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Effects of a Mobile and Web App (Thought Spot) on Mental Health Help-Seeking Among College and University Students: Randomized Controlled Trial.

Background: Mental health disorders are the most prevalent health issues among postsecondary students, yet few solutions to this emerging crisis exist. While mobile health technologies are touted as promising solutions for the unmet mental health needs of these students, the efficacy of these tools remains unclear. In response to these gaps, this study evaluates Thought Spot, a mobile and web app created through participatory design research. Objective: The goal of the research is to examine the impact of Thought Spot on mental health and wellness help-seeking intentions, behaviors, attitudes, self-stigma, and self-efficacy among postsecondary students in Canada. Methods: A 2-armed randomized controlled trial involving students from three postsecondary institutions was conducted. Students were eligible if they were aged 17 to 29 years, enrolled in full-time or part-time studies, functionally competent in English, and had access to a compatible digital device. The usual care group received a mental health services information pamphlet. The intervention group received the Thought Spot app on their digital device. Thought Spot is a standalone app that allows users to add, review, and search crowdsourced information about nearby mental health and wellness services. Users can also track their mood on the app. Outcomes were self-assessed through questionnaires collected at baseline and 3 and 6 months. The primary outcome was change in formal help-seeking intentions from baseline to 6 months, measured by the General Help-Seeking Questionnaire. A mixed-effects model was used to compare the impact of usual care and intervention on the primary outcome (formal help-seeking intentions). Secondary outcomes included changes in informal help-seeking intentions and help-seeking behaviors, help-seeking attitudes, self-stigma, and self-efficacy. Results: A total of 481 students were randomized into two groups: 240 to usual care, and 241 to the intervention group. There were no significant differences in help-seeking intentions between the usual care and intervention groups over 6 months (F2,877=0.85; P=.43, f=0.04). Both groups demonstrated similar increases in formal help-seeking intentions at 3 and 6 months (F2,877=23.52; P<.001, f=0.21). Compared with males, females sought more help from formal resources (OR 1.86; 95% CI 1.22 to 2.83, P=.001). Females were less likely to seek help from informal sources than males (OR 0.80; 95% CI 0.22 to 0.73, P<.001). Conclusions: Prompting postsecondary students about mental health and help-seeking appears to increase help-seeking intentions. mHealth interventions may be as effective as information pamphlets in increasing formal help-seeking but may confer a small advantage in driving help-seeking from informal sources. Although there is enthusiasm, developers and health policy experts should exercise caution and thoroughly evaluate these types of digital tools. Future studies should explore the cost-effectiveness of digital interventions and develop strategies for improving their efficacy. Trial registration: ClinicalTrials.gov NCT03412461; https://clinicaltrials.gov/ct2/show/NCT03412461. International registered report identifier (irrid): RR2-10.2196/resprot.6446.

Journal of medical Internet research · randomised controlled trial · 45 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 →

Is volunteering a public health intervention? A systematic review and meta-analysis of the health and survival of volunteers.

Background: Volunteering has been advocated by the United Nations, and American and European governments as a way to engage people in their local communities and improve social capital, with the potential for public health benefits such as improving wellbeing and decreasing health inequalities. Furthermore, the US Corporation for National and Community Service Strategic Plan for 2011-2015 focused on increasing the impact of national service on community needs, supporting volunteers' wellbeing, and prioritising recruitment and engagement of underrepresented populations. The aims of this review were to examine the effect of formal volunteering on volunteers' physical and mental health and survival, and to explore the influence of volunteering type and intensity on health outcomes. Methods: Experimental and cohort studies comparing the physical and mental health outcomes and mortality of a volunteering group to a non-volunteering group were identified from twelve electronic databases (Cochrane Library, Medline, Embase, PsychINFO, CINAHL, ERIC, HMIC, SSCI, ASSIA, Social Care Online, Social Policy and Practice) and citation tracking in January 2013. No language, country or date restrictions were applied. Data synthesis was based on vote counting and random effects meta-analysis of mortality risk ratios. Results: Forty papers were selected: five randomised controlled trials (RCTs, seven papers); four non-RCTs; and 17 cohort studies (29 papers). Cohort studies showed volunteering had favourable effects on depression, life satisfaction, wellbeing but not on physical health. These findings were not confirmed by experimental studies. Meta-analysis of five cohort studies found volunteers to be at lower risk of mortality (risk ratio: 0.78; 95% CI: 0.66, 0.90). There was insufficient evidence to demonstrate a consistent influence of volunteering type or intensity on outcomes. Conclusion: Observational evidence suggested that volunteering may benefit mental health and survival although the causal mechanisms remain unclear. Consequently, there was limited robustly designed research to guide the development of volunteering as a public health promotion intervention. Future studies should explicitly map intervention design to clear health outcomes as well as use pragmatic RCT methodology to test effects.

BMC public health · meta-analysis · 237 citationsread the source →

Outcome of children less than three years old at diagnosis with non-metastatic medulloblastoma treated with chemotherapy on the "Head Start" I and II protocols.

Purpose: To determine the survival of infants and young children with non-metastatic medulloblastoma using intensive myeloablative chemotherapy and autologous hematopoietic progenitor cell rescue (AuHCR). Methods: Twenty-one children less than 3 years old at diagnosis with non-metastatic medulloblastoma were enrolled on two identical serial studies, "Head Start" I and "Head Start" II. After surgery, patients received five cycles of induction chemotherapy consisting of vincristine, cisplatin, cyclophosphamide and etoposide. Following induction, all patients underwent myeloablative chemotherapy using carboplatin, thiotepa and etoposide with AuHCR. Irradiation was used only at relapse. Results: The 5-year event-free (EFS) and overall survival (OS) rates (+/-SE) for all patients, patients with gross total resection, and patients with residual tumor were 52 +/- 11% and 70 +/- 10%, 64 +/- 13% and 79 +/- 11%, and 29 +/- 17% and 57 +/- 19%, respectively. The 5-year EFS and OS ( +/- SE) for patients with desmoplastic and classical medulloblastoma were 67 +/- 16% and 78 +/- 14%, and 42 +/- 14 and 67 +/- 14%, respectively. There were four treatment related deaths. The majority of survivors (71%) avoided irradiation completely. Mean intellectual functioning and quality of life (QoL) for children surviving without irradiation was within average range for a majority of survivors tested. Conclusion: This strategy of brief intensive chemotherapy for young children with non-metastatic medulloblastoma eliminated the need for craniospinal irradiation 52% of the patients, and may preserve QoL and intellectual functioning. The excellent survival rates are somewhat dampened by high toxic mortality.

Pediatric blood & cancer · randomised controlled trial · 155 citationsread the source →

Does sustained-release lithium reduce impulsive gambling and affective instability versus placebo in pathological gamblers with bipolar spectrum disorders?

Objective: Selective serotonin reuptake inhibitors may be effective for some patients with pathological gambling, but those with comorbid conditions, such as bipolar spectrum disorders, may relapse during treatment. To the authors' knowledge, this is the first placebo-controlled treatment study in pathological gamblers with bipolar spectrum disorders; it compares sustained-release lithium carbonate to placebo. Method: Forty pathological gambling patients with bipolar spectrum disorders entered a 10-week randomized, double-blind, placebo-controlled treatment study of sustained-release lithium carbonate. Outcome measures included gambling severity, mood, anxiety, and impulsivity scales. Results: Pathological gambling patients with bipolar spectrum disorders significantly improved while taking sustained-release lithium carbonate compared to placebo on total pathological gambling scores on the Yale-Brown Obsessive Compulsive Scale, including both thoughts/urges and behavior, as well as on the Clinical Global Impression severity of pathological gambling scale. Affective instability (the Clinician-Administered Rating Scale for Mania score) was also lower in the group treated with sustained-release lithium carbonate compared to placebo. Ten (83%) of 12 completers were rated as responders in the sustained-release lithium group versus five (29%) of 17 in the placebo group. Of note, improvement in gambling severity was significantly correlated with improvement in mania ratings. Conclusions: Sustained-released lithium may be an effective treatment in reducing both gambling behavior and affective instability in pathological gamblers with bipolar spectrum disorder. This study highlights the need to identify subgroups of pathological gambling patients with bipolar spectrum conditions because this may have important treatment implications.

The American journal of psychiatry · randomised controlled trial · 114 citationsread the source →

Family-centered advance care planning for teens with cancer.

Importance: Advance care planning (ACP) prepares patients and their families for future health care decisions; however, the needs of adolescent oncology patients for participation in ACP have not been well studied. Objective: To examine the efficacy of family-centered ACP. Design and setting: Two-group randomized controlled trial in a pediatric oncology program. Participants: Sixty adolescents aged 14 to 21 years with cancer and their surrogates or families were enrolled in the study between January 17, 2011, and March 29, 2012. Intervention: Thirty dyads received 3- to 60-minute sessions 1 week apart. Intervention dyads completed (1) the Lyon Family-Centered ACP Survey, (2) the Respecting Choices interview, and (3) Five Wishes. Control subjects received standard care plus information. Main outcome measures: Statement of treatment preferences and Decisional Conflict Scale score. Results: The mean age of the adolescents was 16 years; 36 (60%) were male, 30 (50%) white, 26 (43%) black, and 4 (7%) Asian. Diagnoses were as follows: leukemia (14 patients [47%]), brain tumor (8 [27%]), solid tumor (6 [20%]), and lymphoma (2 [7%]). Significantly increased congruence was observed for intervention dyads compared with controls for 4 of the 6 disease-specific scenarios; for example, for situation 2 ("treatment would extend my life by not more than 2 to 3 months"), intervention dyads demonstrated higher congruence (κ = 0.660; P < .001) vs control dyads (κ = -0.0636; P = .70). Intervention adolescents (100%) wanted their families to do what is best at the time, whereas fewer control adolescents (62%) gave families this leeway. Intervention adolescents were significantly better informed about end-of-life decisions (t = 2.93; effect size, 0.961; 95% CI, 0.742-1.180; P = .007). Intervention families were more likely to concur on limiting treatments than controls. An ethnic difference was found in only one situation. Conclusions: Advance care planning enabled families to understand and honor their adolescents' wishes. Intervention dyads were more likely than controls to limit treatments. Underserved African American families were willing to participate.

JAMA pediatrics · randomised controlled trial · 149 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 →

The role of constraint in the development of nicotine, marijuana, and alcohol dependence in young adulthood.

The personality-related construct of behavioral disinhibition is hypothesized to confer a generalized risk for alcohol and drug dependence. On average, rates of substance use and scores on measures of disinhibition peak in adolescence and decline as people mature into adulthood. The present study investigated this developmental change by evaluating the relationship between disinhibition and substance use disorders using a longitudinal study of 2,608 twins assessed at ages 17, 24, and 29. These ages include the period of highest risk for substance use disorders (ages 17-24) as well as when substance dependence symptoms typically decline (ages 24-29). Disinhibition was measured with the Multidimensional Personality Questionnaire higher-order scale of Constraint, as well as its constituent facet scales of Harm Avoidance, Control, and Traditionalism. Constraint's relationship with substance dependence was statistically significant but small and largely genetic, with the genetic relationship declining from adolescence into adulthood. However, this result appeared to be almost entirely driven by Traditionalism, a propensity to hold traditional moral and social values, and not an obvious component of behavioral disinhibition. The results suggest that personality measures of Control and Harm Avoidance play only a small role in the development of substance dependence during late adolescence, and previous findings linking personality measures of disinhibition and substance use may be driven significantly by social and moral values than deficits in impulse control.

Behavior genetics · cohort or longitudinal · 7 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 →

Postpartum mental illness: perspectives from an Arabian Gulf population.

There is growing awareness of the importance of mental health issues in the perinatal period in Western societies, but very little information is available from Muslim and Arab countries. Qualitative information gathered using focus group discussions of women of childbearing age is presented along with additional information obtained from key informant interviews with grandmothers, husbands, and health care professionals in the United Arab Emirates. The participants were women attending a public sector clinic in Al Ain, Abu Dhabi, and a private clinic in Dubai on a particular day. There were 19 women in the age range 17 to 46 years (M age = 29 yr.). The majority of the women who took part in the study did not recognize postnatal depression as a psychological issue but considered the problems a result of "evil eye" or "Jinn." The present findings suggest the need for initiating awareness programs among women and training of health professionals on the detection and management of postnatal depression.

Psychological reports · cohort or longitudinal · 15 citationsread the source →

The Healthy Activity Program (HAP), a lay counsellor-delivered brief psychological treatment for severe depression, in primary care in India: a randomised controlled trial.

Background: Although structured psychological treatments are recommended as first-line interventions for depression, only a small fraction of people globally receive these treatments because of poor access in routine primary care. We assessed the effectiveness and cost-effectiveness of a brief psychological treatment (Healthy Activity Program [HAP]) for delivery by lay counsellors to patients with moderately severe to severe depression in primary health-care settings. Methods: In this randomised controlled trial, we recruited participants aged 18-65 years scoring more than 14 on the Patient Health Questionnaire 9 (PHQ-9) indicating moderately severe to severe depression from ten primary health centres in Goa, India. Pregnant women or patients who needed urgent medical attention or were unable to communicate clearly were not eligible. Participants were randomly allocated (1:1) to enhanced usual care (EUC) alone or EUC combined with HAP in randomly sized blocks (block size four to six [two to four for men]), stratified by primary health centre and sex, and allocation was concealed with use of sequential numbered opaque envelopes. Physicians providing EUC were masked. Primary outcomes were depression symptom severity on the Beck Depression Inventory version II and remission from depression (PHQ-9 score of <10) at 3 months in the intention-to-treat population, assessed by masked field researchers. Secondary outcomes were disability, days unable to work, behavioural activation, suicidal thoughts or attempts, intimate partner violence, and resource use and costs of illness. We assessed serious adverse events in the per-protocol population. This trial is registered with the ISRCTN registry, number ISRCTN95149997. Findings: Between Oct 28, 2013, and July 29, 2015, we enrolled and randomly allocated 495 participants (247 [50%] to the EUC plus HAP group [two of whom were subsequently excluded because of protocol violations] and 248 [50%] to the EUC alone group), of whom 466 (95%) completed the 3 month primary outcome assessment (230 [49%] in the EUC plus HAP group and 236 [51%] in the EUC alone group). Participants in the EUC plus HAP group had significantly lower symptom severity (Beck Depression Inventory version II in EUC plus HAP group 19·99 [SD 15·70] vs 27·52 [13·26] in EUC alone group; adjusted mean difference -7·57 [95% CI -10·27 to -4·86]; p<0·0001) and higher remission (147 [64%] of 230 had a PHQ-9 score of <10 in the HAP plus EUC group vs 91 [39%] of 236 in the EUC alone group; adjusted prevalence ratio 1·61 [1·34-1·93]) than did those in the EUC alone group. EUC plus HAP showed better results than did EUC alone for the secondary outcomes of disability (adjusted mean difference -2·73 [-4·39 to -1·06]; p=0·001), days out of work (-2·29 [-3·84 to -0·73]; p=0·004), intimate partner physical violence in women (0·53 [0·29-0·96]; p=0·04), behavioural activation (2·17 [1·34-3·00]; p<0·0001), and suicidal thoughts or attempts (0·61 [0·45-0·83]; p=0·001). The incremental cost per quality-adjusted life-year gained was $9333 (95% CI 3862-28 169; 2015 international dollars), with an 87% chance of being cost-effective in the study setting. Serious adverse events were infrequent and similar between groups (nine [4%] in the EUC plus HAP group vs ten [4%] in the EUC alone group; p=1·00). Interpretation: HAP delivered by lay counsellors plus EUC was better than EUC alone was for patients with moderately severe to severe depression in routine primary care in Goa, India. HAP was readily accepted by this previously untreated population and was cost-effective in this setting. HAP could be a key strategy to reduce the treatment gap for depressive disorders, the leading mental health disorder worldwide. Funding: Wellcome Trust.

Lancet (London, England) · randomised controlled trial · 295 citationsread the source →

Telephone counselling for smoking cessation.

Background: Telephone services can provide information and support for smokers. Counselling may be provided proactively or offered reactively to callers to smoking cessation helplines. Objectives: To evaluate the effect of proactive and reactive telephone support to help smokers quit. Search strategy: We searched the Cochrane Tobacco Addiction Group trials register for studies using free text term 'telephone*' or the keywords 'telephone counselling' or 'Hotlines' or 'Telephone' . Date of the most recent search: January 2006. Selection criteria: Randomized or quasi-randomized controlled trials in which proactive or reactive telephone counselling to assist smoking cessation was offered to smokers or recent quitters. Data collection and analysis: Trials were identified and data extracted by one person (LS) and checked by a second (TL). The main outcome measure was the odds ratio for abstinence from smoking after at least six months follow up. We selected the strictest measure of abstinence, using biochemically validated rates where available. We considered participants lost to follow-up to be continuing smokers. Where trials had more than one arm with a less intensive intervention we used only the most similar intervention without the telephone component as the control group in the primary analysis. We assessed statistical heterogeneity amongst sub groups of clinically comparable studies using the I(2) statistic. Where appropriate, we pooled studies using a fixed-effect model. A meta-regression was used to investigate the effect of differences in planned number of calls. Main results: Forty-eight trials met the inclusion criteria. Among smokers who contacted helplines, quit rates were higher for groups randomised to receive multiple sessions of call-back counselling (eight studies, >18,000 participants, odds ratio (OR) for long term cessation 1.41, 95% confidence interval (CI) 1.27 to 1.57). Two of these studies showed a significant benefit of more intensive compared to less intensive intervention. Telephone counselling not initiated by calls to helplines also increased quitting (29 studies, >17,000 participants, OR 1.33, 95% CI 1.21 to 1.47). A meta-regression detected a significant association between the maximum number of planned calls and the effect size. There was clearer evidence of benefit in the subgroup of trials recruiting smokers motivated to quit. Of two studies that provided access to a hotline one showed a significant benefit and one did not. Two studies comparing different counselling approaches during a single session did not detect significant differences. A further seven studies were too diverse to contribute to meta-analyses and are discussed separately. Authors' conclusions: Proactive telephone counselling helps smokers interested in quitting. There is evidence of a dose response; one or two brief calls are less likely to provide a measurable benefit. Three or more calls increases the odds of quitting compared to a minimal intervention such as providing standard self-help materials, brief advice, or compared to pharmacotherapy alone. Telephone quitlines provide an important route of access to support for smokers, and call-back counselling enhances their usefulness.

The Cochrane database of systematic reviews · meta-analysis · 255 citationsread the source →

Heart rate variability

IN FOCUSHeart rate variabilityHarald M. StaussHarald M. StaussDepartment of Exercise Science, University of Iowa, Iowa City, Iowa 52242Published Online:01 Nov 2003https://doi.org/10.1152/ajpregu.00452.2003MoreSectionsPDF (59 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations the rhythm of the heart has not only fascinated cardiologists but also inspired poets and musicians. Indeed, the periodic beat of the heart was used to define the speed of music. In music notation, the traditional Italian term "moderato" originally referred to one beat of the measure per walking pace (76-80 paces/min) or heartbeat (∼72 beats/min). The use of the heartbeat to define the speed of music may imply that the periodicity of the beat of the heart is very constant. However, this is not necessarily the case. In fact, loss of heart rate variability can indicate severe cardiovascular diseases and reliably predict poor outcome of such conditions (18, 22, 27, 47a). This In Focus article reviews sources of heart rate variability, its role as a prognostic marker for cardiovascular diseases, and its application in estimation of cardiac autonomic nervous system activity. All of these topics have been addressed intensely in articles published in the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology during the last two years. In healthy subjects, the sinoatrial node located at the posterior wall of the right atrium initiates each beat of the heart. Due to the unstable membrane potential of the myocytes located in this region, action potentials are generated periodically at a fairly constant frequency. This relatively constant frequency generated by the autorhythmicity of the sinoatrial node is modulated by many factors that add variability to the heart rate signal at different frequencies. According to the Task Force of The European Society of Cardiology and The North American Society of Pacing and Electrophysiology (47a) these frequencies are classified into 1) ultra-low frequencies (ULF; >5-h cycle length) that include the circadian rhythm (6, 9, 34, 54); 2) very low frequencies (VLF; >25-s cycle length) that are supposed to be affected by temperature regulation (1, 7, 34, 52, 54) and humoral systems (9, 36); 3) low frequencies (LF; >6-s cycle length in humans) that are sensitive to changes in cardiac sympathetic (and presumably parasympathetic) nerve activity (27, 30); and 4) high frequencies (HF; 2.5- to 6.0-s cycle length in humans) that are synchronized to the respiratory rhythm (5) and are primarily modulated by cardiac parasympathetic innervation (38).The most prominent oscillation in the ULF band of the heart rate spectrum is the circadian rhythm. The autonomic nervous system contributes significantly to circadian heart rate variability. Using long-term recordings in conscious rabbits, Barrett et al. (6) demonstrated a strong circadian rhythm in heart rate, mean arterial blood pressure, renal blood flow, and renal sympathetic nerve activity. The importance of this study is that it clearly demonstrates that sympathetic nerve discharges exhibit a strong circadian rhythmicity. The paraventricular nucleus of the hypothalamus (PVN) appears to play a central role in mediating the circadian rhythm of autonomic nervous system activity. First, GABAergic and glutamatergic neurons project from the suprachiasmatic nuclei of the hypothalamus (SCN) to spinal-projecting neurons of the PVN (12). The SCN is the major central oscillator that triggers the day/night cycle. It receives photic input from the retina (47) and drives many neuroendocrine, metabolic, autonomic, and behavioral circadian rhythms (14, 16, 21, 31, 35, 44, 46, 50). In addition, microinjections of the inhibitory neurotransmitter GABA into the PVN of anesthetized rats elicit dose-dependent decreases in renal sympathetic nerve activity, whereas bicuculline (a GABA antagonist) increases renal sympathetic nerve activity (56). Second, from the PVN, neurons project to the nucleus of the solitary tract (that integrates inputs from the baroreceptors), the nucleus ambiguus (origin of preganglionic parasympathetic neurons to the heart), the rostroventrolateral medulla (location of sympathetic premotor neurons), and the intermediolateral cell column of the thoracolumbar spinal cord (location of preganglionic sympathetic neurons). Thus PVN neurons can modulate autonomic nervous system activity by sending inputs to major sites of autonomic nervous system regulation. As an example, a pivotal role of the PVN for sympathoexcitation during parturition was recently demonstrated in sheep. The increase in sympathetic nerve activity that accompanies birth in maternal animals was prevented by stereotactic lesioning of the PVN (43). Taken together, a major component of the circadian heart rate variability is elicited by diurnal fluctuations in autonomic nervous system activity, generated by corresponding fluctuations of neuronal activity within the PVN, which depend on circadian inputs originating from the SCN.It has been suggested that thermoregulation affects VLF heart rate variability (10, 26). Cooling the heart causes bradycardia, a mechanism used in heart surgeries. Conversely, fever is known to increase heart rate. Raising body core temperature from 36.0 to 36.6°C caused an increase in heart rate by almost 40 beats/min in male subjects (1), whereas acutely reducing ambient temperature from thermoneutral conditions (35°C) to 29, 23, and 17°C, reduced heart rate from 400 to 250 beats/min in 8-day-old rats (7). In addition, lowering temperature in the isolated working rat heart from 37 to 31°C reduced heart rate from 332 to 215 beats/min and markedly increased heart rate variability (28), indicating that parts of the temperature effects on heart rate and heart rate variability are independent from the autonomic nervous system. In contrast to the tachycardia that accompanies acute elevations in temperature, chronically raising ambient temperature in adult rodents from a standard housing temperature of 21-23°C to thermoneutral conditions (29-30°C) reduced heart rate by roughly 50 beats/min in rats (34) and by 200-300 beats/min in mice (54). The authors of these articles (34, 54) suggested that standard housing temperatures are associated with cold stress that causes parallel activation of brown adipose tissue, cardiac, and vasomotor sympathetic drives that elicits nonshivering thermogenesis and tonically elevates heart rate and arterial blood pressure. These and other studies indicate that both direct effects of temperature on pacemaker activity of the sinus node (28) and indirect effects mediated via the autonomic nervous system (11, 25, 51, 55) mediate temperature effects on heart rate and heart rate variability. Thus fluctuation in temperature is an important source of heart rate variability that should not be underestimated. In a more recent study, this was taken into account by core body temperature correction of heart rate variability (3).Endocrine factors affecting heart rate variability include thyroxine, reproductive hormones, the renin-angiotensin system, steroids, and others. Chronic subcutaneous infusion of angiotensin II in rats markedly increased blood pressure and heart rate variability, expressed as standard deviation (9). In contrast, chronic corticosterone treatment is likely to reduce baroreflex-mediated heart rate variability, because baroreceptor-heart rate (39) and baroreceptor-renal sympathetic nerve activity reflex sensitivity (41) were blunted in chronically corticosterone-treated rats. Furthermore, an interaction between angiotensin II and glucocorticoids was recently described. Intracerebro-ventricular microinjections of angiotensin II AT1 receptor antagonists caused marked decreases in mean blood pressure and heart rate in rats chronically treated with corticosterone but not in control animals (40). This interaction is likely to take place in the central nervous system, because peripheral angiotensin II AT1 receptor blockade did not alter the effects of betamethasone treatment on blood pressure, heart rate, and baroreceptor-heart rate reflex sensitivity in newborn lambs (42).Adenosine is a substance less known to affect heart rate variability. It is produced locally in the heart (53) and binds to A1-adenosinergic receptors, which are among the earliest expressed G protein-coupled receptors in the heart (36). The A1-adenosinergic agonist N6-cyclopentyladenosine dose dependently reduced heart rate in murine embryos, whereas 1,3-dipropyl-8-cyclopentylxanthine, an A1-adenosinergic antagonist, increased heart rate (36). Adenosine also exerts central nervous system effects in various brain areas (15, 20). Microinjections of adenosine into the nucleus of the solitary tract of awake rats caused dose-dependent changes in heart rate: low doses (0.01 nmol) produced a bradycardic response, whereas high doses (2.5-5.0 nmol) elicited a tachycardic response (15). Thus adenosine may indeed be involved in the regulation of heart rate and modulate heart rate variability via local cardiac and central nervous system effects. It has been proposed that the intrinsic cardiac nervous system plays an active role in regulating cardiac function (4, 37, 45, 57). This nervous system consists of sympathetic and parasympathetic neurons and interconnecting local circuits (37). Neurons in the canine right atrial ganglionated plexus (RAGP) spontaneously generate activity even after chronic cardiac autonomic denervation (45). Right atrial neurons in patients undergoing coronary artery bypass surgery generated spontaneous activity that was unrelated to the cardiac cycle but sensitive to changes in systemic arterial pressure, indicating that these neurons receive pressure-sensitive sensory inputs (4). In addition, it has been suggested that substance P acts as a neuromodulator and neurotransmitter in intracardiac ganglia of the guinea pig, modulates the response to vagal inputs, and triggers action potentials at the site of parasympathetic ganglia independent of acetylcholine (57). Furthermore, the right atrial (RAGP) and the posterior atrial ganglionated plexus (PAGP) appear to have different functions. Ablation of the PAGP reduced vagally mediated bradycardia by 26%, whereas RAGP ablation completely abolished this response. Inhibition of sympathetically mediated tachycardia by vagal stimulation was attenuated by ablation of either plexus (37). Thus parasympathetic efferent neurons are primarily located in the RAGP, whereas prejunctional parasympathetic-sympathetic interactions also involve neurons within the PAGP (37). The spontaneous activity of neurons in the intrinsic cardiac nervous system, even after cardiac denervation (45), suggests an active role of this system in regulating heart rate. However, the impact of the intrinsic cardiac nervous system on heart rate variability remains to be elucidated. The importance of the autonomic nervous system for heart rate variability in humans becomes apparent in patients following cardiac transplantation, in whom heart rate variability is markedly reduced (49). Although reinnervation is possible after months and years, initially transplanted hearts can be considered to be denervated. Thus the reduced heart rate variability in cardiac transplanted patients (49) underlines the importance of an intact autonomic innervation for spontaneously occurring heart rate variability. A major component of the chronotropic effect of the autonomic nervous system is linked to cAMP. Intracellular cAMP increases the inward current of Na+ (funny current, If), which determines the rate of the slow diastolic depolarization that precedes each action potential. The activity of adenylate cyclase and thus intracellular cAMP levels are increased by stimulation of sympathetic β1-adrenergic receptors and decreased (via a Gi protein) by stimulation of parasympathetic muscarinic receptors. Thus cardiac sympathetic innervation increases the rate of the slow diastolic depolarization and accelerates heart rate, while cardiac parasympathetic innervation elicits opposite effects. Interestingly, parasympathetic-mediated changes in heart rate occur much faster than sympathetic-mediated effects on heart rate (27, 30, 47a). As a result, cardiac sympathetic nervous system activity can only affect LF components of heart rate variability, whereas the parasympathetic nervous system can also modulate HF components. A hitherto unsolved question in this context is if the rapid heart rate response to parasympathetic stimulation compared with the slow effect of sympathetic inputs is due to 1) different kinetics of β1-adrenergic vs. muscarinic receptors, 2) different kinetics of adenylate cyclase vs. phosphodiesterase, the enzyme that cleaves cAMP, or 3) fast parasympathetic-mediated opening of KACh channels (via muscarinic receptors and a GK protein). Support for the latter possibility comes from experiments in the rabbit sinoatrial node that demonstrated that activation of KACh channels contributes to the initial slowing of heart rate as a result of vagal stimulation (8).On the basis of the different frequency response characteristics of sympathetic and parasympathetic modulation of heart rate, frequency analysis of heart rate variability is often used as a tool to determine "autonomic balance" or sympathetic and parasympathetic nervous system activity (27, 47a). As an example, the wavelet transform was recently used to determine cardiac autonomic responses to reperfusion in patients with thrombolysis after coronary thrombosis. Depending on the location of the infarct, marked alterations in LF or HF spectral power of heart rate or in the LF/HF ratio was observed in all successful reperfusions (48).The HF component corresponds to the frequency of respiration and is driven by the vagus as indicated by the strong respiratory pattern of cardiac vagal motoneurons in the nucleus ambiguus (38). The LF component has been ascribed to sympathetic modulation of cardiac pacemaker activity, because a variety of studies demonstrated that acute interventions that increase sympathetic nervous system activity, such as orthostatic perturbations (17, 19, 33), mental stress (32), or handgrip exercise (13, 24) increases LF spectral power of heart rate (27, 30). In addition to acute perturbations of cardiac sympathetic nerve activity, feedback oscillations generated by the baroreceptor reflex also appear to contribute to LF spectral power of heart rate as it was demonstrated that sinoaortic denervation markedly reduces the LF component (27, 30). Despite the strong modulation of heart rate by the autonomic nervous system, the LF and HF spectral components of heart rate variability may not always be very reliable markers for cardiac sympathetic and parasympathetic "tone" (30). In a recent study, muscle sympathetic nerve activity was recorded together with heart rate variability during application of lower body negative pressure that is known to increase muscle sympathetic nerve activity (17, 33). At higher levels of lower body negative pressure (-15 mmHg), both muscle sympathetic nerve activity and relative LF spectral power of heart rate increased significantly, whereas HF spectral power decreased (17). These findings suggest that LF spectral power reflects cardiac sympathetic "tone." However, no correlation within subjects was found between changes in LF/HF ratio and muscle sympathetic nerve activity (17). Thus heart rate variability does not reliably reflect the sympathetic response to orthostatic stress. Respiration-related fluctuation of heart rate (respiratory sinus arrhythmia) is probably the most often investigated component of heart rate variability, as it is believed that this component reflects respiration-driven vagal modulation of sinus arrhythmia (27). In a recent study, Rentero et al. (38) recorded the electrical activity from cardiac vagal motoneurons in the nucleus ambiguus. Firing of these neurons was modulated by the central respiratory cycle. This and other studies support the view that respiratory sinus arrhythmia is generated by central coupling of the respiratory oscillator with autonomic centers in the brain stem. However, a mechanical cardiopulmonary coupling as a source of respiration-related heart rate variability has also been suggested (5). The Bainbridge reflex causes a tachycardia in response to hypervolemia. This reflex is initiated by atrial mechanoreceptors and uses efferent sympathetic and parasympathetic pathways to modulate heart rate in response to changes in central venous pressure (23). Thus respiratory changes in central blood volume cause corresponding respiratory fluctuations in cardiac autonomic nervous system activity via the Bainbridge reflex. Only the parasympathetic component of the efferent pathway of the reflex can contribute to respiratory sinus arrhythmia, because sympathetic actions on heart rate are too damped to follow the respiratory frequency. The gain and phase of the transfer function between respiratory changes in lung volume and R-R intervals of the ECG were calculated in human subjects during graded changes in central blood volume (5). At the respiratory frequency, the phase was -180 degree, indicating that an inspiratory increase in central blood volume was associated with a decrease in R-R interval (increase in heart rate). Furthermore, the gain of the transfer function at the respiratory frequency steadily increased with increasing central volumes (except at the highest volume). Both of these findings confirm the presence of the Bainbridge reflex in humans (5). Thus, in addition to the central coupling of respiratory oscillators with cardiovascular centers, the Bainbridge reflex may contribute to respiration-related heart rate variability by mechanical cardiopulmonary coupling. There is general agreement that low heart rate variability is an unfavorable prognostic marker for cardiovascular diseases, such as diabetic autonomic neuropathy, hypertension, myocardial infarction, and heart failure (18, 22, 27, 29, 47a). Heart rate variability (variance of R-R intervals) was reduced in patients with mild hypertension (29) compared with normal values (1,134 ± 202 vs. 3,466 ± 1,018 ms2) provided by the Task Force (47a). In the rat model of myocardial infarction-induced congestive heart failure, Francis and colleagues (18) reported loss of spontaneous heart rate variability 6 wk after coronary artery ligation. Interestingly, reduced heart rate variability was also observed in a rat model of depression that is based on chronic (4 wk) mild stress application (22). Because depression is an independent risk factor for coronary artery disease, this finding may realistically model a human disease process. The reduction in heart rate variability was abolished by β-adrenergic receptor blockade, indicating that the reduced heart rate variability in this model of depression is related to elevated cardiac sympathetic tone (22).In summary, heart rate variability is generated by multiple factors not exclusively limited to the autonomic nervous system. Specific frequency components of heart rate variability mirror acute perturbations of the autonomic nervous system but do not always reflect autonomic nervous system activity. Simple statistics of heart rate variability, such as the standard deviation of R-R intervals in the ECG, can reliably predict the prognosis of cardiovascular diseases.I thank Dr. R. McAllen for critically reviewing the manuscript. References 1 Aoki K, Stephens DP, and Johnson JM. Diurnal variation in cutaneous vasodilator and vasoconstrictor systems during heat stress. 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American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · review · 309 citationsread the source →

Consequences of an adolescent onset and persistent course of alcohol dependence in men: adolescent risk factors and adult outcomes.

Background: While there is an extensive literature on the correlates of alcohol use disorders (AUD; alcohol abuse and dependence), there are relatively few prospective studies of representative birth cohorts that have examined the unique effects of an adolescent onset and persistent course of AUD on a wide range of psychosocial variables. Methods: A longitudinal, community-based sample of 530 men was used to examine the impact of an adolescent onset (AUD+ at age 17) and persistent course (AUD+ at age 29) of AUD on adolescent and adult functioning including substance use, antisocial behavior, mental health problems, overall psychosocial functioning, environmental risk and protective factors, and social outcomes such as peer and romantic relationships, marriage, educational and occupational attainment, and parenthood. Results: An adolescent onset of AUD (n = 57) was associated with severe deficits across multiple domains of psychosocial functioning in adolescence. Measures of behavioral disinhibition in adolescence were strong predictors of a persistent course of AUD (n = 93). Nearly 40% of men with an adolescent onset were able to desist by age 29, and were similar, but not identical to men who never experienced an AUD in terms of adult functioning. Men with an adolescent onset and persistent course of AUD exhibited the most severe deficits in functioning. Conclusion: Results emphasize the importance of examining developmental course to understand the etiology of AUD. Our findings are optimistic in that individuals who desist from AUD are able to achieve high levels of psychosocial functioning. Our findings suggest that future research on the persistence of AUD into adulthood should focus on the contributions of behavioral disinhibition and social environment variables including peer and romantic relationships.

Alcoholism, clinical and experimental research · cohort or longitudinal · 77 citationsread the source →

A brief dyadic group based psychoeducation program improves relapse rates in recently remitted bipolar disorder: a pilot randomised controlled trial.

Background: Various adjunctive psychotherapies assist in decreasing relapse and improving outcomes for people with bipolar disorder (BD). Psychoeducation programs involving patient-only or caregiver-only groups have demonstrated some efficacy. We tested in recently remitted BD if a combined group based psychoeducation program involving patient-companion dyads decreased relapse. Method: 58 recently remitted BD out-patients were randomised to receive either treatment as usual (TAU, n=31) or 12 x 90 minute psychoeducation sessions delivered weekly in a group program to the patient and companion (SIMSEP, n=27). After 12 weeks SIMSEP patients reverted to TAU and all patients were followed until week 60 or relapse. The primary outcome measure was relapse requiring hospital or intensive community intervention. Results: 45 patients completed the study. 29 patients remained well at week 60 (SIMSEP n=17, TAU n=12), whilst 16 had relapsed (SIMSEP n=3, TAU n=13). The SIMSEP group were less likely to relapse (Fisher's exact test p=0.013; OR=0.16; 95% CI 0.04-0.70) and had an 11 week longer time to relapse compared to the TAU group (chi-square (1)=8.48, p<0.01). At study completion SIMSEP compared to TAU patients had lower Young Mania Rating Scale scores (Mann-Whitney U=255, p<0.01). Limitations: The study was limited by a small sample size. Conclusion: A brief group psychoeducation program with recently remitted BD patients and their companions resulted in a decreased relapse rate, longer time to relapse, decreased manic symptoms and improved medication adherence suggesting utility in the adjunctive psychotherapeutic treatment of BD.

Journal of affective disorders · randomised controlled trial · 44 citationsread the source →

A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression.

Context: Existing therapies for major depression have a lag of onset of action of several weeks, resulting in considerable morbidity. Exploring pharmacological strategies that have rapid onset of antidepressant effects within a few days and that are sustained would have an enormous impact on patient care. Converging lines of evidence suggest the role of the glutamatergic system in the pathophysiology and treatment of mood disorders. Objective: To determine whether a rapid antidepressant effect can be achieved with an antagonist at the N-methyl-D-aspartate receptor in subjects with major depression. Design: A randomized, placebo-controlled, double-blind crossover study from November 2004 to September 2005. Setting: Mood Disorders Research Unit at the National Institute of Mental Health. Patients Eighteen subjects with DSM-IV major depression (treatment resistant). Interventions: After a 2-week drug-free period, subjects were given an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2 test days, a week apart. Subjects were rated at baseline and at 40, 80, 110, and 230 minutes and 1, 2, 3, and 7 days postinfusion. Main Outcome Measure Changes in scores on the primary efficacy measure, the 21-item Hamilton Depression Rating Scale. Results: Subjects receiving ketamine showed significant improvement in depression compared with subjects receiving placebo within 110 minutes after injection, which remained significant throughout the following week. The effect size for the drug difference was very large (d = 1.46 [95% confidence interval, 0.91-2.01]) after 24 hours and moderate to large (d = 0.68 [95% confidence interval, 0.13-1.23]) after 1 week. Of the 17 subjects treated with ketamine, 71% met response and 29% met remission criteria the day following ketamine infusion. Thirty-five percent of subjects maintained response for at least 1 week. Conclusions: Robust and rapid antidepressant effects resulted from a single intravenous dose of an N-methyl-D-aspartate antagonist; onset occurred within 2 hours postinfusion and continued to remain significant for 1 week.

Archives of general psychiatry · randomised controlled trial · 2568 citationsread the source →

Association between Chronotype and Sleep Quality among Chinese College Students: The Role of Bedtime Procrastination and Sleep Hygiene Awareness.

Chronotype and sleep quality have been shown to play significant roles in influencing people's physical and mental health. The current study focuses on examining the relationship between chronotype and sleep quality among Chinese college students and exploring the mediating role of bedtime procrastination and the moderating role of sleep hygiene awareness. A sample of 2822 college students (female = 71.4%) aged between 17 and 29 years (M = 19.77, SD = 1.41) were included and completed the measures of the Pittsburgh Sleep Quality Index (PSQI), Morningness-Eveningness Questionnaire (MEQ), Bedtime Procrastination Scale (BPS) and Sleep Hygiene Awareness Scale (SHAS). The results showed that evening-type students reported the lowest sleep quality and highest levels of bedtime procrastination. In contrast, the highest sleep quality and lowest levels of bedtime procrastination were shown by morning-type, exhibiting the neither-type students' intermediate chronotype. Bedtime procrastination partially mediated the relationship between chronotype and sleep quality. Furthermore, sleep hygiene awareness moderated the direct effect of chronotype on sleep quality and the effect of chronotype in the path from chronotype to bedtime procrastination. Specifically, higher levels of sleep hygiene awareness could buffer the adverse effect of chronotype on self-reported sleep quality but bolstered the negative effect of chronotype on bedtime procrastination. Our results suggest that individuals with an evening preference are inclined to postpone their bedtime and further experience poorer sleep quality at night. Sleep hygiene awareness may serve as a protective factor for poor nocturnal sleep. Overall, the findings highlight the importance of reducing bedtime procrastination and improving sleep hygiene awareness in the interventions designed to help college students to own a better sleep quality, especially for those with evening chronotypes.

International journal of environmental research and public health · 38 citationsread the source →

Determinants of physical activity and sedentary behaviour in university students: a qualitative study using focus group discussions.

Background: College or university is a critical period regarding unhealthy changes in energy related behaviours in students. The first objective of this explorative study was to identify determinants of physical activity and sedentary behaviour in Belgian university students. Secondly, we aimed to collect ideas and recommendations to increase physical activity and decrease sedentary behaviours in university students. Methods: Using a semi-structured question guide, seven focus group discussions were conducted consisting of 17 male and 29 female university students from a variety of study disciplines, with a mean age of 20.7 ± 1.6 yrs. Using Nvivo9, an inductive thematic approach was used for data analysis. Results: Students reported that both physical and sedentary activities were influenced by individual factors (e.g. perceived enjoyment, self-discipline, time and convenience), their social networks (e.g. (lack of) parental control, modelling, social support), physical environment (e.g. availability and accessibility, travel time/distance, prices), and macro environment (e.g. media and advertising). Furthermore, the relationships between determinants and university students' physical activity and sedentary behaviour seemed to be moderated by university characteristics, such as residency, university lifestyle, exams and academic pressure. Recommendations for future physical activity interventions include improving information strategies regarding on-campus sports activities, cheaper and/or more flexible sports subscriptions and formulas, including 'sports time' into the curricula, and providing university bicycles around campus. Students also believed that increasing students' physical activity might decrease their sedentary behaviour at the same time. Conclusions: The recommendations and ideas discussed in this study may facilitate the development of effective and tailored (multilevel) intervention programs aiming to increase physical activity and decrease sedentary behaviours in university students.

BMC public health · 182 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 →

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 →

Social Interventions to Prevent Heat-Related Mortality in the Older Adult in Rome, Italy: A Quasi-Experimental Study.

This study focuses on the impact of a program aimed at reducing heat-related mortality among older adults residing in central Rome by counteracting social isolation. The mortality of citizens over the age of 75 living in three Urban Areas (UAs) located in central Rome is compared with that of the residents of four adjacent UAs during the summer of 2015. The data, broken down by UA, were provided by the Statistical Office of the Municipality of Rome, which gathers them on a routine basis. During the summer of 2015, 167 deaths were recorded in those UAs in which the Long Live the Elderly (LLE) program was active and 169 in those in which it was not, implying cumulative mortality rates of 25‰ (SD ± 1.4; Cl 95%: 23-29) and 29‰ (SD ± 6.7; Cl 95%: 17-43), respectively. Relative to the summer of 2014, the increase of deaths during the summer of 2015 was greater in UAs in which the LLE program had not been implemented (+97.3% vs. +48.8%). In conclusion, the paper shows the impact of a community-based active monitoring program, focused on strengthening individual relationship networks and the social capital of the community, on mortality in those over 75 during heat waves.

International journal of environmental research and public health · 30 citationsread the source →

Altered fecal microbiota composition in patients with major depressive disorder.

Studies using animal models have shown that depression affects the stability of the microbiota, but the actual structure and composition in patients with major depressive disorder (MDD) are not well understood. Here, we analyzed fecal samples from 46 patients with depression (29 active-MDD and 17 responded-MDD) and 30 healthy controls (HCs). High-throughput pyrosequencing showed that, according to the Shannon index, increased fecal bacterial α-diversity was found in the active-MDD (A-MDD) vs. the HC group but not in the responded-MDD (R-MDD) vs. the HC group. Bacteroidetes, Proteobacteria, and Actinobacteria strongly increased in level, whereas that of Firmicutes was significantly reduced in the A-MDD and R-MDD groups compared with the HC group. Despite profound interindividual variability, levels of several predominant genera were significantly different between the MDD and HC groups. Most notably, the MDD groups had increased levels of Enterobacteriaceae and Alistipes but reduced levels of Faecalibacterium. A negative correlation was observed between Faecalibacterium and the severity of depressive symptoms. These findings enable a better understanding of changes in the fecal microbiota composition in such patients, showing either a predominance of some potentially harmful bacterial groups or a reduction in beneficial bacterial genera. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and depression and to evaluate the suitability of the microbiome as a biomarker.

Brain, behavior, and immunity · 1667 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 →

Psychological interventions to foster resilience in healthcare professionals.

Background: Resilience can be defined as the maintenance or quick recovery of mental health during or after periods of stressor exposure, which may result from a potentially traumatising event, challenging life circumstances, a critical life transition phase, or physical illness. Healthcare professionals, such as nurses, physicians, psychologists and social workers, are exposed to various work-related stressors (e.g. patient care, time pressure, administration) and are at increased risk of developing mental disorders. This population may benefit from resilience-promoting training programmes. Objectives: To assess the effects of interventions to foster resilience in healthcare professionals, that is, healthcare staff delivering direct medical care (e.g. nurses, physicians, hospital personnel) and allied healthcare staff (e.g. social workers, psychologists). Search methods: We searched CENTRAL, MEDLINE, Embase, 11 other databases and three trial registries from 1990 to June 2019. We checked reference lists and contacted researchers in the field. We updated this search in four key databases in June 2020, but we have not yet incorporated these results. Selection criteria: Randomised controlled trials (RCTs) in adults aged 18 years and older who are employed as healthcare professionals, comparing any form of psychological intervention to foster resilience, hardiness or post-traumatic growth versus no intervention, wait-list, usual care, active or attention control. Primary outcomes were resilience, anxiety, depression, stress or stress perception and well-being or quality of life. Secondary outcomes were resilience factors. Data collection and analysis: Two review authors independently selected studies, extracted data, assessed risks of bias, and rated the certainty of the evidence using the GRADE approach (at post-test only). Main results: We included 44 RCTs (high-income countries: 36). Thirty-nine studies solely focused on healthcare professionals (6892 participants), including both healthcare staff delivering direct medical care and allied healthcare staff. Four studies investigated mixed samples (1000 participants) with healthcare professionals and participants working outside of the healthcare sector, and one study evaluated training for emergency personnel in general population volunteers (82 participants). The included studies were mainly conducted in a hospital setting and included physicians, nurses and different hospital personnel (37/44 studies). Participants mainly included women (68%) from young to middle adulthood (mean age range: 27 to 52.4 years). Most studies investigated group interventions (30 studies) of high training intensity (18 studies; > 12 hours/sessions), that were delivered face-to-face (29 studies). Of the included studies, 19 compared a resilience training based on combined theoretical foundation (e.g. mindfulness and cognitive-behavioural therapy) versus unspecific comparators (e.g. wait-list). The studies were funded by different sources (e.g. hospitals, universities), or a combination of different sources. Fifteen studies did not specify the source of their funding, and one study received no funding support. Risk of bias was high or unclear for most studies in performance, detection, and attrition bias domains. At post-intervention, very-low certainty evidence indicated that, compared to controls, healthcare professionals receiving resilience training may report higher levels of resilience (standardised mean difference (SMD) 0.45, 95% confidence interval (CI) 0.25 to 0.65; 12 studies, 690 participants), lower levels of depression (SMD -0.29, 95% CI -0.50 to -0.09; 14 studies, 788 participants), and lower levels of stress or stress perception (SMD -0.61, 95% CI -1.07 to -0.15; 17 studies, 997 participants). There was little or no evidence of any effect of resilience training on anxiety (SMD -0.06, 95% CI -0.35 to 0.23; 5 studies, 231 participants; very-low certainty evidence) or well-being or quality of life (SMD 0.14, 95% CI -0.01 to 0.30; 13 studies, 1494 participants; very-low certainty evidence). Effect sizes were small except for resilience and stress reduction (moderate). Data on adverse effects were available for three studies, with none reporting any adverse effects occurring during the study (very-low certainty evidence). Authors' conclusions: For healthcare professionals, there is very-low certainty evidence that, compared to control, resilience training may result in higher levels of resilience, lower levels of depression, stress or stress perception, and higher levels of certain resilience factors at post-intervention. The paucity of medium- or long-term data, heterogeneous interventions and restricted geographical distribution limit the generalisability of our results. Conclusions should therefore be drawn cautiously. The findings suggest positive effects of resilience training for healthcare professionals, but the evidence is very uncertain. There is a clear need for high-quality replications and improved study designs.

The Cochrane database of systematic reviews · meta-analysis · 227 citationsread the source →

Psychosocial interventions for self-harm in adults.

Background: Self-harm (SH; intentional self-poisoning or self-injury) is common, often repeated, and associated with suicide. This is an update of a broader Cochrane review first published in 1998, previously updated in 1999, and now split into three separate reviews. This review focuses on psychosocial interventions in adults who engage in self-harm. Objectives: To assess the effects of specific psychosocial treatments versus treatment as usual, enhanced usual care or other forms of psychological therapy, in adults following SH. Search methods: The Cochrane Depression, Anxiety and Neurosis Group (CCDAN) trials coordinator searched the CCDAN Clinical Trials Register (to 29 April 2015). This register includes relevant randomised controlled trials (RCTs) from: the Cochrane Library (all years), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). Selection criteria: We included RCTs comparing psychosocial treatments with treatment as usual (TAU), enhanced usual care (EUC) or alternative treatments in adults with a recent (within six months) episode of SH resulting in presentation to clinical services. Data collection and analysis: We used Cochrane's standard methodological procedures. Main results: We included 55 trials, with a total of 17,699 participants. Eighteen trials investigated cognitive-behavioural-based psychotherapy (CBT-based psychotherapy; comprising cognitive-behavioural, problem-solving therapy or both). Nine investigated interventions for multiple repetition of SH/probable personality disorder, comprising emotion-regulation group-based psychotherapy, mentalisation, and dialectical behaviour therapy (DBT). Four investigated case management, and 11 examined remote contact interventions (postcards, emergency cards, telephone contact). Most other interventions were evaluated in only single small trials of moderate to very low quality. There was a significant treatment effect for CBT-based psychotherapy compared to TAU at final follow-up in terms of fewer participants repeating SH (odds ratio (OR) 0.70, 95% confidence interval (CI) 0.55 to 0.88; number of studies k = 17; N = 2665; GRADE: low quality evidence), but with no reduction in frequency of SH (mean difference (MD) -0.21, 95% CI -0.68 to 0.26; k = 6; N = 594; GRADE: low quality).For interventions typically delivered to individuals with a history of multiple episodes of SH/probable personality disorder, group-based emotion-regulation psychotherapy and mentalisation were associated with significantly reduced repetition when compared to TAU: group-based emotion-regulation psychotherapy (OR 0.34, 95% CI 0.13 to 0.88; k = 2; N = 83; GRADE: low quality), mentalisation (OR 0.35, 95% CI 0.17 to 0.73; k = 1; N = 134; GRADE: moderate quality). Compared with TAU, dialectical behaviour therapy (DBT) showed a significant reduction in frequency of SH at final follow-up (MD -18.82, 95% CI -36.68 to -0.95; k = 3; N = 292; GRADE: low quality) but not in the proportion of individuals repeating SH (OR 0.57, 95% CI 0.21 to 1.59, k = 3; N = 247; GRADE: low quality). Compared with an alternative form of psychological therapy, DBT-oriented therapy was also associated with a significant treatment effect for repetition of SH at final follow-up (OR 0.05, 95% CI 0.00 to 0.49; k = 1; N = 24; GRADE: low quality). However, neither DBT vs 'treatment by expert' (OR 1.18, 95% CI 0.35 to 3.95; k = 1; N = 97; GRADE: very low quality) nor prolonged exposure DBT vs standard exposure DBT (OR 0.67, 95% CI 0.08 to 5.68; k = 1; N =18; GRADE: low quality) were associated with a significant reduction in repetition of SH.Case management was not associated with a significant reduction in repetition of SH at post intervention compared to either TAU or enhanced usual care (OR 0.78, 95% CI 0.47 to 1.30; k = 4; N = 1608; GRADE: moderate quality). Continuity of care by the same therapist vs a different therapist was also not associated with a significant treatment effect for repetition (OR 0.28, 95% CI 0.07 to 1.10; k = 1; N = 136; GRADE: very low quality). None of the following remote contact interventions were associated with fewer participants repeating SH compared with TAU: adherence enhancement (OR 0.57, 95% CI 0.32 to 1.02; k = 1; N = 391; GRADE: low quality), mixed multimodal interventions (comprising psychological therapy and remote contact-based interventions) (OR 0.98, 95% CI 0.68 to 1.43; k = 1 study; N = 684; GRADE: low quality), including a culturally adapted form of this intervention (OR 0.83, 95% CI 0.44 to 1.55; k = 1; N = 167; GRADE: low quality), postcards (OR 0.87, 95% CI 0.62 to 1.23; k = 4; N = 3277; GRADE: very low quality), emergency cards (OR 0.82, 95% CI 0.31 to 2.14; k = 2; N = 1039; GRADE: low quality), general practitioner's letter (OR 1.15, 95% CI 0.93 to 1.44; k = 1; N = 1932; GRADE: moderate quality), telephone contact (OR 0.74, 95% CI 0.42 to 1.32; k = 3; N = 840; GRADE: very low quality), and mobile telephone-based psychological therapy (OR not estimable due to zero cell counts; GRADE: low quality).None of the following mixed interventions were associated with reduced repetition of SH compared to either alternative forms of psychological therapy: interpersonal problem-solving skills training, behaviour therapy, home-based problem-solving therapy, long-term psychotherapy; or to TAU: provision of information and support, treatment for alcohol misuse, intensive inpatient and community treatment, general hospital admission, or intensive outpatient treatment. We had only limited evidence on whether the intervention had different effects in men and women. Data on adverse effects, other than planned outcomes relating to suicidal behaviour, were not reported. Authors' conclusions: CBT-based psychological therapy can result in fewer individuals repeating SH; however, the quality of this evidence, assessed using GRADE criteria, ranged between moderate and low. Dialectical behaviour therapy for people with multiple episodes of SH/probable personality disorder may lead to a reduction in frequency of SH, but this finding is based on low quality evidence. Case management and remote contact interventions did not appear to have any benefits in terms of reducing repetition of SH. Other therapeutic approaches were mostly evaluated in single trials of moderate to very low quality such that the evidence relating to these interventions is inconclusive.

The Cochrane database of systematic reviews · meta-analysis · 110 citationsread the source →

Interventions for the treatment of metastatic extradural spinal cord compression in adults.

Background: Metastatic extradural spinal cord compression (MESCC) is treated with radiotherapy, corticosteroids, and surgery, but there is uncertainty regarding their comparative effects. This is an updated version of the original Cochrane review published in theCochrane Database of Systematic Reviews (Issue 4, 2008). Objectives: To determine the efficacy and safety of radiotherapy, surgery and corticosteroids in MESCC. Search methods: In March 2015, we updated previous searches (July 2008 and December 2013) of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, LILACS, CANCERLIT, clinical trials registries, conference proceedings, and references, without language restrictions. We also contacted experts for relevant published, unpublished and ongoing trials. Selection criteria: Randomised controlled trials (RCTs) of radiotherapy, surgery and corticosteroids in adults with MESCC. Data collection and analysis: Three authors independently screened and selected trials, assessed risk of bias, and extracted data. We sought clarifications from trial authors. Where possible, we pooled relative risks with their 95% confidence intervals, using a random effects model if heterogeneity was significant. We assessed overall evidence-quality using the GRADE approach. Main results: This update includes seven trials involving 876 (723 evaluable) adult participants (19 to 87 years) in high-income countries. Most were free of the risk of bias. Different radiotherapy doses and schedulesTwo equivalence trials in people with MESCC and a poor prognosis evaluated different radiotherapy doses and schedules. In one, a single dose (8 Gray (Gy)) of radiotherapy (RT) was as effective as short-course RT (16 Gy in two fractions over one week) in enhancing ambulation in the short term (65% versus 69%; risk ratio (RR) was 0.93, (95% confidence interval (CI) 0.82 to 1.04); 303 participants; moderate quality evidence). The regimens were also equally effective in reducing analgesic and narcotic use (34% versus 40%; RR 0.85, 95% CI 0.62 to 1.16; 271 participants), and in maintaining urinary continence (90% versus 87%; RR 1.03, 95% CI 0.96 to 1.1; 303 participants) in the short term (moderate quality evidence). In the other trial, split-course RT (30 Gy in eight fractions over two weeks) was no different from short-course RT in enhancing ambulation (70% versus 68%; RR 1.02, 95% CI 0.9 to 1.15; 276 participants); reducing analgesic and narcotic use (49% versus 38%; RR 1.27, 95% CI 0.96 to 1.67; 262 participants); and in maintaining urinary continence (87% versus 90%; RR 0.97, 0.93 to 1.02; 275 participants) in the short term (moderate quality evidence). Median survival was similar with the three RT regimens (four months). Local tumour recurrence may be more common with single-dose compared to short-course RT (6% versus 3%; RR 2.21, 95% CI 0.69 to 7.01; 303 participants) and with short-course compared to split-course RT (4% versus 0%; RR 0.1, 95% CI 0.01 to 1.72; 276 participants), but these differences were not statistically significant (low quality evidence). Gastrointestinal adverse effects were infrequent with the three RT regimens (moderate quality evidence), and serious adverse events or post-radiotherapy myelopathy were not noted. We did not find trials comparing radiotherapy schedules in people with MESCC and a good prognosis. Surgery plus radiotherapy compared to radiotherapyLaminectomy plus RT offered no advantage over RT in one small trial with 29 participants (very low quality evidence). In another trial that was stopped early for apparent benefit, decompressive surgery plus RT resulted in better ambulatory rates (84% versus 57%; RR 1.48, 95% CI 1.16 to 1.90; 101 participants, low quality evidence). Narcotic use may also be lower, and bladder control may also be maintained longer than with than RT in selected patients (low quality evidence). Median survival was longer after surgery (126 days versus 100 days), but the proportions surviving at one month (94% versus 86%; RR 1.09, 95% CI 0.96 to 1.24; 101 participants) did not differ significantly (low quality evidence). Serious adverse events were not noted. Significant benefits with surgery occurred only in people younger than 65 years. High dose corticosteroids compared to moderate dose or no corticosteroidsData from three small trials suggest that high-dose steroids may not differ from moderate-dose or no corticosteroids in enhancing ambulation (60% versus 55%; RR 1.08, 95% CI 0.81 to 1.45; 3 RCTs, 105 participants); survival over two years (11% versus 10%; RR 1.11, 95% CI 0.24 to 5.05; 1 RCT, 57 participants); pain reduction (78% versus 91%; RR 0.86, 95% CI 0.62 to 1.20; 1 RCT, 25 participants); or urinary continence (63% versus 53%; RR 1.18, 95% CI 0.66 to 2.13; 1 RCT, 34 participants; low quality evidence). Serious adverse effects were more frequent with high-dose corticosteroids (17% versus 0%; RR 8.02, 95% CI 1.03 to 62.37; 2 RCTs, 77 participants; moderate quality evidence).None of the trials reported satisfaction with care or quality of life in participants. Authors' conclusions: Based on current evidence, ambulant adults with MESCC with stable spines and predicted survival of less than six months will probably benefit as much from one dose of radiation (8 Gy) as from two doses (16 Gy) or eight doses (30 Gy). We are unsure if a single dose is as effective as two or more doses in preventing local tumour recurrence. Laminectomy preceding radiotherapy may offer no benefits over radiotherapy alone. Decompressive surgery followed by radiotherapy may benefit ambulant and non-ambulant adults younger than 65 years of age, with poor prognostic factors for radiotherapy, a single area of compression, paraplegia for less than 48 hours, and a predicted survival of more than six months. We are uncertain whether high doses of corticosteroids offer any benefits over moderate doses or indeed no corticosteroids; but high-dose steroids probably significantly increases the risk of serious adverse effects. Early detection; and treatment based on neurological status, age and estimated survival, are crucial with all treatment modalities. Most of the evidence was of low quality. High-quality evidence from more trials is needed to clarify current uncertainties, and some studies are in progress.

The Cochrane database of systematic reviews · meta-analysis · 39 citationsread the source →

Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: a systematic review and meta-analysis.

Background: Medicinal cannabinoids, including medicinal cannabis and pharmaceutical cannabinoids and their synthetic derivatives, such as tetrahydrocannabinol (THC) and cannabidiol (CBD), have been suggested to have a therapeutic role in certain mental disorders. We analysed the available evidence to ascertain the effectiveness and safety of all types of medicinal cannabinoids in treating symptoms of various mental disorders. Methods: For this systematic review and meta-analysis we searched MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Clinical Trials, and the Cochrane Database of Systematic Reviews for studies published between Jan 1, 1980, and April 30, 2018. We also searched for unpublished or ongoing studies on ClinicalTrials.gov, the EU Clinical Trials Register, and the Australian and New Zealand Clinical Trials Registry. We considered all studies examining any type and formulation of a medicinal cannabinoid in adults (≥18 years) for treating depression, anxiety, attention-deficit hyperactivity disorder (ADHD), Tourette syndrome, post-traumatic stress disorder, or psychosis, either as the primary condition or secondary to other medical conditions. We placed no restrictions on language, publication status, or study type (ie, both experimental and observational study designs were included). Primary outcomes were remission from and changes in symptoms of these mental disorders. The safety of medicinal cannabinoids for these mental disorders was also examined. Evidence from randomised controlled trials was synthesised as odds ratios (ORs) for disorder remission, adverse events, and withdrawals and as standardised mean differences (SMDs) for change in symptoms, via random-effects meta-analyses. The quality of the evidence was assessed with the Cochrane risk of bias tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. This study is registered with PROSPERO (CRD42017059372, CRD42017059373, CRD42017059376, CRD42017064996, and CRD42018102977). Findings: 83 eligible studies (40 randomised controlled trials, n=3067) were included: 42 for depression (23 randomised controlled trials; n=2551), 31 for anxiety (17 randomised controlled trials; n=605), eight for Tourette syndrome (two randomised controlled trials; n=36), three for ADHD (one randomised controlled trial; n=30), 12 for post-traumatic stress disorder (one randomised controlled trial; n=10), and 11 for psychosis (six randomised controlled trials; n=281). Pharmaceutical THC (with or without CBD) improved anxiety symptoms among individuals with other medical conditions (primarily chronic non-cancer pain and multiple sclerosis; SMD -0·25 [95% CI -0·49 to -0·01]; seven studies; n=252), although the evidence GRADE was very low. Pharmaceutical THC (with or without CBD) worsened negative symptoms of psychosis in a single study (SMD 0·36 [95% CI 0·10 to 0·62]; n=24). Pharmaceutical THC (with or without CBD) did not significantly affect any other primary outcomes for the mental disorders examined but did increase the number of people who had adverse events (OR 1·99 [95% CI 1·20 to 3·29]; ten studies; n=1495) and withdrawals due to adverse events (2·78 [1·59 to 4·86]; 11 studies; n=1621) compared with placebo across all mental disorders examined. Few randomised controlled trials examined the role of pharmaceutical CBD or medicinal cannabis. Interpretation: There is scarce evidence to suggest that cannabinoids improve depressive disorders and symptoms, anxiety disorders, attention-deficit hyperactivity disorder, Tourette syndrome, post-traumatic stress disorder, or psychosis. There is very low quality evidence that pharmaceutical THC (with or without CBD) leads to a small improvement in symptoms of anxiety among individuals with other medical conditions. There remains insufficient evidence to provide guidance on the use of cannabinoids for treating mental disorders within a regulatory framework. Further high-quality studies directly examining the effect of cannabinoids on treating mental disorders are needed. Funding: Therapeutic Goods Administration, Australia; Commonwealth Department of Health, Australia; Australian National Health and Medical Research Council; and US National Institutes of Health.

The lancet. Psychiatry · meta-analysis · 309 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 →

Spiritual needs of patients with chronic pain diseases and cancer - validation of the spiritual needs questionnaire.

Purpose: For many patients confronted with chronic diseases, spirituality/religiosity is a relevant resource to cope. While most studies on patients' spiritual needs refer to the care of patients at the end of life, our intention was to develop an instrument to measure spiritual, existential and psychosocial need of patients with chronic diseases. Methods: In an anonymous cross-sectional survey, we applied the Spiritual Needs Questionnaire (SpNQ version 1.2.) to 210 patients (75% women, mean age 54 +/- 12 years) with chronic pain conditions (67%), cancer (28%), other chronic conditions (5%). Patients were recruited at the Community Hospital Herdecke, the Institute for Complementary Medicine (University of Bern), and at a conference of a cancer support group in Herten. Results: Factor analysis of the 19-item instrument (Cronbach's alpha +/- .93) pointed to 4 factors which explain 67% of variance: Religious Needs, Need for Inner Peace, Existentialistic Needs (Reflection / Meaning), and Actively Giving. Within the main sample of patients with chronic pain and cancer, Needs for Inner Peace had the highest scores, followed by Self competent Attention; Existentialistic Needs had low scores, while the Religious Needs scores indicate no interest. Patients with cancer had significantly higher SpNQ scores than patients with chronic pain conditions. There were just some weak associations between Actively Giving and life satisfaction (r +/- .17; p +/- .012), and negatively with the symptom score (r +/- -.29; p < .0001); Need for Inner Peace was weakly associated with satisfaction with treatment efficacy (r +/- .24; p < .0001). Regression analyses reveal that the underlying disease (i.e., cancer) was of outstanding relevance for the patients' spiritual needs. Conclusion: The preliminary results indicate that spiritual needs are conceptually different from life satisfaction, and can be interpreted as the patients' longing for spiritual well-being. Methods how health care professionals may meet their patients' spiritual needs remain to be explored.

European journal of medical research · cohort or longitudinal · 87 citationsread the source →

Islamic fasting leads to an increased abundance of Akkermansia muciniphila and Bacteroides fragilis group: A preliminary study on intermittent fasting.

Background/aims: It has been largely accepted that dietary habits affect intestinal microbiota composition. In this pilot study, we hypothesized that time-restricted feeding, which can be regarded as a type of intermittent fasting, may have a distinct effect on intestinal microbiota. Ramadan fasting is an excellent model to understand how time-restricted feeding affect the microbiota. Materials and methods: A total of nine subjects were included in this study during Ramadan, consisting of 17 h of fasting/day during a 29-day period. Stool samples were collected at baseline and the day of the end of Ramadan. 16S rRNA qPCR assay has been performed for quantification of Akkermansia muciniphila, Faecalibacterium prausnitzii, Bifidobacterium spp., Lactobacillus spp., Bacteroides fragilis group, and Enterobacteriaceae. Blood samples were also collected to test for metabolic and nutritional parameters. Results: A significantly increased abundance of A. muciniphila and B. fragilis group was observed in all subjects after Islamic fasting when compared with the baseline levels (p=0.004 and 0.008, respectively). Serum fasting glucose and total cholesterol levels were also significantly reduced in all of the subjects (p<0.01 and p=0.009, respectively). Conclusion: Islamic fasting, which represents intermittent fasting, leads to an increase in A. muciniphila and B. fragilis group, which were considered as healthy gut microbiota members. Although this is a pilot study, which should be tested with larger sample size, there are a very limited number of studies in the literature on fasting and microbiota in human subjects. Thus, our present findings may contribute to the understanding of fasting-gut microbiota interaction.

The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 70 citationsread the source →

Use of cognitive therapy for relapse prevention in chronic depression

BACKGROUND: There is a lack of data on the cost-effectiveness of relapse prevention in depression. METHOD: A total of 158 subjects with partially remitted major depression despite adequate clinical treatment were randomly allocated to cognitive therapy in addition to antidepressants and clinical management v. antidepressants and clinical management alone. Relapse rates and health care resource utilisation were measured prospectively over 17 months. RESULTS: Cumulative relapse rates in the cognitive therapy group were significantly lower than in the control group (29% v. 47%). The incremental cost incurred in subjects receiving cognitive therapy over 17 months (pound sterling 779; 95% CI pound sterling 387- pound sterling 1170) was significantly lower than the overall mean costs of cognitive therapy (pound sterling 1164; 95% CI pound sterling 1084- pound sterling 1244). The incremental cost-effectiveness ratio ranged from pound sterling 4328 to pound sterling 5027 per additional relapse prevented. CONCLUSIONS: In individuals with depressive symptoms that are resistant to standard treatment, adjunctive cognitive therapy is more costly but more effective than intensive clinical treatment alone.

The British Journal of Psychiatry · randomised controlled trial · 109 citationsread the source →

Sex as a biological determinant in anthropometric, biochemical, and dietary changes during Ramadan intermittent fasting in healthy people: A systematic review.

Aims: Observing Ramadan intermittent fasting (RIF) is associated with different behavioral, dietary, and health-related outcomes among healthy and unwell people. Sex is a major biological determinant that affects various health outcomes and impacts the effectiveness of dietary and lifestyle modifications. This systematic review aimed to identify differences in health-related outcomes following the practice of RIF by the sex of study participants. Methods: A systematic search was conducted across several databases to qualitatively identify studies focused on dietary, anthropometric, and biochemical outcomes associated with RIF in females and males. Results: Of 3870 retrieved studies, sex-based differences were reported in 29 studies that included 3167 healthy people (females n = 1558, 49.2%). Most differences between males and females were reported both before and during RIF. Sex differences were examined for 69 outcomes following RIF and included dietary factors (17 outcomes), anthropometrics (13 outcomes), and biochemical factors (39 outcomes), with the latter including metabolic, hormonal, regulatory, inflammatory, and nutrition-related biochemical markers. Conclusions: Sex-based differences were observed in the examined dietary, anthropometric, and biochemical outcomes associated with the observance of RIF. More attention needs to be directed toward including both sexes in studies focused on the impact of observing RIF and differentiating outcomes based on sex.

Diabetes & metabolic syndrome · systematic review · 6 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 →

Time for action-Improving the design and reporting of behaviour change interventions for antimicrobial stewardship in hospitals: Early findings from a systematic review.

There is strong evidence that self-monitoring and feedback are effective behaviour change techniques (BCTs) across a range of healthcare interventions and that their effectiveness is enhanced by goal setting and action planning. Here we report a summary of the update of a systematic review assessing the application of these BCTs to improving hospital antibiotic prescribing. This paper includes studies with valid prescribing outcomes published before the end of December 2012. We used a structured method for reporting these BCTs in terms of specific characteristics and contacted study authors to request additional intervention information. We identified 116 studies reporting 123 interventions. Reporting of BCTs was poor, with little detail of BCT characteristics. Feedback was only reported for 17 (13.8%) of the interventions, and self-monitoring was used in only 1 intervention. Goals were reported for all interventions but were poorly specified, with only three of the nine characteristics reported for ≥50% of interventions. A goal threshold and timescale were specified for just 1 of the 123 interventions. Only 29 authors (25.0%) responded to the request for additional information. In conclusion, both the content and reporting of interventions for antimicrobial stewardship fell short of scientific principles and practices. There is a strong evidence base regarding BCTs in other contexts that should be applied to antimicrobial stewardship now if we are to further our understanding of what works, for whom, why and in what contexts.

International journal of antimicrobial agents · systematic review · 51 citationsread the source →

Exercise interventions and patient beliefs for people with hip, knee or hip and knee osteoarthritis: a mixed methods review.

Background: Chronic peripheral joint pain due to osteoarthritis (OA) is extremely prevalent and a major cause of physical dysfunction and psychosocial distress. Exercise is recommended to reduce joint pain and improve physical function, but the effect of exercise on psychosocial function (health beliefs, depression, anxiety and quality of life) in this population is unknown. Objectives: To improve our understanding of the complex inter-relationship between pain, psychosocial effects, physical function and exercise. Search methods: Review authors searched 23 clinical, public health, psychology and social care databases and 25 other relevant resources including trials registers up to March 2016. We checked reference lists of included studies for relevant studies. We contacted key experts about unpublished studies. Selection criteria: To be included in the quantitative synthesis, studies had to be randomised controlled trials of land- or water-based exercise programmes compared with a control group consisting of no treatment or non-exercise intervention (such as medication, patient education) that measured either pain or function and at least one psychosocial outcome (self-efficacy, depression, anxiety, quality of life). Participants had to be aged 45 years or older, with a clinical diagnosis of OA (as defined by the study) or self-reported chronic hip or knee (or both) pain (defined as more than six months' duration).To be included in the qualitative synthesis, studies had to have reported people's opinions and experiences of exercise-based programmes (e.g. their views, understanding, experiences and beliefs about the utility of exercise in the management of chronic pain/OA). Data collection and analysis: We used standard methodology recommended by Cochrane for the quantitative analysis. For the qualitative analysis, we extracted verbatim quotes from study participants and synthesised studies of patients' views using framework synthesis. We then conducted an integrative review, synthesising the quantitative and qualitative data together. Main results: Twenty-one trials (2372 participants) met the inclusion criteria for quantitative synthesis. There were large variations in the exercise programme's content, mode of delivery, frequency and duration, participant's symptoms, duration of symptoms, outcomes measured, methodological quality and reporting. Comparator groups were varied and included normal care; education; and attention controls such as home visits, sham gel and wait list controls. Risk of bias was high in one and unclear risk in five studies regarding the randomisation process, high for 11 studies regarding allocation concealment, high for all 21 studies regarding blinding, and high for three studies and unclear for five studies regarding attrition. Studies did not provide information on adverse effects. There was moderate quality evidence that exercise reduced pain by an absolute percent reduction of 6% (95% confidence interval (CI) -9% to -4%, (9 studies, 1058 participants), equivalent to reducing (improving) pain by 1.25 points from 6.5 to 5.3 on a 0 to 20 scale and moderate quality evidence that exercise improved physical function by an absolute percent of 5.6% (95% CI -7.6% to 2.0%; standardised mean difference (SMD) -0.27, 95% CI -0.37 to -0.17, equivalent to reducing (improving) WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) function on a 0 to 100 scale from 49.9 to 44.3) (13 studies, 1599 participants)). Self-efficacy was increased by an absolute percent of 1.66% (95% CI 1.08% to 2.20%), although evidence was low quality (SMD 0.46, 95% CI 0.34 to 0.58, equivalent to improving the ExBeliefs score on a 17 to 85 scale from 64.3 to 65.4), with small benefits for depression from moderate quality evidence indicating an absolute percent reduction of 2.4% (95% CI -0.47% to 0.5%) (SMD -0.16, 95% CI -0.29 to -0.02, equivalent to improving depression measured using HADS (Hospital Anxiety and Depression Scale) on a 0 to 21 scale from 3.5 to 3.0) but no clinically or statistically significant effect on anxiety (SMD -0.11, 95% CI -0.26 to 0.05, 2% absolute improvement, 95% CI -5% to 1% equivalent to improving HADS anxiety on a 0 to 21 scale from 5.8 to 5.4; moderate quality evidence). Five studies measured the effect of exercise on health-related quality of life using the 36-item Short Form (SF-36) with statistically significant benefits for social function, increasing it by an absolute percent of 7.9% (95% CI 4.1% to 11.6%), equivalent to increasing SF-36 social function on a 0 to 100 scale from 73.6 to 81.5, although the evidence was low quality. Evidence was downgraded due to heterogeneity of measures, limitations with blinding and lack of detail regarding interventions. For 20/21 studies, there was a high risk of bias with blinding as participants self-reported and were not blinded to their participation in an exercise intervention. Twelve studies (with 6 to 29 participants) met inclusion criteria for qualitative synthesis. Their methodological rigour and quality was generally good. From the patients' perspectives, ways to improve the delivery of exercise interventions included: provide better information and advice about the safety and value of exercise; provide exercise tailored to individual's preferences, abilities and needs; challenge inappropriate health beliefs and provide better support. An integrative review, which compared the findings from quantitative trials with low risk of bias and the implications derived from the high-quality studies in the qualitative synthesis, confirmed the importance of these implications. Authors' conclusions: Chronic hip and knee pain affects all domains of people's lives. People's beliefs about chronic pain shape their attitudes and behaviours about how to manage their pain. People are confused about the cause of their pain, and bewildered by its variability and randomness. Without adequate information and advice from healthcare professionals, people do not know what they should and should not do, and, as a consequence, avoid activity for fear of causing harm. Participation in exercise programmes may slightly improve physical function, depression and pain. It may slightly improve self-efficacy and social function, although there is probably little or no difference in anxiety. Providing reassurance and clear advice about the value of exercise in controlling symptoms, and opportunities to participate in exercise programmes that people regard as enjoyable and relevant, may encourage greater exercise participation, which brings a range of health benefits to a large population of people.

The Cochrane database of systematic reviews · systematic review · 193 citationsread the source →

A Systematized review of experiences of individuals in Arnett's emerging adulthood stage who live with or are at-risk for genetic conditions.

Emerging adulthood, a distinct developmental period between ages 18 and 29 years, comprises five features: identity exploration, experimentation/possibilities, negativity/instability regarding one's outlook, self-focus, and feeling in-between adolescence and adulthood. A growing literature examines the impact of genetic conditions on individuals who chronologically fit the emerging adulthood period. This systematized literature review uses the emerging adulthood theory to determine whether individuals living with or at-risk for a genetic condition experience the features of this period as well as similarities and differences between these two groups. A literature search yielded 1,303 peer-reviewed papers from the 17 years since emerging adulthood theory was published. Ten papers met inclusion criteria-five for those Living With a genetic condition (e.g., cystic fibrosis) and five for those At-Risk for a genetic condition (e.g., hereditary breast and ovarian cancer). Content analysis yielded themes consistent with the five emerging adulthood features for both individuals Living With and At-Risk for genetic conditions. Negativity/instability was most prevalent, and feeling in-between was least prevalent in both groups. Results further suggest unique challenges related to one's genetic conditions/risk with respect to independence (from family, healthcare providers), career/education, relationships/social life, family planning, and life perspective experiences. Salient differences were apparent between the groups in their experiences of the emerging adulthood features. For instance, Living With individuals reported challenges concerning their ongoing physical symptoms, whereas At-Risk individuals reported challenges regarding genetic testing decisions and anticipation of physical symptoms. Thus, emerging adults Living With and At-Risk for genetic conditions appear to experience the main emerging adulthood features, but they face unique challenges related to their genetic conditions/risk. Understanding emerging adults' experiences can aid genetic counselors in addressing their specific concerns.

Journal of genetic counseling · systematic review · 3 citationsread the source →

Music interventions for improving psychological and physical outcomes in people with cancer.

Background: This is an update of the review published on the Cochrane Library in 2016, Issue 8. Having cancer may result in extensive emotional, physical and social suffering. Music interventions have been used to alleviate symptoms and treatment side effects in people with cancer. This review includes music interventions defined as music therapy offered by trained music therapists, as well as music medicine, which was defined as listening to pre-recorded music offered by medical staff. Objectives: To assess and compare the effects of music therapy and music medicine interventions for psychological and physical outcomes in people with cancer. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 3) in the Cochrane Library, MEDLINE via Ovid, Embase via Ovid, CINAHL, PsycINFO, LILACS, Science Citation Index, CancerLit, CAIRSS, Proquest Digital Dissertations, ClinicalTrials.gov, Current Controlled Trials, the RILM Abstracts of Music Literature, http://www.wfmt.info/Musictherapyworld/ and the National Research Register. We searched all databases, except for the last two, from their inception to April 2020; the other two are no longer functional, so we searched them until their termination date. We handsearched music therapy journals, reviewed reference lists and contacted experts. There was no language restriction. Selection criteria: We included all randomized and quasi-randomized controlled trials of music interventions for improving psychological and physical outcomes in adults and pediatric patients with cancer. We excluded patients undergoing biopsy and aspiration for diagnostic purposes. Data collection and analysis: Two review authors independently extracted the data and assessed the risk of bias. Where possible, we presented results in meta-analyses using mean differences and standardized mean differences. We used post-test scores. In cases of significant baseline difference, we used change scores. We conducted separate meta-analyses for studies with adult participants and those with pediatric participants. Primary outcomes of interest included psychological outcomes and physical symptoms and secondary outcomes included physiological responses, physical functioning, anesthetic and analgesic intake, length of hospitalization, social and spiritual support, communication, and quality of life (QoL) . We used GRADE to assess the certainty of the evidence. Main results: We identified 29 new trials for inclusion in this update. In total, the evidence of this review rests on 81 trials with a total of 5576 participants. Of the 81 trials, 74 trials included adult (N = 5306) and seven trials included pediatric (N = 270) oncology patients. We categorized 38 trials as music therapy trials and 43 as music medicine trials. The interventions were compared to standard care. Psychological outcomes The results suggest that music interventions may have a large anxiety-reducing effect in adults with cancer, with a reported average anxiety reduction of 7.73 units (17 studies, 1381 participants; 95% confidence interval (CI) -10.02 to -5.44; very low-certainty evidence) on the Spielberger State Anxiety Inventory scale (range 20 to 80; lower values reflect lower anxiety). Results also suggested a moderately strong, positive impact of music interventions on depression in adults (12 studies, 1021 participants; standardized mean difference (SMD): -0.41, 95% CI -0.67 to -0.15; very low-certainty evidence). We found no support for an effect of music interventions on mood (SMD 0.47, 95% CI -0.02 to 0.97; 5 studies, 236 participants; very low-certainty evidence). Music interventions may increase hope in adults with cancer, with a reported average increase of 3.19 units (95% CI 0.12 to 6.25) on the Herth Hope Index (range 12 to 48; higher scores reflect greater hope), but this finding was based on only two studies (N = 53 participants; very low-certainty evidence). Physical outcomes We found a moderate pain-reducing effect of music interventions (SMD -0.67, 95% CI -1.07 to -0.26; 12 studies, 632 adult participants; very low-certainty evidence). In addition, music interventions had a small treatment effect on fatigue (SMD -0.28, 95% CI -0.46 to -0.10; 10 studies, 498 adult participants; low-certainty evidence). The results suggest a large effect of music interventions on adult participants' QoL, but the results were highly inconsistent across studies, and the pooled effect size was accompanied by a large confidence interval (SMD 0.88, 95% CI -0.31 to 2.08; 7 studies, 573 participants; evidence is very uncertain). Removal of studies that used improper randomization methods resulted in a moderate effect size that was less heterogeneous (SMD 0.47, 95% CI 0.06 to 0.88, P = 0.02, I2 = 56%). A small number of trials included pediatric oncology participants. The findings suggest that music interventions may reduce anxiety but this finding was based on only two studies (SMD -0.94, 95% CI -1.9 to 0.03; very low-certainty evidence). Due to the small number of studies, we could not draw conclusions regarding the effects of music interventions on mood, depression, QoL, fatigue or pain in pediatric participants with cancer. The majority of studies included in this review update presented a high risk of bias, and therefore the overall certainty of the evidence is low. For several outcomes (i.e. anxiety, depression, pain, fatigue, and QoL) the beneficial treatment effects were consistent across studies for music therapy interventions delivered by music therapists. In contrast, music medicine interventions resulted in inconsistent treatment effects across studies for these outcomes. Authors' conclusions: This systematic review indicates that music interventions compared to standard care may have beneficial effects on anxiety, depression, hope, pain, and fatigue in adults with cancer. The results of two trials suggest that music interventions may have a beneficial effect on anxiety in children with cancer. Too few trials with pediatric participants were included to draw conclusions about the treatment benefits of music for other outcomes. For several outcomes, music therapy interventions delivered by a trained music therapist led to consistent results across studies and this was not the case for music medicine interventions. Moreover, evidence of effect was found for music therapy interventions for QoL and fatigue but not for music medicine interventions. Most trials were at high risk of bias and low or very low certainty of evidence; therefore, these results need to be interpreted with caution.

The Cochrane database of systematic reviews · systematic review · 144 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 →

Interventions for people with type 2 diabetes mellitus fasting during Ramadan.

Background: Fasting during Ramadan is obligatory for adult Muslims, except those who have a medical illness. Many Muslims with type 2 diabetes (T2DM) choose to fast, which may increase their risks of hypoglycaemia and dehydration. Objectives: To assess the effects of interventions for people with type 2 diabetes fasting during Ramadan. Search methods: We searched CENTRAL, MEDLINE, PsycINFO, CINAHL, WHO ICTRP and ClinicalTrials.gov (29 June 2022) without language restrictions. Selection criteria: Randomised controlled trials (RCTs) conducted during Ramadan that evaluated all pharmacological or behavioural interventions in Muslims with T2DM. Data collection and analysis: Two authors screened and selected records, assessed risk of bias and extracted data independently. Discrepancies were resolved by a third author. For meta-analyses we used a random-effects model, with risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes with their associated 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach. Main results: We included 17 RCTs with 5359 participants, with a four-week study duration and at least four weeks of follow-up. All studies had at least one high-risk domain in the risk of bias assessment. Four trials compared dipeptidyl-peptidase-4 (DPP-4) inhibitors with sulphonylurea. DPP-4 inhibitors may reduce hypoglycaemia compared to sulphonylureas (85/1237 versus 165/1258, RR 0.53, 95% CI 0.41 to 0.68; low-certainty evidence). Serious hypoglycaemia was similar between groups (no events were reported in two trials; 6/279 in the DPP-4 versus 4/278 in the sulphonylurea group was reported in one trial, RR 1.49, 95% CI 0.43 to 5.24; very low-certainty evidence). The evidence was very uncertain about the effects of DPP-4 inhibitors on adverse events other than hypoglycaemia (141/1207 versus 157/1219, RR 0.90, 95% CI 0.52 to 1.54) and HbA1c changes (MD -0.11%, 95% CI -0.57 to 0.36) (very low-certainty evidence for both outcomes). No deaths were reported (moderate-certainty evidence). Health-related quality of life (HRQoL) and treatment satisfaction were not evaluated. Two trials compared meglitinides with sulphonylurea. The evidence is very uncertain about the effect on hypoglycaemia (14/133 versus 21/140, RR 0.72, 95% CI 0.40 to 1.28) and HbA1c changes (MD 0.38%, 95% CI 0.35% to 0.41%) (very low-certainty evidence for both outcomes). Death, serious hypoglycaemic events, adverse events, treatment satisfaction and HRQoL were not evaluated. One trial compared sodium-glucose co-transporter-2 (SGLT-2) inhibitors with sulphonylurea. SGLT-2 may reduce hypoglycaemia compared to sulphonylurea (4/58 versus 13/52, RR 0.28, 95% CI 0.10 to 0.79; low-certainty evidence). The evidence was very uncertain for serious hypoglycaemia (one event reported in both groups, RR 0.90, 95% CI 0.06 to 13.97) and adverse events other than hypoglycaemia (20/58 versus 18/52, RR 1.00, 95% CI 0.60 to 1.67) (very low-certainty evidence for both outcomes). SGLT-2 inhibitors result in little or no difference in HbA1c (MD 0.27%, 95% CI -0.04 to 0.58; 1 trial, 110 participants; low-certainty evidence). Death, treatment satisfaction and HRQoL were not evaluated. Three trials compared glucagon-like peptide 1 (GLP-1) analogues with sulphonylurea. GLP-1 analogues may reduce hypoglycaemia compared to sulphonylurea (20/291 versus 48/305, RR 0.45, 95% CI 0.28 to 0.74; low-certainty evidence). The evidence was very uncertain for serious hypoglycaemia (0/91 versus 1/91, RR 0.33, 95% CI 0.01 to 7.99; very low-certainty evidence). The evidence suggests that GLP-1 analogues result in little to no difference in adverse events other than hypoglycaemia (78/244 versus 55/255, RR 1.50, 95% CI 0.86 to 2.61; very low-certainty evidence), treatment satisfaction (MD -0.18, 95% CI -3.18 to 2.82; very low-certainty evidence) or change in HbA1c (MD -0.04%, 95% CI -0.45% to 0.36%; 2 trials, 246 participants; low-certainty evidence). Death and HRQoL were not evaluated. Two trials compared insulin analogues with biphasic insulin. The evidence was very uncertain about the effects of insulin analogues on hypoglycaemia (47/256 versus 81/244, RR 0.43, 95% CI 0.13 to 1.40) and serious hypoglycaemia (4/131 versus 3/132, RR 1.34, 95% CI 0.31 to 5.89) (very low-certainty evidence for both outcomes). The evidence was very uncertain for the effect of insulin analogues on adverse effects other than hypoglycaemia (109/256 versus 114/244, RR 0.83, 95% CI 0.44 to 1.56; very low-certainty evidence), all-cause mortality (1/131 versus 0/132, RR 3.02, 95% CI 0.12 to 73.53; very low-certainty evidence) and HbA1c changes (MD 0.03%, 95% CI -0.17% to 0.23%; 1 trial, 245 participants; very low-certainty evidence). Treatment satisfaction and HRQoL were not evaluated. Two trials compared telemedicine with usual care. The evidence was very uncertain about the effect of telemedicine on hypoglycaemia compared with usual care (9/63 versus 23/58, RR 0.42, 95% CI 0.24 to 0.74; very low-certainty evidence), HRQoL (MD 0.06, 95% CI -0.03 to 0.15; very low-certainty evidence) and HbA1c change (MD -0.84%, 95% CI -1.51% to -0.17%; very low-certainty evidence). Death, serious hypoglycaemia, AEs other than hypoglycaemia and treatment satisfaction were not evaluated. Two trials compared Ramadan-focused patient education with usual care. The evidence was very uncertain about the effect of Ramadan-focused patient education on hypoglycaemia (49/213 versus 42/209, RR 1.17, 95% CI 0.82 to 1.66; very low-certainty evidence) and HbA1c change (MD -0.40%, 95% CI -0.73% to -0.06%; very low-certainty evidence). Death, serious hypoglycaemia, adverse events other than hypoglycaemia, treatment satisfaction and HRQoL were not evaluated. One trial compared drug dosage reduction with usual care. The evidence is very uncertain about the effect of drug dosage reduction on hypoglycaemia (19/452 versus 52/226, RR 0.18, 95% CI 0.11 to 0.30; very low-certainty evidence). No participants experienced adverse events other than hypoglycaemia during the study (very low-certainty evidence). Death, serious hypoglycaemia, treatment satisfaction, HbA1c change and HRQoL were not evaluated. Authors' conclusions: There is no clear evidence of the benefits or harms of interventions for individuals with T2DM who fast during Ramadan. All results should be interpreted with caution due to concerns about risk of bias, imprecision and inconsistency between studies, which give rise to low- to very low-certainty evidence. Major outcomes, such as mortality, health-related quality of life and severe hypoglycaemia, were rarely evaluated. Sufficiently powered studies that examine the effects of various interventions on these outcomes are needed.

The Cochrane database of systematic reviews · systematic review · 1 citationsread the source →

Socioeconomic status, structural and functional measures of social support, and mortality: The British Whitehall II Cohort Study, 1985-2009.

The authors examined the associations of social support with socioeconomic status (SES) and with mortality, as well as how SES differences in social support might account for SES differences in mortality. Analyses were based on 9,333 participants from the British Whitehall II Study cohort, a longitudinal cohort established in 1985 among London-based civil servants who were 35-55 years of age at baseline. SES was assessed using participant's employment grades at baseline. Social support was assessed 3 times in the 24.4-year period during which participants were monitored for death. In men, marital status, and to a lesser extent network score (but not low perceived support or high negative aspects of close relationships), predicted both all-cause and cardiovascular mortality. Measures of social support were not associated with cancer mortality. Men in the lowest SES category had an increased risk of death compared with those in the highest category (for all-cause mortality, hazard ratio = 1.59, 95% confidence interval: 1.21, 2.08; for cardiovascular mortality, hazard ratio = 2.48, 95% confidence interval: 1.55, 3.92). Network score and marital status combined explained 27% (95% confidence interval: 14, 43) and 29% (95% confidence interval: 17, 52) of the associations between SES and all-cause and cardiovascular mortality, respectively. In women, there was no consistent association between social support indicators and mortality. The present study suggests that in men, social isolation is not only an important risk factor for mortality but is also likely to contribute to differences in mortality by SES.

American journal of epidemiology · 121 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 →

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 →

Effect of a stepped-care intervention delivered by lay health workers on major depressive disorder among primary care patients in Nigeria (STEPCARE): a cluster-randomised controlled trial.

Background: Little is known about how to scale up care for depression in settings where non-physician lay workers constitute the bulk of frontline providers. We aimed to compare a stepped-care intervention package for depression with usual care enhanced by use of the WHO Mental Health Gap Action Programme intervention guide (mhGAP-IG). Methods: We did a cluster-randomised trial in primary care clinics in Ibadan, Nigeria. Eligible clinics were those with adequate staffing to provide various 24-h clinical services and with regular physician supervision. Clinics (clusters), anonymised and stratified by local government area, were randomly allocated (1:1) with a computer-generated random number sequence to one of two groups: an intervention group in which patients received a stepped-care intervention (eight sessions of individual problem-solving therapy, with an extra two to four sessions if needed) plus enhanced usual care, and a control group in which patients received enhanced usual care only. Patients from enrolled clinics could participate if they were aged 18 years or older, not pregnant, and had moderate to severe depression (scoring ≥11 on the nine-item patient health questionnaire [PHQ-9]). The primary outcome was the proportion of patients with remission of depression at 12 months (a score of ≤6 on the PHQ-9, with assessors masked to group allocation) in the intention-to-treat population. This trial is registered with the International Standard Randomised Controlled Trials Number registry (ISRCTN46754188) and is completed. Findings: 35 of 97 clinics approached were eligible and agreed to participate, of which 18 were allocated to the intervention group and 17 to the control group. 1178 patients (631 [54%] in the intervention group and 547 [46%] in the control group) were recruited between Dec 2, 2013, and June 29, 2015, among whom 976 (83%) were female and baseline mean PHQ-9 score was 13·7 (SD 2·6). Of the 562 (89%) patients in the intervention group and 473 (86%) in the control group who completed 12-month follow-up, similar proportions in each group had remission of depression (425 [76%] in the intervention group vs 366 [77%] in the control group; adjusted odds ratio 1·0 [95% CI 0·70-1·40]). At 12 months, 17 (3%) deaths, one (<1%) psychotic illness, and one (<1%) case of bipolar disorder in the intervention group, and 16 deaths (3%) and one (<1%) case of bipolar disorder in the control group were recorded. No adverse events were judged to be related to the study procedures. Interpretation: For patients with moderate to severe depression receiving care from non-physician primary health-care workers in Nigeria, a stepped-care, problem-solving intervention combined with enhanced usual care is similarly effective to enhanced usual care alone. Enhancing usual care with mhGAP-IG might provide simple and affordable approach to scaling up depression care in sub-Saharan Africa. Funding: UK Medical Research Council.

The Lancet. Global health · randomised controlled trial · 49 citationsread the source →

Effects of Mindfulness Training and Exercise on Cognitive Function in Older Adults: A Randomized Clinical Trial.

Importance: Episodic memory and executive function are essential aspects of cognitive functioning that decline with aging. This decline may be ameliorable with lifestyle interventions. Objective: To determine whether mindfulness-based stress reduction (MBSR), exercise, or a combination of both improve cognitive function in older adults. Design, setting, and participants: This 2 × 2 factorial randomized clinical trial was conducted at 2 US sites (Washington University in St Louis and University of California, San Diego). A total of 585 older adults (aged 65-84 y) with subjective cognitive concerns, but not dementia, were randomized (enrollment from November 19, 2015, to January 23, 2019; final follow-up on March 16, 2020). Interventions: Participants were randomized to undergo the following interventions: MBSR with a target of 60 minutes daily of meditation (n = 150); exercise with aerobic, strength, and functional components with a target of at least 300 minutes weekly (n = 138); combined MBSR and exercise (n = 144); or a health education control group (n = 153). Interventions lasted 18 months and consisted of group-based classes and home practice. Main outcomes and measures: The 2 primary outcomes were composites of episodic memory and executive function (standardized to a mean [SD] of 0 [1]; higher composite scores indicate better cognitive performance) from neuropsychological testing; the primary end point was 6 months and the secondary end point was 18 months. There were 5 reported secondary outcomes: hippocampal volume and dorsolateral prefrontal cortex thickness and surface area from structural magnetic resonance imaging and functional cognitive capacity and self-reported cognitive concerns. Results: Among 585 randomized participants (mean age, 71.5 years; 424 [72.5%] women), 568 (97.1%) completed 6 months in the trial and 475 (81.2%) completed 18 months. At 6 months, there was no significant effect of mindfulness training or exercise on episodic memory (MBSR vs no MBSR: 0.44 vs 0.48; mean difference, -0.04 points [95% CI, -0.15 to 0.07]; P = .50; exercise vs no exercise: 0.49 vs 0.42; difference, 0.07 [95% CI, -0.04 to 0.17]; P = .23) or executive function (MBSR vs no MBSR: 0.39 vs 0.31; mean difference, 0.08 points [95% CI, -0.02 to 0.19]; P = .12; exercise vs no exercise: 0.39 vs 0.32; difference, 0.07 [95% CI, -0.03 to 0.18]; P = .17) and there were no intervention effects at the secondary end point of 18 months. There was no significant interaction between mindfulness training and exercise (P = .93 for memory and P = .29 for executive function) at 6 months. Of the 5 prespecified secondary outcomes, none showed a significant improvement with either intervention compared with those not receiving the intervention. Conclusions and relevance: Among older adults with subjective cognitive concerns, mindfulness training, exercise, or both did not result in significant differences in improvement in episodic memory or executive function at 6 months. The findings do not support the use of these interventions for improving cognition in older adults with subjective cognitive concerns. Trial registration: ClinicalTrials.gov Identifier: NCT02665481.

JAMA · randomised controlled trial · 109 citationsread the source →

An online healthy relationship tool and safety decision aid for women experiencing intimate partner violence (I-DECIDE): a randomised controlled trial.

Background: Evidence for online interventions to help women experiencing intimate partner violence is scarce. We assessed whether an online interactive healthy relationship tool and safety decision aid (I-DECIDE) would increase women's self-efficacy and improve depressive symptoms compared with an intimate partner violence information website. Methods: In this two-group pragmatic randomised controlled trial, we enrolled women who had screened positive for any form of intimate partner violence or fear of a partner in the 6 months before recruitment. Women aged 16-50 years currently residing in Australia, who had safe access to a computer and an internet connection, and who answered positively to one of the screening questions in English were eligible for inclusion. Participants were randomly assigned (1:1) by computer to receive either the intervention or control website. The intervention website consisted of modules on healthy relationships, abuse and safety, and relationship priority setting, and a tailored action plan. The control website was a static intimate partner violence information website. As the initial portion of the website containing the baseline questions was identical for both groups, there was no way for women to tell which group they had been allocated to, and the research team were also masked to participant allocation until after analysis of the 12-month data. Data were collected at baseline, immediately after completion of the website, at 6 months, and 12 months. Primary outcomes were mean general self-efficacy score (immediately after website completion, and at 6 months and 12 months) and mean depression score (at 6 months and 12 months). Data analyses were done according to intention-to-treat principles, accounting for missing data, and adjusted for outcome baseline scores. This trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN 12614001306606. Findings: Between Jan 16, and Aug 28, 2015, 584 patients registered for the study and were assessed for eligibility. 422 eligible participants were randomly allocated to the intervention group (227 patients) or control group (195 patients). 179 (79%) participants in the intervention group and 156 (80%) participants in the control group completed 12-month follow-up. Mean self-efficacy at 6 months and 12 months was lower for participants in the intervention group than for participants in the control group, although this did not meet the prespecified mean difference (6 months: 27·5 [SD 5·1] vs 28·1 [4·4], imputed mean difference 1·3 [95% CI 0·3 to 2·3]; 12 months: 27·8 [SD 5·4] vs 29·0 [5·0], imputed mean difference 1·6 [95% CI 0·5 to 2·7]). We found no difference between groups in depressive symptoms at 6 months or 12 months (6 months: 22·5 [SD 17·1] vs 24·2 [17·2], imputed mean difference -0·3 [95% CI -3·5 to 3·0]; 12 months: 21·9 [SD 19·3] vs 21·5 [19·3], imputed mean difference -1·9 [95% CI -5·6 to 1·7]). Qualitative findings indicated that participants found the intervention supportive and a motivation for action. Interpretation: Our findings highlight the need for further research, development, and refinement of online interventions for women experiencing intimate partner violence, particularly into the duration needed for interventions. Although we detected no meaningful differences between groups, our qualitative results indicated that some women find an online tool a helpful source of motivation and support. Funding: Australian Research Council.

The Lancet. Public health · randomised controlled trial · 43 citationsread the source →

The effects of improving sleep on mental health (OASIS): a randomised controlled trial with mediation analysis.

Background: Sleep difficulties might be a contributory causal factor in the occurrence of mental health problems. If this is true, improving sleep should benefit psychological health. We aimed to determine whether treating insomnia leads to a reduction in paranoia and hallucinations. Methods: We did this single-blind, randomised controlled trial (OASIS) at 26 UK universities. University students with insomnia were randomly assigned (1:1) with simple randomisation to receive digital cognitive behavioural therapy (CBT) for insomnia or usual care, and the research team were masked to the treatment. Online assessments took place at weeks 0, 3, 10 (end of therapy), and 22. The primary outcome measures were for insomnia, paranoia, and hallucinatory experiences. We did intention-to-treat analyses. The trial is registered with the ISRCTN registry, number ISRCTN61272251. Findings: Between March 5, 2015, and Feb 17, 2016, we randomly assigned 3755 participants to receive digital CBT for insomnia (n=1891) or usual practice (n=1864). Compared with usual practice, the sleep intervention at 10 weeks reduced insomnia (adjusted difference 4·78, 95% CI 4·29 to 5·26, Cohen's d=1·11; p<0·0001), paranoia (-2·22, -2·98 to -1·45, Cohen's d=0·19; p<0·0001), and hallucinations (-1·58, -1·98 to -1·18, Cohen's d=0·24; p<0·0001). Insomnia was a mediator of change in paranoia and hallucinations. No adverse events were reported. Interpretation: To our knowledge, this is the largest randomised controlled trial of a psychological intervention for a mental health problem. It provides strong evidence that insomnia is a causal factor in the occurrence of psychotic experiences and other mental health problems. Whether the results generalise beyond a student population requires testing. The treatment of disrupted sleep might require a higher priority in mental health provision. Funding: Wellcome Trust.

The lancet. Psychiatry · randomised controlled trial · 460 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 →

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 →

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 →

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 →

Safety, tolerability, and immunogenicity of a 21-valent pneumococcal conjugate vaccine, V116, in healthy adults: phase 1/2, randomised, double-blind, active comparator-controlled, multicentre, US-based trial.

Background: A pneumococcal conjugate vaccine (PCV) specifically focused on serotypes associated with adult residual disease burden is urgently needed. We aimed to assess V116, an investigational 21-valent PCV, that contains pneumococcal polysaccharides (PnPs), which account for 74-94% of invasive pneumococcal disease in adults aged 65 years or older. Methods: We did a phase 1/2, randomised, double-blind, active comparator-controlled, multicentre, non-inferiority and superiority trial. The phase 1 study was done at two clinical sites in the USA, and the phase 2 study was done in 18 clinical sites in the USA. Eligible participants were healthy adults with or without chronic medical conditions assessed as stable, aged 18-49 years in the phase 1 trial and aged 50 years or older in the phase 2 trial. Participants were excluded if they had a history of invasive pneumococcal disease or other culture-positive pneumococcal disease within the past 3 years, known hypersensitivity to a vaccine component, known or suspected impairment of immunological function, were pregnant or were breastfeeding, or had previously received any pneumococcal vaccine. Participants had to abstain from sexual activity or use protocol approved contraception. All participants were centrally randomly assigned to a vaccine group using an interactive response technology system. Participants and investigators were masked to group assignment. In phase 1, participants were randomly assigned (1:1:1) to receive a single dose of V116-1 (2 μg per pneumococcal polysaccharide [PnP] per 0·5 mL) or V116-2 (4 μg per PnP per 1·0 mL) or the 23-valent unconjugated PnP vaccine, PPSV23 (25 μg per PnP per 0·5 mL). In phase 2, participants were randomly assigned (1:1) to receive one dose of V116 (4 μg per PnP per 1·0 mL) or PPSV23 (25 μg per PnP per 0·5 mL), stratified by age. Safety analyses included all randomly assigned participants who received study vaccine; immunogenicity analyses were per protocol. For both phases, the primary safety outcome was the proportion of participants with solicited injection-site adverse events and solicited systemic adverse events up to day 5 after vaccination and the proportion of participants with vaccine-related serious adverse events to 6 months after vaccination. In phase 2, primary immunogenicity outcomes were to test non-inferiority of V116 compared with PPSV23 as measured by serotype-specific opsonophagocytic antibody geometric mean titres (OPA-GMT) ratios for the serotypes common to the two vaccines at 30 days after vaccination (using a 0·33 margin) and to test superiority of V116 compared with PPSV23 as measured by serotype-specific OPA-GMT ratios for the serotypes unique to V116 at 30 days after vaccination (using a 1·0 margin). This trial is registered with Clinicaltrials.gov, NCT04168190. Findings: Between Dec 6 and 26, 2019, 92 volunteers were screened and 90 (98%) enrolled for phase 1 (59 [66%] women; 31 [34%] men); 30 participants were assigned to each group and received study vaccine. 30 (100%) participants in the V116-1 group, 29 (97%) in the V116-2 group, and 30 (100%) participants in the PPSV23 group were included in the per-protocol immunogenicity evaluation. From Sept 23, 2020, to Jan 12, 2021, 527 volunteers were screened, and 510 (97%) participants were enrolled in the phase 2 trial. 508 participants (>99%; 254 [100%] of 254 participants randomly assigned to the V116 group and 254 [99%] of 256 randomly assigned to PPSV23 group) received study vaccine (281 [55%] women; 227 [45%] men). 252 (99%) of 254 of participants in the V116 group and 254 (99%) of 256 participants in the PPSV23 group were included in the primary immunogenicity analyses. There were no vaccine-related serious adverse events or vaccine-related deaths in either study phase. In both phases, the most common solicited injection site adverse event was injection site pain (phase 1 22 [73%] participants in V116-1 group, 23 [77%] participants in V116-2 group, and 17 [57%] participants in the PPSV23 group; phase 2 118 [46%] of 254 participants in the V116 group and 96 [38%] of 254 in the PPSV23 group]. The most common solicited systemic adverse events in phase 1 was fatigue (eight [27%] participants in the V116-1 group, eight [27%] participants in the V116-2 group, and five [17%] participants in PPSV23 group) and myalgia (eight [27%] participants in the V116-1 group, nine (30%) participants in the V116-2 group, and four (13%) participants in the PPSV23 group]. In phase 2, the most frequently reported solicited systemic adverse event was fatigue (49 [19%] participants in V116 group, and 31 [12%] participants in PPSV23 group). In both phases, most of the solicited adverse events in all vaccine groups were mild and of short duration (≤3 days). V116 met non-inferiority criteria compared with PPSV23 for the 12 shared serotypes and met superiority criteria compared to PPSV23 for the nine unique serotypes. Interpretation: V116 was well tolerated with a safety profile generally similar to PPSV23; consistent with licensed pneumococcal conjugate vaccines. Functional OPA antibodies were induced to all V116 vaccine serotypes. The vaccine was non-inferior to PPSV23 for the 12 serotypes common to both vaccines and superior to PPSV23 for the nine unique serotypes in V116. Our findings support the development of V116 for prevention of pneumococcal disease in adults. Funding: Merck Sharp & Dohme, subsidiary of Merck & Co, Rahway, NJ, USA.

The Lancet. Infectious diseases · randomised controlled trial · 73 citationsread the source →

Effect of the SafeCare© intervention on parenting outcomes among parents in child welfare systems: A cluster randomized trial.

Child maltreatment has long-lasting negative impacts, and interventions are needed to improve caregiver's parenting skills to prevent maltreatment. This paper reports on a randomized trial comparing the SafeCare© model to services as usual (SAU) for child-welfare referred caregivers. SafeCare is an 18-session behavioral parenting program that teaches skills in positive parent-child interactions, home safety, and child health. SAU is generally unstructured and includes support, crisis management, referrals for need, and parenting education. Teams of providers at nine sites were randomized to implement SafeCare (19 teams; 119 providers) or continue SAU (17 teams; 118 providers). Two-hundred eighty eight caregivers (193 SafeCare; 95 SAU) with children aged 0-5 who were receiving services agreed to complete a baseline and 6-month assessment. Assessments measured positive parenting behaviors, parenting stress, protective factors, and neglectful behaviors using validated scales. Participants were primarily white (74.6%), female (87.0%), and low-income (68.6%), and had a mean age of 29. Latent change score models (LCSM) using a sandwich estimator consistent with the trial design were used to examine changes in 13 outcomes. Results indicated that SafeCare had small to medium effects for improving several parenting outcomes including supporting positive child behaviors (d = 0.46), proactive parenting (d = 0.25), and two aspects of parenting stress (d = 0.28 and .30). No differential change between groups was found for other indicators, including all indicators of neglect. Parenting programs such as SafeCare offer a promising mode of intervention for child welfare systems. Scale-up of parenting programs can improve parenting, improve child outcomes, and potentially reduce maltreatment. CLINICALTRIAL.GOV REGISTRATION NUMBER: NCT02549287.

Preventive medicine · randomised controlled trial · 30 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 →

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 →

A family planning clinic-based intervention to address reproductive coercion: a cluster randomized controlled trial.

Objective: We assessed the effectiveness of a provider-delivered intervention targeting reproductive coercion, an important factor in unintended pregnancy. Study design: We randomized 25 family planning clinics (17 clusters) to deliver an education/counseling intervention or usual care. Reproductive coercion and partner violence victimization at 1 year follow-up were primary outcomes. Unintended pregnancy, recognition of sexual and reproductive coercion, self-efficacy to use and use of harm reduction behaviors to reduce victimization and contraception nonuse, and knowledge and use of partner violence resources were secondary outcomes. Analyses included all available data using an intention-to-treat approach. Results: Among 4009 females ages 16 to 29 years seeking care, 3687 completed a baseline survey prior to clinic visit from October 2011 to November 2012; 3017 provided data at 12-20weeks post-baseline (T2) and 2926 at 12months post-baseline (T3) (79% retention). Intervention effects were not significant for reproductive coercion [adjusted risk ratio (ARR) 1.50 (95% confidence interval 0.95-2.35)] or partner violence [ARR 1.07 (0.84-1.38)]. Intervention participants reported improved knowledge of partner violence resources [ARR 4.25 (3.29-5.50)] and self-efficacy to enact harm reduction behaviors [adjusted mean difference 0.06 (0.02-0.10)]. In time point-specific models which included moderating effects of exposure to reproductive coercion at baseline, a higher reproductive coercion score at baseline was associated with a decrease in reproductive coercion 1 year later (T3). Use and sharing of the domestic violence hotline number also increased. Conclusion: This brief clinic intervention did not reduce partner violence victimization. The intervention enhanced two outcomes that may increase safety for women, specifically awareness of partner violence resources and self-efficacy to enact harm reduction behaviors. It also appeared to reduce reproductive coercion among women experiencing multiple forms of such abuse.

Contraception · randomised controlled trial · 93 citationsread the source →

Cognitive behavioural therapy for adults with dissociative seizures (CODES): a pragmatic, multicentre, randomised controlled trial.

Background: Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency. Methods: In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544. Findings: Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0-20] in the CBT plus standardised medical care group vs 7 seizures [1-35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56-1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference -0·53 [95% CI -0·97 to -0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference -4·12 [95% CI -6·35 to -1·89]; p<0·001), less overall psychological distress than the standardised medical care group on the Clinical Outcomes in Routine Evaluation-10 scale (estimated mean difference -1·65 [95% CI -2·96 to -0·35]; p=0·013), and fewer somatic symptoms on the modified Patient Health Questionnaire-15 scale (estimated mean difference -1·67 [95% CI -2·90 to -0·44]; p=0·008). Clinical improvement at 12 months was greater in the CBT plus standardised medical care group than the standardised medical care alone group as reported by patients (estimated mean difference 0·66 [95% CI 0·26 to 1·04]; p=0·001) and by clinicians (estimated mean difference 0·47 [95% CI 0·21 to 0·73]; p<0·001), and the CBT plus standardised medical care group had greater satisfaction with treatment than did the standardised medical care group (estimated mean difference 0·90 [95% CI 0·48 to 1·31]; p<0·001). No significant differences in patient-reported seizure severity (estimated mean difference -0·11 [95% CI -0·50 to 0·29]; p=0·593) or seizure freedom in the last 3 months of the study (estimated odds ratio [OR] 1·77 [95% CI 0·93 to 3·37]; p=0·083) were identified between the groups. Furthermore, no significant differences were identified in the proportion of patients who had a more than 50% reduction in dissociative seizure frequency compared with baseline (OR 1·27 [95% CI 0·80 to 2·02]; p=0·313). Additionally, the 12-item Short Form survey-version 2 scores (estimated mean difference for the Physical Component Summary score 1·78 [95% CI -0·37 to 3·92]; p=0·105; estimated mean difference for the Mental Component Summary score 2·22 [95% CI -0·30 to 4·75]; p=0·084), the Generalised Anxiety Disorder-7 scale score (estimated mean difference -1·09 [95% CI -2·27 to 0·09]; p=0·069), and the Patient Health Questionnaire-9 scale depression score (estimated mean difference -1·10 [95% CI -2·41 to 0·21]; p=0·099) did not differ significantly between groups. Changes in dissociative seizures (rated by others) could not be assessed due to insufficient data. During the 12-month period, the number of adverse events was similar between the groups: 57 (31%) of 186 participants in the CBT plus standardised medical care group reported 97 adverse events and 53 (29%) of 182 participants in the standardised medical care group reported 79 adverse events. Interpretation: CBT plus standardised medical care had no statistically significant advantage compared with standardised medical care alone for the reduction of monthly seizures. However, improvements were observed in a number of clinically relevant secondary outcomes following CBT plus standardised medical care when compared with standardised medical care alone. Thus, adults with dissociative seizures might benefit from the addition of dissociative seizure-specific CBT to specialist care from neurologists and psychiatrists. Future work is needed to identify patients who would benefit most from a dissociative seizure-specific CBT approach. Funding: National Institute for Health Research, Health Technology Assessment programme.

The lancet. Psychiatry · randomised controlled trial · 192 citationsread the source →

Planning for tomorrow whilst living for today: the views of people with dementia and their families on advance care planning.

Background: Advance care planning (ACP) is increasingly prominent in many countries; however, the evidence base for its acceptability and effectiveness is limited especially in conditions where cognition is impaired, as in dementia. Method: This qualitative study used semi-structured interviews with people with mild to moderate dementia (n = 17) and family carers (n = 29) to investigate their views about planning for their future generally and ACP specifically. Results: People with dementia and their families make a number of plans for the future. Most people undertook practical, personal, financial, and legal planning. However participants did not make formal advance care plans with the exception of appointing someone to manage their financial affairs. Five barriers to undertaking ACP were identified: lack of knowledge and awareness, difficulty in finding the right time, a preference for informal plans over written documentation, constraints on choice around future care, and lack of support to make choices about future healthcare. Conclusions: Health and social care professionals can build on people's preferences for informal planning by exploring the assumptions underlying them, providing information about the possible illness trajectory and discussing the options of care available. Health and social care professionals also have a role to play in highlighting the aspects of ACP which seem to be most relevant to the wishes and aspirations of people with dementia.

International psychogeriatrics · 92 citationsread the source →

Decision aids for people facing health treatment or screening decisions.

Background: Decision aids are intended to help people participate in decisions that involve weighing the benefits and harms of treatment options often with scientific uncertainty. Objectives: To assess the effects of decision aids for people facing treatment or screening decisions. Search methods: For this update, we searched from 2009 to June 2012 in MEDLINE; CENTRAL; EMBASE; PsycINFO; and grey literature. Cumulatively, we have searched each database since its start date including CINAHL (to September 2008). Selection criteria: We included published randomized controlled trials of decision aids, which are interventions designed to support patients' decision making by making explicit the decision, providing information about treatment or screening options and their associated outcomes, compared to usual care and/or alternative interventions. We excluded studies of participants making hypothetical decisions. Data collection and analysis: Two review authors independently screened citations for inclusion, extracted data, and assessed risk of bias. The primary outcomes, based on the International Patient Decision Aid Standards (IPDAS), were:A) 'choice made' attributes;B) 'decision-making process' attributes. Secondary outcomes were behavioral, health, and health-system effects. We pooled results using mean differences (MD) and relative risks (RR), applying a random-effects model. Main results: This update includes 33 new studies for a total of 115 studies involving 34,444 participants. For risk of bias, selective outcome reporting and blinding of participants and personnel were mostly rated as unclear due to inadequate reporting. Based on 7 items, 8 of 115 studies had high risk of bias for 1 or 2 items each. Of 115 included studies, 88 (76.5%) used at least one of the IPDAS effectiveness criteria: A) 'choice made' attributes criteria: knowledge scores (76 studies); accurate risk perceptions (25 studies); and informed value-based choice (20 studies); and B) 'decision-making process' attributes criteria: feeling informed (34 studies) and feeling clear about values (29 studies).A) Criteria involving 'choice made' attributes:Compared to usual care, decision aids increased knowledge (MD 13.34 out of 100; 95% confidence interval (CI) 11.17 to 15.51; n = 42). When more detailed decision aids were compared to simple decision aids, the relative improvement in knowledge was significant (MD 5.52 out of 100; 95% CI 3.90 to 7.15; n = 19). Exposure to a decision aid with expressed probabilities resulted in a higher proportion of people with accurate risk perceptions (RR 1.82; 95% CI 1.52 to 2.16; n = 19). Exposure to a decision aid with explicit values clarification resulted in a higher proportion of patients choosing an option congruent with their values (RR 1.51; 95% CI 1.17 to 1.96; n = 13).B) Criteria involving 'decision-making process' attributes:Decision aids compared to usual care interventions resulted in:a) lower decisional conflict related to feeling uninformed (MD -7.26 of 100; 95% CI -9.73 to -4.78; n = 22) and feeling unclear about personal values (MD -6.09; 95% CI -8.50 to -3.67; n = 18);b) reduced proportions of people who were passive in decision making (RR 0.66; 95% CI 0.53 to 0.81; n = 14); andc) reduced proportions of people who remained undecided post-intervention (RR 0.59; 95% CI 0.47 to 0.72; n = 18).Decision aids appeared to have a positive effect on patient-practitioner communication in all nine studies that measured this outcome. For satisfaction with the decision (n = 20), decision-making process (n = 17), and/or preparation for decision making (n = 3), those exposed to a decision aid were either more satisfied, or there was no difference between the decision aid versus comparison interventions. No studies evaluated decision-making process attributes for helping patients to recognize that a decision needs to be made, or understanding that values affect the choice.C) Secondary outcomes Exposure to decision aids compared to usual care reduced the number of people of choosing major elective invasive surgery in favour of more conservative options (RR 0.79; 95% CI 0.68 to 0.93; n = 15). Exposure to decision aids compared to usual care reduced the number of people choosing to have prostate-specific antigen screening (RR 0.87; 95% CI 0.77 to 0.98; n = 9). When detailed compared to simple decision aids were used, fewer people chose menopausal hormone therapy (RR 0.73; 95% CI 0.55 to 0.98; n = 3). For other decisions, the effect on choices was variable. The effect of decision aids on length of consultation varied from 8 minutes shorter to 23 minutes longer (median 2.55 minutes longer) with 2 studies indicating statistically-significantly longer, 1 study shorter, and 6 studies reporting no difference in consultation length. Groups of patients receiving decision aids do not appear to differ from comparison groups in terms of anxiety (n = 30), general health outcomes (n = 11), and condition-specific health outcomes (n = 11). The effects of decision aids on other outcomes (adherence to the decision, costs/resource use) were inconclusive. Authors' conclusions: There is high-quality evidence that decision aids compared to usual care improve people's knowledge regarding options, and reduce their decisional conflict related to feeling uninformed and unclear about their personal values. There is moderate-quality evidence that decision aids compared to usual care stimulate people to take a more active role in decision making, and improve accurate risk perceptions when probabilities are included in decision aids, compared to not being included. There is low-quality evidence that decision aids improve congruence between the chosen option and the patient's values. New for this updated review is further evidence indicating more informed, values-based choices, and improved patient-practitioner communication. There is a variable effect of decision aids on length of consultation. Consistent with findings from the previous review, decision aids have a variable effect on choices. They reduce the number of people choosing discretionary surgery and have no apparent adverse effects on health outcomes or satisfaction. The effects on adherence with the chosen option, cost-effectiveness, use with lower literacy populations, and level of detail needed in decision aids need further evaluation. Little is known about the degree of detail that decision aids need in order to have a positive effect on attributes of the choice made, or the decision-making process.

The Cochrane database of systematic reviews · meta-analysis · 891 citationsread the source →

The Social Epidemiology of Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome

Social epidemiology is defined as the study of the distribution of health outcomes and their social determinants (1). It builds on the classic epidemiologic triangle of host, agent, and environment to focus explicitly on the role of social determinants in infectious disease transmission and progression. These determinants are the “features of and pathways by which societal conditions affect health” (2, p. 697). Early studies of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) focused on individual characteristics and behaviors in determining HIV risk, an approach that Fee and Krieger (3) refer to as “biomedical individualism.” Biomedical individualism is the basis of risk factor epidemiology; by contrast, the social epidemiology perspective emphasizes social conditions as fundamental causes of disease (4) (table 1). Social epidemiologists examine how persons become exposed to risk or protective factors and under what social conditions individual risk factors are related to disease. Social factors are thus the focus of analysis and are not simply adjusted for as potentially confounding factors or used as proxies for unavailable individual-level data. Social factors are indeed critical to understanding nonuniform infectious disease patterns that emerge as a result of the dependent nature of disease transmission or the idea that an outcome in one person is dependent upon outcomes and exposures in others (5, 6). Contact patterns that enhance HIV/AIDS vulnerability may be conceptualized at multiple levels. Figure 1 distinguishes determinants of HIV/AIDS at three levels: individual, social, and structural. Individual factors include biologic, demographic, and behavioral risk factors that may influence the risk of HIV acquisition and disease progression. Social-level factors include critical pathways by which community and network structures link persons to society. These structures are central to understanding the diffusion and differential distribution of HIV/AIDS in population subgroups. Structural-level factors include social and economic factors, as well as laws and policies. These factors, in turn, affect HIV transmission dynamics and the differential distribution of HIV/AIDS. Infectious disease epidemiology provides models of the mechanisms through which social determinants affect HIV transmission (7). For example, the basic reproductive number of an infectious disease, R0 (8), describes secondary infections that arise from a primary infection. In the equation R0 = βCD, β is the probability of infection per contact, C is the number of contacts, and D is the duration of infectivity. The goal of intervention efforts is to reduce the empirical value of these terms by modifying the social conditions under which individual risk factors lead to disease. Examples of factors that affect the component terms of R0 in HIV epidemiology are presented in table 2. In this review, we present existing evidence linking social and structural determinants to HIV/AIDS. In addition, we discuss the implications of these findings for future social epidemiology research on HIV/AIDS as well as the design of more effective HIV/AIDS interventions. We searched the published literature to identify conceptual and empirical research reports on the social epidemiology of HIV/AIDS. Five databases were searched: PsycINFO (American Psychological Association, Washington, DC), PubMed (MEDLINE; National Institutes of Health, Bethesda, Maryland), Social Science Citation Index (Web of Science; Thomson ISI, Stamford, Connecticut), Sociological Abstracts (CSA, Bethesda, Maryland), and Digital Dissertations (ProQuest; UMI, Ann Arbor, Michigan). Searches were designed to include the factors we specified in our framework as social or structural factors (figure 1). Searches were limited to published articles in the English language for the period 1981–2003. The following keywords were included in each search: AIDS/acquired immunodeficiency syndrome, HIV, and epidemiol*. Additional searches were conducted by using combinations of keywords listed in Appendix table 1 corresponding with our framework. We identified four categories of social-level factors of importance to HIV/AIDS epidemiology: cultural context, social networks, neighborhood effects, and social capital. Each uses different conceptual and methodological approaches to examine the effects of social forces on population HIV/AIDS vulnerability. Anthropologist Edward Tylor defined culture as “that complex whole which includes knowledge, belief, art, law, morals, custom, and any other capabilities and habits acquired by man as a member of society” (9, p. 1). Anthropologic and epidemiologic approaches may be integrated in a variety of ways to identify features of the social environment that affect HIV/AIDS risk. One way to explore how the social environment affects HIV/AIDS epidemiology is through the use of mixed research methods. Mixed-methods study designs integrate qualitative and quantitative research methods either sequentially or concurrently (10). In sequential study designs, qualitative methods may be used to explore a topic under study or to explain quantitative epidemiologic findings. Concurrent study designs are meant to confirm, cross-validate, or corroborate findings within a single study. A common type of concurrent mixed methods study is “triangulation,” and this approach has been used extensively in rapid assessments of illicit drug use and HIV/AIDS (11–13). Mixed methods approaches are particularly well suited to the investigation of the often hidden and stigmatizing behavioral and social factors underlying HIV epidemics. One exemplary study combining qualitative methods with quantitative methods was conducted by Beyrer et al. (14) to examine the role of overland heroin trafficking routes in shaping explosive HIV/AIDS epidemics among injection drug users in Southeast Asia. Piecing together data from a variety of sources, including existing epidemiologic data, key informant interviews, and laboratory data, this study revealed that distinct HIV subtypes emerged and recombined along drug trafficking routes originating in Myanmar, one of the world’s largest heroin producers. Along these trafficking routes, communities of injection drug users formed, facilitating the spread of HIV into local communities in Laos, Thailand, Vietnam, India, and China (refer, for example, to Panda et al. (15)). This illustration highlights the broader understanding of HIV/AIDS epidemiology that can be achieved by examining the interplay between contextual factors and social and behavioral factors. Investigation of social networks in HIV/AIDS began with the mapping of relationships between one of the first identified AIDS cases, an airline steward, and a large number of his male sex partners in the early 1980s (16). Social network analysis generates measures of the quality, density, position, and structure of relationships between persons, including dyads (partnerships), personal networks (“egocentric” networks), and larger communities (“sociometric” networks) (17, 18). Social networks can influence health outcomes in direct and indirect ways, including 1) social influence, 2) social engagement and participation, 3) prevalence of infectious disease and network member mixing, 4) access to material goods and informational resources, and 5) social support (19). Researchers have demonstrated that patterns in the structure of relationships—rather than differences in individual risk behaviors alone—explain observed HIV patterns (20, 21). The theoretical foundation for examining social networks in HIV research is closely tied to advances in sexually transmitted disease (STD) epidemiology. A key concept from STD epidemiology is the notion of the “core group,” a small group of disease transmitters responsible for a large proportion of cases (22). Friedman et al. (23) found that individuals’ locations within sociometric risk networks were associated with HIV risk among a group of injection drug users in New York City. Other concepts from STD epidemiology, such as partner concurrency, bridging, and mixing patterns, are also important in understanding HIV risk (24–29). Specific network characteristics that have been associated with HIV/AIDS include the size of subgroups and their distribution in a network (23), the centrality of HIV-positive persons within networks (30), partner selection patterns (24, 31–33), and concurrent sexual partnerships (28). Inclusion of these variables has been shown to improve transmission estimates in mathematical modeling (34, 35). Social and normative influences have also been associated with individual HIV risks (36, 37). Network-related social and normative influences are predictive of illicit drug use (38) and condom use behavior (37, 39), highlighting the importance of network-based interventions for HIV prevention (18). Kelly et al. (40, 41) developed a popular opinion leader model that has been effective in reducing HIV risk in several populations, including men who have sex with men and women in low-income housing (42). The success of this model has led to its adaption for international use by the National Institute of Mental Health Collaborative HIV/STD Prevention Trial in China, India, Peru, Russia, and Zimbabwe. Neighborhoods represent the intersection of social networks and physical spatial locations, a confluence Wallace (43) has called the “sociogeographic networks” through which infectious diseases spread. Early interest in the role of neighborhood social environment in disease transmission was sparked by a study in Colorado Springs, Colorado, in which researchers found that gonorrhea was highly focused geographically in core residential neighborhoods (44). Both direct and indirect mechanisms may determine how neighborhood-level factors shape population HIV/AIDS patterns. Direct mechanisms are those that increase the likelihood of a person coming into contact with someone who is HIV positive, for example, through residential segregation and the social isolation of marginalized populations. Indirect mechanisms include those that increase population vulnerability to HIV/AIDS, such as exposure to poor socioeconomic conditions, high unemployment, or the proliferation of illicit drug markets. A range of neighborhood-level factors have been examined in relation to infectious disease, including poverty and income (45, 46), residential segregation (47), and neighborhood physical environment (48, 49). Current research in neighborhood and area effects on health emphasizes the importance of moving beyond documentation of associations to analyze the social and epidemiologic mechanisms through which neighborhood effects might operate (50–54). Increasing concentrations of affluence and poverty are contributing to what demographer Douglas Massey has called “a radical change in the geographic basis of human society” (55, p. 395). Powerful social and economic forces in US cities are increasing neighborhood segregation by class and race/ethnicity (56, 57). Resulting social disorganization and loss of resources and services in poor neighborhoods are in turn shaping HIV/AIDS patterns at the neighborhood level. In a number of studies in New York City, for example, Wallace (58–63) has examined the complex interplay of public policies such as “planned shrinkage” with HIV epidemic dynamics in the Bronx, documenting the “synergy of plagues” that has accompanied rapid social change and the destruction of essential protective networks in poor communities. Using AIDS surveillance data, ecologic studies conducted in various US cities have also consistently found significant associations between income and poverty measures and neighborhood-level AIDS incidence and prevalence rates, and these findings have been consistent across census block groups (46), census tracts (64), and zip codes (65, 66). Length of survival an AIDS has also been with neighborhood measures of income and the of highly a of health at the population may also a role in shaping HIV/AIDS patterns, associations between HIV/AIDS and income at the neighborhood have not been well segregation by race/ethnicity is neighborhood-level that may an important role in HIV/AIDS may affect infectious disease patterns through the and isolation of persons in one increasing the probability of transmission within that For example, found that measures of residential isolation were protective for at risk of disease. Indirect effects of segregation are associated with of neighborhood and with for those in poor neighborhoods segregation may to understanding disease we of studies examining neighborhood segregation in relation to HIV/AIDS that have been The physical environment of neighborhoods has also been examined in relation to infectious disease. et al. examined gonorrhea and neighborhood physical environment in New by using an of physical to explore and to this the of physical such as and a in social in a of community this concept to public et al. found a significant between neighborhood physical and gonorrhea rates, a by a ecologic study of US physical environment may HIV risk by illicit drug use such as injection behaviors and of the mechanisms through which the observed associations may be and associations between the physical environment and HIV/AIDS is research is to support the design of neighborhood-level HIV/AIDS interventions. has differences are not result from social and economic by policies. are and to p. The of evidence ecologic associations between neighborhood-level factors and infectious disease that to be to identify of and defined social as of social structures that that is the of that in its not be p. Social may affect health through 1) the of 2) access to services and 3) of in a and 4) participation, to policies that are more to published studies have explicitly examined social in the of HIV/AIDS. 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Epidemiologic Reviews · meta-analysis · 394 citationsread the source →

Developing and Evaluating JIApp: Acceptability and Usability of a Smartphone App System to Improve Self-Management in Young People With Juvenile Idiopathic Arthritis.

Background: Flare-ups in juvenile idiopathic arthritis (JIA) are characterized by joint pain and swelling and often accompanied with fatigue, negative emotions, and reduced participation in activities. To minimize the impact of JIA on the physical and psychosocial development and well-being of young people (YP), it is essential to regularly monitor disease activity and side effects, as well as to support self-management such as adherence to treatment plans and engagement in general health-promoting behaviors. Smartphone technology has the potential to engage YP with their health care through convenient self-monitoring and easy access to information. In addition, having a more accurate summary of self-reported fluctuations in symptoms, behaviors, and psychosocial problems can help both YP and health care professionals (HCPs) better understand the patient's condition, identify barriers to self-management, and assess treatment effectiveness and additional health care needs. No comprehensive smartphone app has yet been developed in collaboration with YP with JIA, their parents, and HCPs involved in their care. Objectives: The objective of this study was to design, develop, and evaluate the acceptability and usability of JIApp, a self-management smartphone app system for YP with JIA and HCPs. Methods: We used a qualitative, user-centered design approach involving YP, parents, and HCPs from the rheumatology team. The study was conducted in three phases: (1) phase I focused on developing consensus on the features, content, and design of the app; (2) phase II was used for further refining and evaluating the app prototype; and (3) phase III focused on usability testing of the app. The interview transcripts were analyzed using qualitative content analysis. Results: A total of 29 YP (aged 10-23, median age 17) with JIA, 7 parents, and 21 HCPs were interviewed. Major themes identified as the ones that helped inform app development in phase I were: (1) remote monitoring of symptoms, well-being, and activities; (2) treatment adherence; and (3) education and support. During phase II, three more themes emerged that informed further refinement of the app prototype. These included (4) adapting a reward system to motivate end users for using the app; (5) design of the app interface; and (6) clinical practice integration. The usability testing during phase III demonstrated high rates of overall satisfaction and further affirmed the content validity of the app. Conclusions: We present the development and evaluation of a smartphone app to encourage self-management and engagement with health care for YP with JIA. The app was found to have high levels of acceptability and usability among YP and HCPs and has the potential to improve health care and outcomes for this age group. Future feasibility testing in a prospective study will firmly establish the reliability, efficacy, and cost-effectiveness of such an app intervention for patients with arthritis.

JMIR mHealth and uHealth · 59 citationsread the source →