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Efficacy and safety of the muscarinic receptor agonist KarXT (xanomeline-trospium) in schizophrenia (EMERGENT-2) in the USA: results from a randomised, double-blind, placebo-controlled, flexible-dose phase 3 trial.

Background: New treatments with new mechanisms are urgently needed for people with schizophrenia. Xanomeline is a dual M1 and M4-preferring muscarinic receptor agonist that does not block D2 dopamine receptors, unlike all currently approved treatments for schizophrenia. Xanomeline-trospium (KarXT) combines xanomeline with the peripherally restricted muscarinic receptor antagonist trospium chloride with the goal of ameliorating xanomeline-related adverse events associated with peripheral muscarinic receptors. The EMERGENT-2 trial aimed to assess the efficacy and safety of KarXT in people with schizophrenia experiencing acute psychosis. Methods: EMERGENT-2 was a randomised, double-blind, placebo-controlled, flexible-dose, 5-week, inpatient, phase 3 trial in people with schizophrenia. Participants were adults aged 18-65 years with a diagnosis of schizophrenia who had a recent worsening of psychosis warranting hospital admission, a Positive and Negative Syndrome Scale (PANSS) score of 80 or higher, and a Clinical Global Impression-Severity score of 4 or higher. The participants were recruited from 22 inpatient sites in the USA, and were randomly assigned (1:1) to KarXT or placebo twice per day. Participants randomly assigned to KarXT received 50 mg xanomeline and 20 mg trospium twice per day for the first 2 days and then 100 mg xanomeline and 20 mg trospium twice per day for days 3-7. Beginning on day 8, KarXT dosing was flexible with an optional increase to 125 mg xanomeline and 30 mg trospium twice per day and the option to return to 100 mg xanomeline and 20 mg trospium based on tolerability. The primary endpoint was change from baseline to week 5 in PANSS total score. Efficacy analyses used the modified intention-to-treat population (all randomly assigned participants who received at least one trial medication dose and had at least one post-baseline PANSS assessment). Least squares mean change from baseline, SE, and least squares mean difference between the KarXT and placebo groups at week 5, along with the 95% CI and two-sided p values were calculated for the primary and secondary continuous efficacy endpoints. Safety analyses included all participants receiving at least one trial medication dose and used descriptive statistics. This trial is registered with ClinicalTrials.gov (NCT04659161). Findings: From Dec 16, 2020, to April 13, 2022, of 407 people who were screened, 252 participants meeting enrolment criteria were randomly assigned to the KarXT (n=126) or placebo (n=126). Baseline PANSS total scores were 98·3 (KarXT; n=126) and 97·9 (placebo; n=125). The trial met the primary endpoint with a mean change from baseline to week 5 in PANSS total score that favoured KarXT (-21·2 points, SE 1·7) versus placebo (-11·6 points, 1·6; least squares mean difference -9·6; 95% CI -13·9 to -5·2; p<0·0001, Cohen's d effect size=0·61). All secondary endpoints were also met, and favoured KarXT versus placebo (p<0·05). The most common adverse events with KarXT versus placebo were constipation (27 [21%] vs 13 [10%]), dyspepsia (24 [19%] vs 10 [8%]), headache (17 [14%] vs 15 [12%]), nausea (24 [19%] vs seven [6%]), vomiting (18 [14%] vs one [1%]), hypertension (12 [10%] vs one [1%]), dizziness (11 [9%] vs four [3%]), gastro-oesophageal reflux disease (eight [6%] vs zero [0%]), and diarrhoea (seven [6%] vs four [3%]). Treatment-emergent adverse event rates of extrapyramidal motor symptoms (KarXT, zero [0%] vs placebo, zero [0%]), akathisia (one [1%] vs one [1%]), weight gain (zero [0%] vs one [1%]), and somnolence (six [5%] vs five [4%]) were similar between the KarXT and placebo groups, as were adverse event-related discontinuation rates (nine [7%] vs seven [6%]). Interpretation: In the EMERGENT-2 trial, KarXT was effective in reducing positive and negative symptoms and was generally well tolerated. These results support the potential for KarXT to represent a new class of effective and well tolerated antipsychotic medicines based on activating muscarinic receptors, not the D2 dopamine receptor-blocking mechanism of all current antipsychotic medications. Results from additional trials, including the identical EMERGENT-3 trial and the 52-week, open-label EMERGENT-4 and EMERGENT-5 trials, will provide additional information on the efficacy and safety of KarXT in people with schizophrenia. Funding: Karuna Therapeutics.

Lancet (London, England) · randomised controlled trial · 144 citationsread the source →

Effects of pollution on adolescent mental health: a systematic review protocol.

Background: Whilst there is little uncertainty about the deleterious impact of pollution on human and planetary health, pollution's impact on adolescent mental health is less well understood. This is particularly true for young people in underdeveloped and developing world contexts, about whom research is generally lacking. Furthermore, although adolescent resilience continues to be a research priority, little attention has been paid to adolescent pathways of resilience in the face or aftermath of pollution exposure. The objective of this study will be to examine the associations between pollution and mental health in 10- to 24-year-olds (i.e. adolescents). Methods: We designed and registered a study protocol for a systematic review of studies which link pollution and mental health in adolescents. We will include observational studies (e.g. cohort, case-control, time series analyses) that assess the associations between exposure to any form of pollution and the mental health of 10- to 24-year-olds. The primary outcome will be symptoms associated with neurodevelopmental disorders; disruptive, impulse-control, and conduct disorders; depressive disorders; anxiety disorders; substance disorders; and schizophrenia. No secondary outcomes will be considered. Literature searches will be conducted in multiple electronic databases (from inception onwards), including PubMed, MEDLINE, SCOPUS, Web of Science, CINAHL, PsycINFO, SciELO, ERIC, and Africa-Wide. Two investigators will independently screen all citations, full-text articles, and abstract data. The methodological quality (or bias) of included studies will be appraised using appropriate tools. We will provide a narrative synthesis of the evidence. Discussion: This systematic review will evaluate the evidence on the associations between pollution and the mental health of 10- to 24-year-olds. Our findings will be of potential interest to multiple audiences (including adolescent patients/clients, their families, caregivers, healthcare professionals, scientists, and policy makers) and could be used to develop prevention and intervention strategies as well as focus future research. Results will be published in a peer-reviewed journal. Systematic review registration: PROSPERO CRD42020176664.

Systematic reviews · 4 citationsread the source →

Religiosity and spirituality in the prevention and management of depression and anxiety in young people: a systematic review and meta-analysis.

Historically, religion has had a central role in shaping the psychosocial and moral development of young people. While religiosity and spirituality have been linked to positive mental health outcomes in adults, their role during the developmental context of adolescence, and the mechanisms through which such beliefs might operate, is less well understood. Moreover, there is some evidence that negative aspects of religiosity are associated with poor mental health outcomes. Guided by lived experience consultants, we undertook a systematic review and quality appraisal of 45 longitudinal studies and 29 intervention studies identified from three electronic databases (Medline, PsycINFO and Scopus) exploring the role of religiosity and spiritual involvement (formal and informal) in prevention and management of depression and anxiety in young people aged 10 to 24 years. Most studies were from high-income countries and of low to moderate quality. Meta-analysis of high-quality longitudinal studies (assessed using Joanna Briggs Institute critical appraisal tools, n = 25) showed a trend towards association of negative religious coping (i.e., feeling abandoned by or blaming God) with greater depressive symptoms over time (Pearson's r = 0.09, 95% confidence interval (CI) -0.009, 0.188) whereas spiritual wellbeing was protective against depression (Pearson's r = -0.153, CI -0.187, -0.118). Personal importance of religion was not associated with depressive symptoms overall (Pearson's r = -0.024, CI-0.053, 0.004). Interventions that involved religious and spiritual practices for depression and anxiety in young people were mostly effective, although the study quality was typically low and the heterogeneity in study designs did not allow for a meta-analysis. The lived experience consultants described spirituality and religious involvement as central to their way of life and greatly valued feeling watched over during difficult times. While we require more evidence from low- and middle-income countries, in younger adolescents and for anxiety disorders, the review provides insight into how spirituality and religious involvement could be harnessed to design novel psychological interventions for depression and anxiety in young people. Review RegistrationThe systematic review was funded by Wellcome Trust Mental Health Priority Area 'Active Ingredients' 2021 commission and registered with PROSPERO 2021 (CRD42021281912).

BMC psychiatry · meta-analysis · 46 citationsread the source →

Antenatal breastfeeding education for increasing breastfeeding duration.

Background: Breast milk is well recognised as the best food source for infants. The impact of antenatal breastfeeding (BF) education on the duration of BF has not been evaluated. Objectives: To assess the effectiveness of antenatal breastfeeding (BF) education for increasing BF initiation and duration. Search methods: We searched Cochrane Pregnancy and Childbirth's Trials Register on 1 March 2016, CENTRAL (The Cochrane Library, 2016, Issue 3), MEDLINE (1966 to 1 March 2016) and Scopus (January 1985 to 1 March 2016). We contacted experts and searched reference lists of retrieved articles. Selection criteria: All identified published, unpublished and ongoing randomised controlled trials (RCTs) assessing the effect of formal antenatal BF education or comparing two different methods of formal antenatal BF education, on the duration of BF. We included RCTs that only included antenatal interventions and excluded those that combined antenatal and intrapartum or postpartum BF education components. Cluster-randomised trials were included in this review. Quasi-randomised trials were not eligible for inclusion. Data collection and analysis: We assessed all potential studies identified as a result of the search strategy. Two review authors extracted data from each included study using the agreed form and assessed risk of bias. We resolved discrepancies through discussion. We assessed the quality of the evidence using the GRADE approach. Main results: This review update includes 24 studies (10,056 women). Twenty studies (9789 women) contribute data to analyses. Most studies took place in high-income countries such as the USA, UK, Canada and Australia. In the first five comparisons, we display the included trials according to type of intervention without pooling data. For the 'Summary of findings' we pooled data for a summary effect. Five included studies were cluster-randomised trials: all of these adjusted data and reported adjustments as odds ratios (OR). We have analysed the data using the generic inverse variance method and presented results as odds ratios, because we were unable to derive a cluster-adjusted risk ratio from the published cluster-trial. We acknowledge that the use of odds ratio prevents the pooling of these cluster trials in our main analyses. One method of BF education with standard (routine) careThere were no group differences for duration of any BF in days or weeks. There was no evidence that interventions improved the proportion of women with any BF or exclusive BF at three or six months. Single trials of different interventions were unable to show that education improved initiation of BF, apart from one small trial at high risk of attrition bias. Many trial results marginally favoured the intervention but had wide confidence intervals crossing the line of no effect. BF complications such as mastitis and other BF problems were similar in treatment arms in single trials reporting these outcomes. Multiple methods of BF education versus standard careFor all trials included in this comparison we have presented the cluster-adjusted odds ratios as reported in trial publications. One three-arm study found the intervention of BF booklet plus video plus Lactation Consultant versus standard care improved the proportion of women exclusively BF at three months (OR 2.60, 95% CI 1.25 to 5.40; women = 159) and marginally at six months (OR 2.40, 95% CI 1.00 to 5.76; women = 175). For the same trial, an intervention arm without a lactation consultant but with the BF booklet and video did not have the same effect on proportion of women exclusively BF at three months (OR 1.80, 95% CI 0.80 to 4.05; women = 159) or six months (OR 0.90, 95% CI 0.30 to 2.70; women = 184). One study compared monthly BF sessions and weekly cell phone message versus standard care and reported improvements in the proportion of women exclusively BF at both three and six months (three months OR 1.80, 95% CI 1.10 to 2.95; women = 390; six months OR 2.40, 95% CI 1.40 to 4.11; women = 390). One study found monthly BF sessions and weekly cell phone messages improved initiation of BF over standard care (OR 2.61, 95% CI 1.61 to 4.24; women = 380). BF education session versus standard care, pooled analyses for 'Summary of findings' (SoF)This comparison does not include cluster-randomised trials reporting adjusted odds ratios. We did not downgrade any evidence for trials' lack of blinding; no trial had adequate blinding of staff and participants. The SoF table presents risk ratios for all outcomes analysed. For proportion of women exclusively BF there is no evidence that antenatal BF education improved BF at three months (RR 1.06, 95% CI 0.90 to 1.25; women = 822; studies = 3; moderate quality evidence) or at six months (RR 1.07, 95% CI 0.87 to 1.30; women = 2161; studies = 4; moderate quality evidence). For proportion of women with any BF there were no group differences in BF at three (average RR 0.98, 95% CI 0.82 to 1.18; women = 654; studies = 2; I² = 60%; low-quality evidence) or six months (average RR 1.05, 95% CI 0.90 to 1.23; women = 1636; studies = 4; I² = 61%; high-quality evidence). There was no evidence that antenatal BF education could improve initiation of BF (average RR 1.01, 95% CI 0.94 to 1.09; women = 3505; studies = 8; I² = 69%; high-quality evidence). Where we downgraded evidence this was due to small sample size or wide confidence intervals crossing the line of no effect, or both. There was insufficient data for subgroup analysis of mother's occupation or education. Authors' conclusions: There was no conclusive evidence supporting any antenatal BF education for improving initiation of BF, proportion of women giving any BF or exclusively BF at three or six months or the duration of BF. There is an urgent need to conduct a high-quality, randomised controlled study to evaluate the effectiveness and adverse effects of antenatal BF education, especially in low- and middle-income countries. Evidence in this review is primarily relevant to high-income settings.

The Cochrane database of systematic reviews · meta-analysis · 86 citationsread the source →

Widowhood and cognitive decline in adults aged 50 and over: A systematic review and meta-analysis.

While widowhood is known to be associated with poorer physical and mental health outcomes, studies examining the association of widowhood with cognition have yielded mixed results. This review aimed to elucidate the link between widowhood and cognitive decline. A systematic search of Medline, Embase, PsycInfo, CINAHL and Scopus (until December 2020) was conducted to identify studies on the association between widowhood (vs. being married) and cognition in cognitively healthy adults aged 50 +. A cross-sectional meta-analysis (of 10 studies; n = 24,668) found a significant association of widowhood with cognition (g = - 0.36, 95% CI [- 0.47, - 0.25], p = < 0.001). Meta-regressions suggested that study design, cognitive domain measured, sample age, difference in mean age between widowed and married groups, and study continent did not account for observed heterogeneity. A longitudinal meta-analysis (of 3 studies; n = 10,378) found that the "continually widowed" group (from baseline to follow-up) showed significantly steeper declines in cognition compared to the "continually married" group (g = - 0.15, 95%CI [- 0.19, - 0.10], p = < 0.001). Findings indicate that widowhood may be a risk factor for cognitive decline. As there are no effective treatments for cognitive impairment, studying mechanisms by which widowhood might be associated with poorer cognition could inform prevention programs for those who have experienced spousal bereavement.

Ageing research reviews · meta-analysis · 33 citationsread the source →

A systematic review of the associations between biodiversity and children's mental health and wellbeing.

There is a growing interest in how exposure to biodiversity influences mental health and wellbeing; however, few studies have focused on children. The aim of this review was to identify studies that used components of biodiversity and children's health outcomes to assess if there were any themes that could be used to inform urban design and understand the mechanisms behind associations. We used a PROSPERO registered protocol to identify eligible studies following pre-defined inclusion criteria. After searching five databases, 25 studies were included in the review. From these articles we extracted data on the biodiversity exposure and mental health and wellbeing outcomes. Five categories of biodiversity exposure were identified, including species diversity (n = 1; 4%), functional diversity (n = 6; 26%), ecological community (n = 9; 36%), green space metrics (n = 4; 16%), and high-level classifications (n = 6; 24%). Children's health and wellbeing were tabulated into seven categories: play (n = 10; 40%), wellbeing (n = 6; 24%), mental health and cognitive functioning (n = 5; 20%), attention deficit hyperactivity disorder (ADHD)-related behaviours (n = 4; 16%), preferences for nature (n = 3; 12%), academic achievement (n = 2; 8%), and restoration (n = 2; 8%). The high heterogeneity of biodiversity and health measures reduced our ability to identify relationships across studies and formally test for an exposure-dose response. Future research that uses standardised and transferable biodiversity measurements at multiple scales, has stronger reporting rigour, greater consideration of potential modifiers, and increased representation of studies from the Majority World are essential for building a stronger evidence base to deliver child-centred biodiverse landscapes.

Environmental research · systematic review · 2 citationsread the source →

Parent-only interventions for childhood overweight or obesity in children aged 5 to 11 years.

Background: Child and adolescent overweight and obesity have increased globally, and are associated with short- and long-term health consequences. Objectives: To assess the efficacy of diet, physical activity and behavioural interventions delivered to parents only for the treatment of overweight and obesity in children aged 5 to 11 years. Search methods: We performed a systematic literature search of databases including the Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS as well trial registers. We checked references of identified trials and systematic reviews. We applied no language restrictions. The date of the last search was March 2015 for all databases. Selection criteria: We selected randomised controlled trials (RCTs) of diet, physical activity and behavioural interventions delivered to parents only for treating overweight or obesity in children aged 5 to 11 years. Data collection and analysis: Two review authors independently assessed trials for risk of bias and evaluated overall study quality using the GRADE instrument. Where necessary, we contacted authors for additional information. Main results: We included 20 RCTs, including 3057 participants. The number of participants ranged per trial between 15 and 645. Follow-up ranged between 24 weeks and two years. Eighteen trials were parallel RCTs and two were cluster RCTs. Twelve RCTs had two comparisons and eight RCTs had three comparisons. The interventions varied widely; the duration, content, delivery and follow-up of the interventions were heterogeneous. The comparators also differed. This review categorised the comparisons into four groups: parent-only versus parent-child, parent-only versus waiting list controls, parent-only versus minimal contact interventions and parent-only versus other parent-only interventions. Trial quality was generally low with a large proportion of trials rated as high risk of bias on individual risk of bias criteria. In trials comparing a parent-only intervention with a parent-child intervention, the body mass index (BMI) z score change showed a mean difference (MD) at the longest follow-up period (10 to 24 months) of -0.04 (95% confidence interval (CI) -0.15 to 0.08); P = 0.56; 267 participants; 3 trials; low quality evidence. In trials comparing a parent-only intervention with a waiting list control, the BMI z score change in favour of the parent-only intervention at the longest follow-up period (10-12 months) had an MD of -0.10 (95% CI -0.19 to -0.01); P = 0.04; 136 participants; 2 trials; low quality evidence. BMI z score change of parent-only interventions when compared with minimal contact control interventions at the longest follow-up period (9 to 12 months) showed an MD of 0.01 (95% CI -0.07 to 0.09); P = 0.81; 165 participants; 1 trial; low quality evidence. There were few similarities between interventions and comparators across the included trials in the parent-only intervention versus other parent-only interventions and we did not pool these data. Generally, these trials did not show substantial differences between their respective parent-only groups on BMI outcomes. Other outcomes such as behavioural measures, parent-child relationships and health-related quality of life were reported inconsistently. Adverse effects of the interventions were generally not reported, two trials stated that there were no serious adverse effects. No trials reported on all-cause mortality, morbidity or socioeconomic effects. All results need to be interpreted cautiously because of their low quality, the heterogeneous interventions and comparators, and the high rates of non-completion. Authors' conclusions: Parent-only interventions may be an effective treatment option for overweight or obese children aged 5 to 11 years when compared with waiting list controls. Parent-only interventions had similar effects compared with parent-child interventions and compared with those with minimal contact controls. However, the evidence is at present limited; some of the trials had a high risk of bias with loss to follow-up being a particular issue and there was a lack of evidence for several important outcomes. The systematic review has identified 10 ongoing trials that have a parent-only arm, which will contribute to future updates. These trials will improve the robustness of the analyses by type of comparator, and may permit subgroup analysis by intervention component and the setting. Trial reports should provide adequate details about the interventions to be replicated by others. There is a need to conduct and report cost-effectiveness analyses in future trials in order to establish whether parent-only interventions are more cost-effective than parent-child interventions.

The Cochrane database of systematic reviews · systematic review · 70 citationsread the source →

Social Media Use and Health and Well-being of Lesbian, Gay, Bisexual, Transgender, and Queer Youth: Systematic Review.

Background: Lesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals are at higher risk of poor mental health and well-being. Social media platforms can provide LGBTQ youths with a space that counters heteronormative environments and potentially supports mental health and well-being. Mental health includes an individual's state of psychological and emotional well-being and not merely the absence of mental disorders. Objective: We sought to identify how LGBTQ youths and adolescents use social media for connection with other LGBTQ peers and groups, identity development, and social support and how these affect mental health and well-being. Methods: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) procedures were used to guide this review. Searches were conducted in ACM Digital Library, CINAHL, Ovid Embase, Ovid MEDLINE, and Web of Science in March 2021. This review focused on LGBTQ youths aged 10 to 24 years. Included peer-reviewed studies must comprise social media; explore peer connection, identity development, or social support; and be published from 2012 onward. In total, 2 researchers extracted data and performed quality assessments independently using the Newcastle-Ottawa Scale for quantitative articles and the Critical Appraisal Skills Programme for qualitative articles. Qualitative synthesis was performed on articles that satisfied the eligibility criteria. Results: A total of 26 studies (n=15, 58% qualitative; n=8, 31% quantitative; n=3, 12% mixed methods) met the inclusion criteria. Of the 8 quantitative studies, 6 (75%) were cross-sectional, and 2 (25%) were cohort studies. All studies ranged from moderate to high quality. Social media was a popular tool used by LGBTQ youths to connect with LGBTQ communities. In qualitative data, we found that LGBTQ youths negotiated and explored identity and obtained support from peers on social media. Instagram, Tumblr, and Twitter were commonly used to access LGBTQ content owing to ease of anonymity. Identity management was the most studied social media affordance, important to LGBTQ youths for strategic disclosure. Key strategies for managing identities included being anonymous, censoring locations or content, restricting audiences, and using multiple accounts. Quantitative studies (3/8, 38%) showed that social media was associated with reduced mental health concerns and increased well-being among LGBTQ youths. Mental health concerns arising from social media use were attributed to discrimination, victimization, and policies that did not accommodate changed identities. Conclusions: We found that social media may support the mental health and well-being of LGBTQ youths through peer connection, identity management, and social support, but findings were limited by weaknesses in the evidence. More robust and longitudinal studies are needed to determine the relationship between social media use and LGBTQ mental health, particularly among adolescents. The findings may inform interventions to promote social media health literacy and the mental health and well-being of this vulnerable group. Trial registration: PROSPERO CRD42020222535; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=222535.

Journal of medical Internet research · systematic review · 84 citationsread the source →

A systematic review of longitudinal risk factors for loneliness in older adults.

Objectives: To effectively reduce loneliness in older adults, interventions should be based on firm evidence regarding risk factors for loneliness in that population. This systematic review aimed to identify, appraise and synthesise longitudinal studies of risk factors for loneliness in older adults. Methods: Searches were performed in June 2018 in PsycINFO, Scopus, Sociology Collection and Web of Science. Inclusion criteria were: population of older adults (M = 60+ years at outcome); longitudinal design; study conducted in an OECD country; article published in English in a peer-review journal. Article relevance and quality assessments were made by at least two independent reviewers. Results: The search found 967 unique articles, of which 34 met relevance and quality criteria. The Netherlands and the United States together contributed 19 articles; 17 analysed national samples while 7 studies provided the data for 19 articles. One of two validated scales was used to measure loneliness in 24 articles, although 10 used a single item. A total of 120 unique risk factors for loneliness were examined. Risk factors with relatively consistent associations with loneliness were: not being married/partnered and partner loss; a limited social network; a low level of social activity; poor self-perceived health; and depression/depressed mood and an increase in depression. Conclusion: Despite the range of factors examined in the reviewed articles, strong evidence for a longitudinal association with loneliness was found for relatively few, while there were surprising omissions from the factors investigated. Future research should explore longitudinal risk factors for emotional and social loneliness.

Aging & mental health · systematic review · 278 citationsread the source →

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

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

The lancet. Psychiatry · meta-analysis · 309 citationsread the source →

Drug therapy for obstructive sleep apnoea in adults.

Background: The treatment of choice for moderate to severe obstructive sleep apnoea (OSA) is continuous positive airways pressure (CPAP) via a mask during sleep. However this is not tolerated by all patients and its role in mild OSA is not proven. Drug therapy has been proposed as an alternative to CPAP in some patients with mild to moderate sleep apnoea and could be of value in patients intolerant of CPAP. A number of mechanisms have been proposed by which drugs could reduce the severity of OSA. These include an increase in tone in the upper airway dilator muscles, an increase in ventilatory drive, a reduction in the proportion of REM sleep, an increase in cholinergic tone during sleep, a reduction in airway resistance and a reduction in surface tension in the upper airway. Objectives: To determine the efficacy of drug therapies in the treatment of sleep apnoea. Search strategy: We carried out searches on the Cochrane Airways Group Specialised Register of trials. Searches were current as of July 2005. Selection criteria: Randomised, placebo controlled trials involving adult patients with confirmed OSA . We excluded trials if continuous positive airways pressure, mandibular devices or oxygen therapy were used. No restriction was placed upon publication language or trial duration. Data collection and analysis: Two reviewers independently assessed studies for inclusion, undertook data extraction according to pre-specified entry criteria, and quality assessment of studies. No response for further information was forthcoming from study authors. Results were expressed as mean differences and 95% Confidence Intervals (CI). Main results: Twenty-six trials of 21 drugs, involving 394 participants contributed data to the review. Most of the studies were small and many trials had methodological limitations. Each of the studies states that the subjects had OSA but diagnostic criteria were not always explicit and it is possible that some patients with central apnoeas may have been recruited. Six drugs had some impact on OSA severity and two altered daytime symptoms. One study reported that apnoea hypopnea index (AHI) was lower following treatment with intranasal fluticasone compared with placebo (23.3 versus 30.3) in 24 participants with sleep apnoea and rhinitis. Subjective alertness in the daytime also improved. Physostigmine gave an AHI of 41 compared to 54 on placebo (10 participants) and in a similar study Mirtazipine 15 mg produced an AHI of 13 compared to 23.7 for placebo (10 participants). Topical nasal lubricant given twice overnight resulted in an AHI of 14 compared to 24 with placebo (10 participants). These three latter studies were of single night crossover design and so there are no data on the acceptability of these treatments or their effect on symptoms. Paroxetine was shown to reduce AHI to 23.3 compared to 30.3 for placebo, most of the 20 participants tolerated the treatment but there was no improvement in daytime symptoms. Acetazolamide also reduced the AHI (one crossover trial of nine patients, mean difference 24 (95% CI 4 to 44). However there was no symptomatic benefit from the drug and it was poorly tolerated in the long term. Protriptyline led to a symptomatic improvement (improved versus not improved) in two out of three crossover trials (13 participants, Peto Odds Ratio 29.2 (95% CI 2.8 to 301.1) but there was no change in the apnoea frequency. In one trial naltrexone did reduce AHI, but total sleep time favoured placebo. No significant beneficial effects were found for medroxy progesterone, clonidine, mibefradil, cilazapril, buspirone, aminophylline, theophylline doxapram, ondansetron or sabeluzole. Authors' conclusions: There is insufficient evidence to recommend the use of drug therapy in the treatment of OSA. Small studies have reported positive effects of certain agents on short-term outcome. Certain agents have been shown to reduce the AHI in largely unselected populations with OSA by between 24 and 45%. For fluticasone, mirtazipine, physostigmine and nasal lubricant, studies of longer duration are required to establish whether this has an impact on daytime symptoms. Individual patients had more complete responses to particular drugs. It is likely that better matching of drugs to patients according to the dominant mechanism of their OSA will lead to better results and this also needs further study.

The Cochrane database of systematic reviews · meta-analysis · 52 citationsread the source →

The feasibility of low-intensity psychological therapy for depression co-occurring with autism in adults: The Autism Depression Trial (ADEPT) - a pilot randomised controlled trial.

Low-intensity cognitive behaviour therapy including behavioural activation is an evidence-based treatment for depression, a condition frequently co-occurring with autism. The feasibility of adapting low-intensity cognitive behaviour therapy for depression to meet the needs of autistic adults via a randomised controlled trial was investigated. The adapted intervention (guided self-help) comprised materials for nine individual sessions with a low-intensity psychological therapist. Autistic adults (n = 70) with depression (Patient Health Questionnaire-9 score ⩾10) recruited from National Health Service adult autism services and research cohorts were randomly allocated to guided self-help or treatment as usual. Outcomes at 10-, 16- and 24-weeks post-randomisation were blind to treatment group. Rates of retention in the study differed by treatment group with more participants attending follow-up in the guided self-help group than treatment as usual. The adapted intervention was well-received, 86% (n = 30/35) of participants attended the pre-defined 'dose' of five sessions of treatment and 71% (25/35) attended all treatment sessions. The findings of this pilot randomised controlled trial indicate that low-intensity cognitive behaviour therapy informed by behavioural activation can be successfully adapted to meet the needs of autistic people. Evaluation of the effectiveness of this intervention in a full scale randomised controlled trial is now warranted.

Autism : the international journal of research and practice · randomised controlled trial · 29 citationsread the source →

Telephone-Based Cognitive Behavioral Therapy for Insomnia in Perimenopausal and Postmenopausal Women With Vasomotor Symptoms: A MsFLASH Randomized Clinical Trial.

Importance: Effective, practical, nonpharmacologic therapies are needed to treat menopause-related insomnia symptoms in primary and women's specialty care settings. Objective: To evaluate the efficacy of telephone-based cognitive behavioral therapy for insomnia (CBT-I) vs menopause education control (MEC). Design, setting, and participants: A single-site, randomized clinical trial was conducted from September 1, 2013, to August 31, 2015, in western Washington State among 106 perimenopausal or postmenopausal women aged 40 to 65 years with moderate insomnia symptoms (Insomnia Severity Index [ISI] score, ≥12) and 2 or more daily hot flashes. Blinded assessments were conducted at baseline, 8, and 24 weeks postrandomization. An intent-to-treat analysis was conducted. Interventions: Six CBT-I or MEC telephone sessions in 8 weeks. Participants submitted weekly electronic sleep diaries and received group-specific written educational materials. The CBT-I sessions included sleep restriction, stimulus control, sleep hygiene education, cognitive restructuring, and behavioral homework; MEC sessions provided information about menopause and women's health. Main outcomes and measures: Primary outcome was scores on the ISI (score range, 0-28; scores ≥15 indicate moderate to severe insomnia). Secondary outcome was scores on the Pittsburgh Sleep Quality Index (score range, 0-21; higher scores indicate worse sleep quality). Additional outcomes included sleep and hot flash diary variables and hot flash interference. Results: At 8 weeks, ISI scores had decreased 9.9 points among 53 women receiving CBT-I (mean [SD] age, 55.0 [3.5] years) and 4.7 points among 53 women receiving MEC (age, 54.7 [4.7] years), a mean between-group difference of 5.2 points (95% CI, -6.1 to -3.3; P < .001). Pittsburgh Sleep Quality Index scores decreased 4.0 points in women receiving CBT-I and 1.4 points in women receiving MEC, a mean between-group difference of 2.7 points (95% CI, -3.9 to -1.5; P < .001). Significant group differences were sustained at 24 weeks. At 8 and 24 weeks, 33 of 47 women (70%) and 37 of 44 (84%) in the CBT-I group, respectively, had ISI scores in the no-insomnia range compared with 10 of 41 (24%) and 16 of 37 (43%) in the MEC group, respectively. The CBT-I group also had greater improvements in diary-reported sleep latency, wake time, and sleep efficiency. There were no between-group differences in frequency of daily hot flashes, but hot flash interference was significantly decreased at 8 weeks for the CBT-I group (-15.7; 95% CI, -20.4 to -11.0) compared with the MEC group (-7.1; 95% CI, -14.6 to 0.4) (P = .03), differences that were maintained at 24 weeks for the CBT-I group (-22.8; 95% CI, -28.6 to -16.9) and MEC group (-11.6; 95% CI, -19.4 to -3.8) (P = .003). Conclusions and relevance: Telephone-based CBT-I improved sleep in perimenopausal and postmenopausal women with insomnia and hot flashes. Results support further development and testing of centralized CBT-I programs for treating menopausal insomnia. Trial registration: clinicaltrials.gov Identifier: NCT01936441.

JAMA internal medicine · randomised controlled trial · 114 citationsread the source →

Computerized Cognitive Training for Amelioration of Cognitive Late Effects Among Childhood Cancer Survivors: A Randomized Controlled Trial.

Purpose: Children receiving CNS-directed therapy for cancer are at risk for cognitive problems, with few available empirically supported interventions. Cognitive problems indicate neurodevelopmental disruption that may be modifiable with intervention. This study evaluated short-term efficacy of a computerized cognitive training program and neural correlates of cognitive change. Patient and methods: A total of 68 survivors of childhood acute lymphoblastic leukemia (ALL) or brain tumor (BT) with identified cognitive deficits were randomly assigned to computerized cognitive intervention (male, n = 18; female, n = 16; ALL, n = 23; BT, n = 11; mean age ± standard deviation, 12.21 ± 2.47 years) or waitlist (male, n = 18; female, n = 16; ALL, n = 24; BT, n = 10; median age ± standard deviation, 11.82 ± 2.42 years). Intervention participants were asked to complete 25 training sessions at home with weekly, telephone-based coaching. Cognitive assessments and functional magnetic resonance imaging scans (intervention group) were completed pre- and postintervention, with immediate change in spatial span backward as the primary outcome. Results: Survivors completing the intervention (n = 30; 88%) demonstrated greater improvement than controls on measures of working memory (mean ± SEM; eg, Wechsler Intelligence Scale for Children [fourth edition; WISC-IV] spatial span backward, 3.13 ± 0.58 v 0.75 ± 0.43; P = .002; effect size [ES], 0.84), attention (eg, WISC-IV spatial span forward, 3.30 ± 0.71 v 1.25 ± 0.39; P = .01; ES, 0.65), and processing speed (eg, Conners' Continuous Performance Test hit reaction time, -2.10 ± 1.47 v 2.54 ± 1.25; P = .02; ES, .61) and showed greater reductions in reported executive dysfunction (eg, Conners' Parent Rating Scale III, -6.73 ± 1.51 v 0.41 ± 1.53; P = .002; ES, 0.84). Functional magnetic resonance imaging revealed significant pre- to post-training reduction in activation of left lateral prefrontal and bilateral medial frontal areas. Conclusion: Study findings show computerized cognitive training is feasible and efficacious for childhood cancer survivors, with evidence for training-related neuroplasticity.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology · randomised controlled trial · 119 citationsread the source →

Prebiotics and probiotics for depression and anxiety: A systematic review and meta-analysis of controlled clinical trials.

With growing interest in the gut microbiome, prebiotics and probiotics have received considerable attention as potential treatments for depression and anxiety. We conducted a random-effects meta-analysis of 34 controlled clinical trials evaluating the effects of prebiotics and probiotics on depression and anxiety. Prebiotics did not differ from placebo for depression (d = -.08, p = .51) or anxiety (d = .12, p = .11). Probiotics yielded small but significant effects for depression (d = -.24, p < .01) and anxiety (d = -.10, p = .03). Sample type was a moderator for probiotics and depression, with a larger effect observed for clinical/medical samples (d = -.45, p < .001) than community ones. This effect increased to medium-to-large in a preliminary analysis restricted to psychiatric samples (d = -.73, p < .001). There is general support for antidepressant and anxiolytic effects of probiotics, but the pooled effects were reduced by the paucity of trials with clinical samples. Additional randomized clinical trials with psychiatric samples are necessary fully to evaluate their therapeutic potential.

Neuroscience and biobehavioral reviews · meta-analysis · 360 citationsread the source →

A lay navigator-led, early palliative care intervention for African American and rural family caregivers of individuals with advanced cancer (Project Cornerstone): Results of a pilot randomized trial.

Background: The objective of this study was to assess the feasibility, acceptability, and potential efficacy of ENABLE (Educate, Nurture, Advise, Before Life Ends) Cornerstone-a lay navigator-led, early palliative care telehealth intervention for African American/Black and/or rural-dwelling family caregivers of individuals with advanced cancer (ClinicalTrials.gov identifier NCT03464188). Methods: This was a pilot randomized trial (November 2019 to March 2021). Family caregivers of patients with newly diagnosed, stage III/IV, solid-tumor cancers were randomized to receive either an intervention or usual care. Intervention caregivers were paired with a specially trained lay navigator who delivered 6 weekly, 20-minute to 60-minute telehealth coaching sessions plus monthly follow-up for 24 weeks, reviewing skills in stress management, self-care, getting help, staying organized, and future planning. Feasibility was assessed according to the completion of sessions and questionnaires (predefined as a completion rate ≥80%). Acceptability was determined through intervention participants' ratings of their likelihood of recommending the intervention. Measures of caregiver distress and quality of life were collected at 8 and 24 weeks. Results: Sixty-three family caregivers were randomized (usual care, n = 32; intervention, n = 31). Caregivers completed 65% of intervention sessions and 87% of questionnaires. Average ratings for recommending the program were 9.4, from 1 (not at all likely) to 10 (extremely likely). Over 24 weeks, the mean ± SE Hospital Anxiety and Depression Scale score improved by 0.30 ± 1.44 points in the intervention group and worsened by 1.99 ± 1.39 points in the usual care group (difference, -2.29; Cohen d, -0.32). The mean between-group difference scores in caregiver quality of life was -1.56 (usual care - intervention; d, -0.07). Similar outcome results were observed for patient participants. Conclusions: The authors piloted ENABLE Cornerstone, an intervention for African American and rural-dwelling advanced cancer family caregivers. The acceptability of the intervention and data collection rates were high, and the preliminary efficacy for caregiver distress was promising. Lay summary: To date, very few programs have been developed to support under-resourced cancer family caregivers. To address this need, the authors successfully pilot tested an early palliative care program, called Educate, Nurture, Advise, Before Life Ends (ENABLE) Cornerstone, for African American and rural family caregivers of individuals with advanced cancer. Cornerstone is led by specially trained lay people and involves a series of weekly phone sessions focused on coaching caregivers to manage stress and provide effective support to patients with cancer. The authors are now testing Cornerstone in a larger trial. If the program demonstrates benefit, it may yield a model of caregiver support that could be widely implemented.

Cancer · randomised controlled trial · 47 citationsread the source →

Cognitive-behavioural therapy for young children with anxiety disorders: Comparison of a Child + Parent condition versus a Parent Only condition.

The present study compared the efficacy of a group-based cognitive-behavioural treatment (GCBT) delivered exclusively to parents of young anxious children (between 4 and 8 years of age) with the same intervention delivered to both children and parents, relative to a Wait-list Control condition. Parents of children in the Parent Only condition (N = 25) received 10 weekly sessions of GCBT whereas children and parents in the Parent + Child condition (N = 24) each received 10 weekly sessions of GCBT. Intent-to-treat analyses indicated that both active treatment conditions were superior to the Wait-list condition (N = 11), with 55.3% of children in the Parent Only condition and 54.8% of children in the Parent + Child condition no longer meeting criteria for their principal diagnosis at post-treatment. These treatment gains were maintained in both treatment conditions at six-month and 12-month follow-up assessments. There were no significant differences between the two active conditions on other outcome measures including parental psychopathology and parenting style. However, an unexpected finding was that parenting satisfaction and to some extent parenting competence reduced significantly from pre- to post-treatment regardless of the active treatment condition. The present results suggest that GCBT delivered exclusively to parents of young anxious children may be a viable treatment alternative for improving accessibility to efficacious treatments for children with anxiety disorders and for reducing costs associated with mental health care delivery.

Behaviour research and therapy · randomised controlled trial · 67 citationsread the source →

Exercise on prescription for women aged 40-74 recruited through primary care: two year randomised controlled trial.

Objective: To assess the effectiveness of a primary care based programme of exercise on prescription among relatively inactive women over a two year period. Design: Randomised controlled trial. Setting: 17 primary care practices in Wellington, New Zealand Participants: 1089 women aged 40-74 not undertaking 30 minutes of moderate intensity physical activity on at least five days of the week Intervention: Brief physical activity intervention led by nurse with six month follow-up visit and monthly telephone support over nine months. Main outcome measure: Physical activity assessed at baseline and 12 and 24 months. Secondary outcomes were quality of life (SF-36), weight, waist circumference, blood pressure, concentrations of fasting serum lipids, glycated haemoglobin (HbA(1c)), glucose, insulin, and physical fitness. Results: Mean age was 58.9 (SD 7) years. Trial retention rates were 93% and 89% at 12 and 24 months, respectively. At baseline, 10% of intervention participants and 11% of control participants were achieving 150 minutes of at least moderate intensity physical activity a week. At 12 months rates increased to 43% and 30% and at 24 months to 39.3% and 32.8% (P<0.001), respectively. SF-36 physical functioning (P=0.03) and mental health (P<0.05) scores improved more in intervention compared with control participants, but role physical scores were significantly lower (P<0.01). There were no significant differences in clinical outcomes. More falls (P<0.001) and injuries (P=0.03) were recorded in the intervention group. Conclusions: This programme of exercise on prescription increased physical activity and quality of life over two years, although falls and injuries also increased. This finding supports the use of exercise on prescription programmes as part of population strategies to reduce physical inactivity. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ANZCTRN012605000490673.

BMJ (Clinical research ed.) · randomised controlled trial · 108 citationsread the source →

Interactions among insulin resistance, inflammation factors, obesity-related gene polymorphisms, environmental risk factors, and diet in the development of gestational diabetes mellitus.

Purpose: The aim of this study was to investigate the correlations and interactions between the polymorphisms of insulin resistance-related genes (ADIPOQ rs2241766), inflammation factors (TNF-α rs1800629, IL-6 rs1800795), obesity-related genes (GNB3 rs5443, ADRB rs1042714), and risk factors for gestational diabetes mellitus (GDM) such as diet structure in the development of GDM. Materials and methods: This research was conducted among women who visited the third-affiliate hospital of Zhengzhou University for pregnancy checkups from 1 June 2014 to 30 December 2014. Based on the results of a 75-g glucose tolerance test (OGTT), 140 pregnant women with GDM were randomly selected as a part of the GDM group and140 healthy, pregnant women as part of the control group. Relevant clinical and laboratory data for the child and the mother including her pregnancy outcomes and the delivery mode were collected for the epidemiological survey. Results: The results showed that risk factors for GDM are advanced age, the hepatitis B virus, family history of diabetes, high body mass index before pregnancy, and weight gain of ≥10 kg before 24-week gestation. We found that diet structures were severely unbalanced. The polymorphisms rs2241766 and rs5443 were found to potentially be associated with GDM; moreover, a positive interaction was demonstrated between rs2241766 and age, and a negative interaction was demonstrated with weight gain of ≥10 kg before 24-week gestation. Conclusion: Our findings demonstrate that both environmental risk factors and genetic background contribute to the development of GDM.

The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 31 citationsread the source →

Health Care Professionals' Responses to Religious or Spiritual Statements by Surrogate Decision Makers During Goals-of-Care Discussions.

Importance: Although many patients and their families view religion or spirituality as an important consideration near the end of life, little is known about the extent to which religious or spiritual considerations arise during goals-of-care conversations in the intensive care unit. Objectives: To determine how frequently surrogate decision makers and health care professionals discuss religious or spiritual considerations during family meetings in the intensive care unit and to characterize how health care professionals respond to such statements by surrogates. Design, setting, and participants: A multicenter prospective cohort study was conducted between October 8, 2009, and October 24, 2012, regarding 249 goals-of-care conversations between 651 surrogate decision makers and 441 health care professionals in 13 intensive care units across the United States. Audio-recorded conversations between surrogate decision makers and health care professionals were analyzed, transcribed, and qualitatively coded. Data analysis took place from March 10, 2012, through May 24, 2014. Exposures: Goals-of-care conferences. Main outcomes and measures: Constant comparative methods to develop a framework for coding religious and spiritual statements were applied to the transcripts. Participants completed demographic questionnaires that included religious affiliation and religiosity. Results: Of 457 surrogate decision makers, 355 (77.6%) endorsed religion or spirituality as fairly or very important in their life. Discussion of religious or spiritual considerations occurred in 40 of 249 conferences (16.1%). Surrogates were the first to raise religious or spiritual considerations in most cases (26 of 40). Surrogates' statements (n=59) fell into the following 5 main categories: references to their religious or spiritual beliefs, including miracles (n=34); religious practices (n=19); religious community (n=8); the notion that the physician is God's instrument to promote healing (n=4); and the interpretation that the end of life is a new beginning for their loved one (n=4). Some statements fell into more than 1 category. In response to surrogates' religious or spiritual statements, health care professionals redirected the conversation to medical considerations (n=15), offered to involve hospital spiritual care providers or the patient's own religious or spiritual community (n=14), expressed empathy (n=13), acknowledged surrogates' statements (n=11), or explained their own religious or spiritual beliefs (n=3). In only 8 conferences did health care professionals attempt to further understand surrogates' beliefs, for example, by asking questions about the patient's religion. Conclusions and relevance: Among a cohort of surrogate decision makers with a relatively high degree of religiosity, discussion of religious or spiritual considerations occurred in fewer than 20% of goals-of-care conferences in intensive care units, and health care professionals rarely explored the patient's or family's religious or spiritual ideas.

JAMA internal medicine · cohort or longitudinal · 94 citationsread the source →

Donepezil preserves cognition and global function in patients with severe Alzheimer disease.

Objective: To evaluate the efficacy and safety of donepezil for severe Alzheimer disease (AD). Methods: Patients with severe AD (Mini-Mental State Examination [MMSE] scores 1 to 12 and Functional Assessment Staging [FAST] scores > or =6) were enrolled in this multinational, double-blind, placebo-controlled trial at 98 sites. Patients were randomized to donepezil 10 mg daily or placebo for 24 weeks. Primary endpoints were the Severe Impairment Battery (SIB) and Clinician's Interview-Based Impression of Change-Plus caregiver input (CIBIC-Plus). Secondary endpoints included the MMSE, the Alzheimer Disease Cooperative Study-Activities of Daily Living-severe version (ADCS-ADL-sev), the Neuropsychiatric Inventory (NPI), the Caregiver Burden Questionnaire (CBQ), and the Resource Utilization for Severe Alzheimer Disease Patients (RUSP). Efficacy analyses were performed in the intent-to-treat (ITT) population using last post-baseline observation carried forward (LOCF). Safety assessments were performed for patients receiving > or =1 dose of donepezil or placebo. Results: Patients were randomized to donepezil (n = 176) or placebo (n = 167). Donepezil was superior to placebo on SIB score change from baseline to endpoint (least squares mean difference 5.32; p = 0.0001). CIBIC-Plus and MMSE scores favored donepezil at endpoint (p = 0.0473 and p = 0.0267). Donepezil was not significantly different from placebo on the ADCS-ADL-sev, NPI, CBQ, or RUSP. Adverse events reported were consistent with the known cholinergic effects of donepezil and with the safety profile in patients with mild to moderate AD. Conclusion: Patients with severe AD demonstrated greater efficacy compared to placebo on measures of cognition and global function.

Neurology · randomised controlled trial · 155 citationsread the source →

Pharmacokinetics of once-daily darunavir-ritonavir and atazanavir-ritonavir over 72 hours following drug cessation.

The object of this study was to investigate the pharmacokinetics of darunavir-ritonavir and atazanavir-ritonavir once-daily dosing over 72 h (h) following drug intake cessation. Volunteers received darunavir-ritonavir at 800 and 100 mg, respectively, once daily for 10 days, followed by a 7-day washout period, and atazanavir-ritonavir at 300 and 100 mg, respectively, once daily for 10 days. Full pharmacokinetic profiles were assessed for each phase for the 72 h following day 10. Pharmacokinetic parameters were determined over 24 h and to the last measurable concentration by noncompartmental methods. Seventeen subjects completed the study. The geometric mean (GM) terminal elimination half-life to 72 h of darunavir was 6.48 h, which was lower than the 0- to 24-h half-life (10.70 h). The terminal elimination half-life of atazanavir was 6.74 h, which was lower than the 0- to 24-h half-life (13.72 h). All subjects but one had darunavir concentrations higher than the target of 550 ng/ml for protease-resistant HIV isolates (equivalent to 10 times the protein-binding-corrected 50% inhibitory concentration [IC(50)] for wild-type virus) at 24 h postdose, and 14 out of 17 had concentrations higher than the target at 30 h postdose (GM of 1,088 and 851 ng/ml). All subjects had atazanavir concentrations above the suggested minimum effective concentration of 150 ng/ml (equivalent to 10 times the protein-binding-corrected IC(50) for wild-type virus) at 24 and 30 h postdose (GM of 693 and 392 ng/ml). Two of 17 and 5 of 17 subjects were above target at 48 h postdose while on darunavir-ritonavir and atazanavir-ritonavir. Ritonavir half-life to 72 h was 6.84 h with darunavir and 6.07 with atazanavir. This study investigated the pharmacokinetic forgiveness of two boosted protease inhibitors. Although the rates of decline of darunavir and atazanavir slightly increased as ritonavir concentrations declined, most individuals had concentrations 6 h after the end of the ideal dosing interval of 24 h which were above the cutoff used to define therapeutic concentrations.

Antimicrobial agents and chemotherapy · clinical trial · 31 citationsread the source →

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

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

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

Therapist-delivered Internet psychotherapy for depression in primary care: a randomised controlled trial.

Background: Despite strong evidence for its effectiveness, cognitive-behavioural therapy (CBT) remains difficult to access. Computerised programs have been developed to improve accessibility, but whether these interventions are responsive to individual needs is unknown. We investigated the effectiveness of CBT delivered online in real time by a therapist for patients with depression in primary care. Methods: In this multicentre, randomised controlled trial, 297 individuals with a score of 14 or more on the Beck depression inventory (BDI) and a confirmed diagnosis of depression were recruited from 55 general practices in Bristol, London, and Warwickshire, UK. Participants were randomly assigned, by a computer-generated code, to online CBT in addition to usual care (intervention; n=149) or to usual care from their general practitioner while on an 8-month waiting list for online CBT (control; n=148). Participants, researchers involved in recruitment, and therapists were masked in advance to allocation. The primary outcome was recovery from depression (BDI score <10) at 4 months. Analysis was by intention to treat. This trial is registered, number ISRCTN 45444578. Findings: 113 participants in the intervention group and 97 in the control group completed 4-month follow-up. 43 (38%) patients recovered from depression (BDI score <10) in the intervention group versus 23 (24%) in the control group at 4 months (odds ratio 2.39, 95% CI 1.23-4.67; p=0.011), and 46 (42%) versus 26 (26%) at 8 months (2.07, 1.11-3.87; p=0.023). Interpretation: CBT seems to be effective when delivered online in real time by a therapist, with benefits maintained over 8 months. This method of delivery could broaden access to CBT. Funding: BUPA Foundation.

Lancet (London, England) · randomised controlled trial · 214 citationsread the source →

The effects of social deprivation on adolescent development and mental health.

Adolescence (the stage between 10 and 24 years) is a period of life characterised by heightened sensitivity to social stimuli and the increased need for peer interaction. The physical distancing measures mandated globally to contain the spread of COVID-19 are radically reducing adolescents' opportunities to engage in face-to-face social contact outside their household. In this interdisciplinary Viewpoint, we describe literature from a variety of domains that highlight how social deprivation in adolescence might have far-reaching consequences. Human studies have shown the importance of peer acceptance and peer influence in adolescence. Animal research has shown that social deprivation and isolation have unique effects on brain and behaviour in adolescence compared with other stages of life. However, the decrease in adolescent face-to-face contact might be less detrimental due to widespread access to digital forms of social interaction through technologies such as social media. The findings reviewed highlight how physical distancing might have a disproportionate effect on an age group for whom peer interaction is a vital aspect of development.

The Lancet. Child & adolescent health · review · 645 citationsread the source →

Interventions to address the mental health of adolescents and young adults living with or affected by HIV: state of the evidence.

Introduction: Adolescents and young adults (AYA) remain vulnerable to HIV-infection and significant co-morbid mental health challenges that are barriers to treatment and prevention efforts. Globally millions of AYA are living with HIV (AYALH) and/or have been affected by HIV in their families (AYAAH), with studies highlighting the need for mental health programmes. With no current guidelines for delivering mental health interventions for AYALH or AYAAH, a scoping review was undertaken to explore current evidence-based mental health interventions for AYALH and AYAAH to inform future work. Methods: The review, targeting work between 2014 and 2020, initially included studies of evidence-based mental health interventions for AYALH and AYAAH, ages 10 to 24 years, that used traditional mental health treatments. Given the few studies identified, we expanded our search to include psychosocial interventions that had mental health study outcomes. Results and discussion: We identified 13 studies, seven focused on AYALH, five on AYAAH, and one on both. Most studies took place in sub-Saharan Africa. Depression was targeted in eight studies with the remainder focused on a range of emotional and behavioural symptoms. Few studies used evidence-based approaches such as Cognitive Behaviour Therapy; psychosocial approaches included mental health treatments, group-based and family strengthening interventions, economic empowerment combined with family strengthening, group-based mindfulness and community interventions. Eleven studies were randomized control trials with four pilot studies. There was variation in sample size, treatment delivery mode (individual focus, group-based, family focus), and measures of effectiveness across studies. Most used trained lay counsellors as facilitators, with few using trained mental health professionals. Eleven studies reported positive intervention effects on mental health. Conclusions: Despite the need for mental health interventions for AYALH and AYAAH, we know surprisingly little about mental health treatment for this vulnerable population. There are some promising approaches, but more work is needed to identify evidence-based approaches and corresponding mechanisms of change. Given limited resources, integrating mental health treatment into healthcare settings and using digital health approaches may support more standardized and scalable treatments. Greater emphasis on implementation science frameworks is needed to create sustainable mental health treatment for AYALH and AYAAH globally.

Journal of the International AIDS Society · review · 60 citationsread the source →

Neurophysiological Approach by Self-Control of Your Stress-Related Autonomic Nervous System with Depression, Stress and Anxiety Patients.

Background: Heart Rate Variability Biofeedback (HRVB) is a treatment in which patients learn self-regulation of a physiological dysregulated vagal nerve function. While the therapeutic approach of HRVB is promising for a variety of disorders, it has not yet been regularly offered in a mental health treatment setting. Aim: To provide a systematic review about the efficacy of HRV-Biofeedback in treatment of anxiety, depression, and stress related disorders. Method: Systematic review in PubMed and Web of Science in 2020 with terms HRV, biofeedback, Post-Traumatic Stress Disorder (PTSD), depression, panic disorder, and anxiety disorder. Selection, critical appraisal, and description of the Random Controlled Trials (RCT) studies. Combined with recent meta-analyses. Results: The search resulted in a total of 881 studies. After critical appraisal, nine RCTs have been selected as well as two other relevant studies. The RCTs with control groups treatment as usual, muscle relaxation training and a "placebo"-biofeedback instrument revealed significant clinical efficacy and better results compared with control conditions, mostly significant. In the depression studies average reduction at the Beck Depression Inventory (BDI) scale was 64% (HRVB plus Treatment as Usual (TAU) versus 25% (control group with TAU) and 30% reduction (HRVB) at the PSQ scale versus 7% (control group with TAU). In the PTSD studies average reduction at the BDI-scale was 53% (HRV plus TAU) versus 24% (control group with TAU) and 22% (HRVB) versus 10% (TAU) with the PTSD Checklist (PCL). In other systematic reviews significant effects have been shown for HRV-Biofeedback in treatment of asthma, coronary artery disease, sleeping disorders, postpartum depression and stress and anxiety. Conclusion: This systematic review shows significant improvement of the non-invasive HRVB training in stress related disorders like PTSD, depression, and panic disorder, in particular when combined with cognitive behavioral therapy or different TAU. Effects were visible after four weeks of training, but clinical practice in a longer daily self-treatment of eight weeks is more promising. More research to integrate HRVB in treatment of stress related disorders in psychiatry is warranted, as well as research focused on the neurophysiological mechanisms.

International journal of environmental research and public health · systematic review · 49 citationsread the source →

Physical activity behaviours in adolescence: current evidence and opportunities for intervention.

Young people aged 10-24 years constitute 24% of the world's population; investing in their health could yield a triple benefit-eg, today, into adulthood, and for the next generation. However, in physical activity research, this life stage is poorly understood, with the evidence dominated by research in younger adolescents (aged 10-14 years), school settings, and high-income countries. Globally, 80% of adolescents are insufficiently active, and many adolescents engage in 2 h or more daily recreational screen time. In this Series paper, we present the most up-to-date global evidence on adolescent physical activity and discuss directions for identifying potential solutions to enhance physical activity in the adolescent population. Adolescent physical inactivity probably contributes to key global health problems, including cardiometabolic and mental health disorders, but the evidence is methodologically weak. Evidence-based solutions focus on three key components of the adolescent physical activity system: supportive schools, the social and digital environment, and multipurpose urban environments. Despite an increasing volume of research focused on adolescents, there are still important knowledge gaps, and efforts to improve adolescent physical activity surveillance, research, intervention implementation, and policy development are urgently needed.

Lancet (London, England) · review · 523 citationsread the source →

Psychological therapies for people with borderline personality disorder.

Background: Borderline personality disorder (BPD) is a relatively common personality disorder with a major impact on health services as those affected often present in crisis, often self-harming. Objectives: To evaluate the effects of psychological interventions for people with borderline personality disorder. Search strategy: We conducted a systematic search of 26 specialist and general bibliographic databases (December 2002) and searched relevant reference lists for further trials. Selection criteria: All relevant clinical randomised controlled trials involving psychological treatments for people with BPD. The definition of psychological treatments included behavioural, cognitive-behavioural, psychodynamic and psychoanalytic. Data collection and analysis: We independently selected, quality assessed and data extracted studies. For binary outcomes we calculated a standard estimation of the risk ratio (RR), its 95% confidence interval (CI), and where possible the number need to help/harm (NNT/H). For continuous outcomes, endpoint data were preferred to change data. Non-skewed data from valid scales were summated using a weighted mean difference (WMD). Main results: We identified seven studies involving 262 people, and five separate comparisons. Comparing dialectical behaviour therapy (DBT) with treatment as usual studies found no difference for the outcome of still meeting SCID-II criteria for the diagnosis of BPD by six months (n=28, 1 RCT, RR 0.69 CI 0.35 to 1.38) or admission to hospital in previous three months (n=28, 1 RCT, RR 0.77 CI 0.28 to 2.14). Self harm or parasuicide may decrease at 6 to 12 months (n=63, 1 RCT, RR 0.81 CI 0.66 to 0.98, NNT 12 CI 7 to 108). One study detected statistical difference in favour of people receiving DBT compared with those allocated to treatment as usual for average scores of suicidal ideation at 6 months (n=20, MD -15.30 CI -25.46 to -5.14). There was no difference for the outcome of leaving the study early (n=155, 3 RCTs, RR 0.74 CI 0.52 to 1.04). For the outcome of interviewer-assessed alcohol free days, skewed data are reported and tend to favour DBT. When a substance abuse focused DBT was compared with comprehensive validation therapy plus 12-step substance misuse programme no clear differences were found for service outcomes (n=23, 1 RCT, RR imprisoned 1.09 CI 0.64 to 1.87) or leaving the study early (n=23, 1 RCT, RR 7.58 CI 0.44 to 132.08). When dialectical behaviour therapy-oriented treatment is compared with client centred therapy no differences were found for service outcomes (n=24, 1 RCT, RR admitted 0.33 CI 0.08 to 1.33). However, fewer people in the DBT group displayed indicators of parasuicidal behaviour (n=24, RR 0.13 CI 0.02 to 0.85, NNT 2 CI 2 to 11). There were no differences for outcomes of anxiety and depression (n=24, 1 RCT, RR anxiety BAI >/=10 0.60 CI 0.32 to 1.12; RR depression HDRS >/=10 0.43 CI 0.14 to 1.28) but people who received DBT had less general psychiatric severity than those in the control (MD BPRS at 6 months -7.41 CI -13.72 to -1.10). Finally this one relevant study reports skewed data for suicidal ideation with considerably lower scores for people allocated to DBT. When psychoanalytically oriented partial hospitalization was compared with general psychiatric care the former tended to come off best. People who received treatment in a psychoanalytic orientated day hospital were less likely to be admitted into inpatient care when measured at different time points (e.g. n=44, RR admitted to inpatient 24 hour care >18 to 24 months 0.05 CI 0.00 to 0.77, NNT 3 CI 3 to 10) Fewer people in psychoanalytically oriented partial hospitalization needed day hospital intervention in the 18 months after discharge (n=44, 1 RCT, RR 0.04 CI 0.00 to 0.59, NNT 2 CI 2 to 8). More people in the control group took psychotropic medication by the 30 to 36 month follow-up, than those receiving psychoanalytic treatment (n=44, 1 RCT, RR 0.44 CI 0.25 to 0.80, NNT 3 CI 2 to 7). Anxiety and depression scores were generally lower in the psychoanalytically oriented partial hospitalization group (n=44, 1 RCT, RR >/=14 on BDI 0.52 CI 0.34 to 0.80, NNT 3 CI 3 to 6), as are global severity scores. People receiving psychoanalytic care in a day hospital had better social improvement in social adjustment using the SAS-SR at 6 to 12 months compared with people in general psychiatric care (MD -0.70 CI -1.08 to -0.32). Rates of attrition were the same (n=44, 1 RCT, RR leaving the study early 1.00 CI 0.23 to 4.42). Authors' conclusions: This review suggests that some of the problems frequently encountered by people with borderline personality disorder may be amenable to talking/behavioural treatments but all therapies remain experimental and the studies are too few and small to inspire full confidence in their results. These findings require replication in larger 'real-world' studies.

The Cochrane database of systematic reviews · meta-analysis · 52 citationsread the source →

Antenatal anxiety disorder as a predictor of postnatal depression: a longitudinal study.

Previous research has implicated high levels of antenatal anxiety as a predictor of postnatal depression, but there is a paucity of evidence on the relationship between the various forms of anxiety and postnatal depression. A longitudinal study of 246 mothers (56 with antenatal generalised anxiety disorder (GAD), 68 with antenatal generalised social phobia, 28 with both disorders in the antenatal period, and 94 with no antenatal GAD or social phobia) allowed us to explore whether antenatal social phobia and GAD predict high Edinburgh Postnatal Depression Scale (EPDS) scores (probable depression >12) at 10-14 days, 10-12 weeks, 10 months, 14 months, and 24 months postnatally. We found that, after accounting for the presence of other antenatal anxiety disorders, antenatal depression, maternal age at child's birth, socio-economic status and ethnicity in the models, antenatal GAD independently predicted depression at all time points after delivery. A less robust relationship was found for antenatal social phobia, which predicted postnatal depression at only 10 months after birth. One possibility consistent with our findings is that there may be differences in the timing of postnatal depression with different forms of antenatal anxiety disorders.

Journal of affective disorders · 68 citationsread the source →

Post-deployment screening for mental disorders and tailored advice about help-seeking in the UK military: a cluster randomised controlled trial.

Background: The effectiveness of post-deployment screening for mental disorders has not been assessed in a randomised controlled trial. We aimed to assess whether post-deployment screening for post-traumatic stress disorder (PTSD), depression, anxiety, or alcohol misuse was effective. We defined screening as the presumptive identification of a previously unrecognised disorder using tests to distinguish those who probably had the disorder from those who probably did not so that those people with a probable disorder could be referred appropriately, and assessed effectiveness and consequences for help-seeking by the odds ratio at follow-up between those receiving tailored help-seeking advice and those who received general mental health advice. Methods: We did a cluster randomised controlled trial among Royal Marines and Army personnel in the UK military after deployment to Afghanistan. Platoons were randomly assigned (1:1 initially, then 2:1) by stratified block randomisation with randomly varying block sizes of two and four to the screening group, which received tailored help-seeking advice, or the control group, which received general mental health advice. Initial assessment took place 6-12 weeks after deployment; follow-up assessments were done 10-24 months later. Follow-up measures were the PTSD Checklist-Civilian Version, Patient Health Questionnaire-9, Generalised Anxiety Disorder-7 scale, Alcohol Use Disorder Identification Test (AUDIT), and self-reported help-seeking from clinical and welfare providers comparing those receiving tailored advice and those receiving only general advice. All participants and all investigators other than the person who analysed the data were masked to allocation. The primary outcomes were PTSD, depression or generalised anxiety disorder, and alcohol misuse at follow-up. A key secondary outcome was assessment of whether post-deployment screening followed by tailored advice would modify help-seeking behaviour. Comparisons were made between screening and control groups, with primary analyses by intention to treat. This trial is registered with the ISRCTN Registry, number ISRCTN19965528. Findings: Between Oct 24, 2011, and Oct 31, 2014, 434 platoons comprising 10 190 personnel were included: 274 (6350 personnel) in the screening group and 160 (3840 personnel) in the control group. 5577 (88%) of 6350 personnel received screening and 3996 (63%) completed follow-up, whereas 3149 (82%) of 3840 received the control questionnaire and 2369 (62%) completed follow-up. 1958 (35%) of 5577 personnel in the screening group declined to see the tailored advice, but those with PTSD (83%) or anxiety or depression (84%) were more likely than non-cases (64%) to view the advice (both p<0·0001). At follow-up, there were no significant differences in prevalence between groups for PTSD (adjusted odds ratio 0·92, 95% CI 0·75-1·14), depression or anxiety (0·91, 0·71-1·16), alcohol misuse (0·88, 0·73-1·06), or seeking support for mental disorders (0·92, 0·78-1·08). Interpretation: Post-deployment screening for mental disorders based on tailored advice was not effective at reducing prevalence of mental health disorders nor did it increase help-seeking. Countries that have implemented post-deployment screening programmes for mental disorders should consider monitoring the outcomes of their programmes. Funding: The US Army Medical Research and Materiel Command-Military Operational Medicine Research Program (USAMRMC-MOMRP).

Lancet (London, England) · randomised controlled trial · 38 citationsread the source →

Longitudinal associations between father- and mother-child interactions, coparenting, and child cardiometabolic health.

Objective: This study aimed to examine the longitudinal connections between early observed parenting and coparenting relationship quality and children's later cardiometabolic health outcomes. Method: Structural equation modeling was used to examine (a) the associations between fathers' and mothers' sensitive engagement with their children and competitive-withdrawn coparenting during infancy (10 months) and toddlerhood (24 months); (b) the extent to which these parenting and coparenting factors predicted four markers of children's cardiometabolic health in middle childhood (∼7 years); and (c) indirect pathways from parenting and coparenting at 10 months to cardiometabolic markers (C-reactive protein [CRP], interleukin-6, total cholesterol, and glycated hemoglobin [HbA1c]) at 7 years, via parenting and coparenting at 24 months, within a longitudinal, cross-lagged framework. The sample comprised 292 child-father-mother triads from a randomized trial of Family Foundations, a preventive intervention focused on enhancing coparenting interactions between first-time parents. Results: Fathers' sensitive engagement at 10 months was negatively associated with their competitive-withdrawn coparenting at 24 months, which subsequently predicted lower levels of child CRP and HbA1c. Furthermore, fathers' competitive-withdrawn coparenting at 24 months explained the association between their sensitive engagement at 10 months and later child CRP and HbA1c. These associations were not significant in a parallel model for mothers. Conclusion: These findings highlight the influence of child-father interactions and coparenting dynamics on long-term child health. Promoting supportive coparenting and positive paternal involvement may represent valuable preventive strategies for reducing child cardiometabolic risk. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Health psychology : official journal of the Division of Health Psychology, American Psychological Association · 1 citationsread the source →

Influence of gender on attention-deficit/hyperactivity disorder in Europe--ADORE.

Background: Attention-deficit/hyperactivity disorder (ADHD) in girls in Europe is poorly understood; it is not known whether they exhibit similar symptom patterns or co-existing problems and receive the same type of treatment as boys. Objective: To examine gender differences for referral patterns, social demographic factors, ADHD core symptomatology, co-existing health problems, psychosocial functioning and treatment. Methods: Baseline data from the ADHD Observational Research in Europe (ADORE) study, a 24-month, naturalistic, longitudinal observational study in 10 European countries of children (aged 6-18 years) with hyperactive/inattentive/impulsive symptoms but no previous diagnosis of ADHD, were analysed by gender. Results: Data from 1,478 children were analysed: 231 girls (15.7%) and 1,222 boys (84.3%) (gender data missing for 25 patients). Gender ratios (girl:boy) varied by country, ranging from 1:3 to 1:16. Comparisons showed few gender effects in core ADHD symptomatology and clinical correlates of ADHD. Compared with boys, girls had significantly more parent-rated emotional symptoms and prosocial behaviour and were more likely to be the victim of bullying and less likely to be the bully. Girls and boys had similar levels of co-existing psychiatric and physical health problems, and received the same type of treatment. Conclusions: Fewer girls than boys are referred for ADHD treatment, but they have a similar pattern of impairment and receive similar treatment.

European child & adolescent psychiatry · cohort or longitudinal · 140 citationsread the source →

Autologous Mesenchymal Stem Cells Improve Motor Recovery in Subacute Ischemic Stroke: a Randomized Clinical Trial.

While preclinical stroke studies have shown that mesenchymal stem cells (MSCs) promote recovery, few randomized controlled trials (RCT) have assessed cell therapy in humans. In this RCT, we assessed the safety, feasibility, and efficacy of intravenous autologous bone marrow-derived MSCs in subacute stroke. ISIS-HERMES was a single-center, open-label RCT, with a 2-year follow-up. We enrolled patients aged 18-70 years less than 2 weeks following moderate-severe ischemic carotid stroke. Patients were randomized 2:1 to receive intravenous MSCs or not. Primary outcomes assessed feasibility and safety. Secondary outcomes assessed global and motor recovery. Passive wrist movement functional MRI (fMRI) activity in primary motor cortex (MI) was employed as a motor recovery biomarker. We compared "treated" and "control" groups using as-treated analyses. Of 31 enrolled patients, 16 patients received MSCs. Treatment feasibility was 80%, and there were 10 and 16 adverse events in treated patients, and 12 and 24 in controls at 6-month and 2-year follow-up, respectively. Using mixed modeling analyses, we observed no treatment effects on the Barthel Index, NIHSS, and modified-Rankin scores, but significant improvements in motor-NIHSS (p = 0.004), motor-Fugl-Meyer scores (p = 0.028), and task-related fMRI activity in MI-4a (p = 0.031) and MI-4p (p = 0.002). Intravenous autologous MSC treatment following stroke was safe and feasible. Motor performance and task-related MI activity results suggest that MSCs improve motor recovery through sensorimotor neuroplasticity. ClinicalTrials.gov Identifier NCT00875654.

Translational stroke research · randomised controlled trial · 145 citationsread the source →

A Brief Exposure-Based Treatment vs Cognitive Processing Therapy for Posttraumatic Stress Disorder: A Randomized Noninferiority Clinical Trial

Importance: Written exposure therapy (WET), a 5-session intervention, has been shown to efficaciously treat posttraumatic stress disorder (PTSD). However, this treatment has not yet been directly compared with a first-line PTSD treatment such as cognitive processing therapy (CPT). Objective: To determine if WET is noninferior to CPT in patients with PTSD. Design, Setting, and Participants: In this randomized clinical trial conducted at a Veterans Affairs medical facility between February 28, 2013, and November 6, 2016, 126 veteran and nonveteran adults were randomized to either WET or CPT. Inclusion criteria were a primary diagnosis of PTSD and stable medication therapy. Exclusion criteria included current psychotherapy for PTSD, high risk of suicide, diagnosis of psychosis, and unstable bipolar illness. Analysis was performed on an intent-to-treat basis. Interventions: Participants assigned to CPT (n = 63) received 12 sessions and participants assigned to WET (n = 63) received 5 sessions. The CPT protocol that includes written accounts was delivered individually in 60-minute weekly sessions. The first WET session requires 60 minutes while the remaining 4 sessions require 40 minutes. Main Outcomes and Measures: The primary outcome was the total score on the Clinician-Administered PTSD Scale for DSM-5; noninferiority was defined by a score of 10 points. Blinded evaluations were conducted at baseline and 6, 12, 24, and 36 weeks after the first treatment session. Treatment dropout was also examined. Results: For the 126 participants (66 men and 60 women; mean [SD] age, 43.9 [14.6] years), improvements in PTSD symptoms in the WET condition were noninferior to improvements in the CPT condition at each of the assessment periods. The largest difference between treatments was observed at the 24-week assessment (mean difference, 4.31 points; 95% CI, -1.37 to 9.99). There were significantly fewer dropouts in the WET vs CPT condition (4 [6.4%] vs 25 [39.7%]; χ21 = 12.84, Cramer V = 0.40). Conclusions and Relevance: Although WET involves fewer sessions, it was noninferior to CPT in reducing symptoms of PTSD. The findings suggest that WET is an efficacious and efficient PTSD treatment that may reduce attrition and transcend previously observed barriers to PTSD treatment for both patients and providers. Trial Registration: clinicaltrials.gov Identifier: NCT01800773.

JAMA Psychiatry · randomised controlled trial · 233 citationsread the source →

Perspectives on Early Screening and Prompt Intervention to Identify and Treat Maternal Perinatal Mental Health. Protocol for a Prospective Multicenter Study in Italy.

Background: The most common mental disorders in women during the perinatal (antenatal and postnatal) period are depressive syndromes and anxiety syndromes. The global prevalence of maternal perinatal depression ranges from 10 to 20%, while the prevalence of perinatal anxiety ranges from 10 to 24%. The comorbidity of mood and anxiety disorders in perinatal women is common, reaching 40%. In Italy, a few studies have been undertaken to evaluate the prevalence of perinatal depression and anxiety, and there is still a scarcity of research and intervention programs regarding primary prevention. Three of the main aims of this study are: (1) to evaluate the prevalence of maternal perinatal depression and anxiety in a large sample of women attending healthcare centers in Italy; (2) to investigate the psychosocial risks and protective factors associated with maternal perinatal depression and anxiety; (3) to evaluate the effectiveness of a manualized psychological intervention (Milgrom et al., 1999) to treat perinatal depression; (4) to evaluate the psychometric properties of both the Edinburgh Postnatal Depression Scale and the Patient Health Questionnaire-9 in detecting perinatal depression; and (5) to evaluate the influence of maternal depression and anxiety on the development of infant temperament. Methods: This is a prospective cohort study, which merges an observational design and a pre-post intervention design. The study includes a 1-year recruitment period and a one-year follow-up period. The methodological strategy includes: (1) self-report questionnaires on maternal depression, anxiety, health status, quality of life and psychosocial risks; (2) a self-report questionnaire to measure the infant's temperament; (3) a clinical interview; (4) a structured diagnostic interview; and (5) a psychological intervention. Discussion: The results of this study may contribute to our knowledge about prevalence of antenatal and postnatal depression and anxiety (during both the trimesters of pregnancy and the first six trimesters after birth) and about the effectiveness of early psychological intervention in the perinatal health services.

Frontiers in psychology · 20 citationsread the source →

Effects of oxytocin on attention to emotional faces in healthy volunteers and highly socially anxious males.

Background: Evidence suggests that individuals with social anxiety demonstrate vigilance to social threat, whilst the peptide hormone oxytocin is widely accepted as supporting affiliative behaviour in humans. Methods: This study investigated whether oxytocin can affect attentional bias in social anxiety. In a double-blind, randomized, placebo-controlled, within-group study design, 26 healthy and 16 highly socially anxious (HSA) male volunteers (within the HSA group, 10 were diagnosed with generalized social anxiety disorder) were administered 24 IU of oxytocin or placebo to investigate attentional processing in social anxiety. Attentional bias was assessed using the dot-probe paradigm with angry, fearful, happy and neutral face stimuli. Results: In the baseline placebo condition, the HSA group showed greater attentional bias for emotional faces than healthy individuals. Oxytocin reduced the difference between HSA and non-socially anxious individuals in attentional bias for emotional faces. Moreover, it appeared to normalize attentional bias in HSA individuals to levels seen in the healthy population in the baseline condition. The biological mechanisms by which oxytocin may be exerting these effects are discussed. Conclusions: These results, coupled with previous research, could indicate a potential therapeutic use of this hormone in treatment for social anxiety.

The international journal of neuropsychopharmacology · randomised controlled trial · 23 citationsread the source →

Informing Human Trafficking Clinical Care Through Two Systematic Reviews on Sexual Assault and Intimate Partner Violence.

Background: There is a lack of evidence on the clinical management of patients who have suffered human trafficking. Synthesizing the evidence from similar patient populations may provide valuable insight. This review summarizes findings on therapeutic interventions for survivors of sexual assault and intimate partner violence (IPV). Method: We conducted two systematic reviews using the MEDLINE database. We included only randomized controlled trials of therapies with primary outcomes related to health for survivors of sexual assault and IPV. For the sexual assault review, there were 78 abstracts identified, 16 full-text articles reviewed, and 10 studies included. For the IPV review, there were 261 abstracts identified, 24 full-text articles reviewed, and 17 studies included. Analysis compared study size, intervention type, patient population, primary health outcomes, and treatment effect. Results: Although our search included physical and mental health outcomes, almost all the studies meeting inclusion and exclusion criteria focused on mental health. The interventions for sexual assault included spiritually focused group therapy, interference control training, image rehearsal therapy, sexual revictimization prevention, educational videos, cognitive behavioral therapy, and exposure therapy. The interventions in the IPV review included group social support therapy, exposure therapy, empowerment sessions, physician counseling, stress management programs, forgiveness therapy, motivational interviewing, and interpersonal psychotherapy. Conclusions: Insights from these reviews included the importance of culturally specific group therapy, the central role of survivor empowerment, and the overwhelming focus on mental health. These key features provide guidance for the development of interventions to improve the health of human trafficking survivors.

Trauma, violence & abuse · systematic review · 10 citationsread the source →

Annual Research Review: Umbrella synthesis of meta-analyses on child maltreatment antecedents and interventions: differential susceptibility perspective on risk and resilience.

Child maltreatment in the family context is a prevalent and pervasive phenomenon in many modern societies. The global perpetration of child abuse and neglect stands in stark contrast to its almost universal condemnation as exemplified in the United Nation's Convention on the Rights of the Child. Much work has been devoted to the task of prevention, yet a grand synthesis of the literature is missing. Focusing on two core elements of prevention, that is, antecedents for maltreatment and the effectiveness of (preventative) interventions, we performed an umbrella review of meta-analyses published between January 1, 2014, and December 17, 2018. Meta-analyses were systematically collected, assessed, and integrated following a uniform approach to allow their comparison across domains. From this analysis of thousands of studies including almost 1.5 million participants, the following risk factors were derived: parental experience of maltreatment in his or her own childhood (d = .47), low socioeconomic status of the family (d = .34), dependent and aggressive parental personality (d = .45), intimate partner violence (d = .41), and higher baseline autonomic nervous system activity (d = .24). The effect size for autonomic stress reactivity was not significant (d = -.10). The umbrella review of interventions to prevent or reduce child maltreatment showed modest intervention effectiveness (d = .23 for interventions targeting child abuse potential or families with self-reported maltreatment and d = .27 for officially reported child maltreatment cases). Despite numerous studies on child maltreatment, some large gaps in our knowledge of antecedents exist. Neurobiological antecedents should receive more research investment. Differential susceptibility theory may shed more light on questions aimed at breaking the intergenerational transmission of maltreatment and on the modest (preventive) intervention effects. In combination with family-based interaction-focused interventions, large-scale socioeconomic experiments such as cash transfer trials and experiments with vouchers to move to a lower-poverty area might be tested to prevent or reduce child maltreatment. Prevalence, antecedents, and preventive interventions of prenatal maltreatment deserve continuing scientific, clinical, and policy attention.

Journal of child psychology and psychiatry, and allied disciplines · systematic review · 137 citationsread the source →

Diet, physical activity and behavioural interventions for the treatment of overweight or obese adolescents aged 12 to 17 years.

Background: Adolescent overweight and obesity has increased globally, and can be associated with short- and long-term health consequences. Modifying known dietary and behavioural risk factors through behaviour changing interventions (BCI) may help to reduce childhood overweight and obesity. This is an update of a review published in 2009. Objectives: To assess the effects of diet, physical activity and behavioural interventions for the treatment of overweight or obese adolescents aged 12 to 17 years. Search methods: We performed a systematic literature search in: CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, LILACS, and the trial registers ClinicalTrials.gov and ICTRP Search Portal. We checked references of identified studies and systematic reviews. There were no language restrictions. The date of the last search was July 2016 for all databases. Selection criteria: We selected randomised controlled trials (RCTs) of diet, physical activity and behavioural interventions for treating overweight or obesity in adolescents aged 12 to 17 years. Data collection and analysis: Two review authors independently assessed risk of bias, evaluated the overall quality of the evidence using the GRADE instrument and extracted data following the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. We contacted trial authors for additional information. Main results: We included 44 completed RCTs (4781 participants) and 50 ongoing studies. The number of participants in each trial varied (10 to 521) as did the length of follow-up (6 to 24 months). Participants ages ranged from 12 to 17.5 years in all trials that reported mean age at baseline. Most of the trials used a multidisciplinary intervention with a combination of diet, physical activity and behavioural components. The content and duration of the intervention, its delivery and the comparators varied across trials. The studies contributing most information to outcomes of weight and body mass index (BMI) were from studies at a low risk of bias, but studies with a high risk of bias provided data on adverse events and quality of life. The mean difference (MD) of the change in BMI at the longest follow-up period in favour of BCI was -1.18 kg/m2 (95% confidence interval (CI) -1.67 to -0.69); 2774 participants; 28 trials; low quality evidence. BCI lowered the change in BMI z score by -0.13 units (95% CI -0.21 to -0.05); 2399 participants; 20 trials; low quality evidence. BCI lowered body weight by -3.67 kg (95% CI -5.21 to -2.13); 1993 participants; 20 trials; moderate quality evidence. The effect on weight measures persisted in trials with 18 to 24 months' follow-up for both BMI (MD -1.49 kg/m2 (95% CI -2.56 to -0.41); 760 participants; 6 trials and BMI z score MD -0.34 (95% CI -0.66 to -0.02); 602 participants; 5 trials).There were subgroup differences showing larger effects for both BMI and BMI z score in studies comparing interventions with no intervention/wait list control or usual care, compared with those testing concomitant interventions delivered to both the intervention and control group. There were no subgroup differences between interventions with and without parental involvement or by intervention type or setting (health care, community, school) or mode of delivery (individual versus group).The rate of adverse events in intervention and control groups was unclear with only five trials reporting harms, and of these, details were provided in only one (low quality evidence). None of the included studies reported on all-cause mortality, morbidity or socioeconomic effects.BCIs at the longest follow-up moderately improved adolescent's health-related quality of life (standardised mean difference 0.44 ((95% CI 0.09 to 0.79); P = 0.01; 972 participants; 7 trials; 8 comparisons; low quality of evidence) but not self-esteem. Trials were inconsistent in how they measured dietary intake, dietary behaviours, physical activity and behaviour. Authors' conclusions: We found low quality evidence that multidisciplinary interventions involving a combination of diet, physical activity and behavioural components reduce measures of BMI and moderate quality evidence that they reduce weight in overweight or obese adolescents, mainly when compared with no treatment or waiting list controls. Inconsistent results, risk of bias or indirectness of outcome measures used mean that the evidence should be interpreted with caution. We have identified a large number of ongoing trials (50) which we will include in future updates of this review.

The Cochrane database of systematic reviews · meta-analysis · 257 citationsread the source →

Does pulmonary rehabilitation address treatable traits? A systematic review.

Background: There is growing interest in a "treatable traits" approach to pulmonary rehabilitation in chronic airways disease. The frequency with which pulmonary rehabilitation programmes address treatable traits is unknown. Methods: Randomised controlled trials of pulmonary rehabilitation compared to usual care in patients with stable chronic airways disease were included. The components of pulmonary rehabilitation delivered were extracted and mapped to treatable traits in pulmonary, extrapulmonary and behavioural/lifestyle domains. Meta-analysis was used to evaluate the impact of addressing >1 treatable trait on exercise capacity and health-related quality of life (HRQoL). Results: 116 trials were included (6893 participants). Almost all pulmonary rehabilitation programmes addressed deconditioning (97% of trials). The most commonly addressed extrapulmonary traits were nutritional status (obesity and cachexia, 18% each) and mood disturbance (anxiety and depression, 10% each). Behavioural/lifestyle traits most frequently addressed were nonadherence (46%), poor inhalation technique (24%) and poor family/social support (19%). Exercise capacity and HRQoL outcomes did not differ between studies that addressed deconditioning alone and those that targeted additional traits, but heterogeneity was high. Conclusion: Aside from deconditioning, treatable traits are infrequently addressed in existing trials of pulmonary rehabilitation. The potential of the treatable traits approach to improve pulmonary rehabilitation outcomes remains to be explored.

European respiratory review : an official journal of the European Respiratory Society · meta-analysis · 12 citationsread the source →

Does Stepping Stones Triple P plus Acceptance and Commitment Therapy improve parent, couple, and family adjustment following paediatric acquired brain injury? A randomised controlled trial.

Objective: To evaluate the efficacy of a behavioural family intervention, Stepping Stones Triple P (SSTP), combined with an Acceptance and Commitment Therapy (ACT) workshop in improving parent, family and couple outcomes following paediatric acquired brain injury (ABI). Participants and setting: Fifty-nine parents (90% mothers) of children (mean age 7 years; 35 males, 24 females) with ABI. Intervention: Participants were randomly assigned to a treatment (10-week group SSTP and ACT program) or a care-as-usual (CAU) control condition (10 weeks). Those in the CAU condition received the treatment after the waitlist period. Outcomes: Self-report measures of parent psychological distress, parent psychological flexibility, parenting confidence, family functioning, and couple relationship, assessed at: pre-intervention, post-intervention, and 6-months post-intervention. Results: Post-intervention, the treatment group showed significant, small to medium improvements relative to the CAU group (at the p < .05 level) on parent psychological distress, parent psychological flexibility, parent confidence in managing behaviours, family adjustment,and number of disagreements between parents. Most improvements were maintained at 6-months. Conclusions: Parent skills training and ACT may be efficacious in improving parent, family, and couple outcomes in families of children with an ABI.

Behaviour research and therapy · randomised controlled trial · 53 citationsread the source →

Feasibility of time-restricted eating and impacts on cardiometabolic health in 24-h shift workers: The Healthy Heroes randomized control trial.

Over a quarter of the workforce in industrialized countries does shift work, which increases the risk for cardiometabolic disease. Yet shift workers are often excluded from lifestyle intervention studies to reduce this risk. In a randomized control trial with 137 firefighters who work 24-h shifts (23-59 years old, 9% female), 12 weeks of 10-h time-restricted eating (TRE) was feasible, with TRE participants decreasing their eating window (baseline, mean 14.13 h, 95% CI 13.78-14.47 h; intervention, 11.13 h, 95% CI 10.73-11.54 h, p = 3.29E-17) with no adverse effects, and improved quality of life assessed via SF-36 (ClinicalTrials.gov: NCT03533023). Compared to the standard of care (SOC) arm, TRE significantly decreased VLDL particle size. In participants with elevated cardiometabolic risks at baseline, there were significant reductions in TRE compared to SOC in glycated hemoglobin A1C and diastolic blood pressure. For individuals working a 24-h shift schedule, TRE is feasible and can improve cardiometabolic health, especially for individuals with increased risk. VIDEO ABSTRACT.

Cell metabolism · randomised controlled trial · 149 citationsread the source →

Virtual Reality-Based Early Neurocognitive Stimulation in Critically Ill Patients: A Pilot Randomized Clinical Trial.

This study focuses on the application of a non-immersive virtual reality (VR)-based neurocognitive intervention in critically ill patients. Our aim was to assess the feasibility of direct outcome measures to detect the impact of this digital therapy on patients' cognitive and emotional outcomes. Seventy-two mechanically ventilated adult patients were randomly assigned to the "treatment as usual" (TAU, n = 38) or the "early neurocognitive stimulation" (ENRIC, n = 34) groups. All patients received standard intensive care unit (ICU) care. Patients in the ENRIC group also received adjuvant neurocognitive stimulation during the ICU stay. Outcome measures were a full neuropsychological battery and two mental health questionnaires. A total of 42 patients (21 ENRIC) completed assessment one month after ICU discharge, and 24 (10 ENRIC) one year later. At one-month follow-up, ENRIC patients had better working memory scores (p = 0.009, d = 0.363) and showed up to 50% less non-specific anxiety (11.8% vs. 21.1%) and depression (5.9% vs. 10.5%) than TAU patients. A general linear model of repeated measures reported a main effect of group, but not of time or group-time interaction, on working memory, with ENRIC patients outperforming TAU patients (p = 0.008, ηp2 = 0.282). Our results suggest that non-immersive VR-based neurocognitive stimulation may help improve short-term working memory outcomes in survivors of critical illness. Moreover, this advantage could be maintained in the long term. An efficacy trial in a larger sample of participants is feasible and must be conducted.

Journal of personalized medicine · 29 citationsread the source →

Identity and the body: Trajectories of body esteem from adolescence to emerging adulthood.

Although Erikson (1968) originally conceptualized identity development as a process of becoming at home in one's body, little work has been done linking identity development and research on the body. This study examines how trajectories of the development of body esteem over time are related to young people's sense of identity and psychological functioning in a longitudinal sample from age 10 to 24 (N = 967). Using group-based trajectory modeling, three cubic subgroups were determined for each of the three types of body esteem: appearance, weight, and attribution. These groups demonstrated significant variations in the ways in which body esteem changes over time. These trajectory groups importantly differed in relationship to gender, identity coherence, identity confusion, and psychological functioning. Results are discussed in terms of the need to use a sociocultural perspective to explore the body's relation to identity development and the importance of disaggregating mean-level findings using person-centered approaches to determine high-risk groups. (PsycINFO Database Record

Developmental psychology · 35 citationsread the source →

Predictors of Engagement in a Virtual Support Intervention for Caregivers of Adults With Heart Failure: An Explanatory Sequential Mixed Methods Study.

Background: Ensuring that consumers are active partners in their personal healthcare is an important goal. We developed and tested a 10-session virtual self-care intervention delivered by health coaches (Virtual Caregiver Coach for You) to informal caregivers of patients with heart failure. Trial results were promising, yet caregivers were not uniformly engaged in the intervention. The aim of this study was to explore factors associated with intervention engagement. Methods: This explanatory sequential mixed methods study was conducted in 3 steps. First, quantitative data on sociodemographic characteristics, caregiving, stress, burden, coping, and treatment credibility and expectancy were analyzed with respect to the number of completed sessions. We used multivariable logistic regression to identify salient predictors of intervention engagement operationalized as completing ≥ 8 of the 10 sessions. Then, 24 caregivers were interviewed to explore personal, intrapersonal, interpersonal, and situational factors associated with intervention engagement. Transcribed interviews were analyzed using content analysis and integrated with the quantitative data in step 3. Results: Race (Black or other people of color), insufficient income, being a parent or grandparent caregiver, and a high number of daily caregiving hours reduced the odds of completing 8 or more sessions, while perceived intervention credibility increased the odds of completing the sessions. Interviews revealed 3 themes explaining the completion of relatively fewer sessions: (1) challenges with life balance, (2) practical day-to-day issues, and 3) not understanding the intervention. Conclusions: Major variables influencing the engagement of heart failure caregivers in this supportive self-care intervention were identified. Accounting for these issues in intervention design and refinement may promote engagement in support programs by the very populations who need such interventions the most.

The Journal of cardiovascular nursingread the source →

Sympathetic nervous system synchrony: An exploratory study of its relationship with the therapeutic alliance and outcome in couple therapy.

In previous research, we found that sympathetic nervous system synchrony, measured via electrodermal activity (EDA), occurs between participants at the start of couple therapy. The aim now was to test whether this synchrony changes during the therapy process, and how any changes may be related to clients' and therapists' evaluations of the working alliance, and the outcome of therapy. Twelve different couple therapy processes were analyzed (24 clients, plus 10 therapists, working in pairs; hence, 4 persons per session) using EDA concordance indices and questionnaires (Outcome Rating Scale, Session Rating Scale, and Clinical Outcomes in Routine Evaluation-Outcome Measure). EDA synchrony between the couples increased from the beginning to the end of therapy. This seemed to be connected to a positive linear trend in female clients' well-being during the therapy process. There were no statistically significant changes in the EDA synchrony between the cotherapists, or between the clients and the therapists. We found specific changes in the EDA synchrony to be related to changes in the therapeutic alliance, and/or changes in the clients' well-being. Heightened EDA synchrony was frequently related to a better outcome; nevertheless, there was one instance in which decreasing synchrony seemed to be more beneficial. It appears that couple therapy can bring spouses closer together also on a physiological level, which could be especially important for the well-being of women. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Psychotherapy (Chicago, Ill.) · 20 citationsread the source →

5-year mental health and eating pattern outcomes following bariatric surgery in adolescents: a prospective cohort study.

Background: Mental health problems are prevalent among adolescents with severe obesity, but long-term mental health outcomes after adolescent bariatric surgery are not well known. We aimed to assess mental health outcomes over 5 years of follow-up after Roux-en-Y gastric bypass surgery in adolescents who participated in the Adolescent Morbid Obesity Surgery (AMOS) study. Methods: This was a non-randomised matched-control study in adolescents aged 13-18 years who had a BMI of 40 kg/m2 or higher, or 35 kg/m2 or higher in addition to obesity-related comorbidity; who had previously undergone failed comprehensive conservative treatment; and were of pubertal Tanner stage III or higher, with height growth velocity beyond peak. A contemporary control group, matched for BMI, age, and sex, who underwent conventional obesity treatment, was obtained from the Swedish Childhood Obesity Treatment Register. Data on dispensed psychiatric drugs and specialist treatment for mental disorders were retrieved from national registers with complete coverage. In the surgical group only, questionnaires were used to assess self-esteem (Rosenberg Self-Esteem [RSE] score), mood (Mood Adjective Checklist [MACL]), and eating patterns (Binge Eating Scale [BES] and Three-Factor Eating Questionnaire-R21 [TFEQ]). This study is registered with ClinicalTrials.gov (NCT00289705). Findings: Between April 10, 2006, and May 20, 2009, 81 adolescents (53 [65%] female) underwent Roux-en-Y gastric bypass surgery, and 80 control participants received conventional treatment. The proportion of participants prescribed psychiatric drugs did not differ between groups in the years before study inclusion (pre-baseline; absolute risk difference 5% [95% CI -7 to 16], p=0·4263) or after intervention (10% [-6 to 24], p=0·2175). Treatment for mental and behavioural disorders did not differ between groups before baseline (2% [-10 to 14], p=0·7135); however, adolescents in the surgical group had more specialised psychiatric treatment in the 5 years after obesity treatment than did the control group (15% [1 to 28], p=0·0410). There were few patients who discontinued psychiatric treatment post-surgery (three [4%] receiving psychiatric drug treatment and six [7%] receiving specialised care for a mental disorder before surgery). In the surgical group, self-esteem (RSE score) was improved after 5 years (mixed model mean 21·6 [95% CI 19·9 to 23·4]) relative to baseline (18·9 [17·4 to 20·4], p=0·0059), but overall mood (MACL score) was not (2·8 [2·7 to 2·9] at 5 years vs 2·7 [2·6 to 2·8] at baseline, p=0·0737). Binge eating was improved at 5 years (9·3 [7·4 to 11·2]) relative to baseline (15·0 [13·5 to 16·5], p<0·0001). Relative changes in BMI were not associated with the presence or absence of binge eating at baseline. Interpretation: Mental health problems persist in adolescents 5 years after bariatric surgery despite substantial weight loss. Although bariatric surgery can improve many aspects of health, alleviation of mental health problems should not be expected, and a multidisciplinary bariatric team should offer long-term mental health support after surgery. Funding: Swedish Research Council, VINNOVA, Västra Götalandsregionen, ALF VG-region, Region Stockholm, Swedish Child Diabetes Foundation, Swedish Heart and Lung Foundation, Tore Nilsson's Foundation, SUS Foundations and Donations, Capio Research Foundation, and Mary von Sydow's Foundation.

The Lancet. Child & adolescent health · 44 citationsread the source →

Multidisciplinary biopsychosocial rehabilitation for chronic low back pain: Cochrane systematic review and meta-analysis.

Objective: To assess the long term effects of multidisciplinary biopsychosocial rehabilitation for patients with chronic low back pain. Design: Systematic review and random effects meta-analysis of randomised controlled trials. Data sources: Electronic searches of Cochrane Back Review Group Trials Register, CENTRAL, Medline, Embase, PsycINFO, and CINAHL databases up to February 2014, supplemented by hand searching of reference lists and forward citation tracking of included trials. Study selection criteria: Trials published in full; participants with low back pain for more than three months; multidisciplinary rehabilitation involved a physical component and one or both of a psychological component or a social or work targeted component; multidisciplinary rehabilitation was delivered by healthcare professionals from at least two different professional backgrounds; multidisciplinary rehabilitation was compared with a non- multidisciplinary intervention. Results: Forty one trials included a total of 6858 participants with a mean duration of pain of more than one year who often had failed previous treatment. Sixteen trials provided moderate quality evidence that multidisciplinary rehabilitation decreased pain (standardised mean difference 0.21, 95% confidence interval 0.04 to 0.37; equivalent to 0.5 points in a 10 point pain scale) and disability (0.23, 0.06 to 0.40; equivalent to 1.5 points in a 24 point Roland-Morris index) compared with usual care. Nineteen trials provided low quality evidence that multidisciplinary rehabilitation decreased pain (standardised mean difference 0.51, -0.01 to 1.04) and disability (0.68, 0.16 to 1.19) compared with physical treatments, but significant statistical heterogeneity across trials was present. Eight trials provided moderate quality evidence that multidisciplinary rehabilitation improves the odds of being at work one year after intervention (odds ratio 1.87, 95% confidence interval 1.39 to 2.53) compared with physical treatments. Seven trials provided moderate quality evidence that multidisciplinary rehabilitation does not improve the odds of being at work (odds ratio 1.04, 0.73 to 1.47) compared with usual care. Two trials that compared multidisciplinary rehabilitation with surgery found little difference in outcomes and an increased risk of adverse events with surgery. Conclusions: Multidisciplinary biopsychosocial rehabilitation interventions were more effective than usual care (moderate quality evidence) and physical treatments (low quality evidence) in decreasing pain and disability in people with chronic low back pain. For work outcomes, multidisciplinary rehabilitation seems to be more effective than physical treatment but not more effective than usual care.

BMJ (Clinical research ed.) · meta-analysis · 626 citationsread the source →

Impact of mobile health interventions during the perinatal period on maternal psychosocial outcomes: a systematic review.

Objective: The objective of this review was to evaluate the effectiveness of mother-targeted mobile health (mHealth) education interventions during the perinatal period on maternal psychosocial outcomes in high-income countries. Introduction: The perinatal period is an exciting yet challenging period for mothers that requires physical, emotional and social adjustment to new norms and expectations. In recent years, there has been an increase in the use of mHealth by new mothers who are seeking health information through online or mobile applications. While there have been systematic reviews on the impact of mHealth interventions on maternal and newborn health in low- and middle-income countries, the impact of these interventions on maternal psychosocial health outcomes in high-income countries remains uncertain. Inclusion criteria: This review considered studies of mHealth education interventions targeting mothers in high-income countries (as defined by the World Bank) during the perinatal period. Interventions must have started between the antenatal period (conception through birth) through six weeks postpartum. All experimental study designs were included. Outcomes included self-efficacy, social support, postpartum anxiety and postpartum depression. Methods: PubMed, CINAHL, PsycINFO and Embase were searched for published studies in English on December 16, 2018. Gray literature was also searched for non-peer reviewed articles, including Google Scholar, mHealth intelligence and clinical trials databases. Critical appraisal was undertaken by two independent reviewers using standardized critical appraisal instruments from JBI. Quantitative data were extracted from included studies independently by two reviewers using the standardized data extraction tool from JBI. All conflicts were solved through consensus with a third reviewer. Quantitative data were, where possible, pooled in statistical meta-analysis using RevMan. Where statistical pooling was not possible, findings were reported narratively. Results: Of the 1,607 unique articles identified, 106 full-text papers were screened and 24 articles were critically appraised, with 21 included in the final review. Eleven were quasi-experimental and 10 were randomized controlled trials. The mHealth intervention approach varied, with text message and mobile applications being the most common. Length of intervention ranged from four weeks to six months. The topics of the mHealth intervention varied widely, with the most common topic being postpartum depression. Mothers who received an mHealth intervention targeting postpartum depression showed a decreased score on the Edinburgh Postnatal Depression Scale when measured post-intervention (odds ratio = -6.01, 95% confidence interval = -8.34 to -3.67, p < 0.00001). The outcomes related to self-efficacy, social support and anxiety showed mixed findings of effectiveness (beneficial and no change) across the studies identified. Conclusions: This review provides insight into the effectiveness of mHealth interventions targeting mothers in high-income countries in the perinatal period to enhance four psychosocial outcomes: self-efficacy, social support, anxiety and depression. Despite a wide variety of outcome measurements used, the predominant findings suggest that there are insufficient data to conclude that mHealth interventions can improve self-efficacy and anxiety outcomes. Potential benefits on social support were related to interventions targeting postnatal behaviors. Postpartum depression was the mostly commonly reported outcome. Findings related to the comparison of pre-post outcomes and intervention versus control demonstrated that mHealth interventions targeting postpartum depression were associated with a reduction in postpartum depression.

JBI evidence synthesis · meta-analysis · 41 citationsread the source →

Burden of 375 diseases and injuries, risk-attributable burden of 88 risk factors, and healthy life expectancy in 204 countries and territories, including 660 subnational locations, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023.

Background: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. Methods: The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. Findings: Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant). Interpretation: Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. Funding: Gates Foundation and Bloomberg Philanthropies.

Lancet (London, England) · 257 citationsread the source →

Early Time-Restricted Feeding Reduces Appetite and Increases Fat Oxidation But Does Not Affect Energy Expenditure in Humans.

Objective: Eating earlier in the daytime to align with circadian rhythms in metabolism enhances weight loss. However, it is unknown whether these benefits are mediated through increased energy expenditure or decreased food intake. Therefore, this study performed the first randomized trial to determine how meal timing affects 24-hour energy metabolism when food intake and meal frequency are matched. Methods: Eleven adults with overweight practiced both early time-restricted feeding (eTRF) (eating from 8 am to 2 pm) and a control schedule (eating from 8 am to 8 pm) for 4 days each. On the fourth day, 24-hour energy expenditure and substrate oxidation were measured by whole-room indirect calorimetry, in conjunction with appetite and metabolic hormones. Results: eTRF did not affect 24-hour energy expenditure (Δ = 10 ± 16 kcal/d; P = 0.55). Despite the longer daily fast (intermittent fasting), eTRF decreased mean ghrelin levels by 32 ± 10 pg/mL (P = 0.006), made hunger more even-keeled (P = 0.006), and tended to increase fullness (P = 0.06-0.10) and decrease the desire to eat (P = 0.08). eTRF also increased metabolic flexibility (P = 0.0006) and decreased the 24-hour nonprotein respiratory quotient (Δ = -0.021 ± 0.010; P = 0.05). Conclusions: Meal-timing interventions facilitate weight loss primarily by decreasing appetite rather than by increasing energy expenditure. eTRF may also increase fat loss by increasing fat oxidation.

Obesity (Silver Spring, Md.) · 226 citationsread the source →

Parenting Interventions for Refugees and Forcibly Displaced Families: A Systematic Review.

Globally, an estimated 79.5 million individuals have been displaced, nearly 40% of whom are children. Parenting interventions may have the potential to improve outcomes for displaced families. To investigate this, we conducted a systematic review to identify the types of caregiver or parenting interventions that have been evaluated among displaced families, to assess their efficacy across a range of contexts, and to describe their cultural and contextual adaptations. The review followed PRISMA guidelines. At stage one, all articles describing caregiver/parenting interventions for forcibly displaced families were included to provide a scoping review of the state of the literature. At stage two, only randomized controlled trials (RCTs) and quasi-experimental designs were included, allowing for quantitative analysis of program effects. A total of 30 articles (24 studies) were identified in stage one. 95.8% of these articles were published in the past 10 years. Of these, 14 articles (10 studies) used an RCT or quasi-experimental design to assess program efficacy or effectiveness. Relative to control groups, those assigned to caregiving programs showed significant, beneficial effects across the domains of parenting behaviors and attitudes, child psychosocial and developmental outcomes, and parent mental health. Cultural adaptations and recruitment and engagement strategies are described. The evidence base for caregiving programs for displaced families has expanded in recent years but remains limited. Caregiving/parenting programs show promise for reducing the negative effects of forced displacement on families, but future studies are needed to understand which programs show the greatest potential for scalability.

Clinical child and family psychology review · systematic review · 34 citationsread the source →

Effects of digital Cognitive Behavioural Therapy for Insomnia on cognitive function: study protocol for a randomised controlled trial.

Background: The daytime effects of insomnia pose a significant burden to patients and drive treatment seeking. In addition to subjective deficits, meta-analytic data show that patients experience reliable objective impairments across several cognitive domains. While Cognitive Behavioural Therapy for Insomnia (CBT-I) is an effective and scalable treatment, we know little about its impact upon cognitive function. Trials of CBT-I have typically used proxy measures for cognitive functioning, such as fatigue or work performance scales, and no study has assessed self-reported impairment in cognitive function as a primary outcome. Moreover, only a small number of studies have assessed objective cognitive performance, pre-to-post CBT-I, with mixed results. This study specifically aims to (1) investigate the impact of CBT-I on cognitive functioning, assessed through both self-reported impairment and objective performance measures, and (2) examine whether change in sleep mediates this impact. Methods/design: We propose a randomised controlled trial of 404 community participants meeting criteria for Insomnia Disorder. In the DISCO trial (D efining the I mpact of improved S leep on CO gnitive function (DISCO)) participants will be randomised to digital automated CBT-I delivered by a web and/or mobile platform (in addition to treatment as usual (TAU)) or to a wait-list control (in addition to TAU). Online assessments will take place at 0 (baseline), 10 (post-treatment), and 24 (follow-up) weeks. At week 25, all participants allocated to the wait-list group will be offered digital CBT-I, at which point the controlled element of the trial will be complete. The primary outcome is self-reported cognitive impairment at post-treatment (10 weeks). Secondary outcomes include objective cognitive performance, insomnia severity, sleepiness, fatigue, and self-reported cognitive failures and emotional distress. All main analyses will be carried out on completion of follow-up assessments and will be based on the intention-to-treat principle. Further analyses will determine to what extent observed changes in self-reported cognitive impairment and objective cognitive performance are mediated by changes in sleep. The trial is supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) based at Oxford University Hospitals NHS Trust and University of Oxford, and by the NIHR Oxford Health BRC. Discussion: This study will be the first large-scale examination of the impact of digital CBT-I on self-reported cognitive impairment and objective cognitive performance. Trial registration: ISRCTN, ID: ISRCTN89237370 . Registered on 17 October 2016.

Trials · 10 citationsread the source →

Acute Finnish sauna heat exposure induces stronger immune cell than cytokine responses.

Regular exposure to Finnish sauna bathing (FSB) has been associated with reduced morbidity and mortality. This study aimed to examine the acute effects of FSB on immune cell mobilization, circulating cytokines, and their associations with changes in body temperature. A total of 51 adults - 27 women (mean age 50 ± 9 years, body mass index (BMI) 27 ± 5 kg/m2) and 24 men (mean age 50 ± 10 years, BMI 27 ± 3 kg/m2) - were exposed to a 30-minute session of acute FSB at a temperature of + 73°C. Venous blood samples were collected at baseline, immediately after and 30 minutes after the FSB and analyzed for immune cells and 37 cytokines. Subjects were allowed to drink water throughout. FSB increased body temperature from 36.4 ± 0.5°C to 38.4 ± 0.7°C, without altering plasma volume. Total white blood cell (WBC) count rose significantly and remained slightly elevated 30 minutes post-sauna in women. Neutrophil and lymphocyte counts increased immediately after the FSB but returned to baseline after 30 minutes, whereas MXD cells (monocytes, eosinophils, basophils) remained elevated. The levels of only two cytokines changed significantly. Although only a few correlations were observed between changes in immune cells and cytokines, 18 significant associations were identified between changes in body temperature and circulating cytokines - particularly immediately post-sauna - but not with WBC changes. Thus, a 30-minute session of acute FSB induces immune cell mobilization. The observed associations between changes in body temperature and circulating cytokines suggest that sauna-induced heat stress, along with immune activation, may partly mediate the health benefits of FSB.

Temperature (Austin, Tex.)read the source →

Efficacy of cognitive behavioural therapy for sleep improvement in patients with persistent delusions and hallucinations (BEST): a prospective, assessor-blind, randomised controlled pilot trial.

Background: Sleep disturbance occurs in most patients with delusions or hallucinations and should be treated as a clinical problem in its own right. However, cognitive behavioural therapy (CBT)-the best evidence-based treatment for insomnia-has not been tested in this patient population. We aimed to pilot procedures for a randomised trial testing CBT for sleep problems in patients with current psychotic experiences, and to provide a preliminary assessment of potential benefit. Methods: We did this prospective, assessor-blind, randomised controlled pilot trial (Better Sleep Trial [BEST]) at two mental health centres in the UK. Patients (aged 18-65 years) with persistent distressing delusions or hallucinations in the context of insomnia and a schizophrenia spectrum diagnosis were randomly assigned (1:1), via a web-based randomisation system with minimisation to balance for sex, insomnia severity, and psychotic experiences, to receive either eight sessions of CBT plus standard care (medication and contact with the local clinical team) or standard care alone. Research assessors were masked to group allocation. Assessment of outcome was done at weeks 0, 12 (post-treatment), and 24 (follow-up). The primary efficacy outcomes were insomnia assessed by the Insomnia Severity Index (ISI) and delusions and hallucinations assessed by the Psychotic Symptoms Rating Scale (PSYRATS) at week 12. We did analysis by intention to treat, with an aim to provide confidence interval estimation of treatment effects. This study is registered with ISRCTN, number 33695128. Findings: Between Dec 14, 2012, and May 22, 2013, and Nov 7, 2013, and Aug 26, 2014, we randomly assigned 50 patients to receive CBT plus standard care (n=24) or standard care alone (n=26). The last assessments were completed on Feb 10, 2015. 48 (96%) patients provided follow-up data. 23 (96%) patients offered CBT took up the intervention. Compared with standard care, CBT led to reductions in insomnia in the large effect size range at week 12 (adjusted mean difference 6.1, 95% CI 3.0-9.2, effect size d=1.9). By week 12, nine (41%) of 22 patients receiving CBT and one (4%) of 25 patients receiving standard care alone no longer had insomnia, with ISI scores lower than the cutoff for insomnia. The treatment effect estimation for CBT covered a range from reducing but also increasing delusions (adjusted mean difference 0.3, 95% CI -2.0 to 2.6) and hallucinations (-1.9, -6.5 to 2.7). Three patients, all in the CBT group, had five adverse events, although none were regarded as related to study treatment. Interpretation: Our findings show that CBT for insomnia might be highly effective for improving sleep in patients with persistent delusions or hallucinations. A larger, suitably powered phase 3 study is now needed to provide a precise estimate of the effects of CBT for sleep problems, both on sleep and psychotic experiences. Funding: Research for Patient Benefit Programme, National Institute for Health Research.

The lancet. Psychiatry · randomised controlled trial · 160 citationsread the source →

Mind-Body Exercise for Anxiety and Depression in COPD Patients: A Systematic Review and Meta-Analysis.

Objectives: Mind-body exercise has been generally recognized as a beneficial strategy to improve mental health in those with Chronic Obstructive Pulmonary Disease (COPD). However, to date, no attempt has been made to collate this literature. The aim of the present study was to systematically analyze the effects of mind-body exercise for COPD patients with anxiety and depression and provide scientific evidence-based exercise prescription. Methods: both Chinese and English databases (PubMed, the Cochrane Library, EMBASE, Web of Science, Google Scholar, Chinese National Knowledge Infrastructure, Wanfang, Baidu Scholar) were used as sources of data to search randomized controlled trials (RCT) relating to mind-body exercise in COPD patients with anxiety and depression that were published between January 1982 to June 2019. 13 eligible RCT studies were finally used for meta-analysis. Results: Mind-body exercise (tai chi, health qigong, yoga) had significant benefits on COPD patients with anxiety (SMD= -0.76, 95% CI -0.91 to -0.60, p=0.04, I2=47.4%) and depression (SMD= -0.86, 95% CI -1.14 to -0.58, p=0.000, I2=71.4%). Sub-group analysis indicated that, for anxiety, 30-60 min exercise session for 24 weeks of health qigong or yoga had a significant effect on patients with COPD who are more than 70 years and have more than a 10-year disease course. For depression, 2-3 times a week, 30-60 min each time of health qigong had a significant effect on patients with COPD patients who are more than 70 years old and have less than a 10-year disease course. Conclusions: Mind-body exercise could reduce levels of anxiety and depression in those with COPD. More robust RCT are required on this topic.

International journal of environmental research and public health · meta-analysis · 103 citationsread the source →

Health impacts of parental migration on left-behind children and adolescents: a systematic review and meta-analysis.

Background: Globally, a growing number of children and adolescents are left behind when parents migrate. We investigated the effect of parental migration on the health of left behind-children and adolescents in low-income and middle-income countries (LMICs). Methods: For this systematic review and meta-analysis we searched MEDLINE, Embase, CINAHL, the Cochrane Library, Web of Science, PsychINFO, Global Index Medicus, Scopus, and Popline from inception to April 27, 2017, without language restrictions, for observational studies investigating the effects of parental migration on nutrition, mental health, unintentional injuries, infectious disease, substance use, unprotected sex, early pregnancy, and abuse in left-behind children (aged 0-19 years) in LMICs. We excluded studies in which less than 50% of participants were aged 0-19 years, the mean or median age of participants was more than 19 years, fewer than 50% of parents had migrated for more than 6 months, or the mean or median duration of migration was less than 6 months. We screened studies using systematic review software and extracted summary estimates from published reports independently. The main outcomes were risk and prevalence of health outcomes, including nutrition (stunting, wasting, underweight, overweight and obesity, low birthweight, and anaemia), mental health (depressive disorder, anxiety disorder, conduct disorders, self-harm, and suicide), unintentional injuries, substance use, abuse, and infectious disease. We calculated pooled risk ratios (RRs) and standardised mean differences (SMDs) using random-effects models. This study is registered with PROSPERO, number CRD42017064871. Findings: Our search identified 10 284 records, of which 111 studies were included for analysis, including a total of 264 967 children (n=106 167 left-behind children and adolescents; n=158 800 children and adolescents of non-migrant parents). 91 studies were done in China and focused on effects of internal labour migration. Compared with children of non-migrants, left-behind children had increased risk of depression and higher depression scores (RR 1·52 [95% CI 1·27-1·82]; SMD 0·16 [0·10-0·21]), anxiety (RR 1·85 [1·36-2·53]; SMD 0·18 [0·11-0·26]), suicidal ideation (RR 1·70 [1·28-2·26]), conduct disorder (SMD 0·16 [0·04-0·28]), substance use (RR 1·24 [1·00-1·52]), wasting (RR 1·13 [1·02-1·24]) and stunting (RR 1·12 [1·00-1·26]). No differences were identified between left-behind children and children of non-migrants for other nutrition outcomes, unintentional injury, abuse, or diarrhoea. No studies reported outcomes for other infectious diseases, self-harm, unprotected sex, or early pregnancy. Study quality varied across the included studies, with 43% of studies at high or unclear risk of bias across five or more domains. Interpretation: Parental migration is detrimental to the health of left-behind children and adolescents, with no evidence of any benefit. Policy makers and health-care professionals need to take action to improve the health of these young people. Funding: Wellcome Trust.

Lancet (London, England) · meta-analysis · 330 citationsread the source →

Sleep interventions for osteoarthritis and spinal pain: a systematic review and meta-analysis of randomized controlled trials.

Objectives: To determine if sleep interventions improve pain and sleep in people with osteoarthritis (OA) and/or spinal pain compared to control/placebo. Design: Medline, Embase, AMED, PsycINFO, CENTRAL, CINAHL and PEDro were searched from their inception date to July 2017. Keywords relating to "sleep", "OA", "spinal pain", and "randomized controlled trial (RCT)" were combined. Included RCTs investigated the use of sleep interventions for people with OA and/or spinal pain, and measured at least one sleep and health related outcome. Meta-analyses were performed to pool mean differences for pain and sleep quality. Prospero: CRD42016036315. Results: Of 1445 unique records, 24 studies were included. Sixteen studies included participants with spinal pain, seven with OA, and one included a mixed population. Sleep interventions included established sleep interventions (ESI) [cognitive behavioural therapy (CBT) and pharmacological interventions], and a range of others. Intervention periods ranged from 4 to 10 weeks. Thirteen studies were of moderate to high quality (PEDro ≥ 6/10). Due to high heterogeneity between studies we also performed sub-group and sensitivity analyses. ESI decreased Insomnia Severity Index (ISI) for people with low back pain (LBP) (pooled mean difference: -6.78/28, 95% confidence interval (95% CI): [-9.47, -4.09], I2 = 40%) and OA (-2.41, [-4.19, -0.63], 0%). However ESI decreased pain for people with LBP (pooled mean difference: visual analogue scale (VAS) -12.77/100, 95% CI: [-17.57, -7.97], I2 = 0%), but not OA (-2.32, [-7.18, 2.54], 27%). Conclusion: ESI appeared to improve sleep and pain for people with LBP, and sleep for people with OA. However more vigorous studies need to be conducted.

Osteoarthritis and cartilage · meta-analysis · 41 citationsread the source →

Effectiveness of brief alcohol interventions in primary care populations.

Background: Excessive drinking is a significant cause of mortality, morbidity and social problems in many countries. Brief interventions aim to reduce alcohol consumption and related harm in hazardous and harmful drinkers who are not actively seeking help for alcohol problems. Interventions usually take the form of a conversation with a primary care provider and may include feedback on the person's alcohol use, information about potential harms and benefits of reducing intake, and advice on how to reduce consumption. Discussion informs the development of a personal plan to help reduce consumption. Brief interventions can also include behaviour change or motivationally-focused counselling. This is an update of a Cochrane Review published in 2007. Objectives: To assess the effectiveness of screening and brief alcohol intervention to reduce excessive alcohol consumption in hazardous or harmful drinkers in general practice or emergency care settings. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and 12 other bibliographic databases to September 2017. We searched Alcohol and Alcohol Problems Science Database (to December 2003, after which the database was discontinued), trials registries, and websites. We carried out handsearching and checked reference lists of included studies and relevant reviews. Selection criteria: We included randomised controlled trials (RCTs) of brief interventions to reduce hazardous or harmful alcohol consumption in people attending general practice, emergency care or other primary care settings for reasons other than alcohol treatment. The comparison group was no or minimal intervention, where a measure of alcohol consumption was reported. 'Brief intervention' was defined as a conversation comprising five or fewer sessions of brief advice or brief lifestyle counselling and a total duration of less than 60 minutes. Any more was considered an extended intervention. Digital interventions were not included in this review. Data collection and analysis: We used standard methodological procedures expected by Cochrane. We carried out subgroup analyses where possible to investigate the impact of factors such as gender, age, setting (general practice versus emergency care), treatment exposure and baseline consumption. Main results: We included 69 studies that randomised a total of 33,642 participants. Of these, 42 studies were added for this update (24,057 participants). Most interventions were delivered in general practice (38 studies, 55%) or emergency care (27 studies, 39%) settings. Most studies (61 studies, 88%) compared brief intervention to minimal or no intervention. Extended interventions were compared with brief (4 studies, 6%), minimal or no intervention (7 studies, 10%). Few studies targeted particular age groups: adolescents or young adults (6 studies, 9%) and older adults (4 studies, 6%). Mean baseline alcohol consumption was 244 g/week (30.5 standard UK units) among the studies that reported these data. Main sources of bias were attrition and lack of provider or participant blinding. The primary meta-analysis included 34 studies (15,197 participants) and provided moderate-quality evidence that participants who received brief intervention consumed less alcohol than minimal or no intervention participants after one year (mean difference (MD) -20 g/week, 95% confidence interval (CI) -28 to -12). There was substantial heterogeneity among studies (I² = 73%). A subgroup analysis by gender demonstrated that both men and women reduced alcohol consumption after receiving a brief intervention. We found moderate-quality evidence that brief alcohol interventions have little impact on frequency of binges per week (MD -0.08, 95% CI -0.14 to -0.02; 15 studies, 6946 participants); drinking days per week (MD -0.13, 95% CI -0.23 to -0.04; 11 studies, 5469 participants); or drinking intensity (-0.2 g/drinking day, 95% CI -3.1 to 2.7; 10 studies, 3128 participants).We found moderate-quality evidence of little difference in quantity of alcohol consumed when extended and no or minimal interventions were compared (-14 g/week, 95% CI -37 to 9; 6 studies, 1296 participants). There was little difference in binges per week (-0.08, 95% CI -0.28 to 0.12; 2 studies, 456 participants; moderate-quality evidence) or difference in days drinking per week (-0.45, 95% CI -0.81 to -0.09; 2 studies, 319 participants; moderate-quality evidence). Extended versus no or minimal intervention provided little impact on drinking intensity (9 g/drinking day, 95% CI -26 to 9; 1 study, 158 participants; low-quality evidence).Extended intervention had no greater impact than brief intervention on alcohol consumption, although findings were imprecise (MD 2 g/week, 95% CI -42 to 45; 3 studies, 552 participants; low-quality evidence). Numbers of binges were not reported for this comparison, but one trial suggested a possible drop in days drinking per week (-0.5, 95% CI -1.2 to 0.2; 147 participants; low-quality evidence). Results from this trial also suggested very little impact on drinking intensity (-1.7 g/drinking day, 95% CI -18.9 to 15.5; 147 participants; very low-quality evidence).Only five studies reported adverse effects (very low-quality evidence). No participants experienced any adverse effects in two studies; one study reported that the intervention increased binge drinking for women and two studies reported adverse events related to driving outcomes but concluded they were equivalent in both study arms. Sources of funding were reported by 67 studies (87%). With two exceptions, studies were funded by government institutes, research bodies or charitable foundations. One study was partly funded by a pharmaceutical company and a brewers association, another by a company developing diagnostic testing equipment. Authors' conclusions: We found moderate-quality evidence that brief interventions can reduce alcohol consumption in hazardous and harmful drinkers compared to minimal or no intervention. Longer counselling duration probably has little additional effect. Future studies should focus on identifying the components of interventions which are most closely associated with effectiveness.

The Cochrane database of systematic reviews · meta-analysis · 409 citationsread the source →