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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 →

Evaluation of a Violence-Prevention Programme with Jamaican Primary School Teachers: A Cluster Randomised Trial.

This study investigated the effect of a school-based violence prevention programme implemented in Grade 1 classrooms in Jamaican primary schools. Fourteen primary schools were randomly assigned to receive training in classroom behaviour management (n = 7 schools, 27 teachers/classrooms) or to a control group (n = 7 schools, 28 teachers/classrooms). Four children from each class were randomly selected to participate in the evaluation (n = 220 children). Teachers were trained through a combination of workshop and in-class support sessions, and received a mean of 11.5 h of training (range = 3-20) over 8 months. The primary outcomes were observations of (1) teachers' use of violence against children and (2) class-wide child aggression. Teachers in intervention schools used significantly less violence against children (effect size (ES) = -0.73); benefits to class-wide child aggression were not significant (ES = -0.20). Intervention teachers also provided a more emotionally supportive classroom environment (ES = 1.22). No benefits were found to class-wide prosocial behaviour, teacher wellbeing, or child mental health. The intervention benefited children's early learning skills, especially oral language and self-regulation skills (ES = 0.25), although no benefits were found to achievement in maths calculation, reading and spelling. A relatively brief teacher-training programme reduced violence against children by teachers and increased the quality of the classroom environment.

International journal of environmental research and public health · randomised controlled trial · 19 citationsread the source →

3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial.

Background: Post-traumatic stress disorder (PTSD) is prevalent in military personnel and first responders, many of whom do not respond to currently available treatments. This study aimed to assess the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treating chronic PTSD in this population. Methods: We did a randomised, double-blind, dose-response, phase 2 trial at an outpatient psychiatric clinic in the USA. We included service personnel who were 18 years or older, with chronic PTSD duration of 6 months or more, and who had a Clinician-Administered PTSD Scale (CAPS-IV) total score of 50 or greater. Using a web-based randomisation system, we randomly assigned participants (1:1:2) to three different dose groups of MDMA plus psychotherapy: 30 mg (active control), 75 mg, or 125 mg. We masked investigators, independent outcome raters, and participants until after the primary endpoint. MDMA was administered orally in two 8-h sessions with concomitant manualised psychotherapy. The primary outcome was mean change in CAPS-IV total score from baseline to 1 month after the second experimental session. Participants in the 30 mg and 75 mg groups subsequently underwent three 100-125 mg MDMA-assisted psychotherapy sessions in an open-label crossover, and all participants were assessed 12 months after the last MDMA session. Safety was monitored through adverse events, spontaneously reported expected reactions, vital signs, and suicidal ideation and behaviour. This study is registered with ClinicalTrials.gov, number NCT01211405. Findings: Between Nov 10, 2010, and Jan 29, 2015, 26 veterans and first responders met eligibility criteria and were randomly assigned to receive 30 mg (n=7), 75 mg (n=7), or 125 mg (n=12) of MDMA plus psychotherapy. At the primary endpoint, the 75 mg and 125 mg groups had significantly greater decreases in PTSD symptom severity (mean change CAPS-IV total scores of -58·3 [SD 9·8] and -44·3 [28·7]; p=0·001) than the 30 mg group (-11·4 [12·7]). Compared with the 30 mg group, Cohen's d effect sizes were large: 2·8 (95% CI 1·19-4·39) for the 75 mg group and 1·1 (0·04-2·08) for the 125 mg group. In the open-label crossover with full-dose MDMA (100-125 mg), PTSD symptom severity significantly decreased in the group that had previously received 30 mg (p=0·01), whereas no further significant decreases were observed in the group that previously achieved a large response after 75 mg doses in the blinded segment (p=0·81). PTSD symptoms were significantly reduced at the 12-month follow-up compared with baseline after all groups had full-dose MDMA (mean CAPS-IV total score of 38·8 [SD 28·1] vs 87·1 [16·1]; p<0·0001). 85 adverse events were reported by 20 participants. Of these adverse events, four (5%) were serious: three were deemed unrelated and one possibly related to study drug treatment. Interpretation: Active doses (75 mg and 125 mg) of MDMA with adjunctive psychotherapy in a controlled setting were effective and well tolerated in reducing PTSD symptoms in veterans and first responders. Funding: Multidisciplinary Association for Psychedelic Studies.

The lancet. Psychiatry · randomised controlled trial · 258 citationsread the source →

Shift Work and Poor Mental Health: A Meta-Analysis of Longitudinal Studies.

Background. Shift work is characterized by employees working outside the standard hours of 7:00 am to 6:00 pm. Because shift work includes night work, the normal sleep-wake cycle (circadian rhythm) is disrupted, with potential consequences for shift workers' physical and mental health. Objectives. To assess the pooled effects of shift work on mental health and to evaluate whether these differ in men and women. Search Methods. We searched PubMed, Scopus, and Web of Science databases for peer-reviewed or government reports published up to August 2018Selection Criteria. To be included, studies had to be longitudinal or case-control studies of shift work exposure associated with adverse mental health outcomes. For subanalyses, we grouped these outcomes as anxiety symptoms, depressive symptoms, or general poor mental health symptoms. Data Collection and Analysis. We followed the Meta-Analysis of Observational Studies in Epidemiology Group guidelines. We extracted adjusted risk estimates for each study to calculate pooled effect sizes (ESs) using random effect models and metaregression analysis to explore sources of heterogeneity. Main Results. We included 7 longitudinal studies, with 28 431 unique participants. Shift work was associated with increased overall risk of adverse mental health outcomes combined (ES = 1.28; 95% confidence interval [CI] = 1.02, 1.62; I2 = 70.6%) and specifically for depressive symptoms (ES = 1.33; 95% CI = 1.02, 1.74; I2 = 31.5%). Gender differences explained more than 90% of heterogeneity, with female shift workers more likely to experience depressive symptoms than female non-shift workers (odds ratio = 1.73; 95% CI = 1.39, 2.14).Authors' Conclusions. To our knowledge, this is the first meta-analysis to investigate the pooled effects of shift work on the risk of poor mental health, including subanalyses by type of poor mental health and gender. Shift workers, particularly women, are at increased risk for poor mental health, particularly depressive symptoms. Public Health Implications. Depression accounts for 4.3% of the global burden of disease and incidence, with mental disorders worldwide predicted to cost US $16.3 million by 2030. With 1 in 5 people in the United States and Europe doing shift work, and the increased risk of poor mental health among shift workers, shift work industries are a priority context for reducing this burden. Workplace health promotion programs and policies are needed to minimize shift workers' risk of poor mental health.

American journal of public health · meta-analysis · 248 citationsread the source →

Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus.

Background: The appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear. Methods: In this multicenter, double-blind, randomized, controlled trial, we compared the efficacy of intravenous doxycycline, azithromycin, or a combination of both in treating severe scrub typhus. Patients who were 15 years of age or older with severe scrub typhus with at least one organ involvement were enrolled. The patients were assigned to receive a 7-day course of intravenous doxycycline, azithromycin, or both (combination therapy). The primary outcome was a composite of death from any cause at day 28, persistent complications at day 7, and persistent fever at day 5. Results: Among 794 patients (median age, 48 years) who were included in the modified intention-to-treat analysis, complications included those that were respiratory (in 62%), hepatic (in 54%), cardiovascular (in 42%), renal (in 30%), and neurologic (in 20%). The use of combination therapy resulted in a lower incidence of the composite primary outcome than the use of doxycycline (33% and 47%, respectively), for a risk difference of -13.3 percentage points (95% confidence interval [CI], -21.6 to -5.1; P = 0.002). The incidence with combination therapy was also lower than that with azithromycin (48%), for a risk difference of -14.8 percentage points (95% CI, -23.1 to -6.5; P<0.001). No significant difference was seen between the azithromycin and doxycycline groups (risk difference, 1.5 percentage points; 95% CI, -7.0 to 10.0; P = 0.73). The results in the per-protocol analysis were similar to those in the primary analysis. Adverse events and 28-day mortality were similar in the three groups. Conclusions: Combination therapy with intravenous doxycycline and azithromycin was a better therapeutic option for the treatment of severe scrub typhus than monotherapy with either drug alone. (Funded by the India Alliance and Wellcome Trust; INTREST Clinical Trials Registry-India number, CTRI/2018/08/015159.).

The New England journal of medicine · randomised controlled trial · 58 citationsread the source →

Intrinsic circadian period of sighted patients with circadian rhythm sleep disorder, free-running type.

Background: Circadian rhythm sleep disorder, free-running type (FRT), is an intractable sleep disorder in which sleep and wake times progressively delay each day even in normal living environments. This disorder severely affects the social functioning of patients because of periodic nighttime insomnia, excessive daytime sleepiness, and a high rate of comorbid psychiatric disorders. Although abnormal regulation of the biological clock is suspected, the pathophysiology of FRT has yet to be elucidated. In this study, the endogenous circadian period, τ, of FRT patients with normal vision was compared with that of healthy individuals whose circadian rhythms are entrained to a 24-hour cycle. Methods: Six FRT patients and 17 healthy individuals (9 intermediate chronotypes and 8 evening chronotypes) were subjected to a 7-day, 28-hour sleep-wake schedule according to the forced desynchrony protocol. Phase shifts in melatonin rhythm were measured under constant routine conditions to calculate τ. Results: In FRT patients, τ was significantly longer than in intermediate chronotypes, whereas in evening chronotypes, it ranged widely and was not significantly different from that in FRT patients. Moreover, τ of melatonin rhythm in FRT patients showed no significant correlation with τ of sleep-wake cycles measured before the study. Conclusions: The findings suggest that although a prolongation of τ may be involved in the onset mechanism of FRT, a prolonged τ is not the only factor involved. It appears that several factors including abnormal entrainment of circadian rhythms are involved in the onset of FRT in a multilayered manner.

Biological psychiatry · randomised controlled trial · 25 citationsread the source →

Emollients improve treatment results with topical corticosteroids in childhood atopic dermatitis: a randomized comparative study.

The aim of the study was to investigate whether adding emollients to the standard topical corticosteroid therapy influences the outcome of children with atopic dermatitis. Fifty-two children aged between 2 and 12 yr were divided randomly in two subgroups consisting of 26 children each. Both groups applied 0.1% methylprednisolone aceponate cream on lesional atopic skin once daily for 2 wk and were observed for another 4 wk after treatment discontinuation. Group B used additionally emollients for the whole study period. Patients were evaluated at days 0 (baseline), 7, 14 (end of therapy), 28 and 42 (follow-up). Both groups demonstrated significant improvement of disease severity according to EASI (Eczema Area and Severity Index) scale (group A: 6.8 +/- 3.59 before and 0.87 +/- 1.25 after therapy, p < 0.001; group B: 9.6 +/- 8.39 before and 1.11 +/- 2.37 after therapy, p < 0.001). Xerosis improved significantly better in group B compared to group A, both clinically (group A: 1.38 +/- 0.57 scores before and 1.5 +/- 0.58 scores after therapy, p = 0.11; group B: 1.62 +/- 0.64 scores before and 0.12 +/- 0.33 scores after therapy, p < 0.001), and by corneometry assessment (group A: 41.7 +/- 9.1 units before and 51.3 +/- 11.3 units after therapy, p < 0.001; group B: 38.9 +/- 12.9 units before and 58.2 +/- 13.5 units after therapy, p < 0.001). A trend towards faster resolving of pruritus in group B (group A: 5.44 +/- 2.6 scores before and 3.22 +/- 2.31 scores after therapy, p = 0.001; group B: 5.87 +/- 2.79 scores before and 2.24 +/- 1.59 scores after therapy, p < 0.001) was also observed. In group B, the improvement was maintained for couple of weeks after treatment discontinuation, while in group A recurrence of the disease was noted (EASI at day 42 in group A vs. group B: 5.29 +/- 5.6 vs. 1.25 +/- 1.4, p = 0.01). Similar results were also observed for xerosis (p < 0.001) and pruritus (p = 0.002). Concomitant usage of emollients significantly improves xerosis and pruritus during corticosteroid treatment of atopic dermatitis and enables to maintain clinical improvement after therapy discontinuation.

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · randomised controlled trial · 67 citationsread the source →

Psychological mechanisms associated with food security status and BMI in adults: a mixed methods study.

Objective: This study examined psychological constructs (delay discounting, grit, future time perspective and subjective social status) in relation to food security status and body weight. Design: A simultaneous triangulation mixed methods design was used to collect quantitative and qualitative data. Quantitative data were collected in fifty-six adults. Independent variables included food security status (food secure or food insecure) and BMI category (normal weight or overweight/obese). Participants, matched on race (African American and White), were categorised into four food security status by BMI category groups. Psychological constructs were measured via validated questionnaires. Qualitative data were collected in a subsample of twelve participants via in-depth interviews. Setting: This study was conducted in Baton Rouge, Louisiana. Participants: The sample was 66 % female and 48 % African American with a mean age of 32·3 (sd 9·2) years and BMI of 28·8 (sd 7·7) kg/m2. Results: Quantitative results showed that food-insecure participants with overweight/obesity had greater delay discounting (-3·78 v. -6·16, P = 0·01; -3·78 v. -5·75, P = 0·02) and poorer grit (3·37 v. 3·99, P = 0·02; 3·37 v. 4·02, P = 0·02 ) than their food-secure counterparts and food-insecure participants with normal weight. Food-insecure participants with overweight/obesity also had a shorter time period for financial planning (0·72 v. 4·14, P = 0·02) than food-secure participants with normal weight. Qualitative data largely supported quantitative findings with participants discussing varied perceptions of psychological constructs. Conclusions: This study found differences in delaying gratification, grit and financial planning between food security status and body weight groups.

Public health nutrition · 11 citationsread the source →

Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.

Background: Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods: We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings: In 2019, there were 12·2 million (95% UI 11·0-13·6) incident cases of stroke, 101 million (93·2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6·55 million (6·00-7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8-12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1-6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0-73·0), prevalent strokes increased by 85·0% (83·0-88·0), deaths from stroke increased by 43·0% (31·0-55·0), and DALYs due to stroke increased by 32·0% (22·0-42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0-18·0), mortality decreased by 36·0% (31·0-42·0), prevalence decreased by 6·0% (5·0-7·0), and DALYs decreased by 36·0% (31·0-42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0-24·0) and incidence rates increased by 15·0% (12·0-18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5-3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5-3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57-8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97-3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01-1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7-90·8] DALYs or 55·5% [48·2-62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3-48·6] DALYs or 24·3% [15·7-33·2]), high fasting plasma glucose (28·9 million [19·8-41·5] DALYs or 20·2% [13·8-29·1]), ambient particulate matter pollution (28·7 million [23·4-33·4] DALYs or 20·1% [16·6-23·0]), and smoking (25·3 million [22·6-28·2] DALYs or 17·6% [16·4-19·0]). Interpretation: The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Funding: Bill & Melinda Gates Foundation.

The Lancet. Neurology · 5441 citationsread the source →

A multilevel, multicomponent childhood obesity prevention group-randomized controlled trial improves healthier food purchasing and reduces sweet-snack consumption among low-income African-American youth.

Background: Consumption of foods and beverages rich in sugar remains high across all races and ages in the United States. Interventions to address childhood obesity and decrease sugar intake are needed, particularly in low-income settings. Methods: B'more Healthy Communities for Kids (BHCK) was a group-randomized, controlled trial implemented among 9-15-year olds in 30 low-income areas of Baltimore. We increased access to low-sugar foods and beverages at wholesalers and small food stores. Concurrently, we encouraged their purchase and consumption by children through youth-led nutrition education in recreation centers, in-store promotions, text messaging and a social media program directed at caregivers. Sugar consumption (sugar sweetened beverage (SSB), sweets) in youth was assessed pre- (n = 534) and post-intervention (n = 401) using the Block Kids Food Frequency Questionnaire. Purchasing of 38 healthier and 28 less healthier food/beverage varieties in the previous 7 days was assessed via self-report. Multilevel models at the community and individual levels were used. Analyses were stratified by age (younger: 9-12-year olds (n = 339) vs older: 13-15 (n = 170)). Models were controlled for child's sex, race, total daily caloric intake, and caregiver's age and sex. Results: Overall baseline mean healthier food purchasing was 2.5 (+ 3.6; min. 0, max. 34 items per week), and unhealthier food purchasing 4.6 (+ 3.7; 0-19 items per week). Mean intake at baseline for kcal from SSB was 176 (+ 189.1) and 153 (+ 142.5), and % of calories from sweets (i.e. cookies, cakes, pies, donuts, candy, ice cream, sweetened cereals, and chocolate beverages) was 15.9 (+ 9.7) and 15.9 (+ 7.7) in comparison and intervention youth, respectively. Intervention youth increased healthier foods and beverages purchases by 1.4 more items per week than comparison youth (β = 1.4; 95% CI: 0.1; 2.8). After the intervention, there was a 3.5% decrease in kcal from sweets for older intervention youth, compared to the control group (β = - 3.5; 95% CI: -7.76; - 0.05). No impact was seen on SSB consumption. Conclusion: BHCK successfully increased healthier food purchasing variety in youth, and decreased % calories from sweet snacks in older youth. Multilevel, multicomponent environmental childhood obesity programs are a promising strategy to improve eating behaviors among low-income urban youth. Trial registration: NCT02181010 (July 2, 2014, retrospectively registered).

Nutrition journal · randomised controlled trial · 47 citationsread the source →

Randomized proof of concept trial of GLYX-13, an N-methyl-D-aspartate receptor glycine site partial agonist, in major depressive disorder nonresponsive to a previous antidepressant agent.

Background: Approximately 45% of patients with major depressive disorder (MDD) do not remit when treated with biogenic amine antidepressants. Consequently, there is a significant need for antidepressant agents with different mechanisms of action. Early proof of concept (POC) studies with such novel agents play a significant role in helping drug developers identify agents and mechanisms of action that merit more intensive research. Studies have demonstrated that high affinity N-methyl-Daspartate (NMDA) receptor blockers (eg, ketamine) can produce rapid antidepressant effects in patients who have not responded to currently available agents, but treatment with these agents is accompanied by psychotomimetic effects that make their use problematic. This column describes a POC study involving GLYX-13, an N-methyl-D-aspartate receptor glycine site functional partial agonist. Method: In this double-blind, randomized, placebo-controlled study, a single intravenous (IV) dose of GLYX-13 (1, 5, 10, or 30 mg/kg) or placebo was administered to 116 subjects with MDD who had not benefitted from a trial of at least one biogenic amine antidepressant during the current episode. The primary outcome measure was score on the Hamilton Depression Rating Scale-17 (Ham-D17), which was used to rate overall depressive symptoms at baseline and at 24 hours and days 3, 7, 14, and, in some arms, days 21 and 28 after administration. Results: GLYX-13, 5 or 10 mg/kg IV, reduced depressive symptoms as assessed by the Ham-D17 at days 1 through 7. Onset of action as assessed using the Bech-6 occurred within 2 hours. GLYX-13 did not elicit psychotomimetic or other significant side effects. Conclusion: In this early POC study, GLYX-13 reduced depressive symptoms within 2 hours and this effect was maintained for 7 days on average in subjects with MDD who had not responded to another antidepressant agent during the current depressive episode. The findings of this study support the hypothesis that modulation of the NMDA receptor is a valid target for the development of antidepressant drugs and the need for additional studies to further evaluate the effects of GLYX-13. POC studies such as the one described here play a pivotal role in allowing drug researchers to decide whether to move forward with larger and more expensive studies, and they enable them to focus available resources on those molecules that appear to have the most therapeutic promise. Based on the POC study described here, a multiple dose study has been completed which showed sustained therapeutic benefit with repeated dosing of GLYX-13 for more than 6 weeks. Phase 3 studies are now being planned.

Journal of psychiatric practice · randomised controlled trial · 139 citationsread the source →

The combined effect of very low nicotine content cigarettes, used as an adjunct to usual Quitline care (nicotine replacement therapy and behavioural support), on smoking cessation: a randomized controlled trial.

Aim: To determine the combined effect of very low nicotine content (VLNC) cigarettes and usual Quitline care [nicotine replacement therapy (NRT) and behavioural support] on smoking abstinence, in smokers motivated to quit. Design: Single-blind, parallel randomized trial. Setting: New Zealand. PARTICIPANTS Smokers who called the Quitline for quitting support were randomized to either VLNC cigarettes to use whenever they had an urge to smoke for up to 6 weeks after their quit date, in combination with usual Quitline care (8 weeks of NRT patches and/or gum or lozenges, plus behavioural support) or to usual Quitline care alone. Measurements: The primary outcome was 7-day point-prevalence smoking abstinence 6 months after quit day. Secondary outcomes included continuous abstinence, cigarette consumption, withdrawal, self-efficacy, alcohol use, serious adverse events and views on the use of the VLNC cigarettes at 3 and 6 weeks and 3 and 6 months. Findings: A total of 1410 participants were randomized (705 in each arm), with a 24% loss to follow-up at 6 months. Participants in the intervention group were more likely to have quit smoking at 6 months compared to the usual care group [7-day point-prevalence abstinence 33 versus 28%, relative risk (RR) = 1.18, 95% confidence interval (CI): 1.01, 1.39, P = 0.037; continuous abstinence 23 versus 15%, RR = 1.50, 95% CI: 1.20, 1.87, P = 0.0003]. The median time to relapse in the intervention group was 2 months compared to 2 weeks in the usual care group (P < 0.0001). Conclusions: Addition of very low nicotine content cigarettes to standard Quitline smoking cessation support may help some smokers to become abstinent.

Addiction (Abingdon, England) · randomised controlled trial · 67 citationsread the source →

Telemedicine for Anger Management Therapy in a Rural Population of Combat Veterans With Posttraumatic Stress Disorder

Article AbstractObjective: To demonstrate the noninferiority of a telemedicine modality, videoteleconferencing, compared to traditional in-person service delivery of a group psychotherapy intervention for rural combat veterans with posttraumatic stress disorder (PTSD).Method: A randomized controlled noninferiority trial of 125 male veterans with PTSD (according to DSM criteria on the Clinician-Administered PTSD Scale) and anger difficulties was conducted at 3 Veterans Affairs outpatient clinics. Participants were randomly assigned to receive anger management therapy delivered in a group setting with the therapist either in-person (n†‰=†‰64) or via videoteleconferencing (n†‰=†‰61). Participants were assessed at baseline, midtreatment (3 weeks), posttreatment (6 weeks), and 3 and 6 months posttreatment. The primary clinical outcome was reduction of anger difficulties, as measured by the anger expression and trait anger subscales of the State-Trait Anger Expression Inventory-2 (STAXI-2) and by the Novaco Anger Scale total score (NAS-T). Data were collected from August 2005 to October 2008.Results: Participants in both groups showed significant and clinically meaningful reductions in anger symptoms, with posttreatment and 3 and 6 months posttreatment effect sizes ranging from .12 to .63. Using a noninferiority margin of 2 points for STAXI-2 subscales anger expression and trait anger and 4 points for NAS-T outcomes, participants in the videoteleconferencing condition demonstrated a reduction in anger symptoms similar ("non-inferior") to symptom reductions in the in-person groups. Additionally, no significant between-group differences were found on process variables, including attrition, adherence, satisfaction, and treatment expectancy. Participants in the in-person condition reported significantly higher group therapy alliance. Conclusions: Clinical and process outcomes indicate delivering cognitive-behavioral group treatment for PTSD-related anger problems via videoteleconferencing is an effective and feasible way to increase access to evidence-based care for veterans residing in rural or remote locations. Trial Registration: clinicaltrials.gov Identifier: NCT00122109J Clin Psychiatry 2010;71(7):855-863Submitted: August 11, 2009; accepted September 28, 2009.Online ahead of print: January 26, 2010 (doi:10.4088/JCP.09m05604blu).Corresponding author: Leslie A. Morland, PsyD, National Center for PTSD-Pacific Islands Division, Department of Veterans Affairs Pacific Islands Healthcare System, 3375 Koapaka St, Suite I-560, Honolulu, HI 96819 (Leslie. Morland@va.gov).

The Journal of Clinical Psychiatry · randomised controlled trial · 279 citationsread the source →

The mental health status of Chinese rural-urban migrant workers : comparison with permanent urban and rural dwellers.

Objectives: There are currently around 120 million rural-urban migrants in China. Elsewhere migration has been associated with increased vulnerability to mental health problems. This study was conducted to explore the mental health status and help seeking behaviours of migrant workers in Hangzhou city, Zhejiang Province, and to compare them with permanent urban and rural dwellers. Methods: A self-completion questionnaire including items relating to sociodemographics, health and lifestyles and mental health, was completed by 4453 migrant workers and 1957 urban workers in Hangzhou city, and by 1909 rural residents in Western Zhejiang Province. Results: The mean age of the migrants was 27 years, (male 29 years, female 25 years). They worked long hours (28% >12 h per day, 81% 6 or 7 days per week) and their living conditions were very basic. On the SF-36 mental health scale migrants had lower scores (52.4) than rural residents (60.4, P < 0.0001) but scored higher than urban residents (47.2, P = 0.003). The difference between urbanites and migrants disappeared after adjustment for confounders (P = 0.06). Independent predictors of better mental health status among migrants were being unmarried, migrating with a partner, higher salary, good self-reported health and good relationships with co-workers. There were small significant differences in suicide ideation and attempts between the three groups with suicide ideation commonest in migrants and suicide attempts most common in the rural population. Fewer than 1% across all three groups had received any professional help for depression or anxiety. Conclusion: Rural-urban migrant workers in this part of China are not especially vulnerable to poor mental health. This may result from a sense of well being associated with upward economic mobility and improved opportunities, and the relatively high social capital in migrant communities.

Social psychiatry and psychiatric epidemiology · cohort or longitudinal · 105 citationsread the source →

Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK.

Background: A rise in the incidence of some autoimmune disorders has been described. However, contemporary estimates of the overall incidence of autoimmune diseases and trends over time are scarce and inconsistent. We aimed to investigate the incidence and prevalence of 19 of the most common autoimmune diseases in the UK, assess trends over time, and by sex, age, socioeconomic status, season, and region, and we examine rates of co-occurrence among autoimmune diseases. Methods: In this UK population-based study, we used linked primary and secondary electronic health records from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex and ethnicity. Eligible participants were men and women (no age restriction) with acceptable records, approved for Hospital Episodes Statistics and Office of National Statistics linkage, and registered with their general practice for at least 12 months during the study period. We calculated age and sex standardised incidence and prevalence of 19 autoimmune disorders from 2000 to 2019 and used negative binomial regression models to investigate temporal trends and variation by age, sex, socioeconomic status, season of onset, and geographical region in England. To characterise co-occurrence of autoimmune diseases, we calculated incidence rate ratios (IRRs), comparing incidence rates of comorbid autoimmune disease among individuals with a first (index) autoimmune disease with incidence rates in the general population, using negative binomial regression models, adjusted for age and sex. Findings: Among the 22 009 375 individuals included in the study, 978 872 had a new diagnosis of at least one autoimmune disease between Jan 1, 2000, and June 30, 2019 (mean age 54·0 years [SD 21·4]). 625 879 (63·9%) of these diagnosed individuals were female and 352 993 (36·1%) were male. Over the study period, age and sex standardised incidence rates of any autoimmune diseases increased (IRR 2017-19 vs 2000-02 1·04 [95% CI 1·00-1·09]). The largest increases were seen in coeliac disease (2·19 [2·05-2·35]), Sjogren's syndrome (2·09 [1·84-2·37]), and Graves' disease (2·07 [1·92-2·22]); pernicious anaemia (0·79 [0·72-0·86]) and Hashimoto's thyroiditis (0·81 [0·75-0·86]) significantly decreased in incidence. Together, the 19 autoimmune disorders examined affected 10·2% of the population over the study period (1 912 200 [13·1%] women and 668 264 [7·4%] men). A socioeconomic gradient was evident across several diseases, including pernicious anaemia (most vs least deprived area IRR 1·72 [1·64-1·81]), rheumatoid arthritis (1·52 [1·45-1·59]), Graves' disease (1·36 [1·30-1·43]), and systemic lupus erythematosus (1·35 [1·25-1·46]). Seasonal variations were observed for childhood-onset type 1 diabetes (more commonly diagnosed in winter) and vitiligo (more commonly diagnosed in summer), and regional variations were observed for a range of conditions. Autoimmune disorders were commonly associated with each other, particularly Sjögren's syndrome, systemic lupus erythematosus, and systemic sclerosis. Individuals with childhood-onset type 1 diabetes also had significantly higher rates of Addison's disease (IRR 26·5 [95% CI 17·3-40·7]), coeliac disease (28·4 [25·2-32·0]), and thyroid disease (Hashimoto's thyroiditis 13·3 [11·8-14·9] and Graves' disease 6·7 [5·1-8·5]), and multiple sclerosis had a particularly low rate of co-occurrence with other autoimmune diseases. Interpretation: Autoimmune diseases affect approximately one in ten individuals, and their burden continues to increase over time at varying rates across individual diseases. The socioeconomic, seasonal, and regional disparities observed among several autoimmune disorders in our study suggest environmental factors in disease pathogenesis. The inter-relations between autoimmune diseases are commensurate with shared pathogenetic mechanisms or predisposing factors, particularly among connective tissue diseases and among endocrine diseases. Funding: Research Foundation Flanders.

Lancet (London, England) · 508 citationsread the source →

Toll-Like Receptor 4/MyD88-Mediated Signaling of Hepcidin Expression Causing Brain Iron Accumulation, Oxidative Injury, and Cognitive Impairment After Intracerebral Hemorrhage.

Background: Disturbance of brain iron metabolism after intracerebral hemorrhage (ICH) results in oxidative brain injury and cognition impairment. Hepcidin plays an important role in regulating iron metabolism, and we have reported that serum hepcidin is positively correlated with poor outcomes in patients with ICH. However, the roles of hepcidin in brain iron metabolism after ICH remain largely unknown. Methods: Parabiosis and ICH models combined with in vivo and in vitro experiments were used to investigate the roles of hepcidin in brain iron metabolism after ICH. Results: Increased hepcidin-25 was found in serum and primarily in astrocytes after ICH. The brain iron efflux, oxidative brain injury, and cognition impairment were improved in Hepc-/- ICH mice but aggravated by the human hepcidin-25 peptide in C57BL/6 ICH mice. Data obtained in in vitro studies showed that increased hepcidin inhibited the intracellular iron efflux of brain microvascular endothelial cells but was rescued by a hepcidin antagonist, fursultiamine. Using parabiosis ICH models also shows that increased serum hepcidin prevents brain iron efflux. In addition, Toll-like receptor 4 (TLR4)/MyD88 signaling pathway increased hepcidin expression by promoting interleukin-6 expression and signal transducer and activator of transcription 3 phosphorylation. TLR4-/- and MyD88-/- mice exhibited improvement in brain iron efflux at 7, 14, and 28 days after ICH, and the TLR4 antagonist (6R)-6-[N-(2-chloro-4-fluorophenyl) sulfamoyl] cyclohex-1-ene-1-carboxylate significantly decreased brain iron levels at days 14 and 28 after ICH and improved cognition impairment at day 28. Conclusions: The results presented here show that increased hepcidin expression caused by inflammation prevents brain iron efflux via inhibition of the intracellular iron efflux of brain microvascular endothelial cells entering into circulation and aggravating oxidative brain injury and cognition impairment, which identifies a mechanistic target for muting inflammation to promote brain iron efflux and to attenuate oxidative brain injury after ICH.

Circulation · 119 citationsread the source →

Comparison of Telomere Length in Age-Matched Primiparous and Multiparous Brahman Cows.

Physiological and psychological stressors have been associated with the attrition of telomeres, which are the protective caps of chromosomes. This study compares the telomere length (TL) in 4-year-old Brahman cows grouped by the first parity (n = 8) and the second parity (n = 11). The cows were bled via jugular venipuncture, weighed, and had their body condition scores recorded at Day -28 prior to calving and at Day + 7 and Day + 28 post-calving. The duration of labor (Dlabor) and parturition ease were recorded. The peripheral leukocytes were isolated, the leukocyte blood count with differential was recorded, and the genomic DNA was extracted. The relative quantity of telomere products, which is proportional to the average TL, was determined via multiplex quantitative PCR using the ratio (T/S ratio) of bovine telomere and β-globulin DNA. Standards of the bovine telomere (1012-107 dilution series) and β-globulin (109-104 dilution series) genes were utilized to produce relative copy numbers. The samples were assayed in triplicate and were included if the triplicate Cq difference was less than 0.25 cycles. The parity was the fixed effect, and the random effects included the sire and day repeated with the cow as the subject. Statistical significance was not observed in the leukocyte number or type (p > 0.1). A reduction in the TL of approximately 9225 telomeric copies was found between Parity 1 and Parity 2 (p = 0.02). A trend was found between the TL and Dlabor (p = 0.06). The stress of parturition and raising the first calf of a cow's life may be responsible for TL attenuation. Parity may be considered a stressor of cow longevity.

Animals : an open access journal from MDPI · 2 citationsread the source →

Prevalence of Health Misinformation on Social Media: Systematic Review.

Background: Although at present there is broad agreement among researchers, health professionals, and policy makers on the need to control and combat health misinformation, the magnitude of this problem is still unknown. Consequently, it is fundamental to discover both the most prevalent health topics and the social media platforms from which these topics are initially framed and subsequently disseminated. Objective: This systematic review aimed to identify the main health misinformation topics and their prevalence on different social media platforms, focusing on methodological quality and the diverse solutions that are being implemented to address this public health concern. Methods: We searched PubMed, MEDLINE, Scopus, and Web of Science for articles published in English before March 2019, with a focus on the study of health misinformation in social media. We defined health misinformation as a health-related claim that is based on anecdotal evidence, false, or misleading owing to the lack of existing scientific knowledge. We included (1) articles that focused on health misinformation in social media, including those in which the authors discussed the consequences or purposes of health misinformation and (2) studies that described empirical findings regarding the measurement of health misinformation on these platforms. Results: A total of 69 studies were identified as eligible, and they covered a wide range of health topics and social media platforms. The topics were articulated around the following six principal categories: vaccines (32%), drugs or smoking (22%), noncommunicable diseases (19%), pandemics (10%), eating disorders (9%), and medical treatments (7%). Studies were mainly based on the following five methodological approaches: social network analysis (28%), evaluating content (26%), evaluating quality (24%), content/text analysis (16%), and sentiment analysis (6%). Health misinformation was most prevalent in studies related to smoking products and drugs such as opioids and marijuana. Posts with misinformation reached 87% in some studies. Health misinformation about vaccines was also very common (43%), with the human papilloma virus vaccine being the most affected. Health misinformation related to diets or pro-eating disorder arguments were moderate in comparison to the aforementioned topics (36%). Studies focused on diseases (ie, noncommunicable diseases and pandemics) also reported moderate misinformation rates (40%), especially in the case of cancer. Finally, the lowest levels of health misinformation were related to medical treatments (30%). Conclusions: The prevalence of health misinformation was the highest on Twitter and on issues related to smoking products and drugs. However, misinformation on major public health issues, such as vaccines and diseases, was also high. Our study offers a comprehensive characterization of the dominant health misinformation topics and a comprehensive description of their prevalence on different social media platforms, which can guide future studies and help in the development of evidence-based digital policy action plans.

Journal of medical Internet research · systematic review · 808 citationsread the source →

Black Cumin (Nigella sativa L.) Seed Press Cake as a Novel Material for the Development of New Non-Dairy Beverage Fermented with Kefir Grains.

In recent years, there has been a growing interest from the food industry in new products that are increasingly desired by consumers because of the functional ingredients they contain. This category certainly includes fermented plant-based beverages, which combine the properties of plant substrates with the beneficial effects of fermentation on human health. In our study, two trial variants containing 20% and 30% black cumin (Nigella sativa L.) seed press cake (BCPC) were inoculated with kefir grain cultures and then incubated at 25 °C for 24 h. The resulting beverages were stored under refrigeration (6 °C) for 28 days. During storage, pH, total free amino acids, reducing sugars, changes in the microbial population, viscosity, textural parameters, and color were measured on days 1, 5, 7, 14, 21, and 28. Throughout the storage period, the number of lactic acid bacteria, as well as yeasts, exceeded the recommended minimum level. Numerous changes in product parameters were observed in the tested beverages as a result of fermentation compared to non-fermented products. This study indicates the possibility of using BCPC as a valuable matrix for the production of a functional kefir-like beverage.

Microorganisms · 8 citationsread the source →

Single-arm trial of the second version of an acceptance & commitment therapy smartphone application for smoking cessation.

Background: The first randomized trial of a smartphone application (app) for adult smoking cessation (SmartQuit 1.0) revealed key features that predict cessation. These findings guided the revision of this Acceptance & Commitment Therapy (ACT)-based application (SmartQuit 2.0), which was primarily tested to examine participant receptivity, short-term cessation and reduction, and the relationship between program completion, smoking cessation and reduction. Secondarily, outcomes were descriptively compared with the SmartQuit1.0 trial. Method: Adult participants (78% female, 25% with high school or less education, 30% unemployed) were recruited into the single-arm pilot trial (N=99) of SmartQuit 2.0 with a two-month follow-up (85% retention). Results: Regarding receptivity, 84% of participants were satisfied with SmartQuit 2.0 (vs. 59% for SmartQuit1.0), 73% would recommend it to a friend (vs. 48% for SmartQuit1.0), 81% found the ACT exercises useful for quitting (vs. 44% for SmartQuit1.0). At the 2-month follow-up, the quit rates were 21% for 7-day point prevalence (vs. 23% for SmartQuit1.0), 11% for 30-day point prevalence (vs. 13% for SmartQuit1.0), and 75% of participants reduced their smoking frequency (vs. 57% for SmartQuit1.0). Among program completers (24% of total sample), the quit rates were 33% for 7-day point prevalence, 28% for 30-day point prevalence, and 88% of participants reduced their smoking frequency. Conclusions: The revised app had high user receptivity, modest quit rates, and high smoking reduction rates. Program completion may be key to boosting the app's effectiveness.

Drug and alcohol dependence · 66 citationsread the source →

Quality of Life and Mental Health in Children and Adolescents after the First Year of the COVID-19 Pandemic: A Large Population-Based Survey in South Tyrol, Italy.

Background: Methodological heterogeneity of studies and geographical variation limit conclusions about the impact of the COVID-19 pandemic on the mental health of youth. This study aimed to explore the health-related quality of life and mental health of children and adolescents in the second year of the pandemic in South Tyrol, Italy. Methods: An online survey representative for the age and gender of the children and adolescents in South Tyrol was conducted among 5159 families with children and adolescents aged 7-19 years, between 28 May and 16 June 2021. The survey collecting parental ratings and self-rated questionnaires from children and adolescents aged 11-19 years included instruments to measure health-related quality of life (KIDSCREEN-10), mental health problems (SDQ), anxiety (SCARED), and depression (CES-DC). The results were compared with data from corresponding studies conducted in Germany. Results: Decreased health-related quality of life and increased conduct problems, peer-related mental health problems, anxiety, and depressive and psychosomatic symptoms in children and adolescents observed in the second year of the pandemic in Germany were confirmed in the second year in South Tyrol. Children and adolescents with low socioeconomic status, a migration background, and limited living space were significantly affected. Female sex and older age were associated with increased psychosocial problems and a positive family climate supported the mental health of children and adolescents during the pandemic. Conclusions: Confirmation of findings of decreased health-related quality of life and increased emotional problems after the first year of the pandemic supports the ongoing call for low-threshold health promotion, prevention, and early intervention programs to support children and adolescents who have been severely affected by the pandemic.

International journal of environmental research and public health · 36 citationsread the source →

Global vascular surgeons' experience, stressors, and coping during the coronavirus disease 2019 pandemic.

Background: The coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented challenges for health care systems globally. We designed and administered a global survey to examine the effects of COVID-19 on vascular surgeons and explore the COVID-19-related stressors faced, coping strategies used, and support structures available. Methods: The Pandemic Practice, Anxiety, Coping, and Support Survey for Vascular Surgeons was an anonymous cross-sectional survey sponsored by the Society for Vascular Surgery Wellness Task Force. The survey analysis evaluated the effects of COVID-19-related stressors on vascular surgeons measured using the Generalized Anxiety Disorder 7-item scale. The 28-item Brief Coping Orientation to Problems Experienced inventory was used to assess the active and avoidant coping strategies. Survey data were collected using REDCap (Research Electronic Data Capture) from April 14, 2020 to April 24, 2020 inclusive. Additional qualitative data were collected using open-ended questions. Univariable and multivariable analyses of the factors associated with the anxiety levels and qualitative analysis were performed. Results: A total of 1609 survey responses (70.5% male; 82.5% vascular surgeons in practice) from 58 countries (43.4% from United States; 43.4% from Brazil) were eligible for analysis. Some degree of anxiety was reported by 54.5% of the respondents, and 23.3% reported moderate or severe anxiety. Most respondents (∼60%) reported using active coping strategies and the avoidant coping strategy of "self-distraction," and 20% used other avoidant coping strategies. Multivariable analysis identified the following factors as significantly associated with increased self-reported anxiety levels: staying in a separate room at home or staying at the hospital or a hotel after work (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.08-1.79), donning and doffing personal protective equipment (OR, 1.81; 95% CI, 1.41-2.33), worry about potential adverse patient outcomes due to care delay (OR, 1.47; 95% CI, 1.16-1.87), and financial concerns (OR, 1.90; 95% CI, 1.49-2.42). The factors significantly associated with decreased self-reported anxiety levels were hospital support (OR, 0.83; 95% CI, 0.76-0.91) and the use of positive reframing as an active coping strategy (OR, 0.88; 95% CI, 0.81-0.95). Conclusions: Vascular surgeons globally have been experiencing multiple COVID-19-related stressors during this devastating crisis. These findings have highlighted the continued need for hospital systems to support their vascular surgeons and the importance of national societies to continue to invest in peer-support programs as paramount to promoting the well-being of vascular surgeons during and after the COVID-19 pandemic.

Journal of vascular surgery · 30 citationsread the source →

Use of rumination and activity monitoring for the identification of dairy cows with health disorders: Part I. Metabolic and digestive disorders.

The objectives of this study were to evaluate (1) the performance of an automated health-monitoring system (AHMS) to identify cows with metabolic and digestive disorders-including displaced abomasum, ketosis, and indigestion-based on an alert system (health index score, HIS) that combines rumination time and physical activity; (2) the number of days between the first HIS alert and clinical diagnosis (CD) of the disorders by farm personnel; and (3) the daily rumination time, physical activity, and HIS patterns around CD. Holstein cattle (n=1,121; 451 nulliparous and 670 multiparous) were fitted with a neck-mounted electronic rumination and activity monitoring tag (HR Tags, SCR Dairy, Netanya, Israel) from at least -21 to 80 d in milk (DIM). Raw data collected in 2-h periods were summarized per 24 h as daily rumination and activity. A HIS (0 to 100 arbitrary units) was calculated daily for individual cows with an algorithm that used rumination and activity. A positive HIS outcome was defined as a HIS of <86 during at least 1 d from -5 to 2 d after CD. Blood concentrations of nonesterified fatty acids, β-hydroxybutyrate, total calcium, and haptoglobin were determined in a subgroup of cows (n=459) at -11±3, -4±3, 0, 3±1, 7±1, 14±1, and 28±1 DIM. The sensitivity of the HIS was 98% [95% confidence interval (CI): 93, 100] for displaced abomasum (n=41); 91% (95% CI: 83, 99) for ketosis (n=54); 89% (95% CI: 68, 100) for indigestion (n=9); and 93% (95% CI: 89, 98) for all metabolic and digestive disorders combined (n=104). Days (mean and 95% CI) from the first positive HIS <86 and CD were -3 (-3.7, -2.3), -1.6 (-2.3, -1.0), -0.5 (-1.5, 0.5), and -2.1 (-2.5, -1.6) for displaced abomasum, ketosis, indigestion, and all metabolic and digestive disorders, respectively. The patterns of rumination, activity, and HIS for cows flagged by the AHMS were characterized by lower levels than for cows without a health disorder and cows not flagged by the AHMS from -5 to 5 d after CD, depending on the disorder and parameter. Differences between cows without health disorders and those flagged by the AHMS for blood markers of metabolic and health status confirmed the observations of the CD and AHMS alerts. The overall sensitivity and timing of the AHMS alerts for cows with metabolic and digestive disorders indicated that AHMS that combine rumination and activity could be a useful tool for identifying cows with metabolic and digestive disorders.

Journal of dairy science · 106 citationsread the source →

Immunity duration of a recombinant adenovirus type-5 vector-based Ebola vaccine and a homologous prime-boost immunisation in healthy adults in China: final report of a randomised, double-blind, placebo-controlled, phase 1 trial.

Background: The 2013-15 Ebola virus disease epidemic in west Africa greatly accelerated the development of Ebola vaccine. We aimed to analyse the immune persistence induced by one shot of an adenovirus type-5 vector-based Ebola virus vaccine up to 6 months and the effect of boosting with a homologous vector in healthy adults in China. Methods: In a randomised, double-blind, placebo-controlled, phase 1 clinical trial in one site in Jiangsu Province, China, 120 healthy adults aged 18-60 years received an initial dose of intramuscular adenovirus type-5 Ebola virus vaccine of 4·0 × 1010 viral particles, 1·6 × 1011 viral particles, or placebo, and were followed up to day 168. Participants were subsequently re-recruited to receive a booster dose of the same vaccine or placebo, in the same dose, at month 6. Women who were pregnant, breastfeeding, or planned to become pregnant during the next month were excluded. Randomisation was conducted by computer-generated block randomisation. Randomisation data were unmasked for interim analysis of the data obtained between days 0-28 but not disclosed to participants or site staff. Safety and immunogenicity analysis were done on the intention-to-treat population. We aimed to assess the safety profile of the experimental vaccine and the immunity responses to a single-dose immunisation or a homologous prime-boost regimen. Primary outcomes were Ebola glycoprotein-specific ELISA antibody responses 28 days post-boost and the occurrences of adverse reactions post-boost. The original trial and the extended booster study were registered with ClinicalTrials.gov, numbers NCT02326194 and NCT02533791, respectively. Findings: Between Dec 28, 2014, and Jan 9, 2015, we enrolled 210 volunteers. 90 participants were not randomised due to not meeting inclusion criteria (61), meeting exclusion criteria (4), or withdrawal of consent (25). 120 people were randomly assigned to receive intramuscular Ebola vaccine at 4·0 × 1010 viral particles (low dose, n=40), Ebola vaccine at 1·6 × 1011 viral particles (high dose, n=40), or placebo (n=40, in two groups of 20). After prime vaccination, the geometric mean titer (GMT) of ELISA EC90 peaked at 682·7 (95% CI 424·3-1098·5) in the low-dose vaccine group and 1305·7 (970·1-1757·2) in the high-dose vaccine group at day 28, and then fell gradually through the next a few months to 575·5 (394·8-838·8) in the high-dose vaccine group and 197·9 (107·9-362·7) in the low-dose vaccine group at day 168. No specific response was recorded in the placebo group with a GMT of 5·0. Of the 120 participants involved in the initial trial, ten participants declined to participate, and 110 were included in the boost immunisation: 38 received the low dose, 35 received the high dose, and 37 received the placebo. At day 28 after boost vaccination, the ELISA EC90 titres rapidly rose to 6110 (95% CI 4705-7935) in the low-dose group and to 11825 (8904-15705) in the high dose group. 78 of 110 participants reported at least one solicited adverse reaction within the first 7 days after booster administration. Both of the groups who received vaccine showed significantly higher incidence of mild or moderate solicited adverse reactions than did the placebo group. Interpretation: The adenovirus 5-vectored Ebola vaccine of 1·6 × 1011 viral particles was highly immunogenic and safe. The lower dose of 4·0 × 1010 viral particles was also safe, but immunogenicity seemed to be more vulnerable to the pre-existing immunity of adenovirus 5. A homologous priming-boosting regimen with adenovirus type-5 Ebola vaccine at 6 months interval was able to elicit greater antibody responses with longer duration. These results support an immunisation strategy to implement a booster injection for a more durable protection against Ebola virus disease. Funding: Chinese Ministry of Science and Technology and The National Health and Family Planning Commission, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology.

The Lancet. Global health · randomised controlled trial · 76 citationsread the source →

The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis.

Study question: What is the reported overall prevalence of polycystic ovary syndrome (PCOS) according to the criteria of the National Institutes of Health (NIH), Rotterdam or the Androgen Excess and PCOS Society (AE-PCOS Society)? Summary answer: The reported overall prevalence of PCOS (95% CI) according to diagnostic criteria of the NIH, Rotterdam and the AE-PCOS Society is 6% (5-8%, n = 18 trials), 10% (8-13%, n = 15 trials) and 10% (7-13%, n = 10 trials), respectively. What is already known: PCOS is the most common endocrine disorder among women of reproductive age. Although many studies have investigated the prevalence of PCOS, there are discrepancies in their results, in part due to the use of various definitions of the syndrome and its subphenotypes, differences between study cohorts, ethnicities, and types of recruitment and sampling. Study design, size, duration: A systematic review and meta-analysis were performed on all published studies that have reported the prevalence of PCOS according to at least one subset of diagnostic criteria. Participants/materials, setting, methods: To identify relevant studies based on the PRISMA statement, PubMed and Ovid databases were searched up to September 2015 by two blind investigators using the terms 'PCOS', 'polycystic ovarian disease', 'Stein Leventhal syndrome', 'Androgen Excess Society', 'National Institute of Health', 'Rotterdam', 'ESHRE/ASRM', 'criteria' and 'prevalence'. Articles that represented the prevalence of PCOS according to at least one subset of diagnostic criteria were included. Exclusion criteria were a focus on adolescent subjects, an absence of data on prevalence, inappropriate design or non-English reporting. An appraisal tool to evaluate the methodological quality of the available studies was generated by the authors. Main results and the role of chance: A total of 55 reports remained following screening of the abstracts and text for the subject of the study. Of these, 24 articles were eligible and evaluated for qualitative and quantitative synthesis. Since heterogeneity was observed among studies, a random-effects model was used to estimate the prevalence and its 95% CI. The proportions of PCOS prevalence (95% CI) according to the diagnostic criteria of NIH, Rotterdam and AE-PCOS Society were 6% (5-8%, n = 18 trials), 10% (8-13%, n = 15 trials) and 10% (7-13%, n = 10 trials), respectively. When only unselected population studies were included, the given rates were 6% (5-8%, n = 3 trials), 9% (7-12%, n = 6 trials) and 10% (7-14%, n = 3 trials). The respective proportions for hirsutism, hyperandrogenaemia, polycystic ovaries (PCO) and oligo-anovulation were 13% (8-20%, n = 14 trials), 11% (8-15%, n = 9 trials), 28% (22-35%, n = 12 trials) and 15% (12-18%, n = 19 trials), respectively. Limitations, reasons for caution: The effects of ethnic differences, particularly, on the presence or severity of hirsutism cannot be ruled out in any way. In addition, there was a lack of standardization in defining phenotypes of the syndrome and selection bias was evident in most of the studies regarding recruitment of the cohorts. Wider implications of the findings: Geographical differences in frequencies of the components of the syndrome, such as oligo-anovulation and clinical/biochemical androgen excess, must be taken into account in the development and implementation of regional diagnostic and precision treatment strategies. Further efforts and resources are required to increase standardization of the methods and comparability of the study results on prevalence and phenotypic characterization of PCOS around the globe. Study funding/competing interests: No funding to declare. The authors have no conflicts of interest to declare. Registration number: None.

Human reproduction (Oxford, England) · meta-analysis · 918 citationsread the source →

From grief, guilt pain and stigma to hope and pride - a systematic review and meta-analysis of mixed-method research of the psychosocial impact of stillbirth.

Background: Despite improvements in maternity healthcare services over the last few decades, more than 2.7 million babies worldwide are stillborn each year. The global health agenda is silent about stillbirth, perhaps, in part, because its wider impact has not been systematically analysed or understood before now across the world. Our study aimed to systematically review, evaluate and summarise the current evidence regarding the psychosocial impact of stillbirth to parents and their families, with the aim of improving guidance in bereavement care worldwide. Methods: Systematic review and meta-summary (quantitative aggregation of qualitative findings) of quantitative, qualitative, and mixed-methods studies. All languages and countries were included. Results: Two thousand, six hundred and nineteen abstracts were identified; 144 studies were included. Frequency effect sizes (FES %) were calculated for each theme, as a measure of their prevalence in the literature. Themes ranged from negative psychological symptoms post bereavement (77 · 1) and in subsequent pregnancies (27 · 1), to disenfranchised grief (31 · 2), and incongruent grief (28 · 5), There was also impact on siblings (23 · 6) and on the wider family (2 · 8). They included mixed-feelings about decisions made when the baby died (12 · 5), avoidance of memories (13 · 2), anxiety over other children (7 · 6), chronic pain and fatigue (6 · 9), and a different approach to the use of healthcare services (6 · 9). Some themes were particularly prominent in studies of fathers; grief suppression (avoidance)(18 · 1), employment difficulties, financial debt (5 · 6), and increased substance use (4 · 2). Others found in studies specific to mothers included altered body image (3 · 5) and impact on quality of life (2 · 1). Counter-intuitively, Some themes had mixed connotations. These included parental pride in the baby (5 · 6), motivation for engagement in healthcare improvement (4 · 2) and changed approaches to life and death, self-esteem, and own identity (25 · 7). In studies from low/middle income countries, stigmatisation (13 · 2) and pressure to prioritise or delay conception (9) were especially prevalent. Conclusion: Experiencing the birth of a stillborn child is a life-changing event. The focus of the consequences may vary with parent gender and country. Stillbirth can have devastating psychological, physical and social costs, with ongoing effects on interpersonal relationships and subsequently born children. However, parents who experience the tragedy of stillbirth can develop resilience and new life-skills and capacities. Future research should focus on developing interventions that may reduce the psychosocial cost of stillbirth.

BMC pregnancy and childbirth · meta-analysis · 201 citationsread the source →

Cognitive behavioural therapy with exposure and response prevention in the treatment of obsessive-compulsive disorder: A systematic review and meta-analysis of randomised controlled trials.

Background: Cognitive behavioural therapy (CBT), incorporating exposure and response prevention (ERP) is widely recognised as the psychological treatment of choice for obsessive-compulsive disorder (OCD). Uncertainty remains however about the magnitude of the effect of CBT with ERP and the impact of moderating factors in patients with OCD. Method: This systematic review and meta-analysis assessed randomised-controlled trials of CBT with ERP in patients of all ages with OCD. The study was preregistered in PROSPERO (CRD42019122311). The primary outcome was end-of-trial OCD symptom scores. The moderating effects of patient-related and study-related factors including type of control intervention and risk of bias were examined. Additional exploratory analyses assessed the effects of treatment fidelity and impact of researcher allegiance. Results: Thirty-six studies were included, involving 2020 patients (537 children/adolescents and 1483 adults) with 1005 assigned to CBT with ERP and 1015 to control conditions. When compared against all control conditions, a large pooled effect size (ES) emerged in favour of CBT with ERP (g = 0.74: 95% CI = 0.51 to 0.97 k = 36), which appeared to diminish with increasing age. While CBT with ERP was more effective than psychological placebo (g = 1.13 95% CI 0.71 to 1.55, k = 10), it was no more effective than other active forms of psychological therapy (g = -0.05: 95% CI -0.27 to 0.16, k = 8). Similarly, whereas CBT with ERP was significantly superior when compared to all forms of pharmacological treatment (g = 0.36: 95% CI 0.7 to 0.64, k = 7), the effect became marginal when compared with adequate dosages of pharmacotherapy for OCD (g = 0.32: 95% CI -0.00 to 0.64, k = 6).A minority of studies (k = 8) were deemed to be at low risk of bias. Moreover, three quarters of studies (k = 28) demonstrated suspected researcher allegiance and these studies reported a large ES (g = 0.95: 95% CI 0.69 to 1.2), while those without suspected researcher allegiance (k = 8) indicated that CBT with ERP was not efficacious (g = 0.02: 95% CI -0.29 to 0.33). Conclusions: A large effect size was found for CBT with ERP in reducing the symptoms of OCD, but depends upon the choice of comparator control. This meta-analysis also highlights concerns about the methodological rigor and reporting of published studies of CBT with ERP in OCD. In particular, efficacy was strongly linked to researcher allegiance and this requires further future investigation.

Comprehensive psychiatry · meta-analysis · 117 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 →

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 →

Probiotics for the prevention of pediatric antibiotic-associated diarrhea.

Background: Antibiotics alter the microbial balance commonly resulting in antibiotic-associated diarrhea (AAD). Probiotics may prevent AAD via providing gut barrier, restoration of the gut microflora, and other potential mechanisms of action. Objectives: The primary objectives were to assess the efficacy and safety of probiotics (any specified strain or dose) used for the prevention of AAD in children. Search methods: MEDLINE, Embase, CENTRAL, CINAHL, and the Web of Science (inception to 28 May 2018) were searched along with registers including the ISRCTN and Clinicaltrials.gov. We also searched the NICE Evidence Services database as well as reference lists from relevant articles. Selection criteria: Randomized, parallel, controlled trials in children (0 to 18 years) receiving antibiotics, that compare probiotics to placebo, active alternative prophylaxis, or no treatment and measure the incidence of diarrhea secondary to antibiotic use were considered for inclusion. Data collection and analysis: Study selection, data extraction, and risk of bias assessment were conducted independently by two authors. Dichotomous data (incidence of AAD, adverse events) were combined using a pooled risk ratio (RR) or risk difference (RD), and continuous data (mean duration of diarrhea) as mean difference (MD), along with corresponding 95% confidence interval (95% CI). We calculated the number needed to treat for an additional beneficial outcome (NNTB) where appropriate. For studies reporting on microbiome characteristics using heterogeneous outcomes, we describe the results narratively. The certainty of the evidence was evaluated using GRADE. Main results: Thirty-three studies (6352 participants) were included. Probiotics assessed included Bacillus spp., Bifidobacterium spp., Clostridium butyricum, Lactobacilli spp., Lactococcus spp., Leuconostoc cremoris, Saccharomyces spp., orStreptococcus spp., alone or in combination. The risk of bias was determined to be high in 20 studies and low in 13 studies. Complete case (patients who did not complete the studies were not included in the analysis) results from 33 trials reporting on the incidence of diarrhea show a precise benefit from probiotics compared to active, placebo or no treatment control. After 5 days to 12 weeks of follow-up, the incidence of AAD in the probiotic group was 8% (259/3232) compared to 19% (598/3120) in the control group (RR 0.45, 95% CI 0.36 to 0.56; I² = 57%, 6352 participants; NNTB 9, 95% CI 7 to 13; moderate certainty evidence). Nineteen studies had loss to follow-up ranging from 1% to 46%. After making assumptions for those lost, the observed benefit was still statistically significant using an extreme plausible intention-to-treat (ITT) analysis, wherein the incidence of AAD in the probiotic group was 12% (436/3551) compared to 19% (664/3468) in the control group (7019 participants; RR 0.61; 95% CI 0.49 to 0.77; P <0.00001; I² = 70%). An a priori available case subgroup analysis exploring heterogeneity indicated that high dose (≥ 5 billion CFUs per day) is more effective than low probiotic dose (< 5 billion CFUs per day), interaction P value = 0.01. For the high dose studies the incidence of AAD in the probiotic group was 8% (162/2029) compared to 23% (462/2009) in the control group (4038 participants; RR 0.37; 95% CI 0.30 to 0.46; P = 0.06; moderate certainty evidence). For the low dose studies the incidence of AAD in the probiotic group was 8% (97/1155) compared to 13% (133/1059) in the control group (2214 participants; RR 0.68; 95% CI 0.46 to 1.01; P = 0.02). Again, assumptions for loss to follow-up using an extreme plausible ITT analysis was statistically significant. For high dose studies the incidence of AAD in the probiotic group was 13% (278/2218) compared to 23% (503/2207) in control group (4425 participants; RR 0.54; 95% CI 0.42 to 0.70; P <0.00001; I² = 68%; moderate certainty evidence).None of the 24 trials (4415 participants) that reported on adverse events reported any serious adverse events attributable to probiotics. Adverse event rates were low. After 5 days to 4 weeks follow-up, 4% (86/2229) of probiotics participants had an adverse event compared to 6% (121/2186) of control participants (RD 0.00; 95% CI -0.01 to 0.01; P < 0.00001; I² = 75%; low certainty evidence). Common adverse events included rash, nausea, gas, flatulence, abdominal bloating, and constipation. After 10 days to 12 weeks of follow-up, eight studies recorded data on our secondary outcome, the mean duration of diarrhea; with probiotics reducing diarrhea duration by almost one day (MD -0.91; 95% CI -1.38 to -0.44; P <0.00001; low certainty evidence). One study reported on microbiome characteristics, reporting no difference in changes with concurrent antibiotic and probiotic use. Authors' conclusions: The overall evidence suggests a moderate protective effect of probiotics for preventing AAD (NNTB 9, 95% CI 7 to 13). Using five criteria to evaluate the credibility of the subgroup analysis on probiotic dose, the results indicate the subgroup effect based on high dose probiotics (≥ 5 billion CFUs per day) was credible. Based on high-dose probiotics, the NNTB to prevent one case of diarrhea is 6 (95% CI 5 to 9). The overall certainty of the evidence for the primary endpoint, incidence of AAD based on high dose probiotics was moderate due to the minor issues with risk of bias and inconsistency related to a diversity of probiotic agents used. Evidence also suggests that probiotics may moderately reduce the duration of diarrhea, a reduction by almost one day. The benefit of high dose probiotics (e.g. Lactobacillus rhamnosus orSaccharomyces boulardii) needs to be confirmed by a large well-designed multi-centered randomized trial. It is premature to draw firm conclusions about the efficacy and safety of 'other' probiotic agents as an adjunct to antibiotics in children. Adverse event rates were low and no serious adverse events were attributable to probiotics. Although no serious adverse events were observed among inpatient and outpatient children, including small studies conducted in the intensive care unit and in the neonatal unit, observational studies not included in this review have reported serious adverse events in severely debilitated or immuno-compromised children with underlying risk factors including central venous catheter use and disorders associated with bacterial/fungal translocation.

The Cochrane database of systematic reviews · meta-analysis · 162 citationsread the source →

Therapist-supported Internet cognitive behavioural therapy for anxiety disorders in adults.

Background: Cognitive behavioural therapy (CBT) is an evidence-based treatment for anxiety disorders. Many people have difficulty accessing treatment, due to a variety of obstacles. Researchers have therefore explored the possibility of using the Internet to deliver CBT; it is important to ensure the decision to promote such treatment is grounded in high quality evidence. Objectives: To assess the effects of therapist-supported Internet CBT (ICBT) on remission of anxiety disorder diagnosis and reduction of anxiety symptoms in adults as compared to waiting list control, unguided CBT, or face-to-face CBT. Effects of treatment on quality of life and patient satisfaction with the intervention were also assessed. Search methods: We searched the Cochrane Depression, Anxiety and Neurosis Review Group Specialised Register (CCDANCTR) to 16 March 2015. The CCDANCTR includes relevant randomised controlled trials from MEDLINE, EMBASE, PsycINFO and CENTRAL. We also searched online clinical trial registries and reference lists of included studies. We contacted authors to locate additional trials. Selection criteria: Each identified study was independently assessed for inclusion by two authors. To be included, studies had to be randomised controlled trials of therapist-supported ICBT compared to a waiting list, attention, information, or online discussion group; unguided CBT (that is, self-help); or face-to-face CBT. We included studies that treated adults with an anxiety disorder (panic disorder, agoraphobia, social phobia, post-traumatic stress disorder, acute stress disorder, generalized anxiety disorder, obsessive compulsive disorder, and specific phobia) defined according to the Diagnostic and Statistical Manual of Mental Disorders III, III-R, IV, IV-TR or the International Classification of Disesases 9 or 10. Data collection and analysis: Two authors independently assessed the risk of bias of included studies and judged overall study quality. We used data from intention-to-treat analyses wherever possible. We assessed treatment effect for the dichotomous outcome of clinically important improvement in anxiety using a risk ratio (RR) with 95% confidence interval (CI). For disorder-specific and general anxiety symptom measures and quality of life we assessed continuous scores using standardized mean differences (SMD). We examined statistical heterogeneity using the I(2) statistic. Main results: We screened 1736 citations and selected 38 studies (3214 participants) for inclusion. The studies examined social phobia (11 trials), panic disorder with or without agoraphobia (8 trials), generalized anxiety disorder (5 trials), post-traumatic stress disorder (2 trials), obsessive compulsive disorder (2 trials), and specific phobia (2 trials). Eight remaining studies included a range of anxiety disorder diagnoses. Studies were conducted in Sweden (18 trials), Australia (14 trials), Switzerland (3 trials), the Netherlands (2 trials), and the USA (1 trial) and investigated a variety of ICBT protocols. Three primary comparisons were identified, therapist-supported ICBT versus waiting list control, therapist-supported versus unguided ICBT, and therapist-supported ICBT versus face-to-face CBT.Low quality evidence from 11 studies (866 participants) contributed to a pooled risk ratio (RR) of 3.75 (95% CI 2.51 to 5.60; I(2) = 50%) for clinically important improvement in anxiety at post-treatment, favouring therapist-supported ICBT over a waiting list, attention, information, or online discussion group only. The SMD for disorder-specific symptoms at post-treatment (28 studies, 2147 participants; SMD -1.06, 95% CI -1.29 to -0.82; I(2) = 83%) and general anxiety symptoms at post-treatment (19 studies, 1496 participants; SMD -0.75, 95% CI -0.98 to -0.52; I(2) = 78%) favoured therapist-supported ICBT; the quality of the evidence for both outcomes was low. One study compared unguided CBT to therapist-supported ICBT for clinically important improvement in anxiety at post-treatment, showing no difference in outcome between treatments (54 participants; very low quality evidence). At post-treatment there were no clear differences between unguided CBT and therapist-supported ICBT for disorder-specific anxiety symptoms (5 studies, 312 participants; SMD -0.22, 95% CI -0.56 to 0.13; I(2) = 58%; very low quality evidence) or general anxiety symptoms (2 studies, 138 participants; SMD 0.28, 95% CI -2.21 to 2.78; I(2) = 0%; very low quality evidence).Compared to face-to-face CBT, therapist-supported ICBT showed no significant differences in clinically important improvement in anxiety at post-treatment (4 studies, 365 participants; RR 1.09, 95% CI 0.89 to 1.34; I(2) = 0%; low quality evidence). There were also no clear differences between face-to-face and therapist supported ICBT for disorder-specific anxiety symptoms at post-treatment (7 studies, 450 participants; SMD 0.06, 95% CI -0.25 to 0.37; I(2) = 60%; low quality evidence) or general anxiety symptoms at post-treatment (5 studies, 317 participants; SMD 0.17, 95% CI -0.35 to 0.69; I(2) = 78%; low quality evidence).Overall, risk of bias in included studies was low or unclear for most domains. However, due to the nature of psychosocial intervention trials, blinding of participants and personnel, and outcome assessment tended to have a high risk of bias. Heterogeneity across a number of the meta-analyses was substantial, some was explained by type of anxiety disorder or may be meta-analytic measurement artefact due to combining many assessment measures. Adverse events were rarely reported. Authors' conclusions: Therapist-supported ICBT appears to be an efficacious treatment for anxiety in adults. The evidence comparing therapist-supported ICBT to waiting list, attention, information, or online discussion group only control was low to moderate quality, the evidence comparing therapist-supported ICBT to unguided ICBT was very low quality, and comparisons of therapist-supported ICBT to face-to-face CBT were low quality. Further research is needed to better define and measure any potential harms resulting from treatment. These findings suggest that therapist-supported ICBT is more efficacious than a waiting list, attention, information, or online discussion group only control, and that there may not be a significant difference in outcome between unguided CBT and therapist-supported ICBT; however, this latter finding must be interpreted with caution due to imprecision. The evidence suggests that therapist-supported ICBT may not be significantly different from face-to-face CBT in reducing anxiety. Future research should explore heterogeneity among studies which is reducing the quality of the evidence body, involve equivalence trials comparing ICBT and face-to-face CBT, examine the importance of the role of the therapist in ICBT, and include effectiveness trials of ICBT in real-world settings. A timely update to this review is needed given the fast pace of this area of research.

The Cochrane database of systematic reviews · meta-analysis · 158 citationsread the source →

Health and financial costs of adverse childhood experiences in 28 European countries: a systematic review and meta-analysis.

Background: Adverse childhood experiences (ACEs) are associated with increased health risks across the life course. We aimed to estimate the annual health and financial burden of ACEs for 28 European countries. Methods: In this systematic review and meta-analysis, we searched MEDLINE, CINAHL, PsycINFO, Applied Social Sciences Index and Abstracts, Criminal Justice Databases, and Education Resources Information Center for quantitative studies (published Jan 1, 1990, to Sept 8, 2020) that reported prevalence of ACEs and risks of health outcomes associated with ACEs. Pooled relative risks were calculated for associations between ACEs and harmful alcohol use, smoking, illicit drug use, high body-mass index, depression, anxiety, interpersonal violence, cancer, type 2 diabetes, cardiovascular disease, stroke, and respiratory disease. Country-level ACE prevalence was calculated using available data. Country-level population attributable fractions (PAFs) due to ACEs were generated and applied to 2019 estimates of disability-adjusted life-years. Financial costs (US$ in 2019) were estimated using an adapted human capital approach. Findings: In most countries, interpersonal violence had the largest PAFs due to ACEs (range 14·7-53·5%), followed by harmful alcohol use (15·7-45·0%), illicit drug use (15·2-44·9%), and anxiety (13·9%-44·8%). Harmful alcohol use, smoking, and cancer had the highest ACE-attributable costs in many countries. Total ACE-attributable costs ranged from $0·1 billion (Montenegro) to $129·4 billion (Germany) and were equivalent to between 1·1% (Sweden and Turkey) and 6·0% (Ukraine) of nations' gross domestic products. Interpretation: Availability of ACE data varies widely between countries and country-level estimates cannot be directly compared. However, findings suggest ACEs are associated with major health and financial costs across European countries. The cost of not investing to prevent ACEs must be recognised, particularly as countries look to recover from the COVID-19 pandemic, which interrupted services and education, and potentially increased risk factors for ACEs. Funding: WHO Regional Office for Europe.

The Lancet. Public health · meta-analysis · 140 citationsread the source →

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

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

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

Cognitive behavioural therapy for anxiety disorders in children and adolescents.

Background: Previous Cochrane Reviews have shown that cognitive behavioural therapy (CBT) is effective in treating childhood anxiety disorders. However, questions remain regarding the following: up-to-date evidence of the relative efficacy and acceptability of CBT compared to waiting lists/no treatment, treatment as usual, attention controls, and alternative treatments; benefits across a range of outcomes; longer-term effects; outcomes for different delivery formats; and amongst children with autism spectrum disorders (ASD) and children with intellectual impairments. Objectives: To examine the effect of CBT for childhood anxiety disorders, in comparison with waitlist/no treatment, treatment as usual (TAU), attention control, alternative treatment, and medication. Search methods: We searched the Cochrane Common Mental Disorders Controlled Trials Register (all years to 2016), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO (each to October 2019), international trial registries, and conducted grey literature searches. Selection criteria: We included randomised controlled trials of CBT that involved direct contact with the child, parent, or both, and included non-CBT comparators (waitlist/no treatment, treatment as usual, attention control, alternative treatment, medication). Participants were younger than age 19, and met diagnostic criteria for an anxiety disorder diagnosis. Primary outcomes were remission of primary anxiety diagnosis post-treatment, and acceptability (number of participants lost to post-treatment assessment), and secondary outcomes included remission of all anxiety diagnoses, reduction in anxiety symptoms, reduction in depressive symptoms, improvement in global functioning, adverse effects, and longer-term effects. Data collection and analysis: We used standard methodological procedures as recommended by Cochrane. We used GRADE to assess the quality of the evidence. Main results: We included 87 studies and 5964 participants in quantitative analyses. Compared with waitlist/no treatment, CBT probably increases post-treatment remission of primary anxiety diagnoses (CBT: 49.4%, waitlist/no treatment: 17.8%; OR 5.45, 95% confidence interval (CI) 3.90 to 7.60; n = 2697, 39 studies, moderate quality); NNTB 3 (95% CI 2.25 to 3.57) and all anxiety diagnoses (OR 4.43, 95% CI 2.89 to 6.78; n = 2075, 28 studies, moderate quality). Low-quality evidence did not show a difference between CBT and TAU in post-treatment primary anxiety disorder remission (OR 3.19, 95% CI 0.90 to 11.29; n = 487, 8 studies), but did suggest CBT may increase remission from all anxiety disorders compared to TAU (OR 2.74, 95% CI 1.16 to 6.46; n = 203, 5 studies). Compared with attention control, CBT may increase post-treatment remission of primary anxiety disorders (OR 2.28, 95% CI 1.33 to 3.89; n = 822, 10 studies, low quality) and all anxiety disorders (OR 2.75, 95% CI 1.22 to 6.17; n = 378, 5 studies, low quality). There was insufficient available data to compare CBT to alternative treatments on post-treatment remission of primary anxiety disorders, and low-quality evidence showed there may be little to no difference between these groups on post-treatment remission of all anxiety disorders (OR 0.89, 95% CI 0.35 to 2.23; n = 401, 4 studies) Low-quality evidence did not show a difference for acceptability between CBT and waitlist/no treatment (OR 1.09, 95% CI 0.85 to 1.41; n=3158, 45 studies), treatment as usual (OR 1.37, 95% CI 0.73 to 2.56; n = 441, 8 studies), attention control (OR 1.00, 95% CI 0.68 to 1.49; n = 797, 12 studies) and alternative treatment (OR 1.58, 95% CI 0.61 to 4.13; n=515, 7 studies). No adverse effects were reported across all studies; however, in the small number of studies where any reference was made to adverse effects, it was not clear that these were systematically monitored. Results from the anxiety symptom outcomes, broader outcomes, longer-term outcomes and subgroup analyses are provided in the text. We did not find evidence of consistent differences in outcomes according to delivery formats (e.g. individual versus group; amount of therapist contact time) or amongst samples with and without ASD, and no studies included samples of children with intellectual impairments. Authors' conclusions: CBT is probably more effective in the short-term than waiting lists/no treatment, and may be more effective than attention control. We found little to no evidence across outcomes that CBT is superior to usual care or alternative treatments, but our confidence in these findings are limited due to concerns about the amount and quality of available evidence, and we still know little about how best to efficiently improve outcomes.

The Cochrane database of systematic reviews · meta-analysis · 162 citationsread the source →

Cognitive behavioural therapy for tinnitus.

Background: Tinnitus affects up to 21% of the adult population with an estimated 1% to 3% experiencing severe problems. Cognitive behavioural therapy (CBT) is a collection of psychological treatments based on the cognitive and behavioural traditions in psychology and often used to treat people suffering from tinnitus. Objectives: To assess the effects and safety of CBT for tinnitus in adults. Search methods: The Cochrane ENT Information Specialist searched the ENT Trials Register; CENTRAL (2019, Issue 11); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 25 November 2019. Selection criteria: Randomised controlled trials (RCTs) of CBT versus no intervention, audiological care, tinnitus retraining therapy or any other active treatment in adult participants with tinnitus. Data collection and analysis: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were the impact of tinnitus on disease-specific quality of life and serious adverse effects. Our secondary outcomes were: depression, anxiety, general health-related quality of life, negatively biased interpretations of tinnitus and other adverse effects. We used GRADE to assess the certainty of evidence for each outcome. Main results: We included 28 studies (mostly from Europe) with a total of 2733 participants. All participants had had tinnitus for at least three months and their average age ranged from 43 to 70 years. The duration of the CBT ranged from 3 to 22 weeks and it was mostly conducted in hospitals or online. There were four comparisons and we were interested in outcomes at end of treatment, and 6 and 12 months follow-up. The results below only refer to outcomes at end of treatment due to an absence of evidence at the other follow-up time points. CBT versus no intervention/wait list control Fourteen studies compared CBT with no intervention/wait list control. For the primary outcome, CBT may reduce the impact of tinnitus on quality of life at treatment end (standardised mean difference (SMD) -0.56, 95% confidence interval (CI) -0.83 to -0.30; 10 studies; 537 participants; low certainty). Re-expressed as a score on the Tinnitus Handicap Inventory (THI; range 0 to 100) this is equivalent to a score 10.91 points lower in the CBT group, with an estimated minimal clinically important difference (MCID) for this scale being 7 points. Seven studies, rated as moderate certainty, either reported or informed us via personal communication about serious adverse effects. CBT probably results in little or no difference in adverse effects: six studies reported none and in one study one participant in the CBT condition worsened (risk ratio (RR) 3.00, 95% CI 0.13 to 69.87). For the secondary outcomes, CBT may result in a slight reduction in depression (SMD -0.34, 95% CI-0.60 to -0.08; 8 studies; 502 participants; low certainty). However, we are uncertain whether CBT reduces anxiety, improves health-related quality of life or reduces negatively biased interpretations of tinnitus (all very low certainty). From seven studies, no other adverse effects were reported (moderate certainty). CBT versus audiological care Three studies compared CBT with audiological care. CBT probably reduces the impact of tinnitus on quality of life when compared with audiological care as measured by the THI (range 0 to 100; mean difference (MD) -5.65, 95% CI -9.79 to -1.50; 3 studies; 444 participants) (moderate certainty; MCID = 7 points). No serious adverse effects occurred in the two included studies reporting these, thus risk ratios were not calculated (moderate certainty). The evidence suggests that CBT may slightly reduce depression but may result in little or no difference in anxiety or health-related quality of life (all low certainty) when compared with audiological care. CBT may reduce negatively biased interpretations of tinnitus when compared with audiological care (low certainty). No other adverse effects were reported for either group (moderate certainty). CBT versus tinnitus retraining therapy (TRT) One study compared CBT with TRT (including bilateral sound generators as per TRT protocol). CBT may reduce the impact of tinnitus on quality of life as measured by the THI when compared with TRT (range 0 to 100) (MD -15.79, 95% CI -27.91 to -3.67; 1 study; 42 participants; low certainty). For serious adverse effects three participants deteriorated during the study: one in the CBT (n = 22) and two in the TRT group (n = 20) (RR 0.45, 95% CI 0.04 to 4.64; low certainty). We are uncertain whether CBT reduces depression and anxiety or improves health-related quality of life (low certainty). CBT may reduce negatively biased interpretations of tinnitus. No data were available for other adverse effects. CBT versus other active control Sixteen studies compared CBT with another active control (e.g. relaxation, information, Internet-based discussion forums). CBT may reduce the impact of tinnitus on quality of life when compared with other active treatments (SMD -0.30, 95% CI -0.55 to -0.05; 12 studies; 966 participants; low certainty). Re-expressed as a THI score this is equivalent to 5.84 points lower in the CBT group than the other active control group (MCID = 7 points). One study reported that three participants deteriorated: one in the CBT and two in the information only group (RR 1.70, 95% CI 0.16 to 18.36; low certainty). CBT may reduce depression and anxiety (both low certainty). We are uncertain whether CBT improves health-related quality of life compared with other control. CBT probably reduces negatively biased interpretations of tinnitus compared with other treatments. No data were available for other adverse effects. Authors' conclusions: CBT may be effective in reducing the negative impact that tinnitus can have on quality of life. There is, however, an absence of evidence at 6 or 12 months follow-up. There is also some evidence that adverse effects may be rare in adults with tinnitus receiving CBT, but this could be further investigated. CBT for tinnitus may have small additional benefit in reducing symptoms of depression although uncertainty remains due to concerns about the quality of the evidence. Overall, there is limited evidence for CBT for tinnitus improving anxiety, health-related quality of life or negatively biased interpretations of tinnitus.

The Cochrane database of systematic reviews · meta-analysis · 131 citationsread the source →

Treatment of premenstrual dysphoric disorder with a new drospirenone-containing oral contraceptive formulation.

Purpose: This multicenter, double-blind, placebo-controlled crossover study evaluated the efficacy of a new oral contraceptive (OC) formulation containing drospirenone 3 mg and ethinyl estradiol (EE) 20 mug in treating symptoms of premenstrual dysphoric disorder (PMDD). Method: The OC formulation or placebo was administered for 24 days in a 28-day cycle (24/4), rather than the usual 21-day active treatment, 7-day inert-pill regimen. Participants (N=64) were randomized to either study treatment for three cycles and then after a washout period of one treatment-free cycle switched to the alternate treatment. Results: The mean decrease from baseline for total Daily Record of Severity of Problems (DRSP) scores while using drospirenone/EE was significantly greater than for placebo (-12.47, 95% CI=-18.28, -6.66; p<.001). A positive response (i.e., a score of 1 or 2 in the Clinical Global Impressions-Improvement scale) occurred in 61.7% and 31.8% of subjects while taking drospirenone/EE and placebo, respectively (p=.009). Conclusion: Drospirenone/EE, given in a 24/4 regimen, was superior to placebo for improving symptoms associated with PMDD.

Contraception · randomised controlled trial · 145 citationsread the source →

Parenting for Lifelong Health for Young Children: a randomized controlled trial of a parenting program in South Africa to prevent harsh parenting and child conduct problems.

Background: Parenting programs suitable for delivery at scale in low-resource contexts are urgently needed. We conducted a randomized trial of Parenting for Lifelong Health (PLH) for Young Children, a low-cost 12-session program designed to increase positive parenting and reduce harsh parenting and conduct problems in children aged 2-9. Methods: Two hundred and ninety-six caregivers, whose children showed clinical levels of conduct problems (Eyberg Child Behavior Inventory Problem Score, >15), were randomly assigned using a 1:1 ratio to intervention or control groups. At t0 , and at 4-5 months (t1 ) and 17 months (t2 ) after randomization, research assistants blind to group assignment assessed (through caregiver self-report and structured observation) 11 primary outcomes: positive parenting, harsh parenting, and child behavior; four secondary outcomes: parenting stress, caregiver depression, poor monitoring/supervision, and social support. Trial registration: ClinicalTrials.gov (NCT02165371); Pan African Clinical Trial Registry (PACTR201402000755243); Violence Prevention Trials Register (http://www.preventviolence.info/Trials?ID=24). Results: Caregivers attended on average 8.4 sessions. After adjustment for 30 comparisons, strongest results were as follows: at t1 , frequency of self-reported positive parenting strategies (10% higher in the intervention group, p = .003), observed positive parenting (39% higher in the intervention group, p = .003), and observed positive child behavior (11% higher in the intervention group, p = .003); at t2, both observed positive parenting and observed positive child behavior were higher in the intervention group (24%, p = .003; and 17%, p = .003, respectively). Results with p-values < .05 prior to adjustment were as follows: At t1 , the intervention group self-reported 11% fewer child problem behaviors, 20% fewer problems with implementing positive parenting strategies, and less physical and psychological discipline (28% and 14% less, respectively). There were indications that caregivers reported 20% less depression but 7% more parenting stress at t1 . Group differences were nonsignificant for observed negative child behavior, and caregiver-reported child behavior, poor monitoring or supervision, and caregiver social support. Conclusions: PLH for Young Children shows promise for increasing positive parenting and reducing harsh parenting.

Journal of child psychology and psychiatry, and allied disciplines · randomised controlled trial · 88 citationsread the source →

Cardiovascular effects of pulmonary exposure to single-wall carbon nanotubes.

Background: Engineered nanosized materials, such as single-wall carbon nanotubes (SWCNT), are emerging as technologically important in different industries. Objective: The unique physical characteristics and the pulmonary toxicity of SWCNTs raised concerns that respiratory exposure to these materials may be associated with cardiovascular adverse effects. Methods: In these studies we evaluated aortic mitochondrial alterations by oxidative stress assays, including quantitative polymerase chain reaction of mitochondrial (mt) DNA and plaque formation by morphometric analysis in mice exposed to SWCNTs. Results: A single intrapharyngeal instillation of SWCNTs induced activation of heme oxygenase-1 (HO-1), a marker of oxidative insults, in lung, aorta, and heart tissue in HO-1 reporter transgenic mice. Furthermore, we found that C57BL/6 mice, exposed to SWCNT (10 and 40 mug/mouse), developed aortic mtDNA damage at 7, 28, and 60 days after exposure. mtDNA damage was accompanied by changes in aortic mitochondrial glutathione and protein carbonyl levels. Because these modifications have been related to cardiovascular diseases, we evaluated whether repeated exposure to SWCNTs (20 mug/mouse once every other week for 8 weeks) stimulates the progression of atherosclerosis in ApoE(-/-) transgenic mice. Although SWCNT exposure did not modify the lipid profiles of these mice, it resulted in accelerated plaque formation in ApoE(-/-) mice fed an atherogenic diet. Plaque areas in the aortas, measured by the en face method, and in the brachiocephalic arteries, measured histopathologically, were significantly increased in the SWCNT-treated mice. This response was accompanied by increased mtDNA damage but not inflammation. Conclusions: Taken together, the findings are of sufficient significance to warrant further studies to evaluate the systemic effects of SWCNT under workplace or environmental exposure paradigms.

Environmental health perspectives · 207 citationsread the source →

Very preterm birth influences parental mental health and family outcomes seven years after birth.

Objective: To evaluate the long-term influence of very preterm birth on parental mental health, family functioning, and parenting stress at age 2 and 7 years. Study design: Participants were 183 children born very preterm (<30 weeks gestation; n = 148 families) and 69 term-born children (n = 66 families). When children were age 7 years, parents were assessed based on the Hospital Anxiety and Depression Scale, the Family Assessment Device, the Parenting Stress Index, and the Social Support Questionnaire. Similar measures were evaluated at age 2 years. Results: When the children were age 7 years, parents of the very preterm-born children were more likely to report moderate to severe anxiety symptoms (P = .03), higher levels of depression symptoms (P = .03), poorer family functioning (P < .05), and higher levels of parenting stress (P < .001) compared with parents of the children born at term. Group differences in parenting stress and family functioning persisted after adjustment for social risk and child neurodevelopmental disability. There was strong evidence of a relationship between family functioning and parent-related stress at age 2 and 7 years (P < .001), but little evidence that parental mental health problems at 2 years were predictive of anxiety (P = .15) or depression (P = .28) at 7 years for parents of very preterm children. Conclusion: These findings demonstrate that very preterm birth has a negative influence on parent and family functioning at 7 years after birth, which for some families is consistent with their functioning at 2 years. These results have implications for the support required by parents of very preterm children.

The Journal of pediatrics · 143 citationsread the source →

Treatment Approaches for Problematic Pornography Use: A Systematic Review.

Problematic pornography use (PPU) is an emerging condition associated with several negative psychological and sexual outcomes. This study aimed to systematically review treatment approaches for PPU. Potentially eligible studies were searched for in PubMed/MEDLINE, Embase, PsycINFO, and Web of Science up to April 1, 2023. The quality of the evidence was assessed with the use of the Joanna Briggs Institute's checklists, the Cochrane risk-of-bias tools, and the GRADE approach. A total of 8936 references were retrieved, and 28 studies were included in the systematic review (n = 500 participants). Included studies were case reports (k = 16), case series (k = 1), quasi-experimental investigations (k = 7), and randomized clinical trials (k = 4). The majority of included studies presented overall low quality and significant risk of bias, with all interventions receiving a low or very low rating according to the GRADE approach. Most studies investigated psychological interventions, with the predominance of second and third wave cognitive behavioral therapy interventions. Pharmacological treatments included opioid antagonists (naltrexone in most cases) and antidepressants, while one study investigated a protocol that included rTMS. Several investigations described the combination of psychological and pharmacological approaches. Most studies did not report on side effects, with online and self-help interventions presenting significant issues in terms of treatment adherence. Even though there are promising options that may have efficacy for the treatment of patients with PPU, the literature in the topic still presents significant limitations that compromise the reaching of more definitive conclusions.

Archives of sexual behavior · systematic review · 9 citationsread the source →

Social capital and physical health: An updated review of the literature for 2007-2018.

Purpose: Social capital is frequently indicated as a determinant of population health. Despite an increase in the frequency of public health studies including such measures, our understanding of social capital's effects on health remains unclear. In 2008, a systematic review of the "first decade" of research on social capital and health was published in the textbook Social Capital and Health. Our study intends to update and expand upon this original review to account for developments in the literature over the second decade of research on social capital and health. Methods: We employed a systematic review of empirical studies investigating the relationship between measures of social capital and physical health outcomes published between January 1, 2007 and December 31, 2018. To identify potential studies, we conducted searches of PubMed, Embase, and PsychINFO databases in January 2019 using combinations of "social capital" and "physical health" search terms. Results: We identified 1,608 unique articles and reviewed 145 studies meeting our inclusion criteria. The most frequently examined health condition was self-reported health (57%), followed by mortality (12%), cardiovascular diseases (10%), obesity (7%), diabetes (6%), infectious diseases (5%), and cancers (3%). Of these studies, 127 (88%) reported at least partial support for a protective association between social capital and health. However, only 41 (28%) reported exclusively positive findings. The majority (59%) of results were mixed, suggesting a nuanced relationship between social capital and health. This finding could also be indicative of differences in study design, which showed substantial variation. Conclusions: Despite limitations in the literature, our review chronicles an evolution in the field of social capital and health in terms of size and sophistication. Overall, these studies suggest that social capital may be an important protective factor for some physical health outcomes, but further research is needed to confirm and clarify these findings.

Social science & medicine (1982) · systematic review · 137 citationsread the source →

Behavioural and cognitive-behavioural interventions for outwardly directed aggressive behaviour in people with intellectual disabilities.

Background: Outwardly directed aggressive behaviour in people with intellectual disabilities is a significant issue that may lead to poor quality of life, social exclusion and inpatient psychiatric admissions. Cognitive and behavioural approaches have been developed to manage aggressive behaviour but the effectiveness of these interventions on reducing aggressive behaviour and other outcomes are unclear. This is the third update of this review and adds nine new studies, resulting in a total of 15 studies in this review. Objectives: To evaluate the efficacy of behavioural and cognitive-behavioural interventions on outwardly directed aggressive behaviour compared to usual care, wait-list controls or no treatment in people with intellectual disability. We also evaluated enhanced interventions compared to non-enhanced interventions. Search methods: We used standard, extensive Cochrane search methods. The latest search date was March 2022. We revised the search terms to include positive behaviour support (PBS). Selection criteria: We included randomised and quasi-randomised trials of children and adults with intellectual disability of any duration, setting and any eligible comparator. Data collection and analysis: We used standard Cochrane methods. Our primary outcomes were change in 1. aggressive behaviour, 2. ability to control anger, and 3. adaptive functioning, and 4. Adverse effects: Our secondary outcomes were change in 5. mental state, 6. medication, 7. care needs and 8. quality of life, and 9. frequency of service utilisation and 10. user satisfaction data. We used GRADE to assess certainty of evidence for each outcome. We expressed treatment effects as mean differences (MD) or odds ratios (OR), with 95% confidence intervals (CI). Where possible, we pooled data using a fixed-effect model. Main results: This updated version comprises nine new studies giving 15 included studies and 921 participants. The update also adds new interventions including parent training (two studies), mindfulness-based positive behaviour support (MBPBS) (two studies), reciprocal imitation training (RIT; one study) and dialectical behavioural therapy (DBT; one study). It also adds two new studies on PBS. Most studies were based in the community (14 studies), and one was in an inpatient forensic service. Eleven studies involved adults only. The remaining studies involved children (one study), children and adolescents (one study), adolescents (one study), and adolescents and adults (one study). One study included boys with fragile X syndrome. Six studies were conducted in the UK, seven in the USA, one in Canada and one in Germany. Only five studies described sources of funding. Four studies compared anger management based on cognitive behaviour therapy to a wait-list or no treatment control group (n = 263); two studies compared PBS with treatment as usual (TAU) (n = 308); two studies compared carer training on mindfulness and PBS with PBS only (n = 128); two studies involving parent training on behavioural approaches compared to wait-list control or TAU (n = 99); one study of mindfulness to a wait-list control (n = 34); one study of adapted dialectal behavioural therapy compared to wait-list control (n = 21); one study of RIT compared to an active control (n = 20) and one study of modified relaxation compared to an active control group (n = 12). There was moderate-certainty evidence that anger management may improve severity of aggressive behaviour post-treatment (MD -3.50, 95% CI -6.21 to -0.79; P = 0.01; 1 study, 158 participants); very low-certainty evidence that it might improve self-reported ability to control anger (MD -8.38, 95% CI -14.05 to -2.71; P = 0.004, I2 = 2%; 3 studies, 212 participants), adaptive functioning (MD -21.73, 95% CI -36.44 to -7.02; P = 0.004; 1 study, 28 participants) and psychiatric symptoms (MD -0.48, 95% CI -0.79 to -0.17; P = 0.002; 1 study, 28 participants) post-treatment; and very low-certainty evidence that it does not improve quality of life post-treatment (MD -5.60, 95% CI -18.11 to 6.91; P = 0.38; 1 study, 129 participants) or reduce service utilisation and costs at 10 months (MD 102.99 British pounds, 95% CI -117.16 to 323.14; P = 0.36; 1 study, 133 participants). There was moderate-certainty evidence that PBS may reduce aggressive behaviour post-treatment (MD -7.78, 95% CI -15.23 to -0.32; P = 0.04, I2 = 0%; 2 studies, 275 participants) and low-certainty evidence that it probably does not reduce aggressive behaviour at 12 months (MD -5.20, 95% CI -13.27 to 2.87; P = 0.21; 1 study, 225 participants). There was low-certainty evidence that PBS does not improve mental state post-treatment (OR 1.44, 95% CI 0.83 to 2.49; P = 1.21; 1 study, 214 participants) and very low-certainty evidence that it might not reduce service utilisation at 12 months (MD -448.00 British pounds, 95% CI -1660.83 to 764.83; P = 0.47; 1 study, 225 participants). There was very low-certainty evidence that mindfulness may reduce incidents of physical aggression (MD -2.80, 95% CI -4.37 to -1.23; P < 0.001; 1 study; 34 participants) and low-certainty evidence that MBPBS may reduce incidents of aggression post-treatment (MD -10.27, 95% CI -14.86 to -5.67; P < 0.001, I2 = 87%; 2 studies, 128 participants). Reasons for downgrading the certainty of evidence were risk of bias (particularly selection and performance bias); imprecision (results from single, often small studies, wide CIs, and CIs crossing the null effect); and inconsistency (statistical heterogeneity). Authors' conclusions: There is moderate-certainty evidence that cognitive-behavioural approaches such as anger management and PBS may reduce outwardly directed aggressive behaviour in the short term but there is less certainty about the evidence in the medium and long term, particularly in relation to other outcomes such as quality of life. There is some evidence to suggest that combining more than one intervention may have cumulative benefits. Most studies were small and there is a need for larger, robust randomised controlled trials, particularly for interventions where the certainty of evidence is very low. More trials are needed that focus on children and whether psychological interventions lead to reductions in the use of psychotropic medications.

The Cochrane database of systematic reviews · systematic review · 6 citationsread the source →

Long-term outcomes of childhood sexual abuse: an umbrella review.

Background: Although many meta-analyses have examined the association between childhood sexual abuse and subsequent outcomes, the scope, validity, and quality of this evidence has not been comprehensively assessed. We aimed to systematically review existing meta-analyses on a wide range of long-term psychiatric, psychosocial, and physical health outcomes of childhood sexual abuse, and evaluate the quality of the literature. Methods: In this umbrella review, we searched four databases (PsycINFO, PubMed, Cumulative Index to Nursing and Allied Health Literature, and Global Health) from inception to Dec 31, 2018, to identify meta-analyses of observational studies that examined the association between childhood sexual abuse (before 18 years of age) and long-term consequences (after 18 years). We compared odds ratios (ORs) across different outcomes. We also examined measures of quality, including heterogeneity between studies and evidence for publication bias. This study is registered with PROSPERO, CRD42016049701. Findings: We identified 19 meta-analyses that included 559 primary studies, covering 28 outcomes in 4 089 547 participants. Childhood sexual abuse was associated with 26 of 28 specific outcomes: specifically, six of eight adult psychiatric diagnoses (ORs ranged from 2·2 [95% CI 1·8-2·8] to 3·3 [2·2-4·8]), all studied negative psychosocial outcomes (ORs ranged from 1·2 [1·1-1·4] to 3·4 [2·3-4·8]), and all physical health conditions (ORs ranged from 1·4 [1·3-1·6] to 1·9 [1·4-2·8]). Strongest psychiatric associations with childhood sexual abuse were reported for conversion disorder (OR 3·3 [95% CI 2·2-4·8]), borderline personality disorder (2·9 [2·5-3·3]), anxiety (2·7 [2·5-2·8]), and depression (2·7 [2·4-3·0]). The systematic reviews for two psychiatric outcomes (post-traumatic stress disorder and schizophrenia) and one psychosocial outcome (substance misuse) met high quality standards. Quality was low for meta-analyses on borderline personality disorder and anxiety, and moderate for conversion disorder. Assuming causality, population attributable risk fractions for outcomes ranged from 1·7% (95% CI 0·7-3·3) for unprotected sexual intercourse to 14·4% (8·8-19·9) for conversion disorder. Interpretation: Although childhood sexual abuse was associated with a wide range of psychosocial and health outcomes, systematic reviews on only two psychiatric disorders (post-traumatic stress disorder and schizophrenia) and one psychosocial outcome (substance misuse) were of a high quality. Whether services should prioritise interventions that mitigate developing certain psychiatric disorders following childhood abuse requires further review. Higher-quality meta-analyses for specific outcomes and more empirical studies on the developmental pathways from childhood sexual abuse to later outcomes are necessary. Funding: Wellcome Trust.

The lancet. Psychiatry · systematic review · 459 citationsread the source →

Twitter as a Tool for Health Research: A Systematic Review.

Background: Researchers have used traditional databases to study public health for decades. Less is known about the use of social media data sources, such as Twitter, for this purpose. Objectives: To systematically review the use of Twitter in health research, define a taxonomy to describe Twitter use, and characterize the current state of Twitter in health research. Search methods: We performed a literature search in PubMed, Embase, Web of Science, Google Scholar, and CINAHL through September 2015. Selection criteria: We searched for peer-reviewed original research studies that primarily used Twitter for health research. Data collection and analysis: Two authors independently screened studies and abstracted data related to the approach to analysis of Twitter data, methodology used to study Twitter, and current state of Twitter research by evaluating time of publication, research topic, discussion of ethical concerns, and study funding source. Main results: Of 1110 unique health-related articles mentioning Twitter, 137 met eligibility criteria. The primary approaches for using Twitter in health research that constitute a new taxonomy were content analysis (56%; n = 77), surveillance (26%; n = 36), engagement (14%; n = 19), recruitment (7%; n = 9), intervention (7%; n = 9), and network analysis (4%; n = 5). These studies collectively analyzed more than 5 billion tweets primarily by using the Twitter application program interface. Of 38 potential data features describing tweets and Twitter users, 23 were reported in fewer than 4% of the articles. The Twitter-based studies in this review focused on a small subset of data elements including content analysis, geotags, and language. Most studies were published recently (33% in 2015). Public health (23%; n = 31) and infectious disease (20%; n = 28) were the research fields most commonly represented in the included studies. Approximately one third of the studies mentioned ethical board approval in their articles. Primary funding sources included federal (63%), university (13%), and foundation (6%). Conclusions: We identified a new taxonomy to describe Twitter use in health research with 6 categories. Many data elements discernible from a user's Twitter profile, especially demographics, have been underreported in the literature and can provide new opportunities to characterize the users whose data are analyzed in these studies. Twitter-based health research is a growing field funded by a diversity of organizations. Public health implications. Future work should develop standardized reporting guidelines for health researchers who use Twitter and policies that address privacy and ethical concerns in social media research.

American journal of public health · systematic review · 368 citationsread the source →

Adverse childhood experiences are associated with adult sleep disorders: a systematic review.

Adverse childhood experiences (ACEs) represent substantial threats to public health and affect about 58% of youth in the US. In addition to their acute effects such as injury and physical trauma, ACEs are associated with an increased risk of several negative health outcomes throughout the life course. Emerging evidence suggests that sleep disorders may be one such outcome, but existing studies have not been systematically reviewed and summarized. We conducted a systematic review to summarize the evidence concerning the relationship between ACEs and sleep disorders and disturbances, with a focus on adult women. Original publications were identified through searches of the electronic databases MEDLINE, Embase, and Web of Science using the keywords "childhood," "adversity," "abuse," and "sleep" as well as searches of the reference lists of eligible studies. Studies evaluating ACEs that occurred before 18 years of age and sleep outcomes that were assessed at 18 years or older were adjudicated and included. A total of 30 publications were identified. Of the 30 studies, 28 were retrospective analyses and there was vast heterogeneity in the types of ACEs and sleep outcomes measured. The majority of retrospective studies (N = 25 of 28) documented statistically significant associations between sleep disorders including sleep apnea, narcolepsy, nightmare distress, sleep paralysis, and psychiatric sleep disorders with a history of childhood adversity. In many studies, the strengths of associations increased with the number and severity of adverse experiences. These associations were corroborated by the two prospective studies published to date. Notably, investigators have documented statistically significant associations between family conflict at 7-15 years of age and insomnia at 18 years of age (odds ratio, OR = 1.4; 95% confidence interval, CI = 1.2-1.7) and between childhood sexual abuse and sleep disturbances 10 years later in adult women (β = 0.24, p <0.05). There is a growing scientific body of knowledge suggesting an association between ACEs and multiple sleep disorders in adulthood. The available evidence indicates the need to develop treatment strategies such as trauma-informed care for survivors of abuse who suffer from sleep disorders and disturbances. Further, longitudinal studies among diverse populations are needed to improve the overall understanding of this association and to investigate potential gender and racial/ethnic disparities in the strength of the association.

Sleep medicine · systematic review · 272 citationsread the source →

Using Mindfulness to Manage Moral Injury in Veterans: Feasibility and Satisfaction of a Pilot Randomized Controlled Trial.

Objective: The present study assessed program feasibility and satisfaction among recent-era veterans who participated in Mindfulness to Manage Moral Injury (MMMI), a live facilitated web-based 7-week mindfulness-based program targeting moral injury among veterans. Method: In total, 56 post-9/11 veterans were recruited with 28 randomized to the MMMI condition and 28 to the Education and Support (ES) condition. Most participants identified as being White (71.4%), male (66.1%), and had a reported mean age of 41.50 years (Median = 39.50, SD = 9.26). Results: Among the 56 participants, 82.1% attended at least one treatment session and 44.6% completed all seven sessions. There were no significant differences in the average number of sessions attended between the MMMI (M = 4.79, SD = 2.70) and the ES (M = 4.68, SD = 2.84) conditions, t(54) = 0.145, p = 0.87. Regarding randomization, there were no statistically significant differences on almost all demographic (i.e., years in military, gender, ethnicity) characteristics and baseline scores on all outcomes across treatment conditions, thus ensuring randomization was adequately met. Of the 56 who consented, 41 (73.21%) completed most study components (i.e., completed baseline and follow-up surveys, at least 1 weekly survey, and attended at least one treatment session). Regarding treatment satisfaction, individuals in the MMMI condition reported higher treatment satisfaction (Cohen's d = 0.66). Conclusions: Preliminary findings suggest MMMI is feasible and acceptable and may be able to reach veterans who may not seek traditional Veterans Affairs Medical Center care or who prefer a web-based program. Given its promise for the treatment of moral injury among veterans, MMMI warrants additional large-scale clinical-trial testing.

Journal of clinical psychology · randomised controlled trial · 3 citationsread the source →

A randomized trial of motivational interviewing and facilitated contraceptive access to prevent rapid repeat pregnancy among adolescent mothers.

Background: Most interventions designed to reduce teen pregnancy rates have not focused on pregnant and/or parenting adolescents. Therefore, a large randomized controlled trial was conducted regarding a motivational interviewing program entitled Teen Options to Prevent Pregnancy in a low-income sample of adolescent mothers. This program recommended monthly sessions between a participant and a registered nurse over 18 months. This program also featured facilitated birth control access through transportation assistance and a part-time contraceptive clinic. Objective: The impact of this program on rapid repeat pregnancies at 18 months after enrollment was evaluated. Study design: Five hundred ninety-eight adolescent females were enrolled from 7 obstetrics-gynecology clinics and 5 postpartum units of a large hospital system in a Midwestern city. Each participant was enrolled at least 28 weeks pregnant or less than 9 weeks postpartum. Each participant was randomized to either the Teen Options to Prevent Pregnancy intervention or a usual-care control condition. Intervention participants averaged 4.5 hours of assistance. Participants were contacted by blinded research staff at 6 and 18 months to complete self-report surveys. Differences in outcomes between the intervention and control groups were assessed using ordinary least-squares regression. Results: There was an 18.1% absolute reduction in self-reported repeat pregnancy in the intervention group relative to the control group (20.5% vs 38.6%%; P < .001). There was a 13.7% absolute increase in self-reported long-acting reversible contraception use in the intervention group relative to the control group (40.2% vs 26.5%, P = .002). There was no evidence of harmful effects of the intervention on sexual risk behaviors, such as having sexual intercourse without a condom or greater number of partners. Conclusion: The Teen Options to Prevent Pregnancy program represents one of the few evidence-based interventions to reduce rapid repeat teen pregnancy. This relatively brief intervention may be a viable alternative to more time-intensive programs that adolescent mothers may be unable or unwilling to receive.

American journal of obstetrics and gynecology · randomised controlled trial · 20 citationsread the source →

Assessing the effectiveness of mindfulness-based programs on mental health during pregnancy and early motherhood - a randomized control trial.

Background: The process of entering motherhood is highly stressful for women, with 15-85% of new mothers experiencing postpartum blues or depression. This study was designed to evaluate the efficacy of a mindfulness-based childbirth and parenting program in improving psychological health during the postpartum period. Methods: This research was a randomized controlled trial with single blinding. Recruitment began after the participating hospital granted formal approval. A total of 74 women between 13 and 28-weeks gestation were allocated either to the intervention group or to the comparison group. The intervention program included a series of eight, 3-h classes held once weekly and 1 day of 7-h silent meditation. Psychological health was assessed at baseline and 3-months postpartum. Results: Significant differences in stress and depression were observed in both groups over time. Stress scores and depression scores were significantly better in the intervention group than in the comparison group at 3-months postpartum (F = 7.19, p = .009 and F = 7.36, p = .008, respectively). No significant difference between the groups was identified for mindfulness scores at 3-months postpartum. Conclusions: The intervention program effectively reduced postpartum self-perceived stress and depression, suggesting that this program provides acceptable and long-term benefits to women during pregnancy and the postpartum period. The teaching and practice of mindfulness meditation and parenting education during pregnancy may help reduce stress and depression in pregnant women as they transition into parenthood. Trial registration: The ClinicalTrials.gov identifier for this study is: NCT03185910 . The study was retrospectively registered on 14 June 2017.

BMC pregnancy and childbirth · randomised controlled trial · 55 citationsread the source →

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

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

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

Behavioural activation to mitigate the psychological impacts of COVID-19 restrictions on older people in England and Wales (BASIL+): a pragmatic randomised controlled trial.

Background: Older adults were more likely to be socially isolated during the COVID-19 pandemic, with increased risk of depression and loneliness. We aimed to investigate whether a behavioural activation intervention delivered via telephone could mitigate depression and loneliness in at-risk older people during the COVID-19 pandemic. Methods: BASIL+ (Behavioural Activation in Social Isolation) was a pragmatic randomised controlled trial conducted among patients recruited from general practices in England and Wales, and was designed to assess the effectiveness of behavioural activation in mitigating depression and loneliness among older people during the COVID-19 pandemic. Eligible participants were aged 65 years and older, socially isolated, with a score of 5 or higher on the Patient Health Questionnaire-9 (PHQ-9), and had multiple long-term conditions. Participants were allocated in a 1:1 ratio to the intervention (behavioural activation) or control groups by use of simple randomisation without stratification. Behavioural activation was delivered by telephone; participants were offered up to eight weekly sessions with trained BASIL+ Support Workers. Behavioural activation was adapted to maintain social connections and encourage socially reinforcing activities. Participants in the control group received usual care with existing COVID-19 wellbeing resources. The primary clinical outcome was self-reported depression severity, assessed by the PHQ-9, at 3 months. Outcomes were assessed masked to allocation and analysis was by treatment allocation. This trial is registered with the ISRCTN registry (ISRCTN63034289). Findings: Between Feb 8, 2021, and Feb 28, 2022, 449 eligible participants were identified and 435 from 26 general practices were recruited and randomly assigned (1:1) to the behavioural activation intervention (n=218) or to the control group (usual care with signposting; n=217). The mean age of participants was 75·7 years (SD 6·7); 270 (62·1%) of 435 participants were female, and 418 (96·1%) were White. Participants in the intervention group attended an average of 5·2 (SD 2·9) of eight remote behavioural activation sessions. The adjusted mean difference in PHQ-9 scores between the control and intervention groups at 3 months was -1·65 (95% CI -2·54 to -0·75, p=0·0003). No adverse events were reported that were attributable to the behavioural activation intervention. Interpretation: Behavioural activation is an effective and potentially scalable intervention that can reduce symptoms of depression and emotional loneliness in at-risk groups in the short term. The findings of this trial add to the range of strategies to improve the mental health of older adults with multiple long-term conditions. These results can be helpful to policy makers beyond the pandemic in reducing the global burden of depression and addressing the health impacts of loneliness, particularly in at-risk groups. Funding: UK National Institute for Health and Care Research.

The lancet. Healthy longevity · randomised controlled trial · 19 citationsread the source →

Cognitive behavioural therapy and short-term psychoanalytical psychotherapy versus a brief psychosocial intervention in adolescents with unipolar major depressive disorder (IMPACT): a multicentre, pragmatic, observer-blind, randomised controlled superiority trial.

Background: Psychological treatments for adolescents with unipolar major depressive disorder are associated with diagnostic remission within 28 weeks in 65-70% of patients. We aimed to assess the medium-term effects and costs of psychological therapies on maintenance of reduced depression symptoms 12 months after treatment. Methods: We did this multicentre, pragmatic, observer-blind, randomised controlled superiority trial (IMPACT) at 15 National Health Service child and adolescent mental health service (CAMHS) clinics in three regions in England. Adolescent patients (aged 11-17 years) with a diagnosis of DSM IV major depressive disorder were randomly assigned (1:1:1), via a web-based randomisation service, to receive cognitive behavioural therapy (CBT) or short-term psychoanalytical therapy versus a reference brief psychological intervention. Randomisation was stochastically minimised by age, sex, self-reported depression sum score, and region. Patients and clinicians were aware of group allocation, but allocation was concealed from outcome assessors. Patients were followed up and reassessed at weeks 6, 12, 36, 52, and 86 post-randomisation. The primary outcome was self-reported depression symptoms at weeks 36, 52, and 86, as measured with the self-reported Mood and Feelings Questionnaire (MFQ). Because our aim was to compare the two psychological therapies with the brief psychosocial intervention, we first established whether CBT was inferior to short-term psychoanalytical psychotherapy for the same outcome. Primary analysis was by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN83033550. Findings: Between June 29, 2010, and Jan 17, 2013, we randomly assigned 470 patients to receive the brief psychosocial intervention (n=158), CBT (n=155), or short-term psychoanalytical therapy (n=157); 465 patients comprised the intention-to-treat population. 392 (84%) patients had available data for primary analysis by the end of follow-up. Treatment fidelity and differentiation were established between the three interventions. The median number of treatment sessions differed significantly between patients in the brief psychosocial intervention group (n=6 [IQR 4-11]), CBT group (n=9 [5-14]), and short-term psychoanalytical therapy group (n=11 [5-23]; p<0·0001), but there was no difference between groups in the average duration of treatment (27·5 [SD 21·5], 24·9 [17·7], 27·9 [16·8] weeks, respectively; Kruskal-Wallis p=0·238). Self-reported depression symptoms did not differ significantly between patients given CBT and those given short-term psychoanalytical therapy at weeks 36 (treatment effect 0·179, 95% CI -3·731 to 4·088; p=0·929), 52 (0·307, -3·161 to 3·774; p=0·862), or 86 (0·578, -2·948 to 4·104; p=0·748). These two psychological treatments had no superiority effect compared with brief psychosocial intervention at weeks 36 (treatment effect -3·234, 95% CI -6·611 to 0·143; p=0·061), 52 (-2·806, -5·790 to 0·177; p=0·065), or 86 (-1·898, -4·922 to 1·126; p=0·219). Physical adverse events (self-reported breathing problems, sleep disturbances, drowsiness or tiredness, nausea, sweating, and being restless or overactive) did not differ between the groups. Total costs of the trial interventions did not differ significantly between treatment groups. Interpretation: We found no evidence for the superiority of CBT or short-term psychoanalytical therapy compared with a brief psychosocial intervention in maintenance of reduced depression symptoms 12 months after treatment. Short-term psychoanalytical therapy was as effective as CBT and, together with brief psychosocial intervention, offers additional patient choice for psychological therapy, alongside CBT, for adolescents with moderate to severe depression who are attending routine specialist CAMHS clinics. Funding: National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme, and the Department of Health.

The lancet. Psychiatry · randomised controlled trial · 149 citationsread the source →

Efficacy of Smartphone Applications for Smoking Cessation: A Randomized Clinical Trial.

Importance: Smoking is a leading cause of premature death globally. Smartphone applications for smoking cessation are ubiquitous and address barriers to accessing traditional treatments, yet there is limited evidence for their efficacy. Objective: To determine the efficacy of a smartphone application for smoking cessation based on acceptance and commitment therapy (ACT) vs a National Cancer Institute smoking cessation application based on US clinical practice guidelines (USCPG). Design, setting, and participants: A 2-group, stratified, double-blind, individually randomized clinical trial was conducted from May 27, 2017, to September 28, 2018, among 2415 adult cigarette smokers (n = 1214 for the ACT-based smoking cessation application group and n = 1201 for the USCPG-based smoking cessation application group) with 3-, 6-, and 12-month postrandomization follow-up. The study was prespecified in the trial protocol. Follow-up data collection started on August 26, 2017, and ended at the last randomized participant's 12-month follow-up survey on December 23, 2019. Data were analyzed from February 25 to April 3, 2020. The primary analysis was performed on a complete-case basis, with intent-to-treat missing as smoking and multiple imputation sensitivity analyses. Interventions: iCanQuit, an ACT-based smoking cessation application, which taught acceptance of smoking triggers, and the National Cancer Institute QuitGuide, a USCPG-based smoking cessation application, which taught avoidance of smoking triggers. Main outcomes and measures: The primary outcome was self-reported 30-day point prevalence abstinence (PPA) at 12 months after randomization. Secondary outcomes were 7-day PPA at 12 months after randomization, prolonged abstinence, 30-day and 7-day PPA at 3 and 6 months after randomization, missing data imputed with multiple imputation or coded as smoking, and cessation of all tobacco products (including e-cigarettes) at 12 months after randomization. Results: Participants were 2415 adult cigarette smokers (1700 women [70.4%]; 1666 White individuals [69.0%] and 868 racial/ethnic minorities [35.9%]; mean [SD] age at enrollment, 38.2 [10.9] years) from all 50 US states. The 3-month follow-up data retention rate was 86.7% (2093), the 6-month retention rate was 88.4% (2136), and the 12-month retention rate was 87.2% (2107). For the primary outcome of 30-day PPA at the 12-month follow-up, iCanQuit participants had 1.49 times higher odds of quitting smoking compared with QuitGuide participants (28.2% [293 of 1040] vs 21.1% [225 of 1067]; odds ratio [OR], 1.49; 95% CI, 1.22-1.83; P < .001). Effect sizes were very similar and statistically significant for 7-day PPA at the 12-month follow-up (OR, 1.35; 95% CI, 1.12-1.63; P = .002), prolonged abstinence at the 12-month follow-up (OR, 2.00; 95% CI, 1.45-2.76; P < .001), abstinence from all tobacco products (including e-cigarettes) at the 12-month follow-up (OR, 1.60; 95% CI, 1.28-1.99; P < .001), 30-day PPA at 3-month follow-up (OR, 2.20; 95% CI, 1.68-2.89; P < .001), 30-day PPA at 6-month follow-up (OR, 2.03; 95% CI, 1.63-2.54; P < .001), 7-day PPA at 3-month follow-up (OR, 2.04; 95% CI, 1.64-2.54; P < .001), and 7-day PPA at 6-month follow-up (OR, 1.73; 95% CI, 1.42-2.10; P < .001). Conclusions and relevance: This trial provides evidence that, compared with a USCPG-based smartphone application, an ACT-based smartphone application was more efficacious for quitting cigarette smoking and thus can be an impactful treatment option. Trial registration: ClinicalTrials.gov Identifier: NCT02724462.

JAMA internal medicine · randomised controlled trial · 159 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 →

Cancer and Aging: Reflections for Elders (CARE): A pilot randomized controlled trial of a psychotherapy intervention for older adults with cancer.

Objective: Cancer and Aging: Reflections for Elders (CARE) is a novel, telephone-delivered intervention designed to alleviate distress in older cancer patients. This pilot randomized controlled trial tested the feasibility and initial efficacy of CARE, drawing from age-appropriate developmental themes and well-established coping theory. Method: Eligible patients were ≥70 years old; ≥6 months post-diagnosis of lung, prostate, breast, lymphoma, or gynecological cancer; on active cancer treatment or within 6 months of ending cancer treatment; and had elevated scores on the Distress Thermometer (≥4) or Hospital Anxiety and Depression Scale (≥6). Participants completed five sessions of psychotherapy over 7 weeks with assessments at study entry, post-intervention, and 2 months post-intervention. Primary outcomes were feasibility and initial efficacy on anxiety and depression; secondary outcomes included demoralization, coping, loneliness, and spiritual well-being. Results: Fifty-nine participants were randomized to either the CARE arm (n = 31) or the enhanced Social Work Control arm (n = 28). The intervention was feasible and tolerable, meeting a priori criteria for rates of eligibility, acceptance, retention, assessment, and treatment fidelity. Upon completion of the intervention, participants in the CARE arm demonstrated lower mean depression scores (d = 0.58 [CI: 0.04-1.12], P = 0.01) and trended towards increased coping-planning (d = 0.30 [CI: -0.83 to 0.24], P = 0.18). Promising trends in anxiety (d = 0.41 [CI: -0.17 to 0.98], P = 0.10) emerged at 2 months post-intervention; effects for coping-planning dissipated. Conclusion: These pilot data suggest the CARE intervention is feasibly delivered, potentially impacts important psychosocial variables, and is accessible for older, frail patients with cancer. Future research will evaluate this intervention on a larger scale.

Psycho-oncology · randomised controlled trial · 37 citationsread the source →

A brief transdiagnostic psychological intervention for Afghan asylum seekers and refugees in Austria: a randomized controlled trial.

Background: Asylum seekers and refugees are at great risk for developing mental disorders. Afghan refugees are a particularly vulnerable group with a low average education and mental health literacy level. Traumatic experiences and hardship before and during migration are predictive of mental health problems. However, post-migration living difficulties (PMLDs) also account for a large proportion of mental distress in such populations, which, critically, are not sufficiently considered in treatment protocols and research investigations. Indeed, the evidence base for the treatment of refugees and asylum seekers is sparse and limited mainly to trauma-specific treatments, where refugees may likely suffer from other mental health problems such as depression or anxiety. Methods/design: This trial is the first evaluation of a short-term, transdiagnostic treatment protocol for treatment-seeking Afghan refugees which addresses mental health problems and PMLDs while using an adapted version of the Problem Management Plus (PM+) protocol. Here, we will investigate the efficacy of an intervention manual with a prospective, single-center, randomized, assessor-blind, two-group trial among refugees who are on a waiting list for professional mental health treatment. Furthermore, we will investigate participants' subjective experiences with the intervention manual via in-depth interviews. One hundred twenty people will be assessed and randomly allocated to either the intervention arm or a treatment-as-usual arm. Clinical psychologists will conduct the treatment, and the sessions will take place with a Dari interpreter. The protocol consists of six 90-min sessions. The primary endpoint is the general symptom distress measure, assessed with the General Health Questionnaire 28 (GHQ-28). Secondary endpoints are the Post-Migration Living Difficulties Checklist (PMLDC), the International Trauma Questionnaire (ITQ), the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF), the Psychological Outcome Profile (PSYCHLOPS), service and health care use (assessed with several items), and the Immigrant Integration Index (IPL-12). Discussion: This trial may provide substantial evidence for a brief transdiagnostic psychological intervention. Here, we intend to contribute to the treatment of mental health problems among Afghan refugees. The assessment of subjective experience with this treatment manual, as well as the evaluation of its clinical applicability, may optimize treatment acceptance and outcomes across a wide range of mental health problems among refugees. Trial registration: German Clinical Trials Register (DRKS) registration number: DRKS00016538. Universal Trial Number: U1111-1226-3285. Registered on January 7, 2019. https://www.drks.de/drks_web/setLocale_EN.do.

Trials · randomised controlled trial · 16 citationsread the source →

Standard gastroenterologist versus multidisciplinary treatment for functional gastrointestinal disorders (MANTRA): an open-label, single-centre, randomised controlled trial.

Background: Functional gastrointestinal disorders are common and costly to the health-care system. Most specialist care is provided by a gastroenterologist, but only a minority of patients have improvement in symptoms. Although they have proven to be effective, psychological, behavioural, and dietary therapies are not provided routinely. We aimed to compare the outcome of gastroenterologist-only standard care with multidisciplinary care. Methods: In an open-label, single-centre, pragmatic trial, consecutive new referrals of eligible patients aged 18-80 years with Rome IV criteria-defined functional gastrointestinal disorders were randomly assigned (1:2) to receive gastroenterologist-only standard care or multidisciplinary clinic care. The multidisciplinary clinic included gastroenterologists, dietitians, gut-focused hypnotherapists, psychiatrists, and behavioural (biofeedback) physiotherapists. Randomisation was stratified by Rome IV disorder and whether referred from gastroenterology or colorectal clinic. Outcomes were assessed at clinic discharge or 9 months after the initial visit. The primary outcome was a score of 4 (slightly better) or 5 (much better) on a 5-point Likert scale assessing global symptom improvement. Modified intention-to-treat analysis included all patients who attended at least one clinic visit and who had answered the primary outcome question. This study is registered with ClinicalTrials.gov, NCT03078634. Findings: Between March 16, 2017, and May 10, 2018, 1632 patients referred to the hospital gastrointestinal clinics were screened, of whom 442 were eligible for a screening telephone call and 188 were randomly assigned to receive either standard care (n=65) or multidisciplinary care (n=123). 144 patients formed the modified intention-to-treat analysis (n=46 in the standard-care group and n=98 in the multidisciplinary-care group), 90 (63%) of whom were women. 61 (62%) of 98 patients in the multidisciplinary-care group patients saw allied clinicians. 26 (57%) patients in the standard-care group and 82 (84%) patients in the multidisciplinary-care group had global symptom improvement (risk ratio 1·50 [95% CI 1·13-1·93]; p=0·00045). 29 (63%) patients in the standard-care group and 81 (83%) patients in the multidisciplinary-care group had adequate relief of symptoms in the past 7 days (p=0·010). Patients in the multidisciplinary-care group were more likely to experience a 50% or higher reduction in all Gastrointestinal Symptom Severity Index symptom clusters than were patients in the standard-care group. Of the patients with irritable bowel syndrome, a 50-point or higher reduction in IBS-SSS occurred in 10 (38%) of 26 patients in the standard care group compared with 39 (66%) of 59 patients in the multidisciplinary-care group (p=0·017). Of the patients with functional dyspepsia, a 50% reduction in the Nepean Dyspepsia Index was noted in three (11%) of 11 patients in the standard-care group and in 13 (46%) of 28 in the multidisciplinary-care group (p=0·47). After treatment, the median HADS scores were higher in the standard-care group than in the multidisciplinary-care group (13 [8-20] vs 10 [6-16]; p=0·096) and the median EQ-5D-5L quality of life visual analogue scale was lower in the standard-care group compared with the multidisciplinary-care group (70 [IQR 50-80] vs 75 [65-85]; p=0·0087). The eight SF-36 scales did not differ between the groups at discharge. After treatment, median Somatic Symptom Scale-8 score was higher in the standard-care group than in the multidisciplinary-care group (10 [IQR 7-7] vs 9 [5-13]; p=0·082). Cost per successful outcome was higher in the standard-care group than the multidisciplinary-care group. Interpretation: Integrated multidisciplinary clinical care appears to be superior to gastroenterologist-only care in relation to symptoms, specific functional disorders, psychological state, quality of life, and cost of care for the treatment of functional gastrointestinal disorders. Consideration should be given to providing multidisciplinary care for patients with a functional gastrointestinal disorder. Funding: None.

The lancet. Gastroenterology & hepatology · randomised controlled trial · 89 citationsread the source →

Inactivated poliovirus vaccine given alone or in a sequential schedule with bivalent oral poliovirus vaccine in Chilean infants: a randomised, controlled, open-label, phase 4, non-inferiority study.

Background: Bivalent oral poliovirus vaccine (bOPV; types 1 and 3) is expected to replace trivalent OPV (tOPV) globally by April, 2016, preceded by the introduction of at least one dose of inactivated poliovirus vaccine (IPV) in routine immunisation programmes to eliminate vaccine-associated or vaccine-derived poliomyelitis from serotype 2 poliovirus. Because data are needed on sequential IPV-bOPV schedules, we assessed the immunogenicity of two different IPV-bOPV schedules compared with an all-IPV schedule in infants. Methods: We did a randomised, controlled, open-label, non-inferiority trial with healthy, full-term (>2·5 kg birthweight) infants aged 8 weeks (± 7 days) at six well-child clinics in Santiago, Chile. We used supplied lists to randomly assign infants (1:1:1) to receive three polio vaccinations (IPV by injection or bOPV as oral drops) at age 8, 16, and 24 weeks in one of three sequential schedules: IPV-bOPV-bOPV, IPV-IPV-bOPV, or IPV-IPV-IPV. We did the randomisation with blocks of 12 stratified by study site. All analyses were done in a masked manner. Co-primary outcomes were non-inferiority of the bOPV-containing schedules compared with the all-IPV schedule for seroconversion (within a 10% margin) and antibody titres (within two-thirds log2 titres) to poliovirus serotypes 1 and 3 at age 28 weeks, analysed in the per-protocol population. Secondary outcomes were seroconversion and titres to serotype 2 and faecal shedding for 4 weeks after a monovalent OPV type 2 challenge at age 28 weeks. Safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01841671, and is closed to new participants. Findings: Between April 25 and August 1, 2013, we assigned 570 infants to treatment: 190 to IPV-bOPV-bOPV, 192 to IPV-IPV-bOPV, and 188 to IPV-IPV-IPV. 564 (99%) were vaccinated and included in the intention-to-treat cohort, and 537 (94%) in the per-protocol analyses. In the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups, respectively, the proportions of children with seroconversion to type 1 poliovirus were 166 (98·8%) of 168, 95% CI 95·8-99·7; 178 (100%), 97·9-100·0; and 175 (100%), 97·9-100·0. Proportions with seroconvsion to type 3 poliovirus were 163 (98·2%) of 166, 94·8-99·4; 177 (100%), 97·9-100·0, and 172 (98·9%) of 174, 95·9-99·7. Non-inferiority was thus shown for the bOPV-containing schedules compared with the all-IPV schedule, with no significant differences between groups. In the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups, respectively, the proportions of children with seroprotective antibody titres to type 1 poliovirus were 168 (98·8%) of 170, 95% CI 95·8-99·7; 181 (100%), 97·9-100·0; and 177 (100%), 97·9-100·0. Proportions to type 3 poliovirus were 166 (98·2%) of 169, 94·9-99·4; 180 (100%), 97·9-100·0; and 174 (98·9%) of 176, 96·0-99·7. Non-inferiority comparisons could not be done for this outcome because median titres for the groups receiving OPV were greater than the assay's upper limit of detection (log2 titres >10·5). The proportions of children seroconverting to type 2 poliovirus in the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups, respectively, were 130 (77·4%) of 168, 95% CI 70·5-83·0; 169 (96·0%) of 176, 92·0-98·0; and 175 (100%), 97·8-100. IPV-bOPV schedules resulted in almost a 0·3 log reduction of type 2 faecal shedding compared with the IPV-only schedule. No participants died during the trial; 81 serious adverse events were reported, of which one was thought to be possibly vaccine-related (intestinal intussusception). Interpretation: Seroconversion rates against polioviruses types 1 and 3 were non-inferior in sequential schedules containing IPV and bOPV, compared with an all-IPV schedule, and proportions of infants with protective antibodies were high after all three schedules. One or two doses of bOPV after IPV boosted intestinal immunity for poliovirus type 2, suggesting possible cross protection. Additionally, there was evidence of humoral priming for type 2 from one dose of IPV. Our findings could give policy makers flexibility when choosing a vaccination schedule, especially when trying to eliminate vaccine-associated and vaccine-derived poliomyelitis. Funding: Bill & Melinda Gates Foundation.

The Lancet. Infectious diseases · randomised controlled trial · 60 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 →

Smoking cessation for people with severe mental illness (SCIMITAR+): a pragmatic randomised controlled trial.

Background: People with severe mental illnesses such as schizophrenia are three times more likely to smoke than the wider population, contributing to widening health inequalities. Smoking remains the largest modifiable risk factor for this health inequality, but people with severe mental illness have not historically engaged with smoking cessation services. We aimed to test the effectiveness of a combined behavioural and pharmacological smoking cessation intervention targeted specifically at people with severe mental illness. Methods: In the smoking cessation intervention for severe mental illness (SCIMITAR+) trial, a pragmatic, randomised controlled study, we recruited heavy smokers with bipolar disorder or schizophrenia from 16 primary care and 21 community-based mental health sites in the UK. Participants were eligible if they were aged 18 years or older, and smoked at least five cigarettes per day. Exclusion criteria included substantial comorbid drug or alcohol problems and people who lacked capacity to consent at the time of recruitment. Using computer-generated random numbers, participants were randomly assigned (1:1) to a bespoke smoking cessation intervention or to usual care. Participants, mental health specialists, and primary care physicians were unmasked to assignment. The bespoke smoking cessation intervention consisted of behavioural support from a mental health smoking cessation practitioner and pharmacological aids for smoking cessation, with adaptations for people with severe mental illness-such as, extended pre-quit sessions, cut down to quit, and home visits. Access to pharmacotherapy was via primary care after discussion with the smoking cessation specialist. Under usual care participants were offered access to local smoking cessation services not specifically designed for people with severe mental illnesses. The primary endpoint was smoking cessation at 12 months ascertained via carbon monoxide measurements below 10 parts per million and self-reported cessation for the past 7 days. Secondary endpoints were biologically verified smoking cessation at 6 months; number of cigarettes smoked per day, Fagerström Test for Nicotine Dependence (FTND) and Motivation to Quit (MTQ) questionnaire; general and mental health functioning determined via the Patient Health Questionnaire-9 (PHQ-9), the Generalised Anxiety Disorder-7 (GAD-7) questionnaire, and 12-Item Short Form Health Survey (SF-12); and body-mass index (BMI). This trial was registerd with the ISRCTN registry, number ISRCTN72955454, and is complete. Findings: Between Oct 7, 2015, and Dec 16, 2016, 526 eligible patients were randomly assigned to the bespoke smoking cessation intervention (n=265) or usual care (n=261). 309 (59%) participants were male, median age was 47·2 years (IQR 36·3-54·5), with high nicotine dependence (mean 24 cigarettes per day [SD 13·2]), and the most common severe mental disorders were schizophrenia or other psychotic illness (n=343 [65%]), bipolar disorder (n=115 [22%]), and schizoaffective disorder (n=66 [13%]). 234 (88%) of intervention participants engaged with the treatment programme and attended 6·4 (SD 3·5) quit smoking sessions, with an average duration of 39 min (SD 17; median 35 min, range 5-120). Verified quit data at 12 months were available for 219 (84%) of 261 usual care and 223 (84%) of 265 intervention participants. The proportion of participants who had quit at 12 months was higher in the intervention group than in the usual care group, but non-significantly (34 [15%] of 223 [13% of those assigned to group] vs 22 [10%] of 219 [8% of those assigned to group], risk difference 5·2%, 95% CI -1·0 to 11·4; odds ratio [OR] 1·6, 95% CI 0·9 to 2·9; p=0·10). The proportion of participants who quit at 6 months was significantly higher in the intervention group than in the usual care group (32 [14%] of 226 vs 14 [6%] of 217; risk difference 7·7%, 95% CI 2·1 to 13·3; OR 2·4, 95% CI 1·2 to 4·6; p=0·010). The incidence rate ratio for number of cigarettes smoked per day at 6 months was 0·90 (95% CI 0·80 to 1·01; p=0·079), and at 12 months was 1·00 (0·89 to 1·13; p=0·95). At both 6 months and 12 months, the intervention group was non-significantly favoured in the FTND (adjusted mean difference 6 months -0·18, 95% CI -0·53 to 0·17, p=0·32; and 12 months -0·01, -0·39 to 0·38, p=0·97) and MTQ questionnaire (adjusted mean difference 0·58, -0·01 to 1·17, p=0·056; and 12 months 0·64, 0·04 to 1·24, p=0·038). The PHQ-9 showed no difference between the groups (adjusted mean difference at 6 months 0·20, 95% CI -0·85 to 1·24 vs 12 months -0·12, -1·18 to 0·94). For the SF-12 survey, we saw evidence of improvement in physical health in the intervention group at 6 months (adjusted mean difference 1·75, 95% CI 0·21 to 3·28), but this difference was not evident at 12 months (0·59, -1·07 to 2·26); and we saw no difference in mental health between the groups at 6 or 12 months (adjusted mean difference at 6 months -0·73, 95% CI -2·82 to 1·36, and 12 months -0·41, -2·35 to 1·53). The GAD-7 questionnaire showed no difference between the groups (adjusted mean difference at 6 months -0·32 95% CI -1·26 to 0·62 vs 12 months -0·10, -1·05 to 0·86). No difference in BMI was seen between the groups (adjusted mean difference 6 months 0·16, 95% CI -0·54 to 0·85; 12 months 0·25, -0·62 to 1·13). Interpretation: This bespoke intervention is a candidate model of smoking cessation for clinicians and policy makers to address high prevalence of smoking. The incidence of quitting at 6 months shows that smoking cessation can be achieved, but the waning of this effect by 12 months means more effort is needed for sustained quitting. Funding: National Institute for Health Research Health Technology Assessment Programme.

The lancet. Psychiatry · randomised controlled trial · 134 citationsread the source →

Symptom-Onset Dosing of Sertraline for the Treatment of Premenstrual Dysphoric Disorder: A Randomized Clinical Trial.

Importance: Serotonin reuptake inhibitors (SRIs) are efficacious treatments for premenstrual dysphoric disorder (PMDD) when given daily or for half of the menstrual cycle during the luteal phase. Preliminary studies suggest that SRI treatment can be shortened to the interval from symptom onset through the beginning of menses. Objective: To determine the efficacy of symptom-onset dosing with the SRI sertraline hydrochloride for treatment of PMDD. Design, setting, and participants: A double-blind, placebo-controlled, multisite, parallel-group randomized clinical trial conducted September 1, 2007, to February 29, 2012, at 3 university medical centers. In all, 252 women with PMDD started treatment at symptom onset and continued until the first few days of menses for 6 menstrual cycles. Intent-to-treat analyses were performed February 28, 2014, through April 21, 2015. Interventions: Placebo or sertraline hydrochloride, 50 to 100 mg/d, during the symptomatic interval. Main outcomes and measures: Premenstrual Tension Scale (PMTS) score was the primary outcome measure (score range, 0-36; 36 indicates most severe score). Secondary outcome measures included the Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C) (score range, 0-84; 84 indicates most severe score), Daily Record of Severity of Problems (DRSP) (total and subscale scores; higher scores indicate most severe problems), Clinical Global Impression (CGI) scales (score range, 1-7; 7 indicates most severe symptoms and least improvement), and Michelson SSRI (Selective SRI) Withdrawal Symptoms Scale scores (range, 0-51; higher scores indicate more severe withdrawal symptoms). Results: Among the participants, 125 with PMDD were randomized to sertraline, and 127 to placebo. At baseline the mean (SD) PMTS scores for sertaline and placebo were 22.3 (4.8) and 21.4 (4.5), respectively, which declined to 11.7 (6.8) and 12.0 (6.9), respectively; group mean difference, 1.88 (95% CI, 0.01-3.75; P = .06). The mean (SD) estimated difference in IDS-C scores between baseline (35.4 [10.7] for sertraline; 32.8 [10.4] for placebo) and the end point (15.3 [10.7] for sertraline; 17.8 [11.0] for placebo) favored the sertraline group by 5.14 (95% CI, 1.97-8.31) points (P = .02). Compared with the placebo group, those assigned to sertraline showed greater improvement on the total DRSP score (estimated mean difference, 1.09 [95% CI, 0.96-1.25] points; P = .02) and Anger/Irritability DRSP subscale score (1.22 [95% CI, 1.05-1.41] points; P < .01) and were more likely to respond to treatment (77 of 115 patients [67.0%] for sertraline and 65 of 124 [52.4%] for placebo; χ21 = 5.23; P = .02). The mean (SD) number of symptomatic days before treatment diminished over time (sertraline, -0.7 [3.4] days; placebo, -1.0 [3.2] days), with no group differences in symptomatic days or the Michelson SSRI Withdrawal Symptoms Scale. Conclusions and relevance: Depending on the symptom scale, women with PMDD may or may not benefit from SRI treatment during the interval from the onset of premenstrual symptoms through the first few days of menses. Abrupt treatment cessation was not associated with discontinuation symptoms. Trial registration: clinicaltrials.gov Identifier: NCT00536198.

JAMA psychiatry · randomised controlled trial · 51 citationsread the source →