 95% CI 1.02 to 2.79; studies = six; Heterogeneity: Tau² = 0.24; I² = 76%; moderate quality evidence). Results for ANC coverage (at least four and at least one visit) and for perinatal mortality had substantial statistical heterogeneity. Single interventions did not improve the proportion of women receiving tetanus protection (average OR 1.03, 95% CI 0.92 to 1.15; studies = 8; Heterogeneity: Tau² = 0.01; I² = 57%). No study reported onintermittent prophylactic treatment for malaria. Comparison 2: Two or more interventions versus no interventionWe found no improvements in ANC coverage of four or more visits (average OR 1.48, 95% CI 0.99 to 2.21; participants = 7840; studies = six; Heterogeneity: Tau² = 0.10; I² = 48%; low quality evidence) or pregnancy-related deaths (average OR 0.70, 95% CI 0.39 to 1.26; participants = 13,756; studies = three; Heterogeneity: Tau² = 0.00; I² = 0%; moderate quality evidence). However, combined interventions led to improvements in ANC coverage of at least one visit (average OR 1.79, 95% CI 1.47 to 2.17; studies = five; Heterogeneity: Tau² = 0.00; I² = 0%; moderate quality evidence), perinatal mortality (average OR 0.74, 95% CI 0.57 to 0.95; studies = five; Heterogeneity: Tau² = 0.06; I² = 83%; moderate quality evidence) and low birthweight (average OR 0.61, 95% CI 0.46 to 0.80; studies = two; Heterogeneity: Tau² = 0.00; I² = 0%; moderate quality evidence). Meta-analyses for both ANC coverage four or more visits and perinatal mortality had substantial statistical heterogeneity. Combined interventions improved the proportion of women who had tetanus protection (average OR 1.48, 95% CI 1.18 to 1.87; studies = 3; Heterogeneity: Tau² = 0.01; I² = 33%). No trial in this comparison reported on intermittent prophylactic treatment for malaria. Comparison 3: Two interventions compared head to head. No trials found. Comparison 4: One intervention versus a combination of interventionsThere was no difference in ANC coverage (four or more visits and at least one visit), pregnancy-related deaths, deliveries in a health facility or perinatal mortality. No trials in this comparison reported on low birthweight orintermittent prophylactic treatment of malaria. Authors' conclusions: Implications for practice - Single interventions may improve ANC coverage (at least one visit and four or more visits) and deliveries in health facilities. Combined interventions may improve ANC coverage (at least one visit), reduce perinatal mortality and reduce the occurrence of low birthweight. The effects of the interventions are unrelated to whether they are community or health system interventions. Implications for research - More details should be provided in reporting numbers of events, group totals and the ICCs used to adjust for cluster effects. Outcomes should be reported uniformly so that they are comparable to commonly-used population indicators. We recommend further cluster-RCTs of pregnant women and women in their reproductive years, using combinations of interventions and looking at outcomes that are important to pregnant women, such as maternal and perinatal morbidity and mortality, alongside the explanatory outcomes along the pathway of care: ANC coverage, the services provided during ANC and deliveries in health facilities.

The Cochrane database of systematic reviews · meta-analysis · 117 citationsread the source →

Psychosocial interventions following self-harm in adults: a systematic review and meta-analysis.

Background: Self-harm (intentional acts of non-fatal self-poisoning or self-injury) is common, particularly in young adults aged 15-35 years, often repeated, and strongly associated with suicide. Effective aftercare of individuals who self-harm is therefore important. We have undertaken a Cochrane systematic review and meta-analysis of the effectiveness of psychosocial interventions for self-harm in adults. Methods: We searched five electronic databases (CCDANCTR-Studies and References, CENTRAL, MEDLINE, Embase, and PsycINFO) between Jan 1, 1998, and April 29, 2015, for randomised controlled trials of psychosocial interventions for adults after a recent (within 6 months) episode of self-harm. Most interventions were assessed in single trials. We report results for interventions for which at least three randomised controlled trials comparing interventions with treatment as usual have been published and hence might contribute to clinical guidance. The primary outcome was repetition of self-harm at the conclusion of treatment and at 6, 12, and 24 months' follow-up analysed, when available, with the intention-to-treat method; if this was not possible, we analysed with all available case data. Findings: We identified 29 non-overlapping randomised controlled trials with three independent trials of the same intervention. Cognitive-behavioural-based psychotherapy (CBT; comprising cognitive-behavioural and problem-solving therapy) was associated with fewer participants repeating self-harm at 6 months' (odds ratio 0·54, 95% CI 0·34-0·85; 12 trials; n=1317) and at 12 months' follow-up (0·80, 0·65-0·98; ten trials; n=2232). There were also significant improvements in the secondary outcomes of depression, hopelessness, suicidal ideation, and problem solving. Patients receiving dialectical behaviour therapy (in three trials) were not less likely to repeat self-harm compared with those provided with treatment as usual at 6 months (odds ratio [OR] 0·59, 95% CI 0·16-2·15; n=267, three trials) or at 12 months (0·36, 0·05-2·47; n=172, two trials). However, the secondary endpoint of frequency of self-harm was associated with a significant reduction with use of dialectical behaviour therapy (mean difference -18·82, 95% CI -36·68 to -0·95). Four trials each of case management (OR 0·78, 95% CI 0·47-1·30; n=1608) and sending regular postcards (OR 0·87, 95% CI 0·62-1·23; n=3277) did not reduce repetition of self-harm. Interpretation: CBT seems to be effective in patients after self-harm. Dialectical behaviour therapy did not reduce the proportion of patients repeating self-harm but did reduce the frequency of self-harm. However, aside from CBT, there were few trials of other promising interventions, precluding firm conclusions as to their effectiveness. Funding: National Institute for Health Research.

The lancet. Psychiatry · meta-analysis · 141 citationsread the source →

Mental health of migrants with pre-migration exposure to armed conflict: a systematic review and meta-analysis.

Background: Exposure to armed conflict has been associated with negative mental health consequences. We aimed to estimate the prevalence of generalised anxiety disorder, major depressive disorder, and post-traumatic stress disorder among migrants exposed to armed conflict. Methods: In this systematic review and meta-analysis, we searched online databases (Cochrane Library, Embase, LILACS, PsycInfo [via Ovid], PubMed, and Web of Science Core Collection) for relevant observational studies published between Jan 1, 1994, and June 28, 2021. We included studies that used standardised psychiatric interviews to assess generalised anxiety disorder, major depressive disorder, or post-traumatic stress disorder among migrants (refugees or internally displaced persons; aged ≥18 years) with pre-migration exposure to armed conflict. We excluded studies in which exposure to armed conflict could not be ascertained, studies that included a clinical population or people with chronic diseases that can trigger the onset of mental disease, and studies published before 1994. We used a random effects model to estimate each mental health disorder's pooled prevalence and random effects meta-regression to assess sources of heterogeneity. Two independent reviewers assessed the risk of bias for each study using the Joanna Briggs Institute Checklist for Prevalence Studies. The protocol was registered with PROSPERO, CRD42020209251. Findings: Of the 13 935 studies identified, 34 met our inclusion criteria; these studies accounted for 15 549 migrants. We estimated a prevalence of current post-traumatic stress disorder of 31% (95% CI 23-40); prevalence of current major depressive disorder of 25% (17-34); and prevalence of generalised anxiety disorder of 14% (5-35). Younger age was associated with a higher prevalence of current post-traumatic stress disorder (odds ratio 0·95 [95% CI 0·90-0·99]), lifetime post-traumatic stress disorder (0·88 [0·83-0·92]), and current generalised anxiety disorder (0·87 [0·78-0·97]). A longer time since displacement was associated with a lower lifetime prevalence of post-traumatic stress disorder (0·88 [0·81-0·95]) and major depressive disorder (0·81 [0·77-0·86]). Migrating to a middle-income (8·09 [3·06-21·40]) or low-income (39·29 [11·96-129·70]) country was associated with increased prevalence of generalised anxiety disorder. Interpretation: Migrants who are exposed to armed conflict are at high risk of mental health disorders. The mental health-care needs of migrants should be assessed soon after resettlement, and adequate care should be provided, with particular attention paid to young adults. Funding: Marie Skłodowska-Curie Actions (Horizon 2020-COFUND), MinCiencias (Colombia), and Swiss National Science Foundation.

The Lancet. Public health · meta-analysis · 111 citationsread the source →

Diet, physical activity and behavioural interventions for the treatment of overweight or obese children from the age of 6 to 11 years.

Background: Child and adolescent overweight and obesity has increased globally, and can be associated with significant short- and long-term health consequences. This is an update of a Cochrane review published first in 2003, and updated previously in 2009. However, the update has now been split into six reviews addressing different childhood obesity treatments at different ages. Objectives: To assess the effects of diet, physical activity and behavioural interventions (behaviour-changing interventions) for the treatment of overweight or obese children aged 6 to 11 years. Search methods: We searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, LILACS as well as trial registers ClinicalTrials.gov and ICTRP Search Portal. We checked references of studies and systematic reviews. We did not apply any language restrictions. The date of the last search was July 2016 for all databases. Selection criteria: We selected randomised controlled trials (RCTs) of diet, physical activity, and behavioural interventions (behaviour-changing interventions) for treating overweight or obese children aged 6 to 11 years, with a minimum of six months' follow-up. We excluded interventions that specifically dealt with the treatment of eating disorders or type 2 diabetes, or included participants with a secondary or syndromic cause of obesity. Data collection and analysis: Two review authors independently screened references, extracted data, assessed risk of bias, and evaluated the quality of the evidence using the GRADE instrument. We contacted study authors for additional information. We carried out meta-analyses according to the statistical guidelines in the Cochrane Handbook for Systematic Reviews of Interventions. Main results: We included 70 RCTs with a total of 8461 participants randomised to either the intervention or control groups. The number of participants per trial ranged from 16 to 686. Fifty-five trials compared a behaviour-changing intervention with no treatment/usual care control and 15 evaluated the effectiveness of adding an additional component to a behaviour-changing intervention. Sixty-four trials were parallel RCTs, and four were cluster RCTs. Sixty-four trials were multicomponent, two were diet only and four were physical activity only interventions. Ten trials had more than two arms. The overall quality of the evidence was low or very low and 62 trials had a high risk of bias for at least one criterion. Total duration of trials ranged from six months to three years. The median age of participants was 10 years old and the median BMI z score was 2.2.Primary analyses demonstrated that behaviour-changing interventions compared to no treatment/usual care control at longest follow-up reduced BMI, BMI z score and weight. Mean difference (MD) in BMI was -0.53 kg/m2 (95% confidence interval (CI) -0.82 to -0.24); P < 0.00001; 24 trials; 2785 participants; low-quality evidence. MD in BMI z score was -0.06 units (95% CI -0.10 to -0.02); P = 0.001; 37 trials; 4019 participants; low-quality evidence and MD in weight was -1.45 kg (95% CI -1.88 to -1.02); P < 0.00001; 17 trials; 1774 participants; low-quality evidence. Thirty-one trials reported on serious adverse events, with 29 trials reporting zero occurrences RR 0.57 (95% CI 0.17 to 1.93); P = 0.37; 4/2105 participants in the behaviour-changing intervention groups compared with 7/1991 participants in the comparator groups). Few trials reported health-related quality of life or behaviour change outcomes, and none of the analyses demonstrated a substantial difference in these outcomes between intervention and control. In two trials reporting on minutes per day of TV viewing, a small reduction of 6.6 minutes per day (95% CI -12.88 to -0.31), P = 0.04; 2 trials; 55 participants) was found in favour of the intervention. No trials reported on all-cause mortality, morbidity or socioeconomic effects, and few trials reported on participant views; none of which could be meta-analysed. As the meta-analyses revealed substantial heterogeneity, we conducted subgroup analyses to examine the impact of type of comparator, type of intervention, risk of attrition bias, setting, duration of post-intervention follow-up period, parental involvement and baseline BMI z score. No subgroup effects were shown for any of the subgroups on any of the outcomes. Some data indicated that a reduction in BMI immediately post-intervention was no longer evident at follow-up at less than six months, which has to be investigated in further trials. Authors' conclusions: Multi-component behaviour-changing interventions that incorporate diet, physical activity and behaviour change may be beneficial in achieving small, short-term reductions in BMI, BMI z score and weight in children aged 6 to 11 years. The evidence suggests a very low occurrence of adverse events. The quality of the evidence was low or very low. The heterogeneity observed across all outcomes was not explained by subgrouping. Further research is required of behaviour-changing interventions in lower income countries and in children from different ethnic groups; also on the impact of behaviour-changing interventions on health-related quality of life and comorbidities. The sustainability of reduction in BMI/BMI z score and weight is a key consideration and there is a need for longer-term follow-up and further research on the most appropriate forms of post-intervention maintenance in order to ensure intervention benefits are sustained over the longer term.

The Cochrane database of systematic reviews · meta-analysis · 299 citationsread the source →

Accuracy of Wristband Fitbit Models in Assessing Sleep: Systematic Review and Meta-Analysis.

Background: Wearable sleep monitors are of high interest to consumers and researchers because of their ability to provide estimation of sleep patterns in free-living conditions in a cost-efficient way. Objective: We conducted a systematic review of publications reporting on the performance of wristband Fitbit models in assessing sleep parameters and stages. Methods: In adherence with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we comprehensively searched the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane, Embase, MEDLINE, PubMed, PsycINFO, and Web of Science databases using the keyword Fitbit to identify relevant publications meeting predefined inclusion and exclusion criteria. Results: The search yielded 3085 candidate articles. After eliminating duplicates and in compliance with inclusion and exclusion criteria, 22 articles qualified for systematic review, with 8 providing quantitative data for meta-analysis. In reference to polysomnography (PSG), nonsleep-staging Fitbit models tended to overestimate total sleep time (TST; range from approximately 7 to 67 mins; effect size=-0.51, P<.001; heterogenicity: I2=8.8%, P=.36) and sleep efficiency (SE; range from approximately 2% to 15%; effect size=-0.74, P<.001; heterogenicity: I2=24.0%, P=.25), and underestimate wake after sleep onset (WASO; range from approximately 6 to 44 mins; effect size=0.60, P<.001; heterogenicity: I2=0%, P=.92) and there was no significant difference in sleep onset latency (SOL; P=.37; heterogenicity: I2=0%, P=.92). In reference to PSG, nonsleep-staging Fitbit models correctly identified sleep epochs with accuracy values between 0.81 and 0.91, sensitivity values between 0.87 and 0.99, and specificity values between 0.10 and 0.52. Recent-generation Fitbit models that collectively utilize heart rate variability and body movement to assess sleep stages performed better than early-generation nonsleep-staging ones that utilize only body movement. Sleep-staging Fitbit models, in comparison to PSG, showed no significant difference in measured values of WASO (P=.25; heterogenicity: I2=0%, P=.92), TST (P=.29; heterogenicity: I2=0%, P=.98), and SE (P=.19) but they underestimated SOL (P=.03; heterogenicity: I2=0%, P=.66). Sleep-staging Fitbit models showed higher sensitivity (0.95-0.96) and specificity (0.58-0.69) values in detecting sleep epochs than nonsleep-staging models and those reported in the literature for regular wrist actigraphy. Conclusions: Sleep-staging Fitbit models showed promising performance, especially in differentiating wake from sleep. However, although these models are a convenient and economical means for consumers to obtain gross estimates of sleep parameters and time spent in sleep stages, they are of limited specificity and are not a substitute for PSG.

Journal of medical Internet research · meta-analysis · 310 citationsread the source →

Adherence to physical activity guidelines in older adults, using objectively measured physical activity in a population-based study.

Background: Physical activity (PA) levels in older adults decline with age. The prevalence and correlates of adherence to current UK PA guidelines in older adults has not been studied using objectively measured PA, which can examine precisely whether PA is carried out in bouts of specified length and intensity. Methods: Free living men and women aged 70-93 years from 25 towns in the United Kingdom, participating in parallel on-going population based cohort studies were invited (by post) to wear a GT3x accelerometer over the hip for one week in 2010-12. Adherence to UK PA guidelines was defined as ≥150 minutes/week of moderate or vigorous PA (MVPA) in bouts of ≥10 minutes; the effect of different intensities and durations were examined. Results: 1593 men and 857 women participated (responses 51% and 29% respectively). 15% men and 10% women achieved ≥150 minutes/week of MVPA (defined as >1040 cpm) in bouts lasting ≥10 minutes. With MVPA defined as >1952 cpm, prevalences were 7% and 3% respectively. Those adhering to guidelines were younger, had fewer chronic health conditions, less depression, less severe mobility limitations, but higher exercise self-efficacy and exercise outcomes expectations. They rated their local environment more highly for social activities and leisure facilities, having somewhere nice to go for a walk and feeling safe after dark, They left the house on more days per week, were more likely to use active transport (cycle or walk) and to walk a dog regularly. Conclusions: Few older adults attain current PA guidelines. Health promotion to extend the duration of moderate-intensity activity episodes to 10 minutes or more could yield important health gains among older adults. However future studies will need to clarify whether attaining guideline amounts of PA in spells lasting 10 minutes or more is critical for reducing chronic disease risks as well as improving cardiometabolic risk factors.

BMC public health · 185 citationsread the source →

Combining GFR and albuminuria to classify CKD improves prediction of ESRD.

Despite the high prevalence of chronic kidney disease (CKD), relatively few individuals with CKD progress to ESRD. A better understanding of the risk factors for progression could improve the classification system of CKD and strategies for screening. We analyzed data from 65,589 adults who participated in the Nord-Trøndelag Health (HUNT 2) Study (1995 to 1997) and found 124 patients who progressed to ESRD after 10.3 yr of follow-up. In multivariable survival analysis, estimated GFR (eGFR) and albuminuria were independently and strongly associated with progression to ESRD: Hazard ratios for eGFR 45 to 59, 30 to 44, and 15 to 29 ml/min per 1.73 m(2) were 6.7, 18.8, and 65.7, respectively (P < 0.001 for all), and for micro- and macroalbuminuria were 13.0 and 47.2 (P < 0.001 for both). Hypertension, diabetes, male gender, smoking, depression, obesity, cardiovascular disease, dyslipidemia, physical activity and education did not add predictive information. Time-dependent receiver operating characteristic analyses showed that considering both the urinary albumin/creatinine ratio and eGFR substantially improved diagnostic accuracy. Referral based on current stages 3 to 4 CKD (eGFR 15 to 59 ml/min per 1.73 m(2)) would include 4.7% of the general population and identify 69.4% of all individuals progressing to ESRD. Referral based on our classification system would include 1.4% of the general population without losing predictive power (i.e., it would detect 65.6% of all individuals progressing to ESRD). In conclusion, all levels of reduced eGFR should be complemented by quantification of urinary albumin to predict optimally progression to ESRD.

Journal of the American Society of Nephrology : JASN · 328 citationsread the source →

Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial.

Objective: Depression is the leading cause of disability worldwide, and half of patients with depression have treatment-resistant depression. Intermittent theta-burst stimulation (iTBS) is approved by the U.S. Food and Drug Administration for the treatment of treatment-resistant depression but is limited by suboptimal efficacy and a 6-week duration. The authors addressed these limitations by developing a neuroscience-informed accelerated iTBS protocol, Stanford neuromodulation therapy (SNT; previously referred to as Stanford accelerated intelligent neuromodulation therapy, or SAINT). This protocol was associated with a remission rate of ∼90% after 5 days of open-label treatment. Here, the authors report the results of a sham-controlled double-blind trial of SNT for treatment-resistant depression. Methods: Participants with treatment-resistant depression currently experiencing moderate to severe depressive episodes were randomly assigned to receive active or sham SNT. Resting-state functional MRI was used to individually target the region of the left dorsolateral prefrontal cortex most functionally anticorrelated with the subgenual anterior cingulate cortex. The primary outcome was score on the Montgomery-Åsberg Depression Rating Scale (MADRS) 4 weeks after treatment. Results: At the planned interim analysis, 32 participants with treatment-resistant depression had been enrolled, and 29 participants who continued to meet inclusion criteria received either active (N=14) or sham (N=15) SNT. The mean percent reduction from baseline in MADRS score 4 weeks after treatment was 52.5% in the active treatment group and 11.1% in the sham treatment group. Conclusions: SNT, a high-dose iTBS protocol with functional-connectivity-guided targeting, was more effective than sham stimulation for treatment-resistant depression. Further trials are needed to determine SNT's durability and to compare it with other treatments.

The American journal of psychiatry · randomised controlled trial · 530 citationsread the source →

Multifactorial and multiple component interventions for preventing falls in older people living in the community.

Background: Falls and fall-related injuries are common, particularly in those aged over 65, with around one-third of older people living in the community falling at least once a year. Falls prevention interventions may comprise single component interventions (e.g. exercise), or involve combinations of two or more different types of intervention (e.g. exercise and medication review). Their delivery can broadly be divided into two main groups: 1) multifactorial interventions where component interventions differ based on individual assessment of risk; or 2) multiple component interventions where the same component interventions are provided to all people. Objectives: To assess the effects (benefits and harms) of multifactorial interventions and multiple component interventions for preventing falls in older people living in the community. Search methods: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature, trial registers and reference lists. Date of search: 12 June 2017. Selection criteria: Randomised controlled trials, individual or cluster, that evaluated the effects of multifactorial and multiple component interventions on falls in older people living in the community, compared with control (i.e. usual care (no change in usual activities) or attention control (social visits)) or exercise as a single intervention. Data collection and analysis: Two review authors independently selected studies, assessed risks of bias and extracted data. We calculated the rate ratio (RaR) with 95% confidence intervals (CIs) for rate of falls. For dichotomous outcomes we used risk ratios (RRs) and 95% CIs. For continuous outcomes, we used the standardised mean difference (SMD) with 95% CIs. We pooled data using the random-effects model. We used the GRADE approach to assess the quality of the evidence. Main results: We included 62 trials involving 19,935 older people living in the community. The median trial size was 248 participants. Most trials included more women than men. The mean ages in trials ranged from 62 to 85 years (median 77 years). Most trials (43 trials) reported follow-up of 12 months or over. We assessed most trials at unclear or high risk of bias in one or more domains. Forty-four trials assessed multifactorial interventions and 18 assessed multiple component interventions. (I2 not reported if = 0%).Multifactorial interventions versus usual care or attention controlThis comparison was made in 43 trials. Commonly-applied or recommended interventions after assessment of each participant's risk profile were exercise, environment or assistive technologies, medication review and psychological interventions. Multifactorial interventions may reduce the rate of falls compared with control: rate ratio (RaR) 0.77, 95% CI 0.67 to 0.87; 19 trials; 5853 participants; I2 = 88%; low-quality evidence. Thus if 1000 people were followed over one year, the number of falls may be 1784 (95% CI 1553 to 2016) after multifactorial intervention versus 2317 after usual care or attention control. There was low-quality evidence of little or no difference in the risks of: falling (i.e. people sustaining one or more fall) (RR 0.96, 95% CI 0.90 to 1.03; 29 trials; 9637 participants; I2 = 60%); recurrent falls (RR 0.87, 95% CI 0.74 to 1.03; 12 trials; 3368 participants; I2 = 53%); fall-related hospital admission (RR 1.00, 95% CI 0.92 to 1.07; 15 trials; 5227 participants); requiring medical attention (RR 0.91, 95% CI 0.75 to 1.10; 8 trials; 3078 participants). There is low-quality evidence that multifactorial interventions may reduce the risk of fall-related fractures (RR 0.73, 95% CI 0.53 to 1.01; 9 trials; 2850 participants) and may slightly improve health-related quality of life but not noticeably (SMD 0.19, 95% CI 0.03 to 0.35; 9 trials; 2373 participants; I2 = 70%). Of three trials reporting on adverse events, one found none, and two reported 12 participants with self-limiting musculoskeletal symptoms in total. Multifactorial interventions versus exerciseVery low-quality evidence from one small trial of 51 recently-discharged orthopaedic patients means that we are uncertain of the effects on rate of falls or risk of falling of multifactorial interventions versus exercise alone. Other fall-related outcomes were not assessed. Multiple component interventions versus usual care or attention controlThe 17 trials that make this comparison usually included exercise and another component, commonly education or home-hazard assessment. There is moderate-quality evidence that multiple interventions probably reduce the rate of falls (RaR 0.74, 95% CI 0.60 to 0.91; 6 trials; 1085 participants; I2 = 45%) and risk of falls (RR 0.82, 95% CI 0.74 to 0.90; 11 trials; 1980 participants). There is low-quality evidence that multiple interventions may reduce the risk of recurrent falls, although a small increase cannot be ruled out (RR 0.81, 95% CI 0.63 to 1.05; 4 trials; 662 participants). Very low-quality evidence means that we are uncertain of the effects of multiple component interventions on the risk of fall-related fractures (2 trials) or fall-related hospital admission (1 trial). There is low-quality evidence that multiple interventions may have little or no effect on the risk of requiring medical attention (RR 0.95, 95% CI 0.67 to 1.35; 1 trial; 291 participants); conversely they may slightly improve health-related quality of life (SMD 0.77, 95% CI 0.16 to 1.39; 4 trials; 391 participants; I2 = 88%). Of seven trials reporting on adverse events, five found none, and six minor adverse events were reported in two. Multiple component interventions versus exerciseThis comparison was tested in five trials. There is low-quality evidence of little or no difference between the two interventions in rate of falls (1 trial) and risk of falling (RR 0.93, 95% CI 0.78 to 1.10; 3 trials; 863 participants) and very low-quality evidence, meaning we are uncertain of the effects on hospital admission (1 trial). One trial reported two cases of minor joint pain. Other falls outcomes were not reported. Authors' conclusions: Multifactorial interventions may reduce the rate of falls compared with usual care or attention control. However, there may be little or no effect on other fall-related outcomes. Multiple component interventions, usually including exercise, may reduce the rate of falls and risk of falling compared with usual care or attention control.

The Cochrane database of systematic reviews · systematic review · 293 citationsread the source →

Barriers and facilitators influencing the sustainment of health behaviour interventions in schools and childcare services: a systematic review.

Background: Sustainment has been defined as the sustained use or delivery of an intervention in practice following cessation of external implementation support. This review aimed to identify and synthesise factors (barriers and facilitators) that influence the sustainment of interventions (policies, practices, or programmes) in schools and childcare services that address the leading risk factors of chronic disease. Methods: Seven electronic databases and relevant reference lists were searched for articles, of any design, published in English, from inception to March 2020. Articles were included if they qualitatively and/or quantitatively reported on school or childcare stakeholders' (including teachers, principals, administrators, or managers) perceived barriers or facilitators to the sustainment of interventions addressing poor diet/nutrition, physical inactivity, obesity, tobacco smoking, or harmful alcohol use. Two independent reviewers screened texts, and extracted and coded data guided by the Integrated Sustainability Framework, an existing multi-level sustainability-specific framework that assesses factors of sustainment. Results: Of the 13,158 articles identified, 31 articles met the inclusion criteria (8 quantitative, 12 qualitative, 10 mixed-methods, and 1 summary article). Overall, 29 articles were undertaken in schools (elementary n=17, middle n=3, secondary n=4, or a combination n=5) and two in childcare settings. The main health behaviours targeted included physical activity (n=9), diet (n=3), both diet and physical activity (n=15), and smoking (n=4), either independently (n=1) or combined with other health behaviours (n=3). Findings suggest that the majority of the 59 barriers and 74 facilitators identified to impact on intervention sustainment were similar across school and childcare settings. Factors predominantly relating to the 'inner contextual factors' of the organisation including: availability of facilities or equipment, continued executive or leadership support present, and team cohesion, support, or teamwork were perceived by stakeholders as influential to intervention sustainment. Conclusions: Identifying strategies to improve the sustainment of health behaviour interventions in these settings requires a comprehensive understanding of factors that may impede or promote their ongoing delivery. This review identified multi-level factors that can be addressed by strategies to improve the sustainment of such interventions, and suggests how future research might address gaps in the evidence base. Trial registration: This review was prospectively registered on PROSPERO: CRD42020127869 , Jan. 2020.

Implementation science : IS · systematic review · 126 citationsread the source →

Additional behavioural support as an adjunct to pharmacotherapy for smoking cessation.

Background: Pharmacotherapies for smoking cessation increase the likelihood of achieving abstinence in a quit attempt. It is plausible that providing support, or, if support is offered, offering more intensive support or support including particular components may increase abstinence further. Objectives: To evaluate the effect of adding or increasing the intensity of behavioural support for people using smoking cessation medications, and to assess whether there are different effects depending on the type of pharmacotherapy, or the amount of support in each condition. We also looked at studies which directly compare behavioural interventions matched for contact time, where pharmacotherapy is provided to both groups (e.g. tests of different components or approaches to behavioural support as an adjunct to pharmacotherapy). Search methods: We searched the Cochrane Tobacco Addiction Group Specialised Register, clinicaltrials.gov, and the ICTRP in June 2018 for records with any mention of pharmacotherapy, including any type of nicotine replacement therapy (NRT), bupropion, nortriptyline or varenicline, that evaluated the addition of personal support or compared two or more intensities of behavioural support. Selection criteria: Randomised or quasi-randomised controlled trials in which all participants received pharmacotherapy for smoking cessation and conditions differed by the amount or type of behavioural support. The intervention condition had to involve person-to-person contact (defined as face-to-face or telephone). The control condition could receive less intensive personal contact, a different type of personal contact, written information, or no behavioural support at all. We excluded trials recruiting only pregnant women and trials which did not set out to assess smoking cessation at six months or longer. Data collection and analysis: For this update, screening and data extraction followed standard Cochrane methods. The main outcome measure was abstinence from smoking after at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemically-validated rates, if available. We calculated the risk ratio (RR) and 95% confidence interval (CI) for each study. Where appropriate, we performed meta-analysis using a random-effects model. Main results: Eighty-three studies, 36 of which were new to this update, met the inclusion criteria, representing 29,536 participants. Overall, we judged 16 studies to be at low risk of bias and 21 studies to be at high risk of bias. All other studies were judged to be at unclear risk of bias. Results were not sensitive to the exclusion of studies at high risk of bias. We pooled all studies comparing more versus less support in the main analysis. Findings demonstrated a benefit of behavioural support in addition to pharmacotherapy. When all studies of additional behavioural therapy were pooled, there was evidence of a statistically significant benefit from additional support (RR 1.15, 95% CI 1.08 to 1.22, I² = 8%, 65 studies, n = 23,331) for abstinence at longest follow-up, and this effect was not different when we compared subgroups by type of pharmacotherapy or intensity of contact. This effect was similar in the subgroup of eight studies in which the control group received no behavioural support (RR 1.20, 95% CI 1.02 to 1.43, I² = 20%, n = 4,018). Seventeen studies compared interventions matched for contact time but that differed in terms of the behavioural components or approaches employed. Of the 15 comparisons, all had small numbers of participants and events. Only one detected a statistically significant effect, favouring a health education approach (which the authors described as standard counselling containing information and advice) over motivational interviewing approach (RR 0.56, 95% CI 0.33 to 0.94, n = 378). Authors' conclusions: There is high-certainty evidence that providing behavioural support in person or via telephone for people using pharmacotherapy to stop smoking increases quit rates. Increasing the amount of behavioural support is likely to increase the chance of success by about 10% to 20%, based on a pooled estimate from 65 trials. Subgroup analysis suggests that the incremental benefit from more support is similar over a range of levels of baseline support. More research is needed to assess the effectiveness of specific components that comprise behavioural support.

The Cochrane database of systematic reviews · systematic review · 110 citationsread the source →

Revolutionizing e-health: the transformative role of AI-powered hybrid chatbots in healthcare solutions.

Introduction: The integration of Artificial Intelligence (AI) in healthcare, particularly through hybrid chatbots, is reshaping the industry by enhancing service delivery, patient engagement, and clinical outcomes. These chatbots combine AI with human input to provide intelligent, personalized interactions in areas like diagnostics, chronic disease management, and mental health support. However, gaps remain in trust, data security, system integration, and user experience, which hinder widespread adoption. Key challenges include the hesitancy of patients to trust AI due to concerns over data privacy and the accuracy of medical advice, as well as difficulties in integrating chatbots into existing healthcare infrastructures. The review aims to assess the effectiveness of hybrid AI chatbots in improving healthcare outcomes, reducing costs, and enhancing patient engagement, while identifying barriers to adoption such as cultural adaptability and trust issues. The novelty of the review lies in its comprehensive exploration of both technological advancements and the socio-emotional factors influencing chatbot acceptance. Methods: The review follows a systematic methodology with four core components: eligibility criteria, review selection, data extraction, and data synthesis. Studies focused on AI applications and hybrid chatbots in healthcare, particularly in chronic disease management and mental health support, were included. Publications from 2022 to 2025 were prioritized, and peer-reviewed sources in English were considered. After screening 116 studies, 29 met the criteria for inclusion. Data was extracted using a structured template, capturing study objectives, methodologies, findings, and challenges. Thematic analysis was applied to identify four themes: AI applications, technical advancements, user adoption, and challenges/ethical concerns. Statistical and content analysis methods were employed to synthesize the data comprehensively, ensuring robustness in the findings. Results: Hybrid chatbots in healthcare have shown significant benefits, such as reducing hospital readmissions by up to 25%, improving patient engagement by 30%, and cutting consultation wait times by 15%. They are widely used for chronic disease management, mental health support, and patient education, demonstrating their efficiency in both developed and developing countries. Discussion: The review concludes that overcoming these barriers through infrastructure investment, training, and enhanced transparency is crucial for maximizing the potential of AI in healthcare. Future researchers should focus on long-term outcomes, addressing ethical considerations, and expanding cross-cultural adaptability. Limitations of the review include the narrow scope of some case studies and the absence of long-term data on AI's efficacy in diverse healthcare contexts. Further studies are needed to explore these challenges and the long-term impact of AI-driven healthcare solutions.

Frontiers in public health · systematic review · 23 citationsread the source →

Drugs for preventing postoperative nausea and vomiting in adults after general anaesthesia: a network meta-analysis.

Background: Postoperative nausea and vomiting (PONV) is a common adverse effect of anaesthesia and surgery. Up to 80% of patients may be affected. These outcomes are a major cause of patient dissatisfaction and may lead to prolonged hospital stay and higher costs of care along with more severe complications. Many antiemetic drugs are available for prophylaxis. They have various mechanisms of action and side effects, but there is still uncertainty about which drugs are most effective with the fewest side effects. Objectives: • To compare the efficacy and safety of different prophylactic pharmacologic interventions (antiemetic drugs) against no treatment, against placebo, or against each other (as monotherapy or combination prophylaxis) for prevention of postoperative nausea and vomiting in adults undergoing any type of surgery under general anaesthesia • To generate a clinically useful ranking of antiemetic drugs (monotherapy and combination prophylaxis) based on efficacy and safety • To identify the best dose or dose range of antiemetic drugs in terms of efficacy and safety SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, and reference lists of relevant systematic reviews. The first search was performed in November 2017 and was updated in April 2020. In the update of the search, 39 eligible studies were found that were not included in the analysis (listed as awaiting classification). Selection criteria: Randomized controlled trials (RCTs) comparing effectiveness or side effects of single antiemetic drugs in any dose or combination against each other or against an inactive control in adults undergoing any type of surgery under general anaesthesia. All antiemetic drugs belonged to one of the following substance classes: 5-HT₃ receptor antagonists, D₂ receptor antagonists, NK₁ receptor antagonists, corticosteroids, antihistamines, and anticholinergics. No language restrictions were applied. Abstract publications were excluded. Data collection and analysis: A review team of 11 authors independently assessed trials for inclusion and risk of bias and subsequently extracted data. We performed pair-wise meta-analyses for drugs of direct interest (amisulpride, aprepitant, casopitant, dexamethasone, dimenhydrinate, dolasetron, droperidol, fosaprepitant, granisetron, haloperidol, meclizine, methylprednisolone, metoclopramide, ondansetron, palonosetron, perphenazine, promethazine, ramosetron, rolapitant, scopolamine, and tropisetron) compared to placebo (inactive control). We performed network meta-analyses (NMAs) to estimate the relative effects and ranking (with placebo as reference) of all available single drugs and combinations. Primary outcomes were vomiting within 24 hours postoperatively, serious adverse events (SAEs), and any adverse event (AE). Secondary outcomes were drug class-specific side effects (e.g. headache), mortality, early and late vomiting, nausea, and complete response. We performed subgroup network meta-analysis with dose of drugs as a moderator variable using dose ranges based on previous consensus recommendations. We assessed certainty of evidence of NMA treatment effects for all primary outcomes and drug class-specific side effects according to GRADE (CINeMA, Confidence in Network Meta-Analysis). We restricted GRADE assessment to single drugs of direct interest compared to placebo. Main results: We included 585 studies (97,516 randomized participants). Most of these studies were small (median sample size of 100); they were published between 1965 and 2017 and were primarily conducted in Asia (51%), Europe (25%), and North America (16%). Mean age of the overall population was 42 years. Most participants were women (83%), had American Society of Anesthesiologists (ASA) physical status I and II (70%), received perioperative opioids (88%), and underwent gynaecologic (32%) or gastrointestinal surgery (19%) under general anaesthesia using volatile anaesthetics (88%). In this review, 44 single drugs and 51 drug combinations were compared. Most studies investigated only single drugs (72%) and included an inactive control arm (66%). The three most investigated single drugs in this review were ondansetron (246 studies), dexamethasone (120 studies), and droperidol (97 studies). Almost all studies (89%) reported at least one efficacy outcome relevant for this review. However, only 56% reported at least one relevant safety outcome. Altogether, 157 studies (27%) were assessed as having overall low risk of bias, 101 studies (17%) overall high risk of bias, and 327 studies (56%) overall unclear risk of bias. Vomiting within 24 hours postoperatively Relative effects from NMA for vomiting within 24 hours (282 RCTs, 50,812 participants, 28 single drugs, and 36 drug combinations) suggest that 29 out of 36 drug combinations and 10 out of 28 single drugs showed a clinically important benefit (defined as the upper end of the 95% confidence interval (CI) below a risk ratio (RR) of 0.8) compared to placebo. Combinations of drugs were generally more effective than single drugs in preventing vomiting. However, single NK₁ receptor antagonists showed treatment effects similar to most of the drug combinations. High-certainty evidence suggests that the following single drugs reduce vomiting (ordered by decreasing efficacy): aprepitant (RR 0.26, 95% CI 0.18 to 0.38, high certainty, rank 3/28 of single drugs); ramosetron (RR 0.44, 95% CI 0.32 to 0.59, high certainty, rank 5/28); granisetron (RR 0.45, 95% CI 0.38 to 0.54, high certainty, rank 6/28); dexamethasone (RR 0.51, 95% CI 0.44 to 0.57, high certainty, rank 8/28); and ondansetron (RR 0.55, 95% CI 0.51 to 0.60, high certainty, rank 13/28). Moderate-certainty evidence suggests that the following single drugs probably reduce vomiting: fosaprepitant (RR 0.06, 95% CI 0.02 to 0.21, moderate certainty, rank 1/28) and droperidol (RR 0.61, 95% CI 0.54 to 0.69, moderate certainty, rank 20/28). Recommended and high doses of granisetron, dexamethasone, ondansetron, and droperidol showed clinically important benefit, but low doses showed no clinically important benefit. Aprepitant was used mainly at high doses, ramosetron at recommended doses, and fosaprepitant at doses of 150 mg (with no dose recommendation available). Frequency of SAEs Twenty-eight RCTs were included in the NMA for SAEs (10,766 participants, 13 single drugs, and eight drug combinations). The certainty of evidence for SAEs when using one of the best and most reliable anti-vomiting drugs (aprepitant, ramosetron, granisetron, dexamethasone, ondansetron, and droperidol compared to placebo) ranged from very low to low. Droperidol (RR 0.88, 95% CI 0.08 to 9.71, low certainty, rank 6/13) may reduce SAEs. We are uncertain about the effects of aprepitant (RR 1.39, 95% CI 0.26 to 7.36, very low certainty, rank 11/13), ramosetron (RR 0.89, 95% CI 0.05 to 15.74, very low certainty, rank 7/13), granisetron (RR 1.21, 95% CI 0.11 to 13.15, very low certainty, rank 10/13), dexamethasone (RR 1.16, 95% CI 0.28 to 4.85, very low certainty, rank 9/13), and ondansetron (RR 1.62, 95% CI 0.32 to 8.10, very low certainty, rank 12/13). No studies reporting SAEs were available for fosaprepitant. Frequency of any AE Sixty-one RCTs were included in the NMA for any AE (19,423 participants, 15 single drugs, and 11 drug combinations). The certainty of evidence for any AE when using one of the best and most reliable anti-vomiting drugs (aprepitant, ramosetron, granisetron, dexamethasone, ondansetron, and droperidol compared to placebo) ranged from very low to moderate. Granisetron (RR 0.92, 95% CI 0.80 to 1.05, moderate certainty, rank 7/15) probably has no or little effect on any AE. Dexamethasone (RR 0.77, 95% CI 0.55 to 1.08, low certainty, rank 2/15) and droperidol (RR 0.89, 95% CI 0.81 to 0.98, low certainty, rank 6/15) may reduce any AE. Ondansetron (RR 0.95, 95% CI 0.88 to 1.01, low certainty, rank 9/15) may have little or no effect on any AE. We are uncertain about the effects of aprepitant (RR 0.87, 95% CI 0.78 to 0.97, very low certainty, rank 3/15) and ramosetron (RR 1.00, 95% CI 0.65 to 1.54, very low certainty, rank 11/15) on any AE. No studies reporting any AE were available for fosaprepitant. Class-specific side effects For class-specific side effects (headache, constipation, wound infection, extrapyramidal symptoms, sedation, arrhythmia, and QT prolongation) of relevant substances, the certainty of evidence for the best and most reliable anti-vomiting drugs mostly ranged from very low to low. Exceptions were that ondansetron probably increases headache (RR 1.16, 95% CI 1.06 to 1.28, moderate certainty, rank 18/23) and probably reduces sedation (RR 0.87, 95% CI 0.79 to 0.96, moderate certainty, rank 5/24) compared to placebo. The latter effect is limited to recommended and high doses of ondansetron. Droperidol probably reduces headache (RR 0.76, 95% CI 0.67 to 0.86, moderate certainty, rank 5/23) compared to placebo. We have high-certainty evidence that dexamethasone (RR 1.00, 95% CI 0.91 to 1.09, high certainty, rank 16/24) has no effect on sedation compared to placebo. No studies assessed substance class-specific side effects for fosaprepitant. Direction and magnitude of network effect estimates together with level of evidence certainty are graphically summarized for all pre-defined GRADE-relevant outcomes and all drugs of direct interest compared to placebo in http://doi.org/10.5281/zenodo.4066353. Authors' conclusions: We found high-certainty evidence that five single drugs (aprepitant, ramosetron, granisetron, dexamethasone, and ondansetron) reduce vomiting, and moderate-certainty evidence that two other single drugs (fosaprepitant and droperidol) probably reduce vomiting, compared to placebo. Four of the six substance classes (5-HT₃ receptor antagonists, D₂ receptor antagonists, NK₁ receptor antagonists, and corticosteroids) were thus represented by at least one drug with important benefit for prevention of vomiting. Combinations of drugs were generally more effective than the corresponding single drugs in preventing vomiting. NK₁ receptor antagonists were the most effective drug class and had comparable efficacy to most of the drug combinations. 5-HT₃ receptor antagonists were the best studied substance class. For most of the single drugs of direct interest, we found only very low to low certainty evidence for safety outcomes such as occurrence of SAEs, any AE, and substance class-specific side effects. Recommended and high doses of granisetron, dexamethasone, ondansetron, and droperidol were more effective than low doses for prevention of vomiting. Dose dependency of side effects was rarely found due to the limited number of studies, except for the less sedating effect of recommended and high doses of ondansetron. The results of the review are transferable mainly to patients at higher risk of nausea and vomiting (i.e. healthy women undergoing inhalational anaesthesia and receiving perioperative opioids). Overall study quality was limited, but certainty assessments of effect estimates consider this limitation. No further efficacy studies are needed as there is evidence of moderate to high certainty for seven single drugs with relevant benefit for prevention of vomiting. However, additional studies are needed to investigate potential side effects of these drugs and to examine higher-risk patient populations (e.g. individuals with diabetes and heart disease).

The Cochrane database of systematic reviews · systematic review · 127 citationsread the source →

The effectiveness of case-based learning in health professional education. A BEME systematic review: BEME Guide No. 23.

Background: Case-based learning (CBL) is a long established pedagogical method, which is defined in a number of ways depending on the discipline and type of 'case' employed. In health professional education, learning activities are commonly based on patient cases. Basic, social and clinical sciences are studied in relation to the case, are integrated with clinical presentations and conditions (including health and ill-health) and student learning is, therefore, associated with real-life situations. Although many claims are made for CBL as an effective learning and teaching method, very little evidence is quoted or generated to support these claims. We frame this review from the perspective of CBL as a type of inquiry-based learning. Aim: To explore, analyse and synthesise the evidence relating to the effectiveness of CBL as a means of achieving defined learning outcomes in health professional prequalification training programmes. Method: Selection criteria: We focused the review on CBL for prequalification health professional programmes including medicine, dentistry, veterinary science, nursing and midwifery, social care and the allied health professions (physiotherapy, occupational therapy, etc.). Papers were required to have outcome data on effectiveness. Search strategies: The search covered the period from 1965 to week 4 September 2010 and the following databases: ASSIA, CINAHL, EMBASE, Education Research, Medline and Web of Knowledge (WoK). Two members of the topic review group (TRG) independently reviewed the 173 abstracts retrieved from Medline and compared findings. As there was good agreement on inclusion, one went onto review the WoK and ASSIA EndNote databases and the other the Embase, CINAHL and Education Research databases to decide on papers to submit for coding. Coding and data analysis: The TRG modified the standard best evidence medical education coding sheet to fit our research questions and assessed each paper for quality. After a preliminary reliability exercise, each full paper was read and graded by one reviewer with the papers scoring 3-5 (of 5) for strength of findings being read by a second reviewer. A summary of each completed coding form was entered into an Excel spread sheet. The type of data in the papers was not amenable to traditional meta-analysis because of the variability in interventions, information given, student numbers (and lack of) and timings. We, therefore, adopted a narrative synthesis method to compare, contrast, synthesise and interpret the data, working within a framework of inquiry-based learning. Results: The final number of coded papers for inclusion was 104. The TRG agreed that 23 papers would be classified as of higher quality and significance (22%). There was a wide diversity in the type, timing, number and length of exposure to cases and how cases were defined. Medicine was the most commonly included profession. Numbers of students taking part in CBL varied from below 50 to over 1000. The shortest interventions were two hours, and one case, whereas the longest was CBL through a whole year. Group sizes ranged from students working alone to over 30, with the majority between 2 and 15 students per group. The majority of studies involved single cohorts of students (61%), with 29% comparing multiple groups, 8% involving different year groups and 2% with historical controls. The outcomes evaluation was either carried out postintervention only (78 papers; 75%), preintervention and postintervention (23 papers; 22%) or during and postintervention (3 papers; <3%). Our analysis provided the basis for discussion of definitions of CBL, methods used and advocated, topics and learning outcomes and whether CBL is effective based on the evaluation data. Conclusion: Overwhelmingly, students enjoy CBL and think that it enhances their learning. The empirical data taken as a whole are inconclusive as to the effects on learning compared with other types of activity. Teachers enjoy CBL, partly because it engages, and is perceived to motivate, students. CBL seems to foster learning in small groups though whether this is the case delivery or the group learning effect is unclear.

Medical teacher · systematic review · 534 citationsread the source →

Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial.

Background: The antiviral efficacy of remdesivir against SARS-CoV-2 is still controversial. We aimed to evaluate the clinical efficacy of remdesivir plus standard of care compared with standard of care alone in patients admitted to hospital with COVID-19, with indication of oxygen or ventilator support. Methods: DisCoVeRy was a phase 3, open-label, adaptive, multicentre, randomised, controlled trial conducted in 48 sites in Europe (France, Belgium, Austria, Portugal, Luxembourg). Adult patients (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and illness of any duration were eligible if they had clinical evidence of hypoxaemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzymes, severe chronic kidney disease, any contraindication to one of the studied treatments or their use in the 29 days before random assignment, or use of ribavirin, as well as pregnancy or breastfeeding. Participants were randomly assigned (1:1:1:1:1) to receive standard of care alone or in combination with remdesivir, lopinavir-ritonavir, lopinavir-ritonavir and interferon beta-1a, or hydroxychloroquine. Randomisation used computer-generated blocks of various sizes; it was stratified on severity of disease at inclusion and on European administrative region. Remdesivir was administered as 200 mg intravenous infusion on day 1, followed by once daily, 1-h infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. The primary outcome was the clinical status at day 15 measured by the WHO seven-point ordinal scale, assessed in the intention-to-treat population. Safety was assessed in the modified intention-to-treat population and was one of the secondary outcomes. This trial is registered with the European Clinical Trials Database, EudraCT2020-000936-23, and ClinicalTrials.gov, NCT04315948. Findings: Between March 22, 2020, and Jan 21, 2021, 857 participants were enrolled and randomly assigned to remdesivir plus standard of care (n=429) or standard of care only (n=428). 15 participants were excluded from analysis in the remdesivir group, and ten in the control group. At day 15, the distribution of the WHO ordinal scale was: (1) not hospitalised, no limitations on activities (61 [15%] of 414 in the remdesivir group vs 73 [17%] of 418 in the control group); (2) not hospitalised, limitation on activities (129 [31%] vs 132 [32%]); (3) hospitalised, not requiring supplemental oxygen (50 [12%] vs 29 [7%]); (4) hospitalised, requiring supplemental oxygen (76 [18%] vs 67 [16%]); (5) hospitalised, on non-invasive ventilation or high flow oxygen devices (15 [4%] vs 14 [3%]); (6) hospitalised, on invasive mechanical ventilation or extracorporeal membrane oxygenation (62 [15%] vs 79 [19%]); (7) death (21 [5%] vs 24 [6%]). The difference between treatment groups was not significant (odds ratio 0·98 [95% CI 0·77-1·25]; p=0·85). There was no significant difference in the occurrence of serious adverse events between treatment groups (remdesivir, 135 [33%] of 406 vs control, 130 [31%] of 418; p=0·48). Three deaths (acute respiratory distress syndrome, bacterial infection, and hepatorenal syndrome) were considered related to remdesivir by the investigators, but only one by the sponsor's safety team (hepatorenal syndrome). Interpretation: No clinical benefit was observed from the use of remdesivir in patients who were admitted to hospital for COVID-19, were symptomatic for more than 7 days, and required oxygen support. Funding: European Union Commission, French Ministry of Health, Domaine d'intérêt majeur One Health Île-de-France, REACTing, Fonds Erasme-COVID-Université Libre de Bruxelles, Belgian Health Care Knowledge Centre, Austrian Group Medical Tumor, European Regional Development Fund, Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation. Translation: For the French translation of the abstract see Supplementary Materials section.

The Lancet. Infectious diseases · randomised controlled trial · 264 citationsread the source →

Chronic migraine headache prevention with noninvasive vagus nerve stimulation: The EVENT study.

Objective: To evaluate the feasibility, safety, and tolerability of noninvasive vagus nerve stimulation (nVNS) for the prevention of chronic migraine (CM) attacks. Methods: In this first prospective, multicenter, double-blind, sham-controlled pilot study of nVNS in CM prophylaxis, adults with CM (≥15 headache d/mo) entered the baseline phase (1 month) and were subsequently randomized to nVNS or sham treatment (2 months) before receiving open-label nVNS treatment (6 months). The primary endpoints were safety and tolerability. Efficacy endpoints in the intent-to-treat population included change in the number of headache days per 28 days and acute medication use. Results: Fifty-nine participants (mean age, 39.2 years; mean headache frequency, 21.5 d/mo) were enrolled. During the randomized phase, tolerability was similar for nVNS (n = 30) and sham treatment (n = 29). Most adverse events were mild/moderate and transient. Mean changes in the number of headache days were -1.4 (nVNS) and -0.2 (sham) (Δ = 1.2; p = 0.56). Twenty-seven participants completed the open-label phase. For the 15 completers initially assigned to nVNS, the mean change from baseline in headache days after 8 months of treatment was -7.9 (95% confidence interval -11.9 to -3.8; p < 0.01). Conclusions: Therapy with nVNS was well-tolerated with no safety issues. Persistent prophylactic use may reduce the number of headache days in CM; larger sham-controlled studies are needed. Clinicaltrialsgov identifier: NCT01667250. Classification of evidence: This study provides Class II evidence that for patients with CM, nVNS is safe, is well-tolerated, and did not significantly change the number of headache days. This pilot study lacked the precision to exclude important safety issues or benefits of nVNS.

Neurology · randomised controlled trial · 162 citationsread the source →

Print versus a culturally-relevant Facebook and text message delivered intervention to promote physical activity in African American women: a randomized pilot trial.

Background: African American women report insufficient physical activity and are disproportionally burdened by associated disease conditions; indicating the need for innovative approaches to promote physical activity in this underserved population. Social media platforms (i.e. Facebook) and text messaging represent potential mediums to promote physical activity. This paper reports the results of a randomized pilot trial evaluating a theory-based (Social Cognitive Theory) multi-component intervention using Facebook and text-messages to promote physical activity among African American women. Methods: Participants (N = 29) were randomly assigned to receive one of two multi-component physical activity interventions over 8 weeks: a culturally-relevant, Social Cognitive Theory-based, intervention delivered by Facebook and text message (FI) (n = 14), or a non-culturally tailored print-based intervention (PI) (n = 15) consisting of promotion brochures mailed to their home. The primary outcome of physical activity was assessed by ActiGraph GT3X+ accelerometers. Secondary outcomes included self-reported physical activity, physical activity-related psychosocial variables, and participant satisfaction. Results: All randomized participants (N = 29) completed the study. Accelerometer measured physical activity showed that FI participants decreased sedentary time (FI = -74 minutes/week vs. PI = +118 minute/week) and increased light intensity (FI = +95 minutes/week vs. PI = +59 minutes/week) and moderate-lifestyle intensity physical activity (FI = + 27 minutes/week vs. PI = -34 minutes/week) in comparison to PI participants (all P's < .05). No between group differences for accelerometer measured moderate-to-vigorous intensity physical activity were observed (P > .05). Results of secondary outcomes showed that in comparison to the PI, FI participants self-reported greater increases in moderate-to-vigorous physical activity (FI = +62 minutes/week vs. PI = +6 minutes/week; P = .015) and had greater enhancements in self-regulation for physical activity (P < .001) and social support from family for physical activity (P = .044). Satisfaction with the FI was also high: 100% reported physical activity-related knowledge gains and 100% would recommend the program to a friend. Conclusions: A culturally-relevant Facebook and text message delivered physical activity program was associated with several positive outcomes, including decreased sedentary behavior, increased light- and moderate-lifestyle intensity physical activity, enhanced psychosocial outcomes, and high participant satisfaction. Future studies with larger samples are warranted to further explore the efficacy of technology-based approaches to promote physical activity among African American women. Trial registration: ClinicalTrials.gov NCT02372565 . Registered 25 February 2015.

BMC women's health · randomised controlled trial · 105 citationsread the source →

Educating religious leaders to promote uptake of male circumcision in Tanzania: a cluster randomised trial.

Background: Male circumcision is being widely deployed as an HIV prevention strategy in countries with high HIV incidence, but its uptake in sub-Saharan Africa has been below targets. We did a study to establish whether educating religious leaders about male circumcision would increase uptake in their village. Methods: In this cluster randomised trial in northwest Tanzania, eligible villages were paired by proximity (<60 km) and the time that a free male circumcision outreach campaign from the Tanzanian Ministry of Health became available in their village. All villages received the standard male circumcision outreach activities provided by the Ministry of Health. Within the village pairs, villages were randomly assigned by coin toss to receive either additional education for Christian church leaders on scientific, religious, and cultural aspects of male circumcision (intervention group), or standard outreach only (control group). Church leaders or their congregations were not masked to random assignment. The educational intervention consisted of a 1-day seminar co-taught by a Tanzanian pastor and a Tanzanian clinician who worked with the Ministry of Health, and meetings with the study team every 2 weeks thereafter, for the duration of the circumcision campaign. The primary outcome was the proportion of male individuals in a village who were circumcised during the campaign, using an intention-to-treat analysis that included all men in the village. This trial is registered with ClinicalTrials.gov, number NCT 02167776. Findings: Between June 15, 2014, and Dec 10, 2015, we provided education for church leaders in eight intervention villages and compared the outcomes with those in eight control villages. In the intervention villages, 52·8% (30 889 of 58 536) of men were circumcised compared with 29·5% (25 484 of 86 492) of men in the eight control villages (odds ratio 3·2 [95% CI, 1·4-7·3]; p=0·006). Interpretation: Education of religious leaders had a substantial effect on uptake of male circumcision, and should be considered as part of male circumcision programmes in other sub-Saharan African countries. This study was conducted in one region in Tanzania; however, we believe that our intervention is generalisable. We equipped church leaders with knowledge and tools, and ultimately each leader established the most culturally-appropriate way to promote male circumcision. Therefore, we think that the process of working through religious leaders can serve as an innovative model to promote healthy behaviour, leading to HIV prevention and other clinically relevant outcomes, in a variety of settings. Funding: Bill & Melinda Gates Foundation, National Institutes of Health, and the Mulago Foundation.

Lancet (London, England) · randomised controlled trial · 31 citationsread the source →

Opioid treatment at release from jail using extended-release naltrexone: a pilot proof-of-concept randomized effectiveness trial.

Background and aims: Relapse to addiction following incarceration is common. We estimated the feasibility and effectiveness of extended-release naltrexone (XR-NTX) as relapse prevention among opioid-dependent male adults leaving a large urban jail. Design: Eight-week, proof-of-concept, open-label, non-blinded randomized effectiveness trial. Setting: New York City jails and Bellevue Hospital Center Adult Primary Care clinics, USA. Participants: From January 2010 to July 2013, 34 opioid-dependent adult males with no stated interest in agonist treatments (methadone, buprenorphine) received a counseling and referral intervention and were randomized to XR-NTX (n = 17) versus no medication (n = 17) within one week prior to jail release. Intervention: XR-NTX (Vivitrol(®) ; Alkermes Inc.), a long-acting injectable mu opioid receptor antagonist. Measures: The primary intent-to-treat outcome was post-release opioid relapse at week 4, defined as ≥10 days of opioid misuse by self-report and urine toxicologies. Secondary outcomes were proportion of urine samples negative for opioids and rates of opioid abstinence, intravenous drug use (IVDU), cocaine use, community treatment participation, re-incarceration and overdose. Findings: Acceptance of XR-NTX was high; 15 of 17 initiated treatment. Rates of the primary outcome of week 4 opioid relapse were lower among XR-NTX participants: 38 versus 88% [P<0.004; odds ratio (OR) = 0.08, 95% confidence interval (CI) = 0.01-0.48]; more XR-NTX urine samples were negative for opioids, 59 versus 29% (P<0.009; OR = 3.5, 95% CI = 1.4-8.5). There were no significant differences in the remaining secondary outcomes, including rates of IVDU, cocaine use, re-incarceration and overdose. Conclusion: Extended-release naltrexone is associated with significantly lower rates of opioid relapse among men in the United States following release from jail when compared with a no medication treatment-as-usual condition.

Addiction (Abingdon, England) · randomised controlled trial · 79 citationsread the source →

Promoting school climate and health outcomes with the SEHER multi-component secondary school intervention in Bihar, India: a cluster-randomised controlled trial.

Background: School environments affect health and academic outcomes. With increasing secondary school retention in low-income and middle-income countries, promoting quality school social environments could offer a scalable opportunity to improve adolescent health and wellbeing. Methods: We did a cluster-randomised trial to assess the effectiveness of a multi-component whole-school health promotion intervention (SEHER) with integrated economic and process evaluations in grade 9 students (aged 13-14 years) at government-run secondary schools in the Nalanda district of Bihar state, India. Schools were randomly assigned (1:1:1) to three groups: the SEHER intervention delivered by a lay counsellor (the SEHER Mitra [SM] group), the SEHER intervention delivered by a teacher (teacher as SEHER Mitra [TSM] group), and a control group in which only the standard government-run classroom-based life-skills Adolescence Education Program was implemented. The primary outcome was school climate measured with the Beyond Blue School Climate Questionnaire (BBSCQ). Students were assessed at the start of the academic year (June, 2015) and again 8 months later at the end of the academic year (March, 2016) via self-completed questionnaires. This study is registered with ClinicalTrials.gov, number NCT02484014. Findings: Of the 112 eligible schools in the Nalanda district, 75 were randomly selected to participate in the trial. We randomly assigned 25 schools to each of the three groups. One school subsequently dropped out of the TSM group, leaving 24 schools in this group. The baseline survey included a total of 13 035 participants, and the endpoint survey included 14 414 participants. Participants in the SM-delivered intervention schools had substantially higher school climate scores at endpoint survey than those in the control group (BBSCQ baseline-adjusted mean difference [aMD] 7·57 [95% CI 6·11-9·03]; effect size 1·88 [95% CI 1·44-2·32], p<0·0001) and the TSM-delivered intervention (aMD 7·57 [95% CI 6·06-9·08]; effect size 1·88 [95% CI 1·43-2·34], p<0·0001). There was no effect of the TSM-delivered intervention compared with control (aMD -0·009 [95% CI -1·53 to 1·51], effect size 0·00 [95% CI -0·45 to 0·44], p=0·99). Compared with the control group, participants in the SM-delivered intervention schools had moderate to large improvements in the secondary outcomes of depression (aMD -1·23 [95% CI -1·89 to -0·57]), bullying (aMD -0·91 [95% CI -1·15 to -0·66]), violence victimisation (odds ratio [OR] 0·62 [95% CI 0·46-0·84]), violence perpetration (OR 0·68 [95% CI 0·48-0·96]), attitude towards gender equity (aMD 0·41 [95% CI 0·21-0·61]), and knowledge of reproductive and sexual health (aMD 0·29 [95% CI 0·06-0·53]). Similar results for these secondary outcomes were noted for the comparison between SM-delivered intervention schools and TSM-delivered intervention schools (depression: aMD -1·23 [95% CI -1·91 to -0·55]; bullying: aMD -0·83 [95% CI -1·08 to -0·57]; violence victimisation: OR 0·49 [95% CI 0·35-0·67]; violence perpetration: OR 0·49 [95% CI 0·34-0·71]; attitude towards gender equity: aMD 0·23 [95% CI 0·02-0·44]; and knowledge of reproductive and sexual health: aMD 0·22 [95% CI -0·02 to 0·47]). However, no effects on these secondary outcomes were observed for the TSM-delivered intervention schools compared with the control group (depression: aMD -0·03 [95% CI -0·70 to 0·65]; bullying: aMD -0·08 [95% CI -0·34 to 0·18]; violence victimisation: OR 1·27 [95% CI 0·93-1·73]; violence perpetration: OR 1·37 [95% CI 0·95-1·95]; attitude towards gender equity: aMD 0·17 [95% CI -0·09 to 0·38]; and knowledge of reproductive and sexual health: aMD 0·06 [95% CI -0·18 to 0·32]). Interpretation: The multi-component whole-school SEHER health promotion intervention had substantial beneficial effects on school climate and health-related outcomes when delivered by lay counsellors, but no effects when delivered by teachers. Future research should focus on the evaluation of the scaling up of the SEHER intervention in diverse contexts and delivery agents. Funding: John D. and Catherine T. MacArthur Foundation, USA and the United Nations Population Fund India Office.

Lancet (London, England) · randomised controlled trial · 121 citationsread the source →

Adherence to sleep restriction therapy - An evaluation of existing measures.

Sleep restriction, a key element of cognitive behavioural therapy for insomnia, involves considerable behavioural changes in patients' lives, leading to side-effects like increased daytime sleepiness. Studies on sleep restriction rarely report adherence, and when assessed it is often limited to the average number of therapy sessions attended. This study aims to systematically evaluate different measures of adherence to cognitive behavioural therapy for insomnia and their relationship with treatment outcome. This is a secondary analysis of data from a randomized controlled trial investigating cognitive behavioural therapy for insomnia (Johann et al. (2020) Journal of Sleep Research, 29, e13102). The sample included 23 patients diagnosed with insomnia according to DSM-5 criteria who underwent 8 weeks of cognitive behavioural therapy for insomnia. The following adherence measures based on sleep diary data were used: number of sessions completed; deviations from agreed time in bed; average percentage of patients deviating from bedtime by 15, 30 or 60 min; variability of bedtime and wake-up time; change in time in bed from pre- to post-assessment. Treatment outcome was assessed using the Insomnia Severity Index. Multiple regression models were employed, and insomnia severity was controlled for. Results showed that none of the adherence measures predict insomnia severity. Baseline insomnia severity, dysfunctional thoughts and attitudes about sleep, depression or perfectionism did not predict adherence. The limited variance in the outcome parameter due to most patients benefiting from treatment and the small sample size may explain these findings. Additionally, using objective measures like actigraphy could provide a better understanding of adherence behaviour. Lastly, the presence of perfectionism in patients with insomnia may have mitigated adherence problems in this study.

Journal of sleep research · randomised controlled trial · 7 citationsread the source →

Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy.

Objective: Evaluate the seizure-reduction response and safety of mesial temporal lobe (MTL) brain-responsive stimulation in adults with medically intractable partial-onset seizures of mesial temporal lobe origin. Methods: Subjects with mesial temporal lobe epilepsy (MTLE) were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Results: There were 111 subjects with MTLE; 72% of subjects had bilateral MTL onsets and 28% had unilateral onsets. Subjects had one to four leads placed; only two leads could be connected to the device. Seventy-six subjects had depth leads only, 29 had both depth and strip leads, and 6 had only strip leads. The mean follow-up was 6.1 ± (standard deviation) 2.2 years. The median percent seizure reduction was 70% (last observation carried forward). Twenty-nine percent of subjects experienced at least one seizure-free period of 6 months or longer, and 15% experienced at least one seizure-free period of 1 year or longer. There was no difference in seizure reduction in subjects with and without mesial temporal sclerosis (MTS), bilateral MTL onsets, prior resection, prior intracranial monitoring, and prior vagus nerve stimulation. In addition, seizure reduction was not dependent on the location of depth leads relative to the hippocampus. The most frequent serious device-related adverse event was soft tissue implant-site infection (overall rate, including events categorized as device-related, uncertain, or not device-related: 0.03 per implant year, which is not greater than with other neurostimulation devices). Significance: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including patients with unilateral or bilateral MTLE who are not candidates for temporal lobectomy or who have failed a prior MTL resection.

Epilepsia · randomised controlled trial · 236 citationsread the source →

A mindfulness-based intervention to increase resilience to stress in university students (the Mindful Student Study): a pragmatic randomised controlled trial.

Background: The rising number of young people going to university has led to concerns about an increasing demand for student mental health services. We aimed to assess whether provision of mindfulness courses to university students would improve their resilience to stress. Methods: We did this pragmatic randomised controlled trial at the University of Cambridge, UK. Students aged 18 years or older with no severe mental illness or crisis (self-assessed) were randomly assigned (1:1), via remote survey software using computer-generated random numbers, to receive either an 8 week mindfulness course adapted for university students (Mindfulness Skills for Students [MSS]) plus mental health support as usual, or mental health support as usual alone. Participants and the study management team were aware of group allocation, but allocation was concealed from the researchers, outcome assessors, and study statistician. The primary outcome was self-reported psychological distress during the examination period, as measured with the Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM), with higher scores indicating more distress. The primary analysis was by intention to treat. This trial is registered with the Australia and New Zealand Clinical Trials Registry, number ACTRN12615001160527. Findings: Between Sept 28, 2015, and Jan 15, 2016, we randomly assigned 616 students to the MSS group (n=309) or the support as usual group (n=307). 453 (74%) participants completed the CORE-OM during the examination period and 182 (59%) MSS participants completed at least half of the course. MSS reduced distress scores during the examination period compared with support as usual, with mean CORE-OM scores of 0·87 (SD 0·50) in 237 MSS participants versus 1·11 (0·57) in 216 support as usual participants (adjusted mean difference -0·14, 95% CI -0·22 to -0·06; p=0·001), showing a moderate effect size (β -0·44, 95% CI -0·60 to -0·29; p<0·0001). 123 (57%) of 214 participants in the support as usual group had distress scores above an accepted clinical threshold compared with 88 (37%) of 235 participants in the MSS group. On average, six students (95% CI four to ten) needed to be offered the MSS course to prevent one from experiencing clinical levels of distress. No participants had adverse reactions related to self-harm, suicidality, or harm to others. Interpretation: Our findings show that provision of mindfulness training could be an effective component of a wider student mental health strategy. Further comparative effectiveness research with inclusion of controls for non-specific effects is needed to define a range of additional, effective interventions to increase resilience to stress in university students. Funding: University of Cambridge and National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care East of England.

The Lancet. Public health · randomised controlled trial · 217 citationsread the source →

Uptake of antiretroviral therapy and male circumcision after community-based HIV testing and strategies for linkage to care versus standard clinic referral: a multisite, open-label, randomised controlled trial in South Africa and Uganda.

Background: Male circumcision decreases HIV acquisition by 60%, and antiretroviral therapy (ART) almost eliminates HIV transmission from HIV-positive people who are virally suppressed; however, coverage of these interventions has lagged behind targets. We aimed to assess whether community-based HIV testing with counsellor support and point-of-care CD4 cell count testing would increase uptake of ART and male circumcision. Methods: We did this multisite, open-label, randomised controlled trial in six research-naive communities in rural South Africa and Uganda. Eligible HIV-positive participants (aged ≥16 years) were randomly assigned (1:1:1) in a factorial design to receive lay counsellor clinic linkage facilitation, lay counsellor follow-up home visits, or standard-of-care clinic referral, and then (1:1) either point-of-care CD4 cell count testing or referral for CD4 testing. HIV-negative uncircumcised men (aged 16-49 years) who could receive secure mobile phone text messages were randomly assigned (1:1:1) to receive text message reminders, lay counsellor visits, or standard clinic referral. The study biostatistician generated the randomisation schedule via a computer-generated random number program with varying block sizes (multiples of six or three) stratified by country. Primary outcomes for HIV-positive people were obtaining a CD4 cell count, linkage to an HIV clinic, ART initiation, and viral suppression at 9 months, and for HIV-negative uncircumcised men were visiting a circumcision facility and uptake of male circumcision at 3 months. We assessed social harms as a safety outcome throughout the study. We did the primary analyses by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02038582. Findings: Between June 6, 2013, and March 11, 2015, 15 332 participants were tested. 2339 (15%) participants tested HIV positive, of whom 1325 (57%) were randomly assigned to receive lay counsellor clinic linkage facilitation (n=437), lay counsellor follow-up home visits (n=449), or standard clinic referral (n=439), and then point-of-care CD4 cell testing (n=206, n=220, and n=213, respectively) or referral for CD4 testing (n=231, n=229, and n=226, respectively). 12 993 (85%) participants tested HIV negative, of whom 750 (6%) uncircumcised men were randomly assigned to receive clinic referral (n=230), text message reminders (n=288), or lay counsellor follow-up visits (n=232). 1218 (93%) of 1303 HIV-positive participants were linked to care, but only 488 (37%) participants initiated ART. Overall, 635 (50%) of 1272 HIV-positive individuals achieved viral suppression at 9 months: 219 (52%) of 419 participants in the clinic facilitation group, 202 (47%) of 431 participants in the lay counsellor follow-up group, and 214 (51%) of 422 participants in the clinic referral group, with no significant differences between groups (p=0·668 for clinic facilitation and p=0·273 for lay counsellor follow-up vs clinic referral). 523 (72%) of 734 HIV-negative men visited a circumcision facility, with no difference between groups. 62 (28%) of 224 men were circumcised in the male circumcision clinic referral group compared with 137 (48%) of 284 men in the text message reminder group (relative risk 1·72, 95% CI 1·36-2·17; p<0·0001) and 106 (47%) of 226 men in the lay counsellor follow-up group (1·67, 1·29-2·14; p=0·0001). No cases of study-related social harm were reported, including probing about partnership separation, unintended disclosure, gender-based violence, and stigma. Interpretation: All the community-based strategies achieved high rates of linkage of HIV-positive people to HIV clinics, roughly a third of whom initiated ART, and of those more than 80% were virally suppressed at 9 months. Uptake of male circumcision was almost two-times higher in men who received text message reminders or lay counsellor visits than in those who received standard-of-care clinic referral. Clinic barriers to ART initiation should be addressed in future strategies to increase the proportion of HIV-positive people accessing treatment and achieving viral suppression. Funding: National Institute of Allergy and Infectious Diseases, National Institutes of Health.

The lancet. HIV · randomised controlled trial · 65 citationsread the source →

Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: a randomised controlled, open-label, multicentre trial.

Background: Treatment of patients with ileocaecal Crohn's disease who have not responded to conventional therapy is commonly scaled up to biological agents, but surgery can also offer excellent short-term and long-term results. We compared laparoscopic ileocaecal resection with infliximab to assess how they affect health-related quality of life. Methods: In this randomised controlled, open-label trial, in 29 teaching hospitals and tertiary care centres in the Netherlands and the UK, adults with non-stricturing, ileocaecal Crohn's disease, in whom conventional therapy has failed were randomly allocated (1:1) by an internet randomisation module with biased-coin minimisation for participating centres and perianal fistula to receive laparoscopic ileocaecal resection or infliximab. Eligible patients were aged 18-80 years, had active Crohn's disease of the terminal ileum, and had not responded to at least 3 months of conventional therapy with glucocorticosteroids, thiopurines, or methotrexate. Patients with diseased terminal ileum longer than 40 cm or abdominal abscesses were excluded. The primary outcome was quality of life on the Inflammatory Bowel Disease Questionnaire (IBDQ) at 12 months. Secondary outcomes were general quality of life, measured by the Short Form-36 (SF-36) health survey and its physical and mental component subscales, days unable to participate in social life, days on sick leave, morbidity (additional procedures and hospital admissions), and body image and cosmesis. Analyses of the primary outcome were done in the intention-to-treat population, and safety analyses were done in the per-protocol population. This trial is registered at the Dutch Trial Registry (NTR1150). Findings: Between May 2, 2008, and October 14, 2015, 73 patients were allocated to have resection and 70 to receive infliximab. Corrected for baseline differences, the mean IBDQ score at 12 months was 178·1 (95% CI 171·1-185·0) in the resection group versus 172·0 (164·3-179·6) in the infliximab group (mean difference 6·1 points, 95% CI -4·2 to 16·4; p=0·25). At 12 months, the mean SF-36 total score was 112·1 (95% CI 108·0-116·2) in the resection group versus 106·5 (102·1-110·9) in the infliximab group (mean difference 5·6, 95% CI -0·4 to 11·6), the mean physical component score was 47·7 (45·7-49·7) versus 44·6 (42·5-46·8; mean difference 3·1, 4·2 to 6·0), and the mean mental component score was 49·5 (47·0-52·1) versus 46·1 (43·3-48·9; mean difference 3·5, -0·3 to 7·3). Mean numbers of days of sick leave were 3·4 days (SD 7·1) in the resection group versus 1·4 days (4·7) in the infliximab group (p<0·0001), days not able to take part in social life were 1·8 days (6·3) versus 1·1 days (4·5; p=0·20), days of scheduled hospital admission were 6·5 days (3·8) versus 6·8 days (3·2; p=0·84), and the number of patients who had unscheduled hospital admissions were 13 (18%) of 73 versus 15 (21%) of 70 (p=0·68). Body-image scale mean scores in the patients who had resection were 16·0 (95% CI 15·2-16·8) at baseline versus 17·8 (17·1-18·4) at 12 months, and cosmetic scale mean scores were 17·6 (16·6-18·6) versus 18·6 (17·6-19·6). Surgical intervention-related complications classified as IIIa or worse on the Clavien-Dindo scale occurred in four patients in the resection group. Treatment-related serious adverse events occurred in two patients in the infliximab group. During a median follow-up of 4 years (IQR 2-6), 26 (37%) of 70 patients in the infliximab group had resection, and 19 (26%) of 73 patients in the resection group received anti-TNF. Interpretation: Laparoscopic resection in patients with limited (diseased terminal ileum <40 cm), non-stricturing, ileocaecal Crohn's disease in whom conventional therapy has failed could be considered a reasonable alternative to infliximab therapy. Funding: Netherlands Organisation for Health Research and Development.

The lancet. Gastroenterology & hepatology · randomised controlled trial · 228 citationsread the source →

Cognitive behavioural therapy and short-term psychoanalytical psychotherapy versus a brief psychosocial intervention in adolescents with unipolar major depressive disorder (IMPACT): a multicentre, pragmatic, observer-blind, randomised controlled superiority trial.

Background: Psychological treatments for adolescents with unipolar major depressive disorder are associated with diagnostic remission within 28 weeks in 65-70% of patients. We aimed to assess the medium-term effects and costs of psychological therapies on maintenance of reduced depression symptoms 12 months after treatment. Methods: We did this multicentre, pragmatic, observer-blind, randomised controlled superiority trial (IMPACT) at 15 National Health Service child and adolescent mental health service (CAMHS) clinics in three regions in England. Adolescent patients (aged 11-17 years) with a diagnosis of DSM IV major depressive disorder were randomly assigned (1:1:1), via a web-based randomisation service, to receive cognitive behavioural therapy (CBT) or short-term psychoanalytical therapy versus a reference brief psychological intervention. Randomisation was stochastically minimised by age, sex, self-reported depression sum score, and region. Patients and clinicians were aware of group allocation, but allocation was concealed from outcome assessors. Patients were followed up and reassessed at weeks 6, 12, 36, 52, and 86 post-randomisation. The primary outcome was self-reported depression symptoms at weeks 36, 52, and 86, as measured with the self-reported Mood and Feelings Questionnaire (MFQ). Because our aim was to compare the two psychological therapies with the brief psychosocial intervention, we first established whether CBT was inferior to short-term psychoanalytical psychotherapy for the same outcome. Primary analysis was by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN83033550. Findings: Between June 29, 2010, and Jan 17, 2013, we randomly assigned 470 patients to receive the brief psychosocial intervention (n=158), CBT (n=155), or short-term psychoanalytical therapy (n=157); 465 patients comprised the intention-to-treat population. 392 (84%) patients had available data for primary analysis by the end of follow-up. Treatment fidelity and differentiation were established between the three interventions. The median number of treatment sessions differed significantly between patients in the brief psychosocial intervention group (n=6 [IQR 4-11]), CBT group (n=9 [5-14]), and short-term psychoanalytical therapy group (n=11 [5-23]; p<0·0001), but there was no difference between groups in the average duration of treatment (27·5 [SD 21·5], 24·9 [17·7], 27·9 [16·8] weeks, respectively; Kruskal-Wallis p=0·238). Self-reported depression symptoms did not differ significantly between patients given CBT and those given short-term psychoanalytical therapy at weeks 36 (treatment effect 0·179, 95% CI -3·731 to 4·088; p=0·929), 52 (0·307, -3·161 to 3·774; p=0·862), or 86 (0·578, -2·948 to 4·104; p=0·748). These two psychological treatments had no superiority effect compared with brief psychosocial intervention at weeks 36 (treatment effect -3·234, 95% CI -6·611 to 0·143; p=0·061), 52 (-2·806, -5·790 to 0·177; p=0·065), or 86 (-1·898, -4·922 to 1·126; p=0·219). Physical adverse events (self-reported breathing problems, sleep disturbances, drowsiness or tiredness, nausea, sweating, and being restless or overactive) did not differ between the groups. Total costs of the trial interventions did not differ significantly between treatment groups. Interpretation: We found no evidence for the superiority of CBT or short-term psychoanalytical therapy compared with a brief psychosocial intervention in maintenance of reduced depression symptoms 12 months after treatment. Short-term psychoanalytical therapy was as effective as CBT and, together with brief psychosocial intervention, offers additional patient choice for psychological therapy, alongside CBT, for adolescents with moderate to severe depression who are attending routine specialist CAMHS clinics. Funding: National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme, and the Department of Health.

The lancet. Psychiatry · randomised controlled trial · 149 citationsread the source →

Whole-Body Hyperthermia for the Treatment of Major Depressive Disorder: A Randomized Clinical Trial.

Importance: Limitations of current antidepressants highlight the need to identify novel treatments for major depressive disorder. A prior open trial found that a single session of whole-body hyperthermia (WBH) reduced depressive symptoms; however, the lack of a placebo control raises the possibility that the observed antidepressant effects resulted not from hyperthermia per se, but from nonspecific aspects of the intervention. Objective: To test whether WBH has specific antidepressant effects when compared with a sham condition and to evaluate the persistence of the antidepressant effects of a single treatment. Design, setting, and participants: A 6-week, randomized, double-blind study conducted between February 2013 and May 2015 at a university-based medical center comparing WBH with a sham condition. All research staff conducting screening and outcome procedures were blinded to randomization status. Of 338 individuals screened, 34 were randomized, 30 received a study intervention, and 29 provided at least 1 postintervention assessment and were included in a modified intent-to-treat efficacy analysis. Participants were medically healthy, aged 18 to 65 years, met criteria for major depressive disorder, were free of psychotropic medication use, and had a baseline 17-item Hamilton Depression Rating Scale score of 16 or greater. Interventions: A single session of active WBH vs a sham condition matched for length of WBH that mimicked all aspects of WBH except intense heat. Main outcomes and measures: Between-group differences in postintervention Hamilton Depression Rating Scale scores. Results: The mean (SD) age was 36.7 (15.2) years in the WBH group and 41.47 (12.54) years in the sham group. Immediately following the intervention, 10 participants (71.4%) randomized to sham treatment believed they had received WBH compared with 15 (93.8%) randomized to WBH. When compared with the sham group, the active WBH group showed significantly reduced Hamilton Depression Rating Scale scores across the 6-week postintervention study period (WBH vs sham; week 1: -6.53, 95% CI, -9.90 to -3.16, P < .001; week 2: -6.35, 95% CI, -9.95 to -2.74, P = .001; week 4: -4.50, 95% CI, -8.17 to -0.84, P = .02; and week 6: -4.27, 95% CI, -7.94 to -0.61, P = .02). These outcomes remained significant after evaluating potential moderating effects of between-group differences in baseline expectancy scores. Adverse events in both groups were generally mild. Conclusions and relevance: Whole-body hyperthermia holds promise as a safe, rapid-acting, antidepressant modality with a prolonged therapeutic benefit. Trial registration: clinicaltrials.gov Identifier: NCT01625546.

JAMA psychiatry · randomised controlled trial · 94 citationsread the source →

Internet-based behavioural activation with lay counsellor support versus online minimal psychoeducation without support for treatment of depression: a randomised controlled trial in Indonesia.

Background: Depression is one of the leading contributors to the global burden of disease. However, treatment availability is often very poor in low-income and middle-income countries. In a randomised clinical trial, we investigated the efficacy of internet-based behavioural activation with lay counsellor support compared with online minimal psychoeducation without support for depression in Indonesia (a middle-income country). Methods: We did a community-based, two-group, randomised controlled trial in Indonesia. Eligible participants were aged 16 years or older, scored 10 or above on the Patient Health Questionnaire 9 (PHQ-9), met the criteria for major depressive disorder or persistent depressive disorder based on the Structured Clinical Interview for DSM-5, were proficient in Bahasa Indonesia, and could use the internet. Participants were randomly allocated (1:1) by a research assistant using a web-based randomisation program to online behavioural activation with lay support (termed Guided Act and Feel Indonesia [GAF-ID]) or online psychoeducation without further support. Randomisation was done within a random permuted block design and was stratified by sex and depression severity (ie, PHQ-9 10-14 vs ≥15). The primary outcome was self-reported PHQ-9 score at 10 weeks from baseline. Research assistants were masked to group allocation until after the assessment of the primary outcome. Interventions were described to participants during the consent procedure and after randomisation, but no indication was given as to which was the intervention of interest and which was the control. Analysis was by intention to treat. The trial was registered in the Netherlands Trial Register, number NTR5920. It is closed to new particpants, and follow-up has been completed. Findings: Between Sept 6, 2016, and May 1, 2017, 313 participants were enrolled and randomly assigned, 159 to the GAF-ID group and 154 to the online psychoeducation group. At 10 weeks, PHQ-9 scores were significantly lower in the GAF-ID group than in the online psychoeducation group (mean difference -1·26 points [95% CI -2·29 to -0·23]; p=0·017), and participants in the GAF-ID group had a 50% higher chance of remission at 10 weeks (relative risk 1·50 [95% CI 1·19 to 1·88]; p<0·0001). An effect size of 0·24 for the GAF-ID group compared with the control group at 10 weeks was sustained over time (effect size 0·24 at 3 months, and 0·27 at 6 months). No adverse events were reported in either group. Interpretation: To our knowledge, ours is the first adequately powered randomised clinical trial of an internet-based intervention for depression in a low-income or middle-income country. Online behavioural activation with lay counsellor support efficaciously reduced symptoms of depression, and could help to bridge the mental health gap in low-income and middle-income countries. Funding: Indonesia Endowment Fund for Education, University of Groningen.

The lancet. Psychiatry · randomised controlled trial · 66 citationsread the source →