Search the source libraries

Benefits of supervised group exercise programme for women being treated for early stage breast cancer: pragmatic randomised controlled trial.

Objectives: To determine functional and psychological benefits of a 12 week supervised group exercise programme during treatment for early stage breast cancer, with six month follow-up. Design: Pragmatic randomised controlled prospective open trial. Setting: Three National Health Service oncology clinics in Scotland and community exercise facilities. Participants: 203 women entered the study; 177 completed the six month follow-up. Interventions: Supervised 12 week group exercise programme in addition to usual care, compared with usual care. Main outcome measures: Functional assessment of cancer therapy (FACT) questionnaire, Beck depression inventory, positive and negative affect scale, body mass index, seven day recall of physical activity, 12 minute walk test, and assessment of shoulder mobility. Results: Mixed effects models with adjustment for baseline values, study site, treatment at baseline, and age gave intervention effect estimates (intervention minus control) at 12 weeks of 129 (95% confidence interval 83 to 176) for metres walked in 12 minutes, 182 (75 to 289) for minutes of moderate intensity activity reported in a week, 2.6 (1.6 to 3.7) for shoulder mobility, 2.5 (1.0 to 3.9) for breast cancer specific subscale of quality of life, and 4.0 (1.8 to 6.3) for positive mood. No significant effect was seen for general quality of life (FACT-G), which was the primary outcome. At the six month follow-up, most of these effects were maintained and an intervention effect for breast cancer specific quality of life emerged. No adverse effects were noted. Conclusion: Supervised group exercise provided functional and psychological benefit after a 12 week intervention and six months later. Clinicians should encourage activity for their patients. Policy makers should consider the inclusion of exercise opportunities in cancer rehabilitation services. Trial registration Current controlled trials ISRCTN12587864 [controlled-trials.com].

BMJ (Clinical research ed.) · randomised controlled trial · 270 citationsread the source →

Smartphone-delivered self-management for first-episode psychosis: the ARIES feasibility randomised controlled trial.

Objectives: To test the feasibility and acceptability of a randomised controlled trial (RCT) to evaluate a Smartphone-based self-management tool in Early Intervention in Psychosis (EIP) services. Design: A two-arm unblinded feasibility RCT. Setting: Six NHS EIP services in England. Participants: Adults using EIP services who own an Android Smartphone. Participants were recruited until the recruitment target was met (n=40). Interventions: Participants were randomised with a 1:1 allocation to one of two conditions: (1) treatment as usual from EIP services (TAU) or (2) TAU plus access to My Journey 3 on their own Smartphone. My Journey 3 features a range of self-management components including access to digital recovery and relapse prevention plans, medication tracking and symptom monitoring. My Journey 3 use was at the users' discretion and was supported by EIP service clinicians. Participants had access for a median of 38.1 weeks. Primary and secondary outcome measures: Feasibility outcomes included recruitment, follow-up rates and intervention engagement. Participant data on mental health outcomes were collected from clinical records and from research assessments at baseline, 4 months and 12 months. Results: 83% and 75% of participants were retained in the trial at the 4-month and 12-month assessments. All treatment group participants had access to My Journey 3 during the trial, but technical difficulties caused delays in ensuring timely access to the intervention. The median number of My Journey 3 uses was 16.5 (IQR 8.5 to 23) and median total minutes spent using My Journey 3 was 26.8 (IQR 18.3 to 57.3). No serious adverse events were reported. Conclusions: Recruitment and retention were feasible. Within a trial context, My Journey 3 could be successfully delivered to adults using EIP services, but with relatively low usage rates. Further evaluation of the intervention in a larger trial may be warranted, but should include attention to implementation. Trial registration: ISRCTN10004994.

BMJ open · randomised controlled trial · 27 citationsread the source →

Evaluation of agomelatine for the treatment of sleep problems in adults with autism spectrum disorder and co-morbid intellectual disability.

Purpose: Intellectual disability (ID) and autism spectrum disorder (ASD) are common, co-occurring developmental disorders and are frequently associated with sleep problems. This study aimed to assess the effectiveness and tolerability of agomelatine as a pharmacotherapy for sleep problems in ASD adults with ID. Method: A randomised, crossover, triple-blind, placebo-controlled clinical trial, with two three-month periods of treatment starting with either agomelatine or placebo and a washout period of two weeks. Ambulatory circadian monitoring (24 hours/7 days) evaluated total sleep time (TST) as the primary outcome variable. Results: Participants (N=23; 35±12 years old; 83% male) had a median of three (interquartile range (IQR) 1-4) co-morbidities and were taking a median of five (IQR 2-7) prescribed drugs. Before agomelatine or placebo treatment, all subjects presented with insomnia symptoms, including sleep latency (100% abnormal, 55±23 minutes) or TST (55% abnormal, 449±177 minutes), and 66% had circadian rhythm sleep-wake abnormalities with rhythm phase advancements according to the M5 sleep phase marker values. During the three-month agomelatine treatment, night TST significantly increased by a mean of 83 minutes (16% abnormal, 532±121 minutes), together with a phase correction (M5 1:45±2:28 hours vs. 3:15±2:20 hours), improving sleep stability in wrist temperature rhythm (0.43±0.29 vs. 0.52±0.18 AU). Adverse events were mild and transient. Conclusions: Agomelatine was effective and well tolerated for treating insomnia and circadian rhythm sleep problems present in adults with ASD and ID.

Journal of psychopharmacology (Oxford, England) · randomised controlled trial · 15 citationsread the source →

Focal psychodynamic therapy, cognitive behaviour therapy, and optimised treatment as usual in outpatients with anorexia nervosa (ANTOP study): randomised controlled trial.

Background: Psychotherapy is the treatment of choice for patients with anorexia nervosa, although evidence of efficacy is weak. The Anorexia Nervosa Treatment of OutPatients (ANTOP) study aimed to assess the efficacy and safety of two manual-based outpatient treatments for anorexia nervosa--focal psychodynamic therapy and enhanced cognitive behaviour therapy--versus optimised treatment as usual. Methods: The ANTOP study is a multicentre, randomised controlled efficacy trial in adults with anorexia nervosa. We recruited patients from ten university hospitals in Germany. Participants were randomly allocated to 10 months of treatment with either focal psychodynamic therapy, enhanced cognitive behaviour therapy, or optimised treatment as usual (including outpatient psychotherapy and structured care from a family doctor). The primary outcome was weight gain, measured as increased body-mass index (BMI) at the end of treatment. A key secondary outcome was rate of recovery (based on a combination of weight gain and eating disorder-specific psychopathology). Analysis was by intention to treat. This trial is registered at http://isrctn.org, number ISRCTN72809357. Findings: Of 727 adults screened for inclusion, 242 underwent randomisation: 80 to focal psychodynamic therapy, 80 to enhanced cognitive behaviour therapy, and 82 to optimised treatment as usual. At the end of treatment, 54 patients (22%) were lost to follow-up, and at 12-month follow-up a total of 73 (30%) had dropped out. At the end of treatment, BMI had increased in all study groups (focal psychodynamic therapy 0·73 kg/m(2), enhanced cognitive behaviour therapy 0·93 kg/m(2), optimised treatment as usual 0·69 kg/m(2)); no differences were noted between groups (mean difference between focal psychodynamic therapy and enhanced cognitive behaviour therapy -0·45, 95% CI -0·96 to 0·07; focal psychodynamic therapy vs optimised treatment as usual -0·14, -0·68 to 0·39; enhanced cognitive behaviour therapy vs optimised treatment as usual -0·30, -0·22 to 0·83). At 12-month follow-up, the mean gain in BMI had risen further (1·64 kg/m(2), 1·30 kg/m(2), and 1·22 kg/m(2), respectively), but no differences between groups were recorded (0·10, -0·56 to 0·76; 0·25, -0·45 to 0·95; 0·15, -0·54 to 0·83, respectively). No serious adverse events attributable to weight loss or trial participation were recorded. Interpretation: Optimised treatment as usual, combining psychotherapy and structured care from a family doctor, should be regarded as solid baseline treatment for adult outpatients with anorexia nervosa. Focal psychodynamic therapy proved advantageous in terms of recovery at 12-month follow-up, and enhanced cognitive behaviour therapy was more effective with respect to speed of weight gain and improvements in eating disorder psychopathology. Long-term outcome data will be helpful to further adapt and improve these novel manual-based treatment approaches. Funding: German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF), German Eating Disorders Diagnostic and Treatment Network (EDNET).

Lancet (London, England) · randomised controlled trial · 230 citationsread the source →

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

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

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

Percutaneous mitral valve repair for mitral regurgitation in high-risk patients: results of the EVEREST II study.

Background: The EVEREST II (Endovascular Valve Edge-to-Edge REpair STudy) High-Risk registry and REALISM Continued Access Study High-Risk Arm are prospective registries of patients who received the MitraClip device (Abbott Vascular, Santa Clara, California) for mitral regurgitation (MR) in the United States. Objectives: The purpose of this study was to report 12-month outcomes in high-risk patients treated with the percutaneous mitral valve edge-to-edge repair. Methods: Patients with grades 3 to 4+ MR and a surgical mortality risk of ≥12%, based on the Society of Thoracic Surgeons risk calculator or the estimate of a surgeon coinvestigator following pre-specified protocol criteria, were enrolled. Results: In the studies, 327 of 351 patients completed 12 months of follow-up. Patients were elderly (76 ± 11 years of age), with 70% having functional MR and 60% having prior cardiac surgery. The mitral valve device reduced MR to ≤2+ in 86% of patients at discharge (n = 325; p < 0.0001). Major adverse events at 30 days included death in 4.8%, myocardial infarction in 1.1%, and stroke in 2.6%. At 12 months, MR was ≤2+ in 84% of patients (n = 225; p < 0.0001). From baseline to 12 months, left ventricular (LV) end-diastolic volume improved from 161 ± 56 ml to 143 ± 53 ml (n = 203; p < 0.0001) and LV end-systolic volume improved from 87 ± 47 ml to 79 ± 44 ml (n = 202; p < 0.0001). New York Heart Association functional class improved from 82% in class III/IV at baseline to 83% in class I/II at 12 months (n = 234; p < 0.0001). The 36-item Short Form Health Survey physical and mental quality-of-life scores improved from baseline to 12 months (n = 191; p < 0.0001). Annual hospitalization rate for heart failure fell from 0.79% pre-procedure to 0.41% post-procedure (n = 338; p < 0.0001). Kaplan-Meier survival estimate at 12 months was 77.2%. Conclusions: The percutaneous mitral valve device significantly reduced MR, improved clinical symptoms, and decreased LV dimensions at 12 months in this high-surgical-risk cohort. (Endovascular Valve Edge-to-Edge REpair STudy [EVERESTIIRCT]; NCT00209274).

Journal of the American College of Cardiology · randomised controlled trial · 321 citationsread the source →

Long-term results with vagus nerve stimulation in children with pharmacoresistant epilepsy.

Purpose: To retrospectively review our experience with VNS in pediatric patients with pharmacoresistant epilepsy and examine the seizure-frequency outcome and rates of discontinuation in two age groups: adolescent and pre-adolescent children. Results: Complete pre- and post-VNS data were available for 46/49 patients. Median age at implantation was 12.1 (range 2.3-17.9) and median duration of epilepsy 8.0 (1.9-16.9) years. Twenty-one patients (45.6%) were under 12 years at the time of surgery. Median follow-up was 2 years; follow-up exceeded 4 years in 9/46 patients. As compared to baseline, median seizure-frequency reduction in the setting of declining numbers was 56% at 3 months, 50% at 6, 63% at 12, 83% at 24 and 74% at 36 months. When a last observation carried forward analysis was employed median seizure-frequency reduction in the range of 60% was observed at 1, 2 and 3 years post-VNS. Twenty patients (43.5%) had >75% seizure-frequency reduction. No response (increase or <50% reduction) was observed in 19/46 (41.3%). Five patients (10.1%) were seizure-free for more than 6 months by their last follow-up. There was no difference in the number of AEDs used before and after VNS. The long-term discontinuation rate was 21.7% and reflected a lack of clinical response or infection. Conclusions: In this series VNS was well-tolerated and effective as add-on therapy for refractory seizures in children of all ages. Response was even more favorable in the younger group (<12 years at implantation). Infection and lack of efficacy were the most common reasons for discontinuation of long-term VNS therapy in this group.

Seizure · cohort or longitudinal · 119 citationsread the source →

A randomised clinical trial to evaluate the acceptability and efficacy of an early phase, online, guided augmentation of outpatient care for adults with anorexia nervosa.

Background: Outpatient interventions for adult anorexia nervosa typically have a modest impact on weight and eating disorder symptomatology. This study examined whether adding a brief online intervention focused on enhancing motivation to change and the development of a recovery identity (RecoveryMANTRA) would improve outcomes in adults with anorexia nervosa. Methods: Participants with anorexia nervosa (n = 187) were recruited from 22 eating disorder outpatient services throughout the UK. They were randomised to receiving RecoveryMANTRA in addition to treatment as usual (TAU) (n = 99; experimental group) or TAU only (n = 88; control group). Outcomes were measured at end-of-intervention (6 weeks), 6 and 12 months. Results: Adherence rates to RecoveryMANTRA were 83% for the online guidance sessions and 77% for the use of self-help materials (workbook and/or short video clips). Group differences in body mass index at 6 weeks (primary outcome) were not significant. Group differences in eating disorder symptoms, psychological wellbeing and work and social adjustment (at 6 weeks and at follow-up) were not significant, except for a trend-level greater reduction in anxiety at 6 weeks in the RecoveryMANTRA group (p = 0.06). However, the RecoveryMANTRA group had significantly higher levels of confidence in own ability to change (p = 0.02) and alliance with the therapist at the outpatient service (p = 0.005) compared to the control group at 6 weeks. Conclusions: Augmenting outpatient treatment for adult anorexia nervosa with a focus on recovery and motivation produced short-term reductions in anxiety and increased confidence to change and therapeutic alliance.

Psychological medicine · randomised controlled trial · 35 citationsread the source →

Does active referral by a doctor or 12-Step peer improve 12-Step meeting attendance? Results from a pilot randomised control trial.

Background: Active engagement in 12-Step self-help groups (SHG) is associated with improvements in substance use outcomes during and after treatment, yet levels of participation in SHG meetings in the U.K. remain low. Method: An RCT investigating the impact of active referral to SHG, delivered by doctors or 12-Step peers during inpatient treatment on both inpatient and post-treatment meeting attendance was conducted. 151 inpatients with alcohol, opiate, crack-cocaine or benzodiazepine dependence undergoing detoxification, received one of two active referral interventions: 12-Step peer intervention (PI), doctor intervention (DI), or no intervention (NI). 83% of the sample was followed up, 2-3 months following discharge. Results: Active referral interventions significantly increased attendance at 12-Step meetings during inpatient treatment (88% versus 73%, p<.05). Rates of post-discharge meeting attendance were PI=64%, DI=48%, NI=33%, with those in the PI group significantly (OR=3.6; CI=1.3, 9.8) more likely to have attended. Inpatient meeting attenders were three times as likely to have attended meetings post-discharge (59% versus 20%, p<.01), and post-discharge meeting attenders reported significantly higher abstinence rates (60.8% versus 39.2%, p<.05) at follow-up. However, abstinence rates did not differ significantly across intervention groups (44% [PI], 41% [DI] and 36% [NI]). Conclusion: Attendance at 12-Step SHGs is associated with greater rates of abstinence and active referral, especially by 12-Step peers, increases 12-Step SHG attendance rates. However, improved clinical outcomes among attendees might not occur until stronger recovery peer support networks are established. These results show promise for the benefit of incorporating Twelve Step Facilitation into U.K. treatment settings.

Drug and alcohol dependence · randomised controlled trial · 43 citationsread the source →

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

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

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

Efficacy and acceptability of psychosocial interventions in asylum seekers and refugees: systematic review and meta-analysis.

AimsIn the past few years, there has been an unprecedented increase in the number of forcibly displaced migrants worldwide, of which a substantial proportion is refugees and asylum seekers. Refugees and asylum seekers may experience high levels of psychological distress, and show high rates of mental health conditions. It is therefore timely and particularly relevant to assess whether current evidence supports the provision of psychosocial interventions for this population. We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) assessing the efficacy and acceptability of psychosocial interventions compared with control conditions (treatment as usual/no treatment, waiting list, psychological placebo) aimed at reducing mental health problems in distressed refugees and asylum seekers. Methods: We used Cochrane procedures for conducting a systematic review and meta-analysis of RCTs. We searched for published and unpublished RCTs assessing the efficacy and acceptability of psychosocial interventions in adults and children asylum seekers and refugees with psychological distress. Post-traumatic stress disorder (PTSD), depressive and anxiety symptoms at post-intervention were the primary outcomes. Secondary outcomes include: PTSD, depressive and anxiety symptoms at follow-up, functioning, quality of life and dropouts due to any reason. Results: We included 26 studies with 1959 participants. Meta-analysis of RCTs revealed that psychosocial interventions have a clinically significant beneficial effect on PTSD (standardised mean difference [SMD] = -0.71; 95% confidence interval [CI] -1.01 to -0.41; I2 = 83%; 95% CI 78-88; 20 studies, 1370 participants; moderate quality evidence), depression (SMD = -1.02; 95% CI -1.52 to -0.51; I2 = 89%; 95% CI 82-93; 12 studies, 844 participants; moderate quality evidence) and anxiety outcomes (SMD = -1.05; 95% CI -1.55 to -0.56; I2 = 87%; 95% CI 79-92; 11 studies, 815 participants; moderate quality evidence). This beneficial effect was maintained at 1 month or longer follow-up, which is extremely important for populations exposed to ongoing post-migration stressors. For the other secondary outcomes, we identified a non-significant trend in favour of psychosocial interventions. Most evidence supported interventions based on cognitive behavioural therapies with a trauma-focused component. Limitations of this review include the limited number of studies collected, with a relatively low total number of participants, and the limited available data for positive outcomes like functioning and quality of life. Conclusions: Considering the epidemiological relevance of psychological distress and mental health conditions in refugees and asylum seekers, and in view of the existing data on the effectiveness of psychosocial interventions, these interventions should be routinely made available as part of the health care of distressed refugees and asylum seekers. Evidence-based guidelines and implementation packages should be developed accordingly.

Epidemiology and psychiatric sciences · meta-analysis · 138 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 →

Motivating factors and barriers towards exercise in severe mental illness: a systematic review and meta-analysis.

Exercise can improve clinical outcomes in people with severe mental illness (SMI). However, this population typically engages in low levels of physical activity with poor adherence to exercise interventions. Understanding the motivating factors and barriers towards exercise for people with SMI would help to maximize exercise participation. A search of major electronic databases was conducted from inception until May 2016. Quantitative studies providing proportional data on the motivating factors and/or barriers towards exercise among patients with SMI were eligible. Random-effects meta-analyses were undertaken to calculate proportional data and 95% confidence intervals (CI) for motivating factors and barriers toward exercise. From 1468 studies, 12 independent studies of 6431 psychiatric patients were eligible for inclusion. Meta-analyses showed that 91% of people with SMI endorsed 'improving health' as a reason for exercise (N = 6, n = 790, 95% CI 80-94). Among specific aspects of health and well-being, the most common motivations were 'losing weight' (83% of patients), 'improving mood' (81%) and 'reducing stress' (78%). However, low mood and stress were also identified as the most prevalent barriers towards exercise (61% of patients), followed by 'lack of support' (50%). Many of the desirable outcomes of exercise for people with SMI, such as mood improvement, stress reduction and increased energy, are inversely related to the barriers of depression, stress and fatigue which frequently restrict their participation in exercise. Providing patients with professional support to identify and achieve their exercise goals may enable them to overcome psychological barriers, and maintain motivation towards regular physical activity.

Psychological medicine · meta-analysis · 301 citationsread the source →

Annual Research Review: Prevention of psychosis in adolescents - systematic review and meta-analysis of advances in detection, prognosis and intervention.

Background: The clinical high-risk state for psychosis (CHR-P) paradigm has facilitated the implementation of psychosis prevention into clinical practice; however, advancements in adolescent CHR-P populations are less established. Methods: We performed a PRISMA/MOOSE-compliant systematic review of the Web of Science database, from inception until 7 October 2019, to identify original studies conducted in CHR-P children and adolescents (mean age <18 years). Findings were systematically appraised around core themes: detection, prognosis and intervention. We performed meta-analyses (employing Q statistics and I 2 test) regarding the proportion of CHR-P subgroups, the prevalence of baseline comorbid mental disorders, the risk of psychosis onset and the type of interventions received at baseline. Quality assessment and publication bias were also analysed. Results: Eighty-seven articles were included (n = 4,667 CHR-P individuals). Quality of studies ranged from 3.5 to 8 (median 5.5) on a modified Newcastle-Ottawa scale. Detection: Individuals were aged 15.6 ± 1.2 years (51.5% males), mostly (83%) presenting with attenuated positive psychotic symptoms. CHR-P psychometric accuracy improved when caregivers served as additional informants. Comorbid mood (46.4%) and anxiety (31.4%) disorders were highly prevalent. Functioning and cognition were impaired. Neurobiological studies were inconclusive. Prognosis: Risk for psychosis was 10.4% (95%CI: 5.8%-18.1%) at 6 months, 20% (95%CI: 15%-26%) at 12 months, 23% (95%CI: 18%-29%) at 24 months and 23.3% (95%CI: 17.3%-30.7%) at ≥36 months. Interventions: There was not enough evidence to recommend one specific treatment (including cognitive behavioural therapy) over the others (including control conditions) to prevent the transition to psychosis in this population. Randomised controlled trials suggested that family interventions, cognitive remediation and fish oil supplementation may improve cognition, symptoms and functioning. At baseline, 30% of CHR-P adolescents were prescribed antipsychotics and 60% received psychotherapy. Conclusions: It is possible to detect and formulate a group-level prognosis in adolescents at risk for psychosis. Future interventional research is required.

Journal of child psychology and psychiatry, and allied disciplines · meta-analysis · 129 citationsread the source →

Childhood maltreatment and unfavourable clinical outcomes in bipolar disorder: a systematic review and meta-analysis.

Background: Bipolar disorder affects up to one in 25 individuals and identification of early risk indicators of negative outcomes could facilitate early detection of patients with greatest clinical needs and risk. We aimed to investigate the association between childhood maltreatment and key negative outcomes in patients with bipolar disorder. Methods: For this systematic review and meta-analysis we searched MEDLINE, PsycINFO, and Embase to identify articles published before Jan 1, 2015, examining the association of maltreatment (physical, sexual, or emotional abuse, neglect, or family conflict) before age 18 years with clinical features and course of illness in bipolar disorder. Data were extracted from published reports and any missing information was requested from investigators. We did 12 independent random-effects meta-analyses to quantify the associations between childhood maltreatment and course of illness or clinical features. Findings: We initially identified 527 records and after unsuitable studies were removed, our search yielded 148 publications of which 30 were used in the meta-analysis. Patients with bipolar disorder and history of childhood maltreatment had greater mania severity (six studies, 780 participants; odds ratio [OR] 2·02, 95% CI 1·21-3·39, p=0·008), greater depression severity (eight studies, 1007 participants; 1·57, 1·25-1·99, p=0·0001), greater psychosis severity (seven studies, 1494 participants; 1·49, 1·10-2·04, p=0·011), higher risk of comorbidity with post-traumatic stress disorder (eight studies, 2494 participants; 3·60, 2·45-5·30, p<0·0001), anxiety disorders (seven studies, 5091 participants; 1·90, 1·39-2·61, p<0·0001), substance misuse disorders (11 studies, 5469 participants; 1·84, 1·41-2·39, p<0·0001), alcohol misuse disorder (eight studies, 5040 participants; 1·44, 1·13-1·83, p=0·003), earlier age of bipolar disorder onset (14 studies, 5733 participants; 1·85, 1·43-2·40, p<0·0001), higher risk of rapid cycling (eight studies, 3010 participants; 1·89, 1·45-2·48, p<0·0001), greater number of manic episodes (seven studies, 3909 participants; 1·26, 1·09-1·47, p=0·003), greater number of depressive episodes (eight studies, 4025 participants; 1·38, 1·07-1·79, p=0·013), and higher risk of suicide attempt (13 studies, 3422 participants; 2·25, 1·88-2·70, p<0·0001) compared with those with bipolar disorder without childhood maltreatment. Overall, these associations were not explained by publication bias, undue effects of individual studies, or variation in study quality. Interpretation: Childhood maltreatment predicts unfavourable clinical features and course of illness in patients with bipolar disorder. Funding: None.

The lancet. Psychiatry · meta-analysis · 278 citationsread the source →

Psychosocial interventions for self-harm in adults.

Background: Self-harm (SH; intentional self-poisoning or self-injury regardless of degree of suicidal intent or other types of motivation) is a growing problem in most counties, often repeated, and associated with suicide. There has been a substantial increase in both the number of trials and therapeutic approaches of psychosocial interventions for SH in adults. This review therefore updates a previous Cochrane Review (last published in 2016) on the role of psychosocial interventions in the treatment of SH in adults. Objectives: To assess the effects of psychosocial interventions for self-harm (SH) compared to comparison types of care (e.g. treatment-as-usual, routine psychiatric care, enhanced usual care, active comparator) for adults (aged 18 years or older) who engage in SH. Search methods: We searched the Cochrane Common Mental Disorders Specialised Register, the Cochrane Library (Central Register of Controlled Trials [CENTRAL] and Cochrane Database of Systematic reviews [CDSR]), together with MEDLINE, Ovid Embase, and PsycINFO (to 4 July 2020). Selection criteria: We included all randomised controlled trials (RCTs) comparing interventions of specific psychosocial treatments versus treatment-as-usual (TAU), routine psychiatric care, enhanced usual care (EUC), active comparator, or a combination of these, in the treatment of adults with a recent (within six months of trial entry) episode of SH resulting in presentation to hospital or clinical services. The primary outcome was the occurrence of a repeated episode of SH over a maximum follow-up period of two years. Secondary outcomes included treatment adherence, depression, hopelessness, general functioning, social functioning, suicidal ideation, and suicide. Data collection and analysis: We independently selected trials, extracted data, and appraised trial quality. For binary outcomes, we calculated odds ratio (ORs) and their 95% confidence intervals (CIs). For continuous outcomes, we calculated mean differences (MDs) or standardised mean differences (SMDs) and 95% CIs. The overall quality of evidence for the primary outcome (i.e. repetition of SH at post-intervention) was appraised for each intervention using the GRADE approach. Main results: We included data from 76 trials with a total of 21,414 participants. Participants in these trials were predominately female (61.9%) with a mean age of 31.8 years (standard deviation [SD] 11.7 years). On the basis of data from four trials, individual cognitive behavioural therapy (CBT)-based psychotherapy may reduce repetition of SH as compared to TAU or another comparator by the end of the intervention (OR 0.35, 95% CI 0.12 to 1.02; N = 238; k = 4; GRADE: low certainty evidence), although there was imprecision in the effect estimate. At longer follow-up time points (e.g., 6- and 12-months) there was some evidence that individual CBT-based psychotherapy may reduce SH repetition. Whilst there may be a slightly lower rate of SH repetition for dialectical behaviour therapy (DBT) (66.0%) as compared to TAU or alternative psychotherapy (68.2%), the evidence remains uncertain as to whether DBT reduces absolute repetition of SH by the post-intervention assessment. On the basis of data from a single trial, mentalisation-based therapy (MBT) reduces repetition of SH and frequency of SH by the post-intervention assessment (OR 0.35, 95% CI 0.17 to 0.73; N = 134; k = 1; GRADE: high-certainty evidence). A group-based emotion-regulation psychotherapy may also reduce repetition of SH by the post-intervention assessment based on evidence from two trials by the same author group (OR 0.34, 95% CI 0.13 to 0.88; N = 83; k = 2; moderate-certainty evidence). There is probably little to no effect for different variants of DBT on absolute repetition of SH, including DBT group-based skills training, DBT individual skills training, or an experimental form of DBT in which participants were given significantly longer cognitive exposure to stressful events. The evidence remains uncertain as to whether provision of information and support, based on the Suicide Trends in At-Risk Territories (START) and the SUicide-PREvention Multisite Intervention Study on Suicidal behaviors (SUPRE-MISS) models, have any effect on repetition of SH by the post-intervention assessment. There was no evidence of a difference for psychodynamic psychotherapy, case management, general practitioner (GP) management, remote contact interventions, and other multimodal interventions, or a variety of brief emergency department-based interventions. Authors' conclusions: Overall, there were significant methodological limitations across the trials included in this review. Given the moderate or very low quality of the available evidence, there is only uncertain evidence regarding a number of psychosocial interventions for adults who engage in SH. Psychosocial therapy based on CBT approaches may result in fewer individuals repeating SH at longer follow-up time points, although no such effect was found at the post-intervention assessment and the quality of evidence, according to the GRADE criteria, was low. Given findings in single trials, or trials by the same author group, both MBT and group-based emotion regulation therapy should be further developed and evaluated in adults. DBT may also lead to a reduction in frequency of SH. Other interventions were mostly evaluated in single trials of moderate to very low quality such that the evidence relating to the use of these interventions is inconclusive at present.

The Cochrane database of systematic reviews · meta-analysis · 84 citationsread the source →

Psychological interventions for antisocial personality disorder.

Background: Antisocial personality disorder (AsPD) is associated with poor mental health, criminality, substance use and relationship difficulties. This review updates Gibbon 2010 (previous version of the review). Objectives: To evaluate the potential benefits and adverse effects of psychological interventions for adults with AsPD. Search methods: We searched CENTRAL, MEDLINE, Embase, 13 other databases and two trials registers up to 5 September 2019. We also searched reference lists and contacted study authors to identify studies. Selection criteria: Randomised controlled trials of adults, where participants with an AsPD or dissocial personality disorder diagnosis comprised at least 75% of the sample randomly allocated to receive a psychological intervention, treatment-as-usual (TAU), waiting list or no treatment. The primary outcomes were aggression, reconviction, global state/functioning, social functioning and adverse events. Data collection and analysis: We used standard methodological procedures expected by Cochrane. Main results: This review includes 19 studies (eight new to this update), comparing a psychological intervention against TAU (also called 'standard Maintenance'(SM) in some studies). Eight of the 18 psychological interventions reported data on our primary outcomes. Four studies focussed exclusively on participants with AsPD, and 15 on subgroups of participants with AsPD. Data were available from only 10 studies involving 605 participants. Eight studies were conducted in the UK and North America, and one each in Iran, Denmark and the Netherlands. Study duration ranged from 4 to 156 weeks (median = 26 weeks). Most participants (75%) were male; the mean age was 35.5 years. Eleven studies (58%) were funded by research councils. Risk of bias was high for 13% of criteria, unclear for 54% and low for 33%. Cognitive behaviour therapy (CBT) + TAU versus TAU One study (52 participants) found no evidence of a difference between CBT + TAU and TAU for physical aggression (odds ratio (OR) 0.92, 95% CI 0.28 to 3.07; low-certainty evidence) for outpatients at 12 months post-intervention. One study (39 participants) found no evidence of a difference between CBT + TAU and TAU for social functioning (mean difference (MD) -1.60 points, 95% CI -5.21 to 2.01; very low-certainty evidence), measured by the Social Functioning Questionnaire (SFQ; range = 0-24), for outpatients at 12 months post-intervention. Impulsive lifestyle counselling (ILC) + TAU versus TAU One study (118 participants) found no evidence of a difference between ILC + TAU and TAU for trait aggression (assessed with Buss-Perry Aggression Questionnaire-Short Form) for outpatients at nine months (MD 0.07, CI -0.35 to 0.49; very low-certainty evidence). One study (142 participants) found no evidence of a difference between ILC + TAU and TAU alone for the adverse event of death (OR 0.40, 95% CI 0.04 to 4.54; very low-certainty evidence) or incarceration (OR 0.70, 95% CI 0.27 to 1.86; very low-certainty evidence) for outpatients between three and nine months follow-up. Contingency management (CM) + SM versus SM One study (83 participants) found evidence that, compared to SM alone, CM + SM may improve social functioning measured by family/social scores on the Addiction Severity Index (ASI; range = 0 (no problems) to 1 (severe problems); MD -0.08, 95% CI -0.14 to -0.02; low-certainty evidence) for outpatients at six months. 'Driving whilst intoxicated' programme (DWI) + incarceration versus incarceration One study (52 participants) found no evidence of a difference between DWI + incarceration and incarceration alone on reconviction rates (hazard ratio 0.56, CI -0.19 to 1.31; very low-certainty evidence) for prisoner participants at 24 months. Schema therapy (ST) versus TAU One study (30 participants in a secure psychiatric hospital, 87% had AsPD diagnosis) found no evidence of a difference between ST and TAU for the number of participants who were reconvicted (OR 2.81, 95% CI 0.11 to 74.56, P = 0.54) at three years. The same study found that ST may be more likely to improve social functioning (assessed by the mean number of days until patients gain unsupervised leave (MD -137.33, 95% CI -271.31 to -3.35) compared to TAU, and no evidence of a difference between the groups for overall adverse events, classified as the number of people experiencing a global negative outcome over a three-year period (OR 0.42, 95% CI 0.08 to 2.19). The certainty of the evidence for all outcomes was very low. Social problem-solving (SPS) + psychoeducation (PE) versus TAU One study (17 participants) found no evidence of a difference between SPS + PE and TAU for participants' level of social functioning (MD -1.60 points, 95% CI -5.43 to 2.23; very low-certainty evidence) assessed with the SFQ at six months post-intervention. Dialectical behaviour therapy versus TAU One study (skewed data, 14 participants) provided very low-certainty, narrative evidence that DBT may reduce the number of self-harm days for outpatients at two months post-intervention compared to TAU. Psychosocial risk management (PSRM; 'Resettle') versus TAU One study (skewed data, 35 participants) found no evidence of a difference between PSRM and TAU for a number of officially recorded offences at one year after release from prison. It also found no evidence of difference between the PSRM and TAU for the adverse event of death during the study period (OR 0.89, 95% CI 0.05 to 14.83, P = 0.94, 72 participants (90% had AsPD), 1 study, very low-certainty evidence). Authors' conclusions: There is very limited evidence available on psychological interventions for adults with AsPD. Few interventions addressed the primary outcomes of this review and, of the eight that did, only three (CM + SM, ST and DBT) showed evidence that the intervention may be more effective than the control condition. No intervention reported compelling evidence of change in antisocial behaviour. Overall, the certainty of the evidence was low or very low, meaning that we have little confidence in the effect estimates reported. The conclusions of this update have not changed from those of the original review, despite the addition of eight new studies. This highlights the ongoing need for further methodologically rigorous studies to yield further data to guide the development and application of psychological interventions for AsPD and may suggest that a new approach is required.

The Cochrane database of systematic reviews · meta-analysis · 32 citationsread the source →

Cognitive behavioural therapy (CBT), third-wave CBT and interpersonal therapy (IPT) based interventions for preventing depression in children and adolescents.

Background: Depression is common in young people. It has a marked negative impact and is associated with self-harm and suicide. Preventing its onset would be an important advance in public health. This is an update of a Cochrane review that was last updated in 2011. Objectives: To determine whether evidence-based psychological interventions (including cognitive behavioural therapy (CBT), interpersonal therapy (IPT) and third wave CBT)) are effective in preventing the onset of depressive disorder in children and adolescents. Search methods: We searched the specialised register of the Cochrane Common Mental Disorders Group (CCMDCTR to 11 September 2015), which includes relevant randomised controlled trials from the following bibliographic databases: The Cochrane Library (all years), EMBASE (1974 to date), MEDLINE (1950 to date) and PsycINFO (1967 to date). We searched conference abstracts and reference lists of included trials and reviews, and contacted experts in the field. Selection criteria: We included randomised controlled trials of an evidence-based psychological prevention programme compared with any comparison control for young people aged 5 to 19 years, who did not currently meet diagnostic criteria for depression. Data collection and analysis: Two authors independently assessed trials for inclusion and rated their risk of bias. We adjusted sample sizes to take account of cluster designs and multiple comparisons. We contacted trial authors for additional information where needed. We assessed the quality of evidence for the primary outcomes using GRADE. Main results: We included 83 trials in this review. The majority of trials (67) were carried out in school settings with eight in colleges or universities, four in clinical settings, three in the community and four in mixed settings. Twenty-nine trials were carried out in unselected populations and 53 in targeted populations. For the primary outcome of depression diagnosis at medium-term follow-up (up to 12 months), there were 32 trials with 5965 participants and the risk of having a diagnosis of depression was reduced for participants receiving an intervention compared to those receiving no intervention (risk difference (RD) -0.03, 95% confidence interval (CI) -0.05 to -0.01; P value = 0.01). We rated this evidence as moderate quality according to the GRADE criteria. There were 70 trials (73 trial arms) with 13,829 participants that contributed to the analysis for the primary outcome of depression symptoms (self-rated) at the post-intervention time point, with results showing a small but statistically significant effect (standardised mean difference (SMD) -0.21, 95% CI -0.27 to -0.15; P value < 0.0001). This effect persisted to the short-term assessment point (up to three months) (SMD -0.31, 95% CI -0.45 to -0.17; P value < 0.0001; 16 studies; 1558 participants) and medium-term (4 to 12 months) assessment point (SMD -0.12, 95% CI -0.18 to -0.05; P value = 0.0002; 53 studies; 11,913 participants); however, the effect was no longer evident at the long-term follow-up. We rated this evidence as low to moderate quality according to the GRADE criteria. The evidence from this review is unclear with regard to whether the type of population modified the overall effects; there was statistically significant moderation of the overall effect for depression symptoms (P value = 0.0002), but not for depressive disorder (P value = 0.08). For trials implemented in universal populations there was no effect for depression diagnosis (RD -0.01, 95% CI -0.03 to 0.01) and a small effect for depression symptoms (SMD -0.11, 95% CI -0.17 to -0.05). For trials implemented in targeted populations there was a statistically significantly beneficial effect of intervention (depression diagnosis RD -0.04, 95% CI -0.07 to -0.01; depression symptoms SMD -0.32, 95% CI -0.42 to -0.23). Of note were the lack of attention placebo-controlled trials in targeted populations (none for depression diagnosis and four for depression symptoms). Among trials implemented in universal populations a number used an attention placebo comparison in which the intervention consistently showed no effect. Authors' conclusions: Overall the results show small positive benefits of depression prevention, for both the primary outcomes of self-rated depressive symptoms post-intervention and depression diagnosis up to 12 months (but not beyond). Estimates of numbers needed to treat to benefit (NNTB = 11) compare well with other public health interventions. However, the evidence was of moderate to low quality using the GRADE framework and the results were heterogeneous. Prevention programmes delivered to universal populations showed a sobering lack of effect when compared with an attention placebo control. Interventions delivered to targeted populations, particularly those selected on the basis of depression symptoms, had larger effect sizes, but these seldom used an attention placebo comparison and there are practical difficulties inherent in the implementation of targeted programmes. We conclude that there is still not enough evidence to support the implementation of depression prevention programmes. Future research should focus on current gaps in our knowledge. Given the relative lack of evidence for universal interventions compared with attention placebo controls and the poor results from well-conducted effectiveness trials of universal interventions, in our opinion any future such trials should test a depression prevention programme in an indicated targeted population using a credible attention placebo comparison group. Depressive disorder as the primary outcome should be measured over the longer term, as well as clinician-rated depression. Such a trial should consider scalability as well as the potential for the intervention to do harm.

The Cochrane database of systematic reviews · meta-analysis · 136 citationsread the source →

Dismantling, optimising, and personalising internet cognitive behavioural therapy for depression: a systematic review and component network meta-analysis using individual participant data.

Background: Internet cognitive behavioural therapy (iCBT) is a viable delivery format of CBT for depression. However, iCBT programmes include training in a wide array of cognitive and behavioural skills via different delivery methods, and it remains unclear which of these components are more efficacious and for whom. Methods: We did a systematic review and individual participant data component network meta-analysis (cNMA) of iCBT trials for depression. We searched PubMed, PsycINFO, Embase, and the Cochrane Library for randomised controlled trials (RCTs) published from database inception to Jan 1, 2019, that compared any form of iCBT against another or a control condition in the acute treatment of adults (aged ≥18 years) with depression. Studies with inpatients or patients with bipolar depression were excluded. We sought individual participant data from the original authors. When these data were unavailable, we used aggregate data. Two independent researchers identified the included components. The primary outcome was depression severity, expressed as incremental mean difference (iMD) in the Patient Health Questionnaire-9 (PHQ-9) scores when a component is added to a treatment. We developed a web app that estimates relative efficacies between any two combinations of components, given baseline patient characteristics. This study is registered in PROSPERO, CRD42018104683. Findings: We identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42·0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD -1·83 [95% credible interval (CrI) -2·90 to -0·80]) and that relaxation might be harmful (1·20 [95% CrI 0·17 to 2·27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0·32 [95% CrI 0·13 to 0·93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components. Interpretation: The individual patient data cNMA revealed potentially helpful, less helpful, or harmful components and delivery formats for iCBT packages. iCBT packages aiming to be effective and efficient might choose to include beneficial components and exclude ones that are potentially detrimental. Our web app can facilitate shared decision making by therapist and patient in choosing their preferred iCBT package. Funding: Japan Society for the Promotion of Science.

The lancet. Psychiatry · systematic review · 158 citationsread the source →

Sociodemographic, physical, mental and social factors in the cessation of breastfeeding before 6 months: a systematic review.

Background: The World Health Organization recommends exclusive breastfeeding as the main source of nutrition for infants during their first 6 months of life. However, despite this well-known recommendation, not all mothers breastfeed, whether partly or fully, during this time. Objective: The aim of this systematic literature review was to compile evidence regarding sociodemographic, physical, mental and social factors that influence breastfeeding mothers to stop breastfeeding before the infant reaches 6 months. Search method: A systematic search was conducted in four databases. Selection criteria: Studies with quantitative research were included. Data collection and analysis: Totally, 186 abstracts were read, 83 seemed relevant but 18 were found to be duplicates. Finally, 27 articles met the inclusion criteria and were included. The quality assessment was carried out with a quality assessment template from the Swedish Council on Technology and Assessment, and the grading of the result was carried out according to GRADE. Results: The association of breastfeeding cessation between the mother's young age, low level of education, return to work within 12-week postpartum, caesarean birth and inadequate milk supply was found to have a low level of evidence. The link found between depressions among the mothers with the cessation of breastfeeding was found to have a very low level of evidence. Conclusions: Sociodemographic factors appeared to have caused cessation of breastfeeding in some of the included articles. The preventive work should focus on how to improve the knowledge of healthcare professionals and targeted interventions must address mothers who are at risk of ceasing breastfeeding before the recommended time.

Scandinavian journal of caring sciences · systematic review · 61 citationsread the source →

Effect of a high-intensity exercise program on physical function and mental health in nursing home residents with dementia: an assessor blinded randomized controlled trial.

Background: Dementia is among the leading causes of functional loss and disability in older adults. Research has demonstrated that nursing home patients without dementia can improve their function in activities of daily living, strength, balance and mental well being by physical exercise. The evidence on effect of physical exercise among nursing home patients with dementia is scarce and ambiguous. Thus, the primary objective of this study was to investigate the effect of a high intensity functional exercise program on the performance of balance in nursing home residents with dementia. The secondary objective was to examine the effect of this exercise on muscle strength, mobility, activities of daily living, quality of life and neuropsychiatric symptoms. Design and methods: This single blinded randomized controlled trial was conducted among 170 persons with dementia living in nursing homes. Mean age was 86.7 years (SD = 7.4) and 74% were women. The participants were randomly allocated to an intervention (n = 87) or a control group (n = 83). The intervention consisted of intensive strengthening and balance exercises in small groups twice a week for 12 weeks. The control condition was leisure activities. Results: The intervention group improved the score on Bergs Balance Scale by 2.9 points, which was significantly more than the control group who improved by 1.2 points (p = 0.02). Having exercised 12 times or more was significantly associated with improved strength after intervention (p<0.05). The level of apathy was lower in the exercise group after the intervention, compared to the control group (p = 0.048). Conclusion: The results from our study indicate that a high intensity functional exercise program improved balance and muscle strength as well as reduced apathy in nursing home patients with dementia. Trial registration: ClinicalTrials.gov NCT02262104.

PloS one · randomised controlled trial · 121 citationsread the source →

A prospective longitudinal study of the prevalence of post-traumatic stress disorder resulting from childbirth events.

Background: Childbirth has been linked to postpartum impairment. However, controversy exists regarding the onset and prevalence of post-traumatic stress disorder (PTSD) after childbirth, with seminal studies being limited by methodological issues. This longitudinal prospective study examined the prevalence of PTSD following childbirth in a large sample while controlling for pre-existing PTSD and affective symptomatology. Method: Pregnant women in their third trimester were recruited over a 12-month period and interviewed to identify PTSD and anxiety and depressive symptoms during the last trimester of pregnancy, 4-6 weeks postpartum, 12 weeks postpartum and 24 weeks postpartum. Results: Of the 1067 women approached, 933 were recruited into the study. In total, 866 (93%) were retained to 4-6 weeks, 826 (89%) were retained to 12 weeks and 776 (83%) were retained to 24 weeks. Results indicated that, uncontrolled, 3.6% of women met PTSD criteria at 4-6 weeks postpartum, 6.3% at 12 weeks postpartum and 5.8% at 24 weeks postpartum. When controlling for PTSD and partial PTSD due to previous traumatic events as well as clinically significant anxiety and depression during pregnancy, PTSD rates were less at 1.2% at 4-6 weeks, 3.1% at 12 weeks and 3.1% at 24 weeks postpartum. Conclusions: This is the first study to demonstrate the occurrence of full criteria PTSD resulting from childbirth after controlling for pre-existing PTSD and partial PTSD and clinically significant depression and anxiety in pregnancy. The findings indicate that PTSD can result from a traumatic birth experience, though this is not the normative response.

Psychological medicine · 209 citationsread the source →

Food for Thought: A Randomised Controlled Trial of Emotional Freedom Techniques and Cognitive Behavioural Therapy in the Treatment of Food Cravings.

Addressing the internal determinants of dysfunctional eating behaviours (e.g. food cravings) in the prevention and treatment of obesity has been increasingly recognised. This study compared Emotional Freedom Techniques (EFT) to Cognitive Behavioural Therapy (CBT) for food cravings in adults who were overweight or obese (N = 83) in an 8-week intervention. Outcome data were collected at baseline, post-intervention, and at 6- and 12-months follow-up. Overall, EFT and CBT demonstrated comparable efficacy in reducing food cravings, one's responsiveness to food in the environment (power of food), and dietary restraint, with Cohen's effect size values suggesting moderate to high practical significance for both interventions. Results also revealed that both EFT and CBT are capable of producing treatment effects that are clinically meaningful, with reductions in food cravings, the power of food, and dietary restraint normalising to the scores of a non-clinical community sample. While reductions in BMI were not observed, the current study supports the suggestion that psychological interventions are beneficial for food cravings and both CBT and EFT could serve as vital adjunct tools in a multidisciplinary approach to managing obesity.

Applied psychology. Health and well-being · randomised controlled trial · 18 citationsread the source →

Structured group education programme and accompanying mHealth intervention to promote physical activity in women with a history of gestational diabetes: A randomised controlled trial.

Aims: Assess effectiveness of a hybrid intervention targeting physical activity in women with prior gestational diabetes. Methods: Randomised controlled trial with parallel arms. 293 women (35.1 ± 5.1 years; 40% ethnic minority) recruited from two hospitals and randomised to routine care or hybrid lifestyle intervention comprising two group sessions and access to a mobile web app. Primary outcome was a change in objectively measured physical activity at 12 months. Secondary outcomes included self-efficacy for exercise, quality of life and anxiety and depression. Linear regression compared outcome measures between groups. Results: 83% of intervention participants attended at least one group session, of who 66% registered to use the app. There was a non-significant increase in physical activity at 12 months (between-group difference of 0.95 mg [95% CI: -0.46 to 2.37]), equivalent to approximately 500 steps per day. Intervention participants reported higher self-efficacy for exercise (0.54, 95% CI: 0.05 to 1.102; p = 0.029), lower anxiety (-0.91, 95% CI: -1.74 to -0.09; p = 0.031), and higher quality of life (0.05, 95% CI: 0.004 to 0.09; p = 0.032), compared to controls. Conclusions: The intervention improved confidence in exercise and quality of life. Further research is needed to improve participant engagement with physical activity interventions in multi-ethnic populations with a history of gestational diabetes.

Diabetic medicine : a journal of the British Diabetic Association · randomised controlled trial · 9 citationsread the source →

The Efficacy of Three Modalities of Internet-Based Psychotherapy for Non-Treatment-Seeking Online Problem Gamblers: A Randomized Controlled Trial.

Background: Internet-based interventions targeted at the most at-risk gamblers could reduce the treatment gap for addictive disorders. Currently, no clinical trial has included non-treatment-seeking patients who have been recruited directly in their gambling environment. This study was the first exclusively Internet-based randomized controlled trial among non-help-seeking problem gamblers with naturalistic recruitment in their gambling environment. Objective: The aim of this study was to assess the efficacy of three modalities of Internet-based psychotherapies with or without guidance, compared to a control condition, among problem gamblers who play online poker. Methods: All active poker gamblers on the Winamax website were systematically offered screening. All problem poker gamblers identified with a Problem Gambling Severity Index (PGSI) score of ≥ 5 were eligible to be included in the trial. Problem gamblers were randomized into four groups: (1) waiting list (control group), (2) personalized normalized feedback on their gambling status by email, (3) an email containing a self-help book to be downloaded with a Cognitive Behavioral Therapy (CBT) program without guidance, and (4) the same CBT program emailed weekly by a trained psychologist with personalized guidance. Efficacy was assessed based on the change in PGSI between baseline and 6 weeks (end of treatment) or 12 weeks (maintenance) and supported by player account-based gambling data automatically collected at the three time points. Results: All groups met high attrition rates (83%), but the group with guidance had a significantly higher dropout rate than the other three groups, including the control group. Although all groups showed some improvement, with a mean decrease of 1.35 on the PGSI, no significant difference in efficacy between the groups was observed. One-third of the problem gamblers fell below the problem gambling threshold at 6 weeks. Conclusions: Guidance could have aversively affected problem gamblers who had not sought help. Despite the lack of significant difference in efficacy between groups, this naturalistic trial provides a basis for the development of future Internet-based trials in individuals with gambling disorders. Comorbidities, natural course of illness, and intrinsic motivation seem to be critical issues to consider in future designs. Trial registration: ANSM 2013-A00794-41.

Journal of medical Internet research · randomised controlled trial · 48 citationsread the source →

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

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

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

Clinical effectiveness and acceptability of structured group psychoeducation versus optimised unstructured peer support for patients with remitted bipolar disorder (PARADES): a pragmatic, multicentre, observer-blind, randomised controlled superiority trial.

Background: Group psychoeducation is a low-cost National Institute for Health and Care Excellence-recommended treatment for bipolar disorder. However, the clinical effectiveness and acceptability of this intervention are unclear compared with unstructured peer support matched for delivery and aim of treatment, and for previous bipolar history. We aimed to assess the clinical effectiveness and acceptability of structured group psychoeducation versus optimised unstructured peer support for patients with remitted bipolar disorder. Methods: We did this pragmatic, multicentre, parallel-group, observer-blind, randomised controlled superiority trial at eight community sites in two regions in England. Participants aged 18 years or older with bipolar disorder and no episode in the preceding 4 weeks were recruited via self-referral or secondary care referral. Participants were individually randomly assigned (1:1), via a computer-generated stochastic allocation sequence, to attend 21 2-h weekly sessions of either structured group psychoeducation or optimised unstructured peer support. Randomisation was minimised by number of previous episodes (one to seven, eight to 19, or ≥20) and stratified by clinical site. Outcome assessors were masked to group allocation. The primary outcome was time from randomisation to next bipolar episode, with planned moderator analysis of number of previous bipolar episodes and qualitative interview of participant experience. We did analysis by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN62761948. Findings: Between Sept 28, 2009, and Jan 9, 2012, we randomly assigned 304 participants to receive psychoeducation (n=153) or peer support (n=151); all (100%) participants had complete primary outcome data. Attendance at psychoeducation groups was higher than at peer-support groups (median 14 sessions [IQR three to 18] vs nine sessions [two to 17]; p=0·026). At 96 weeks, 89 (58%) participants in the psychoeducation group had experienced a next bipolar episode compared with 98 (65%) participants in the peer-support group; time to next bipolar episode did not differ between groups (hazard ratio [HR] 0·83, 95% CI 0·62-1·11; p=0·217). Planned moderator analysis showed that psychoeducation was most beneficial in participants with few (one to seven) previous bipolar episodes (χ2; HR 0·28, 95% CI 0·12-0·68; p=0·034). Four (1%) participants (one in the psychoeducation group and three in the peer-support group) died during follow-up; these deaths were deemed unrelated to the study interventions or procedures. Interpretation: Structured group psychoeducation was no more clinically effective than similarly intensive unstructured peer support, but was more acceptable and improved outcome in participants with fewer previous bipolar episodes. Optimum provision of structured psychological interventions, such as group psychoeducation, early in the course of bipolar disorder might have important benefits on the course of illness, and merits further research. Funding: National Institute for Health Research.

The lancet. Psychiatry · randomised controlled trial · 42 citationsread the source →

Comparative effectiveness of cognitive behavioural therapy, modafinil, and their combination for treating fatigue in multiple sclerosis (COMBO-MS): a randomised, statistician-blinded, parallel-arm trial.

Background: Fatigue is one of the most disabling symptoms reported by people with multiple sclerosis. Although behavioural and pharmacological interventions might be partly beneficial, their combined effects have not been evaluated for multiple sclerosis fatigue, or examined with sufficient consideration of characteristics that might affect treatment response. In this comparative effectiveness research trial, we compared the effectiveness of cognitive behavioural therapy (CBT), modafinil, and their combination for treating multiple sclerosis fatigue. Methods: This randomised, analyst-blinded, parallel-arm, comparative effectiveness trial was done at two universities in the USA. Adults (aged ≥18 years) with multiple sclerosis and problematic fatigue (Fatigue Severity Scale [FSS] score ≥4) were randomly assigned (1:1:1), using a web-based treatment assignment system with minimisation, to receive CBT, modafinil, or both for 12 weeks. Statisticians were masked to group assignment, but participants, study neurologists, CBT interventionalists, and coordinators were not masked to treatment assignment. The primary outcome was the change in Modified Fatigue Impact Scale (MFIS) from baseline to 12 weeks, assessed using multiple linear regression, adjusted for age, sex, study site, anxiety, pain, baselines MFIS score, and physical activity. Analyses were done by intent to treat. The trial was registered with clinicaltrials.gov, NCT03621761, and is completed. Findings: Between Nov 15, 2018, and June 2, 2021, 336 participants were randomly assigned treatment (114 assigned to CBT, 114 assigned to modafinil, and 108 assigned to combination therapy). At 12 weeks, CBT (n=103), modafinil (n=107), and combination therapy (n=102) were associated with clinically meaningful within-group MFIS reductions of 15·20 (SD 11·90), 16·90 (15·90), and 17·30 (16·20) points, respectively. Change in MFIS scores from baseline to 12 weeks did not differ between groups: relative to combination therapy, the adjusted total mean difference in MFIS change score was 1·88 (95% CI -2·21 to 5·96) for CBT and 1·20 (-2·83 to 5·23) for modafinil. Most common adverse events for modafinil-containing treatment groups included insomnia (eight [7%] for modafinil and eight [7%] for combination therapy) and anxiety (three [3%] for modafinil and nine [8%] for combination therapy). Interpretation: Modafinil, CBT, and combination therapy were associated with similar reductions in the effects of multiple sclerosis fatigue at 12 weeks. Combination therapy was not associated with augmented improvement compared with the individual interventions. Further research is needed to determine whether effects of these interventions on multiple sclerosis-related fatigue is influenced by sleep hygiene and sleepiness. No serious adverse events related to the study drug were encountered. Funding: Patient-Centered Outcomes Research Institute and National Multiple Sclerosis Society.

The Lancet. Neurology · randomised controlled trial · 6 citationsread the source →

A randomised trial comparing weight loss with aerobic exercise in overweight individuals with coronary artery disease: The CUT-IT trial.

Background: We aimed to compare the effect of aerobic interval training (AIT) versus a low energy diet (LED) on physical fitness, body composition, cardiovascular risk factors and symptoms in overweight individuals with coronary artery disease (CAD). Methods and design: Seventy non-diabetic participants with CAD, a BMI>28 kg/m(2) and aged 45 to 75 years were randomised to 12 weeks' AIT at 90% peak heart rate three times a week or LED (800-1000 kcal/day) for 8-10 weeks followed by 2-4 weeks' weight maintenance diet. Results: Twenty-six (74%) AIT and 29 (83%) LED participants completed intervention per protocol. VO2peak (mL/kg fat free mass(0.67)/min) increased by 10.4% (p = 0.002) following AIT, whereas no change was observed after LED (-3.0%, p = 0.095). The LED group lost 10.6% body weight and 26.6% body fat mass (p < 0.001) compared to 1.6% (p = 0.002) and 5.5% (p < 0.001) following AIT. Waist circumference and visceral abdominal fat were reduced by both interventions but were most pronounced following LED (between-group, p < 0.001). Total cholesterol, non-HDL-C and triglycerides decreased significantly in both groups whereas HDL-C and blood pressure were unchanged. Six participants had their antihypertensive treatment reduced following LED (between-group, p = 0.032). Canadian Cardiovascular Society (CCS), New York Heart Association (NYHA) and anxiety scores were improved, while depressive symptoms remained unchanged. Intention-to-treat analyses including 65 participants (93%) were similar to per protocol analysis. Conclusion: Both interventions were feasible and effective in achieving the desired effects. LED was superior in improving body composition and blood pressure, whereas effects on lipids and symptoms were similar in the two groups. Thus, both AIT and LED improve the cardiovascular risk profile in overweight individuals with contemporarily treated CAD.

European journal of preventive cardiology · randomised controlled trial · 30 citationsread the source →

Acceptance and commitment therapy for symptom interference in metastatic breast cancer patients: a pilot randomized trial.

Purpose: Breast cancer is the leading cause of cancer mortality in women worldwide. With medical advances, metastatic breast cancer (MBC) patients often live for years with many symptoms that interfere with activities. However, there is a paucity of efficacious interventions to address symptom-related suffering and functional interference. Thus, this study examined the feasibility and preliminary efficacy of telephone-based acceptance and commitment therapy (ACT) for symptom interference with functioning in MBC patients. Methods: Symptomatic MBC patients (N = 47) were randomly assigned to six telephone sessions of ACT or six telephone sessions of education/support. Patients completed measures of symptom interference and measures assessing the severity of pain, fatigue, sleep disturbance, depressive symptoms, and anxiety. Results: The eligibility screening rate (64%) and high retention (83% at 8 weeks post-baseline) demonstrated feasibility. When examining within-group change, ACT participants showed decreases in symptom interference (i.e., fatigue interference and sleep-related impairment; Cohen's d range = - 0.23 to - 0.31) at 8 and 12 weeks post-baseline, whereas education/support participants showed minimal change in these outcomes (d range = - 0.03 to 0.07). Additionally, at 12 weeks post-baseline, ACT participants showed moderate decreases in fatigue and sleep disturbance (both ds = - 0.43), whereas education/support participants showed small decreases in these outcomes (ds = - 0.24 and - 0.18 for fatigue and sleep disturbance, respectively). Both the ACT and education/support groups showed reductions in depressive symptoms (ds = - 0.27 and - 0.28) at 12 weeks post-baseline. Group differences in all outcomes were not statistically significant. Conclusions: ACT shows feasibility and promise in improving fatigue and sleep-related outcomes in MBC patients and warrants further investigation.

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · randomised controlled trial · 62 citationsread the source →

Web-based acceptance and commitment therapy for depressive symptoms with minimal support: a randomized controlled trial.

Low-intensity interventions for people suffering from depressive symptoms are highly desirable. The aim of the present study was to investigate the outcomes of a web-based acceptance and commitment therapy (ACT)-based intervention without face-to-face contact for people suffering from depressive symptoms. Participants (N = 39) with depressive symptoms were randomly assigned to an Internet-delivered acceptance and commitment therapy (iACT) intervention or a waiting list control condition (WLC). Participants were evaluated with standardized self-reporting measures (Beck Depression Inventory [BDI-II], Symptom Checklist-90 [SCL-90], Acceptance and Action Questionnaire [AAQ-2], Five Facet Mindfulness Questionnaire [FFMQ], Automatic Thoughts Questionnaire [ATQ], and White Bear Suppression Inventory [WBSI]) at pre- and post-measurement. Long-term effects in the iACT group were examined using a 12-month follow-up. The iACT program comprised home assignments, online feedback given by master's-level students of psychology over a 7-week intervention period, and automated email-based reminders. Significant effects were observed in favor of the iACT group on depression symptomatology (between effect sizes [ESs] at post-treatment, iACT/WLC, g = .83), psychological and physiological symptoms (g = .60), psychological flexibility (g = .67), mindfulness skills (g = .53), and frequency of automatic thoughts (g = .57) as well as thought suppression (g = .53). The treatment effects in the iACT group were maintained over the 12-month follow-up period (within-iACT ES: BDI-II, g = 1.33; SCL-90, g = 1.04; ATQF/B [Frequency/Believability], FFMQ, WBSI, AAQ-II, g = .74-1.08). The iACT participants stated that they would be happy to recommend the same intervention to others with depressive symptoms. We conclude that an ACT-based guided Internet-delivered treatment with minimal contact can be effective for people with depressive symptoms.

Behavior modification · randomised controlled trial · 65 citationsread the source →

Efficacy of Gabapentin for the Treatment of Alcohol Use Disorder in Patients With Alcohol Withdrawal Symptoms: A Randomized Clinical Trial.

Importance: Although an estimated 30 million people meet criteria for alcohol use disorder (AUD), few receive appropriate pharmacotherapy. A more personalized, symptom-specific, approach might improve efficacy and acceptance. Objective: To examine whether gabapentin would be useful in the treatment of AUD, especially in those with the most alcohol withdrawal symptoms. Design, setting, and participants: This double-blind randomized clinical trial conducted between November 2014 and June 2018 evaluated gabapentin vs placebo in community-recruited participants screened and treated in an academic outpatient setting over a 16-week treatment period. A total of 145 treatment-seeking individuals who met Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for AUD and were not receiving other AUD intervention were screened, and 96 who also met recent alcohol withdrawal criteria were randomized to treatment after 3 abstinent days. Daily drinking was recorded, and percentage of disialo carbohydrate-deficient transferrin in the blood, a heavy drinking marker, was collected at baseline and monthly during treatment. Interventions: Gabapentin up to 1200 mg/d, orally, vs placebo along with 9 medical management visits (20 minutes each). Main outcomes and measures: The percentage of individuals with no heavy drinking days and those with total abstinence were compared between treatment groups and further evaluated based on prestudy alcohol withdrawal symptoms. Results: Of 96 randomized individuals, 90 were evaluable (44 in the gabapentin arm and 46 in the placebo arm), with a mean (SD) age of 49.6 (10.1) years; 69 were men (77%) and 85 were white (94%). The evaluable participants had 83% baseline heavy drinking days (4 or more drinks/day for women, 5 or more for men) and met 4.5 alcohol withdrawal criteria from the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). More gabapentin-treated individuals had no heavy drinking days (12 of 44 participants [27%]) compared with placebo (4 of 46 participants [9%]), a difference of 18.6% (95% CI, 3.1-34.1; P = .02; number needed to treat [NNT], 5.4), and more total abstinence (8 of 44 [18%]) compared with placebo (2 of 46 [4%]), a difference of 13.8% (95% CI, 1.0-26.7; P = .04; NNT, 6.2). The prestudy high-alcohol withdrawal group had positive gabapentin effects on no heavy drinking days (P < .02; NNT, 3.1) and total abstinence (P = .003; NNT, 2.7) compared with placebo, while within the low-alcohol withdrawal group, there were no significant differences. These findings were similar for other drinking variables, where gabapentin was more efficacious than placebo in the high-alcohol withdrawal group only. Gabapentin caused more dizziness, but this did not affect efficacy. Conclusions and relevance: These data, combined with others, suggest gabapentin might be most efficacious in people with AUD and a history of alcohol withdrawal symptoms. Future studies should evaluate sleep changes and mood during early recovery as mediators of gabapentin efficacy. Trial registration: ClinicalTrials.gov Identifier: NCT02349477.

JAMA internal medicine · randomised controlled trial · 119 citationsread the source →

Effects of a Home-Based and Volunteer-Administered Physical Training, Nutritional, and Social Support Program on Malnutrition and Frailty in Older Persons: A Randomized Controlled Trial.

Objectives: The aim of this study was to examine the effects of a home-based and volunteer-administered physical training and nutritional intervention program compared with social support intervention on nutritional and frailty status in prefrail and frail community-dwelling older persons. Design: This was a randomized controlled trial in which community-dwelling persons (mean age = 83 years) were recruited and randomly assigned to the physical training and nutritional intervention group (PTN, n = 39) and the social support group (SoSu, n = 41). The study was conducted by trained lay nonprofessionals. Setting: The community-dwelling older persons in both groups were visited twice a week by trained nonprofessional volunteers (buddies) in Vienna, Austria. Participants: Eighty prefrail and frail adults aged 65 years or older. Intervention: In the PTN group, both the buddies and older persons performed 6 strength exercises within a circuit training session and discussed nutrition-related aspects. The active control group (SoSu) had the opportunity to perform cognitive training in addition to the social contact. Measurements: Outcome measures as nutritional (Mini Nutritional Assessment long form [MNA-LF]) and frailty status (Frailty Instrument for Primary Care of the Survey of Health, Ageing and Retirement in Europe [SHARE-FI]) were obtained at baseline and after 12 weeks. Results: Significant improvements in the MNA-LF score (1.54 points, 95% confidence interval [CI] 0.51-2.56; P = .004) and the SHARE-FI score (-0.71 discrete factor score values, 95% CI -1.07, -0.35; P < .001) were observed in the PTN group after 12 weeks. In both groups, the prevalence of impaired nutritional status and frailty decreased significantly over time. The prevalence of impaired nutritional status decreased by 25% in the PTN group and by 23% in the SoSu group. Moreover, the prevalence of frailty decreased by 17% in the PTN group and by 16% in the SoSu group. The presence of impaired nutritional status at baseline was independently associated with greater changes in the nutritional (adjusted odds ratio [OR] 3.18, 95% CI 1.26-7.98; P = .014) and frailty status (adjusted OR 3.16, 95% CI 1.01-9.93; P = .049) after 12 weeks. Conclusion: The results indicate that a home-based physical training, nutritional, and social support intervention conducted by nonprofessionals is feasible and can help to tackle malnutrition and frailty in older persons living at home. Furthermore, social support alone also can result in improvement. In particular, older adults with impaired nutritional status at baseline can benefit more from the intervention. Such a home visit program might also have the potential to prevent future health risks and could allay isolation and loneliness.

Journal of the American Medical Directors Association · randomised controlled trial · 126 citationsread the source →

The effects of volunteering on loneliness among lonely older adults: the HEAL-HOA dual randomised controlled trial.

Background: Previous randomised controlled trials have largely relied on self-reported volunteer work to assess the effects of volunteering and have rarely provided structured volunteering activities during the intervention period. The present study aimed to investigate the effects of social volunteering work over 12 months on loneliness among older adults during the COVID-19 pandemic. Methods: A dual randomised controlled trial was done in Hong Kong to investigate the long-term effects of telephone-delivered psychosocial interventions by older Chinese volunteers who were screened as lonely, for older adult recipients who had low income, lived alone, felt lonely, and were digitally excluded. Participants were included if they were aged 50-70 years; had provided consent to be trained and serve as a volunteer for at least 2 h per week for 6 months; had at least 3 years of secondary school education; had no severe self-reported physical, mental, or cognitive health problems; were not working full or part-time; had engaged in formal volunteering fewer than four times within the past year; and were lonely (ie, had a score of at least 6 on the three-item UCLA Loneliness Scale). Participants were allocated into either the volunteering or control group (psychoeducation programme) using a random number method. The details of group allocation were concealed as the research assistant responsible for randomisation was different to the research assistants responsible for recruitment and assessments (who were masked to the condition). Following a 6-week training, the volunteers delivered a psychosocial intervention to older intervention recipients for 6 months. The primary outcome was loneliness measured with the 20-item UCLA Loneliness Scale and the De Jong Gierveld (DJG) Loneliness Scales at 6 months and 12 months. Assessments were performed before training (baseline; T1), at 6 months (T2), and at 12 months after training (T3). The intention-to-treat principle was used to compare the effects of volunteering between the two groups. The trial was registered in the Clinical Trials Registry of the University of Hong Kong Clinical Trials Centre (HKUCTR-2929). This trial has completed. Findings: Between May 3, 2021, and Oct 6, 2022, a total of 375 individuals were recruited to the trial, including 84 males (22%) and 291 females (78%). 185 were randomly assigned to the volunteering group (56 to deliver a mindfulness intervention, 65 to deliver a behavioural activation intervention, and 64 to deliver a befriending intervention) and 190 were assigned to the control group. 311 (83%) of 375 participants were 60 years or older (median 64 years [SD 4·86]). Participants in the volunteering group reported a significantly lower level of loneliness at T2 (dppc2 ranged from -0·41 to -0·70) compared with T1 than participants in the control condition. There was a significant decrease in loneliness measured using the UCLA Loneliness Scale at T2 in the volunteering group but such a decline was not shown in the control group (condition × time interaction, estimate 0·19 [95% CI 0·08 to 0·29], p=0·00058, dppc2=-0·41). Similarly, when measured with the DJG Loneliness Scale, there was a significantly greater decrease in loneliness in the volunteering group compared with the control group at T2, including a medium to large effect size on total DJG scores (estimate 1·34 [95% CI 0·83 to 1·84], p<0·0001, dppc2=-0·70) and a medium effect size on emotional (estimate 0·63 [0·35 to 0·90], p<0·0001, dppc2=-0·59) and social subscales (estimate 0·71 [95% CI 0·37 to 1·05], p<0·0001, dppc2=-0·58). Although most of the positive effects of volunteering were not sustained at T3, the volunteers who continued to volunteer for more than 2 h per week at T3 reported lower levels of loneliness than those who did not maintain volunteering. Interpretation: This randomised controlled trial demonstrates the beneficial effect of volunteering on reducing loneliness in older adults who feel lonely, and that this benefit can be maintained through continued participation in voluntary work. Future intervention programmes should strengthen older adults' commitment to volunteer. Funding: Research Grants Committee of the Hong Kong Special Administrative Region, China.

The lancet. Healthy longevity · randomised controlled trial · 16 citationsread the source →

Internet Cognitive Behavioral Therapy for Women With Postnatal Depression: A Randomized Controlled Trial of MumMoodBooster.

Background: There are few published controlled trials examining the efficacy of Internet-based treatment for postnatal depression (PND) and none that assess diagnostic status (clinical remission) as the primary outcome. This is despite the need to improve treatment uptake and accessibility because fewer than 50% of postnatally depressed women seek help, even when identified as depressed. Objective: In a randomized controlled trial (RCT), we aimed to test the efficacy of a 6-session Internet intervention (the MumMoodBooster program, previously evaluated in a feasibility trial) in a sample of postnatal women with a clinical diagnosis of depression. The MumMoodBooster program is a cognitive behavioral therapy (CBT) intervention, is highly interactive, includes a partner website, and was supported by low-intensity telephone coaching. Methods: This was a parallel 2-group RCT (N=43) comparing the Internet CBT treatment (n=21) to treatment as usual (n=22). At baseline and at 12 weeks after enrollment, women's diagnostic status was assessed by telephone with the Standardized Clinical Interview for DSM-IV (SCID-IV) and symptom severity with the Beck Depression Inventory (BDI-II). Depression symptoms were measured repeatedly throughout the study period with the Patient Health Questionnaire (PHQ-9). Results: At the end of the study, 79% (15/19) of women who received the Internet CBT treatment no longer met diagnostic criteria for depression on the SCID-IV (these outcome data were missing for 2 intervention participants). This contrasted with only 18% (4/22) remission in the treatment as usual condition. Depression scores on the BDI-II showed a large effect favoring the intervention group (d=.83, 95% CI 0.20-1.45). Small to medium effects were found on the PHQ-9 and on measures of anxiety and stress. Adherence to the program was very good with 86% (18/21) of users completing all sessions; satisfaction with the program was rated 3.1 out of 4 on average. Conclusions: Our results suggest that our Internet CBT program, MumMoodBooster, is an effective treatment option for women clinically diagnosed with PND. This is one of only two controlled evaluations of specialized online psychological treatment among women clinically diagnosed with PND. MumMoodBooster appears to be a feasible, effective treatment option, which is potentially accessible to large numbers of women in metropolitan, rural, and remote areas. Future work might be focused profitably on establishing comparability with face-to-face treatments and purely self-guided delivery. We have commenced a larger RCT comparing MumMoodBooster with face-to-face CBT. Trial registration: Australian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12613000113752; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363561 (Archived by WebCite® at http://www.webcitation.org/6f64kuyLf).

Journal of medical Internet research · randomised controlled trial · 137 citationsread the source →

Effect of an early perinatal depression intervention on long-term child development outcomes: follow-up of the Thinking Healthy Programme randomised controlled trial.

Background: Perinatal depression has been linked with deleterious child development outcomes, yet maternal depression interventions have not been shown to have lasting effects on child development, and evidence is not available from countries of low or middle income. In the Thinking Healthy Programme cluster-randomised controlled trial, a perinatal depression intervention was assessed in Pakistan in 2006-07. The intervention significantly reduced depression levels 12 months post partum compared with a control. We aimed to assess the effect of this same intervention on the cognitive, socioemotional, and physical development of children at around age 7 years. Methods: Mother-child dyads who participated in the Thinking Healthy Programme cluster-randomised controlled trial were interviewed when the index child was about 7 years old. A reference group of 300 mothers who did not have prenatal depression and, therefore, did not receive the original intervention, was enrolled with their children at the same time. The primary cognitive outcome was the score on the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV); primary socioemotional outcomes included scores on the Strengths and Difficulties Questionnaire (SDQ) and the Spence Children's Anxiety Scale (SCAS); and primary physical outcomes were height-for-age, weight-for-age, and body-mass index (BMI)-for-age Z scores. Generalised linear modelling with random effects to account for clustering was the main method of analysis. Analyses were by intention to treat. The Thinking Healthy Programme cluster-randomised trial was registered at ISRCTN.com, number ISRCTN65316374. Findings: Of 705 participating mother-child dyads interviewed at the end of the Thinking Healthy Programme randomised controlled trial, 584 (83%) dyads were enrolled. 289 mothers had received the intervention and 295 had received a control consisting of enhanced usual care. The mean age of the children was 7·6 years (SD 0·1). Overall, cognitive, socioemotional, or physical development outcomes did not differ between children in the intervention or control groups whose mothers had prenatal depression. When compared with the reference group of children whose mothers did not have prenatal depression, the Thinking Healthy Programme trial children had worse socioemotional outcomes; mean scores were significantly higher on the SDQ for total difficulty (11·34 vs 10·35; mean difference 0·78, 95% CI 0·09-1·47; p=0·03) and on the SCAS for anxiety (21·33 vs 17·57; mean difference 2·93, 1·15-4·71; p=0·0013). Cognitive and physical outcomes did not differ. Interpretation: Our findings show that cognitive, socioemotional, and physical developmental outcomes of children at age 7 years whose mother had prenatal depression did not differ between those who received the Thinking Healthy Programme intervention and those who received the control. Further investigation is needed to understand what types of complex interventions or approaches are needed for long-term gains in maternal and child wellbeing. Prolonged, detailed, and frequent follow-up is warranted for all interventions. Funding: Grand Challenges Canada (Government of Canada), Saving Brains programme.

The lancet. Psychiatry · randomised controlled trial · 76 citationsread the source →

Psychotherapy for depression in older veterans via telemedicine: a randomised, open-label, non-inferiority trial.

Background: Many older adults with major depression, particularly veterans, do not have access to evidence-based psychotherapy. Telemedicine could increase access to best-practice care for older adults facing barriers of mobility, stigma, and geographical isolation. We aimed to establish non-inferiority of behavioural activation therapy for major depression delivered via telemedicine to same-room care in largely male, older adult veterans. Methods: In this randomised, controlled, open-label, non-inferiority trial, we recruited veterans (aged ≥58 years) meeting DSM-IV criteria for major depressive disorder from the Ralph H Johnson Veterans Affairs Medical Center and four associated community outpatient-based clinics in the USA. We excluded actively psychotic or demented people, those with both suicidal ideation and clear intent, and those with substance dependence. The study coordinator randomly assigned participants (1:1; block size 2-6; stratified by race; computer-generated randomisation sequence by RGK) to eight sessions of behavioural activation for depression either via telemedicine or in the same room. The primary outcome was treatment response according to the Geriatric Depression Scale (GDS) and Beck Depression Inventory (BDI; defined as a 50% reduction in symptoms from baseline at 12 months), and Structured Clinical Interview for DSM-IV, clinician version (defined as no longer being diagnosed with major depressive disorder at 12 months follow-up), in the per-protocol population (those who completed at least four treatment sessions and for whom all outcome measurements were done). Those assessing outcomes were masked. The non-inferiority margin was 15%. This trial is registered with ClinicalTrials.gov, number NCT00324701. Findings: Between April 1, 2007, and July 31, 2011, we screened 780 patients, and the study coordinator randomly assigned participants to either telemedicine (120 [50%]) or same-room treatment (121 [50%]). We included 100 (83%) patients in the per-protocol analysis in the telemedicine group and 104 (86%) in the same-room group. Treatment response according to GDS did not differ significantly between the telemedicine (22 [22·45%, 90% CI 15·52-29·38] patients) and same-room (21 [20·39%, 90% CI 13·86-26·92]) groups, with an absolute difference of 2·06% (90% CI -7·46 to 11·58). Response according to BDI also did not differ significantly (telemedicine 19 [24·05%, 90% CI 16·14-31·96] patients; same room 19 [23·17%, 90% CI 15·51-30·83]), with an absolute difference of 0·88% (90% CI -10·13 to 11·89). Response on the Structured Clinical Interview for DSM-IV, clinician version, also did not differ significantly (39 [43·33%, 90% CI 34·74-51·93] patients in the telemedicine group and 46 [48·42%, 90% CI 39·99-56·85] in the same-room group), with a difference of -5·09% (-17·13 to 6·95; p=0·487). Results from the intention-to-treat population were similar. MEM analyses showed that no significant differences existed between treatment trajectories over time for BDI and GDS. The criteria for non-inferiority were met. We did not note any adverse events. Interpretation: Telemedicine-delivered psychotherapy for older adults with major depression is not inferior to same-room treatment. This finding shows that evidence-based psychotherapy can be delivered, without modification, via home-based telemedicine, and that this method can be used to overcome barriers to care associated with distance from and difficulty with attendance at in-person sessions in older adults. Funding: US Department of Veterans Affairs.

The lancet. Psychiatry · randomised controlled trial · 123 citationsread the source →

Clinical and cost-effectiveness of nurse-delivered sleep restriction therapy for insomnia in primary care (HABIT): a pragmatic, superiority, open-label, randomised controlled trial.

Background: Insomnia is prevalent and distressing but access to the first-line treatment, cognitive behavioural therapy (CBT), is extremely limited. We aimed to assess the clinical and cost-effectiveness of sleep restriction therapy, a key component of CBT, which has the potential to be widely implemented. Methods: We did a pragmatic, superiority, open-label, randomised controlled trial of sleep restriction therapy versus sleep hygiene. Adults with insomnia disorder were recruited from 35 general practices across England and randomly assigned (1:1) using a web-based randomisation programme to either four sessions of nurse-delivered sleep restriction therapy plus a sleep hygiene booklet or a sleep hygiene booklet only. There was no restriction on usual care for either group. Outcomes were assessed at 3 months, 6 months, and 12 months. The primary endpoint was self-reported insomnia severity at 6 months measured with the insomnia severity index (ISI). The primary analysis included participants according to their allocated group and who contributed at least one outcome measurement. Cost-effectiveness was evaluated from the UK National Health Service and personal social services perspective and expressed in terms of incremental cost per quality-adjusted life year (QALY) gained. The trial was prospectively registered (ISRCTN42499563). Findings: Between Aug 29, 2018, and March 23, 2020 we randomly assigned 642 participants to sleep restriction therapy (n=321) or sleep hygiene (n=321). Mean age was 55·4 years (range 19-88), with 489 (76·2%) participants being female and 153 (23·8%) being male. 580 (90·3%) participants provided data for at least one outcome measurement. At 6 months, mean ISI score was 10·9 (SD 5·5) for sleep restriction therapy and 13·9 (5·2) for sleep hygiene (adjusted mean difference -3·05, 95% CI -3·83 to -2·28; p<0·0001; Cohen's d -0·74), indicating that participants in the sleep restriction therapy group reported lower insomnia severity than the sleep hygiene group. The incremental cost per QALY gained was £2076, giving a 95·3% probability that treatment was cost-effective at a cost-effectiveness threshold of £20 000. Eight participants in each group had serious adverse events, none of which were judged to be related to intervention. Interpretation: Brief nurse-delivered sleep restriction therapy in primary care reduces insomnia symptoms, is likely to be cost-effective, and has the potential to be widely implemented as a first-line treatment for insomnia disorder. Funding: The National Institute for Health and Care Research Health Technology Assessment Programme.

Lancet (London, England) · randomised controlled trial · 59 citationsread the source →

Early intervention for psychosis.

Background: Proponents of early intervention have argued that outcomes might be improved if more therapeutic efforts were focused on the early stages of schizophrenia or on people with prodromal symptoms. Early intervention in schizophrenia has two elements that are distinct from standard care: early detection, and phase-specific treatment (phase-specific treatment is a psychological, social or physical treatment developed, or modified, specifically for use with people at an early stage of the illness).Early detection and phase-specific treatment may both be offered as supplements to standard care, or may be provided through a specialised early intervention team. Early intervention is now well established as a therapeutic approach in America, Europe and Australasia. Objectives: To evaluate the effects of: (a) early detection; (b) phase-specific treatments; and (c) specialised early intervention teams in the treatment of people with prodromal symptoms or first-episode psychosis. Search strategy: We searched the Cochrane Schizophrenia Group Trials Register (March 2009), inspected reference lists of all identified trials and reviews and contacted experts in the field. Selection criteria: We included all randomised controlled trials (RCTs) designed to prevent progression to psychosis in people showing prodromal symptoms, or to improve outcome for people with first-episode psychosis. Eligible interventions, alone and in combination, included: early detection, phase-specific treatments, and care from specialised early intervention teams. We accepted cluster-randomised trials but excluded non-randomised trials. Data collection and analysis: We reliably selected studies, quality rated them and extracted data. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) and used intention-to-treat analysis (ITT). Main results: Studies were diverse, mostly small, undertaken by pioneering researchers and with many methodological limitations (18 RCTs, total n=1808). Mostly, meta-analyses were inappropriate. For the six studies addressing prevention of psychosis for people with prodromal symptoms, olanzapine seemed of little benefit (n=60, 1 RCT, RR conversion to psychosis 0.58 CI 0.3 to 1.2), and cognitive behavioural therapy (CBT) equally so (n=60, 1 RCT, RR conversion to psychosis 0.50 CI 0.2 to 1.7). A risperidone plus CBT plus specialised team did have benefit over specialist team alone at six months (n=59, 1 RCT, RR conversion to psychosis 0.27 CI 0.1 to 0.9, NNT 4 CI 2 to 20), but this was not seen by 12 months (n=59, 1 RCT, RR 0.54 CI 0.2 to 1.3). Omega 3 fatty acids (EPA) had advantage over placebo (n=76, 1 RCT, RR transition to psychosis 0.13 CI 0.02 to 1.0, NNT 6 CI 5 to 96). We know of no replications of this finding. The remaining trials aimed to improve outcome in first-episode psychosis. Phase-specific CBT for suicidality seemed to have little effect, but the single study was small (n=56, 1 RCT, RR suicide 0.81 CI 0.05 to 12.26). Family therapy plus a specialised team in the Netherlands did not clearly affect relapse (n=76, RR 1.05 CI 0.4 to 3.0), but without the specialised team in China it may (n=83, 1 RCT, RR admitted to hospital 0.28 CI 0.1 to 0.6, NNT 3 CI 2 to 6). The largest and highest quality study compared specialised team with standard care. Leaving the study early was reduced (n=547, 1 RCT, RR 0.59 CI 0.4 to 0.8, NNT 9 CI 6 to 18) and compliance with treatment improved (n=507, RR stopped treatment 0.20 CI 0.1 to 0.4, NNT 9 CI 8 to 12). The mean number of days spent in hospital at one year were not significantly different (n=507, WMD, -1.39 CI -2.8 to 0.1), neither were data for 'Not hospitalised' by five years (n=547, RR 1.05 CI 0.90 to 1.2). There were no significant differences in numbers 'not living independently' by one year (n=507, RR 0.55 CI 0.3 to 1.2). At five years significantly fewer participants in the treatment group were 'not living independently' (n=547, RR 0.42 CI 0.21 to 0.8, NNT 19 CI 14 to 62). When phase-specific treatment (CBT) was compared with befriending no significant differences emerged in the number of participants being hospitalised over the 12 months (n=62, 1 RCT, RR 1.08 CI 0.59 to 1.99).Phase-specific treatment E-EPA oils suggested no benefit (n=80, 1 RCT, RR no response 0.90 CI 0.6 to 1.4) as did phase-specific treatment brief intervention (n=106, 1 RCT, RR admission 0.86 CI 0.4 to 1.7). Phase-specific ACE found no benefit but participants given vocational intervention were more likely to be employed (n=41, 1 RCT, RR 0.39 CI 0.21 to 0.7, NNT 2 CI 2 to 4). Phase-specific cannabis and psychosis therapy did not show benefit (n=47, RR cannabis use 1.30 CI 0.8 to 2.2) and crisis assessment did not reduce hospitalisation (n=98, RR 0.85 CI 0.6 to 1.3). Weight was unaffected by early behavioural intervention. Authors' conclusions: There is emerging, but as yet inconclusive evidence, to suggest that people in the prodrome of psychosis can be helped by some interventions. There is some support for specialised early intervention services, but further trials would be desirable, and there is a question of whether gains are maintained. There is some support for phase-specific treatment focused on employment and family therapy, but again, this needs replicating with larger and longer trials.

The Cochrane database of systematic reviews · meta-analysis · 133 citationsread the source →

Adolescent end of life preferences and congruence with their parents' preferences: results of a survey of adolescents with cancer.

Background: Little is known about how well family members accurately represent adolescents when making EOL decisions on their behalf. This study reports on surveys given to adolescents with cancer and their parents as part of a larger study facilitating advanced care discussions, as well as the results of a survey for health care providers. Procedure: Trained facilitators administered surveys orally to adolescents and families in the intervention arm of the FAmily CEntered Advance Care Planning (ACP) for Teens with Cancer (FACE-TC) study. In addition, a post-hoc survey was sent to oncology providers. Results: Seventeen adolescent/family dyads completed this survey. Seventy five percent of adolescents believed it was appropriate to discuss EOL decisions early and only 12% were not comfortable discussing death. Most preferred to be at home if dying. There were substantial areas of congruence between adolescents and their surrogates, but lower agreement on the importance of dying a natural death, dying at home and "wanting to know if I were dying." Among providers, 83% felt their patients' participation in the study was helpful to the patients and 78% felt it was helpful to them as providers. Conclusions: Adolescents with cancer were comfortable discussing EOL, and the majority preferred to talk about EOL issues before they are facing EOL. There were substantive areas of agreement between adolescents and their surrogates, but important facets of adolescents' EOL wishes were not known by their families, reinforcing the importance of eliciting individual preferences and engaging dyads so parents can understand their children's wishes.

Pediatric blood & cancer · clinical trial · 96 citationsread the source →

Benefits of physical exercise training on cognition and quality of life in frail older adults.

Objectives: Frailty is a state of vulnerability associated with increased risks of fall, hospitalization, cognitive deficits, and psychological distress. Studies with healthy senior suggest that physical exercise can help improve cognition and quality of life. Whether frail older adults can show such benefits remains to be documented. Method: A total of 83 participants aged 61-89 years were assigned to an exercise-training group (3 times a week for 12 weeks) or a control group (waiting list). Frailty was determined by a complete geriatric examination using specific criteria. Pre- and post-test measures assessed physical capacity, cognitive performance, and quality of life. Results: Compared with controls, the intervention group showed significant improvement in physical capacity (functional capacities and physical endurance), cognitive performance (executive functions, processing speed, and working memory), and quality of life (global quality of life, leisure activities, physical capacity, social/family relationships, and physical health). Benefits were overall equivalent between frail and nonfrail participants. Discussion: Physical exercise training leads to improved cognitive functioning and psychological well-being in frail older adults.

The journals of gerontology. Series B, Psychological sciences and social sciences · randomised controlled trial · 194 citationsread the source →

Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression.

Background: Ketamine is reported to have rapid antidepressant effects; however, there is limited understanding of the time-course of ketamine effects beyond a single infusion. A previous report including 10 participants with treatment-resistant major depression (TRD) found that six ketamine infusions resulted in a sustained antidepressant effect. In the current report, we examined the pattern and durability of antidepressant effects of repeated ketamine infusions in a larger sample, inclusive of the original. Methods: Participants with TRD (n = 24) underwent a washout of antidepressant medication followed by a series of up to six IV infusions of ketamine (.5 mg/kg) administered open-label three times weekly over a 12-day period. Participants meeting response criteria were monitored for relapse for up to 83 days from the last infusion. Results: The overall response rate at study end was 70.8%. There was a large mean decrease in Montgomery-Åsberg Depression Rating Scale score at 2 hours after the first ketamine infusion (18.9 ± 6.6, p < .001), and this decrease was largely sustained for the duration of the infusion period. Response at study end was strongly predicted by response at 4 hours (94% sensitive, 71% specific). Among responders, median time to relapse after the last ketamine infusion was 18 days. Conclusions: Ketamine was associated with a rapid antidepressant effect in TRD that was predictive of a sustained effect. Future controlled studies will be required to identify strategies to maintain an antidepressant response among patients who benefit from a course of ketamine.

Biological psychiatry · clinical trial · 595 citationsread the source →

Netmums: a phase II randomized controlled trial of a guided Internet behavioural activation treatment for postpartum depression.

Background: Despite the high prevalence of postnatal depression (PND), few women seek help. Internet interventions may overcome many of the barriers to PND treatment use. We report a phase II evaluation of a 12-session, modular, guided Internet behavioural activation (BA) treatment modified to address postnatal-specific concerns [Netmums Helping With Depression (NetmumsHWD)]. Method: To assess feasibility, we measured recruitment and attrition to the trial and examined telephone session support and treatment adherence. We investigated sociodemographic and psychological predictors of treatment adherence. Effectiveness outcomes were estimated with the Edinburgh Postnatal Depression Scale (EPDS), Generalized Anxiety Disorder-7, Work and Social Adjustment Scale, Postnatal Bonding Questionnaire, and Social Provisions Scale. Results: A total of 249 women were recruited via a UK parenting site, Netmums.com. A total of 83 women meeting DSM-IV criteria for major depressive disorder were randomized to NetmumsHWD (n = 41) or treatment-as-usual (TAU; n = 42). Of the 83 women, 71 (86%) completed the EPDS at post-treatment, and 71% (59/83) at the 6-month follow-up. Women completed an average of eight out of 12 telephone support sessions and five out of 12 modules. Working women and those with less support completed fewer modules. There was a large effect size favouring women who received NetmumsHWD on depression, work and social impairment, and anxiety scores at post-treatment compared with women in the TAU group, and a large effect size on depression at 6 months post-treatment. There were small effect sizes for postnatal bonding and perceived social support. Conclusions: A supported, modular, Internet BA programme can be feasibly delivered to postpartum women, offering promise to improve depression, anxiety and functioning.

Psychological medicine · randomised controlled trial · 134 citationsread the source →

Enhanced treatment for depression in primary care: long-term outcomes of a psycho-educational prevention program alone and enriched with psychiatric consultation or cognitive behavioral therapy

BACKGROUND: The long-term outcome of major depression is often unfavorable, and because most cases of depression are managed by general practitioners (GPs), this places stress on the need to improve treatment in primary care. This study evaluated the long-term effects of enhancing the GP's usual care (UC) with three experimental interventions. METHOD: A randomized controlled trial was conducted from 1998 to 2003. The main inclusion criterion was receiving GP treatment for a depressive episode. We compared: (1) UC (n=72) with UC enhanced with: (2) a psycho-educational prevention (PEP) program (n=112); (3) psychiatrist-enhanced PEP (n=37); and (4) brief cognitive behavioral therapy followed by PEP (CBT-enhanced PEP) (n=44). We assessed depression status quarterly during a 3-year follow-up. RESULTS: Pooled across groups, depressive disorder-free and symptom-free times during follow-up were 83% and 17% respectively. Almost 64% of the patients had a relapse or recurrence, the median time to recurrence was 96 weeks, and the mean Beck Depression Inventory (BDI) score over 12 follow-up assessments was 9.6. Unexpectedly, PEP patients had no better outcomes than UC patients. However, psychiatrist-enhanced PEP and CBT-enhanced PEP patients reported lower BDI severity during follow-up than UC patients [mean difference 2.07 (95% confidence interval (CI) 1.13-3.00) and 1.62 (95% CI 0.70-2.55) respectively] and PEP patients [2.37 (95% CI 1.35-3.39) and 1.93 (95% CI 0.92-2.94) respectively]. CONCLUSIONS: The PEP program had no extra benefit compared to UC and may even worsen outcome in severely depressed patients. Enhancing treatment of depression in primary care with psychiatric consultation or brief CBT seems to improve the long-term outcome, but findings need replication as the interventions were combined with the ineffective PEP program.

Psychological Medicine · randomised controlled trial · 70 citationsread the source →

A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial).

Background: There have been increasing concerns regarding the safety and efficacy of neuroleptics in people with dementia, but there are very few long-term trials to inform clinical practice. The aim of this study was to determine the impact of long-term treatment with neuroleptic agents upon global cognitive decline and neuropsychiatric symptoms in patients with Alzheimer disease. Methods and findings: Design: Randomised, blinded, placebo-controlled parallel two-group treatment discontinuation trial. Setting: Oxfordshire, Newcastle and Gateshead, London and Edinburgh, United Kingdom. Participants: Patients currently prescribed the neuroleptics thioridazine, chlorpromazine, haloperidol trifluoperazine or risperidone for behavioural or psychiatric disturbance in dementia for at least 3 mo. Interventions: Continue neuroleptic treatment for 12 mo or switch to an identical placebo. Outcome measures: Primary outcome was total Severe Impairment Battery (SIB) score. Neuropsychiatric symptoms were evaluated with the Neuropsychiatric Inventory (NPI). Results: 165 patients were randomised (83 to continue treatment and 82 to placebo, i.e., discontinue treatment), of whom 128 (78%) commenced treatment (64 continue/64 placebo). Of those, 26 were lost to follow-up (13 per arm), resulting in 51 patients per arm analysed for the primary outcome. There was no significant difference between the continue treatment and placebo groups in the estimated mean change in SIB scores between baseline and 6 mo; estimated mean difference in deterioration (favouring placebo) -0.4 (95% confidence interval [CI] -6.4 to 5.5), adjusted for baseline value (p = 0.9). For neuropsychiatric symptoms, there was no significant difference between the continue treatment and placebo groups (n = 56 and 53, respectively) in the estimated mean change in NPI scores between baseline and 6 mo; estimated mean difference in deterioration (favouring continue treatment) -2.4 (95% CI -8.2 to 3.5), adjusted for baseline value (p = 0.4). Both results became more pronounced at 12 mo. There was some evidence to suggest that those patients with initial NPI >/= 15 benefited on neuropsychiatric symptoms from continuing treatment. Conclusions: For most patients with AD, withdrawal of neuroleptics had no overall detrimental effect on functional and cognitive status. Neuroleptics may have some value in the maintenance treatment of more severe neuropsychiatric symptoms, but this benefit must be weighed against the side effects of therapy. Trial registration: Cochrane Central Registry of Controlled Trials/National Research Register (#ISRCTN33368770).

PLoS medicine · randomised controlled trial · 138 citationsread the source →

Cognitive-behavioural therapy and family intervention for relapse prevention and symptom reduction in psychosis: Randomised controlled trial

BACKGROUND: Family intervention reduces relapse rates in psychosis. Cognitive-behavioural therapy (CBT) improves positive symptoms but effects on relapse rates are not established. AIMS: To test the effectiveness of CBT and family intervention in reducing relapse, and in improving symptoms and functioning in patients who had recently relapsed with non-affective psychosis. METHOD: A multicentre randomised controlled trial (ISRCTN83557988) with two pathways: those without carers were allocated to treatment as usual or CBT plus treatment as usual, those with carers to treatment as usual, CBT plus treatment as usual or family intervention plus treatment as usual. The CBT and family intervention were focused on relapse prevention for 20 sessions over 9 months. RESULTS: A total of 301 patients and 83 carers participated. Primary outcome data were available on 96% of the total sample. The CBT and family intervention had no effects on rates of remission and relapse or on days in hospital at 12 or 24 months. For secondary outcomes, CBT showed a beneficial effect on depression at 24 months and there were no effects for family intervention. In people with carers, CBT significantly improved delusional distress and social functioning. Therapy did not change key psychological processes. CONCLUSIONS: Generic CBT for psychosis is not indicated for routine relapse prevention in people recovering from a recent relapse of psychosis and should currently be reserved for those with distressing medication-unresponsive positive symptoms. Any CBT targeted at this acute population requires development. The lack of effect of family intervention on relapse may be attributable to the low overall relapse rate in those with carers.

The British Journal of Psychiatry · randomised controlled trial · 297 citationsread the source →

Cognitive-behavioral therapy vs risperidone for augmenting serotonin reuptake inhibitors in obsessive-compulsive disorder: a randomized clinical trial.

Importance: Obsessive-compulsive disorder (OCD) is one of the world's most disabling illnesses according to the World Health Organization. Serotonin reuptake inhibitors (SRIs) are the only medications approved by the Food and Drug Administration to treat OCD, but few patients achieve minimal symptoms from an SRI alone. In such cases, practice guidelines recommend adding antipsychotics or cognitive-behavioral therapy consisting of exposure and ritual prevention (EX/RP). Objective: To compare the effects of these 2 SRI augmentation strategies vs pill placebo for the first time, to our knowledge, in adults with OCD. Design, setting, and participants: A randomized clinical trial (conducted January 2007-August 2012) at 2 academic outpatient research clinics that specialize in OCD and anxiety disorders. Patients (aged 18-70 years) were eligible if they had OCD of at least moderate severity despite a therapeutic SRI dose for at least 12 weeks prior to entry. Of 163 who were eligible, 100 were randomized (risperidone, n = 40; EX/RP, n = 40; and placebo, n = 20), and 86 completed the trial. Interventions: While continuing their SRI at the same dose, patients were randomized to the addition of 8 weeks of risperidone (up to 4 mg/d), EX/RP (17 sessions delivered twice weekly), or pill placebo. Independent assessments were conducted every 4 weeks. Main outcome and measure: The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) to measure OCD severity. Results: Patients randomized to EX/RP had significantly greater reduction in week 8 Y-BOCS scores based on mixed-effects models (vs risperidone: mean [SE], -9.72 [1.38]; P < .001 vs placebo: mean [SE], -10.10 [1.68]; P < .001). Patients receiving risperidone did not significantly differ from those receiving placebo (mean [SE], -0.38 [1.72]; P = .83). More patients receiving EX/RP responded (Y-BOCS score decrease ≥25%: 80% for EX/RP, 23% for risperidone, and 15% for placebo; P < .001). More patients receiving EX/RP achieved minimal symptoms (Y-BOCS score ≤12: 43% for EX/RP, 13% for risperidone, and 5% for placebo; P = .001). Adding EX/RP was also superior to risperidone and placebo in improving insight, functioning, and quality of life. Conclusions and relevance: Adding EX/RP to SRIs was superior to both risperidone and pill placebo. Patients with OCD receiving SRIs who continue to have clinically significant symptoms should be offered EX/RP before antipsychotics given its superior efficacy and less negative adverse effect profile. Trial registration: clinicaltrials.gov Identifier: NCT00389493.

JAMA psychiatry · randomised controlled trial · 143 citationsread the source →

Safety and efficacy of resistance exercise in prostate cancer patients with bone metastases.

Background: Due to concerns of fragility fracture, exercise is a perceived contraindication for prostate cancer patients with bone metastases. These patients experience significant functional impairment and muscle atrophy, which may lead to an increased likelihood of skeletal complicaTIOns (i.e., pathological fracture, bone pain) and/or falls. Safe resistance exercise prescription may counteract this effect. The aim of this feasibility trial was to determine the safety and efficacy of resistance exercise by prostate cancer survivors with bone metastatic disease. Methods: Twenty men with established bone metastases secondary to prostate cancer were randomly assigned to a 12-week resistance exercise program in which exercise prescription was based on the location of bone lesions (n=10) or usual care (n=10). Outcomes included safety and tolerance of the exercise program, physical function, physical activity level, body composition, fatigue, quality of life and psychological distress. Outcomes were compared between groups using analysis of covariance adjusted for baseline values. Results: Participants had significant disease load with 65% of participants presenting with two or more regions affected by bone metastases and an average Gleason score of 8.2±0.9. Five participants (exercise=2; usual care=3) did not complete the intervention, three of which were due to advancing disease (exercise=2; usual care=1). No adverse events or skeletal complications occurred during the supervised exercise sessions. The exercise program was well tolerated as evidenced by high attendance (83%) and compliance rates (93%), and the ability of the participants to exercise at an intensity within the target range for cancer survivors (rating of perceived exertion =13.8±1.5). The change in physical function (muscle strength ∼11%; submaximal aerobic exercise capacity ∼5% and ambulation ∼12%), physical activity level (∼24%) and lean mass (∼3%) differed significantly between groups following the intervention, with favorable changes in the exercise group compared with the usual care group. No significant between-group differences were observed for fatigue, quality of life or psychological distress. Conclusions: This initial evidence involving a small sample size suggests that appropriately designed and supervised resistance exercise may be safe and well tolerated by prostate cancer patients with bone metastatic disease and can lead to improvements in physical function, physical activity levels and lean mass. Future trials involving larger sample sizes are required to expand these preliminary findings.

Prostate cancer and prostatic diseases · randomised controlled trial · 150 citationsread the source →

Beneficial effects of short-term nutritional counselling at the primary health-care level among Brazilian adults.

Objective: To evaluate the impact of a low-cost nutritional intervention in changing the lifestyle of adults. Design: Randomised clinical trial. Setting: Primary health-care centre in São José do Rio Preto, São Paulo State, Brazil. Subjects: We randomly assigned 104 adults (83 women and 21 men aged 30-65 years, body mass index 24-35 kg m(-2), non-diabetic) into two groups: nutrition counselling and control. Each subject in the intervention group received three individualised nutritional counselling sessions during the first 6 months aimed at increasing intakes of fruits, vegetables and olive oil, reducing saturated fat and improving physical activity. Body composition, biochemical indicators and lifestyle were assessed at baseline and at 6 months and 1 year in both groups. Results: After 6 months of follow-up, body weight, waist circumference, diastolic blood pressure, fasting blood glucose, total and low-density lipoprotein cholesterol, total and saturated fat, and dietary energy and cholesterol levels showed a more significant decrease among subjects in the intervention group than in the control group (P < 0.05). Moreover, the intervention group showed significantly greater improvement in each intervention goal, such as reduced intake of saturated fat and increased intakes of fruits, vegetables, fibre and olive oil (P < 0.05). After 12 months of follow-up, most of the outcomes were maintained. Conclusions: The low-cost nutritional intervention programme improved serum lipids profile and weight control, and appeared to be feasible for use at a primary health-care centre in a developing country.

Public health nutrition · randomised controlled trial · 41 citationsread the source →

The effectiveness of SPARX, a computerised self help intervention for adolescents seeking help for depression: randomised controlled non-inferiority trial.

Objective: To evaluate whether a new computerised cognitive behavioural therapy intervention (SPARX, Smart, Positive, Active, Realistic, X-factor thoughts) could reduce depressive symptoms in help seeking adolescents as much or more than treatment as usual. Design: Multicentre randomised controlled non-inferiority trial. Setting: 24 primary healthcare sites in New Zealand (youth clinics, general practices, and school based counselling services). Participants: 187 adolescents aged 12-19, seeking help for depressive symptoms, with no major risk of self harm and deemed in need of treatment by their primary healthcare clinicians: 94 were allocated to SPARX and 93 to treatment as usual. Interventions: Computerised cognitive behavioural therapy (SPARX) comprising seven modules delivered over a period of between four and seven weeks, versus treatment as usual comprising primarily face to face counselling delivered by trained counsellors and clinical psychologists. Outcomes: The primary outcome was the change in score on the children's depression rating scale-revised. Secondary outcomes included response and remission on the children's depression rating scale-revised, change scores on the Reynolds adolescent depression scale-second edition, the mood and feelings questionnaire, the Kazdin hopelessness scale for children, the Spence children's anxiety scale, the paediatric quality of life enjoyment and satisfaction questionnaire, and overall satisfaction with treatment ratings. Results: 94 participants were allocated to SPARX (mean age 15.6 years, 62.8% female) and 93 to treatment as usual (mean age 15.6 years, 68.8% female). 170 adolescents (91%, SPARX n = 85, treatment as usual n = 85) were assessed after intervention and 168 (90%, SPARX n = 83, treatment as usual n = 85) were assessed at the three month follow-up point. Per protocol analyses (n = 143) showed that SPARX was not inferior to treatment as usual. Post-intervention, there was a mean reduction of 10.32 in SPARX and 7.59 in treatment as usual in raw scores on the children's depression rating scale-revised (between group difference 2.73, 95% confidence interval -0.31 to 5.77; P=0.079). Remission rates were significantly higher in the SPARX arm (n = 31, 43.7%) than in the treatment as usual arm (n = 19, 26.4%) (difference 17.3%, 95% confidence interval 1.6% to 31.8%; P = 0.030) and response rates did not differ significantly between the SPARX arm (66.2%, n = 47) and treatment as usual arm (58.3%, n = 42) (difference 7.9%, -7.9% to 24%; P = 0.332). All secondary measures supported non-inferiority. Intention to treat analyses confirmed these findings. Improvements were maintained at follow-up. The frequency of adverse events classified as "possibly" or "probably" related to the intervention did not differ between groups (SPARX n = 11; treatment as usual n = 11). Conclusions: SPARX is a potential alternative to usual care for adolescents presenting with depressive symptoms in primary care settings and could be used to address some of the unmet demand for treatment. Trial registration: Australian New Zealand Clinical Trials ACTRN12609000249257.

BMJ (Clinical research ed.) · randomised controlled trial · 316 citationsread the source →

Promoting mental health in small-medium enterprises: an evaluation of the "Business in Mind" program.

Background: Workplace mental health promotion (WMHP) aims to prevent and effectively manage the social and economic costs of common mental illnesses such as depression. The mental health of managers and employees within small-medium enterprises (SMEs) is a neglected sector in occupational health research and practice, despite the fact that this sector is the most common work setting in most economies. The availability and propensity of SME staff to attend face-to-face training/therapy or workshop style interventions often seen in corporate or public sector work settings is a widely recognised problem. The 'Business in Mind' program employs a DVD mode of delivery that is convenient for SME managers, particularly those operating in regional and remote areas where internet delivery may not be optimal. The objective of the intervention program is to improve the mental health of SME managers, and examine whether employees of managers' whose mental health improves, report positive change in their psychosocial work environment. The mechanisms via which we aim to improve managers' mental health are through the development of their psychological capital (a higher order construct comprised of hope, self efficacy, resilience and optimism) and their skills and capacities for coping with work stress. Methods/design: The effectiveness of two versions of the program (self administered and telephone facilitated) will be assessed using a randomised trial with an active control condition (psychoeducation only). We aim to recruit a minimum of 249 managers and a sample of their employees. This design allows for 83 managers per group, as power analyses showed that this number would allow for attrition of 20% and still enable detection of an effect size of 0.5. The intervention will be implemented over a three month period and postal surveys will assess managers and employees in each group at baseline, intervention completion, and at 6 month follow up. The intervention groups (managers only) will also be assessed at 12 and 24 month follow-up to examine maintenance of effects. Primary outcomes are managers' levels of psychological capital (hope, resilience, self-efficacy and optimism), coping strategies, anxiety and depression symptoms, self-reported health, job satisfaction and job tension. Secondary outcomes are participating managers subordinates' perceptions of manager support, relational justice, emotional climate and job tension. In order to provide an economic evaluation of the intervention, both employees and manager rates of absenteeism and presenteeism will also be assessed. Discussion: The intervention being trialled is expected to improve both primary and secondary outcomes. If proven efficacious, the intervention could be disseminated to reach a much larger proportion of the business community.

BMC public health · randomised controlled trial · 23 citationsread the source →

The safety and efficacy of ±3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study

Case reports indicate that psychiatrists administered ±3,4-methylenedioxymethamphetamine (MDMA) as a catalyst to psychotherapy before recreational use of MDMA as 'Ecstasy' resulted in its criminalization in 1985. Over two decades later, this study is the first completed clinical trial evaluating MDMA as a therapeutic adjunct. Twenty patients with chronic posttraumatic stress disorder, refractory to both psychotherapy and psychopharmacology, were randomly assigned to psychotherapy with concomitant active drug (n = 12) or inactive placebo (n = 8) administered during two 8-h experimental psychotherapy sessions. Both groups received preparatory and follow-up non-drug psychotherapy. The primary outcome measure was the Clinician-Administered PTSD Scale, administered at baseline, 4 days after each experimental session, and 2 months after the second session. Neurocognitive testing, blood pressure, and temperature monitoring were performed. After 2-month follow-up, placebo subjects were offered the option to re-enroll in the experimental procedure with open-label MDMA. Decrease in Clinician-Administered PTSD Scale scores from baseline was significantly greater for the group that received MDMA than for the placebo group at all three time points after baseline. The rate of clinical response was 10/12 (83%) in the active treatment group versus 2/8 (25%) in the placebo group. There were no drug-related serious adverse events, adverse neurocognitive effects or clinically significant blood pressure increases. MDMA-assisted psychotherapy can be administered to posttraumatic stress disorder patients without evidence of harm, and it may be useful in patients refractory to other treatments.

Journal of Psychopharmacology · randomised controlled trial · 674 citationsread the source →

The National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA): A Multisite Study of Adolescent Development and Substance Use.

Objective: During adolescence, neurobiological maturation occurs concurrently with social and interpersonal changes, including the initiation of alcohol and other substance use. The National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) is designed to disentangle the complex relationships between onset, escalation, and desistance of alcohol use and changes in neurocognitive functioning and neuromaturation. Method: A sample of 831 youth, ages 12-21 years, was recruited at five sites across the United States, oversampling those at risk for alcohol use problems. Most (83%) had limited or no history of alcohol or other drug use, and a smaller portion (17%) exceeded drinking thresholds. A comprehensive assessment of biological development, family background, psychiatric symptomatology, and neuropsychological functioning-in addition to anatomical, diffusion, and functional brain magnetic resonance imaging-was completed at baseline. Results: The NCANDA sample of youth is nationally representative of sex and racial/ethnic groups. More than 50% have at least one risk characteristic for subsequent heavy drinking (e.g., family history, internalizing or externalizing symptoms). As expected, those who exceeded drinking thresholds (n = 139) differ from those who did not (n = 692) on identified factors associated with early alcohol use and problems. Conclusions: NCANDA successfully recruited a large sample of adolescents and comprehensively assessed psychosocial functioning across multiple domains. Based on the sample's risk profile, NCANDA is well positioned to capture the transition into drinking and alcohol problems in a large portion of the cohort, as well as to help disentangle the associations between alcohol use, neurobiological maturation, and neurocognitive development and functioning.

Journal of studies on alcohol and drugs · cohort or longitudinal · 228 citationsread the source →

Long-term trends in child maltreatment in England and Wales, 1858-2016: an observational, time-series analysis.

Background: It is unclear whether child maltreatment is increasing or decreasing in England and Wales. More evidence is needed, from multiple sources and over longer periods of time, to explore trends in child maltreatment. We investigated whether the annual incidence of child maltreatment has changed over time, using official record data and time-series methods to establish long-term trends. Methods: In this observational time-series analysis, we used six data sources (Government records for child mortality, police-recorded child homicides, crimes against children, child protection, and children in care; and NSPCC data) to estimate the incidence of child maltreatment in England and Wales and examine long-term trends. We included nationally representative data that could estimate the incidence of child maltreatment for more than 25 years. Our primary outcomes were the number of victims (age <20 years) or perpetrators (age >16 years) of child maltreatment per 12-month period in England, including or excluding Wales. We fitted Poisson regression models with year as the exposure and the number of victims or perpetrators of child maltreatment as the outcome (adjusted for population age-structure and size). When a linear trend was not appropriate, we fitted generalised additive models with penalised splines to visualise trends. Findings: The incidence of child mortality by homicide or assault decreased by 90% (2·7 per 100 000 children) between 1858 and 2016 and the incidence of people guilty of child cruelty or neglect decreased by 83% (6·7 per 100 000 adults) between 1893 and 2016, whereas child protection registrations increased by 182% (328·7 per 100 000 children) between 1988 and 2016. Crimes against children and children entering care increased between 2000 and 2016. In 2016, 40 children died by homicide, with twice as many adolescent (15-19 years) deaths than infant (age <1 year) deaths. In 2016, 67 700 children were placed on the child protection register and neglect and emotional abuse were the most common reasons. Interpretation: Although long-term trends have decreased, child maltreatment remains a major public health problem in England and Wales. Further research is needed to establish whether adolescents are a particularly vulnerable age group and whether neglect and emotional abuse are increasing. Future child protection policies and practices should respond to these areas of growing need. Funding: Andrew W Mellon Foundation and Clarendon through The Oxford Research Centre in the Humanities, Oxford.

The Lancet. Public health · cohort or longitudinal · 22 citationsread the source →

Change in metacognitions predicts outcome in obsessive-compulsive disorder patients undergoing treatment with exposure and response prevention.

Wells' (Wells, A. (1997). Cognitive therapy of anxiety disorders: a practice manual and conceptual guide. Chichester, UK: Wiley) metacognitive model of obsessive-compulsive disorder (OCD) predicts that metacognitions must change in order for psychological treatment to be effective. The aim of this study was to explore: (1) if metacognitions change in patients undergoing exposure treatment for OCD; (2) to determine the extent to which cognitive and metacognitive change predicts symptom improvement and recovery. The sample consisted of 83 outpatients with a diagnosis of OCD who completed exposure and response prevention treatment. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Metacognitions Questionnaire (MCQ-30) and the Obsessive Beliefs Questionnaire (OBQ-44) were administered before treatment, after treatment, and at 12-month follow-up. Treatment resulted in significant changes in symptoms, metacognition score, responsibility and perfectionism. Regression analysis using post-treatment Y-BOCS as the dependent variable indicated that when the overlap between predictors was controlled for, only changes in metacognition were significant. Changes in metacognitions explained 22% of the variance in symptoms at post-treatment when controlling for pre-treatment symptoms and changes in mood. A further regression revealed that two MCQ-30 subscales made individual contributions. The patients had significantly higher scores compared to community controls on the MCQ-30. Patients who achieved clinical significant change had lower scores on the MCQ-30 compared to patients who did not change. The results did not change significantly from post-treatment to follow-up assessment. These findings provide further support for the importance of metacognitions in treating OCD.

Behaviour research and therapy · clinical trial · 68 citationsread the source →

The influence of substance dependence and mood disorders on outcome from pathological gambling: five-year follow-up.

A prospective study of the role of comorbid substance abuse and dependence and mood disorders in the outcome from pathological gambling. A naturalistic sample of pathological gamblers who had recently quit gambling (N = 101) was followed and data were available for 83% of participants at 3 months, 80% at 12 months, and 52% at 5 years. Those participants with a drug diagnosis during their lifetime were less likely to have a minimum 3 month period of abstinence, and those who had been involved in gambling treatment were more likely to have a minimum 12 months of continuous abstinence. Lifetime gambling problem severity and involvement in gambling treatment were most commonly associated with a shorter time to achieving a period of abstinence of any length. Lifetime history of a mood disorder also predicted a longer time to reach a minimum 3 months of continuous abstinence. Both gambling treatment and an alcohol diagnosis follow up predicted an increase in the odds of experiencing a relapse from a minimum 6 month period of abstinence. Overall, comorbid mental health disorders are predictive of shorter term but not longer term outcome.

Journal of gambling studies · 44 citationsread the source →

Heterogeneity of phenotypes in severe asthmatics. The Belgian Severe Asthma Registry (BSAR).

Unlabelled: The Belgian severe asthma registry is a web-based registry encompassing demographic, clinical, functional and inflammatory data of severe asthmatics (SA), aiming at improving awareness, knowledge on its natural history and subphenotypes, and offering tools to optimize care of this asthma population. Methods: The cross-sectional analyses of this registry included 350 SA as defined by the ATS (2000) from 9 Belgian centres, with at least one year follow up. Results: Mean age was 55 ± 14 yrs. SA were more frequently female (57%) and atopic (70%). Late-onset asthma (≥40 yr) was observed in 31% of SA. Current smokers represented 12% while 31% were ex-smokers. In addition to high doses ICS + LABA, 65% of patients were receiving LTRA, 27% anti-IgE and 24% maintenance oral corticosteroids (8 mg (Interquartile range-IQR:4-8) methylprednisolone). Despite impaired airflow (median FEV1:67%; IQR: 52-81) only 65% had a post-bronchodilator FEV1/FVC ratio <70%. The median blood eosinophil count was 240/mm³. The median FENO was 26 ppb (IQR: 15-43) and 22% of SA had FENO ≥ 50 ppb. Induced sputum was successful in 86 patients. Eosinophilic asthma (sputum Eos ≥ 3%) was the predominant phenotype (55%) while neutrophilic (sputum Neu ≥ 76%) and paucigranulocytic asthma accounted for 22% and 17% respectively. Comorbidities included rhinitis and chronic rhinosinusitis (49%), nasal polyposis (19%), oesophageal reflux (36%), overweight and obesity (47%) and depression (19%). In addition, 8% had aspirin-induced asthma and 3% ABPA. Asthma was not well-controlled in 83% according to ACT < 20 and 77% with ACQ > 1.5. Conclusion: In this cohort of patients with severe asthma, the majority displayed indices of persistent airflow limitation and eosinophilic inflammation despite high-dose corticosteroids, suggesting potential for eosinophil-targeted biotherapies.

Respiratory medicine · cohort or longitudinal · 199 citationsread the source →

Evaluation of Parental Dental Fear and Anxiety (DFA) on Adolescent Dental Treatment

INTRODUCTION Dental anxiety is a negative state of mind of a dental patient, which is shown to be excessive and unreasonable.[1] Dental fear is a normal emotional response to particularly alarming stimuli in situations related to dental treatment.[1] Dental fear and anxiety (DFA) are often used together to describe different types of fear experienced in the dental environment.[2] American Academy of Pediatrics divides adolescents into three age groups: early 11–14 years, middle 15–17 years, and late 18–21 years.[3] Five specific pathways for DFA were seen in adolescent dental patients. One of which being the parental pathway plays an important role in the transmission of fear hindering their child’s dental treatment.[4] Parental DFA is usually an excessive perturbing of the things that could go wrong in child’s oral health and is an important factor that has an impact on adolescents receiving dental treatment and maintenance of their oral health. It is necessary to recognize and know how parental DFA affects the dental treatment of adolescents. Thus, this review aimed at evaluating the parental influence of DFA on dental treatment of adolescents. MATERIALS AND METHODS DATA EXTRACTION AND LITERATURE SEARCH STRATEGY A broad search of literature published between 2005 and 2021 from electronic databases through Scopus, PubMed, Google Scholar, and Web of Science was performed. These studies were conducted in different countries as mentioned in Table 1. This review article includes eight cross-sectional studies, three longitudinal studies, and one descriptive study. The age group of children included ranged from 10 to 19 years. Table 1: Summary study design, data collection, dental fear and anxiety assessment scales used analysis, and interpretation of reviewed articlesThe search was carried out using the following keywords: dental anxiety, parental dental anxiety, adolescent, and dental treatment. The terms used to formulate the search strategies were parent OR mother OR father AND dental fear OR dental anxiety AND adolescent AND dental treatment. Data extracted were independently reviewed and disagreements were solved by discussion. A flowchart representing the method of article selection for the review is shown in Figure 1.Figure 1: Flowchart representing the method of article selectionINCLUSION CRITERIA We included the studies in which parental dental anxiety was a major criterion affecting different dental health conditions. Articles referring to adolescents (10–19 years) facing different oral health problems were also included in the study. EXCLUSION CRITERIA Abstracts that were not giving relevant data, data from unpublished articles, parental dental anxiety in medically compromised and specially challenged adolescents, and articles that did not include the adolescent age group were excluded from the study. RESULTS Approximately 83 publications were found related. Screening identified 10 articles that fulfilled the criteria of inclusion; full-text versions were retrieved and their references were screened for further relevant articles. Checking the subreference list, another two relevant articles were found. Thus, 12 articles were considered for this review that met the final inclusion criteria. Of 12 articles reviewed, 8 studies[56789101112] used validated assessment scales as mentioned by authors for measuring parental DFA. The authors have not specified the validation of assessment scales used for the other four studies.[13141516] The various DFA assessment scales used in the reviewed articles are mentioned in Table 2. Summary study design, data collection, analysis, and interpretation of reviewed articles are mentioned in Table 1.Table 2: Tabular representation of dental fear and anxiety assessment scales usedDISCUSSION Dental anxiety being primarily a negative parental factor was found to affect children from assessing regular dental care. Among the reviewed articles based on the outcome, we found that three articles explained about a relationship between parental DFA and adolescent dental treatment,[67,13] and the remaining nine articles explained about the correlation between parental DFA scores with adolescent DFA scores.[6891011,13141516] No significant association was observed between parental DFA and adolescent DFA scores in two of the studies,[78] whereas two studies showed positive association only during early adolescence.[914] Other five studies showed a significant positive correlation of parental DFA with their children’s dental anxiety,[10111215,16] of which three studies also suggested fathers as mediating role in transmission of DFA to their children.[1011,15] RELATIONSHIP BETWEEN PARENTAL DENTAL FEAR AND ANXIETY AND ADOLESCENT DENTAL TREATMENT Adolescent dental treatment utilization mainly depends on parental/caretaker’s decision-making and their dental care obtaining habits. In childhood and even adolescence, this becomes very crucial for the development of good oral health behavior like regular visits to the dentist and preventive dental care.[17] Another postulated process is “social learning” wherein, media, friends, and relatives portray dentists in negative light or image leading to formation of DFA. These processes of information transmission and vicarious experience lead to negative portrayal of dentists and pessimistic expectations about the dentist’s role. All these predispose to DFA.[18] The absence of anxiety among parents would have a positive influence on a child.[19] Parental dental anxiety along with family income, economic stability, parental oral health literacy, and oral health practices is found to be a few factors that affect adolescent’s oral health-related quality of life (QOL).[202122] Dental anxiety being primarily a negative parental factor was found to affect children from accessing regular dental care, whereas parental self-dental utilization being a positive parental factor showed a positive impact on a child’s dental utilization.[23] Parents with higher anxiety levels were found to start brushing their children’s teeth at an earlier age; hence, a significant correlation was found between parent’s anxiety levels and the age at which the child starts to brush.[24] Dental health status of children was found to be better with more a positive attitude of parents toward dentistry.[25] Among the articles reviewed, two articles were found to have parental DFA during fixed orthodontic treatment of the adolescents which included the use of extraoral appliances. These two studies used different anxiety measurement scales for assessing parental DFA before and during the treatment procedures.[513] Poorer QOL is seen in families of adolescents with malocclusion as compared with the families of adolescents without any occlusal variation; the impact may have effects on parental or guardian’s emotions.[26] Both of the studies assessed state and trait dental anxiety of parents (STAI scale). State anxiety is transient, fluctuates, and varies in intensity. Trait anxiety is a personality trait; it is stable with time.[2728] The result showed that parent’s trait anxiety levels did not change during orthodontic treatment.[513] State anxiety was found to be within normal range and changed according to intensity of pressure.[13] There was an incidence of high levels of state anxiety and depression in both parents and patients under treatment with extra oral orthodontic appliances after 1 year of active treatment. Among patients waiting for orthodontic treatment and among their parents no statistically significant differences were noted in their trait anxiety levels.[5] The extra oral appliances had a negative effect on patient’s and parent’s anxiety levels which might indirectly affect the ongoing dental treatment. It was therefore recommended for clinicians to have alternate treatment modalities in mind to address this challenge.[5] Apart from orthodontic treatment, adolescents are also found commonly with traumatic dental injuries (TDIs) involving dentine/pulp or fracture of the root. A family’s QOL in such conditions was assessed using the family impact scale (FIS). This scale had four subscales, in which parental emotion was one of the subscales assessed. Parental emotion had a significant negative impact on the severity of TDI and severe untreated TDI of an adolescent can be a source of family distress.[629,30] EVIDENCE OF ASSOCIATION OF DENTAL FEAR AND ANXIETY BETWEEN PARENTS AND THEIR ADOLESCENTS Previous studies have shown that parents exhibit an influence on their children’s DFA through modeling and information.[31] The DFA experienced in childhood may lead into adulthood causing a predictor for dental treatment avoidance in adulthood.[3233] Among the reviewed articles, we found a correlation between the parental dental DFA scores with their adolescent’s DFA scores. Parent’s DFA and children’s DFA were assessed using the same dental anxiety measuring scale in nine of the studies,[6891011,13141516] and three studies[57,12] used different scales to measure anxiety levels in parents and children’s. Two of the studies showed no significant association between the anxiety level of adolescents and that of their parents.[78] One of the studies suggested that when a child reached adolescence, parental DFA does not directly contribute to child DFA. Other factors such as the presence of a sibling and family structure (single-parent family, nuclear) are found to play a significant role.[7] Lending support to the former findings, there was no relation between anxiety levels of adolescents (12–17 years) and that of their parents, whereas in the same study a positive association was found when the child is 8–11 years of age.[8] Two studies suggested a positive association in early adolescence.[914] In one of these two studies, mother’s and adolescents dental fear scores had a significant association at the age of 12 years and 18 years in given treatment scenarios such as “feeling about having their teeth scraped and polished, having teeth drilled and having an injection in gum,” whereas there was no significant association between dental fear scores of mother’s and adolescence at 15 years of age.[9] In another study reviewed, in early adolescence (11–12 years), there was a statistically significant association between parental and adolescent dental fear but in mid-adolescence (15–16 years) there was only an association with parental dental fear with their daughters.[14] It was found in the Finnish population, by eliminating dental fear among 30 years and elderly population, 41% of irregular attendees could become regular attenders.[34] In contrast, other five studies showed a significant positive correlation of parental DFA with their children’s dental anxiety.[10111215,16] Fearful parents of adolescents of age (11–16 years) assumed that their child had fear irrespective of whether the child had fear or not.[16] Three of these studies, where parental DFA was assessed in both the parents, suggested that the father also has a mediating role in the transmission of DFA to the children of age group 11–17 years,[10] 7–15 years,[11] and 7–12 years,[15] respectively. Father’s DFA is one of the best predictors of adolescence DFA[1035] and it is also found that child’s dental anxiety is best predicted by the parent’s fear of pain.[12] Previous studies have suggested that children experience fear and anxiety in their early life due to a lack of cognitive ability without having a clear perception of fearful situation and have been influenced by their parent’s fear and anxiety.[36] It is still unclear of the association of DFA between parents and late adolescents.[9] It was found that limited studies were found in the area of adolescent oral health. In the available literature, definite assessment methods were not used to assess the anxiety levels among parents. Furthermore, studies focused on late adolescence are indicated to establish the changes in oral health due to parental DFA. Adolescence is the transitional phase between childhood and adulthood and is a crucial period where they develop decision-making and independence; this has an impact on dental treatment-seeking behavior. The influence of parental dental anxiety might worsen the scenario. Parental DFA is seen to have a direct impact on the treatment itself.[56,20] Previously reviewed articles show a strong association of parental DFA and child’s DFA below 8 years of age.[37] In this study, we found parental DFA showed a positive association with their adolescent’s DFA, which thus hinders their dental treatment. There is a need to give attention to psychological parameters before and during the treatment of both parents and adolescents. Therefore, identifying parental dental anxiety prior to the treatment and intervention helps to reduce or eliminate DFA in children and further improves their dental treatment utilization. This study adds value in sensitizing dental professionals toward addressing parental concerns while treating adolescents and recommendations for appropriate implementations in teaching curricula and policies regarding the same. There is more potential to understand the background of parental DFA in single parents and in mother and father alone and also the factors that made them vulnerable. Parental education/counselling regarding various dental treatment procedures using appropriate methods such as focus group discussion will help to reduce DFA among the parental populations. ACKNOWLEDGEMENT We thank Health Sciences Library, Manipal Manipal Academy of Higher Education, Manipal, Udupi, Karnataka, India and Department of Psychiatry, Kasturba Medical College and Hospital, Manipal, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka, India. FINANCIAL SUPPORT AND SPONSORSHIP This study was self-funded. CONFLICTS OF INTEREST There are no conflicts of interest. AUTHORS CONTRIBUTIONS Idea and conceptualization: Ramprasad Vasthare. Literature search: Thrisha Hegde, Bhavyashri P. Manuscript writing: Thrisha Hegde, Bhavyashri P, Ramprasad Vasthare, Karthik M, Ravindra Munoli. Editing of the review: Ramprasad Vasthare, Thrisha Hegde, Bhavyashri P, Karthik M, Ravindra Munoli. Intellectual inputs: Ramprasad Vasthare, Ravindra Munoli, Karthik M. ETHICAL POLICY AND INSTITUTIONAL REVIEW BOARD STATEMENT Not applicable as this was a narrative review. PATIENT DECLARATION OF CONSENT Not applicable. DATA AVAILABILITY STATEMENT Data of literature search is available on appropriate request to the corresponding author.

Journal of International Society of Preventive and Community Dentistry · review · 16 citationsread the source →

Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy: Advances in Diagnosis and Treatment.

Importance: Cerebral palsy describes the most common physical disability in childhood and occurs in 1 in 500 live births. Historically, the diagnosis has been made between age 12 and 24 months but now can be made before 6 months' corrected age. Objectives: To systematically review best available evidence for early, accurate diagnosis of cerebral palsy and to summarize best available evidence about cerebral palsy-specific early intervention that should follow early diagnosis to optimize neuroplasticity and function. Evidence review: This study systematically searched the literature about early diagnosis of cerebral palsy in MEDLINE (1956-2016), EMBASE (1980-2016), CINAHL (1983-2016), and the Cochrane Library (1988-2016) and by hand searching. Search terms included cerebral palsy, diagnosis, detection, prediction, identification, predictive validity, accuracy, sensitivity, and specificity. The study included systematic reviews with or without meta-analyses, criteria of diagnostic accuracy, and evidence-based clinical guidelines. Findings are reported according to the PRISMA statement, and recommendations are reported according to the Appraisal of Guidelines, Research and Evaluation (AGREE) II instrument. Findings: Six systematic reviews and 2 evidence-based clinical guidelines met inclusion criteria. All included articles had high methodological Quality Assessment of Diagnostic Accuracy Studies (QUADAS) ratings. In infants, clinical signs and symptoms of cerebral palsy emerge and evolve before age 2 years; therefore, a combination of standardized tools should be used to predict risk in conjunction with clinical history. Before 5 months' corrected age, the most predictive tools for detecting risk are term-age magnetic resonance imaging (86%-89% sensitivity), the Prechtl Qualitative Assessment of General Movements (98% sensitivity), and the Hammersmith Infant Neurological Examination (90% sensitivity). After 5 months' corrected age, the most predictive tools for detecting risk are magnetic resonance imaging (86%-89% sensitivity) (where safe and feasible), the Hammersmith Infant Neurological Examination (90% sensitivity), and the Developmental Assessment of Young Children (83% C index). Topography and severity of cerebral palsy are more difficult to ascertain in infancy, and magnetic resonance imaging and the Hammersmith Infant Neurological Examination may be helpful in assisting clinical decisions. In high-income countries, 2 in 3 individuals with cerebral palsy will walk, 3 in 4 will talk, and 1 in 2 will have normal intelligence. Conclusions and relevance: Early diagnosis begins with a medical history and involves using neuroimaging, standardized neurological, and standardized motor assessments that indicate congruent abnormal findings indicative of cerebral palsy. Clinicians should understand the importance of prompt referral to diagnostic-specific early intervention to optimize infant motor and cognitive plasticity, prevent secondary complications, and enhance caregiver well-being.

JAMA pediatrics · review · 1059 citationsread the source →

Prevalence of depressive disorders and treatment in China: a cross-sectional epidemiological study.

Background: In China, depressive disorders have been estimated to be the second leading cause of years lived with disability. However, nationally representative epidemiological data for depressive disorders, in particular use of mental health services by adults with these disorders, are unavailable in China. The present study, part of the China Mental Health Survey, 2012-15, aims to describe the socioeconomic characteristics and the use of mental health services in people with depressive disorders in China. Methods: The China Mental Health Survey was a cross-sectional epidemiological survey of mental disorders in a multistage clustered-area probability sample of adults of Chinese nationality (≥18 years) from 157 nationwide representative population-based disease surveillance points in 31 provinces across China. Trained investigators interviewed the participants with the Composite International Diagnostic Interview 3.0 to ascertain the presence of lifetime and 12-month depressive disorders according to DSM-IV criteria, including major depressive disorder, dysthymic disorder, and depressive disorder not otherwise specified. Participants with 12-month depressive disorders were asked whether they received any treatment for their emotional problems during the past 12 months and, if so, the specific types of treatment providers. The Sheehan Disability Scale (SDS) was used to assess impairments associated with 12-month depressive symptoms. Data-quality control procedures included logic check by computers, sequential recording check, and phone-call check by the quality controllers, and reinterview check by the psychiatrists. Data were weighted according to the age-sex-residence distribution data from China's 2010 census population survey to adjust for differential probabilities of selection and differential response, as well as to post-stratify the sample to match the population distribution. Findings: 28 140 respondents (12 537 [44·6%] men and 15 603 [55·4%] women) completed the survey between July 22, 2013, and March 5, 2015. Ethnicity data (Han or non-Han) were collected for only a subsample. Prevalence of any depressive disorders was higher in women than men (lifetime prevalence odds ratio [OR] 1·44 [95% CI 1·20-1·72] and 12-month prevalence OR 1·41 [1·12-1·78]), in unemployed people than employed people (lifetime OR 2·38 [95% CI 1·68-3·38] and 12-month OR 2·80 [95% CI 1·88-4·18]), and in people who were separated, widowed, or divorced compared with those who were married or cohabiting (lifetime OR 1·87 [95% CI 1·39-2·51] and 12-month OR 1·85 [95% CI 1·40-2·46]). Overall, 574 (weighted % 75·9%) of 744 people with 12-month depressive disorders had role impairment of any SDS domain: 439 (83·6%) of 534 respondents with major depressive disorder, 207 (79·8%) of 254 respondents with dysthymic disorder, and 122 (59·9%) of 189 respondents with depressive disorder not otherwise specified. Only an estimated 84 (weighted % 9·5%) of 1007 participants with 12-month depressive disorders were treated in any treatment sector: 38 (3·6%) in speciality mental health, 20 (1·5%) in general medical, two (0·3%) in human services, and 21 (2·7%) in complementary and alternative medicine. Only 12 (0·5%) of 1007 participants with depressive disorders were treated adequately. Interpretation: Depressive disorders in China were more prevalent in women than men, unemployed people than employed, and those who were separated, widowed, or divorced than people who were married or cohabiting. Most people with depressive disorders reported social impairment. Treatment rates were very low, and few people received adequate treatment. National programmes are needed to remove barriers to availability, accessibility, and acceptability of care for depression in China. Funding: National Health Commission and Ministry of Science and Technology of People's Republic of China. Translation: For the Chinese translation of the abstract see Supplementary Materials section.

The lancet. Psychiatry · 591 citationsread the source →