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Metabolic and bariatric surgery versus intensive non-surgical treatment for adolescents with severe obesity (AMOS2): a multicentre, randomised, controlled trial in Sweden.

Background: Severe obesity in adolescents has a profound impact on current and future health. Metabolic and bariatric surgery (MBS) is increasingly used in adolescents internationally. However, to our knowledge, there are no randomised trials examining the currently most used surgical techniques. Our aim was to evaluate changes in BMI and secondary health and safety outcomes after MBS. Methods: The Adolescent Morbid Obesity Surgery 2 (AMOS2) study is a randomised, open-label, multicentre trial done at three university hospitals in Sweden (located in Stockholm, Gothenburg, and Malmö). Adolescents aged 13-16 years with a BMI of at least 35 kg/m2, who had attended treatment for obesity for at least 1 year, passed assessments from a paediatric psychologist and a paediatrician, and had a Tanner pubertal stage of at least 3, were randomly assigned (1:1) to MBS or intensive non-surgical treatment. Exclusion criteria included monogenic or syndromic obesity, major psychiatric illness, and regular self-induced vomiting. Computerised randomisation was stratified for sex and recruitment site. Allocation was concealed for both staff and participants until the end of the inclusion day, and then all participants were unmasked to treatment intervention. One group underwent MBS (primarily gastric bypass), while the other group received intensive non-surgical treatment starting with 8 weeks of low-calorie diet. The primary outcome was 2-year change in BMI, analysed as intention-to-treat. The trial is registered at ClinicalTrials.gov, NCT02378259. Findings: 500 people were assessed for eligibility between Aug 27, 2014, and June 7, 2017. 450 participants were excluded (397 did not meet inclusion criteria, 39 declined to participate, and 14 were excluded for various other reasons). Of the 50 remaining participants, 25 (19 females and six males) were randomly assigned to receive MBS and 25 (18 females and seven males) were assigned to intensive non-surgical treatment. Three participants (6%; one in the MBS group and two in the intensive non-surgical treatment group) did not participate in the 2-year follow-up, and in total 47 (94%) participants were assessed for the primary endpoint. Mean age of participants was 15·8 years (SD 0·9) and mean BMI at baseline was 42·6 kg/m2 (SD 5·2). After 2 years, BMI change was -12·6 kg/m2 (-35·9 kg; n=24) among adolescents undergoing MBS (Roux-en-Y gastric bypass [n=23], sleeve gastrectomy [n=2]) and -0·2 kg/m2 (0·4 kg; [n=23]) among participants in the intensive non-surgical treatment group (mean difference -12·4 kg/m2 [95% CI -15·5 to -9·3]; p<0·0001). Five (20%) patients in the intensive non-surgical group crossed over to MBS during the second year. Adverse events (n=4) after MBS were mild but included one cholecystectomy. Regarding safety outcomes, surgical patients had a reduction in bone mineral density, while controls were unchanged after 2 years (z-score change mean difference -0·9 [95% CI -1·2 to -0·6]). There were no significant differences between the groups in vitamin and mineral levels, gastrointestinal symptoms (except less reflux in the surgical group), or in mental health at the 2-year follow-up. Interpretation: MBS is an effective and well tolerated treatment for adolescents with severe obesity resulting in substantial weight loss and improvements in several aspects of metabolic health and physical quality of life over 2 years, and should be considered in adolescents with severe obesity. Funding: Sweden's Innovation Agency, Swedish Research Council Health.

The Lancet. Child & adolescent health · randomised controlled trial · 45 citationsread the source →

Identifying Brief Message Content for Interventions Delivered via Mobile Devices to Improve Medication Adherence in People With Type 2 Diabetes Mellitus: A Rapid Systematic Review.

Background: Current interventions to support medication adherence in people with type 2 diabetes are generally resource-intensive and ineffective. Brief messages, such as those delivered via short message service (SMS) systems, are increasingly used in digital health interventions to support adherence because they can be delivered on a wide scale and at low cost. The content of SMS text messages is a crucial intervention feature for promoting behavior change, but it is often unclear what the rationale is for chosen wording or any underlying mechanisms targeted for behavioral change. There is little guidance for developing and optimizing brief message content for use in mobile device-delivered interventions. Objective: This review aimed to (1) identify theoretical constructs (ie, the targets that interventions aim to change) and behavioral strategies (ie, features of intervention content) found to be associated with medication adherence in patients with type 2 diabetes and (2) map these onto a standard taxonomy for behavior change techniques (BCTs, that is, active ingredients of interventions used to promote behavioral change, to produce an evidence-based set of approaches that have shown promise of improving adherence in previous studies and which could be further tested in digital health interventions. Methods: A rapid systematic review of existing relevant systematic reviews was conducted. MEDLINE and PsycINFO databases were searched from inception to April 10, 2017. Inclusion criteria were (1) systematic reviews of quantitative data if the studies reviewed identified predictors of or correlates with medication adherence or evaluated medication adherence-enhancing interventions and included adult participants taking medication to manage a chronic physical health condition, and (2) systematic reviews of qualitative studies of experiences of medication adherence for adult participants with type 2 diabetes. Data were extracted on review characteristics and BCTs, theoretical constructs, or behavioral strategies associated with improved adherence. Constructs and strategies were mapped onto the BCT version 1 taxonomy. Results: A total of 1701 references were identified; 25 systematic reviews (19 quantitative reviews, 3 qualitative reviews, and 3 mixed-method reviews) were included. Moreover, 20 theoretical constructs (eg, self-efficacy) and 19 behavioral strategies (eg, habit analysis) were identified in the included reviews. In total, 46 BCTs were identified as being related to medication adherence in type 2 diabetes (eg, habit formation, prompts or cues, and information about health consequences). Conclusions: We identified 46 promising BCTs related to medication adherence in type 2 diabetes on which the content of brief messages delivered through mobile devices to improve adherence could be based. By using explicit systematic review methods and linking our findings to a standardized taxonomy of BCTs, we have described a novel approach for the development of digital message content. Future brief message interventions that aim to support medication adherence could incorporate the identified BCTs.

Journal of medical Internet research · systematic review · 31 citationsread the source →

Populations and Interventions for Palliative and End-of-Life Care: A Systematic Review.

Importance: Evidence supports palliative care effectiveness. Given workforce constraints and the costs of new services, payers and providers need help to prioritize their investments. They need to know which patients to target, which personnel to hire, and which services best improve outcomes. Objective: To inform how payers and providers should identify patients with "advanced illness" and the specific interventions they should implement, we reviewed the evidence to identify (1) individuals appropriate for palliative care and (2) elements of health service interventions (personnel involved, use of multidisciplinary teams, and settings of care) effective in achieving better outcomes for patients, caregivers, and the healthcare system. Evidence review: Systematic searches of MEDLINE, EMBASE, PsycINFO, Web of Science, and Cochrane Database of Systematic Reviews databases (1/1/2001-1/8/2015). Results: Randomized controlled trials (124) met inclusion criteria. The majority of studies in cancer (49%, 38 of 77 studies) demonstrated statistically significant patient or caregiver outcomes (e.g., p < 0.05), as did those in congestive heart failure (CHF) (62%, 13 of 21), chronic obstructive pulmonary disease (COPD; 58%, 11 of 19), and dementia (60%, 15 of 25). Most prognostic criteria used clinicians' judgment (73%, 22 of 30). Most interventions included a nurse (70%, 69 of 98), and many were nurse-only (39%, 27 of 69). Social workers were well represented, and home-based approaches were common (56%, 70 of 124). Home interventions with visits were more effective than those without (64%, 28 of 44; vs. 46%, 12 of 26). Interventions improved communication and care planning (70%, 12 of 18), psychosocial health (36%, 12 of 33, for depressive symptoms; 41%, 9 of 22, for anxiety), and patient (40%, 8 of 20) and caregiver experiences (63%, 5 of 8). Many interventions reduced hospital use (65%, 11 of 17), but most other economic outcomes, including costs, were poorly characterized. Palliative care teams did not reliably lower healthcare costs (20%, 2 of 10). Conclusions: Palliative care improves cancer, CHF, COPD, and dementia outcomes. Effective models include nurses, social workers, and home-based components, and a focus on communication, psychosocial support, and the patient or caregiver experience. High-quality research on intervention costs and cost outcomes in palliative care is limited.

Journal of palliative medicine · systematic review · 135 citationsread the source →

Therapeutic mechanisms of psilocybin: Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression.

Background: Psilocybin has shown promise as a treatment for depression but its therapeutic mechanisms are not properly understood. In contrast to the presumed actions of antidepressants, we recently found increased amygdala responsiveness to fearful faces one day after open-label treatment with psilocybin (25 mg) in 19 patients with treatment-resistant depression, which correlated with treatment efficacy. Aims: Aiming to further unravel the therapeutic mechanisms of psilocybin, the present study extends this basic activation analysis. We hypothesised changed amygdala functional connectivity, more precisely decreased amygdala-ventromedial prefrontal cortex functional connectivity, during face processing after treatment with psilocybin. Methods: Psychophysiological interaction analyses were conducted on functional magnetic resonance imaging data from a classic face/emotion perception task, with the bilateral amygdala and ventromedial prefrontal cortex time-series as physiological regressors. Average parameter estimates (beta weights) of significant clusters were correlated with clinical outcomes at one week. Results: Results showed decreased ventromedial prefrontal cortex-right amygdala functional connectivity during face processing post- (versus pre-) treatment; this decrease was associated with levels of rumination at one week. This effect was driven by connectivity changes in response to fearful and neutral (but not happy) faces. Independent whole-brain analyses also revealed a post-treatment increase in functional connectivity between the amygdala and ventromedial prefrontal cortex to occipital-parietal cortices during face processing. Conclusion: These results are consistent with the idea that psilocybin therapy revives emotional responsiveness on a neural and psychological level, which may be a key treatment mechanism for psychedelic therapy. Future larger placebo-controlled studies are needed to examine the replicability of the current findings.

Journal of psychopharmacology (Oxford, England) · clinical trial · 145 citationsread the source →

Duloxetine 60 mg once-daily in the treatment of painful physical symptoms in patients with major depressive disorder.

Background: While emotional symptoms such as depressed mood and loss of interest have traditionally been considered to constitute the core symptoms of major depressive disorder (MDD), the prevalence and importance of painful physical symptoms such as back pain, abdominal pain, and musculoskeletal pain is becoming increasingly appreciated. Antidepressants possessing dual serotonin/norepinephrine (5-HT/NE) reuptake inhibition may demonstrate greater efficacy in the alleviation of pain. The efficacy of duloxetine, a balanced and potent dual reuptake inhibitor of 5-HT and NE, was evaluated within a cohort of depressed patients with associated painful physical symptoms. Methods: In this multicenter, double-blind, placebo-controlled study, patients meeting DSM-IV criteria for MDD were randomized to receive placebo (N=141) or duloxetine 60 mg QD (N=141). Patients were required to have a 17-item Hamilton Rating Scale for Depression (HAMD17) total score 15, a Clinical Global Impression of Severity (CGI-S) score 4, and a Brief Pain Inventory (BPI) Average Pain score 2 at baseline. The primary efficacy measure was the BPI Average Pain score, while secondary measures included other BPI items, the HAMD17 total score, CGI-S, the Patient Global Impression of Improvement (PGI-I) scale, Visual Analog Scales (VAS) for pain, and the Symptom Questionnaire, Somatic Subscale (SQSS). Safety was evaluated by recording treatment-emergent adverse events (spontaneously reported), vital signs, and laboratory analytes. Results: Mean changes in BPI Average Pain for duloxetine- and placebo-treated patients differed significantly at most visits, but only approached significance at endpoint p=0.066. For the main effect of treatment (pooling all visits), significant advantages for duloxetine-treated patients were found in 10 of 11 assessed BPI pain severity and pain interference items, in addition to VAS overall pain and back pain. Mean changes in pain measures for duloxetine-treated patients corresponded to improvements of 25-50%, compared with 19-39% for placebo. Mean changes at endpoint in depression rating scales (HAMD17, CGI-S, PGI-I) did not differ significantly between duloxetine and placebo treatment groups due to unusually high placebo response. The magnitude of placebo treatment effects (as measured by HAMD17 total score and Maier subscale) was significantly smaller in patients with 1 previous depressive episode, compared to those patients with no previous episodes. In patients with 1 previous depressive episode the advantage of duloxetine over placebo was similar to previous studies. Rates of discontinuation due to adverse events were 14.2% vs. 2.1% for duloxetine and placebo, respectively p<0.001. Treatment-emergent adverse events reported at a significantly higher rate by duloxetine-treated patients included nausea, dry mouth, fatigue, and decreased appetite. Conclusions: In this study, duloxetine (60 mg QD) was shown to be an effective treatment for the painful physical symptoms which are frequently associated with depression. Improvements in pain severity occurred independently of changes in depressive symptom severity.

Journal of psychiatric research · randomised controlled trial · 120 citationsread the source →

Feasibility and Preliminary Efficacy of the MADE4Life Program: A Pilot Randomized Controlled Trial.

Background: The aim was to assess the feasibility and preliminary efficacy of a community-based physical activity (PA) intervention targeting mothers and daughters. Methods: A randomized controlled trial of 48 primary school-aged girls and their 40 mothers were randomized to (i) Mothers And Daughters Exercising for Life (MADE4Life) (n = 21 mothers, n = 25 daughters) or (ii) wait-list control (n = 19 mothers, n = 23 daughters). The 8-week program involved 8 sessions; 25-minute separate mothers and daughters education sessions and 60-minutes PA together. Assessments were at baseline, postintervention and 3-month postintervention. Primary outcome measure was daughters' moderate-to- vigorous physical activity (MVPA) (accelerometer). Secondary outcomes included accelerometer-assessed light/moderate/vigorous PA, BMI, waist circumference, body composition, blood pressure, resting heart rate, sedentary behaviors and mothers' self-reported PA, parenting measures, and cognitions. Intention-to-treat analysis used linear mixed models. Results: Recruitment and retention goals were exceeded. Attendance rates, program acceptability and satisfaction were high. There was no significant group-by-time effect for daughters' %MVPA (-0.08; 95%CI -1.49, 1.33, d = -0.03) or other secondary outcomes for girls (postintervention range d = 0.01 to -0.46). Significant intervention effects were found for mothers' %VPA (P = .04, d = 0.25) and role modeling (P = .02, d = 0.66). Conclusion: MADE4Life was both feasible and acceptable. Although very small effect sizes were found for the daughters, significant changes were seen for mothers (d = 0.25 to 0.66). Future fully powered trials targeting PA in mothers and daughters is warranted.

Journal of physical activity & health · randomised controlled trial · 26 citationsread the source →

Effect of marital status on the outcome of patients undergoing elective or urgent coronary revascularization.

Background: Marriage confers various health advantages in the general population. However, the added value of marriage among patients who undergo percutaneous coronary intervention (PCI) beyond the standard cardiovascular risk factors is not clear. This study aimed to assess the effects of marital status on outcomes of patients undergoing elective or urgent PCI. Methods: Clinical observational analysis of consecutive patients undergoing elective or urgent PCI from 1993 to 2011 was performed. Patients were stratified by marital status, comparing married to unmarried patients. Clinical outcome up to 12 months was obtained by telephone contact or office visit. A total of 11,216 patients were included in the present analysis; 55% were married and 45% unmarried. Results: Significant differences in baseline characteristics were noted, including a lower prevalence of hypertension (86% vs 88%), diabetes (34% vs 38%), and smoking (19% vs 25%) among married vs unmarried patients, respectively (P < .001). However, married patients had a higher prevalence of hypercholesterolemia and family history of coronary artery disease. Early and late major adverse cardiac event rates were significantly lower for married vs unmarried patients up to 1 year (13.3% vs 8.2%, P < .001). Married status was independently associated with improved outcome in multivariable analysis (hazard ratio 0.7, 95% CI 0.6-0.9). Conclusions: Married patients who undergo urgent or elective PCI have superior short- and long-term outcomes up to 1 year when compared with unmarried patients. These benefits persist after adjustment for multiple traditional cardiovascular risk factors.

American heart journal · cohort or longitudinal · 25 citationsread the source →

Binge-Eating Disorder in Adults: A Systematic Review and Meta-analysis.

Background: The best treatment options for binge-eating disorder are unclear. Purpose: To summarize evidence about the benefits and harms of psychological and pharmacologic therapies for adults with binge-eating disorder. Data sources: English-language publications in EMBASE, the Cochrane Library, Academic OneFile, CINAHL, and ClinicalTrials.gov through 18 November 2015, and in MEDLINE through 12 May 2016. Study selection: 9 waitlist-controlled psychological trials and 25 placebo-controlled trials that evaluated pharmacologic (n = 19) or combination (n = 6) treatment. All were randomized trials with low or medium risk of bias. Data extraction: 2 reviewers independently extracted trial data, assessed risk of bias, and graded strength of evidence. Data synthesis: Therapist-led cognitive behavioral therapy, lisdexamfetamine, and second-generation antidepressants (SGAs) decreased binge-eating frequency and increased binge-eating abstinence (relative risk, 4.95 [95% CI, 3.06 to 8.00], 2.61 [CI, 2.04 to 3.33], and 1.67 [CI, 1.24 to 2.26], respectively). Lisdexamfetamine (mean difference [MD], -6.50 [CI, -8.82 to -4.18]) and SGAs (MD, -3.84 [CI, -6.55 to -1.13]) reduced binge-eating-related obsessions and compulsions, and SGAs reduced symptoms of depression (MD, -1.97 [CI, -3.67 to -0.28]). Headache, gastrointestinal upset, sleep disturbance, and sympathetic nervous system arousal occurred more frequently with lisdexamfetamine than placebo (relative risk range, 1.63 to 4.28). Other forms of cognitive behavioral therapy and topiramate also increased abstinence and reduced binge-eating frequency and related psychopathology. Topiramate reduced weight and increased sympathetic nervous system arousal, and lisdexamfetamine reduced weight and appetite. Limitations: Most study participants were overweight or obese white women aged 20 to 40 years. Many treatments were examined only in single studies. Outcomes were measured inconsistently across trials and rarely assessed beyond end of treatment. Conclusion: Cognitive behavioral therapy, lisdexamfetamine, SGAs, and topiramate reduced binge eating and related psychopathology, and lisdexamfetamine and topiramate reduced weight in adults with binge-eating disorder. Primary funding source: Agency for Healthcare Research and Quality.

Annals of internal medicine · meta-analysis · 159 citationsread the source →

Psychosocial interventions for psychostimulant misuse.

Background: Psychostimulant misuse is a continuously growing medical and social burden. There is no evidence proving the efficacy of pharmacotherapy. Psychosocial interventions could be a valid approach to help patients in reducing or ceasing drug consumption. Objectives: To assess the effects of psychosocial interventions for psychostimulant misuse in adults. Search methods: We searched the Cochrane Drugs and Alcohol Group Specialised Register (via CRSLive); Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; CINAHL; Web of Science and PsycINFO, from inception to November 2015. We also searched for ongoing and unpublished studies via ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (apps.who.int/trialsearch/).All searches included non-English language literature. We handsearched references of topic-related systematic reviews and the included studies. Selection criteria: We included randomised controlled trials comparing any psychosocial intervention with no intervention, treatment as usual (TAU) or a different intervention in adults with psychostimulant misuse or dependence. Data collection and analysis: We used the standard methodological procedures expected by Cochrane. Main results: We included a total of 52 trials (6923 participants).The psychosocial interventions considered in the studies were: cognitive behavioural therapy (19 studies), contingency management (25 studies), motivational interviewing (5 studies), interpersonal therapy (3 studies), psychodynamic therapy (1 study), 12-step facilitation (4 studies).We judged most of the studies to be at unclear risk of selection bias; blinding of personnel and participants was not possible for the type of intervention, so all the studies were at high risk of performance bias with regard to subjective outcomes; the majority of studies did not specify whether the outcome assessors were blind. We did not consider it likely that the objective outcomes were influenced by lack of blinding. The comparisons made were: any psychosocial intervention versus no intervention (32 studies), any psychosocial intervention versus TAU (6 studies), and one psychosocial intervention versus an alternative psychosocial intervention (13 studies). Five of included studies did not provide any useful data for inclusion in statistical synthesis. We found that, when compared to no intervention, any psychosocial treatment: reduced the dropout rate (risk ratio (RR): 0.83, 95% confidence interval (CI) 0.76 to -0.91, 24 studies, 3393 participants, moderate quality evidence); increased continuous abstinence at the end of treatment (RR: 2.14, 95% CI 1.27 to -3.59, 8 studies, 1241 participants, low quality evidence); did not significantly increase continuous abstinence at the longest follow-up (RR: 2.12, 95% CI 0.77 to -5.86, 4 studies, 324 participants, low quality evidence); significantly increased the longest period of abstinence: (standardised mean difference (SMD): 0.48, 95% CI 0.34 to 0.63, 10 studies, 1354 participants, high quality evidence). However, it should be noted that the in the vast majority of the studies in this comparison the specific psychosocial treatment assessed in the experimental arm was given in add on to treatment as usual or to another specific psychosocial or pharmacological treatment which was received by both groups. So, many of the control groups in this comparison were not really untreated. Receiving some amount of treatment is not the same as not receiving any intervention, so we could argue that the overall effect of the experimental psychosocial treatment could be smaller if given in add on to TAU or to another intervention than if given to participants not receiving any intervention; this could translate to a smaller magnitude of the effect of the psychosocial intervention when it is given in add on. When compared to TAU, any psychosocial treatment reduced dropout rate (RR: 0.72, 95% CI 0.59 to 0.89, 6 studies, 516 participants, moderate quality evidence), did not increase continuous abstinence at the end of treatment (RR: 1.27, 95% CI 0.94 to 1.72, 2 studies, 224 participants, low quality evidence), did not increase longest period of abstinence (MD -3.15 days, 95% CI -10.35 to 4.05, 1 study, 110 participants, low quality evidence). No studies in this comparison assessed the outcome of continuous abstinence at longest follow-up. There were few studies comparing two or more psychosocial interventions, with small sample sizes and considerable heterogeneity in terms of the types of interventions assessed. None reported significant results. None of the studies reported harms related to psychosocial interventions. Authors' conclusions: The addition of any psychosocial treatment to treatment as usual (usually characterised by group counselling or case management) probably reduces the dropout rate and increases the longest period of abstinence. It may increase the number of people achieving continuous abstinence at the end of treatment, although this might not be maintained at longest follow-up. The most studied and the most promising psychosocial approach to be added to treatment as usual is probably contingency management. However, the other approaches were only analysed in a few small studies, so we cannot rule out the possibility that the results were not significant because of imprecision. When compared to TAU, any psychosocial treatment may improve adherence, but it may not improve abstinence at the end of treatment or the longest period of abstinence. The majority of the studies took place in the United States, and this could limit the generalisability of the findings, because the effects of psychosocial treatments could be strongly influenced by the social context and ethnicity. The results of our review do not answer the most relevant clinical question, demonstrating which is the most effective type of psychosocial approach. Further studies should directly compare contingency management with the other psychosocial approaches.

The Cochrane database of systematic reviews · review · 54 citationsread the source →

A longitudinal, randomized, controlled trial of advance care planning for teens with cancer: anxiety, depression, quality of life, advance directives, spirituality.

Purpose: To test the feasibility, acceptability and safety of a pediatric advance care planning intervention, Family-Centered Advance Care Planning for Teens With Cancer (FACE-TC). Methods: Adolescent (age 14-20 years)/family dyads (N = 30) with a cancer diagnosis participated in a two-armed, randomized, controlled trial. Exclusion criteria included severe depression and impaired mental status. Acceptability was measured by the Satisfaction Questionnaire. General Estimating Equations models assessed the impact of FACE-TC on 3-month post-intervention outcomes as measured by the Pediatric Quality of Life Inventory 4.0 Generic Core Scale, the Pediatric Quality of Life Inventory 4.0 Cancer-Specific Module, the Beck Depression and Anxiety Inventories, the Spiritual Well-Being Scale of the Functional Assessment of Chronic Illness Therapy-IV, and advance directive completion. Results: Acceptability was demonstrated with enrollment of 72% of eligible families, 100% attendance at all three sessions, 93% retention at 3-month post-intervention, and 100% data completion. Intervention families rated FACE-TC worthwhile (100%), whereas adolescents' ratings increased over time (65%-82%). Adolescents' anxiety decreased significantly from baseline to 3 months post-intervention in both groups (β = -5.6; p = .0212). Low depressive symptom scores and high quality of life scores were maintained by adolescents in both groups. Advance directives were located easily in medical records (100% of FACE-TC adolescents vs. no controls). Oncologists received electronic copies. Total Spirituality scores (β = 8.1; p = .0296) were significantly higher among FACE-TC adolescents versus controls. The FACE-TC adolescents endorsed the best time to bring up end-of-life decisions: 19% before being sick, 19% at diagnosis, none when first ill or hospitalized, 25% when dying, and 38% for all of the above. Conclusions: Family-Centered Advance Care Planning for Teens With Cancer demonstrated feasibility and acceptability. Courageous adolescents willingly participated in highly structured, in-depth pediatric advance care planning conversations safely.

The Journal of adolescent health : official publication of the Society for Adolescent Medicine · randomised controlled trial · 111 citationsread the source →

Meta-analysis of the prospective relation between alliance and outcome in child and adolescent psychotherapy.

In the youth treatment literature, the alliance has been defined and measured as a consensual or collaborative bond. In this article, we review varied definitions of the alliance, enumerate its frequent measures, and present clinical examples. We provide a meta-analytic review on the relation between the therapeutic alliance and treatment outcome in child and adolescent psychotherapy. In particular, this review only includes prospective studies of youth therapy that used an explicit measure of alliance. The meta-analysis of 28 studies revealed a weighted random effect size of r = .19 (k = 28, N = 2419, p < .01, 95% confidence interval [.13, .25]), which is a small to medium effect (equivalent to d = 0.39) consistent with the adult alliance literature and with prior youth meta-analyses. Given that a medium-large amount of heterogeneity was observed in effect sizes (I2 = 64.19%), theory- and method-based moderators were examined. Multiple moderators of the alliance-outcome association were found, including diagnosis class, type of therapy, study design (randomized controlled trials [RCT] vs. nonrandomized trials [non-RCT]), and treatment setting (inpatient vs. outpatient). Research limitations, patient contributions, and diversity considerations follow. The article concludes with research-informed practices for building and maintaining the therapeutic alliance with youth. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Psychotherapy (Chicago, Ill.) · meta-analysis · 93 citationsread the source →

Home-visiting intervention to improve child care among American Indian adolescent mothers: a randomized trial.

Objective: To assess the impact of a paraprofessional-delivered home-visiting intervention to promote child care knowledge, skills, and involvement among pregnant American Indian adolescents. Design: Randomized controlled trial comparing a family-strengthening intervention with a breastfeeding education program. Setting: One Apache and 3 Navajo communities. Participants: Fifty-three pregnant American Indian adolescents were randomly assigned to intervention (n = 28) or control (n = 25) groups. Follow-up data were available for 19 intervention and 22 control participants. Intervention Paraprofessionals delivered 41 prenatal and infant care lessons in participants' homes from 28 weeks' gestation to 6 months post partum. Main outcome measures: Child care knowledge, skills, and involvement. Results: Mothers in the intervention compared with the control group had significantly higher parent knowledge scores at 2 months (adjusted mean difference [AMD], +14.9 [95% confidence interval (CI), +7.5 to +22.4]) and 6 months post partum (AMD, +15.3 [95% CI, +5.9 to +24.7]). Intervention group mothers scored significantly higher on maternal involvement scales at 2 months post partum (AMD, +1.5 [95% CI, -0.02 to +3.02]), and scores approached significance at 6 months post partum (AMD, +1.1 [95% CI, -0.06 to +2.2]). No between-group differences were found for child care skills. Conclusions: A paraprofessional-delivered, family-strengthening home-visiting program significantly increased mothers' child care knowledge and involvement. A longer and larger trial is needed to understand the intervention's potential to improve adolescent parenting and related child outcomes in American Indian communities.

Archives of pediatrics & adolescent medicine · randomised controlled trial · 50 citationsread the source →

Islamophobia, Health, and Public Health: A Systematic Literature Review.

Background: In 2017, a "Muslim ban" on immigrants to the United States was coupled with a continued rise in Islamophobia and hate crimes toward Muslims. Islamophobia undermines health equity, yet delineating the effects of Islamophobia globally is challenging as it affects a myriad of groups (geographically, racially, and socially). Additionally, stereotypes equate all Muslims with populations from the Middle East and South Asia. To date, health research pays insufficient attention to Islamophobia, Muslims, and those racialized to be Muslim. Objectives: This literature review advances our understanding of racism and health by examining the racialization of religion, by specifically examining Islamophobia as a form of discrimination. Search methods: Per PRISMA guidelines, we conducted a search in October 2017 using PubMed-MEDLINE and a combination of terms. We identified additional articles using other search engines. For inclusion, articles needed to include a descriptor of discrimination, contain an identifier of Muslim or Muslim-like identity (i.e., groups commonly perceived as Muslim, including Arabs, Middle Easterners, North Africans, and South Asians), include a health outcome, be in English, and be published between 1990 and 2017. Selection criteria: We identified 111 unique peer-reviewed articles. We excluded articles that did not meet the following criteria: (1) examined Islamophobia, discrimination, or racism among a Muslim or Muslim-like population; (2) included a health outcome or discussion of health disparities; and (3) was conducted in North America, Europe, Australia, or New Zealand. This yielded 53 articles. Results: The majority of studies (n = 34; 64%) were quantitative. The remaining studies were qualitative (n = 7; 13%), mixed methods (n = 2; 4%), or reviews (n = 10; 19%). Most studies were based in the United States (n = 31; 58%). Nearly half of the reviewed studies examined mental health (n = 24; 45%), and one fourth examined physical health or health behaviors (n = 13; 25%). Others focused on both physical and mental health (n = 10; 19%) or health care seeking (n = 7; 13%). Studies showed associations between Islamophobia and poor mental health, suboptimal health behaviors, and unfavorable health care-seeking behaviors. Conclusions: This study elucidates the associations between Islamophobia, health, and socioecological determinants of health. Future studies should examine the intersectional nature of Islamophobia and include validated measures, representative samples, subgroup analyses, and comparison groups. More methodologically rigorous studies of Islamophobia and health are needed. Public Health Implications. Addressing the discrimination-related poor health that Muslims and racialized Muslim-like subgroups experience is central to the goals of health equity and assurance of the fundamental right to health.

American journal of public health · systematic review · 73 citationsread the source →

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

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

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

The mental health impacts of receiving a breast cancer diagnosis: A meta-analysis.

Background: Receiving a breast cancer diagnosis can be a turning point with negative impacts on mental health, treatment and prognosis. This meta-analysis sought to determine the nature and prevalence of clinically significant psychological distress-related symptoms in the wake of a breast cancer diagnosis. Methods: Ten databases were searched between March and August 2020. Thirty-nine quantitative studies were meta-analysed. Results: The prevalence of clinically significant symptoms was 39% for non-specific distress (n = 13), 34% for anxiety (n = 19), 31% for post-traumatic stress (n = 7) and 20% for depression (n = 25). No studies reporting breast cancer patients' well-being in our specific time frame were found. Conclusion: Mental health can be impacted in at least four domains following a diagnosis of breast cancer and such effects are commonplace. This study outlines a clear need for mitigating the impacts on mental health brought about by breast cancer diagnosis. CRD42020203990.

British journal of cancer · meta-analysis · 112 citationsread the source →

Incubation of Cue-Induced Craving in Adults Addicted to Cocaine Measured by Electroencephalography.

Importance: A common trigger for relapse in drug addiction is the experience of craving via exposure to cues previously associated with drug use. Preclinical studies have consistently demonstrated incubation of cue-induced drug-seeking during the initial phase of abstinence, followed by a decline over time. In humans, the incubation effect has been shown for alcohol, nicotine, and methamphetamine addictions, but not for heroin or cocaine addiction. Understanding the trajectory of cue-induced craving during abstinence in humans is of importance for addiction medicine. Objective: To assess cue-induced craving for cocaine in humans using both subjective and objective indices of cue-elicited responses. Design, setting, and participants: Seventy-six individuals addicted to cocaine with varying durations of abstinence (ie, 2 days, 1 week, 1 month, 6 months, and 1 year) participated in this laboratory-based cross-sectional study from June 19, 2007, to November 26, 2012. The late positive potential component of electroencephalography, a recognized marker of incentive salience, was used to track motivated attention to drug cues across these self-selected groups. Participants also completed subjective ratings of craving for cocaine before presentation of a cue, and ratings of cocaine "liking" (hedonic feelings toward cocaine) and "wanting" (craving for cocaine) after presentation of cocaine-related pictures. Data analysis was conducted from June 5, 2015, to March 30, 2016. Main outcomes and measures: The late positive potential amplitudes and ratings of liking and wanting cocaine in response to cocaine-related pictures were quantified and compared across groups. Results: Among the 76 individuals addicted to cocaine, 19 (25%) were abstinent for 2 days, 20 (26%) were abstinent for 1 week, 15 (20%) were abstinent for 1 month, 12 (16%) were abstinent for 6 months, and 10 (13%) were abstinent for 1 year. In response to drug cues, the mean (SD) late positive potential amplitudes showed a parabolic trajectory that was higher at 1 (1.26 [1.36] µV) and 6 (1.17 [1.19] µV) months of abstinence and lower at 2 days (0.17 [1.09] µV), 1 week (0.36 [1.26] µV), and 1 year (-0.27 [1.74] µV) of abstinence (P = .02, partial η2 = 0.16). In contrast, the subjective assessment of baseline craving (mean [SD] rating: 2 days, 26.05 [9.85]; 1 week, 18.70 [11.01]; 1 month, 10.87 [10.70]; 6 months, 6.92 [8.47]; and 1 year, 3.00 [3.77]) and cue-induced liking (mean [SD] rating: 2 days, 3.06 [2.34]; 1 week, 2.33 [2.87]; 1 month, 1.15 [2.03]; 6 months, 1.00 [2.24]; and 1 year, 1.00 [1.26]) and wanting (mean [SD] rating: 2 days, 3.44 [2.62]; 1 week, 2.72 [2.87]; 1 month, 1.46 [2.33]; 6 months, 1.00 [2.16]; and 1 year, 1.00 [1.55]) of cocaine showed a linear decline from 2 days to 1 year of abstinence (P ≤ .001, partial η2 > 0.26). Conclusions and relevance: The late positive potential responses to drug cues, indicative of motivated attention, showed a trajectory similar to that reported in animal models. In contrast, we did not detect incubation of subjective cue-induced craving. Thus, the objective electroencephalographic measure may possibly be a better indicator of vulnerability to cue-induced relapse than subjective reports of craving, although this hypothesis must be empirically tested. These results suggest the importance of deploying intervention between 1 month and 6 months of abstinence, when addicted individuals may be most vulnerable to, and perhaps least cognizant of, risk of relapse.

JAMA psychiatry · 184 citationsread the source →

Enacted Stigma, Mental Health, and Protective Factors Among Transgender Youth in Canada.

Purpose: We aimed to assess the Minority Stress Model which proposes that the stress of experiencing stigma leads to adverse mental health outcomes, but social supports (e.g., school and family connectedness) will reduce this negative effect. Methods: We measured stigma-related experiences, social supports, and mental health (self-injury, suicide, depression, and anxiety) among a sample of 923 Canadian transgender 14- to 25-year-old adolescents and young adults using a bilingual online survey. Logistic regression models were conducted to analyze the relationship between these risk and protective factors and dichotomous mental health outcomes among two separate age groups, 14- to 18-year-old and 19- to 25-year-old participants. Results: Experiences of discrimination, harassment, and violence (enacted stigma) were positively related to mental health problems and social support was negatively associated with mental health problems in all models among both age groups. Among 14-18 year olds, we examined school connectedness, family connectedness, and perception of friends caring separately, and family connectedness was always the strongest protective predictor in multivariate models. In all the mental health outcomes we examined, transgender youth reporting low levels of enacted stigma experiences and high levels of protective factors tended to report favorable mental health outcomes. Conversely, the majority of participants reporting high levels of enacted stigma and low levels of protective factors reported adverse mental health outcomes. Conclusion: While these findings are limited by nonprobability sampling procedures and potential additional unmeasured risk and protective factors, the results provide positive evidence for the Minority Stress Model in this population and affirm the need for policies and programs to support schools and families to support transgender youth.

Transgender health · 115 citationsread the source →

Combat sports and wellbeing: advancing health and inclusion in athletes and practitioners. An opinion paper

Historically, combat sports have been predominantly conceptualized within the framework of elite competition, emphasizing physical aptitude, technical proficiency, and strategic execution (1-3). Despite their traditional and peculiar constitutions and developments, disciplines such as judo, karate, taekwondo, wrestling, fencing, boxing, and mixed martial arts have commonly been associated with high-performance athletes striving for competitive excellence on national and international stages (1, 4-6). However, contemporary discourse increasingly recognizes their expansive role in contributing to physical and psychological well-being, and social inclusion of the practitioners (7, 8). This paradigmatic shift underscores the capacity of combat sports to function as inclusive and accessible modalities for fostering multidimensional health benefits across diverse populations, including individuals with disabilities and other marginalized groups (9-13).The interdisciplinary exploration of physical activity and health highlights the intricate interrelationship between structured sports engagement and holistic well-being (14). Whilst conventional team and individual sports have long been acknowledged for their physiological and psychosocial benefits, combat sports exhibit distinct characteristics that might amplify these advantages (15, 16). Within combat sports, the synergistic interplay of rigorous physical conditioning, the cognitive engagement, adherence to rules, competition dynamics, respect, externalizing emotions regulation, are intertwined with pedagogical and philosophical values, thus presenting a unique framework for enhancing psychological resilience, cognitive adaptability, and emotional control. Consequently, the systematic practice of combat sports has been increasingly examined as a way of promoting mental health, stress modulation, and social cohesion (17, 18).The inclusive nature of many combat sports programmes further accentuates their relevance in dismantling stereotypes, facilitating integration, and fostering equity and social integration (19-21). In fact, they demonstrated significant adaptability to accommodate individuals with disabilities (e.g., physical impairments, developmental, emotional, intellectual disorders), thereby ensuring equitable access and fostering empowerment (9, 22). Adapted judo, para-taekwondo, and other modified combat disciplines provide individuals with disabilities a structured platform to engage in physical activity, cultivate self-efficacy, and develop meaningful social connections within a supportive and adaptive environment (23). From a public health perspective, the integration of combat sports within community-based health initiatives offers a compelling opportunity to engage populations that may not traditionally participate in structured physical activity programmes (7, 8, 19). The distinctive accessibility of combat sports, which cater to practitioners of all skill levels (e.g., from novices to elite athletes) sets them apart from many other sports. While their structured progression, adaptability, and emphasis on holistic development make them a viable option for lifelong and intergenerational participation (19, 24, 25), the mentorship and pedagogical frameworks cultivate positive role modeling, discipline, and intrinsic motivation, which are integral for sustaining long-term adherence to health-promoting behaviors (8).Furthermore, the intersection between combat sports and mental health has increasingly emerged as a focal point within academic and clinical research (17) with empirical evidence suggesting an association between participation and enhanced self-regulation and self-efficacy, and reduction in anxiety and depressive symptomatology (8, 26, 27). In necessitating sustained focus, adaptability, and emotional equilibrium, combat sports inherently require cognitive and affective demands, which align closely with established psychological frameworks that underpin mental well-being (28, 29). Moreover, the integration of mindfulness techniques, stress management strategies, and resilience-building paradigms within combat sports training substantiates their potential as a non-pharmacological intervention for addressing various mental health challenges (e.g., autism spectrum and oppositional defiant disorders) (30, 31).Despite these advantages, the discourse surrounding combat sports and well-being necessitates a critical examination of inherent risks and potential challenges. Issues related to injury risk, hypercompetitive environments, eating disorders, sexual harassment, and the psychological stressors associated with high-intensity training warrant careful scrutiny (32-36). The implementation of evidence-based injury prevention protocols, the establishment of ethically responsible coaching methodologies, and the promotion of safe training environments are imperative to ensure that the benefits of combat sports are maximized while minimizing adverse outcomes. Against this backdrop, this opinion paper seeks to examine the role of combat sports in advancing health and social inclusion among athletes and practitioners. Through a synthesis of contemporary empirical findings, theoretical paradigms, and applied insights, this paper aims to contribute to the evolving discourse on the potential of combat sports as a catalyst for holistic well-being. By delineating the multidimensional impact of combat sports on physical, psychological, and social health, this paper endeavors to underscore their transformative potential as an instrument for fostering individual and community well-being within different populations. DiscussionWhilst an expanding body of research and an evolution in scholarly discourse is recognizing the combat sports’ broader implications for holistic well-being (30, 37), a rigorous evaluation of the investigation methodologies, the validity of hypotheses, and the translational potential of recent findings is necessary to contextualize their significance within the sports and public health sciences, considering their strengths, weaknesses, opportunities, and threats (Figure 1).----------------------------------------ADD FIGURE 1 ABOUT HERE----------------------------------------Empirical evidence robustly shows the positive impact of combat sports on physical fitness, motor coordination, and cardiovascular health (3, 38). These benefits are attributed to the high-intensity, intermittent nature of combat sports training, which enhances aerobic and anaerobic endurance, muscular strength, and neuromuscular control (39). However, concerns regarding injury risk, particularly in striking and contact-intensive disciplines such as boxing, taekwondo, and mixed martial arts, necessitate continued research into injury mitigation strategies, particularly those targeting concussion and repetitive head trauma (6, 35, 40, 41). Moreover, many combat sports have developed styles with reduced or simulated contact to minimize injury risk. For example, the French "boxe éducative" emphasizing technique and control, penalizing any violent behaviors (42) and the value and application of kata (i.e., forms; prearranged, pattern practices) to learning and adopting judo technique in a safe way educating the athlete culturally, to enrich her/him as a person (43).Beyond physical health, recent studies highlight the psychological benefits of combat sports, including reductions in anxiety and depression and improvements in self-efficacy, emotional regulation, resilience, and stress management (27, 44-47). Therefore, combat sports-based interventions for individuals with mental health conditions have yielded promising outcomes (23). Despite these encouraging findings, variability in study designs, participant demographics, and intervention protocols limits their external validity, underscoring the need for further rigorously controlled investigations. Furthermore, some authors claimed that combat sport athletes might present symptoms of low energy availability and high anxiety levels associated with competition- and injury-related psychological stressors, deficits in executive functions and neuropsychological impairments associated with occurrence of concussions, disordered eating and eating disorders associated with weight-loss, and might suffer offensive, frightening, hostile, degrading, humiliating experiences, or sexual harassment, which urge safeguarding actions (32-36).The role of combat sports in fostering social inclusion has gained empirical support, particularly in programmes aimed at individuals with disabilities and marginalized communities (25, 48). For instance, a recent systematic review shows that judo interventions adapted for intellectual disabilities help improve social integration and self-perception and enhance participants' quality of life (49). The development of para-combat sports demonstrates enhanced physical and motor abilities while providing psychosocial benefits to various populations with different disabilities, promoting social integration, self-perception, and community belonging (50, 51). However, longitudinal research is needed to assess the long-term retention rates and sustainability of these benefits. Furthermore, there is a need of studies focused on the most appropriate adapted rules to achieve a fairer competition for ensuring a sense of success in individuals with physical, emotional, mental, hearing or visual impairments participating in adapted sports competitions at local, national, and international levels. Methodological approaches in combat sports research encompass experimental, longitudinal, qualitative, and systematic review designs. While randomized controlled trials remain the gold standard for establishing causality, their application in combat sports research is constrained by ethical concerns, logistical challenges, and the inherently dynamic nature of training environments (52, 53). Consequently, many studies rely on observational designs, which, despite their value in identifying associations, are susceptible to confounding variables and biases (24, 54).Qualitative methodologies have provided critical insights into the lived experiences of combat sports practitioners, offering perspectives on psychological and social dimensions that are often overlooked in quantitative studies (28). Ethnographic research has been particularly instrumental in elucidating the role of combat sports in shaping identity, discipline, and personal development (55). However, limitations in reproducibility and generalizability highlight the need for mixed-methods approaches to generate a more comprehensive understanding of combat sports' impact (25, 56).Additionally, the incorporation of biometric and neurocognitive assessments, such as heart rate variability analysis, functional MRI, and salivary cortisol measurements, has advanced our understanding of the physiological and psychological mechanisms underlying combat sports participation (47, 57, 58). Despite their objective precision, these techniques often face challenges related to cost, accessibility, and limited sample sizes, necessitating the development of scalable and cost-effective methodologies for broader research application. Finally, recent studies show that virtual reality (VR) technology and digital platforms are increasingly becoming part of combat sports training methods. Due to COVID-19 restrictions, martial arts schools and organizations implemented hybrid or online training models, which allowed athletes to stay engaged. VR boxing programmes provide users with virtual sparring simulations to enhance their motor skills without needing physical interaction. Initial results indicate that VR training enhances response behavior in karate athletes (59). Digital adaptations offer great potential, especially for people with limited mobility or remote locations. However, further studies are necessary to prove their enduring effects on physical health and psychological and social aspects (59-61).Strengths and Weaknesses of Scientific HypothesesThe hypothesis that combat sports confer multidimensional health benefits is strongly supported by empirical evidence spanning physiological, psychological, and social domains (8, 62-64). The integration of physical exertion, cognitive engagement, and structured discipline inherent in combat sports aligns with established theories of exercise psychology, neuroplasticity, and social identity formation (65, 66). This multidimensional perspective provides a robust theoretical foundation for advocating combat sports as a health-promoting activity. Nevertheless, several limitations warrant consideration. The heterogeneity of disciplines, which vary highly in intensity, contact level, and training methodologies, is often inadequately addressed in research, leading to overgeneralized conclusions (17, 39). Often underexamined, individual differences in personality, motivation, and previous trauma history may strongly moderate the psychological outcomes of combat sports participation (35, 67, 68).Additionally, a research focus is needed on concerns regarding the potential for adverse psychological effects (e.g., anxiety, depression, disordered eating behaviors, burnout, and decreased self-esteem), particularly in competitive environments where performance pressure, extreme weight-cutting practices, and aggressive coaching styles are prevalent (69, 70). Indeed, a balanced perspective that considers both benefits and risks is essential for the development of evidence-based recommendations (10, 71).Future DirectionsTo enhance the field, future research should prioritize well-structured longitudinal studies that assess the long-term impact of combat sports participation on physical, psychological, and social health. Standardization of outcome measures, intervention protocols, and participant demographics would facilitate cross-study comparisons and strengthen the reliability of findings (72, 73). Moreover, interdisciplinary collaborations incorporating sports science, psychology, and sociology could provide a more holistic perspective on combat sports' broader implications on practitioners (74).From a policy perspective, to yield valuable insights into combat sports’ practical applications research should investigate their efficacy within public health, educational, and rehabilitation initiatives, particularly for underserved and vulnerable populations (23, 75, 76).Furthermore, while safety remains a primary concern, advancements in protective equipment, training methodologies, education for athletes, coaches, referees and tournament directors, and regulatory frameworks should be continually evaluated to optimize benefits while mitigating risks (40, 41, 58, 77, 78). Ethical considerations, particularly concerning athlete well-being and inclusive participation, should remain a central focus in both research and practical implementation (17, 34, 36).Therefore, key research challenges to be addressed are: 1. Injury risk and safety: a need for injury prevention strategies, especially for concussions and head trauma in striking sports. 2. Psychological wellbeing: risks of stress, anxiety, burnout, and negative self-perception in competitive environments. 3. Inclusion and accessibility: a need for more research on long-term social and psychological benefits for marginalized groups and individuals with disabilities. 4. Methodological limitations: lack of standardized protocols, variability in study designs, and limited reproducibility of findings. 5. Ethical and regulatory issues: concerns over coaching practices, extreme weight-cutting, and athlete wellbeing in high-pressure environments. 6. Technological innovations: more research required on the effectiveness of VR and digital training tools in combat sports. 7. Public health and policy: exploration of combat sports' role in health initiatives, rehabilitation, and educational programs. ConclusionThe evolving discourse on combat sports highlights their potential as a multidimensional tool for well-being promotion. While a substantial body of evidence supports their benefits, a critical examination of methodological limitations, scientific hypotheses, and practical applications is essential for further refine our understanding and enhance their effectiveness. Finally, this article makes a significant contribution not only to the field of martial arts but also to public health and sports psychology. Its interdisciplinary approach calls for scientific collaboration and methodological rigor, reinforces the need for evidence-based policies and can serve as a valuable guide for researchers and policymakers looking to integrate combat sports into strategies for promoting health and social inclusion.

Frontiers in Psychology · 12 citationsread the source →

A Comparative Study of Health Anxiety in Neurology and Psychiatry Settings.

Objectives  Prevalence of health anxiety is highly varied based on different settings and samples studied. This study aimed to assess the prevalence of health anxiety among outpatients attending neurology and psychiatry outpatient setting in tertiary care hospital and understand the clinical correlates. Participants and Methods  This was a cross-sectional study conducted in the outpatient settings including participants fulfilling study criteria. The assessments included semi-structured proforma for demographic and clinical details, general hypochondriasis subscale of Illness Behavior Questionnaire, and Short Health Anxiety Inventory. Data were collected in Epi-info and data analysis was done using STATA12. Results  The health anxiety was reported to be 25% and 19% among psychiatry and neurology outpatients, respectively. Higher education level positively correlated with health anxiety. Skilled workers tend to have higher health anxiety than semiskilled workers. Patients with diagnosis of somatoform disorder and multiple diagnosis scored higher on health anxiety in both the settings. Conclusion  Health anxiety appears to be common in psychiatry and neurology settings and needs further evaluation to understand its impact on consultation and health resource usages.

Journal of neurosciences in rural practice · 3 citationsread the source →

Cognitive empathy across the lifespan.

Aim: To describe the development of cognitive empathy across the lifespan from a very large cohort using a standardized measure of cognitive empathy ability. Method: Participants (n=4545, age bands <5y to >75y, 60% female) were a convenience sample recruited voluntarily from visitors to the Glasgow Science Centre in the UK, who completed the Reading the Mind in the Eyes Test. Results: When compared to preceding age groups, we found significant developmental gains in empathy ability in children aged 6 to 7 years (p=0.048, d=0.45) and again at 10 to 12 years (p=0.042, d=0.23), followed by a slight reduction in ability during adolescence (p=0.087, d=-0.18), and functional maturity in those aged 19 to 25 years (p=0.001, d=0.76). Cognitive empathy abilities remained relatively stable across adulthood but gradually declined in people over 65 years, with notable decline in males over 75 years (p=0.001, d=-0.98). Females performed better than males at all ages. Interpretation: Understanding developmental issues in cognitive empathy could influence approaches to moral and social education for children, and health and social care support for older people. Standardized cognitive empathy tests could also provide novel approaches in the early detection of developmental vulnerabilities in a range of neurological conditions, and within neuropsychiatric and neurodegenerative disorders in which cognitive empathy is known to be impaired. What this paper adds: Cognitive empathy is a late-developing ability and changes across the lifespan. Cognitive empathy increases during childhood but with potentially altered abilities during adolescence. Cognitive empathy matures during early adulthood and gradually declines in older age. There is a female advantage in cognitive empathy abilities.

Developmental medicine and child neurology · 20 citationsread the source →

Differences in psychiatric care utilization between refugees, non-refugee migrants and Swedish-born youth.

Background: The study aimed to examine differences in, and characteristics of psychiatric care utilization in young refugees who came to Sweden as unaccompanied or accompanied minors, compared with that of their non-refugee immigrant and Swedish-born peers. Methods: This register-linkage cohort study included 746 688 individuals between 19 and 25 years of age in 2009, whereof 32 481 were refugees (2896 unaccompanied and 29 585 accompanied) and 32 151 non-refugee immigrants. Crude and multivariate Cox regression models yielding hazard ratios (HR) and 95% confidence intervals (CI) were conducted to investigate subsequent psychiatric care utilization for specific disorders, duration of residence and age at migration. Results: The adjusted HRs for psychiatric care utilization due to any mental disorder was significantly lower in both non-refugee and refugee immigrants when compared to Swedish-born [aHR: 0.78 (95% CI 0.76-0.81) and 0.75 (95% CI 0.72-0.77, respectively)]. Within the refugee group, unaccompanied had slightly lower adjusted risk estimates than accompanied. This pattern was similar for all specific mental disorders except for higher rates in schizophrenia, reaction to severe stress/adjustment disorders and post-traumatic stress disorder. Psychiatric health care utilization was also higher in immigrants with more than 10 years of residency in Sweden entering the country being younger than 6 years of age. Conclusions: For most mental disorders, psychiatric health care utilization in young refugees and non-refugee immigrants was lower than in their Swedish-born peers; exceptions are schizophrenia and stress-related disorders. Arrival in Sweden before the age of 6 years was associated with higher rates of overall psychiatric care utilization.

Psychological medicine · 29 citationsread the source →

Healthcare avoidance due to anticipated discrimination among transgender people: A call to create trans-affirmative environments.

Transgender people encounter interpersonal and structural barriers to healthcare access that contribute to their postponement or avoidance of healthcare, which can lead to poor physical and mental health outcomes. Using the 2015 U.S. Transgender Survey, this study examined avoidance of healthcare due to anticipated discrimination among transgender adults aged 25 to 64 (N = 19,157). Multivariable logistic regression analysis was conducted to test whether gender identity/expression, socio-demographic, and transgender-specific factors were associated with healthcare avoidance. Almost one-quarter of the sample (22.8%) avoided healthcare due to anticipated discrimination. Transgender men had increased odds of healthcare avoidance (AOR = 1.32, 95% CI = 1.21-1.45) relative to transgender women. Living in poverty (AOR = 1.52, 95% CI = 1.40-1.65) and visual non-conformity (AOR = 1.48, 95% CI = 1.33-1.66) were significant risk factors. Having health insurance (AOR = 0.87, 95% CI = 0.79-0.96) and disclosure of transgender identity (AOR = 0.77, 95% CI = 0.68-0.87) were protective against healthcare avoidance. A significant interaction of gender identity/expression with health insurance was found; having health insurance moderated the association between gender identity/expression and healthcare avoidance. Providers should consider gender differences, socio-demographic, and transgender-specific factors to improve accessibility of services to transgender communities. A multi-level and multi-faceted approach should be used to create safe, trans-affirmative environments in health systems.

SSM - population health · 205 citationsread the source →

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

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

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

Premonitory urge to tic in Tourette's is associated with interoceptive awareness.

Background: A contribution of aberrant interoceptive awareness to the perception of premonitory urges in Gilles de la Tourette syndrome (GTS) has been hypothesized. Methods: We assessed interoceptive awareness in 19 adults with GTS and 25 age-matched healthy controls using the heartbeat counting task. We also used multiple regression to explore whether the severity of premonitory urges was predicted by interoceptive awareness or severity of tics and obsessive-compulsive symptoms. Results: We observed lower interoceptive awareness in GTS compared with controls. Interoceptive awareness was the strongest predictor of premonitory urges in GTS, with greater interoceptive awareness being associated with more urges. Greater tic severity was also associated with higher rates of premonitory urges. Conclusion: The observed relationship between severity of premonitory urges and interoceptive awareness suggests that interoception might be involved in self-reported premonitory urges in GTS. High levels of interoceptive awareness might reflect a self-attentive capacity to perceive urges.

Movement disorders : official journal of the Movement Disorder Society · 88 citationsread the source →

Dissociation in Psychiatric Disorders: A Meta-Analysis of Studies Using the Dissociative Experiences Scale.

Objective: Dissociation is a complex, ubiquitous construct in psychopathology. Symptoms of dissociation are present in a variety of mental disorders and have been connected to higher burden of illness and poorer treatment response, and not only in disorders with high levels of dissociation. This meta-analysis offers a systematic and evidence-based study of the prevalence and distribution of dissociation, as assessed by the Dissociative Experiences Scale, within different categories of mental disorders, and it updates an earlier meta-analysis. Method: More than 1,900 original publications were screened, and 216 were included in the meta-analysis, comprising 15,219 individuals in 19 diagnostic categories. Results: The largest mean dissociation scores were found in dissociative disorders (mean scores >35), followed by posttraumatic stress disorder, borderline personality disorder, and conversion disorder (mean scores >25). Somatic symptom disorder, substance-related and addictive disorders, feeding and eating disorders, schizophrenia, anxiety disorder, OCD, and most affective disorders also showed mean dissociation scores >15. Bipolar disorders yielded the lowest dissociation scores (mean score, 14.8). Conclusions: The findings underline the importance of careful psychopathological assessment of dissociative symptoms in the entire range of mental disorders.

The American journal of psychiatry · meta-analysis · 266 citationsread the source →

Age at onset of mental disorders worldwide: large-scale meta-analysis of 192 epidemiological studies.

Promotion of good mental health, prevention, and early intervention before/at the onset of mental disorders improve outcomes. However, the range and peak ages at onset for mental disorders are not fully established. To provide robust, global epidemiological estimates of age at onset for mental disorders, we conducted a PRISMA/MOOSE-compliant systematic review with meta-analysis of birth cohort/cross-sectional/cohort studies, representative of the general population, reporting age at onset for any ICD/DSM-mental disorders, identified in PubMed/Web of Science (up to 16/05/2020) (PROSPERO:CRD42019143015). Co-primary outcomes were the proportion of individuals with onset of mental disorders before age 14, 18, 25, and peak age at onset, for any mental disorder and across International Classification of Diseases 11 diagnostic blocks. Median age at onset of specific disorders was additionally investigated. Across 192 studies (n = 708,561) included, the proportion of individuals with onset of any mental disorders before the ages of 14, 18, 25 were 34.6%, 48.4%, 62.5%, and peak age was 14.5 years (k = 14, median = 18, interquartile range (IQR) = 11-34). For diagnostic blocks, the proportion of individuals with onset of disorder before the age of 14, 18, 25 and peak age were as follows: neurodevelopmental disorders: 61.5%, 83.2%, 95.8%, 5.5 years (k = 21, median=12, IQR = 7-16), anxiety/fear-related disorders: 38.1%, 51.8%, 73.3%, 5.5 years (k = 73, median = 17, IQR = 9-25), obsessive-compulsive/related disorders: 24.6%, 45.1%, 64.0%, 14.5 years (k = 20, median = 19, IQR = 14-29), feeding/eating disorders/problems: 15.8%, 48.1%, 82.4%, 15.5 years (k = 11, median = 18, IQR = 15-23), conditions specifically associated with stress disorders: 16.9%, 27.6%, 43.1%, 15.5 years (k = 16, median = 30, IQR = 17-48), substance use disorders/addictive behaviours: 2.9%, 15.2%, 48.8%, 19.5 years (k = 58, median = 25, IQR = 20-41), schizophrenia-spectrum disorders/primary psychotic states: 3%, 12.3%, 47.8%, 20.5 years (k = 36, median = 25, IQR = 20-34), personality disorders/related traits: 1.9%, 9.6%, 47.7%, 20.5 years (k = 6, median = 25, IQR = 20-33), and mood disorders: 2.5%, 11.5%, 34.5%, 20.5 years (k = 79, median = 31, IQR = 21-46). No significant difference emerged by sex, or definition of age of onset. Median age at onset for specific mental disorders mapped on a time continuum, from phobias/separation anxiety/autism spectrum disorder/attention deficit hyperactivity disorder/social anxiety (8-13 years) to anorexia nervosa/bulimia nervosa/obsessive-compulsive/binge eating/cannabis use disorders (17-22 years), followed by schizophrenia, personality, panic and alcohol use disorders (25-27 years), and finally post-traumatic/depressive/generalized anxiety/bipolar/acute and transient psychotic disorders (30-35 years), with overlap among groups and no significant clustering. These results inform the timing of good mental health promotion/preventive/early intervention, updating the current mental health system structured around a child/adult service schism at age 18.

Molecular psychiatry · meta-analysis · 2420 citationsread the source →

Effectiveness of weight management interventions for adults delivered in primary care: systematic review and meta-analysis of randomised controlled trials.

Objective: To examine the effectiveness of behavioural weight management interventions for adults with obesity delivered in primary care. Design: Systematic review and meta-analysis of randomised controlled trials. Eligibility criteria for selection of studies: Randomised controlled trials of behavioural weight management interventions for adults with a body mass index ≥25 delivered in primary care compared with no treatment, attention control, or minimal intervention and weight change at ≥12 months follow-up. Data sources: Trials from a previous systematic review were extracted and the search completed using the Cochrane Central Register of Controlled Trials, Medline, PubMed, and PsychINFO from 1 January 2018 to 19 August 2021. Data extraction and synthesis: Two reviewers independently identified eligible studies, extracted data, and assessed risk of bias using the Cochrane risk of bias tool. Meta-analyses were conducted with random effects models, and a pooled mean difference for both weight (kg) and waist circumference (cm) were calculated. Main outcome measures: Primary outcome was weight change from baseline to 12 months. Secondary outcome was weight change from baseline to ≥24 months. Change in waist circumference was assessed at 12 months. Results: 34 trials were included: 14 were additional, from a previous review. 27 trials (n=8000) were included in the primary outcome of weight change at 12 month follow-up. The mean difference between the intervention and comparator groups at 12 months was -2.3 kg (95% confidence interval -3.0 to -1.6 kg, I2=88%, P<0.001), favouring the intervention group. At ≥24 months (13 trials, n=5011) the mean difference in weight change was -1.8 kg (-2.8 to -0.8 kg, I2=88%, P<0.001) favouring the intervention. The mean difference in waist circumference (18 trials, n=5288) was -2.5 cm (-3.2 to -1.8 cm, I2=69%, P<0.001) in favour of the intervention at 12 months. Conclusions: Behavioural weight management interventions for adults with obesity delivered in primary care are effective for weight loss and could be offered to members of the public. Systematic review registration: PROSPERO CRD42021275529.

BMJ (Clinical research ed.) · meta-analysis · 79 citationsread the source →

Mediterranean-style diet for the primary and secondary prevention of cardiovascular disease.

Background: The Seven Countries study in the 1960s showed that populations in the Mediterranean region experienced lower coronary heart disease (CHD) mortality probably as a result of different dietary patterns. Later observational studies have confirmed the benefits of adherence to a Mediterranean dietary pattern on cardiovascular disease (CVD) risk factors but clinical trial evidence is more limited. Objectives: To determine the effectiveness of a Mediterranean-style diet for the primary and secondary prevention of CVD. Search methods: We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 9); MEDLINE (Ovid, 1946 to 25 September 2018); Embase (Ovid, 1980 to 2018 week 39); Web of Science Core Collection (Thomson Reuters, 1900 to 26 September 2018); DARE Issue 2 of 4, 2015 (Cochrane Library); HTA Issue 4 of 4, 2016 (Cochrane Library); NHS EED Issue 2 of 4, 2015 (Cochrane Library). We searched trial registers and applied no language restrictions. Selection criteria: We selected randomised controlled trials (RCTs) in healthy adults and adults at high risk of CVD (primary prevention) and those with established CVD (secondary prevention). Both of the following key components were required to reach our definition of a Mediterranean-style diet: high monounsaturated/saturated fat ratio (use of olive oil as main cooking ingredient and/or consumption of other traditional foods high in monounsaturated fats such as tree nuts) and a high intake of plant-based foods, including fruits, vegetables and legumes. Additional components included: low to moderate red wine consumption; high consumption of whole grains and cereals; low consumption of meat and meat products and increased consumption of fish; moderate consumption of milk and dairy products. The intervention could be dietary advice, provision of relevant foods, or both. The comparison group received either no intervention, minimal intervention, usual care or another dietary intervention. Outcomes included clinical events and CVD risk factors. We included only studies with follow-up periods of three months or more defined as the intervention period plus post intervention follow-up. Data collection and analysis: Two review authors independently assessed studies for inclusion, extracted data and assessed risk of bias. We conducted four main comparisons:1. Mediterranean dietary intervention versus no intervention or minimal intervention for primary prevention;2. Mediterranean dietary intervention versus another dietary intervention for primary prevention;3. Mediterranean dietary intervention versus usual care for secondary prevention;4. Mediterranean dietary intervention versus another dietary intervention for secondary prevention. Main results: In this substantive review update, 30 RCTs (49 papers) (12,461 participants randomised) and seven ongoing trials met our inclusion criteria. The majority of trials contributed to primary prevention: comparisons 1 (nine trials) and 2 (13 trials). Secondary prevention trials were included for comparison 3 (two trials) and comparison 4 (four trials plus an additional two trials that were excluded from the main analyses due to published concerns regarding the reliability of the data).Two trials reported on adverse events where these were absent or minor (low- to moderate-quality evidence). No trials reported on costs or health-related quality of life. Primary preventionThe included studies for comparison 1 did not report on clinical endpoints (CVD mortality, total mortality or non-fatal endpoints such as myocardial infarction or stroke). The PREDIMED trial (included in comparison 2) was retracted and re-analysed following concerns regarding randomisation at two of 11 sites. Low-quality evidence shows little or no effect of the PREDIMED (7747 randomised) intervention (advice to follow a Mediterranean diet plus supplemental extra-virgin olive oil or tree nuts) compared to a low-fat diet on CVD mortality (hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.50 to 1.32) or total mortality (HR 1.0, 95% CI 0.81 to 1.24) over 4.8 years. There was, however, a reduction in the number of strokes with the PREDIMED intervention (HR 0.60, 95% CI 0.45 to 0.80), a decrease from 24/1000 to 14/1000 (95% CI 11 to 19), moderate-quality evidence). For CVD risk factors for comparison 1 there was low-quality evidence for a possible small reduction in total cholesterol (-0.16 mmol/L, 95% CI -0.32 to 0.00) and moderate-quality evidence for a reduction in systolic (-2.99 mmHg (95% CI -3.45 to -2.53) and diastolic blood pressure (-2.0 mmHg, 95% CI -2.29 to -1.71), with low or very low-quality evidence of little or no effect on LDL or HDL cholesterol or triglycerides. For comparison 2 there was moderate-quality evidence of a possible small reduction in LDL cholesterol (-0.15 mmol/L, 95% CI -0.27 to -0.02) and triglycerides (-0.09 mmol/L, 95% CI -0.16 to -0.01) with moderate or low-quality evidence of little or no effect on total or HDL cholesterol or blood pressure. Secondary preventionFor secondary prevention, the Lyon Diet Heart Study (comparison 3) examined the effect of advice to follow a Mediterranean diet and supplemental canola margarine compared to usual care in 605 CHD patients over 46 months and there was low-quality evidence of a reduction in adjusted estimates for CVD mortality (HR 0.35, 95% CI 0.15 to 0.82) and total mortality (HR 0.44, 95% CI 0.21 to 0.92) with the intervention. Only one small trial (101 participants) provided unadjusted estimates for composite clinical endpoints for comparison 4 (very low-quality evidence of uncertain effect). For comparison 3 there was low-quality evidence of little or no effect of a Mediterranean-style diet on lipid levels and very low-quality evidence for blood pressure. Similarly, for comparison 4 where only two trials contributed to the analyses there was low or very low-quality evidence of little or no effect of the intervention on lipid levels or blood pressure. Authors' conclusions: Despite the relatively large number of studies included in this review, there is still some uncertainty regarding the effects of a Mediterranean-style diet on clinical endpoints and CVD risk factors for both primary and secondary prevention. The quality of evidence for the modest benefits on CVD risk factors in primary prevention is low or moderate, with a small number of studies reporting minimal harms. There is a paucity of evidence for secondary prevention. The ongoing studies may provide more certainty in the future.

The Cochrane database of systematic reviews · meta-analysis · 230 citationsread the source →

Omega-3 fatty acids for depression in adults.

Background: Major depressive disorder (MDD) is highly debilitating, difficult to treat, has a high rate of recurrence, and negatively impacts the individual and society as a whole. One emerging potential treatment for MDD is n-3 polyunsaturated fatty acids (n-3PUFAs), also known as omega-3 oils, naturally found in fatty fish, some other seafood, and some nuts and seeds. Various lines of evidence suggest a role for n-3PUFAs in MDD, but the evidence is far from conclusive. Reviews and meta-analyses clearly demonstrate heterogeneity between studies. Investigations of heterogeneity suggest differential effects of n-3PUFAs, depending on severity of depressive symptoms, where no effects of n-3PUFAs are found in studies of individuals with mild depressive symptomology, but possible benefit may be suggested in studies of individuals with more severe depressive symptomology. Objectives: To assess the effects of n-3 polyunsaturated fatty acids (also known as omega-3 fatty acids) versus a comparator (e.g. placebo, anti-depressant treatment, standard care, no treatment, wait-list control) for major depressive disorder (MDD) in adults. Search methods: We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Registers (CCDANCTR) and International Trial Registries over all years to May 2015. We searched the database CINAHL over all years of records to September 2013. Selection criteria: We included studies in the review if they: were a randomised controlled trial; provided n-3PUFAs as an intervention; used a comparator; measured depressive symptomology as an outcome; and were conducted in adults with MDD. Primary outcomes were depressive symptomology (continuous data collected using a validated rating scale) and adverse events. Secondary outcomes were depressive symptomology (dichotomous data on remission and response), quality of life, and failure to complete studies. Data collection and analysis: We used standard methodological procedures as expected by Cochrane. Main results: We found 26 relevant studies: 25 studies involving a total of 1438 participants investigated the impact of n-3PUFA supplementation compared to placebo, and one study involving 40 participants investigated the impact of n-3PUFA supplementation compared to antidepressant treatment. For the placebo comparison, n-3PUFA supplementation results in a small to modest benefit for depressive symptomology, compared to placebo: standardised mean difference (SMD) -0.32 (95% confidence interval (CI) -0.12 to -0.52; 25 studies, 1373 participants, very low quality evidence), but this effect is unlikely to be clinically meaningful (an SMD of 0.32 represents a difference between groups in scores on the HDRS (17-item) of approximately 2.2 points (95% CI 0.8 to 3.6)). The confidence intervals include both a possible clinically important effect and a possible negligible effect, and there is considerable heterogeneity between the studies. Although the numbers of individuals experiencing adverse events were similar in intervention and placebo groups (odds ratio (OR) 1.24, 95% CI 0.95 to 1.62; 19 studies, 1207 participants; very low-quality evidence), the confidence intervals include a significant increase in adverse events with n-3PUFAs as well as a small possible decrease. Rates of remission and response, quality of life, and rates of failure to complete studies were also similar between groups, but confidence intervals are again wide. The evidence on which these results are based is very limited. All studies contributing to our analyses were of direct relevance to our research question, but we rated the quality of the evidence for all outcomes as low to very low. The number of studies and number of participants contributing to all analyses were low, and the majority of studies were small and judged to be at high risk of bias on several measures. Our analyses were also likely to be highly influenced by three large trials. Although we judge these trials to be at low risk of bias, they contribute 26.9% to 82% of data. Our effect size estimates are also imprecise. Funnel plot asymmetry and sensitivity analyses (using fixed-effect models, and only studies judged to be at low risk of selection bias, performance bias or attrition bias) also suggest a likely bias towards a positive finding for n-3PUFAs. There was substantial heterogeneity in analyses of our primary outcome of depressive symptomology. This heterogeneity was not explained by the presence or absence of comorbidities or by the presence or absence of adjunctive therapy. Only one study was available for the antidepressant comparison, involving 40 participants. This study found no differences between treatment with n-3PUFAs and treatment with antidepressants in depressive symptomology (mean difference (MD) -0.70 (95% CI -5.88 to 4.48)), rates of response to treatment or failure to complete. Adverse events were not reported in a manner suitable for analysis, and rates of depression remission and quality of life were not reported. Authors' conclusions: At present, we do not have sufficient high quality evidence to determine the effects of n-3PUFAs as a treatment for MDD. Our primary analyses suggest a small-to-modest, non-clinically beneficial effect of n-3PUFAs on depressive symptomology compared to placebo; however the estimate is imprecise, and we judged the quality of the evidence on which this result is based to be low/very low. Sensitivity analyses, funnel plot inspection and comparison of our results with those of large well-conducted trials also suggest that this effect estimate is likely to be biased towards a positive finding for n-3PUFAs, and that the true effect is likely to be smaller. Our data, however, also suggest similar rates of adverse events and numbers failing to complete trials in n-3PUFA and placebo groups, but again our estimates are very imprecise. The one study that directly compares n-3PUFAs and antidepressants in our review finds comparable benefit. More evidence, and more complete evidence, are required, particularly regarding both the potential positive and negative effects of n-3PUFAs for MDD.

The Cochrane database of systematic reviews · meta-analysis · 90 citationsread the source →

Mind matters: A meta-analysis on parental mentalization and sensitivity as predictors of infant–parent attachment.

Major developments in attachment research over the past 2 decades have introduced parental mentalization as a predictor of infant-parent attachment security. Parental mentalization is the degree to which parents show frequent, coherent, or appropriate appreciation of their infants' internal states. The present study examined the triangular relations between parental mentalization, parental sensitivity, and attachment security. A total of 20 effect sizes (N = 974) on the relation between parental mentalization and attachment, 82 effect sizes (N = 6,664) on the relation between sensitivity and attachment, and 24 effect sizes (N = 2,029) on the relation between mentalization and sensitivity were subjected to multilevel meta-analyses. The results showed a pooled correlation of r = .30 between parental mentalization and infant attachment security, and rs of .25 for the correlations between sensitivity and attachment security, and between parental mentalization and sensitivity. A meta-analytic structural equation model was performed to examine the combined effects of mentalization and sensitivity as predictors of infant attachment. Together, the predictors explained 12% of the variance in attachment security. After controlling for the effect of sensitivity, the relation between parental mentalization and attachment remained, r = .24; the relation between sensitivity and attachment remained after controlling for parental mentalization, r = .19. Sensitivity also mediated the relation between parental mentalization and attachment security, r = .07, suggesting that mentalization exerts both direct and indirect influences on attachment security. The results imply that parental mentalization should be incorporated into existing models that map the predictors of infant-parent attachment. (PsycINFO Database Record

Psychological Bulletin · meta-analysis · 414 citationsread the source →

Breastfeeding and Childhood Leukemia Incidence: A Meta-analysis and Systematic Review.

Importance: Childhood cancer is a leading cause of mortality among children and adolescents in the developed world and the incidence increases by 0.9% each year. Leukemia accounts for about 30% of all childhood cancer but its etiology is still mostly unknown. Objective: To conduct a meta-analysis of available scientific evidence on the association between breastfeeding and childhood leukemia. Data sources: A thorough search for articles published between January 1960 and December 2014 researching the association between breastfeeding and childhood leukemia was conducted on PubMed, the Cochrane Library, and Scopus (performed in July and December 2014), supplemented by manual searches of reference lists. Study selection: To be included in the meta-analyses, studies had to be case control; include breastfeeding as a measured exposure and leukemia as a measured outcome; include data on breastfeeding duration in months; and be published in a peer-reviewed journal with full text available in English. Data extraction and synthesis: The search identified 25 relevant studies, 18 of which met all inclusion criteria. No publication bias or heterogeneity among these 18 studies were detected. The quality of each study that met the inclusion criteria was assessed using the Newcastle-Ottawa Scale. Multiple meta-analyses were conducted using the random effect model on raw data in the StatsDirect statistical program. Main outcomes and measures: No or short duration of breastfeeding and the incidence of childhood leukemia. Results: The meta-analysis of all 18 studies indicated that compared with no or shorter breastfeeding, any breastfeeding for 6 months or longer was associated with a 19% lower risk for childhood leukemia (odds ratio, 0.81; 95% CI, 0.73-0.89). A separate meta-analysis of 15 studies indicated that ever breastfed compared with never breastfed was associated with an 11% lower risk for childhood leukemia (odds ratio, 0.89; 95% CI, 0.84-0.94), although the definition of never breastfed differed between studies. All meta-analyses of subgroups of the 18 studies showed similar associations. Based on current meta-analyses results, 14% to 19% of all childhood leukemia cases may be prevented by breastfeeding for 6 months or more. Conclusions and relevance: Breastfeeding is a highly accessible, low-cost public health measure. This meta-analysis that included studies not featured in previous meta-analyses on the subject indicates that promoting breastfeeding for 6 months or more may help lower childhood leukemia incidence, in addition to its other health benefits for children and mothers.

JAMA pediatrics · meta-analysis · 145 citationsread the source →

Combined pharmacotherapy and behavioural interventions for smoking cessation.

Background: Both behavioural support (including brief advice and counselling) and pharmacotherapies (including nicotine replacement therapy (NRT), varenicline and bupropion) are effective in helping people to stop smoking. Combining both treatment approaches is recommended where possible, but the size of the treatment effect with different combinations and in different settings and populations is unclear. Objectives: To assess the effect of combining behavioural support and medication to aid smoking cessation, compared to a minimal intervention or usual care, and to identify whether there are different effects depending on characteristics of the treatment setting, intervention, population treated, or take-up of treatment. Search methods: We searched the Cochrane Tobacco Addiction Group Specialised Register in July 2015 for records with any mention of pharmacotherapy, including any type of NRT, bupropion, nortriptyline or varenicline. Selection criteria: Randomized or quasi-randomized controlled trials evaluating combinations of pharmacotherapy and behavioural support for smoking cessation, compared to a control receiving usual care or brief advice or less intensive behavioural support. We excluded trials recruiting only pregnant women, trials recruiting only adolescents, and trials with less than six months follow-up. Data collection and analysis: Search results were prescreened by one author and inclusion or exclusion of potentially relevant trials was agreed by two authors. Data was extracted by one author and checked by another. The main outcome measure was abstinence from smoking after at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. We calculated the risk ratio (RR) and 95% confidence interval (CI) for each study. Where appropriate, we performed meta-analysis using a Mantel-Haenszel fixed-effect model. Main results: Fifty-three studies with a total of more than 25,000 participants met the inclusion criteria. A large proportion of studies recruited people in healthcare settings or with specific health needs. Most studies provided NRT. Behavioural support was typically provided by specialists in cessation counselling, who offered between four and eight contact sessions. The planned maximum duration of contact was typically more than 30 minutes but less than 300 minutes. Overall, studies were at low or unclear risk of bias, and findings were not sensitive to the exclusion of any of the six studies rated at high risk of bias in one domain. One large study (the Lung Health Study) contributed heterogeneity due to a substantially larger treatment effect than seen in other studies (RR 3.88, 95% CI 3.35 to 4.50). Since this study used a particularly intensive intervention which included extended availability of nicotine gum, multiple group sessions and long term maintenance and recycling contacts, the results may not be comparable with the interventions used in other studies, and hence it was not pooled in other analyses. Based on the remaining 52 studies (19,488 participants) there was high quality evidence (using GRADE) for a benefit of combined pharmacotherapy and behavioural treatment compared to usual care, brief advice or less intensive behavioural support (RR 1.83, 95% CI 1.68 to 1.98) with moderate statistical heterogeneity (I² = 36%).The pooled estimate for 43 trials that recruited participants in healthcare settings (RR 1.97, 95% CI 1.79 to 2.18) was higher than for eight trials with community-based recruitment (RR 1.53, 95% CI 1.33 to 1.76). Compared to the first version of the review, previous weak evidence of differences in other subgroup analyses has disappeared. We did not detect differences between subgroups defined by motivation to quit, treatment provider, number or duration of support sessions, or take-up of treatment. Authors' conclusions: Interventions that combine pharmacotherapy and behavioural support increase smoking cessation success compared to a minimal intervention or usual care. Updating this review with an additional 12 studies (5,000 participants) did not materially change the effect estimate. Although trials differed in the details of their populations and interventions, we did not detect any factors that modified treatment effects apart from the recruitment setting. We did not find evidence from indirect comparisons that offering more intensive behavioural support was associated with larger treatment effects.

The Cochrane database of systematic reviews · meta-analysis · 337 citationsread the source →

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

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

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

Which behaviour change techniques within interventions to prevent weight gain and/or initiate weight loss improve adiposity outcomes in young adults? A systematic review and meta-analysis of randomized controlled trials.

Young adulthood is associated with the highest rate of weight gain compared with any other adult age group. This review evaluates the effectiveness of interventions with adiposity outcomes among young adults and identifies which behaviour change techniques (BCTs) are most effective. BCT utilization was assessed using Michie's 93-item BCT Taxonomy v1. Six electronic databases were searched for randomized controlled trials assessing change in adiposity in young adults (17-35 years) until December 2019; identifying 21,582 articles. Fifty-one studies were included. Meta-analyses for weight (n=19 studies), body mass index (BMI) (n=20 studies), and waist circumference (n=10 studies) demonstrated no significant between-group differences at ≤3 or >3 months. There were no differences between interventions focusing on weight loss or weight-gain prevention. Narrative synthesis showed significant between-group differences in weight change, favouring the intervention in 14/43 (33%) studies. In studies assessing BMI and waist circumference, this was 31% (11/36) and 25% (4/16). Two BCTs had a percentage effectiveness ratio >50% in weight loss interventions; social support (unspecified) and self-monitoring behaviour, and one in weight-gain prevention interventions; and goal-setting (outcome). Findings demonstrate initial potential for these types of BCTs and can help build cumulative evidence towards delivering effective, cost-efficient, and replicable interventions.

Obesity reviews : an official journal of the International Association for the Study of Obesity · meta-analysis · 45 citationsread the source →

Physical activity and exercise for chronic pain in adults: an overview of Cochrane Reviews.

Background: Chronic pain is defined as pain lasting beyond normal tissue healing time, generally taken to be 12 weeks. It contributes to disability, anxiety, depression, sleep disturbances, poor quality of life, and healthcare costs. Chronic pain has a weighted mean prevalence in adults of 20%.For many years, the treatment choice for chronic pain included recommendations for rest and inactivity. However, exercise may have specific benefits in reducing the severity of chronic pain, as well as more general benefits associated with improved overall physical and mental health, and physical functioning. Physical activity and exercise programmes are increasingly being promoted and offered in various healthcare systems, and for a variety of chronic pain conditions. It is therefore important at this stage to establish the efficacy and safety of these programmes, and furthermore to address the critical factors that determine their success or failure. Objectives: To provide an overview of Cochrane Reviews of adults with chronic pain to determine (1) the effectiveness of different physical activity and exercise interventions in reducing pain severity and its impact on function, quality of life, and healthcare use; and (2) the evidence for any adverse effects or harm associated with physical activity and exercise interventions. Methods: We searched theCochrane Database of Systematic Reviews (CDSR) on the Cochrane Library (CDSR 2016, Issue 1) for systematic reviews of randomised controlled trials (RCTs), after which we tracked any included reviews for updates, and tracked protocols in case of full review publication until an arbitrary cut-off date of 21 March 2016 (CDSR 2016, Issue 3). We assessed the methodological quality of the reviews using the AMSTAR tool, and also planned to analyse data for each painful condition based on quality of the evidence. We extracted data for (1) self-reported pain severity, (2) physical function (objectively or subjectively measured), (3) psychological function, (4) quality of life, (5) adherence to the prescribed intervention, (6) healthcare use/attendance, (7) adverse events, and (8) death. Due to the limited data available, we were unable to directly compare and analyse interventions, and have instead reported the evidence qualitatively. Main results: We included 21 reviews with 381 included studies and 37,143 participants. Of these, 264 studies (19,642 participants) examined exercise versus no exercise/minimal intervention in adults with chronic pain and were used in the qualitative analysis. Pain conditions included rheumatoid arthritis, osteoarthritis, fibromyalgia, low back pain, intermittent claudication, dysmenorrhoea, mechanical neck disorder, spinal cord injury, postpolio syndrome, and patellofemoral pain. None of the reviews assessed 'chronic pain' or 'chronic widespread pain' as a general term or specific condition. Interventions included aerobic, strength, flexibility, range of motion, and core or balance training programmes, as well as yoga, Pilates, and tai chi. Reviews were well performed and reported (based on AMSTAR), and included studies had acceptable risk of bias (with inadequate reporting of attrition and reporting biases). However the quality of evidence was low due to participant numbers (most included studies had fewer than 50 participants in total), length of intervention and follow-up (rarely assessed beyond three to six months). We pooled the results from relevant reviews where appropriate, though results should be interpreted with caution due to the low quality evidence. Pain severity: several reviews noted favourable results from exercise: only three reviews that reported pain severity found no statistically significant changes in usual or mean pain from any intervention. However, results were inconsistent across interventions and follow-up, as exercise did not consistently bring about a change (positive or negative) in self-reported pain scores at any single point. Physical function: was the most commonly reported outcome measure. Physical function was significantly improved as a result of the intervention in 14 reviews, though even these statistically significant results had only small-to-moderate effect sizes (only one review reported large effect sizes). Psychological function and quality of life: had variable results: results were either favourable to exercise (generally small and moderate effect size, with two reviews reporting significant, large effect sizes for quality of life), or showed no difference between groups. There were no negative effects. Adherence to the prescribed intervention: could not be assessed in any review. However, risk of withdrawal/dropout was slightly higher in the exercising group (82.8/1000 participants versus 81/1000 participants), though the group difference was non-significant. Healthcare use/attendance: was not reported in any review. Adverse events, potential harm, and death: only 25% of included studies (across 18 reviews) actively reported adverse events. Based on the available evidence, most adverse events were increased soreness or muscle pain, which reportedly subsided after a few weeks of the intervention. Only one review reported death separately to other adverse events: the intervention was protective against death (based on the available evidence), though did not reach statistical significance. Authors' conclusions: The quality of the evidence examining physical activity and exercise for chronic pain is low. This is largely due to small sample sizes and potentially underpowered studies. A number of studies had adequately long interventions, but planned follow-up was limited to less than one year in all but six reviews. There were some favourable effects in reduction in pain severity and improved physical function, though these were mostly of small-to-moderate effect, and were not consistent across the reviews. There were variable effects for psychological function and quality of life. The available evidence suggests physical activity and exercise is an intervention with few adverse events that may improve pain severity and physical function, and consequent quality of life. However, further research is required and should focus on increasing participant numbers, including participants with a broader spectrum of pain severity, and lengthening both the intervention itself, and the follow-up period.

The Cochrane database of systematic reviews · meta-analysis · 484 citationsread the source →

Comparison of paediatric emergency department visits for attempted suicide, self-harm, and suicidal ideation before and during the COVID-19 pandemic: a systematic review and meta-analysis.

Background: There is a lack of consensus about the effect of the COVID-19 pandemic on the mental health of children and adolescents. We aimed to compare rates of paediatric emergency department visits for attempted suicide, self-harm, and suicidal ideation during the pandemic with those before the pandemic. Methods: For this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO for studies published between Jan 1, 2020, and Dec 19, 2022. Studies published in English with data on paediatric (ie, those aged <19 years) emergency department visits before and during the COVID-19 pandemic were included. Case studies and qualitative analyses were excluded. Changes in attempted suicide, self-harm, suicidal ideation, and other mental-illness indicators (eg, anxiety, depression, and psychosis) were expressed as ratios of the rates of emergency department visits during the pandemic compared with those before the pandemic, and we analysed these with a random-effects meta-analysis. This study was registered with PROSPERO, CRD42022341897. Findings: 10 360 non-duplicate records were retrieved, which yielded 42 relevant studies (with 130 sample-estimates) representing 11·1 million emergency department visits for all indications of children and adolescents across 18 countries. The mean age of the samples of children and adolescents across studies was 11·7 years (SD 3·1, range 5·5-16·3), and there were on average 57·6% girls and 43·4% boys as a proportion of emergency department visits for any health reasons (ie, physical and mental). Only one study had data related to race or ethnicity. There was good evidence of an increase in emergency department visits for attempted suicide during the pandemic (rate ratio 1·22, 90% CI 1·08-1·37), modest evidence of an increase in emergency department visits for suicidal ideation (1·08, 0·93-1·25), and good evidence for only a slight change in self-harm (0·96, 0·89-1·04). Rates of emergency department visits for other mental-illness indications showed very good evidence of a decline (0·81, 0·74-0·89), and paediatric visits for all health indications showed strong evidence of a reduction (0·68, 0·62-0·75). When rates for attempted suicide and suicidal ideation were combined as a single measure, there was good evidence of an increase in emergency department visits among girls (1·39, 1·04-1·88) and only modest evidence of an increase among boys (1·06, 0·92-1·24). Self-harm among older children (mean age 16·3 years, range 13·0-16·3) showed good evidence of an increase (1·18, 1·00-1·39), but among younger children (mean age 9·0 years, range 5·5-12·0) there was modest evidence of a decrease (0·85, 0·70-1·05). Interpretation: The integration of mental health support within community health and the education system-including promotion, prevention, early intervention, and treatment-is urgently needed to increase the reach of mental health support that can mitigate child and adolescent mental distress. In future pandemics, increased resourcing in some emergency department settings would help to address their expected increase in visits for acute mental distress among children and adolescents. Funding: None.

The lancet. Psychiatry · meta-analysis · 164 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 →

COVID-19 pandemic and mental health consequences: Systematic review of the current evidence.

Background: During the COVID-19 pandemic general medical complications have received the most attention, whereas only few studies address the potential direct effect on mental health of SARS-CoV-2 and the neurotropic potential. Furthermore, the indirect effects of the pandemic on general mental health are of increasing concern, particularly since the SARS-CoV-1 epidemic (2002-2003) was associated with psychiatric complications. Methods: We systematically searched the database Pubmed including studies measuring psychiatric symptoms or morbidities associated with COVID-19 among infected patients and among none infected groups the latter divided in psychiatric patients, health care workers and non-health care workers. Results: A total of 43 studies were included. Out of these, only two studies evaluated patients with confirmed COVID-19 infection, whereas 41 evaluated the indirect effect of the pandemic (2 on patients with preexisting psychiatric disorders, 20 on medical health care workers, and 19 on the general public). 18 of the studies were case-control studies/compared to norm, while 25 of the studies had no control groups. The two studies investigating COVID-19 patients found a high level of post-traumatic stress symptoms (PTSS) (96.2%) and significantly higher level of depressive symptoms (p = 0.016). Patients with preexisting psychiatric disorders reported worsening of psychiatric symptoms. Studies investigating health care workers found increased depression/depressive symptoms, anxiety, psychological distress and poor sleep quality. Studies of the general public revealed lower psychological well-being and higher scores of anxiety and depression compared to before COVID-19, while no difference when comparing these symptoms in the initial phase of the outbreak to four weeks later. A variety of factors were associated with higher risk of psychiatric symptoms and/or low psychological well-being including female gender, poor-self-related health and relatives with COVID-19. Conclusion: Research evaluating the direct neuropsychiatric consequences and the indirect effects on mental health is highly needed to improve treatment, mental health care planning and for preventive measures during potential subsequent pandemics.

Brain, behavior, and immunity · systematic review · 1974 citationsread the source →

Prevalence and associated factors of mental and substance use problems among adults in Kenya: A community-based cross-sectional study.

Data on the burden and determinants of mental and substance use problems among women in urban and rural informal settlements in Kenya is sparse, thus limiting preventive and treatment efforts in these areas. To bridge the gap, we (a) determined the prevalence of depressive, anxiety and post-traumatic stress disorder (PTSD) symptoms and alcohol and drug use problems among women compared to their spouses and (b) examined the correlates of these outcomes. Data collection for this cross-sectional survey was conducted in 2022 in Mombasa, Kwale and Nairobi counties in Kenya. A total of 1528 adults (1048 women) took part. The 9-Item Patient Health Questionnaire, 7-Item Generalized Anxiety Disorder Scale, Primary Care PTSD Screen for DSM-5, Alcohol Use Disorders Identification Test, and Drug Use Disorders Identification Test were administered alongside other measures. Logistic regression was used to examine the correlates of mental and substance use problems. Overall, the prevalence of mental and substance use problems among women and men respectively was 28% (95% CI 25, 31%) vs 22% (95% CI 18, 26%) [depressive symptoms], 12% (95% CI 10, 14%) vs 8% (95% CI 6, 11%) [general anxiety symptoms], 22% (95% CI 19, 24%) vs 21% (95% CI 17, 25%) [PTSD symptoms], 4% (95% CI 3, 5%) vs 15% (95% CI 12, 19%) [alcohol use problems], and 2% (95% CI 1, 3%) vs 12% (95% CI 9, 15%) [drug use problems]. The prevalence of depressive and anxiety symptoms was significantly higher among women compared to their male counterparts. On the other hand, both current and past-year alcohol and drug use were significantly higher in men than women. Among women, stressful life events, urban residence, food insecurity, family debt, unemployment, poor self-rated health, poor eyesight, and higher educational level were the correlates for elevated depressive, anxiety and PTSD symptoms. Conversely, sexual abuse, living in rented houses, urban residence, verbal abuse, stressful life events, and somatic complaints were the correlates for depressive, anxiety and PTSD symptoms in men. Correlates against mental health problems included social support, higher subjective wellbeing, older age (>50 years), increased vigorous exercise and higher household income (in both sexes). Correlates for current alcohol use in women included stressful life events, urban residence, being sexually active, and living in a single family. Among men, higher household income was associated with current alcohol use. Correlates against current alcohol use included being married, living in a larger household (>5), being a Muslim and having multimorbidity (in both sexes). Correlates for current drug use included unemployment and sexual abuse. Female sex was associated with reduced odds of current drug use. The prevalence of depressive, anxiety and PTSD symptoms, and alcohol use problems is high in the study setting. However, needs vary by gender and study location, highlighting the importance of targeted approaches in mental health services. Our results also highlight the need for integrating mental health services into existing primary care as well as testing and scaling multi-component mental health interventions in this population.

PLOS global public healthread the source →

Prenatal maternal stress programs infant stress regulation.

Objective: Prenatal exposure to inappropriate levels of glucocorticoids (GCs) and maternal stress are putative mechanisms for the fetal programming of later health outcomes. The current investigation examined the influence of prenatal maternal cortisol and maternal psychosocial stress on infant physiological and behavioral responses to stress. Methods: The study sample comprised 116 women and their full term infants. Maternal plasma cortisol and report of stress, anxiety and depression were assessed at 15, 19, 25, 31 and 36 + weeks' gestational age. Infant cortisol and behavioral responses to the painful stress of a heel-stick blood draw were evaluated at 24 hours after birth. The association between prenatal maternal measures and infant cortisol and behavioral stress responses was examined using hierarchical linear growth curve modeling. Results: A larger infant cortisol response to the heel-stick procedure was associated with exposure to elevated concentrations of maternal cortisol during the late second and third trimesters. Additionally, a slower rate of behavioral recovery from the painful stress of a heel-stick blood draw was predicted by elevated levels of maternal cortisol early in pregnancy as well as prenatal maternal psychosocial stress throughout gestation. These associations could not be explained by mode of delivery, prenatal medical history, socioeconomic status or child race, sex or birth order. Conclusions: These data suggest that exposure to maternal cortisol and psychosocial stress exerts programming influences on the developing fetus with consequences for infant stress regulation.

Journal of child psychology and psychiatry, and allied disciplines · 336 citationsread the source →

Childhood trauma is associated with hypothalamic-pituitary-adrenal axis responsiveness in irritable bowel syndrome.

Background & aims: A history of early adverse life events (EALs) is associated with a poorer outcome and higher levels of distress in adult patients with functional gastrointestinal disorders. An EAL is thought to predispose individuals to develop a range of chronic illnesses by inducing persistent changes in the central stress response systems, including the hypothalamic-pituitary-adrenal (HPA) axis. We sought to determine if EALs affect the HPA axis response to a visceral stressor in irritable bowel syndrome (IBS) patients and healthy controls, and to determine if this is affected by sex or related to symptoms or quality of life. Methods: Forty-four IBS patients (25 women, 19 men) and 39 healthy controls (21 women, 18 men) were assessed for gastrointestinal and psychological symptoms and EALs by validated questionnaires and interview. All subjects underwent a visceral stressor (sigmoidoscopy). Salivary cortisol was collected at baseline and serially for 1 hour poststressor. Results: Twenty-one IBS patients and 18 controls had EALs. In subjects with and without IBS, an EAL was associated with higher mean (+/-SD) cortisol levels (0.32 +/- 0.2 vs 0.20 +/- 0.1 microg/dL; P = .003) and higher area under the curve (28.1 +/- 17 vs 18.6 +/- 13 microg x min/dL; P = .005) after the stressor compared with subjects without EALs. In IBS, a faster resolution of cortisol to basal values corresponded to lower symptom severity (r = -0.36, P < .05) and better disease-specific quality of life (r = 0.33, P < .05). Conclusions: HPA axis hyperresponsiveness to a visceral stressor is related more to a history of EALs than to the presence of IBS. However, HPA axis reactivity has a moderating effect on IBS symptoms.

Gastroenterology · 153 citationsread the source →

Rates and risk factors for nonadherence to the medical regimen after adult solid organ transplantation.

Background: Despite the impact of medical regimen nonadherence on health outcomes after organ transplantation, there is mixed and conflicting evidence regarding the prevalence and predictors of posttransplant nonadherence. Clinicians require precise information on nonadherence rates in order to evaluate patients' risks for this problem. Methods: A total of 147 studies of kidney, heart, liver, pancreas/kidney-pancreas, or lung/heart-lung recipients published between 1981 and 2005 were included in a meta-analysis. Average nonadherence rates were calculated for 10 areas of the medical regimen. Correlations between nonadherence and patient psychosocial risk factors were examined. Results: Across all types of transplantation, average nonadherence rates ranged from 1 to 4 cases per 100 patients per year (PPY) for substance use (tobacco, alcohol, illicit drugs), to 19 to 25 cases per 100 PPY for nonadherence to immunosuppressants, diet, exercise, and other healthcare requirements. Rates varied significantly by transplant type in two areas: immunosuppressant nonadherence was highest in kidney recipients (36 cases per 100 PPY vs. 7 to 15 cases in other recipients). Failure to exercise was highest in heart recipients (34 cases per 100 PPY vs. 9 to 22 cases in other recipients). Demographics, social support, and perceived health showed little correlation with nonadherence. Pretransplant substance use predicted posttransplant use. Conclusions: The estimated nonadherence rates, overall and by transplant type, allow clinicians to gauge patient risk and target resources accordingly. Nonadherence rates in some areas--including immunosuppressant use--appear unacceptably high. Weak correlations of most patient psychosocial factors with nonadherence suggest that attention should focus on other classes of variables (e.g., provider-related and systems-level factors), which may be more influential.

Transplantation · 400 citationsread the source →

Mindfulness in primary school children as a route to enhanced life satisfaction, positive outlook and effective emotion regulation

BACKGROUND: Mindfulness programmes as a potential avenue of enhancing pupil wellbeing are beginning to show great promise. However, research concerning the effectiveness of mindfulness training for primary aged school children (7-11 years of age) has been neglected. METHODS: Building on methodological limitations of prior research, this study employed an active controlled design to assess the longer term wellbeing and emotion regulation outcomes after a 6 week mindfulness programme (Living Mindfully Programme, UK), for a group of school children aged between 9 and 10. The programme was delivered by class teachers as part of their normal curriculum entitlement. One hundred and eight children took part from across three schools in North East of England. Participants formed a treatment group (n = 64), active control (n = 19) and wait list control (n = 25). Self-report measures of wellbeing, mindfulness and emotion regulation were collected at pre and post training as well as at 3 months follow up. RESULTS: Reliable findings, judged by medium to large effect sizes across both post intervention, follow-up and between both controls, demonstrated enhancement in a number of domains. Immediately after training and follow up, when compared with the wait list control, children who received mindfulness training showed significant improvements in mindfulness (d = .76 and .77), Positive Outlook (d = .55 and .64) and Life Satisfaction (d = .65 and 0.72). Even when compared to an active control, the effects remained although diminished reflecting the positive impact of the active control condition. Furthermore, a significant positive relationship was found between changes in mindfulness and changes in cognitive reappraisal. CONCLUSIONS: Taken together, this study provides preliminary evidence that the Living Mindfully Primary Programme is feasibly delivered by school staff, enjoyed by the children and may significantly improve particular components of wellbeing. Importantly, higher levels of mindfulness as a result of training may be related to effective emotional regulatory and cognitive reappraisal strategies.

BMC Psychology · 61 citationsread the source →

A mixed methods systematic review of studies examining the relationship between housing and health for people from refugee and asylum seeking backgrounds.

Housing is an important social determinant of health and a key element of refugee integration into countries of resettlement. However, the way in which housing may affect mental and physical health for refugees and asylum seekers has not been systematically examined. This systematic review aimed to explore the effects of housing on health and wellbeing for this population, in order to identify key pathways for public health interventions. The review was undertaken following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Social Care Institute for Excellence (SCIE) guidelines. We identified publications through a search of Medline, PsychInfo, Scopus, Web of Science, Embase, CINAHL, Cohrane Library, Google, ProQuest, OpenGrey, MedNar and WHOLIS. Eligibility criteria included: publication in English between 1997 and 2017, with findings pertaining to the relationship between housing and health for refugees and/or asylum seekers. Out of 2371 items, 25 papers were included with a further five identified through reference lists. Eleven of the papers explored housing and health for those refugees and asylum seekers living within refugee camps, with 19 focusing on countries of resettlement. All studies identified housing issues for refugees and asylum seekers, with physical housing conditions particularly poor in refugee camps, and issues of affordability, suitability, insecure tenure and mobility as well as difficulties securing housing also highlighted in countries of resettlement. Consistent relationships were found between physical aspects of housing and physical and mental health, with other aspects of housing such as safety and overcrowding linked to mental health. There were a number of methodological issues with most of the studies, making it difficult to specify precise pathways. However, improvements to housing quality particularly in refugee camps, and targeted housing interventions more generally for refugees and asylum seekers would likely have an important public health benefit.

Social science & medicine (1982) · systematic review · 46 citationsread the source →

Exercise-based cardiac rehabilitation for coronary heart disease.

Background: Coronary heart disease (CHD) is the most common cause of death globally. However, with falling CHD mortality rates, an increasing number of people living with CHD may need support to manage their symptoms and prognosis. Exercise-based cardiac rehabilitation (CR) aims to improve the health and outcomes of people with CHD. This is an update of a Cochrane Review previously published in 2016. Objectives: To assess the clinical effectiveness and cost-effectiveness of exercise-based CR (exercise training alone or in combination with psychosocial or educational interventions) compared with 'no exercise' control, on mortality, morbidity and health-related quality of life (HRQoL) in people with CHD. Search methods: We updated searches from the previous Cochrane Review, by searching CENTRAL, MEDLINE, Embase, and two other databases in September 2020. We also searched two clinical trials registers in June 2021. Selection criteria: We included randomised controlled trials (RCTs) of exercise-based interventions with at least six months' follow-up, compared with 'no exercise' control. The study population comprised adult men and women who have had a myocardial infarction (MI), coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI), or have angina pectoris, or coronary artery disease. Data collection and analysis: We screened all identified references, extracted data and assessed risk of bias according to Cochrane methods. We stratified meta-analysis by duration of follow-up: short-term (6 to 12 months); medium-term (> 12 to 36 months); and long-term ( > 3 years), and used meta-regression to explore potential treatment effect modifiers. We used GRADE for primary outcomes at 6 to 12 months (the most common follow-up time point).  MAIN RESULTS: This review included 85 trials which randomised 23,430 people with CHD. This latest update identified 22 new trials (7795 participants). The population included predominantly post-MI and post-revascularisation patients, with a mean age ranging from 47 to 77 years. In the last decade, the median percentage of women with CHD has increased from 11% to 17%, but females still account for a similarly small percentage of participants recruited overall ( < 15%). Twenty-one of the included trials were performed in low- and middle-income countries (LMICs). Overall trial reporting was poor, although there was evidence of an improvement in quality over the last decade. The median longest follow-up time was 12 months (range 6 months to 19 years). At short-term follow-up (6 to 12 months), exercise-based CR likely results in a slight reduction in all-cause mortality (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.73 to 1.04; 25 trials; moderate certainty evidence), a large reduction in MI (RR 0.72, 95% CI 0.55 to 0.93; 22 trials; number needed to treat for an additional beneficial outcome (NNTB) 75, 95% CI 47 to 298; high certainty evidence), and a large reduction in all-cause hospitalisation (RR 0.58, 95% CI 0.43 to 0.77; 14 trials;  NNTB 12, 95% CI 9 to 21; moderate certainty evidence). Exercise-based CR likely results in little to no difference in risk of cardiovascular mortality (RR 0.88, 95% CI 0.68 to 1.14; 15 trials; moderate certainty evidence), CABG (RR 0.99, 95% CI 0.78 to 1.27; 20 trials; high certainty evidence), and PCI (RR 0.86, 95% CI 0.63 to 1.19; 13 trials; moderate certainty evidence) up to 12 months' follow-up. We are uncertain about the effects of exercise-based CR on cardiovascular hospitalisation, with a wide confidence interval including considerable benefit as well as harm (RR 0.80, 95% CI 0.41 to 1.59; low certainty evidence). There was evidence of substantial heterogeneity across trials for cardiovascular hospitalisations (I2 = 53%), and of small study bias for all-cause hospitalisation, but not for all other outcomes. At medium-term follow-up, although there may be little to no difference in all-cause mortality (RR 0.90, 95% CI 0.80 to 1.02; 15 trials), MI (RR 1.07, 95% CI 0.91 to 1.27; 12 trials), PCI (RR 0.96, 95% CI 0.69 to 1.35; 6 trials), CABG (RR 0.97, 95% CI 0.77 to 1.23; 9 trials), and all-cause hospitalisation (RR 0.92, 95% CI 0.82 to 1.03; 9 trials), a large reduction in cardiovascular mortality was found (RR 0.77, 95% CI 0.63 to 0.93; 5 trials). Evidence is uncertain for difference in risk of cardiovascular hospitalisation (RR 0.92, 95% CI 0.76 to 1.12; 3 trials). At long-term follow-up, although there may be little to no difference in all-cause mortality (RR 0.91, 95% CI 0.75 to 1.10), exercise-based CR may result in a large reduction in cardiovascular mortality (RR 0.58, 95% CI 0.43 to 0.78; 8 trials) and MI (RR 0.67, 95% CI 0.50 to 0.90; 10 trials). Evidence is uncertain for CABG (RR 0.66, 95% CI 0.34 to 1.27; 4 trials), and PCI (RR 0.76, 95% CI 0.48 to 1.20; 3 trials). Meta-regression showed benefits in outcomes were independent of CHD case mix, type of CR, exercise dose, follow-up length, publication year, CR setting, study location, sample size or risk of bias. There was evidence that exercise-based CR may slightly increase HRQoL across several subscales (SF-36 mental component, physical functioning, physical performance, general health, vitality, social functioning and mental health scores) up to 12 months' follow-up; however, these may not be clinically important differences. The eight trial-based economic evaluation studies showed exercise-based CR to be a potentially cost-effective use of resources in terms of gain in quality-adjusted life years (QALYs). Authors' conclusions: This updated Cochrane Review supports the conclusions of the previous version, that exercise-based CR provides important benefits to people with CHD, including reduced risk of MI, a likely small reduction in all-cause mortality, and a large reduction in all-cause hospitalisation, along with associated healthcare costs, and improved HRQoL up to 12 months' follow-up. Over longer-term follow-up, benefits may include reductions in cardiovascular mortality and MI. In the last decade, trials were more likely to include females, and be undertaken in LMICs, increasing the generalisability of findings. Well-designed, adequately-reported RCTs of CR in people with CHD more representative of usual clinical practice are still needed. Trials should explicitly report clinical outcomes, including mortality and hospital admissions, and include validated HRQoL outcome measures, especially over longer-term follow-up, and assess costs and cost-effectiveness.

The Cochrane database of systematic reviews · systematic review · 330 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 →

Global, regional, and national incidence and mortality burden of non-COVID-19 lower respiratory infections and aetiologies, 1990-2021: a systematic analysis from the Global Burden of Disease Study 2021.

Background: Lower respiratory infections (LRIs) are a major global contributor to morbidity and mortality. In 2020-21, non-pharmaceutical interventions associated with the COVID-19 pandemic reduced not only the transmission of SARS-CoV-2, but also the transmission of other LRI pathogens. Tracking LRI incidence and mortality, as well as the pathogens responsible, can guide health-system responses and funding priorities to reduce future burden. We present estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 of the burden of non-COVID-19 LRIs and corresponding aetiologies from 1990 to 2021, inclusive of pandemic effects on the incidence and mortality of select respiratory viruses, globally, regionally, and for 204 countries and territories. Methods: We estimated mortality, incidence, and aetiology attribution for LRI, defined by the GBD as pneumonia or bronchiolitis, not inclusive of COVID-19. We analysed 26 259 site-years of mortality data using the Cause of Death Ensemble model to estimate LRI mortality rates. We analysed all available age-specific and sex-specific data sources, including published literature identified by a systematic review, as well as household surveys, hospital admissions, health insurance claims, and LRI mortality estimates, to generate internally consistent estimates of incidence and prevalence using DisMod-MR 2.1. For aetiology estimation, we analysed multiple causes of death, vital registration, hospital discharge, microbial laboratory, and literature data using a network analysis model to produce the proportion of LRI deaths and episodes attributable to the following pathogens: Acinetobacter baumannii, Chlamydia spp, Enterobacter spp, Escherichia coli, fungi, group B streptococcus, Haemophilus influenzae, influenza viruses, Klebsiella pneumoniae, Legionella spp, Mycoplasma spp, polymicrobial infections, Pseudomonas aeruginosa, respiratory syncytial virus (RSV), Staphylococcus aureus, Streptococcus pneumoniae, and other viruses (ie, the aggregate of all viruses studied except influenza and RSV), as well as a residual category of other bacterial pathogens. Findings: Globally, in 2021, we estimated 344 million (95% uncertainty interval [UI] 325-364) incident episodes of LRI, or 4350 episodes (4120-4610) per 100 000 population, and 2·18 million deaths (1·98-2·36), or 27·7 deaths (25·1-29·9) per 100 000. 502 000 deaths (406 000-611 000) were in children younger than 5 years, among which 254 000 deaths (197 000-320 000) occurred in countries with a low Socio-demographic Index. Of the 18 modelled pathogen categories in 2021, S pneumoniae was responsible for the highest proportions of LRI episodes and deaths, with an estimated 97·9 million (92·1-104·0) episodes and 505 000 deaths (454 000-555 000) globally. The pathogens responsible for the second and third highest episode counts globally were other viral aetiologies (46·4 million [43·6-49·3] episodes) and Mycoplasma spp (25·3 million [23·5-27·2]), while those responsible for the second and third highest death counts were S aureus (424 000 [380 000-459 000]) and K pneumoniae (176 000 [158 000-194 000]). From 1990 to 2019, the global all-age non-COVID-19 LRI mortality rate declined by 41·7% (35·9-46·9), from 56·5 deaths (51·3-61·9) to 32·9 deaths (29·9-35·4) per 100 000. From 2019 to 2021, during the COVID-19 pandemic and implementation of associated non-pharmaceutical interventions, we estimated a 16·0% (13·1-18·6) decline in the global all-age non-COVID-19 LRI mortality rate, largely accounted for by a 71·8% (63·8-78·9) decline in the number of influenza deaths and a 66·7% (56·6-75·3) decline in the number of RSV deaths. Interpretation: Substantial progress has been made in reducing LRI mortality, but the burden remains high, especially in low-income and middle-income countries. During the COVID-19 pandemic, with its associated non-pharmaceutical interventions, global incident LRI cases and mortality attributable to influenza and RSV declined substantially. Expanding access to health-care services and vaccines, including S pneumoniae, H influenzae type B, and novel RSV vaccines, along with new low-cost interventions against S aureus, could mitigate the LRI burden and prevent transmission of LRI-causing pathogens. Funding: Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care (UK).

The Lancet. Infectious diseases · systematic review · 388 citationsread the source →

School Closures During Social Lockdown and Mental Health, Health Behaviors, and Well-being Among Children and Adolescents During the First COVID-19 Wave: A Systematic Review.

Importance: School closures as part of broader social lockdown measures during the COVID-19 pandemic may be associated with the health and well-being of children and adolescents. Objective: To review published reports on the association of school closures during broader social lockdown with mental health, health behaviors, and well-being in children and adolescents aged 0 to 19 years, excluding associations with transmission of infection. Evidence review: Eleven databases were searched from inception to September 2020, and machine learning was applied for screening articles. A total of 16 817 records were screened, 151 were reviewed in full text, and 36 studies were included. Quality assessment was tailored to study type. A narrative synthesis of results was undertaken because data did not allow meta-analysis. Findings: A total of 36 studies from 11 countries were identified, involving a total of 79 781 children and adolescents and 18 028 parents, which occurred during the first wave of the COVID-19 pandemic (February to July 2020). All evaluated school closure as part of broader social lockdown during the first COVID-19 wave, and the duration of school closure ranged from 1 week to 3 months. Of those, 9 (25%) were longitudinal pre-post studies, 5 (14%) were cohort, 21 (58%) were cross-sectional, and 1 (3%) was a modeling study. Thirteen studies (36%) were high quality, 17 (47%) were medium quality, and 6 (17%) were low quality. Twenty-three studies (64%) were published, 8 (22%) were online reports, and 5 (14%) were preprints. Twenty-five studies (69%) concerning mental health identified associations across emotional, behavioral, and restlessness/inattention problems; 18% to 60% of children and adolescents scored above risk thresholds for distress, particularly anxiety and depressive symptoms, and 2 studies reported no significant association with suicide. Three studies reported that child protection referrals were lower than expected number of referrals originating in schools. Three studies suggested higher screen time usage, 2 studies reported greater social media use, and 6 studies reported lower physical activity. Studies on sleep (10 studies) and diet (5 studies) provided inconclusive evidence on harms. Conclusions and relevance: In this narrative synthesis of reports from the first wave of the COVID-19 pandemic, studies of short-term school closures as part of social lockdown measures reported adverse mental health symptoms and health behaviors among children and adolescents. Associations between school closure and health outcomes and behaviors could not be separated from broader lockdown measures.

JAMA pediatrics · systematic review · 426 citationsread the source →

Peer support interventions for parents and carers of children with complex needs.

Background: Parents and family carers of children with complex needs experience a high level of pressure to meet children's needs while maintaining family functioning and, as a consequence, often experience reduced well-being and elevated psychological distress. Peer support interventions are intended to improve parent and carer well-being by enhancing the social support available to them. Support may be delivered via peer mentoring or through support groups (peer or facilitator led). Peer support interventions are widely available, but the potential benefits and risks of such interventions are not well established. Objectives: To assess the effects of peer support interventions (compared to usual care or alternate interventions) on psychological and psychosocial outcomes, including adverse outcomes, for parents and other family carers of children with complex needs in any setting. Search methods: We searched the following resources. • Cochrane Central Register of Controlled Trials (CENTRAL; latest issue: April 2014), in the Cochrane Library. • MEDLINE (OvidSP) (1966 to 19 March 2014). • Embase (OvidSP) (1974 to 18 March 2014). • Journals@OVID (22 April 2014). • PsycINFO (OvidSP) (1887 to 19 March 2014). • BiblioMap (EPPI-Centre, Health Promotion Research database) (22 April 2014). • ProQuest Dissertations and Theses (26 May 2014). • metaRegister of Controlled Trials (13 May 2014). We conducted a search update of the following databases. • MEDLINE (OvidSP) (2013 to 20 February 2018) (search overlapped to 2013). • PsycINFO (ProQuest) (2013 to 20 February 2018). • Embase (Elsevier) (2013 to 21 February 2018). We handsearched the reference lists of included studies and four key journals (European Child and Adolescent Psychiatry: 31 March 2015; Journal of Autism and Developmental Disorders: 30 March 2015; Diabetes Educator: 7 April 2015; Journal of Intellectual Disability Research: 13 April 2015). We contacted key investigators and consulted key advocacy groups for advice on identifying unpublished data. We ran updated searches on 14 August 2019 and on 25 May 2021. Studies identified in these searches as eligible for full-text review are listed as "Studies awaiting classification" and will be assessed in a future update. Selection criteria: Randomised and cluster randomised controlled trials (RCTs and cluster RCTs) and quasi-RCTs were eligible for inclusion. Controlled before-and-after and interrupted time series studies were eligible for inclusion if they met criteria set by the Cochrane Effective Practice and Organisation of Care Review Group. The comparator could be usual care or an alternative intervention. The population eligible for inclusion consisted of parents and other family carers of children with any complex needs. We applied no restriction on setting. Data collection and analysis: Inclusion decisions were made independently by two  authors, with differences resolved by a third  author. Extraction to data extraction templates was conducted independently by two authors and cross-checked. Risk of bias assessments were made independently by two authors and were reported according to Cochrane guidelines. All measures of treatment effect were continuous and were analysed in Review Manager version 5.3. GRADE assessments were undertaken independently by two review authors, with differences resolved by discussion. Main results: We included 22 studies (21 RCTs, 1 quasi-RCT) of 2404 participants. Sixteen studies compared peer support to usual care; three studies compared peer support to an alternative intervention and to usual care but only data from the usual care arm contributed to results; and three studies compared peer support to an alternative intervention only. We judged risk of bias as moderate to high across all studies, particularly for selection, performance, and detection bias. Included studies contributed data to seven effect estimates compared to usual care: psychological distress (standardised mean difference (SMD) -0.10, 95% confidence interval (CI) -0.32 to 0.11; 8 studies, 864 participants), confidence and self-efficacy (SMD 0.04, 95% CI -0.14 to 0.21; 8 studies, 542 participants), perception of coping (SMD -0.08, 95% CI -0.38 to 0.21; 3 studies, 293 participants), quality of life and life satisfaction (SMD 0.03, 95% CI -0.32 to 0.38; 2 studies, 143 participants), family functioning (SMD 0.15, 95% CI -0.09 to 0.38; 4 studies, 272 participants), perceived social support (SMD 0.31, 95% CI -0.15 to 0.77; 4 studies, 191 participants), and confidence and skill in navigating medical services (SMD 0.05, 95% CI -0.17 to 0.28; 4 studies, 304 participants). In comparisons to alternative interventions, one pooled effect estimate was possible: psychological distress (SMD 0.2, 95% CI -0.38 to 0.79; 2 studies, 95 participants). No studies reported on adverse outcomes. All narratively synthesised data for psychological distress (compared to usual care - 2 studies), family functioning (compared to usual care - 1 study; compared to an alternative intervention - 1 study), perceived social support (compared to usual care - 2 studies), and self-efficacy (compared to alternative interventions - 1 study) were equivocal. Comparisons with usual care showed no difference between intervention and control groups (perceived social support), some effect over time for both groups but more effect for intervention (distress), or mixed effects for intervention (family function). Comparisons with alternative interventions showed no difference between the intervention of interest and the alternative. This may indicate similar effects to the intervention of interest or lack of effect of both, and we are  uncertain which option is likely. We found no clear evidence of effects of peer support interventions on any parent outcome, for any comparator; however, the certainty of evidence for each outcome was low to very low, and true effects may differ substantially from those reported here. We found no evidence of adverse events such as mood contagion,  negative group interactions, or worsened psychological health. Qualitative data suggest that parents and carers value peer support interventions and appreciate emotional support. Authors' conclusions: Parents and carers of children with complex needs perceive peer support interventions as valuable, but this review found no evidence of either benefit or harm. Currently, there is uncertainty about the effects of peer support interventions for parents and carers of children with complex needs. However, given the overall low to very low certainty of available evidence, our estimates showing no effects of interventions may very well change with further research of higher quality.

The Cochrane database of systematic reviews · systematic review · 51 citationsread the source →

Helping themselves to get pregnant: a qualitative longitudinal study on the information-seeking behaviour of infertile couples.

Background: Couples seeking infertility treatment are generally hungry for information about available therapeutic options and how to help themselves achieve pregnancy. This study examined couples' perceptions of the information available from various sources in the context of achieved pregnancy or continuing treatment. Methods: A 3 year prospective interview study started in April 2004, following couples undergoing infertility treatment at a tertiary fertility clinic at Aberdeen Maternity Hospital. Fifty-four couples were invited to participate. Up to three semi-structured interviews took place, and were analysed thematically using a variation of grounded theory. Results: Twenty-seven couples agreed to participate and of the 25 couples followed up, 11 were diagnosed with unexplained infertility. The age range of the women was 22-41 years. All hoped to be given information on helping themselves to achieve pregnancy, spontaneous or assisted, and 19 of the 25 couples became pregnant. Most couples were dissatisfied with the written and verbal information routinely provided by the fertility clinic because it suggested lifestyle changes they had already attempted to adopt. They sought additional information from the internet, books and magazines. Those who became pregnant were generally empowered by the experience and thought that it had helped them to conceive. Women who were still undergoing treatment however, sometimes became distressed, blaming themselves for failing to follow the lifestyle advice provided. Conclusions: Couples, especially those diagnosed with unexplained infertility, seek information to help themselves conceive, but only those who succeed find it an empowering experience.

Human reproduction (Oxford, England) · 49 citationsread the source →

Treatment for overweight and obesity in adult populations: a systematic review and meta-analysis.

Background: Obesity is a major public health issue. This review updates the evidence on the effectiveness of behavioural and pharmacologic treatments for overweight and obesity in adults. Methods: We updated the search conducted in a previous review. Randomized trials of primary-care-relevant behavioural (diet, exercise and lifestyle) and pharmacologic (orlistat and metformin) with or without behavioural treatments in overweight and obese adults were included if 12-month, postbaseline data were provided for weight outcomes. Studies reporting harms were included regardless of design. Data were extracted and pooled wherever possible for 5 weight outcomes, 6 secondary health outcomes and 4 adverse events categories. Results: We identified 68 studies, most consisted of short-term (≤ 12 mo) treatments using diet (n = 8), exercise (n = 4), diet and exercise (n = 10), lifestyle (n = 19), orlistat (n = 25) or metformin (n = 4). Compared with the control groups, intervention participants had a greater weight loss of -3.02 kg (95% confidence interval [CI] -3.52 to -2.52), a greater reduction in waist circumference of -2.78 cm (95% CI -3.34 to -2.22) and a greater reduction in body mass index of -1.11 kg/m(2) (95% CI -1.39 to -0.84). The relative risk for loss of ≥ 5% body weight was 1.77 (95% CI 1.58-1.99, [number needed to treat 5, 95% CI 4-7]), and the relative risk for loss of ≥ 10% body weight was 1.91 (95% CI 1.69-2.16, [number needed to treat 9, 95% CI 7-12]). Incidence of type 2 diabetes was lower among pre-diabetic intervention participants (relative risk 0.62 [95% CI 0.50-0.77], number needed to treat 17 [95% CI 13-29]). With prevalence rates for type 2 diabetes on the rise, weight loss coupled with a reduction in the incidence of type 2 diabetes could potentially have a significant benefit on population health and a possible reduction in need for drug treatments for glycemic control. Interpretation: There is moderate quality evidence that behavioural and pharmacologic plus behvioural, treatments for overweight and obesity in adults lead to clinically important reductions in weight and incidence of type 2 diabetes in pre-diabetic populations. Registration: PROSPERO no. CRD42012002753.

CMAJ open · 58 citationsread the source →

Disasters and youth: a meta-analytic examination of posttraumatic stress.

Objective: Meta-analyze the literature on posttraumatic stress (PTS) symptoms in youths post-disaster. Method: Meta-analytic synthesis of the literature (k = 96 studies; Ntotal = 74,154) summarizing the magnitude of associations between disasters and youth PTS, and key factors associated with variations in the magnitude of these associations. We included peer-reviewed studies published prior to 1/1/2009 that quantitatively examined youth PTS (≤ 18 years at event) after a distinct and identifiable disaster. Results: Despite variability across studies, disasters had a significant effect on youth PTS (small-to-medium magnitude; rpooled = .19, SEr = .03; d = 0.4). Female gender (rpooled = .14), higher death toll (disasters of death toll ≤ 25: rpooled = .09; vs. disasters with ≥ 1,000 deaths: rpooled = .22), child proximity (rpooled = .33), personal loss (rpooled = .16), perceived threat (rpooled = .34), and distress (rpooled = .38) at time of event were each associated with increased PTS. Studies conducted within 1 year post-disaster, studies that used established measures, and studies that relied on child-report data identified a significant effect. Conclusion: Youths are vulnerable to appreciable PTS after disaster, with pre-existing child characteristics, aspects of the disaster experience, and study methodology each associated with variations in the effect magnitude. Findings underscore the importance of measurement considerations in post-disaster research. Areas in need of research include the long-term impact of disasters, disaster-related media exposure, prior trauma and psychopathology, social support, ethnicity/race, prejudice, parental psychopathology, and the effects of disasters in developing regions of the world. Policy and clinical implications are discussed.

Journal of consulting and clinical psychology · meta-analysis · 208 citationsread the source →

The ENCOURAGE mortality risk score and analysis of long-term outcomes after VA-ECMO for acute myocardial infarction with cardiogenic shock.

Purpose: This study was designed to identify factors associated with in-intensive care unit (ICU) death and develop a practical mortality risk score for venoarterial-extracorporeal membrane oxygenation (VA-ECMO)-treated acute myocardial infarction (AMI) patients. Long-term survivors' health-related quality of life (HRQOL), anxiety, depression, and post-traumatic stress disorder (PTSD) frequencies were also assessed. Methods: Data from 138 ECMO-treated AMI patients admitted to two French ICUs (2008-2013) were analyzed. ICU survivors contacted >6 months post-ICU discharge were assessed for HRQOL, psychological and PTSD status. Results: Sixty-five patients (47%) survived to ICU discharge. On the basis of multivariable logistic regression analyses, the ENCOURAGE score was constructed with seven pre-ECMO parameters: age >60, female sex, body mass index >25 kg/m(2), Glasgow coma score <6, creatinine >150 μmol/L, lactate (<2, 2-8, or >8 mmol/L), and prothrombin activity <50%. Six months after ECMO, probabilities of survival were 80, 58, 25, 20, and 7% for ENCOURAGE score classes 0-12, 13-18, 19-22, 23-27, and ≥28, respectively. The ENCOURAGE score ROC AUC [0.84 (95% CI 0.77-0.91)] was significantly better than those of the SAVE, SAPS II, and SOFA scores. Survivors' HRQOL evaluated after median follow-up of 32 months revealed satisfactory mental health but persistent physical and emotional-related difficulties, with 34% (95% CI 20-49%) anxiety, 20% (95% CI 8-32%) depression, and 5% (95% CI 0-12%) PTSD symptoms reported. Conclusions: The ENCOURAGE score might be a useful tool to predict mortality of severe cardiogenic shock AMI patients who received VA-ECMO. However, it now needs prospective validation on other populations of AMI patients.

Intensive care medicine · cohort or longitudinal · 351 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 →

Combined prevention for substance use, depression, and anxiety in adolescence: a cluster-randomised controlled trial of a digital online intervention.

Background: Substance use, depression, and anxiety in adolescence are major public health problems requiring new scalable prevention strategies. We aimed to assess the effectiveness of a combined online universal (ie, delivered to all pupils) school-based preventive intervention targeting substance use, depression, and anxiety in adolescence. Methods: We did a multicentre, cluster-randomised controlled trial in secondary schools in Australia, with pupils in year 8 or 9 (aged 13-14 years). Participating schools were randomly assigned (1:1:1:1) to one of four intervention conditions: (1) Climate Schools-Substance Use, focusing on substance use only; (2) Climate Schools-Mental Health, focusing on depression and anxiety only; (3) Climate Schools-Combined, focusing on the prevention of substance use, depression, and anxiety; or (4) active control. The interventions were delivered in school classrooms in an online delivery format and used a mixture of peer cartoon storyboards and classroom activities that were focused on alcohol, cannabis, anxiety, and depression. The interventions were delivered for 2 years and primary outcomes were knowledge related to alcohol, cannabis, and mental health; alcohol use, including heavy episodic drinking; and depression and anxiety symptoms at 12, 24, and 30 months after baseline. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12613000723785) and an extended follow-up is underway. Findings: Between Sept 1, 2013, and Feb 28, 2014, we recruited 88 schools (12 391 pupils), of whom 71 schools and 6386 (51·5%) pupils were analysed (17 schools dropped out and 1308 pupils declined to participate). We allocated 18 schools (1739 [27·25%] pupils; 1690 [97·2%] completed at least one follow-up) to the substance use condition, 18 schools (1594 [25·0%] pupils; 1560 [97·9%] completed at least one follow-up) to the mental health condition, 16 schools (1497 [23·4%] pupils; 1443 [96·4%] completed at least one follow-up) to the combined condition, and 19 schools (1556 [23·4%] pupils; 1513 [97·2%] completed at least one follow-up) to the control condition. Compared with controls, the combined intervention group had increased knowledge related to alcohol and cannabis at 12, 24, and 30 months (standardised mean difference [SMD] for alcohol 0·26 [95% CI 0·14 to 0·39] and for cannabis 0·17 [0·06 to 0·28] at 30 months), increased knowledge related to mental health at 24 months (0·17 [0·08 to 0·27]), reduced growth in their odds of drinking and heavy episodic drinking at 12, 24, and 30 months (odds ratio for drinking 0·25 [95% CI 0·12 to 0·51], and for heavy episodic drinking 0·15 [0·04 to 0·58] at 30 months), and reduced increases in anxiety symptoms at 12 and 30 months (SMD -0·12 [95% CI -0·22 to -0·01] at 30 months). We found no difference in symptoms or probable diagnosis of depression. The combined intervention group also showed improvement in alcohol use outcomes compared with the substance use and mental health interventions and improvements in anxiety outcomes when compared with the mental health intervention only. Interpretation: Combined online prevention of substance use, depression, and anxiety led to increased knowledge of alcohol, cannabis, and mental health, reduced increase in the odds of any drinking and heavy episodic drinking, and reduced symptoms of anxiety over a 30-month period. These findings provide the first evidence of the effectiveness of an online universal school-based preventive intervention targeting substance use, depression, and anxiety in adolescence. Funding: Australian National Health and Medical Research Council.

The Lancet. Digital health · randomised controlled trial · 62 citationsread the source →

Guided graded exercise self-help plus specialist medical care versus specialist medical care alone for chronic fatigue syndrome (GETSET): a pragmatic randomised controlled trial.

Background: Graded exercise therapy is an effective and safe treatment for chronic fatigue syndrome, but it is therapist intensive and availability is limited. We aimed to test the efficacy and safety of graded exercise delivered as guided self-help. Methods: In this pragmatic randomised controlled trial, we recruited adult patients (18 years and older) who met the UK National Institute for Health and Care Excellence criteria for chronic fatigue syndrome from two secondary-care clinics in the UK. Patients were randomly assigned to receive specialist medical care (SMC) alone (control group) or SMC with additional guided graded exercise self-help (GES). Block randomisation (randomly varying block sizes) was done at the level of the individual with a computer-generated sequence and was stratified by centre, depression score, and severity of physical disability. Patients and physiotherapists were necessarily unmasked from intervention assignment; the statistician was masked from intervention assignment. SMC was delivered by specialist doctors but was not standardised; GES consisted of a self-help booklet describing a six-step graded exercise programme that would take roughly 12 weeks to complete, and up to four guidance sessions with a physiotherapist over 8 weeks (maximum 90 min in total). Primary outcomes were fatigue (measured by the Chalder Fatigue Questionnaire) and physical function (assessed by the Short Form-36 physical function subscale); both were self-rated by patients at 12 weeks after randomisation and analysed in all randomised patients with outcome data at follow-up (ie, by modified intention to treat). We recorded adverse events, including serious adverse reactions to trial interventions. We used multiple linear regression analysis to compare SMC with GES, adjusting for baseline and stratification factors. This trial is registered at ISRCTN, number ISRCTN22975026. Findings: Between May 15, 2012, and Dec 24, 2014, we recruited 211 eligible patients, of whom 107 were assigned to the GES group and 104 to the control group. At 12 weeks, compared with the control group, mean fatigue score was 19·1 (SD 7·6) in the GES group and 22·9 (6·9) in the control group (adjusted difference -4·2 points, 95% CI -6·1 to -2·3, p<0·0001; effect size 0·53) and mean physical function score was 55·7 (23·3) in the GES group and 50·8 (25·3) in the control group (adjusted difference 6·3 points, 1·8 to 10·8, p=0·006; 0·20). No serious adverse reactions were recorded and other safety measures did not differ between the groups, after allowing for missing data. Interpretation: GES is a safe intervention that might reduce fatigue and, to a lesser extent, physical disability for patients with chronic fatigue syndrome. These findings need confirmation and extension to other health-care settings. Funding: UK National Institute for Health Research Research for Patient Benefit Programme and the Sue Estermann Fund.

Lancet (London, England) · randomised controlled trial · 44 citationsread the source →

An internet-based intervention with brief nurse support to manage obesity in primary care (POWeR+): a pragmatic, parallel-group, randomised controlled trial.

Background: The obesity epidemic has major public health consequences. Expert dietetic and behavioural counselling with intensive follow-up is effective, but resource requirements severely restrict widespread implementation in primary care, where most patients are managed. We aimed to estimate the effectiveness and cost-effectiveness of an internet-based behavioural intervention (POWeR+) combined with brief practice nurse support in primary care. Methods: We did this pragmatic, parallel-group, randomised controlled trial at 56 primary care practices in central and south England. Eligible adults aged 18 years or older with a BMI of 30 kg/m(2) or more (or ≥28 kg/m(2) with hypertension, hypercholesterolaemia, or diabetes) registered online with POWeR+-a 24 session, web-based, weight management intervention lasting 6 months. After registration, the website automatically randomly assigned patients (1:1:1), via computer-generated random numbers, to receive evidence-based dietetic advice to swap foods for similar, but healthier, choices and increase fruit and vegetable intake, in addition to 6 monthly nurse follow-up (control group); web-based intervention and face-to-face nurse support (POWeR+Face-to-face [POWeR+F]; up to seven nurse contacts over 6 months); or web-based intervention and remote nurse support (POWeR+Remote [POWeR+R]; up to five emails or brief phone calls over 6 months). Participants and investigators were masked to group allocation at the point of randomisation; masking of participants was not possible after randomisation. The primary outcome was weight loss averaged over 12 months. We did a secondary analysis of weight to measure maintenance of 5% weight loss at months 6 and 12. We modelled the cost-effectiveness of each intervention. We did analysis by intention to treat, with multiple imputation for missing data. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN21244703. Findings: Between Jan 30, 2013, and March 20, 2014, 818 participants were randomly assigned to the control group (n=279), the POWeR+F group (n=269), or the POWeR+R group (n=270). Weight loss averaged over 12 months was recorded in 666 (81%) participants. The control group lost almost 3 kg over 12 months (crude mean weight: baseline 104·38 kg [SD 21·11; n=279], 6 months 101·91 kg [19·35; n=136], 12 months 101·74 kg [19·57; n=227]). The primary imputed analysis showed that compared with the control group, patients in the POWeR+F group achieved an additional weight reduction of 1·5 kg (95% CI 0·6-2·4; p=0·001) averaged over 12 months, and patients in the POWeR+R group achieved an additional 1·3 kg (0·34-2·2; p=0·007). 21% of patients in the control group had maintained a clinically important 5% weight reduction at month 12, compared with 29% of patients in the POWeR+F group (risk ratio 1·56, 0·96-2·51; p=0·070) and 32% of patients in the POWeR+R group (1·82, 1·31-2·74; p=0·004). The incremental overall cost to the health service per kg weight lost with the POWeR+ interventions versus the control strategy was £18 (95% CI -129 to 195) for POWeR+F and -£25 (-268 to 157) for POWeR+R; the probability of being cost-effective at a threshold of £100 per kg lost was 88% and 98%, respectively. No adverse events were reported. Interpretation: Weight loss can be maintained in some individuals by use of novel written material with occasional brief nurse follow-up. However, more people can maintain clinically important weight reductions with a web-based behavioural program and brief remote follow-up, with no increase in health service costs. Future research should assess the extent to which clinically important weight loss can be maintained beyond 1 year. Funding: Health Technology Assessment Programme of the National Institute for Health Research.

The lancet. Diabetes & endocrinology · randomised controlled trial · 85 citationsread the source →

Effect of Long-term Supplementation With Marine Omega-3 Fatty Acids vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial.

Importance: Marine omega-3 fatty acid (omega-3) supplements have been used to treat depression but their ability to prevent depression in the general adult population is unknown. Objective: To test effects of omega-3 supplementation on late-life depression risk and mood scores. Design, setting, and participants: A total of 18 353 adults participated in the VITAL-DEP (Vitamin D and Omega-3 Trial-Depression Endpoint Prevention) ancillary study to VITAL, a randomized trial of cardiovascular disease and cancer prevention among 25 871 US adults. There were 16 657 at risk of incident depression (no previous depression) and 1696 at risk of recurrent depression (previous depression, but not for the past 2 years). Randomization occurred from November 2011 through March 2014; randomized treatment ended on December 31, 2017. Interventions: Randomized 2 × 2 factorial assignment to vitamin D3 (2000 IU/d), marine omega-3 fatty acids (1 g/d of fish oil, including 465 mg of eicosapentaenoic acid and 375 mg of docosahexaenoic acid) or placebo; 9171 were randomized to omega-3 and 9182 were randomized to matching placebo. Main outcomes and measures: Prespecified coprimary outcomes were risk of depression or clinically relevant depressive symptoms (total of incident + recurrent cases); mean difference in mood score (8-item Patient Health Questionnaire [PHQ-8] depression scale). Results: Among 18 353 participants who were randomized (mean age, 67.5 [SD, 7.1] years; 49.2% women), 90.3% completed the trial (93.5% among those alive at the end of the trial); the median treatment duration was 5.3 years. The test for interaction between the omega-3 and the vitamin D agents was not significant (P for interaction = .14). Depression risk was significantly higher comparing omega-3 (651 events, 13.9 per 1000 person-years) with placebo (583 events, 12.3 per 1000 person-years; hazard ratio [HR], 1.13; 95% CI, 1.01-1.26; P = .03). No significant differences were observed comparing omega-3 with placebo groups in longitudinal mood scores: the mean difference in change in PHQ-8 score was 0.03 points (95% CI, -0.01 to 0.07; P = .19). Regarding serious and common adverse events, the respective prevalence values in omega-3 vs placebo groups were major cardiovascular events (2.7% vs 2.9%), all-cause mortality (3.3% vs 3.1%), suicide (0.02% vs 0.01%), gastrointestinal bleeding (2.6% vs 2.7%), easy bruising (24.8% vs 25.1%), and stomach upset or pain (35.2% vs 35.1%). Conclusions and relevance: Among adults aged 50 years or older without clinically relevant depressive symptoms at baseline, treatment with omega-3 supplements compared with placebo yielded mixed results, with a small but statistically significant increase in risk of depression or clinically relevant depressive symptoms but no difference in mood scores, over a median follow-up of 5.3 years. These findings do not support the use of omega-3 supplements in adults to prevent depression. Trial registration: ClinicalTrials.gov Identifiers: NCT01696435 and NCT01169259.

JAMA · randomised controlled trial · 85 citationsread the source →

Early liver transplantation for severe alcohol-related hepatitis not responding to medical treatment: a prospective controlled study.

Background: Early liver transplantation for severe alcohol-related hepatitis is an emerging treatment option. We aimed to assess the risk of alcohol relapse 2 years after early liver transplantation for alcohol-related hepatitis compared with liver transplantation for alcohol-related cirrhosis after at least 6 months of abstinence. Methods: We conducted a multicentre, non-randomised, non-inferiority, controlled study in 19 French and Belgian hospitals. All participants were aged 18 years or older. There were three groups of patients recruited prospectively: patients with severe alcohol-related hepatitis who did not respond to medical treatment and were eligible for early liver transplantation according to a new selection scoring system based on social and addiction items that can be quantified in points (early transplantation group); patients with alcohol-related cirrhosis listed for liver transplantation after at least 6 months of abstinence (standard transplantation group); patients with severe alcohol-related hepatitis not responding to medical treatment not eligible for early liver transplantation according to the selection score (not eligible for early transplantation group), this group did not enter any further liver transplantation processes. We also defined a historical control group of patients with severe alcohol-related hepatitis unresponsive to medical therapy and non-transplanted. The primary outcome was the non-inferiority of 2-year rate of alcohol relapse after transplantation in the early transplantation group compared with the standard transplantation group using the alcohol timeline follow back (TLFB) method and a prespecified non-inferiority margin of 10%. Secondary outcomes were the pattern of alcohol relapse, 2-year survival rate post-transplant in the early transplantation group compared with the standard transplantation group, and 2-year overall survival in the early transplantation group compared with patients in the not eligible for early transplantation group and historical controls. This trial is registered with ClinicalTrials.gov, NCT01756794. Findings: Between Dec 5, 2012, and June 30, 2016, we included 149 patients with severe alcohol-related hepatitis: 102 in the early transplantation group and 47 in the not eligible for early transplantation group. 129 patients were included in the standard transplantation group. 68 patients in the early transplantation group and 93 patients in the standard transplantation group received a liver transplant. 23 (34%) patients relapsed in the early transplantation group, and 23 (25%) patients relapsed in the standard transplantation group; therefore, the non-inferiority of early transplantation versus standard transplantation was not demonstrated (absolute difference 9·1% [95% CI -∞ to 21·1]; p=0·45). The 2-year rate of high alcohol intake was greater in the early transplantation group than the standard transplantation group (absolute difference 16·7% [95% CI 5·8-27·6]) The time spent drinking alcohol was not different between the two groups (standardised difference 0·24 [95% CI -0·07 to 0·55]), but the time spent drinking a large quantity of alcohol was higher in the early transplantation group than the standard transplantation group (standardised difference 0·50 [95% CI 0·17-0·82]). 2-year post-transplant survival was similar between the early transplantation group and the standard transplantation group (hazard ratio [HR] 0·87 [95% CI 0·33-2·26]); 2-year overall survival was higher in the early transplantation group than the not eligible for early transplantation group and historical controls (HR 0·27 [95% CI 0·16-0·47] and 0·21 [0·13-0·32]). Interpretation: We cannot conclude non-inferiority in terms of rate of alcohol relapse post-transplant between early liver transplantation and standard transplantation. High alcohol intake is more frequent after early liver transplantation. This prospective controlled study confirms the important survival benefit related to early liver transplantation for severe alcohol-related hepatitis; and this study provides objective data on survival and alcohol relapse to tailor the management of patients with severe alcohol-related hepatitis. Funding: The present study has been granted by the French Ministry of Health-Programme Hospitalier de Recherche Clinique 2010.

The lancet. Gastroenterology & hepatology · randomised controlled trial · 103 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 →