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Behavioural, educational and respiratory outcomes of antenatal betamethasone for term caesarean section (ASTECS trial).

Objectives: To determine whether antenatal betamethasone prior to elective term caesarean section (CS) affects long term behavioural, cognitive or developmental outcome, and whether the risk of asthma or atopic disease is reduced. Design: A questionnaire based follow-up of a multicentre randomised controlled trial (Antenatal Steroids for Term Elective Caesarean Section, BMJ 2005). Setting: Four UK study centres from the original trial. Participants: 862 participants from the four largest recruiting centres, 92% of the original study. 824 (96%) were traced and 799 (93%) were successfully contacted. Fifty-one percent (407/799) completed and returned the questionnaire. The children were aged 8-15 years (median 12.2 years, 52% girls). 386 gave consent to contact schools with 352 (91%) reports received. Main outcome measures: Questionnaires including a strengths and difficulties questionnaire, International Study of Asthma and Allergies in Childhood, general health and school performance. Results: There were no significant differences between children whose mothers received betamethasone and controls for the mean total strengths and difficulties questionnaire scores and subscores for hyperactivity, emotional symptoms, prosocial behaviour, conduct or peer problems. 25 (12%) children whose mothers received betamethasone had reported learning difficulties compared with 27 (14%) control children. The proportion of children who achieved standard assessment tests KS2 exams level 4 or above for mathematics, English or science was similar as were the rates of ever reported wheeze (30% vs 30%), asthma (24% vs 21%), eczema (34% vs 37%) and hay fever (25% vs 27%). Conclusions: Antenatal betamethasone did not result in any adverse outcomes or reduction in asthma or atopy. It should be considered for elective CS at 37-38 weeks of gestation. Trial registration: : Original trial was preregistration, the trial publication is BMJ. 2005 Sep 24;331(7518):662.

Archives of disease in childhood. Fetal and neonatal edition · randomised controlled trial · 105 citationsread the source →

Workers' health and productivity under occupational heat strain: a systematic review and meta-analysis.

Background: Occupational heat strain (ie, the effect of environmental heat stress on the body) directly threatens workers' ability to live healthy and productive lives. We estimated the effects of occupational heat strain on workers' health and productivity outcomes. Methods: Following PRISMA guidelines for this systematic review and meta-analysis, we searched PubMed and Embase from database inception to Feb 5, 2018, for relevant studies in any labour environment and at any level of occupational heat strain. No restrictions on language, workers' health status, or study design were applied. Occupational heat strain was defined using international health and safety guidelines and standards. We excluded studies that calculated effects using simulations or statistical models instead of actual measurements, and any grey literature. Risk of bias, data extraction, and sensitivity analysis were performed by two independent investigators. Six random-effects meta-analyses estimated the prevalence of occupational heat strain, kidney disease or acute kidney injury, productivity loss, core temperature, change in urine specific gravity, and odds of occupational heat strain occurring during or at the end of a work shift in heat stress conditions. The review protocol is available on PROSPERO, registration number CRD42017083271. Findings: Of 958 reports identified through our systematic search, 111 studies done in 30 countries, including 447 million workers from more than 40 different occupations, were eligible for analysis. Our meta-analyses showed that individuals working a single work shift under heat stress (defined as wet-bulb globe temperature beyond 22·0 or 24·8°C depending on work intensity) were 4·01 times (95% CI 2·45-6·58; nine studies with 11 582 workers) more likely to experience occupational heat strain than an individual working in thermoneutral conditions, while their core temperature was increased by 0·7°C (0·4-1·0; 17 studies with 1090 workers) and their urine specific gravity was increased by 14·5% (0·0031, 0·0014-0·0048; 14 studies with 691 workers). During or at the end of a work shift under heat stress, 35% (31-39; 33 studies with 13 088 workers) of workers experienced occupational heat strain, while 30% (21-39; 11 studies with 8076 workers) reported productivity losses. Finally, 15% (11-19; ten studies with 21 721 workers) of individuals who typically or frequently worked under heat stress (minimum of 6 h per day, 5 days per week, for 2 months of the year) experienced kidney disease or acute kidney injury. Overall, this analysis include a variety of populations, exposures, and occupations to comply with a wider adoption of evidence synthesis, but resulted in large heterogeneity in our meta-analyses. Grading of Recommendations, Assessment, Development and Evaluation analysis revealed moderate confidence for most results and very low confidence in two cases (average core temperature and change in urine specific gravity) due to studies being funded by industry. Interpretation: Occupational heat strain has important health and productivity outcomes and should be recognised as a public health problem. Concerted international action is needed to mitigate its effects in light of climate change and the anticipated rise in heat stress. Funding: EU Horizon 2020 research and innovation programme.

The Lancet. Planetary health · meta-analysis · 253 citationsread the source →

Effects of subcutaneous tirzepatide versus placebo or semaglutide on pancreatic islet function and insulin sensitivity in adults with type 2 diabetes: a multicentre, randomised, double-blind, parallel-arm, phase 1 clinical trial.

Background: Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, shows a remarkable ability to lower blood glucose, enabling many patients with long-standing type 2 diabetes to achieve normoglycaemia. We aimed to understand the physiological mechanisms underlying the action of tirzepatide in type 2 diabetes. Methods: This multicentre, randomised, double-blind, parallel-arm, phase 1 study was done at two centres in Germany. Eligible patients were aged 20-74 years, had type 2 diabetes for at least 6 months, and were being treated with lifestyle advice and stable doses of metformin, with or without one additional stable dose of another oral antihyperglycaemic medicine, 3 months before study entry. Via a randomisation table, patients were randomly assigned (3:3:2) to subcutaneously receive either tirzepatide 15 mg, semaglutide 1 mg, or placebo once per week. Endpoint measurements were done at baseline and the last week of therapy (week 28). The primary endpoint was the effect of tirzepatide versus placebo on the change in clamp disposition index (combining measures of insulin secretion and sensitivity) from baseline to week 28 of treatment and was analysed in the pharmacodynamic analysis set, which comprised all randomly assigned participants who received at least one dose of a study drug and had evaluable pharmacodynamic data. Safety was analysed in the safety population, which comprised all randomly assigned participants who received at least one dose of a study drug. Secondary endpoints included the effect of tirzepatide versus semaglutide on the change in clamp disposition index from baseline to week 28 of treatment, glucose control, total insulin secretion rate, M value (insulin sensitivity), and fasting and postprandial glucagon concentrations. Exploratory endpoints included the change in fasting and postprandial insulin concentrations. This study is registered with ClinicalTrials.gov, NCT03951753, and is complete. Findings: Between June 28, 2019, and April 8, 2021, we screened 184 individuals and enrolled 117 participants, all of whom were included in the safety population (45 in the tirzepatide 15 mg group, 44 in the semaglutide 1 mg group, and 28 in the placebo group). Because of discontinuations and exclusions due to missing or unevaluable data, 39 patients in each treatment group and 24 patients in the placebo group comprised the pharmacodynamic analysis set. With tirzepatide, the clamp disposition index increased from a least squares mean of 0·3 pmol m-2 L min-2 kg-1 (SE 0·03) at baseline by 1·9 pmol m-2 L min-2 kg-1 (0·16) to total 2·3 pmol m-2 L min-2 kg-1 (SE 0·16) at week 28 and, with placebo, the clamp disposition index did not change much from baseline (least squares mean at baseline 0·4 pmol m-2 L min-2 kg-1 [SE 0·04]; change from baseline 0·0 pmol m-2 L min-2 kg-1 [0·03]; least squares mean at week 28 0·3 [SE 0·03]; estimated treatment difference [ETD] tirzepatide vs placebo 1·92 [95% CI 1·59-2·24]; p<0·0001). The improvement with tirzepatide in clamp disposition index was significantly greater than with semaglutide (ETD 0·84 pmol m-2 L min-2 kg-1 [95% CI 0·46-1·21]). This result reflected significant improvements in total insulin secretion rate (ETD 102·09 pmol min-1 m-2 [51·84-152·33]) and insulin sensitivity (ETD 1·52 mg min-1 kg-1 [0·53-2·52]) for tirzepatide versus semaglutide. On meal tolerance testing, tirzepatide significantly reduced glucose excursions (lower insulin and glucagon concentrations) compared with placebo, with effects on these variables being greater than with semaglutide. The safety profiles of tirzepatide and semaglutide were similar, with gastrointestinal adverse events being the most common (11 [24%], 13 [30%], and seven [25%] with nausea; nine [20%], 13 [30%], and six [21%] with diarrhoea; and three [7%], five [11%], and one [4%] with vomiting, for tirzepatide, semaglutide, and placebo, respectively). There were no deaths. Interpretation: The glycaemic efficacy of GIP/GLP-1 receptor agonist tirzepatide in type 2 diabetes results from concurrent improvements in key components of diabetes pathophysiology, namely β-cell function, insulin sensitivity, and glucagon secretion. These effects were large and help to explain the remarkable glucose-lowering ability of tirzepatide seen in phase 3 studies. Funding: Eli Lilly.

The lancet. Diabetes & endocrinology · randomised controlled trial · 202 citationsread the source →

Are interventions focused on gender-norms effective in preventing domestic violence against women in low and lower-middle income countries? A systematic review and meta-analysis.

Background: One in three women experience intimate partner violence worldwide, according to many primary studies. However, systematic review and meta-analysis of intimate partner violence is very limited. Therefore, we set to summarize the findings of existing primary studies to generate evidence for informed decisions to tackle domestic violence against women in low and lower-middle income countries. Methods: Studies were searched from main databases (Medline via PubMed, EMBASE, CINAHL, PopLine and Web of Science), Google scholar and other relevant sources using electronic and manual techniques. Published and unpublished studies written in English and conducted among women aged (15-49 years) from 1994 to 2017 were eligible. Data were extracted independently by two authors, and recorded in Microsoft Excel sheet. Heterogeneity between included studies was assessed using I2, and publication bias was explored using visual inspection of funnel plot. Statistical analysis was carried out to determine the pooled prevalence using Comprehensive Meta-Analysis software. In addition, sub-group analysis was carried out by study-setting and types of intimate partner violence. Results: Fifty two studies were included in the systematic review. Of these, 33 studies were included in the meta-analysis. The pooled prevalence of lifetime intimate partner violence was 55% (95% CI: 52, 59%). Of these, main categories were lifetime physical violence [39% (95% CI: 33, 45%); psychological violence [45% (95% CI: 40, 52%)] and sexual violence [20% (95% CI: 17, 23%)]. Furthermore, the pooled prevalence of current intimate partner violence was 38% (95% CI: 34, 43%). Of these, physical violence [25% (95% CI: 21, 28%)]; psychological violence [30% (95% CI: 24, 36%)] and sexual violence [7.0% (95% CI: 6.6, 7.5%)] were the pooled prevalence for the major types of intimate partner violence. In addition, concurrent intimate partner violence was 13% (95% CI: 12, 15%). Individual, relationship, community and societal level factors were associated with intimate partner violence. Traditional community gender-norm transformation, stakeholders' engagement, women's empowerment, intervention integration and policy/legal framework were highly recommended interventions to prevent intimate partner violence. Conclusion: Lifetime and current intimate partner violence is common and unacceptably high. Therefore, concerned bodies will need to design and implement strategies to transform traditional gender norms, engage stakeholders, empower women and integrate service to prevent violence against women. Protocol registration: PROSPERO: 2017: CRD42017079977 .

Reproductive health · meta-analysis · 43 citationsread the source →

Centrally Assisted Collaborative Telecare for Posttraumatic Stress Disorder and Depression Among Military Personnel Attending Primary Care: A Randomized Clinical Trial.

Importance: It is often difficult for members of the US military to access high-quality care for posttraumatic stress disorder (PTSD) and depression. Objective: To determine effectiveness of a centrally assisted collaborative telecare (CACT) intervention for PTSD and depression in military primary care. Design, setting, and participants: The STEPS-UP study (Stepped Enhancement of PTSD Services Using Primary Care) is a randomized trial comparing CACT with usual integrated mental health care for PTSD or depression. Patients, mostly men in their 20s, were enrolled from 18 primary care clinics at 6 military installations from February 2012 to August 2013 with 12-month follow-up completed in October 2014. Interventions: Randomization was to CACT (n = 332) or usual care (n = 334). The CACT patients received 12 months of stepped psychosocial and pharmacologic treatment with nurse telecare management of caseloads, symptoms, and treatment. Main outcomes and measures: Primary outcomes were severity scores on the PTSD Diagnostic Scale (PDS; scored 0-51) and Symptom Checklist depression items (SCL-20; scored 0-4). Secondary outcomes were somatic symptoms, pain severity, health-related function, and mental health service use. Results: Of 666 patients, 81% were male and the mean (SD) age was 31.1 (7.7) years. The CACT and usual care patients had similar baseline mean (SD) PDS PTSD (29.4 [9.4] vs 28.9 [8.9]) and SCL-20 depression (2.1 [0.6] vs 2.0 [0.7]) scores. Compared with usual care, CACT patients reported significantly greater mean (SE) 12-month decrease in PDS PTSD scores (-6.07 [0.68] vs -3.54 [0.72]) and SCL-20 depression scores -0.56 [0.05] vs -0.31 [0.05]). In the CACT group, significantly more participants had 50% improvement at 12 months compared with usual care for both PTSD (73 [25%] vs 49 [17%]; relative risk, 1.6 [95% CI, 1.1-2.4]) and depression (86 [30%] vs 59 [21%]; relative risk, 1.7 [95% CI, 1.1-2.4]), with a number needed to treat for a 50% improvement of 12.5 (95% CI, 6.9-71.9) and 11.1 (95% CI, 6.2-50.5), respectively. The CACT patients had significant improvements in somatic symptoms (difference between mean 12-month Patient Health Questionnaire 15 changes, -1.37 [95% CI, -2.26 to -0.47]) and mental health-related functioning (difference between mean 12-month Short Form-12 Mental Component Summary changes, 3.17 [95% CI, 0.91 to 5.42]), as well as increases in telephone health contacts and appropriate medication use. Conclusions and relevance: Central assistance for collaborative telecare with stepped psychosocial management modestly improved outcomes of PTSD and depression among military personnel attending primary care. Trial registration: clinicaltrials.gov Identifier: NCT01492348.

JAMA internal medicine · randomised controlled trial · 53 citationsread the source →

Short-term fasting in glioma patients: analysis of diet diaries and metabolic parameters of the ERGO2 trial.

Purpose: The prospective, randomized ERGO2 trial investigated the effect of calorie-restricted ketogenic diet and intermittent fasting (KD-IF) on re-irradiation for recurrent brain tumors. The study did not meet its primary endpoint of improved progression-free survival in comparison to standard diet (SD). We here report the results of the quality of life/neurocognition and a detailed analysis of the diet diaries. Methods: 50 patients were randomized 1:1 to re-irradiation combined with either SD or KD-IF. The KD-IF schedule included 3 days of ketogenic diet (KD: 21-23 kcal/kg/d, carbohydrate intake limited to 50 g/d), followed by 3 days of fasting and again 3 days of KD. Follow-up included examination of cognition, quality of life and serum samples. Results: The 20 patients who completed KD-IF met the prespecified goals for calorie and carbohydrate restriction. Substantial decreases in leptin and insulin and an increase in uric acid were observed. The SD group, of note, had a lower calorie intake than expected (21 kcal/kg/d instead of 30 kcal/kg/d). Neither quality of life nor cognition were affected by the diet. Low glucose emerged as a significant prognostic parameter in a best responder analysis. Conclusion: The strict caloric goals of the ERGO2 trial were tolerated well by patients with recurrent brain cancer. The short diet schedule led to significant metabolic changes with low glucose emerging as a candidate marker of better prognosis. The unexpected lower calorie intake of the control group complicates the interpretation of the results. Clinicaltrials.gov number: NCT01754350; Registration: 21.12.2012.

European journal of nutrition · randomised controlled trial · 38 citationsread the source →

Effect of intermittent versus continuous energy restriction on weight loss, maintenance and cardiometabolic risk: A randomized 1-year trial.

Background & aims: Long-term adherence to conventional weight-loss diets is limited while intermittent fasting has risen in popularity. We compared the effects of intermittent versus continuous energy restriction on weight loss, maintenance and cardiometabolic risk factors in adults with abdominal obesity and ≥1 additional component of metabolic syndrome. Methods & results: In total 112 participants (men [50%] and women [50%]) aged 21-70 years with BMI 30-45 kg/m2 (mean 35.2 [SD 3.7]) were randomized to intermittent or continuous energy restriction. A 6-month weight-loss phase including 10 visits with dieticians was followed by a 6-month maintenance phase without additional face-to-face counselling. The intermittent energy restriction group was advised to consume 400/600 kcal (female/male) on two non-consecutive days. Based on dietary records both groups reduced energy intake by ∼26-28%. Weight loss was similar among participants in the intermittent and continuous energy restriction groups (8.0 kg [SD 6.5] versus 9.0 kg [SD 7.1]; p = 0.6). There were favorable improvements in waist circumference, blood pressure, triglycerides and HDL-cholesterol with no difference between groups. Weight regain was minimal and similar between the intermittent and continuous energy restriction groups (1.1 kg [SD 3.8] versus 0.4 kg [SD 4.0]; p = 0.6). Intermittent restriction participants reported higher hunger scores than continuous restriction participants on a subjective numeric rating scale (4.7 [SD 2.2] vs 3.6 [SD 2.2]; p = 0.002). Conclusions: Both intermittent and continuous energy restriction resulted in similar weight loss, maintenance and improvements in cardiovascular risk factors after one year. However, feelings of hunger may be more pronounced during intermittent energy restriction. Trial registration: www.clinicaltrials.govNCT02480504.

Nutrition, metabolism, and cardiovascular diseases : NMCD · randomised controlled trial · 156 citationsread the source →

A randomized study of cellphone technology to reinforce alcohol abstinence in the natural environment.

Aims: Contingency management (CM) uses tangible incentives to systematically reinforce abstinence and is among the most efficacious psychosocial substance abuse treatments. This study assessed the feasibility and initial efficacy of a portable CM procedure designed to address technical limitations for detecting drinking that have prevented using CM for alcohol problems. Design: Participants received a cellphone, breathalyzer and training on video-recording alcohol breath tests (BrACs) and texting results. For 4 weeks, staff texted participants one to three times daily indicating that a breath alcohol concentration test (BrAC) was due within the hour. Participants were randomized to (1) modest compensation for submitting dated time-stamped BrAC videos regardless of results or (2) the same plus CM with escalating vouchers for on-time alcohol-negative tests (n-BrAC; <02 g/dl). 'Thank-you' texts were sent, with CM patients also informed of results-based earnings. Setting: Participants' natural environment. Participants: Adults (n = 30; ≥ 21 years) who drank frequently but were not physiologically dependent. Measurements: Drinking and related problems were assessed at intake and week 4. BrACs and self-reports of drinking were collected throughout. The primary outcome was the percentage of n-BrACs. Other outcomes were the longest duration of consecutive n-BrACs (longest duration of abstinence) and self-reports of drinking. Findings: On average, 88.6% (10.4%) of BrACs were submitted on time, without group differences (P = 0.18). The percentage of n-BrACs and LDA were greater with CM, and there was an interaction effect on drinking frequency and negative consequences, with decreases over time with CM (P = 0.00; effect sizes d = 0.52-0.62). Conclusion: Cellphone technology may be useful for extending contingency management to treatment for alcohol problems.

Addiction (Abingdon, England) · randomised controlled trial · 88 citationsread the source →

Effect of Sleep Extension on Objectively Assessed Energy Intake Among Adults With Overweight in Real-life Settings: A Randomized Clinical Trial.

Importance: Short sleep duration has been recognized as a risk factor for obesity. Whether extending sleep duration may mitigate this risk remains unknown. Objective: To determine the effects of a sleep extension intervention on objectively assessed energy intake, energy expenditure, and body weight in real-life settings among adults with overweight who habitually curtailed their sleep duration. Design, setting, and participants: This single-center, randomized clinical trial was conducted from November 1, 2014, to October 30, 2020. Participants were adults aged 21 to 40 years with a body mass index (calculated as weight in kilograms divided by height in meters squared) between 25.0 and 29.9 and had habitual sleep duration of less than 6.5 hours per night. Data were analyzed according to the intention-to-treat principle. Interventions: After a 2-week habitual sleep period at baseline, participants were randomized to either an individualized sleep hygiene counseling session that was intended to extend their bedtime to 8.5 hours (sleep extension group) or to continue their habitual sleep (control group). All participants were instructed to continue daily routine activities at home without any prescribed diet or physical activity. Main outcomes and measures: The primary outcome was change in energy intake from baseline, which was objectively assessed as the sum of total energy expenditure and change in body energy stores. Total energy expenditure was measured by the doubly labeled water method. Change in body energy stores was computed using regression of daily home weights and body composition changes from dual-energy x-ray absorptiometry. Sleep duration was monitored by actigraphy. Changes from baseline were compared between the 2 groups using intention-to-treat analysis. Results: Data from 80 randomized participants (mean [SD] age, 29.8 [5.1] years; 41 men [51.3%]) were analyzed. Sleep duration was increased by approximately 1.2 hours per night (95% CI, 1.0 to 1.4 hours; P < .001) in the sleep extension group vs the control group. The sleep extension group had a significant decrease in energy intake compared with the control group (-270 kcal/d; 95% CI, -393 to -147 kcal/d; P < .001). The change in sleep duration was inversely correlated with the change in energy intake (r = -0.41; 95% CI, -0.59 to -0.20; P < .001). No significant treatment effect in total energy expenditure was found, resulting in weight reduction in the sleep extension group vs the control group. Conclusions and relevance: This trial found that sleep extension reduced energy intake and resulted in a negative energy balance in real-life settings among adults with overweight who habitually curtailed their sleep duration. Improving and maintaining healthy sleep duration over longer periods could be part of obesity prevention and weight loss programs. Trial registration: ClinicalTrials.gov Identifier: NCT02253368.

JAMA internal medicine · randomised controlled trial · 109 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 →

Effectiveness of Integrated Palliative and Oncology Care for Patients With Acute Myeloid Leukemia: A Randomized Clinical Trial.

Importance: Patients with acute myeloid leukemia (AML) receiving intensive chemotherapy experience substantial decline in their quality of life (QOL) and mood during their hospitalization for induction chemotherapy and often receive aggressive care at the end of life (EOL). However, the role of specialty palliative care for improving the QOL and care for this population is currently unknown. Objective: To assess the effect of integrated palliative and oncology care (IPC) on patient-reported and EOL outcomes in patients with AML. Design, setting, and participants: We conducted a multisite randomized clinical trial of IPC (n = 86) vs usual care (UC) (n = 74) for patients with AML undergoing intensive chemotherapy. Data were collected from January 2017 through July 2019 at 4 tertiary care academic hospitals in the United States. Interventions: Patients assigned to IPC were seen by palliative care clinicians at least twice per week during their initial and subsequent hospitalizations. Main outcomes and measures: Patients completed the 44-item Functional Assessment of Cancer Therapy-Leukemia scale (score range, 0-176) to assess QOL; the 14-item Hospital Anxiety and Depression Scale (HADS), with subscales assessing symptoms of anxiety and depression (score range, 0-21); and the PTSD Checklist-Civilian version to assess posttraumatic stress disorder (PTSD) symptoms (score range, 17-85) at baseline and weeks 2, 4, 12, and 24. The primary end point was QOL at week 2. We used analysis of covariance adjusting and mixed linear effect models to evaluate patient-reported outcomes. We used Fisher exact test to compare patient-reported discussion of EOL care preferences and receipt of chemotherapy in the last 30 days of life. Results: Of 235 eligible patients, 160 (68.1%) were enrolled; of the 160 participants, the median (range) age was 64.4 (19.7-80.1) years, and 64 (40.0%) were women. Compared with those receiving UC, IPC participants reported better QOL (adjusted mean score, 107.59 vs 116.45; P = .04), and lower depression (adjusted mean score, 7.20 vs 5.68; P = .02), anxiety (adjusted mean score, 5.94 vs 4.53; P = .02), and PTSD symptoms (adjusted mean score, 31.69 vs 27.79; P = .01) at week 2. Intervention effects were sustained to week 24 for QOL (β, 2.35; 95% CI, 0.02-4.68; P = .048), depression (β, -0.42; 95% CI, -0.82 to -0.02; P = .04), anxiety (β, -0.38; 95% CI, -0.75 to -0.01; P = .04), and PTSD symptoms (β, -1.43; 95% CI, -2.34 to -0.54; P = .002). Among patients who died, those receiving IPC were more likely than those receiving UC to report discussing EOL care preferences (21 of 28 [75.0%] vs 12 of 30 [40.0%]; P = .01) and less likely to receive chemotherapy near EOL (15 of 43 [34.9%] vs 27 of 41 [65.9%]; P = .01). Conclusions and relevance: In this randomized clinical trial of patients with AML, IPC led to substantial improvements in QOL, psychological distress, and EOL care. Palliative care should be considered a new standard of care for patients with AML. Trial registration: ClinicalTrials.gov Identifier: NCT02975869.

JAMA oncology · randomised controlled trial · 151 citationsread the source →

Socioeconomic status over the life course and allostatic load in adulthood: results from the Northern Swedish Cohort.

Background: Although several studies have reported rather consistent associations between socioeconomic status (SES) and allostatic load (AL), so far no study has examined the influence of SES over the life course on AL. The aim of the present study was to investigate the association between SES over the life course and AL in mid-adulthood, guided by the conceptual models of cumulative risk, critical period and social chain of risk. Methods: The sample comprises a 27-year prospective cohort (n=1071) from northern Sweden. Participants (n=855, 79.8%) completed questionnaires at the ages of 16, 21, 30 and 43 years. A health examination was performed at age 43 years after an overnight fast, including physical examination and blood sampling, and participants completed 1-day salivary cortisol sampling (four samples). SES was based on parental occupation at age 16 years and participants' own occupation at ages 21, 30 and 43 years. Information on daily smoking, snuff use, high alcohol consumption and physical inactivity was reported by the participants. An AL index was constructed from tertiles of 12 biological parameters. Results: Cumulative socioeconomic disadvantage was related to AL in both women and men. The association was largely explained by health behaviours in men, but was independent of health behaviours in women. In women, an association was observed between AL and SES in adolescence, whereas in men only current SES was related to AL, independently of current health behaviours. Conclusions: SES over the life course influences the level of multi-systemic dysregulation in mid-adulthood, with the strongest support for the cumulative risk model.

Journal of epidemiology and community health · 78 citationsread the source →

Gender differences in rates of depression, PTSD, pain, obesity, and military sexual trauma among Connecticut War Veterans of Iraq and Afghanistan.

Purpose: The current wars in Iraq and Afghanistan have led to an increasing number of female veterans seeking medical and mental healthcare in the Department of Veterans Affairs (VA) healthcare system. To better understand gender differences in healthcare needs among recently returned veterans, we examined the prevalence of positive screenings for depression, posttraumatic stress disorder (PTSD), military sexual trauma (MST), obesity, and chronic pain among female and male veterans of Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) receiving care at the VA Connecticut Healthcare System. Methods: We performed a retrospective, cross-sectional data analysis of OEF/OIF veterans at VA Connecticut who received services in either Primary Care or the Women's Health Clinic between 2001 and 2006. Results: In this study, 1129 electronic medical records (1032 men, 197 women) were examined. Female veterans were more likely to screen positive for MST (14% vs. 1%, p < 0.001) and depression (48% vs. 39%, p = 0.01) and less likely to screen positive for PTSD (21% vs. 33%, p = 0.002). There was no significant gender difference in clinically significant pain scores. Men were more likely than women to have body mass index (BMI) >30 kg/m(2) (21% vs. 13%, p = 0.008). Conclusions: These results suggest that important gender differences exist in the prevalence of positive screenings for MST, depression, obesity, and PTSD. As the VA continues to review and improve its services for women veterans, clinicians, researchers, and senior leaders should consider innovative ways to ensure that female veterans receive the health services they need within the VA system.

Journal of women's health (2002) · cohort or longitudinal · 186 citationsread the source →

Blood Lipid Responses to Diets Enriched with Cottonseed Oil Compared With Olive Oil in Adults with High Cholesterol in a Randomized Trial.

Background: Increasing unsaturated fat intake is beneficial for cardiovascular health, but the type of unsaturated fat to recommend remains equivocal. Objectives: We investigated the effects of an 8-week diet intervention that was rich in either cottonseed oil (CSO; PUFA rich) or olive oil (OO; MUFA rich) on blood lipids in hypercholesterolemic adults. Methods: Forty-three men and women with hypercholesterolemia (53 ± 10 years; BMI, 27.6 ± 4.8 kg/m2) completed this randomized parallel clinical trial consisting of an 8-week partial outpatient feeding intervention. Participants were given meals and snacks accounting for ∼60% of their daily energy needs, with 30% of energy needs from either CSO (n = 21) or OO (n = 22). At pre- and postdiet intervention visits, participants consumed a high-SFA meal (35% of total energy needs; 70% of energy from fat). The primary outcomes of fasting cholesterol profiles and secondary outcomes of postprandial blood lipids and glycemic markers were assessed over a 5-hour period. Results: There were greater reductions from baseline to week 8 in fasting serum total cholesterol (TC; -17.0 ± 3.94 mg/dL compared with -2.18 ± 3.72 mg/dL, respectively; P = 0.008), LDL cholesterol (-19.7 ± 3.94 mg/dL compared with -5.72 ± 4.23 mg/dL, respectively; P = 0.018), non-HDL cholesterol (-20.8 mg/dL ± 4.00 compared with -6.61 ± 4.01 mg/dL, respectively; P = 0.014), and apoB (-11.8 mg/dL ± 2.37 compared with -3.10 ± 2.99 mg/dL, respectively; P = 0.05), in CSO compared with OO. There were also visit effects from baseline to week 8 for increases in HDL cholesterol (CSO, 56.5 ± 2.79 mg/dL to 60.2 ± 3.35 mg/dL, respectively; OO: 59.7 ± 2.63 mg/dL to 64.1 ± 2.24 mg/dL, respectively; P < 0.001), and decreases in the TC:HDL-cholesterol ratio (CSO, 4.30 ± 0.27 mg/dL to 3.78 ± 0.27 mg/dL, respectively; OO, 3.94 ± 0.16 mg/dL to 3.57 ± 0.11 mg/dL, respectively; P < 0.001), regardless of group assignment. In response to the high-SFA meal, there were differences in postprandial plasma glucose (P = 0.003) and triglyceride (P = 0.004) responses and a trend in nonesterified fatty acids (P = 0.11) between groups, showing protection in the postprandial state from an occasional high-SFA fat meal with CSO, but not OO, diet enrichment. Conclusions: CSO, but not OO, diet enrichment caused substantial improvements in fasting and postprandial blood lipids and postprandial glycemia in hypercholesterolemic adults. This trial was registered at clinicaltrials.gov as NCT04397055.

The Journal of nutrition · randomised controlled trial · 17 citationsread the source →

Circadian rhythm of salivary cortisol secretion in female zoo-kept African elephants (Loxodonta africana).

Salivary samples were collected over a 24-hr period from one group of six juvenile (7-12 years) and one group of three adult (24-25 years) African elephant females, Loxodonta africana, and the cortisol concentration was measured in unextracted samples by EIA. Samples were collected during May, June, and November 2012 (n = 147) using cotton swabs at 4-hr intervals from 20:00 to 20:00 of the next day (seven samples per animal in each trial). The animals are kept under standard zoo management: the herd is maintained in their indoor enclosures until 10:00 and then released into the outdoor enclosures until 21:00-21:30 (May/June) and 18:30-19:00 (November). No adult elephant bull was present at the zoo during this time. The results demonstrate a clear diurnal pattern of cortisol secretion with the lowest concentration observed at 20:00 (2.03 ± 0.08 ng/ml saliva) and the peak concentrations at 08:00 (5.26 ± 0.35 ng/ml saliva). Although the cortisol values were higher in the adult cows compared to the juvenile cows in the May-June period, the differences were not significant. However, the values obtained in November from the juvenile group were significantly higher (P < 0.05) than the concentrations measured in this group in June. In conclusion, salivary cortisol in zoo elephants follows a circadian rhythm (sleep-wake cycle) adapted to daily zoo husbandry routines.

Zoo biology · 11 citationsread the source →

Limited Benefit of Sleep Extension on Cognitive Deficits During Total Sleep Deprivation: Illustration With Two Executive Processes.

Introduction: Sleep extension has been associated with better alertness and sustained attention capacities before, during and after sleep loss. However, less is known about such beneficial effect on executive functions (EFs). Our aim was to investigate such effects on two EFs (i.e., inhibition and working memory) for subjects submitted to total sleep deprivation and one-night of recovery. Methods: Fourteen healthy men (26-37 years old) participated in an experimental cross-over design with two conditions: extended sleep (EXT, 9.8 ± 0.1 h of Time In Bed, TIB) and habitual sleep (HAB, 8.2 ± 0.1 h TIB). During these two conditions subjects underwent two consecutive phases: Six nights of either EXT or HAB followed by 3 days in-laboratory: baseline (BASE), TSD (38 h) and after recovery (REC). EFs capacities were assessed through Go-NoGo (inhibition) and 2N-Back (working memory) tasks. Both EFs capacities were measured at different time (BASE/TSD/REC: 09:30, 13:00, 16:00; TSD: 21:00, 00:00, 03:00, 06:30). Results: In both conditions (HAB and EXT), TSD was associated with deficits in inhibition (higher errors and mean reaction time from TSD 09:30 until the end; p < 0.05) and working memory (lower corrects responses from TSD 06:30 or 09:30; p < 0.05). We observed no significant differences between HAB and EXT conditions on EFs capacities during BASE, TSD, and REC periods. Conclusion: Six nights of sleep extension is neither efficient to reduce core EFs deficits related to TSD nor to improve such capacities after a recovery night. These results highlight that sleep extension (six nights of 10 h of TIB) is not effective to limit EFs deficits related to TSD suggesting a disconnection inside cognition between executive and sustained attention processes. Clinical Trials: NCT02352272.

Frontiers in neuroscience · 15 citationsread the source →

Subjective and objective napping and sleep in older adults: are evening naps "bad" for nighttime sleep?

Objectives: To compare objective and subjective measurements of napping and to examine the relationship between evening napping and nocturnal sleep in older adults. Design: For 12 days, participants wore actigraphs and completed sleep diaries. Setting: Community. Participants: One hundred individuals who napped, aged 60 to 89 (including good and poor sleepers with typical age-related medical comorbidities). Measurements: Twelve days of sleep diary and actigraphy provided subjective and objective napping and sleep data. Results: Evening naps (within 2 hours of bedtime) were characteristic of the sample, with peak nap time occurring between 20:30 and 21:00 (average nap time occurred between 14:30 and 15:00). Two categories of nappers were identified: those who took daytime and evening naps and daytime-only. No participants napped during the evening only. Day-and-evening nappers significantly underreported evening napping and demonstrated lower objectively measured sleep onset latencies (20.0 vs 26.5 minutes), less wake after sleep onset (51.4 vs 72.8 minutes), and higher sleep efficiencies (76.8 vs 82%) than daytime-only nappers. Conclusion: Day and evening napping was prevalent in this sample of community-dwelling good and poor sleepers but was not associated with impaired nocturnal sleep. Although the elimination or restriction of napping is a common element of cognitive-behavioral therapy for insomnia, these results suggest that a uniform recommendation to restrict or eliminate napping (particularly evening napping) may not meet the needs of all older individuals with insomnia.

Journal of the American Geriatrics Society · 45 citationsread the source →

Fish oil supplementation during pregnancy and postpartum in mothers with overweight and obesity to improve body composition and metabolic health during infancy: A double-blind randomized controlled trial.

Background: Maternal obesity during pregnancy is associated with an increased risk of obesity and metabolic disease in the offspring. Supplementation with fish oil (FO), which is insulin sensitizing, during pregnancy in mothers with overweight or obesity may prevent the development of greater adiposity and metabolic dysfunction in their children. Objectives: To determine the effects of FO supplementation throughout the second half of pregnancy and lactation in mothers with overweight or obesity on infant body composition and metabolism. Methods: A double-blind randomized controlled trial of 6 g FO (3.55 g/d of n-3 PUFAs) compared with olive oil (control) from mid-pregnancy until 3 mo postpartum. Eligible women had singleton pregnancies at 12-20 wk of gestation, and BMI ≥ 25 kg/m2. The primary outcome was the infant body fat percentage (DXA scans) at 2 wk of age. Secondary outcomes included maternal metabolic markers during pregnancy, infant anthropometry at 2 wk and 3 mo of age, and metabolic markers at 3 mo. Results: A total of 129 mothers were randomized, and 98 infants had a DXA scan at 2 wk. Primary outcome: Imputed and nonimputed analyses showed no effects of FO supplementation on infant body fat percentage at age 2 wk. Secondary outcomes: There were no treatment effects on infant outcomes at 2 wk, but FO infants had a higher BMI z-score (P = 0.025) and ponderal index (P = 0.017) at age 3 mo. FO supplementation lowered maternal triglycerides by 17% at 30 wk of pregnancy (P = 0.0002) and infant triglycerides by 21% at 3 mo of age (P = 0.016) but did not affect maternal or infant insulin resistance. The rate of emergency cesarean section was lower with FO supplementation [aRR = 0.38 (95%CI 0.16, 0.90); P = 0.027]. Conclusions: FO supplementation of mothers with overweight or obesity during pregnancy did not impact infant body composition. There is a need to follow up the offspring to determine whether the observed metabolic effects persist. Clinical trial registry number: This study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617001078347p). In addition, the Universal Trial Number, WHO, was obtained (U1111-1199-5860).

The American journal of clinical nutrition · randomised controlled trial · 13 citationsread the source →

Psychological and social health outcomes of physical activity around menopause: A scoping review of research.

Objective: To chart peer-reviewed literature regarding the psychological and social health outcomes of physical activity (PA) around menopause in a systematic manner. Methods: Nine electronic databases and 10 core journals were searched using specific search strings to identify eligible articles. Manual checking of reference lists was also performed. The selection process was guided by the stages in PRISMA-ScR. Results: Eighty peer-reviewed articles representing 67 studies from 25 countries were included. All articles were published between 1994 and 2021. For all studies, surveys were the primary method of measuring psychological and social health outcomes, in cross-sectional studies (36 papers), intervention studies (33), longitudinal cohort studies (10) and one paper reporting a mixed-method study. The dataset comprised a total of 103,826 women, with an average age of 52.6 and a variety of menopausal states. Most of the studies involved primarily Caucasian, relatively healthy, married and employed participants. Nineteen psychological and social health outcomes were assessed, including psychological menopause symptoms (N = 34), quality of life (N = 33), depression (N = 30), anxiety (N = 11), mental wellbeing (N = 21), perceived stress (N = 9), satisfaction with life (N = 7) and self-esteem (N = 5). Conclusions: Collectively, the findings of these studies indicate a relatively evident positive impact of PA on the respective health outcomes, with only a few studies reporting no association. It is also noteworthy that most studies did not report any difference related to menopausal status. Future studies would benefit from, inter alia, a qualitative approach to lived experiences of psychological and social health outcomes of PA during the menopausal transition.

Maturitas · review · 24 citationsread the source →

Factors that influence the provision of intrapartum and postnatal care by skilled birth attendants in low- and middle-income countries: a qualitative evidence synthesis.

Background: In many low- and middle-income countries women are encouraged to give birth in clinics and hospitals so that they can receive care from skilled birth attendants. A skilled birth attendant (SBA) is a health worker such as a midwife, doctor, or nurse who is trained to manage normal pregnancy and childbirth. (S)he is also trained to identify, manage, and refer any health problems that arise for mother and baby. The skills, attitudes and behaviour of SBAs, and the extent to which they work in an enabling working environment, impact on the quality of care provided. If any of these factors are missing, mothers and babies are likely to receive suboptimal care. Objectives: To explore the views, experiences, and behaviours of skilled birth attendants and those who support them; to identify factors that influence the delivery of intrapartum and postnatal care in low- and middle-income countries; and to explore the extent to which these factors were reflected in intervention studies. Search methods: Our search strategies specified key and free text terms related to the perinatal period, and the health provider, and included methodological filters for qualitative evidence syntheses and for low- and middle-income countries. We searched MEDLINE, OvidSP (searched 21 November 2016), Embase, OvidSP (searched 28 November 2016), PsycINFO, OvidSP (searched 30 November 2016), POPLINE, K4Health (searched 30 November 2016), CINAHL, EBSCOhost (searched 30 November 2016), ProQuest Dissertations and Theses (searched 15 August 2013), Web of Science (searched 1 December 2016), World Health Organization Reproductive Health Library (searched 16 August 2013), and World Health Organization Global Health Library for WHO databases (searched 1 December 2016). Selection criteria: We included qualitative studies that focused on the views, experiences, and behaviours of SBAs and those who work with them as part of the team. We included studies from all levels of health care in low- and middle-income countries. Data collection and analysis: One review author extracted data and assessed study quality, and another review author checked the data. We synthesised data using the best fit framework synthesis approach and assessed confidence in the evidence using the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach. We used a matrix approach to explore whether the factors identified by health workers in our synthesis as important for providing maternity care were reflected in the interventions evaluated in the studies in a related intervention review. Main results: We included 31 studies that explored the views and experiences of different types of SBAs, including doctors, midwives, nurses, auxiliary nurses and their managers. The included studies took place in Africa, Asia, and Latin America. Our synthesis pointed to a number of factors affecting SBAs' provision of quality care. The following factors were based on evidence assessed as of moderate to high confidence. Skilled birth attendants reported that they were not always given sufficient training during their education or after they had begun clinical work. Also, inadequate staffing of facilities could increase the workloads of skilled birth attendants, make it difficult to provide supervision and result in mothers being offered poorer care. In addition, SBAs did not always believe that their salaries and benefits reflected their tasks and responsibilities and the personal risks they undertook. Together with poor living and working conditions, these issues were seen to increase stress and to negatively affect family life. Some SBAs also felt that managers lacked capacity and skills, and felt unsupported when their workplace concerns were not addressed. Possible causes of staff shortages in facilities included problems with hiring and assigning health workers to facilities where they were needed; lack of funding; poor management and bureaucratic systems; and low salaries. Skilled birth attendants and their managers suggested factors that could help recruit, keep, and motivate health workers, and improve the quality of care; these included good-quality housing, allowances for extra work, paid vacations, continuing education, appropriate assessments of their work, and rewards. Skilled birth attendants' ability to provide quality care was also limited by a lack of equipment, supplies, and drugs; blood and the infrastructure to manage blood transfusions; electricity and water supplies; and adequate space and amenities on maternity wards. These factors were seen to reduce SBAs' morale, increase their workload and infection risk, and make them less efficient in their work. A lack of transport sometimes made it difficult for SBAs to refer women on to higher levels of care. In addition, women's negative perceptions of the health system could make them reluctant to accept referral. We identified some other factors that also may have affected the quality of care, which were based on findings assessed as of low or very low confidence. Poor teamwork and lack of trust and collaboration between health workers appeared to negatively influence care. In contrast, good collaboration and teamwork appeared to increase skilled birth attendants' motivation, their decision-making abilities, and the quality of care. Skilled birth attendants' workloads and staff shortages influenced their interactions with mothers. In addition, poor communication undermined trust between skilled birth attendants and mothers. Authors' conclusions: Many factors influence the care that SBAs are able to provide to mothers during childbirth. These include access to training and supervision; staff numbers and workloads; salaries and living conditions; and access to well-equipped, well-organised healthcare facilities with water, electricity, and transport. Other factors that may play a role include the existence of teamwork and of trust, collaboration, and communication between health workers and with mothers. Skilled birth attendants reported many problems tied to all of these factors.

The Cochrane database of systematic reviews · systematic review · 141 citationsread the source →

Association between characteristics of behavioural weight loss programmes and weight change after programme end: systematic review and meta-analysis.

Objective: To determine if the characteristics of behavioural weight loss programmes influence the rate of change in weight after the end of the programme. Design: Systematic review and meta-analysis. Data sources: Trial registries, 11 electronic databases, and forward citation searching (from database inception; latest search December 2019). Randomised trials of behavioural weight loss programmes in adults with overweight or obesity, reporting outcomes at ≥12 months, including at the end of the programme and after the end of the programme. Review methods: Studies were screened by two independent reviewers with discrepancies resolved by discussion. 5% of the studies identified in the searches met the inclusion criteria. One reviewer extracted the data and a second reviewer checked the data. Risk of bias was assessed with Cochrane's risk of bias tool (version 1). The rate of change in weight was calculated (kg/month; converted to kg/year for interpretability) after the end of the programme in the intervention versus control groups by a mixed model with a random intercept. Associations between the rate of change in weight and prespecified variables were tested. Results: Data were analysed from 249 trials (n=59 081) with a mean length of follow-up of two years (longest 30 years). 56% of studies (n=140) had an unclear risk of bias, 21% (n=52) a low risk, and 23% (n=57) a high risk of bias. Regain in weight was faster in the intervention versus the no intervention control groups (0.12-0.32 kg/year) but the difference between groups was maintained for at least five years. Each kilogram of weight lost at the end of the programme was associated with faster regain in weight at a rate of 0.13-0.19 kg/year. Financial incentives for weight loss were associated with faster regain in weight at a rate of 1-1.5 kg/year. Compared with programmes with no meal replacements, interventions involving partial meal replacements were associated with faster regain in weight but not after adjustment for weight loss during the programme. Access to the programme outside of the study was associated with slower regain in weight. Programmes where the intensity of the interaction reduced gradually were also associated with slower regain in weight in the multivariable analysis, although the point estimate suggested that the association was small. Other characteristics did not explain the heterogeneity in regain in weight. Conclusion: Faster regain in weight after weight loss was associated with greater initial weight loss, but greater initial weight loss was still associated with reduced weight for at least five years after the end of the programme, after which data were limited. Continued availability of the programme to participants outside of the study predicted a slower regain in weight, and provision of financial incentives predicted faster regain in weight; no other clear associations were found. Study registration: PROSPERO CRD42018105744.

BMJ (Clinical research ed.) · meta-analysis · 40 citationsread the source →

Prevalence and factors associated with use of khat: a survey of patients entering HIV treatment programs in Ethiopia.

Background: Khat, a plant native to East Africa, has psychoactive constituents similar to amphetamine. Chronic khat use can lead to psychological dependence with multiple physical and mental health harms, complicating clinical management of people living with HIV. In two Ethiopian cities where khat is common, we evaluated prevalence and correlates of khat use among patients new to HIV care. Methods: During 2013-2014, we surveyed 322 patients recently enrolled in HIV clinics in Dire Dawa and Harar about khat use, demographics, smoking and alcohol use, clinical illness, food insecurity, and social support. We analyzed factors associated with khat use in the past year, as well as heaviest use of khat (based on greatest number of hours used in a typical month). Results: 242 (75%) respondents reported lifetime khat use; 209 (65%) reported khat use during the previous year. 54% of khat users started before age 19 years. Although 84% believed that using khat every day is dangerous for health if you have HIV, khat was used in the previous year a median of 5 h/days and 30 days/month; 21% said they felt a need to cut down or control their khat use but had difficulty doing so. Those using khat were more likely to report smoking (46%) and alcohol use (49%) compared to non-khat users (1 and 31% respectively). Those reporting heaviest khat use (≥180 h/typical month) were more likely to rate their health status as poor, have an underweight BMI (≤18.5 kg/m2), report more symptoms of chronic illness, and agree with more statements indicating a negative physical quality of life. In multivariate analysis, heavy users were more likely to be male, Muslim, and non-married. Conclusions: Khat use was common among HIV patients entering care, and associated with symptoms of poorer physical health. Over half started khat use when they were young. Although most believed khat is harmful for HIV patients, a number of respondents reported some difficulty controlling their drug use. In settings where khat is legal and widely utilized, developing interventions for responsible use represent an important health priority as part of comprehensive care for people living with HIV.

Addiction science & clinical practice · 13 citationsread the source →

Mechanisms underlying antidepressant effect of transcutaneous auricular vagus nerve stimulation on CUMS model rats based on hippocampal α7nAchR/NF-κB signal pathway.

Background: Stress-induced neuroinflammation was considered to play a critical role in the pathogenesis of depression. Transcutaneous auricular vagus nerve stimulation (taVNS) is a relatively non-invasive alternative treatment for patients suffering from major depressive disorder. The anti-inflammatory signal of vagus nerve is mediated by α7 nicotinic acetylcholine receptor (α7nAchR), and the hippocampus, the region with the most distribution of α7nAchR, regulates emotions. Here, we investigated the role of α7nAchR mediating hippocampal neuroinflammation in taVNS antidepressant effect though homozygous α7nAChR (-/-) gene knockout and α7nAchR antagonist (methyllycaconitine, MLA). Methods: There were control, model, taVNS, α7nAChR(-/-) + taVNS, hippocampus (Hi) MLA + taVNS and Hi saline + taVNS groups. We used the chronic unpredicted mild stress (CUMS) method to establish depressive model rats for 42 days, excepting control group. After the successful modeling, except the control and model, the rats in the other groups were given taVNS, which was applied through an electroacupuncture apparatus at the auricular concha (2/15 Hz, 2 mA, 30 min/days) for 21 days. Behavioral tests were conducted at baseline, after modeling and after taVNS intervention, including sucrose preference test (SPT), open field test (OFT) and forced swimming test (FST). These tests are widely used to evaluate depression-like behavior in rats. The samples were taken after experiment, the expressions of α7nAchR, NF-κB p65, IL-1β and the morphology of microglia were detected. Results: Depression-like behavior and hippocampal neuroinflammation in CUMS model rats were manifested by down-regulated expression of α7nAchR, up-regulated expression of NF-κB p65 and IL-1β, and the morphology of microglia was in amoebic-like activated state. TaVNS could significantly reverse the above-mentioned phenomena, but had rare improvement effect for α7nAChR(-/-) rats and Hi MLA rats. Conclusion: The antidepressant effect of taVNS is related to hippocampal α7nAchR/NF-κB signal pathway.

Journal of neuroinflammation · 119 citationsread the source →

Interconnection between adolescents' and family members' sleep.

Deficient sleep has been linked to a broad range of physical, cognitive and mental health impacts, in particular during adolescence. It is thus essential to understand its underlying mechanisms, including family factors. The goal of our study was to assess through combined subjective and objective assessments, how family members' daily variations in sleep are interconnected, between parents and siblings of adolescents. A total of 111 participants within 30 families were included, of whom 30 adolescents (14.5 years +/- 2.1 years, 46.7% boys), 30 siblings (12.8 years + /- 3.8, 40% boys), 30 mothers (43.5 years +/- 5.5) and 21 fathers (47.5 years +/- 7.6). Sleep was objectively assessed using parallel actigraphy recordings during a single week for all family members. Adolescents' daily variation in sleep duration and timing displayed many concordances with their siblings' and their mothers' sleep, but not with their fathers' sleep. Adolescents whose parents did not set limits on sleep time or screen use went to bed over an hour later (p < 0.001) and slept over 30 min less on school nights. Our study demonstrates the important role of family sleep on adolescent sleep, through rule-setting and congruence between each family members sleep, in particular regarding sleep duration and timing.

Scientific reports · 1 citationsread the source →

Mental health, migration stressors and suicidal ideation among Latino immigrants in Spain and the United States.

Background: Immigration stress appears to augment the risk for suicide behaviors for Latinos. Yet, specific risk factors that contribute to suicidal ideation (SI) among diverse Latino immigrant populations are not well established. Methods: Data were collected in Boston, Madrid and Barcelona using a screening battery assessing mental health, substance abuse risk, trauma exposure, demographics, and sociocultural factors. Prevalence rates of lifetime and 30-day SI were compared across sites. Logistic regression modeling was used to identify sociodemographic, clinical, and sociocultural-contextual factors associated with 30-day SI. Results: Five hundred and sixty-seven Latino patients from primary care, behavioral health and HIV clinics and community agencies participated. Rates of lifetime SI ranged from 29-35%; rates for 30-day SI were 21-23%. Rates of SI were not statistically different between sites. Factors associated with SI included exposure to discrimination, lower ethnic identity, elevated family conflict, and low sense of belonging (P<0.01). In the adjusted model, higher scores on depression, posttraumatic stress disorder, and trauma exposure were significantly associated with 30-day SI (OR=1.14, 1.04, and 7.76, respectively). Greater number of years living in the host country was significantly associated with increased odds of having SI (OR=2.22) while having citizenship status was associated with lower odds (OR=0.45). Conclusion: Latinos suffering depression, trauma exposure, and immigration stressors are more likely to experience SI. Despite differences in country of origin, education, and other demographic factors between countries, rates of SI did not differ. Recommendations for prevention and clinical practice for addressing suicidal ideation risk among Latino immigrants are discussed.

European psychiatry : the journal of the Association of European Psychiatrists · 58 citationsread the source →

An objective assessment of children's exposure to brand marketing in New Zealand (Kids'Cam): a cross-sectional study.

Background: Marketing promotes values of consumerism and overconsumption, and negatively affects children's wellbeing and psychological development. The threat marketing poses to planetary health is just being realised. However, little is known about children's exposure to marketing at an aggregate level. Using an objective method of wearable cameras, we aimed to determine the nature and extent of children's exposure to marketing. Methods: Kids'Cam was a cross-sectional study of children aged 11-13 years in New Zealand, from which we randomly selected a sample of 90 children. Children wore cameras from when they woke up until they went to sleep for four consecutive days (Thursday-Sunday) that captured images at an angle of 136° every 7 s for exposure to marketing. Marketing brands were categorised into three groups: core food and social marketing messages, harmful commodities (eg, non-core food, alcohol, and gambling), or other. Exposure rates by marketing medium, setting, and product category were calculated using negative binomial regression models. Findings: From June 21, 2014, to June 30, 2015, we recruited 168 children, and randomly selected data from 90 children for the present study. Children in this study were exposed to a mean of 554 brands per 10 h day (95% CI 491-625), nearly a brand a minute, through multiple mediums (predominantly brand labels [36% of exposures] and product packaging [22%]) and mostly in schools (43%) and at home (30%). Food and beverages (20% of exposures) were the dominant product category. The most pervasive marketing brands typically sold a range of products across more than one product category (eg, children were exposed to Nike on average 20 exposures per day). Children were exposed to more than twice as many harmful commodities (mean 76 per 10 h day [95% CI 55-105]) as core food and social marketing messages (32 [26-39]) per day. Interpretation: We found that children are repeatedly exposed to marketing through multiple mediums and across all settings, and our findings suggests that marketing privileges particular messages, for example, marketing of harmful commodities. Given the key role marketing plays in establishing and supporting consumption norms, and perpetuating the normalisation of overconsumption which contributes to environmental degradation, these findings suggest an urgent need to reduce marketing to promote planetary health. Funding: This research was funded by a University of Otago, Dean's Research Grant. The Kids'Cam study was funded by a Health Research Council of New Zealand Programme Grant (13/724).

The Lancet. Planetary health · 10 citationsread the source →

Prevalence of low-grade inflammation in depression: a systematic review and meta-analysis of CRP levels.

Background: Peripheral low-grade inflammation in depression is increasingly seen as a therapeutic target. We aimed to establish the prevalence of low-grade inflammation in depression, using different C-reactive protein (CRP) levels, through a systematic literature review and meta-analysis. Methods: We searched the PubMed database from its inception to July 2018, and selected studies that assessed depression using a validated tool/scale, and allowed the calculation of the proportion of patients with low-grade inflammation (CRP >3 mg/L) or elevated CRP (>1 mg/L). Results: After quality assessment, 37 studies comprising 13 541 depressed patients and 155 728 controls were included. Based on the meta-analysis of 30 studies, the prevalence of low-grade inflammation (CRP >3 mg/L) in depression was 27% (95% CI 21-34%); this prevalence was not associated with sample source (inpatient, outpatient or population-based), antidepressant treatment, participant age, BMI or ethnicity. Based on the meta-analysis of 17 studies of depression and matched healthy controls, the odds ratio for low-grade inflammation in depression was 1.46 (95% CI 1.22-1.75). The prevalence of elevated CRP (>1 mg/L) in depression was 58% (95% CI 47-69%), and the meta-analytic odds ratio for elevated CRP in depression compared with controls was 1.47 (95% CI 1.18-1.82). Conclusions: About a quarter of patients with depression show evidence of low-grade inflammation, and over half of patients show mildly elevated CRP levels. There are significant differences in the prevalence of low-grade inflammation between patients and matched healthy controls. These findings suggest that inflammation could be relevant to a large number of patients with depression.

Psychological medicine · meta-analysis · 606 citationsread the source →

Aerobic exercise for adult patients with major depressive disorder in mental health services: A systematic review and meta-analysis.

Although exercise is associated with depression relief, the effects of aerobic exercise (AE) interventions on clinically depressed adult patients have not been clearly supported. The purpose of this meta-analysis was to examine the antidepressant effects of AE versus nonexercise comparators exclusively for depressed adults (18-65 years) recruited through mental health services with a referral or clinical diagnosis of major depression. Eleven e-databases and bibliographies of 19 systematic reviews were searched for relevant randomized controlled clinical trials. A random effects meta-analysis (Hedges' g criterion) was employed for pooling postintervention scores of depression. Heterogeneity and publication bias were examined. Studies were coded considering characteristics of participants and interventions, outcomes and comparisons made, and study design; accordingly, sensitivity and subgroup analyses were calculated. Across 11 eligible trials (13 comparisons) involving 455 patients, AE was delivered on average for 45 min, at moderate intensity, three times/week, for 9.2 weeks and showed a significantly large overall antidepressant effect (g = -0.79, 95% confidence interval = -1.01, -0.57, P < 0.00) with low and nonstatistically significant heterogeneity (I2 = 21%). No publication bias was found. Sensitivity analyses revealed large or moderate to large antidepressant effects for AE (I2 ≤ 30%) among trials with lower risk of bias, trials with short-term interventions (up to 4 weeks), and trials involving individual preferences for exercise. Subgroup analyses revealed comparable effects for AE across various settings and delivery formats, and in both outpatients and inpatients regardless symptom severity. Notwithstanding the small number of trials reviewed, AE emerged as an effective antidepressant intervention.

Depression and anxiety · meta-analysis · 224 citationsread the source →

Physiological exercise loading suppresses post-traumatic osteoarthritis progression via an increase in bone morphogenetic proteins expression in an experimental rat knee model.

Objective: To evaluate the dose-response relationship of exercise loading in the cartilage-subchondral bone (SB) unit in surgically-induced post-traumatic osteoarthritis (PTOA) of the knee. Design: Destabilized medial meniscus (DMM) surgery was performed on the right knee of 12-week-old male Wistar rats, and sham surgery was performed on the contralateral knee. Four weeks after the surgery, the animals were subjected to moderate (12 m/min) or intense (21 m/min) treadmill exercises for 30 min/day, 5 days/week for 4 weeks. PTOA development in articular cartilage and SB was examined using histological and immunohistochemical analyses, micro-computed tomography (micro-CT) analysis, and biomechanical testing at 8 weeks after surgery. Gremlin-1 was injected to determine the role of bone morphogenetic protein (BMP) signaling on PTOA development following moderate exercise. Results: Moderate exercise increased BMP-2, BMP-4, BMP-6, BMP receptor 2, pSmad-5, and inhibitor of DNA binding protein-1 expression in the superficial zone chondrocytes and suppressed cartilage degeneration, osteophyte growth, SB damage, and osteoclast-mediated SB resorption. However, intense exercise had little effect on BMP expression and even caused progression of these osteoarthritis (OA) changes. Gremlin-1 injection following moderate exercise caused progression of the PTOA development down to the level of the non-exercise DMM-operated knee. Conclusions: Exercise regulated cartilage-SB PTOA development in DMM-operated knees in a dose-dependent manner. Our findings shed light on the important role of BMP expression in superficial zone chondrocytes in attenuation of PTOA development following physiological exercise loading. Further studies to support a mechanism by which BMPs would be beneficial in preventing PTOA progression are warranted.

Osteoarthritis and cartilage · 54 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 →

Personalised digital interventions for reducing hazardous and harmful alcohol consumption in community-dwelling populations.

Background: Excessive alcohol use contributes significantly to physical and psychological illness, injury and death, and a wide array of social harm in all age groups. A proven strategy for reducing excessive alcohol consumption levels is to offer a brief conversation-based intervention in primary care settings, but more recent technological innovations have enabled people to interact directly via computer, mobile device or smartphone with digital interventions designed to address problem alcohol consumption. Objectives: To assess the effectiveness and cost-effectiveness of digital interventions for reducing hazardous and harmful alcohol consumption, alcohol-related problems, or both, in people living in the community, specifically: (i) Are digital interventions more effective and cost-effective than no intervention (or minimal input) controls? (ii) Are digital interventions at least equally effective as face-to-face brief alcohol interventions? (iii) What are the effective component behaviour change techniques (BCTs) of such interventions and their mechanisms of action? (iv) What theories or models have been used in the development and/or evaluation of the intervention? Secondary objectives were (i) to assess whether outcomes differ between trials where the digital intervention targets participants attending health, social care, education or other community-based settings and those where it is offered remotely via the internet or mobile phone platforms; (ii) to specify interventions according to their mode of delivery (e.g. functionality features) and assess the impact of mode of delivery on outcomes. Search methods: We searched CENTRAL, MEDLINE, PsycINFO, CINAHL, ERIC, HTA and Web of Knowledge databases; ClinicalTrials.com and WHO ICTRP trials registers and relevant websites to April 2017. We also checked the reference lists of included trials and relevant systematic reviews. Selection criteria: We included randomised controlled trials (RCTs) that evaluated the effectiveness of digital interventions compared with no intervention or with face-to-face interventions for reducing hazardous or harmful alcohol consumption in people living in the community and reported a measure of alcohol consumption. Data collection and analysis: We used standard methodological procedures expected by The Cochrane Collaboration. Main results: We included 57 studies which randomised a total of 34,390 participants. The main sources of bias were from attrition and participant blinding (36% and 21% of studies respectively, high risk of bias). Forty one studies (42 comparisons, 19,241 participants) provided data for the primary meta-analysis, which demonstrated that participants using a digital intervention drank approximately 23 g alcohol weekly (95% CI 15 to 30) (about 3 UK units) less than participants who received no or minimal interventions at end of follow up (moderate-quality evidence).Fifteen studies (16 comparisons, 10,862 participants) demonstrated that participants who engaged with digital interventions had less than one drinking day per month fewer than no intervention controls (moderate-quality evidence), 15 studies (3587 participants) showed about one binge drinking session less per month in the intervention group compared to no intervention controls (moderate-quality evidence), and in 15 studies (9791 participants) intervention participants drank one unit per occasion less than no intervention control participants (moderate-quality evidence).Only five small studies (390 participants) compared digital and face-to-face interventions. There was no difference in alcohol consumption at end of follow up (MD 0.52 g/week, 95% CI -24.59 to 25.63; low-quality evidence). Thus, digital alcohol interventions produced broadly similar outcomes in these studies. No studies reported whether any adverse effects resulted from the interventions.A median of nine BCTs were used in experimental arms (range = 1 to 22). 'B' is an estimate of effect (MD in quantity of drinking, expressed in g/week) per unit increase in the BCT, and is a way to report whether individual BCTs are linked to the effect of the intervention. The BCTs of goal setting (B -43.94, 95% CI -78.59 to -9.30), problem solving (B -48.03, 95% CI -77.79 to -18.27), information about antecedents (B -74.20, 95% CI -117.72 to -30.68), behaviour substitution (B -123.71, 95% CI -184.63 to -62.80) and credible source (B -39.89, 95% CI -72.66 to -7.11) were significantly associated with reduced alcohol consumption in unadjusted models. In a multivariable model that included BCTs with B > 23 in the unadjusted model, the BCTs of behaviour substitution (B -95.12, 95% CI -162.90 to -27.34), problem solving (B -45.92, 95% CI -90.97 to -0.87), and credible source (B -32.09, 95% CI -60.64 to -3.55) were associated with reduced alcohol consumption. The most frequently mentioned theories or models in the included studies were Motivational Interviewing Theory (7/20), Transtheoretical Model (6/20) and Social Norms Theory (6/20). Over half of the interventions (n = 21, 51%) made no mention of theory. Only two studies used theory to select participants or tailor the intervention. There was no evidence of an association between reporting theory use and intervention effectiveness. Authors' conclusions: There is moderate-quality evidence that digital interventions may lower alcohol consumption, with an average reduction of up to three (UK) standard drinks per week compared to control participants. Substantial heterogeneity and risk of performance and publication bias may mean the reduction was lower. Low-quality evidence from fewer studies suggested there may be little or no difference in impact on alcohol consumption between digital and face-to-face interventions. The BCTs of behaviour substitution, problem solving and credible source were associated with the effectiveness of digital interventions to reduce alcohol consumption and warrant further investigation in an experimental context. Reporting of theory use was very limited and often unclear when present. Over half of the interventions made no reference to any theories. Limited reporting of theory use was unrelated to heterogeneity in intervention effectiveness.

The Cochrane database of systematic reviews · meta-analysis · 210 citationsread the source →

Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic.

Background: Before the COVID-19 pandemic, coronaviruses caused two noteworthy outbreaks: severe acute respiratory syndrome (SARS), starting in 2002, and Middle East respiratory syndrome (MERS), starting in 2012. We aimed to assess the psychiatric and neuropsychiatric presentations of SARS, MERS, and COVID-19. Methods: In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases (from their inception until March 18, 2020), and medRxiv, bioRxiv, and PsyArXiv (between Jan 1, 2020, and April 10, 2020) were searched by two independent researchers for all English-language studies or preprints reporting data on the psychiatric and neuropsychiatric presentations of individuals with suspected or laboratory-confirmed coronavirus infection (SARS coronavirus, MERS coronavirus, or SARS coronavirus 2). We excluded studies limited to neurological complications without specified neuropsychiatric presentations and those investigating the indirect effects of coronavirus infections on the mental health of people who are not infected, such as those mediated through physical distancing measures such as self-isolation or quarantine. Outcomes were psychiatric signs or symptoms; symptom severity; diagnoses based on ICD-10, DSM-IV, or the Chinese Classification of Mental Disorders (third edition) or psychometric scales; quality of life; and employment. Both the systematic review and the meta-analysis stratified outcomes across illness stages (acute vs post-illness) for SARS and MERS. We used a random-effects model for the meta-analysis, and the meta-analytical effect size was prevalence for relevant outcomes, I2 statistics, and assessment of study quality. Findings: 1963 studies and 87 preprints were identified by the systematic search, of which 65 peer-reviewed studies and seven preprints met inclusion criteria. The number of coronavirus cases of the included studies was 3559, ranging from 1 to 997, and the mean age of participants in studies ranged from 12·2 years (SD 4·1) to 68·0 years (single case report). Studies were from China, Hong Kong, South Korea, Canada, Saudi Arabia, France, Japan, Singapore, the UK, and the USA. Follow-up time for the post-illness studies varied between 60 days and 12 years. The systematic review revealed that during the acute illness, common symptoms among patients admitted to hospital for SARS or MERS included confusion (36 [27·9%; 95% CI 20·5-36·0] of 129 patients), depressed mood (42 [32·6%; 24·7-40·9] of 129), anxiety (46 [35·7%; 27·6-44·2] of 129), impaired memory (44 [34·1%; 26·2-42·5] of 129), and insomnia (54 [41·9%; 22·5-50·5] of 129). Steroid-induced mania and psychosis were reported in 13 (0·7%) of 1744 patients with SARS in the acute stage in one study. In the post-illness stage, depressed mood (35 [10·5%; 95% CI 7·5-14·1] of 332 patients), insomnia (34 [12·1%; 8·6-16·3] of 280), anxiety (21 [12·3%; 7·7-17·7] of 171), irritability (28 [12·8%; 8·7-17·6] of 218), memory impairment (44 [18·9%; 14·1-24·2] of 233), fatigue (61 [19·3%; 15·1-23·9] of 316), and in one study traumatic memories (55 [30·4%; 23·9-37·3] of 181) and sleep disorder (14 [100·0%; 88·0-100·0] of 14) were frequently reported. The meta-analysis indicated that in the post-illness stage the point prevalence of post-traumatic stress disorder was 32·2% (95% CI 23·7-42·0; 121 of 402 cases from four studies), that of depression was 14·9% (12·1-18·2; 77 of 517 cases from five studies), and that of anxiety disorders was 14·8% (11·1-19·4; 42 of 284 cases from three studies). 446 (76·9%; 95% CI 68·1-84·6) of 580 patients from six studies had returned to work at a mean follow-up time of 35·3 months (SD 40·1). When data for patients with COVID-19 were examined (including preprint data), there was evidence for delirium (confusion in 26 [65%] of 40 intensive care unit patients and agitation in 40 [69%] of 58 intensive care unit patients in one study, and altered consciousness in 17 [21%] of 82 patients who subsequently died in another study). At discharge, 15 (33%) of 45 patients with COVID-19 who were assessed had a dysexecutive syndrome in one study. At the time of writing, there were two reports of hypoxic encephalopathy and one report of encephalitis. 68 (94%) of the 72 studies were of either low or medium quality. Interpretation: If infection with SARS-CoV-2 follows a similar course to that with SARS-CoV or MERS-CoV, most patients should recover without experiencing mental illness. SARS-CoV-2 might cause delirium in a significant proportion of patients in the acute stage. Clinicians should be aware of the possibility of depression, anxiety, fatigue, post-traumatic stress disorder, and rarer neuropsychiatric syndromes in the longer term. Funding: Wellcome Trust, UK National Institute for Health Research (NIHR), UK Medical Research Council, NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London.

The lancet. Psychiatry · meta-analysis · 1531 citationsread the source →

Tailored or adapted interventions for adults with chronic obstructive pulmonary disease and at least one other long-term condition: a mixed methods review.

Background: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterised by shortness of breath, cough and recurrent exacerbations. People with COPD often live with one or more co-existing long-term health conditions (comorbidities). People with more severe COPD often have a higher number of comorbidities, putting them at greater risk of morbidity and mortality. Objectives: To assess the effectiveness of any single intervention for COPD adapted or tailored to their comorbidity(s) compared to any other intervention for people with COPD and one or more common comorbidities (quantitative data, RCTs) in terms of the following outcomes: Quality of life, exacerbations, functional status, all-cause and respiratory-related hospital admissions, mortality, pain, and depression and anxiety. To assess the effectiveness of an adapted or tailored single COPD intervention (simple or complex) that is aimed at changing the management of people with COPD and one or more common comorbidities (quantitative data, RCTs) compared to usual care in terms of the following outcomes: Quality of life, exacerbations, functional status, all-cause and respiratory-related hospital admissions, mortality, pain, and depression and anxiety. To identify emerging themes that describe the views and experiences of patients, carers and healthcare professionals when receiving or providing care to manage multimorbidities (qualitative data). Search methods: We searched multiple databases including the Cochrane Airways Trials Register, CENTRAL, MEDLINE, Embase, and CINAHL, to identify relevant randomised and qualitative studies. We also searched trial registries and conducted citation searches. The latest search was conducted in January 2021. Selection criteria: Eligible randomised controlled trials (RCTs) compared a) any single intervention for COPD adapted or tailored to their comorbidity(s) compared to any other intervention, or b) any adapted or tailored single COPD intervention (simple or complex) that is aimed at changing the management of people with COPD and one or more comorbidities, compared to usual care. We included qualitative studies or mixed-methods studies to identify themes. Data collection and analysis: We used standard Cochrane methods for analysis of the RCTs. We used Cochrane's risk of bias tool for the RCTs and the CASP checklist for the qualitative studies. We planned to use the Mixed Methods Appraisal tool (MMAT) to assess the risk of bias in mixed-methods studies, but we found none. We used GRADE and CERQual to assess the quality of the quantitative and qualitative evidence respectively. The primary outcome measures for this review were quality of life and exacerbations. Main results: Quantitative studies We included seven studies (1197 participants) in the quantitative analyses, with interventions including telemonitoring, pulmonary rehabilitation, treatment optimisation, water-based exercise training and case management. Interventions were either compared with usual care or with an active comparator (such as land-based exercise training). Duration of trials ranged from 4 to 52 weeks. Mean age of participants ranged from 64 to 72 years and COPD severity ranged from mild to very severe. Trials included either people with COPD and a specific comorbidity (including cardiovascular disease, metabolic syndrome, lung cancer, head or neck cancer, and musculoskeletal conditions), or with one or more comorbidities of any type. Overall, we judged the evidence presented to be of moderate to very low certainty (GRADE), mainly due to the methodological quality of included trials and imprecision of effect estimates. Intervention versus usual care Quality of life as measured by the St George's Respiratory Questionnaire (SGRQ) total score may improve with tailored pulmonary rehabilitation compared to usual care at 52 weeks (mean difference (MD) -10.85, 95% confidence interval (CI) -12.66 to -9.04; 1 study, 70 participants; low-certainty evidence). Tailored pulmonary rehabilitation is likely to improve COPD assessment test (CAT) scores compared with usual care at 52 weeks (MD -8.02, 95% CI -9.44 to -6.60; 1 study, 70 participants, moderate-certainty evidence) and with a multicomponent telehealth intervention at 52 weeks (MD -6.90, 95% CI -9.56 to -4.24; moderate-certainty evidence). Evidence is uncertain about effects of pharmacotherapy optimisation or telemonitoring interventions on CAT improvement compared with usual care. There may be little to no difference in the number of people experiencing exacerbations, or mean exacerbations with case management compared with usual care (OR 1.09, 95% CI 0.75 to 1.57; 1 study, 470 participants; very low-certainty evidence). For secondary outcomes, six-minute walk distance (6MWD) may improve with pulmonary rehabilitation, water-based exercise or multicomponent interventions at 38 to 52 weeks (low-certainty evidence). A multicomponent intervention may result in fewer people being admitted to hospital at 17 weeks, although there may be little to no difference in a telemonitoring intervention. There may be little to no difference between intervention and usual care for mortality. Intervention versus active comparator We included one study comparing water-based and land-based exercise (30 participants). We found no evidence for quality of life or exacerbations. There may be little to no difference between water- and land-based exercise for 6MWD (MD 5 metres, 95% CI -22 to 32; 38 participants; very low-certainty evidence). Qualitative studies One nested qualitative study (21 participants) explored perceptions and experiences of people with COPD and long-term conditions, and of researchers and health professionals who were involved in an RCT of telemonitoring equipment. Several themes were identified, including health status, beliefs and concerns, reliability of equipment, self-efficacy, perceived ease of use, factors affecting usefulness and perceived usefulness, attitudes and intention, self-management and changes in healthcare use. We judged the qualitative evidence presented as of very low certainty overall. Authors' conclusions: Owing to a paucity of eligible trials, as well as diversity in the intervention type, comorbidities and the outcome measures reported, we were unable to provide a robust synthesis of data. Pulmonary rehabilitation or multicomponent interventions may improve quality of life and functional status (6MWD), but the evidence is too limited to draw a robust conclusion. The key take-home message from this review is the lack of data from RCTs on treatments for people living with COPD and comorbidities. Given the variation in number and type of comorbidity(s) an individual may have, and severity of COPD, larger studies reporting individual patient data are required to determine these effects.

The Cochrane database of systematic reviews · meta-analysis · 24 citationsread the source →

Parental correlates in child and adolescent physical activity: a meta-analysis.

Objective: Physical activity (PA) has a profound impact on health and development in children. Parental behaviors (i.e., modeling and support) represent an obvious important factor in child PA. The purpose of this paper was to provide a comprehensive meta-analysis that overcomes the limitations of prior narrative reviews and quantitative reviews with small samples. Methods: Ten major databases were used in the literature search. One-hundred and fifteen studies passed the eligibility criteria. Both fixed and random effects models with correction for sampling and measurement error were examined in the analysis. Moderator analyses investigating the effects of child's developmental age, study design, parental gender, measurement of child PA, and quality rating were performed. Results: Based on the random effects model, the results showed that parental modeling was weakly associated with child PA (summary r = .16, 95% CI .09-.24) and none of the proposed moderators were significant. Separate analyses examining the moderating effects of parental gender and boys' PA found that that father-son PA modeling (r = .29, 95% CI .21-.36) was significantly higher compared to mother-son PA (r = .19, 95% CI .14-.23; p < .05). However, parental gender did not moderate the relationship between parental modeling and girls' PA (p > .05). The random effects model indicated an overall moderate effect size for the parental support and child PA relationship (summary r = .38, 95% CI .30-.46). Here, the only significant moderating variable was the measurement of child PA (objective: r = .20, 95% CI .13-.26; reported: r = .46, 95% CI .37-.55; p < .01). Conclusions: Parental support and modeling relate to child PA, yet our results revealed a significant degree of heterogeneity among the studies that could not be explained well by our proposed moderators.

The international journal of behavioral nutrition and physical activity · meta-analysis · 282 citationsread the source →

Cannabis-based medicines for chronic neuropathic pain in adults.

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

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

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

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

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

The Effects of Resistance Exercise Training on Anxiety: A Meta-Analysis and Meta-Regression Analysis of Randomized Controlled Trials.

Background: The salutary effects of resistance exercise training (RET) are well established, including increased strength and function; however, less is known regarding the effects of RET on mental health outcomes. Aerobic exercise has well-documented positive effects on anxiety, but a quantitative synthesis of RET effects on anxiety is needed. Objectives: To estimate the population effect size for resistance exercise training (RET) effects on anxiety and to determine whether variables of logical, theoretical, and/or prior empirical relation to anxiety moderate the overall effect. Methods: Thirty-one effects were derived from 16 articles published before February 2017, located using Google Scholar, MEDLINE, PsycINFO, PubMed, and Web of Science. Trials involved 922 participants (mean age = 43 ± 21 years, 68% female/32% male) and included both randomization to RET (n = 486) or a non-active control condition (n = 436), and a validated anxiety outcome measured at baseline, mid-, and/or post-intervention. Hedges' d effect sizes were computed and random effects models were used for all analyses. Meta-regression quantified the extent to which participant and trial characteristics moderated the mean effect. Results: RET significantly reduced anxiety symptoms (Δ = 0.31, 95% CI 0.17-0.44; z = 4.43; p < 0.001). Significant heterogeneity was not indicated (Q T(30) = 40.5, p > 0.09; I 2 = 28.3%, 95% CI 10.17-42.81); sampling error accounted for 77.7% of observed variance. Larger effects were found among healthy participants (Δ = 0.50, 95% CI 0.22-0.78) compared to participants with a physical or mental illness (Δ = 0.19, 95% CI 0.06-0.31, z = 2.16, p < 0.04). Effect sizes did not significantly vary according to sex (β = -0.31), age (β = -0.10), control condition (β = 0.08), program length (β = 0.07), session duration (β = 0.08), frequency (β = -0.10), intensity (β = -0.18), anxiety recall time frame (β = 0.21), or whether strength significantly improved (β = 0.19) (all p ≥ 0.06). Conclusions: RET significantly improves anxiety symptoms among both healthy participants and participants with a physical or mental illness. Improvements were not moderated by sex, or based on features of RET. Future trials should compare RET to other empirically-supported therapies for anxiety.

Sports medicine (Auckland, N.Z.) · meta-analysis · 180 citationsread the source →

Prevalence of symptoms of anxiety and depression in patients with inflammatory bowel disease: a systematic review and meta-analysis.

Background: Inflammatory bowel disease (IBD) is a lifelong condition with no cure. Patients with IBD might experience symptoms of common mental disorders such as anxiety and depression because of bidirectional communication via the gut-brain axis and chronicity of symptoms, and because of impaired quality of life and reduced social functioning. However, uncertainties remain about the magnitude of this problem. We aimed to assess prevalence of symptoms of anxiety or depression in adult patients with IBD. Methods: In this systematic review and meta-analysis, we searched MEDLINE, Embase, Embase Classic, and PsycINFO for papers published from inception to Sept 30, 2020, reporting observational studies that recruited at least 100 adult patients with IBD and that reported prevalence of symptoms of anxiety or depression according to validated screening instruments. We excluded studies that only used a structured interview to assess for these symptoms and studies that did not provide extractable data. We extracted data from published study reports and calculated pooled prevalences of symptoms of anxiety and depression, odds ratios (OR), and 95% CIs. Findings: Of 5544 studies identified, 77 fulfilled the eligibility criteria, including 30 118 patients in total. Overall, pooled prevalence of anxiety symptoms was 32·1% (95% CI 28·3-36·0) in 58 studies (I2=96·9%) and pooled prevalence of depression symptoms was 25·2% (22·0-28·5) in 75 studies (I2=97·6%). In studies that reported prevalence of anxiety or depression in patients with Crohn's disease and ulcerative colitis within the same study population, patients with Crohn's disease had higher odds of anxiety symptoms (OR 1·2, 95% CI 1·1-1·4) and depression symptoms (1·2, 1·1-1·4) than patients with ulcerative colitis. Overall, women with IBD were more likely to have symptoms of anxiety than were men with IBD (pooled prevalence 33·8% [95% CI 26·5-41·5] for women vs 22·8% [18·7-27·2] for men; OR 1·7 [95% CI 1·2-2·3]). They were also more likely to have symptoms of depression than men were (pooled prevalence 21·2% [95% CI 15·4-27·6] for women vs 16·2% [12·6-20·3] for men; OR 1·3 [95% CI 1·0-1·8]). The prevalence of symptoms of anxiety (57·6% [95% CI 38·6-75·4]) or depression (38·9% [26·2-52·3]) was higher in patients with active IBD than in patients with inactive disease (38·1% [30·9-45·7] for anxiety symptoms and 24·2% [14·7-35·3] for depression symptoms; ORs 2·5 [95% CI 1·5-4·1] for anxiety and 3·1 [1·9-4·9] for depression). Interpretation: There is a high prevalence of symptoms of anxiety and depression in patients with IBD, with up to a third of patients affected by anxiety symptoms and a quarter affected by depression symptoms. Prevalence was also increased in patients with active disease: half of these patients met criteria for anxiety symptoms and a third met criteria for depression symptoms. Encouraging gastroenterologists to screen for and treat these disorders might improve outcomes for patients with IBD. Funding: None.

The lancet. Gastroenterology & hepatology · meta-analysis · 514 citationsread the source →

Hepatitis B immunoglobulin during pregnancy for prevention of mother-to-child transmission of hepatitis B virus.

Background: Hepatitis is a viral infection of the liver. It is mainly transmitted between people through contact with infected blood, frequently from mother to baby in-utero. Hepatitis B poses significant risk to the fetus and up to 85% of infants infected by their mothers at birth develop chronic hepatitis B virus (HBV) infection. Hepatitis B immunoglobulin (HBIG) is a purified solution of human immunoglobulin that could be administered to the mother, newborn, or both. HBIG offers protection against HBV infection when administered to pregnant women who test positive for hepatitis B envelope antigen (HBeAg) or hepatitis B surface antigen (HBsAg), or both. When HBIG is administered to pregnant women, the antibodies passively diffuse across the placenta to the child. This materno-fetal diffusion is maximal during the third trimester of pregnancy. Up to 1% to 9% infants born to HBV-carrying mothers still have HBV infection despite the newborn receiving HBIG plus active HBV vaccine in the immediate neonatal period. This suggests that additional intervention such as HBIG administration to the mother during the antenatal period could be beneficial to reduce the transmission rate in utero. Objectives: To determine the benefits and harms of hepatitis B immunoglobulin (HBIG) administration to pregnant women during their third trimester of pregnancy for the prevention of mother-to-child transmission of hepatitis B virus infection. Search methods: We searched the The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, Science Citation Index Expanded (Web of Science), SCOPUS, African Journals OnLine, and INDEX MEDICUS up to June 2016. We searched ClinicalTrials.gov and portal of the WHO International Clinical Trials Registry Platform (ICTRP) in December 2016. Selection criteria: We included randomised clinical trials comparing HBIG versus placebo or no intervention in pregnant women with HBV. Data collection and analysis: Two authors extracted data independently. We analysed dichotomous outcome data using risk ratio (RR) and continuous outcome data using mean difference (MD) with 95% confidence intervals (CI). For meta-analyses, we used a fixed-effect model and a random-effects model, along with an assessment of heterogeneity. If there were statistically significant discrepancies in the results, we reported the more conservative point estimate. If the two estimates were equal, we used the estimate with the widest CI as our main result. We assessed bias control using the Cochrane Hepato-Biliary Group suggested bias risk domains and risk of random errors using Trial Sequential Analysis (TSA). We assessed the quality of the evidence using GRADE. Main results: All 36 included trials originated from China and were at overall high risk of bias. The trials included 6044 pregnant women who were HBsAg, HBeAg, or hepatitis B virus DNA (HBV-DNA) positive. Only seven trials reported inclusion of HBeAg-positive mothers. All 36 trials compared HBIG versus no intervention. None of the trials used placebo. Most of the trials assessed HBIG 100 IU (two trials) and HBIG 200 IU (31 trials). The timing of administration of HBIG varied; 30 trials administered three doses of HBIG 200 IU at 28, 32, and 36 weeks of pregnancy. None of the trials reported all-cause mortality or other serious adverse events in the mothers or babies. Serological signs of hepatitis B infection of the newborns were reported as HBsAg, HBeAg, and HBV-DNA positive results at end of follow-up. Twenty-nine trials reported HBsAg status in newborns (median 1.2 months of follow-up after birth; range 0 to 12 months); seven trials reported HBeAg status (median 1.1 months of follow-up after birth; range 0 to 12 months); and 16 trials reported HBV-DNA status (median 1.2 months of follow-up; range 0 to 12 months). HBIG reduced mother-to-child transmission (MTCT) of HBsAg when compared with no intervention (179/2769 (6%) with HBIG versus 537/2541 (21%) with no intervention; RR 0.30, TSA-adjusted CI 0.20 to 0.52; I2 = 36%; 29 trials; 5310 participants; very low quality evidence). HBV-DNA reduced MTCT of HBsAg (104/1112 (9%) with HBV-DNA versus 382/1018 (38%) with no intervention; RR 0.25, TSA-adjusted CI 0.22 to 0.27; I2 = 84%; 16 trials; 2130 participants; low quality evidence). TSA supported both results. Meta-analysis showed that maternal HBIG did not decrease HBeAg in newborns compared with no intervention (184/889 (21%) with HBIG versus 232/875 (27%) with no intervention; RR 0.68, TSA-adjusted CI 0.04 to 6.37; I2 = 90%; 7 trials; 1764 participants; very low quality evidence). TSA could neither support nor refute this observation as data were too sparse. None of the trials reported adverse events of the immunoglobulins on the newborns, presence of local and systemic adverse events on the mothers, or cost-effectiveness of treatment. Authors' conclusions: Due to very low to low quality evidence found in this review, we are uncertain of the effect of benefit of antenatal HBIG administration to the HBV-infected mothers on newborn outcomes, such as HBsAg, HBV-DNA, and HBeAg compared with no intervention. The results of the effects of HBIG on HBsAg and HBeAg are surrogate outcomes (raising risk of indirectness), and we need to be critical while interpreting the findings. We found no data on newborn mortality or maternal mortality or both, or other serious adverse events. Well-designed randomised clinical trials are needed to determine the benefits and harms of HBIG versus placebo in prevention of MTCT of HBV.

The Cochrane database of systematic reviews · meta-analysis · 42 citationsread the source →

Life-course accumulation of neighborhood disadvantage and allostatic load: empirical integration of three social determinants of health frameworks.

Objectives: We examined if the accumulation of neighborhood disadvantages from adolescence to mid-adulthood were related to allostatic load, a measure of cumulative biological risk, in mid-adulthood, and explored whether this association was similar in women and men. Methods: Data were from the participants in the Northern Swedish Cohort (analytical n = 818) at ages 16, 21, 30, and 43 years in 1981, 1986, 1995, and 2008. Personal living conditions were self-reported at each wave. At age 43 years, 12 biological markers were measured to operationalize allostatic load. Registered data for all residents in the cohort participants' neighborhoods at each wave were used to construct a cumulative measure of neighborhood disadvantage. Associations were examined in ordinary least-squares regression models. Results: We found that cumulative neighborhood disadvantage between ages 16 and 43 years was related to higher allostatic load at age 43 years after adjusting for personal living conditions in the total sample (B = 0.11; P = .004) and in men (B = 0.16; P = .004), but not in women (B = 0.07; P = .248). Conclusions: Our findings suggested that neighborhood disadvantage acted cumulatively over the life course on biological wear and tear, and exemplified the gains of integrating social determinants of health frameworks.

American journal of public health · 85 citationsread the source →

Feasibility of Formal Mindfulness-Based Stress-Resilience Training Among Surgery Interns

Importance: Among surgical trainees, burnout and distress are prevalent, but mindfulness has been shown to decrease the risk of depression, suicidal ideation, burnout, and overwhelming stress. In other high-stress populations, formal mindfulness training has been shown to improve mental health, yet this approach has not been tried in surgery. Objective: To test the feasibility and acceptability of modified Mindfulness-Based Stress Reduction (MBSR) training during surgical residency. Design, Setting, and Participants: A pilot randomized clinical trial of modified MBSR vs an active control was conducted with 21 surgical interns in a residency training program at a tertiary academic medical center, from April 30, 2016, to December 2017. Interventions: Weekly 2-hour, modified MBSR classes and 20 minutes of suggested daily home practice over an 8-week period. Main Outcomes and Measures: Feasibility was assessed along 6 domains (demand, implementation, practicality, acceptability, adaptation, and integration), using focus groups, interviews, surveys, attendance, daily practice time, and subjective self-report of experience. Results: Of the 21 residents included in the analysis, 13 were men (62%). Mean (SD [range]) age of the intervention group was 29.0 (2.4 [24-31]) years, and the mean (SD [range]) age of the control group was 27.4 (2.1 [27-33]) years. Formal stress-resilience training was feasible through cultivation of stakeholder support. Modified MBSR was acceptable as evidenced by no attrition; high attendance (12 of 96 absences [13%] in the intervention group and 11 of 72 absences [15%] in the control group); no significant difference in days per week practiced between groups; similar mean (SD) daily practice time between groups with significant differences only in week 1 (control, 28.15 [12.55] minutes; intervention, 15.47 [4.06] minutes; P = .02), week 2 (control, 23.89 [12.93] minutes; intervention, 12.61 [6.06] minutes; P = .03), and week 4 (control, 26.26 [13.12] minutes; intervention, 15.36 [6.13] minutes; P = .04); course satisfaction (based on interviews and focus group feedback); and posttraining-perceived credibility (control, 18.00 [4.24]; intervention, 20.00 [6.55]; P = .03). Mindfulness skills were integrated into personal and professional settings and the independent practice of mindfulness skills continued over 12 months of follow-up (mean days [SD] per week formal practice, 3 [1.0]). Conclusions and Relevance: Formal MBSR training is feasible and acceptable to surgical interns at a tertiary academic center. Interns found the concepts and skills useful both personally and professionally and participation had no detrimental effect on their surgical training or patient care. Trial Registration: ClinicalTrials.gov identifier: NCT03141190.

JAMA Surgery · randomised controlled trial · 130 citationsread the source →

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

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

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

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

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

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

Lifestyle Intervention in Gastroesophageal Reflux Disease.

Background & aims: Gastroesophageal reflux disease (GERD) affects up to 30% of adults in Western populations and is increasing in prevalence. GERD is associated with lifestyle factors, particularly obesity and tobacco smoking, which also threatens the patient's general health. GERD carries the risk of several adverse outcomes and there is widespread use of potent acid-inhibitors, which are associated with long-term adverse effects. The aim of this systematic review was to assess the role of lifestyle intervention in the treatment of GERD. Methods: Literature searches were performed in PubMed (from 1946), EMBASE (from 1980), and the Cochrane Library (no start date) to October 1, 2014. Meta-analyses, systematic reviews, randomized clinical trials (RCTs), and prospective observational studies were included. Results: Weight loss was followed by decreased time with esophageal acid exposure in 2 RCTs (from 5.6% to 3.7% and from 8.0% to 5.5%), and reduced reflux symptoms in prospective observational studies. Tobacco smoking cessation reduced reflux symptoms in normal-weight individuals in a large prospective cohort study (odds ratio, 5.67). In RCTs, late evening meals increased time with supine acid exposure compared with early meals (5.2% point change), and head-of-the-bed elevation decreased time with supine acid exposure compared with a flat position (from 21% to 15%). Conclusions: Weight loss and tobacco smoking cessation should be recommended to GERD patients who are obese and smoke, respectively. Avoiding late evening meals and head-of-the-bed elevation is effective in nocturnal GERD.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · systematic review · 179 citationsread the source →

Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.

Background: Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide in adults. Pharmacological and non-pharmacological treatments are available; however, because of inadequate resources, antidepressants are used more frequently than psychological interventions. Prescription of these agents should be informed by the best available evidence. Therefore, we aimed to update and expand our previous work to compare and rank antidepressants for the acute treatment of adults with unipolar major depressive disorder. Methods: We did a systematic review and network meta-analysis. We searched Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, PsycINFO, the websites of regulatory agencies, and international registers for published and unpublished, double-blind, randomised controlled trials from their inception to Jan 8, 2016. We included placebo-controlled and head-to-head trials of 21 antidepressants used for the acute treatment of adults (≥18 years old and of both sexes) with major depressive disorder diagnosed according to standard operationalised criteria. We excluded quasi-randomised trials and trials that were incomplete or included 20% or more of participants with bipolar disorder, psychotic depression, or treatment-resistant depression; or patients with a serious concomitant medical illness. We extracted data following a predefined hierarchy. In network meta-analysis, we used group-level data. We assessed the studies' risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions, and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. Primary outcomes were efficacy (response rate) and acceptability (treatment discontinuations due to any cause). We estimated summary odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with PROSPERO, number CRD42012002291. Findings: We identified 28 552 citations and of these included 522 trials comprising 116 477 participants. In terms of efficacy, all antidepressants were more effective than placebo, with ORs ranging between 2·13 (95% credible interval [CrI] 1·89-2·41) for amitriptyline and 1·37 (1·16-1·63) for reboxetine. For acceptability, only agomelatine (OR 0·84, 95% CrI 0·72-0·97) and fluoxetine (0·88, 0·80-0·96) were associated with fewer dropouts than placebo, whereas clomipramine was worse than placebo (1·30, 1·01-1·68). When all trials were considered, differences in ORs between antidepressants ranged from 1·15 to 1·55 for efficacy and from 0·64 to 0·83 for acceptability, with wide CrIs on most of the comparative analyses. In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19-1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51-0·84). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43-0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates (1·30-2·32). 46 (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low; and the certainty of evidence was moderate to very low. Interpretation: All antidepressants were more efficacious than placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the analysis, whereas there was more variability in efficacy and acceptability in head-to-head trials. These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants. Funding: National Institute for Health Research Oxford Health Biomedical Research Centre and the Japan Society for the Promotion of Science.

Lancet (London, England) · systematic review · 2220 citationsread the source →

Low-amplitude, left vagus nerve stimulation significantly attenuates ventricular dysfunction and infarct size through prevention of mitochondrial dysfunction during acute ischemia-reperfusion injury.

Background: Right cervical vagus nerve stimulation (VNS) provides cardioprotective effects against acute ischemia-reperfusion injury in small animals. However, inconsistent findings have been reported. Objective: To determine whether low-amplitude, left cervical VNS applied either intermittently or continuously imparts cardioprotection against acute ischemia-reperfusion injury. Methods: Thirty-two isoflurane-anesthetized swine (25-30 kg) were randomized into 4 groups: control (sham operated, no VNS), continuous-VNS (C-VNS; 3.5 mA, 20 Hz), intermittent-VNS (I-VNS; continuously recurring cycles of 21-second ON, 30-second OFF), and I-VNS + atropine (1 mg/kg). Left cervical VNS was applied immediately after left anterior descending artery occlusion (60 minutes) and continued until the end of reperfusion (120 minutes). The ischemic and nonischemic myocardium was harvested for cardiac mitochondrial function assessment. Results: VNS significantly reduced infarct size, improved ventricular function, decreased ventricular fibrillation episodes, and attenuated cardiac mitochondrial reactive oxygen species production, depolarization, and swelling, compared with the control group. However, I-VNS produced the most profound cardioprotective effects, particularly infarct size reduction and decreased ventricular fibrillation episodes, compared to both I-VNS + atropine and C-VNS. These beneficial effects of VNS were abolished by atropine. Conclusions: During ischemia-reperfusion injury, both C-VNS and I-VNS provide significant cardioprotective effects compared with I-VNS + atropine. These beneficial effects were abolished by muscarinic blockade, suggesting the importance of muscarinic receptor modulation during VNS. The protective effects of VNS could be due to its protection of mitochondrial function during ischemia-reperfusion.

Heart rhythm · 99 citationsread the source →

Symptoms and coping in Sri Lanka 20-21 months after the 2004 tsunami.

Background: The estimated prevalence of clinically significant psychiatric and somatic symptoms in adults >1 year after the 2004 Asian tsunami is unknown. Aims: To estimate the prevalence of psychiatric and somatic symptoms and impairment in Sri Lanka 20-21 months after the 2004 Asian tsunami, and to assess coping strategies used by tsunami-affected individuals that contribute to post-tsunami adjustment. Method: Homes from one severely affected area were randomly selected, and adult respondents were sampled utilising a modified Kish method. Instruments were administered in Sinhala to assess exposure, post-traumatic stress disorder (PTSD), depression, anxiety, somatic distress and impairment. Demographic variables and culturally-relevant coping activities were assessed. Results: The prevalence of clinically significant PTSD, depression and anxiety was 21%, 16% and 30% respectively. Respondents reported a mean of eight persistent and bothersome somatic complaints, which were associated with psychiatric symptoms and impairment. Thinking that one's life was in danger was the exposure item most strongly associated with symptoms and impairment. The majority of respondents found their own strength, family and friends, a Western-style hospital and their religious practice to be the most helpful coping aids. Conclusions: A large minority of adults in one area of Sri Lanka reported significant psychiatric and somatic symptoms and impairment 20-21 months after the tsunami. Accurate data about risk for and resilience to impairing symptoms >1 year after disasters are necessary in order to develop rational surveillance and interventions.

The British journal of psychiatry : the journal of mental science · 65 citationsread the source →

Human and economic burden of GAD, subthreshold GAD, and worry in a primary care sample.

Generalized anxiety disorder (GAD) has been associated with significant impairment and estimates of human and economic burden associated with the disorder are substantial. Little has been done, however, to examine impairment associated with subthreshold presentations of the disorder in medically underserved populations. This study compared primary care patients with GAD (n = 30), subthreshold GAD (n = 21), worry (n = 79), and no worry (n = 199) on measures of human and economic burden. On measures of human burden, all three symptomatic groups reported poorer perceived physical health, greater stress, and sleep difficulty. Worried and subthreshold groups also reported lower social support. For economic burden, GAD and worry groups reported a greater number of prescription medications. However, when co-morbid depression was accounted for the effect was no longer significant. Groups did not differ on employment status, number of visits to the clinic in the last 90 days, or physical health. Results are discussed in terms of identification, prevention, and intervention for GAD in primary care settings.

Journal of clinical psychology in medical settings · 31 citationsread the source →

The Effect of Heart Rate Variability Biofeedback Training on Mental Health of Pregnant and Non-Pregnant Women: A Randomized Controlled Trial.

In this study, we examined the efficacy of heart rate variability (HRV)-biofeedback on stress and stress-related mental health problems in women. Furthermore, we examined whether the efficacy differed between pregnant and non-pregnant women. Fifty women (20 pregnant, 30 non-pregnant; mean age 31.6, SD = 5.9) were randomized into an intervention (n = 29) or a waitlist condition (n = 21). All participants completed questionnaires on stress, anxiety, depressive symptoms, sleep, and psychological well-being on three occasions with 6-week intervals. Women in the intervention condition received HRV-biofeedback training between assessment 1 and 2, and women in the waitlist condition received the intervention between assessment 2 and 3. The intervention consisted of a 5-week HRV-biofeedback training program with weekly 60⁻90 min. sessions and daily exercises at home. Results indicated a statistically significant beneficial effect of HRV-biofeedback on psychological well-being for all women, and an additional statistically significant beneficial effect on anxiety complaints for pregnant women. No significant effect was found for the other stress-related complaints. These findings support the use of HRV-biofeedback as a stress-reducing technique among women reporting stress and related complaints in clinical practice to improve their well-being. Furthermore, it supports the use of this technique for reducing anxiety during pregnancy.

International journal of environmental research and public health · randomised controlled trial · 23 citationsread the source →

Does Mindfulness-Based Cognitive Therapy for Migraine Reduce Migraine-Related Disability in People with Episodic and Chronic Migraine? A Phase 2b Pilot Randomized Clinical Trial.

Objective: The current Phase 2b study aimed to evaluate the efficacy of mindfulness-based cognitive therapy for migraine (MBCT-M) to reduce migraine-related disability in people with migraine. Background: Mindfulness-based interventions represent a promising avenue to investigate effects in people with migraine. MBCT teaches mindfulness meditation and cognitive-behavioral skills and directly applies these skills to address disease-related cognitions. Methods: Participants with migraine (6-30 headache days/month) were recruited from neurology office referrals and local and online advertisements in the broader New York City area. During the 30-day baseline period, all participants completed a daily headache diary. Participants who met inclusion and exclusion criteria were randomized in a parallel design, stratified by chronic migraine status, to receive either 8 weekly individual MBCT-M sessions or 8 weeks of waitlist/treatment as usual (WL/TAU). All participants completed surveys including primary outcome evaluations at Months 0, 1, 2, and 4. All participants completed a headache diary during the 30-day posttreatment evaluation period. Primary outcomes were the change from Month 0 to Month 4 in the headache disability inventory (HDI) and the Migraine Disability Assessment (MIDAS) (total score ≥ 21 indicating severe disability); secondary outcomes (headache days/30 days, average headache attack pain intensity, and attack-level migraine-related disability [Migraine Disability Index (MIDI)]) were derived from the daily headache diary. Results: Sixty participants were randomized to receive MBCT-M (n = 31) or WL/TAU (n = 29). Participants (M age = 40.1, SD = 11.7) were predominantly White (n = 49/60; 81.7%) and Non-Hispanic (N = 50/60; 83.3%) women (n = 55/60; 91.7%) with a graduate degree (n = 35/60; 55.0%) who were working full-time (n = 38/60; 63.3%). At baseline, the average HDI score (51.4, SD = 19.0) indicated a moderate level of disability and the majority of participants (50/60, 83.3%) fell in the "Severe Disability" range in the MIDAS. Participants recorded an average of 16.0 (SD = 5.9) headache days/30 days, with an average headache attack pain intensity of 1.7 on a 4-point scale (SD = 0.3), indicating moderate intensity. Average levels of daily disability reported on the MIDI were 3.1/10 (SD = 1.8). For the HDI, mean scores decreased more from Month 0 to Month 4 in the MBCT-M group (-14.3) than the waitlist/treatment as an usual group (-0.2; P < .001). For the MIDAS, the group*month interaction was not significant when accounting for the divided alpha, P = .027; across all participants in both groups, the estimated proportion of participants falling in the "Severe Disability" category fell significantly from 88.3% at Month 0 to 66.7% at Month 4, P < .001. For diary-reported headache days/30 days an average headache attack pain intensity, neither the group*month interaction (Ps = .773 and .888, respectively) nor the time effect (Ps = .059 and .428, respectively) was significant. Mean MIDI scores decreased in the MBCT-M group (-0.6/10), whereas they increased in the waitlist/treatment as an usual group (+0.3/10), P = .007. Conclusions: MBCT-M demonstrated efficacy to reduce headache-related disability and attack-level migraine-related disability. MBCT-M is a promising emerging treatment for addressing migraine-related disability.

Headache · randomised controlled trial · 75 citationsread the source →

Effect of Computer-Assisted Cognitive Behavior Therapy vs Usual Care on Depression Among Adults in Primary Care: A Randomized Clinical Trial.

Importance: Depression is a common disorder that may go untreated or receive suboptimal care in primary care settings. Computer-assisted cognitive behavior therapy (CCBT) has been proposed as a method for improving access to effective psychotherapy, reducing cost, and increasing the convenience and efficiency of treatment for depression. Objectives: To evaluate whether clinician-supported CCBT is more effective than treatment as usual (TAU) in primary care patients with depression and to examine the feasibility and implementation of CCBT in a primary care population with substantial numbers of patients with low income, limited internet access, and low levels of educational attainment. Design, setting, and participants: This randomized clinical trial included adult primary care patients from clinical practices at the University of Louisville who scored 10 or greater on the Patient Health Questionnaire-9 (PHQ-9) and were randomly assigned to CCBT or TAU for 12 weeks of active treatment. Follow-up assessments were conducted 3 and 6 months after treatment completion. Enrollment occurred from June 24, 2016, to May 13, 2019. The last follow-up assessment was conducted on January 30, 2020. Interventions: CCBT included use of the 9-lesson computer program Good Days Ahead, along with as many as 12 weekly telephonic support sessions of approximately 20 minutes with a master's level therapist, in addition to TAU, which consisted of the standard clinical management procedures at the primary care sites. TAU was uncontrolled, but use of antidepressants and psychotherapy other than CCBT was recorded. Main outcomes and measures: The primary outcome measure (PHQ-9) and secondary outcome measures (Automatic Thoughts Questionnaire for negative cognitions, Generalized Anxiety Disorder-7, and the Satisfaction with Life Scale for quality of life) were administered at baseline, 12 weeks, and 3 and 6 months after treatment completion. Satisfaction with treatment was assessed with the Client Satisfaction Questionnaire-8. Results: The sample of 175 patients was predominately female (147 of 174 [84.5%]) and had a high proportion of individuals who identified as racial and ethnic minority groups (African American, 44 of 162 patients who reported [27.2%]; American Indian or Alaska Native, 2 [1.2%]; Hispanic, 4 [2.5%]; multiracial, 14 [8.6%]). An annual income of less than $30 000 was reported by 88 of 143 patients (61.5%). Overall, 95 patients (54.3%) were randomly assigned to CCBT and 80 (45.7%) to TAU. Dropout rates were 22.1% for CCBT (21 patients) and 30.0% for TAU (24 patients). An intent-to-treat analysis found that CCBT led to significantly greater improvement in PHQ-9 scores than TAU at posttreatment (mean difference, -2.5; 95% CI, -4.5 to -0.8; P = .005) and 3 month (mean difference, -2.3; 95% CI, -4.5 to -0.8; P = .006) and 6 month (mean difference, -3.2; 95% CI, -4.5 to -0.8; P = .007) follow-up points. Posttreatment response and remission rates were also significantly higher for CCBT (response, 58.4% [95% CI, 46.4-70.4%]; remission, 27.3% [95% CI, 16.4%-38.2%]) than TAU (response, 33.1% [95% CI, 20.7%-45.5%]; remission, 12.0% [95% CI, 3.3%- 20.7%]). Conclusions and relevance: In this randomized clinical trial, CCBT was found to have significantly greater effects on depressive symptoms than TAU in primary care patients with depression. Because the study population included people with lower income and lack of internet access who typically have been underrepresented or not included in earlier investigations of CCBT, results suggest that this form of treatment can be acceptable and useful in diverse primary care settings. Additional studies with larger samples are needed to address implementation procedures that could enhance the effectiveness of CCBT and to examine potential factors associated with treatment outcome. Trial registration: ClinicalTrials.gov Identifier: NCT02700009.

JAMA network open · randomised controlled trial · 23 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 →

Improving quit rates of web-delivered interventions for smoking cessation: full-scale randomized trial of WebQuit.org versus Smokefree.gov.

Background and aims: Millions of people world-wide use websites to help them quit smoking, but effectiveness trials have an average 34% follow-up data retention rate and an average 9% quit rate. We compared the quit rates of a website using a new behavioral approach called Acceptance and Commitment Therapy (ACT; WebQuit.org) with the current standard of the National Cancer Institute's (NCI) Smokefree.gov website. Design: A two-arm stratified double-blind individually randomized trial (n = 1319 for WebQuit; n = 1318 for Smokefree.gov) with 12-month follow-up. Setting: United States. Participants: Adults (n = 2637) who currently smoked at least five cigarettes per day were recruited from March 2014 to August 2015. At baseline, participants were mean [standard deviation (SD)] age 46.2 years (13.4), 79% women and 73% white. Interventions: WebQuit.org website (experimental) provided ACT for smoking cessation; Smokefree.gov website (comparison) followed US Clinical Practice Guidelines for smoking cessation. Measurements: The primary outcome was self-reported 30-day point prevalence abstinence at 12 months. Findings: The 12-month follow-up data retention rate was 88% (2309 of 2637). The 30-day point prevalence abstinence rates at the 12-month follow-up were 24% (278 of 1141) for WebQuit.org and 26% (305 of 1168) for Smokefree.gov [odds ratio (OR) = 0.91; 95% confidence interval (CI) = 0.76, 1.10; P = 0.334] in the a priori complete case analysis. Abstinence rates were 21% (278 of 1319) for WebQuit.org and 23% (305 of 1318) for Smokefree.gov (OR = 0.89 (0.74, 1.07; P = 0.200) when missing cases were imputed as smokers. The Bayes factor comparing the primary abstinence outcome was 0.17, indicating 'substantial' evidence of no difference between groups. Conclusions: WebQuit.org and Smokefree.gov had similar 30-day point prevalence abstinence rates at 12 months that were descriptively higher than those of prior published website-delivered interventions and telephone counselor-delivered interventions.

Addiction (Abingdon, England) · randomised controlled trial · 71 citationsread the source →

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

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

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

A three-step support strategy for relatives of patients dying in the intensive care unit: a cluster randomised trial.

Background: In relatives of patients dying in intensive care units (ICUs), inadequate team support can increase the prevalence of prolonged grief and other psychological harm. We aimed to evaluate whether a proactive communication and support intervention would improve relatives' outcomes. Methods: We undertook a prospective, multicentre, cluster randomised controlled trial in 34 ICUs in France, to compare standard care with a physician-driven, nurse-aided, three-step support strategy for families throughout the dying process, following a decision to withdraw or withhold life support. Inclusion criteria were relatives of patients older than 18 years with an ICU length of stay 2 days or longer. Participating ICUs were randomly assigned (1:1 ratio) into an intervention cluster and a control cluster. The randomisation scheme was generated centrally by a statistician not otherwise involved in the study, using permutation blocks of non-released size. In the intervention group, three meetings were held with relatives: a family conference to prepare the relatives for the imminent death, an ICU-room visit to provide active support, and a meeting after the patient's death to offer condolences and closure. ICUs randomly assigned to the control group applied their best standard of care in terms of support and communication with relatives of dying patients. The primary endpoint was the proportion of relatives with prolonged grief (measured with PG-13, score ≥30) 6 months after the death. Analysis was by intention to treat, with the bereaved relatives as the unit of observation. The study is registered with ClinicalTrials.gov, NCT02955992. Findings: Between Feb 23, 2017, and Oct 8, 2019, we enrolled 484 relatives of ICU patients to the intervention group and 391 to the control group. 379 (78%) relatives in the intervention group and 309 (79%) in the control group completed the 6-month interview to measure the primary endpoint. The intervention significantly reduced the number of relatives with prolonged grief symptoms (66 [21%] vs 57 [15%]; p=0·035) and the median PG-13 score was significantly lower in the intervention group than in the control group (19 [IQR 14-26] vs 21 [15-29], mean difference 2·5, 95% CI 1·04-3·95). Interpretation: Among relatives of patients dying in the ICU, a physician-driven, nurse-aided, three-step support strategy significantly reduced prolonged grief symptoms. Funding: French Ministry of Health.

Lancet (London, England) · randomised controlled trial · 76 citationsread the source →

Use of the Healthy Lifestyle Coaching Chatbot App to Promote Stair-Climbing Habits Among Office Workers: Exploratory Randomized Controlled Trial

BACKGROUND: Lack of time for exercise is common among office workers given their busy lives. Because of occupational restrictions and difficulty in taking time off, it is necessary to suggest effective ways for workers to exercise regularly. Sustaining lifestyle habits that increase nonexercise activity in daily life can solve the issue of lack of exercise time. Healthy Lifestyle Coaching Chatbot is a messenger app based on the habit formation model that can be used as a tool to provide a health behavior intervention that emphasizes the importance of sustainability and involvement. OBJECTIVE: This study aimed to assess the efficacy of the Healthy Lifestyle Coaching Chatbot intervention presented via a messenger app aimed at stair-climbing habit formation for office workers. METHODS: From February 1, 2018, to April 30, 2018, a total of 106 people participated in the trial after online recruitment. Participants were randomly assigned to the intervention group (n=57) or the control group (n=49). The intervention group received cues and intrinsic and extrinsic rewards for the entire 12 weeks. However, the control group did not receive intrinsic rewards for the first 4 weeks and only received all rewards as in the intervention group from the fifth to twelfth week. The Self-Report Habit Index (SRHI) of participants was evaluated every week, and the level of physical activity was measured at the beginning and end of the trial. SPSS Statistics version 21 (IBM Corp) was used for statistical analysis. RESULTS: After 4 weeks of intervention without providing the intrinsic rewards in the control group, the change in SRHI scores was 13.54 (SD 14.99) in the intervention group and 6.42 (SD 9.42) in the control group, indicating a significant difference between the groups (P=.04). When all rewards were given to both groups, from the fifth to twelfth week, the change in SRHI scores of the intervention and control groups was comparable at 12.08 (SD 10.87) and 15.88 (SD 13.29), respectively (P=.21). However, the level of physical activity showed a significant difference between the groups after 12 weeks of intervention (P=.045). CONCLUSIONS: This study provides evidence that intrinsic rewards are important to enhance the sustainability and effectiveness of an intervention. The Healthy Lifestyle Coaching Chatbot program can be a cost-effective method for healthy habit formation. TRIAL REGISTRATION: Clinical Research Information Service KCT0004009; https://tinyurl.com/w4oo7md.

JMIR mhealth and uhealth · randomised controlled trial · 95 citationsread the source →

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

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

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

Randomized Trial of Communication Facilitators to Reduce Family Distress and Intensity of End-of-Life Care.

Rationale: Communication with family of critically ill patients is often poor and associated with family distress. Objectives: To determine if an intensive care unit (ICU) communication facilitator reduces family distress and intensity of end-of-life care. Methods: We conducted a randomized trial at two hospitals. Eligible patients had a predicted mortality greater than or equal to 30% and a surrogate decision maker. Facilitators supported communication between clinicians and families, adapted communication to family needs, and mediated conflict. Measurements and main results: Outcomes included depression, anxiety, and post-traumatic stress disorder (PTSD) among family 3 and 6 months after ICU and resource use. We identified 488 eligible patients and randomized 168. Of 352 eligible family members, 268 participated (76%). Family follow-up at 3 and 6 months ranged from 42 to 47%. The intervention was associated with decreased depressive symptoms at 6 months (P = 0.017), but there were no significant differences in psychological symptoms at 3 months or anxiety or PTSD at 6 months. The intervention was not associated with ICU mortality (25% control vs. 21% intervention; P = 0.615) but decreased ICU costs among all patients (per patient: $75,850 control, $51,060 intervention; P = 0.042) and particularly among decedents ($98,220 control, $22,690 intervention; P = 0.028). Among decedents, the intervention reduced ICU and hospital length of stay (28.5 vs. 7.7 d and 31.8 vs. 8.0 d, respectively; P < 0.001). Conclusions: Communication facilitators may be associated with decreased family depressive symptoms at 6 months, but we found no significant difference at 3 months or in anxiety or PTSD. The intervention reduced costs and length of stay, especially among decedents. This is the first study to find a reduction in intensity of end-of-life care with similar or improved family distress. Clinical trial registered with www.clinicaltrials.gov (NCT 00720200).

American journal of respiratory and critical care medicine · randomised controlled trial · 263 citationsread the source →

Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial.

Background: Systemic relapses remain a major problem in locally advanced rectal cancer. Using short-course radiotherapy followed by chemotherapy and delayed surgery, the Rectal cancer And Preoperative Induction therapy followed by Dedicated Operation (RAPIDO) trial aimed to reduce distant metastases without compromising locoregional control. Methods: In this multicentre, open-label, randomised, controlled, phase 3 trial, participants were recruited from 54 centres in the Netherlands, Sweden, Spain, Slovenia, Denmark, Norway, and the USA. Patients were eligible if they were aged 18 years or older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, had a biopsy-proven, newly diagnosed, primary, locally advanced rectal adenocarcinoma, which was classified as high risk on pelvic MRI (with at least one of the following criteria: clinical tumour [cT] stage cT4a or cT4b, extramural vascular invasion, clinical nodal [cN] stage cN2, involved mesorectal fascia, or enlarged lateral lymph nodes), were mentally and physically fit for chemotherapy, and could be assessed for staging within 5 weeks before randomisation. Eligible participants were randomly assigned (1:1), using a management system with a randomly varying block design (each block size randomly chosen to contain two to four allocations), stratified by centre, ECOG performance status, cT stage, and cN stage, to either the experimental or standard of care group. All investigators remained masked for the primary endpoint until a prespecified number of events was reached. Patients allocated to the experimental treatment group received short-course radiotherapy (5 × 5 Gy over a maximum of 8 days) followed by six cycles of CAPOX chemotherapy (capecitabine 1000 mg/m2 orally twice daily on days 1-14, oxaliplatin 130 mg/m2 intravenously on day 1, and a chemotherapy-free interval between days 15-21) or nine cycles of FOLFOX4 (oxaliplatin 85 mg/m2 intravenously on day 1, leucovorin [folinic acid] 200 mg/m2 intravenously on days 1 and 2, followed by bolus fluorouracil 400 mg/m2 intravenously and fluorouracil 600 mg/m2 intravenously for 22 h on days 1 and 2, and a chemotherapy-free interval between days 3-14) followed by total mesorectal excision. Choice of CAPOX or FOLFOX4 was per physician discretion or hospital policy. Patients allocated to the standard of care group received 28 daily fractions of 1·8 Gy up to 50·4 Gy or 25 fractions of 2·0 Gy up to 50·0 Gy (per physician discretion or hospital policy), with concomitant twice-daily oral capecitabine 825 mg/m2 followed by total mesorectal excision and, if stipulated by hospital policy, adjuvant chemotherapy with eight cycles of CAPOX or 12 cycles of FOLFOX4. The primary endpoint was 3-year disease-related treatment failure, defined as the first occurrence of locoregional failure, distant metastasis, new primary colorectal tumour, or treatment-related death, assessed in the intention-to-treat population. Safety was assessed by intention to treat. This study is registered with the EudraCT, 2010-023957-12, and ClinicalTrials.gov, NCT01558921, and is now complete. Findings: Between June 21, 2011, and June 2, 2016, 920 patients were enrolled and randomly assigned to a treatment, of whom 912 were eligible (462 in the experimental group; 450 in the standard of care group). Median follow-up was 4·6 years (IQR 3·5-5·5). At 3 years after randomisation, the cumulative probability of disease-related treatment failure was 23·7% (95% CI 19·8-27·6) in the experimental group versus 30·4% (26·1-34·6) in the standard of care group (hazard ratio 0·75, 95% CI 0·60-0·95; p=0·019). The most common grade 3 or higher adverse event during preoperative therapy in both groups was diarrhoea (81 [18%] of 460 patients in the experimental group and 41 [9%] of 441 in the standard of care group) and neurological toxicity during adjuvant chemotherapy in the standard of care group (16 [9%] of 187 patients). Serious adverse events occurred in 177 (38%) of 460 participants in the experimental group and, in the standard of care group, in 87 (34%) of 254 patients without adjuvant chemotherapy and in 64 (34%) of 187 with adjuvant chemotherapy. Treatment-related deaths occurred in four participants in the experimental group (one cardiac arrest, one pulmonary embolism, two infectious complications) and in four participants in the standard of care group (one pulmonary embolism, one neutropenic sepsis, one aspiration, one suicide due to severe depression). Interpretation: The observed decreased probability of disease-related treatment failure in the experimental group is probably indicative of the increased efficacy of preoperative chemotherapy as opposed to adjuvant chemotherapy in this setting. Therefore, the experimental treatment can be considered as a new standard of care in high-risk locally advanced rectal cancer. Funding: Dutch Cancer Foundation, Swedish Cancer Society, Spanish Ministry of Economy and Competitiveness, and Spanish Clinical Research Network.

The Lancet. Oncology · randomised controlled trial · 1212 citationsread the source →

Internet-Assisted Parent Training Intervention for Disruptive Behavior in 4-Year-Old Children: A Randomized Clinical Trial.

Importance: There is a large gap worldwide in the provision of evidence-based early treatment of children with disruptive behavioral problems. Objective: To determine whether an Internet-assisted intervention using whole-population screening that targets the most symptomatic 4-year-old children is effective at 6 and 12 months after the start of treatment. Design, setting, and participants: This 2-parallel-group randomized clinical trial was performed from October 1, 2011, through November 30, 2013, at a primary health care clinic in Southwest Finland. Data analysis was performed from August 6, 2015, to December 11, 2015. Of a screened population of 4656 children, 730 met the screening criteria indicating a high level of disruptive behavioral problems. A total of 464 parents of 4-year-old children were randomized into the Strongest Families Smart Website (SFSW) intervention group (n = 232) or an education control (EC) group (n = 232). Interventions: The SFSW intervention, an 11-session Internet-assisted parent training program that included weekly telephone coaching. Main outcomes and measures: Child Behavior Checklist version for preschool children (CBCL/1.5-5) externalizing scale (primary outcome), other CBCL/1.5-5 scales and subscores, Parenting Scale, Inventory of Callous-Unemotional Traits, and the 21-item Depression, Anxiety, and Stress Scale. All data were analyzed by intention to treat and per protocol. The assessments were made before randomization and 6 and 12 months after randomization. Results: Of the children randomized, 287 (61.9%) were male and 79 (17.1%) lived in other than a family with 2 biological parents. At 12-month follow-up, improvement in the SFSW intervention group was significantly greater compared with the control group on the following measures: CBCL/1.5-5 externalizing scale (effect size, 0.34; P < .001), internalizing scale (effect size, 0.35; P < .001), and total scores (effect size, 0.37; P < .001); 5 of 7 syndrome scales, including aggression (effect size, 0.36; P < .001), sleep (effect size, 0.24; P = .002), withdrawal (effect size, 0.25; P = .005), anxiety (effect size, 0.26; P = .003), and emotional problems (effect size, 0.31; P = .001); Inventory of Callous-Unemotional Traits callousness scores (effect size, 0.19; P = .03); and self-reported parenting skills (effect size, 0.53; P < .001). Conclusions and relevance: The study reveals the effectiveness and feasibility of an Internet-assisted parent training intervention offered for parents of preschool children with disruptive behavioral problems screened from the whole population. The strategy of population-based screening of children at an early age to offering parent training using digital technology and telephone coaching is a promising public health strategy for providing early intervention for a variety of child mental health problems. Trial registration: clinicaltrials.gov Identifier: NCT01750996.

JAMA psychiatry · randomised controlled trial · 99 citationsread the source →