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

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

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

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 →

Meta-analysis: excess mortality after hip fracture among older women and men.

Background: Although an increased risk for death after hip fracture is well established, whether this excess mortality persists over time is unclear. Purpose: To determine the magnitude and duration of excess mortality after hip fracture in older men and women. Data sources: Electronic search of MEDLINE and EMBASE for English and non-English articles from 1957 to May 2009 and manual search of article references. Study selection: Prospective cohort studies were selected by 2 independent reviewers. The studies had to assess mortality in women (22 cohorts) or men (17 cohorts) aged 50 years or older with hip fracture, carry out a life-table analysis, and display the survival curves of the hip fracture group and age- and sex-matched control groups. Data extraction: Survival curve data and items relevant to study validity and generalizability were independently extracted by 2 reviewers. Data synthesis: Time-to-event meta-analyses showed that the relative hazard for all-cause mortality in the first 3 months after hip fracture was 5.75 (95% CI, 4.94 to 6.67) in women and 7.95 (CI, 6.13 to 10.30) in men. Relative hazards decreased substantially over time but did not return to rates seen in age- and sex-matched control groups. Through use of life-table methods, investigators estimated that white women having a hip fracture at age 80 years have excess annual mortality compared with white women of the same age without a fracture of 8%, 11%, 18%, and 22% at 1, 2, 5, and 10 years after injury, respectively. Men with a hip fracture at age 80 years have excess annual mortality of 18%, 22%, 26%, and 20% at 1, 2, 5, and 10 years after injury, respectively. Limitations: Cohort studies varied, sometimes markedly, in size, duration of observation, selection of control populations, ascertainment of death, and adjustment for comorbid conditions. Only published data that displayed findings with survival curves were examined. Publication bias was possible. Conclusion: Older adults have a 5- to 8-fold increased risk for all-cause mortality during the first 3 months after hip fracture. Excess annual mortality persists over time for both women and men, but at any given age, excess annual mortality after hip fracture is higher in men than in women. Primary funding source: Fund for Scientific Research and Willy Gepts Foundation, Universitair Ziekenhuis Brussel.

Annals of internal medicine · meta-analysis · 984 citationsread the source →

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

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

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

Comparative efficacy and acceptability of antidepressants, psychotherapies, and their combination for acute treatment of children and adolescents with depressive disorder: a systematic review and network meta-analysis.

Background: Depressive disorders are common in children and adolescents. Antidepressants, psychotherapies, and their combination are often used in routine clinical practice; however, available evidence on the comparative efficacy and safety of these interventions is inconclusive. Therefore, we sought to compare and rank all available treatment interventions for the acute treatment of depressive disorders in children and adolescents. Methods: We did a systematic review and network meta-analysis. We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, PsycINFO, ProQuest, CINAHL, LiLACS, international trial registries, and the websites of regulatory agencies for published and unpublished randomised controlled trials from database inception until Jan 1, 2019. We included placebo-controlled and head-to-head trials of 16 antidepressants, seven psychotherapies, and five combinations of antidepressant and psychotherapy that are used for the acute treatment of children and adolescents (≤18 years old and of both sexes) with depressive disorder diagnosed according to standard operationalised criteria. Trials recruiting participants with treatment-resistant depression, bipolar disorder, psychotic depression, treatment duration of less than 4 weeks, or an overall sample size of fewer than ten patients were excluded. We extracted data following a predefined hierarchy of outcome measures, and assessed risk of bias and certainty of evidence using validated methods. Primary outcomes were efficacy (change in depressive symptoms) and acceptability (treatment discontinuation due to any cause). We estimated summary standardised mean differences (SMDs) or odds ratios (ORs) with credible intervals (CrIs) using network meta-analysis with random effects. This study was registered with PROSPERO, number CRD42015020841. Findings: From 20 366 publications, we included 71 trials (9510 participants). Depressive disorders in most studies were moderate to severe. In terms of efficacy, fluoxetine plus cognitive behavioural therapy (CBT) was more effective than CBT alone (-0·78, 95% CrI -1·55 to -0·01) and psychodynamic therapy (-1·14, -2·20 to -0·08), but not more effective than fluoxetine alone (-0·22, -0·86 to 0·42). No pharmacotherapy alone was more effective than psychotherapy alone. Only fluoxetine plus CBT and fluoxetine were significantly more effective than pill placebo or psychological controls (SMDs ranged from -1·73 to -0·51); and only interpersonal therapy was more effective than all psychological controls (-1·37 to -0·66). Nortriptyline (SMDs ranged from 1·04 to 2·22) and waiting list (SMDs ranged from 0·67 to 2·08) were less effective than most active interventions. In terms of acceptability, nefazodone and fluoxetine were associated with fewer dropouts than sertraline, imipramine, and desipramine (ORs ranged from 0·17 to 0·50); imipramine was associated with more dropouts than pill placebo, desvenlafaxine, fluoxetine plus CBT, and vilazodone (2·51 to 5·06). Most of the results were rated as "low" to "very low" in terms of confidence of evidence according to Confidence In Network Meta-Analysis. Interpretation: Despite the scarcity of high-quality evidence, fluoxetine (alone or in combination with CBT) seems to be the best choice for the acute treatment of moderate-to-severe depressive disorder in children and adolescents. However, the effects of these interventions might vary between individuals, so patients, carers, and clinicians should carefully balance the risk-benefit profile of efficacy, acceptability, and suicide risk of all active interventions in young patients with depression on a case-by-case basis. Funding: National Key Research and Development Program of China.

The lancet. Psychiatry · systematic review · 248 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 →

Grief-focused cognitive behavioral therapies for prolonged grief symptoms: A systematic review and meta-analysis.

Background: Studies suggest that cognitive behavioral therapies (CBTs) may be efficacious in reducing symptoms of prolonged grief disorder (PGD), but no comprehensive overview and pooled estimate of CBTs' effect on PGD in adulthood exist. We conducted a systematic review and meta-analysis of randomized controlled trials. Method: Studies were selected independently by two researchers based on a systematic literature search in Pubmed, APA PsycInfo, Web of Science, and Embase. Meta-analyses provided pooled effect sizes for the effects of CBTs on PGD symptoms and secondary outcomes. We explored potential moderators of effect, risk of bias of included studies, and evaluated the quality of the meta-analytical evidence through the Grading of Recommendations, Assessment, Development, and Evaluation system. Results: The meta-analysis included 22 studies of 2,602 bereaved adults (averaged study Mage = 49 years). CBTs had a statistically significant medium effect on PGD symptoms at postintervention (K = 22, g = 0.65, 95% CI [0.49, 0.81]), and a large effect at follow-up (K = 7, g = 0.90, 95% CI [0.37, 1.43]). Statistically significant small-to-medium effects were found at postintervention on posttraumatic stress symptoms (K = 10, g = 0.74, 95% CI [0.49, 0.98]), depression (K = 19, g = 0.53, 95% CI [0.36, 0.71]), and anxiety (K = 9, g = 0.35, 95% CI [0.22, 0.49]). The effects on PGD remained unchanged when adjusted for possible outliers. None of the moderator analyses reached statistical significance. Conclusion: This review suggests that CBTs are efficacious in reducing PGD symptoms in adulthood. Generalization of findings should be done with caution due to considerable inconsistency and indirectness of meta-analytic evidence. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Journal of consulting and clinical psychology · meta-analysis · 22 citationsread the source →

The Effect of Intermittent Fasting on Salivary Inflammatory Cytokines and Dopamine Levels.

The current study elucidates potential alterations in inflammatory cytokines and dopamine (DA) levels in saliva following a 21-day fasting regimen during Ramadan and explores their associations with mental health parameters. Forty-four healthy young university students (22 females and 22 males; median age 22 (2) and body mass index 23.40 (6.23) were enrolled, and saliva samples were collected before and after fasting. Cytokine and DA levels were quantified by ELISA and LEGENDplex Human Inflammation Panel, respectively. Participants also completed the Patient Health Questionnaire-9 and Depression Anxiety Stress Scales questionnaires to assess mental health. Data analysis was performed using SPSS. Differences between pre- and postfasting were tested using Wilcoxon's signed-rank test. Mann-Whitney's U test determined disparities in DA and cytokine levels across sex. Simple and multiple linear regression analyses were performed to identify the factors influencing the change in DA. Correlation analysis was employed to explore the relationships between the changes in DA and cytokine levels before and after fasting.A significant increase in inflammatory cytokines such as interleukin (IL)-1β, interferon-α2, tumor necrosis factor-α, IL-23, IL-33, and IL-8 was observed after fasting. Anti-inflammatory cytokine, IL-10, levels remained unchanged. Females had significantly higher levels of proinflammatory cytokines before fasting compared with males, but no significant gender differences were observed after fasting. The current study also showed a significant decrease in DA levels after fasting; however, no significant difference in DA levels across genders was noted. Self-reported mental health status did not significantly change before and after fasting. Multiple linear regression analyses did not suggest potential associations between these variables and changes in DA levels before and after fasting. However, correlation analysis indicated that the change in inflammatory cytokine levels was inversely related to changes in DA levels. Fasting during Ramadan significantly increased salivary cytokine levels and decreased DA levels, indicating potential relationships between immune factors and mental well-being. The findings highlight the complex interplay between inflammation, immunity, and DA regulation during fasting. Further research is warranted to elucidate the potential long-term effects of these associations and their implications for mental health and well-being.

European journal of dentistry · 3 citationsread the source →

Ultra-Low-Dose Buprenorphine as a Time-Limited Treatment for Severe Suicidal Ideation: A Randomized Controlled Trial.

Objective: Suicidal ideation and behavior currently have no quick-acting pharmacological treatments that are suitable for independent outpatient use. Suicidality is linked to mental pain, which is modulated by the separation distress system through endogenous opioids. The authors tested the efficacy and safety of very low dosages of sublingual buprenorphine as a time-limited treatment for severe suicidal ideation. Method: This was a multisite randomized double-blind placebo-controlled trial of ultra-low-dose sublingual buprenorphine as an adjunctive treatment. Severely suicidal patients without substance abuse were randomly assigned to receive either buprenorphine or placebo (in a 2:1 ratio), in addition to their ongoing individual treatments. The primary outcome measure was change in suicidal ideation, as assessed by the Beck Suicide Ideation Scale at the end of each of 4 weeks of treatment. Results: Patients who received ultra-low-dose buprenorphine (initial dosage, 0.1 mg once or twice daily; mean final dosage=0.44 mg/day; N=40) had a greater reduction in Beck Suicide Ideation Scale scores than patients who received placebo (N=22), both after 2 weeks (mean difference -4.3, 95% CI=-8.5, -0.2) and after 4 weeks (mean difference=-7.1, 95% CI=-12.0, -2.3). Concurrent use of antidepressants and a diagnosis of borderline personality disorder did not affect the response to buprenorphine. No withdrawal symptoms were reported after treatment discontinuation at the end of the trial. Conclusions: The time-limited, short-term use of very low dosages of sublingual buprenorphine was associated with decreased suicidal ideation in severely suicidal patients without substance abuse. Further research is needed to establish the efficacy, safety, dosing, and appropriate patient populations for this experimental treatment.

The American journal of psychiatry · randomised controlled trial · 159 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 →

How effects on health equity are assessed in systematic reviews of interventions.

Background: Enhancing health equity has now achieved international political importance with endorsement from the World Health Assembly in 2009.  The failure of systematic reviews to consider effects on health equity is cited by decision-makers as a limitation to their ability to inform policy and program decisions. Objectives: To systematically review methods to assess effects on health equity in systematic reviews of effectiveness. Search strategy: We searched the following databases up to July 2 2010: MEDLINE, PsychINFO, the Cochrane Methodology Register, CINAHL, Education Resources Information Center, Education Abstracts, Criminal Justice Abstracts, Index to Legal Periodicals, PAIS International, Social Services Abstracts, Sociological Abstracts, Digital Dissertations and the Health Technology Assessment Database. We searched SCOPUS to identify articles that cited any of the included studies on October 7 2010. Selection criteria: We included empirical studies of cohorts of systematic reviews that assessed methods for measuring effects on health inequalities. Data collection and analysis: Data were extracted using a pre-tested form by two independent reviewers. Risk of bias was appraised for included studies according to the potential for bias in selection and detection of systematic reviews. Main results: Thirty-four methodological studies were included.  The methods used by these included studies were: 1) Targeted approaches (n=22); 2) gap approaches (n=12) and gradient approach (n=1).  Gender or sex was assessed in eight out of 34 studies, socioeconomic status in ten studies, race/ethnicity in seven studies, age in seven studies, low and middle income countries in 14 studies, and two studies assessed multiple factors across health inequity may exist. Only three studies provided a definition of health equity. Four methodological approaches to assessing effects on health equity were identified: 1) descriptive assessment of reporting and analysis in systematic reviews (all 34 studies used a type of descriptive method); 2) descriptive assessment of reporting and analysis in original trials (12/34 studies); 3) analytic approaches (10/34 studies); and 4) applicability assessment (11/34 studies). Both analytic and applicability approaches were not reported transparently nor in sufficient detail to judge their credibility. Authors' conclusions: There is a need for improvement in conceptual clarity about the definition of health equity, describing sufficient detail about analytic approaches (including subgroup analyses) and transparent reporting of judgments required for applicability assessments in order to assess and report effects on health equity in systematic reviews.

The Cochrane database of systematic reviews · systematic review · 48 citationsread the source →

Effect of Nigella sativa and its bioactive compound on type 2 epithelial to mesenchymal transition: a systematic review.

Background: Nigella sativa or commonly known as black seed or black cumin is one of the most ubiquitous complementary medicine. Epithelial to mesenchymal transition (EMT) of type 2 is defined by the balance between wound healing and tissue fibrosis, which is dependent to the state of inflammation. This systematic review is conducted to provide an overview regarding the reported effect of Nigella sativa and its bioactive compound on the type 2 EMT. Methods: A search was done in EBSCOHOST, OVID and SCOPUS database to obtain potentially relevant articles that were published between 1823 and August 2019. This review includes studies that focus on the effect of Nigella sativa and its bioactive compound on the events related to type 2 EMT. Results: A total of 1393 research articles were found to be potentially related to the effect of Nigella sativa and its bioactive compound, thymoquinone on Type 2 EMT. After screening was done, 22 research articles met inclusion criteria and were included in this review. Majority of the studies, reported better wound healing rate or significant prevention of tissue inflammation and organ fibrosis following Nigella sativa or thymoquinone treatments. In terms of wound healing, studies included reported progression of EMT related pathological changes after treatment with Nigella sativa or thymoquinone. Alternatively, in terms of fibrosis and inflammation, studies included reported reversal of pathological changes related to EMT after treatment with Nigella sativa or thymoquinone. Conclusion: Through this review, Nigella sativa and thymoquinone have been associated with events in Type 2 EMT. They have been shown to promote wound healing, attenuate tissue inflammation, and prevent organ fibrosis via regulation of the EMT process.

BMC complementary and alternative medicine · systematic review · 13 citationsread the source →

The Use of Facebook in Recruiting Participants for Health Research Purposes: A Systematic Review.

Background: Social media is a popular online tool that allows users to communicate and exchange information. It allows digital content such as pictures, videos and websites to be shared, discussed, republished and endorsed by its users, their friends and businesses. Adverts can be posted and promoted to specific target audiences by demographics such as region, age or gender. Recruiting for health research is complex with strict requirement criteria imposed on the participants. Traditional research recruitment relies on flyers, newspaper adverts, radio and television broadcasts, letters, emails, website listings, and word of mouth. These methods are potentially poor at recruiting hard to reach demographics, can be slow and expensive. Recruitment via social media, in particular Facebook, may be faster and cheaper. Objective: The aim of this study was to systematically review the literature regarding the current use and success of Facebook to recruit participants for health research purposes. Methods: A literature review was completed in March 2017 in the English language using MEDLINE, EMBASE, Web of Science, PubMed, PsycInfo, Google Scholar, and a hand search of article references. Papers from the past 12 years were included and number of participants, recruitment period, number of impressions, cost per click or participant, and conversion rate extracted. Results: A total of 35 studies were identified from the United States (n=22), Australia (n=9), Canada (n=2), Japan (n=1), and Germany (n=1) and appraised using the Critical Appraisal Skills Programme (CASP) checklist. All focused on the feasibility of recruitment via Facebook, with some (n=10) also testing interventions, such as smoking cessation and depression reduction. Most recruited young age groups (16-24 years), with the remaining targeting specific demographics, for example, military veterans. Information from the 35 studies was analyzed with median values being 264 recruited participants, a 3-month recruitment period, 3.3 million impressions, cost per click of US $0.51, conversion rate of 4% (range 0.06-29.50), eligibility of 61% (range 17-100), and cost per participant of US $14.41. The studies showed success in penetrating hard to reach populations, finding the results representative of their control or comparison demographic, except for an over representation of young white women. Conclusions: There is growing evidence to suggest that Facebook is a useful recruitment tool and its use, therefore, should be considered when implementing future health research. When compared with traditional recruitment methods (print, radio, television, and email), benefits include reduced costs, shorter recruitment periods, better representation, and improved participant selection in young and hard to reach demographics. It however, remains limited by Internet access and the over representation of young white women. Future studies should recruit across all ages and explore recruitment via other forms of social media.

Journal of medical Internet research · systematic review · 503 citationsread the source →

Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic Prostate Cancer: A Prospective Clinical Trial.

Background: Stereotactic ablative body radiotherapy (SABR) is an emerging treatment option for oligometastatic prostate cancer. However, limited prospective evidence is available. Objective: To determine the safety and feasibility of single fraction SABR for patients with oligometastatic prostate cancer. Secondary endpoints were local and distant progression-free survival (LPFS and DPFS), toxicity, quality of life (QoL), and prostate-specific antigen response. Design, setting, and participants: In a prospective clinical trial, patients were screened with computed tomography, bone scan, and sodium fluoride positron emission tomography scan and had one to three oligometastases. Kaplan-Meier methods were used to determine LPFS and DPFS. Toxicity was graded using Common Terminology Criteria for Adverse Event version 4.0. QoL was assessed using European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-BM22 at 1, 3,12, and 24 mo. Intervention: A single fraction of 20-Gy SABR to each lesion. Results and limitations: Between 2013 and 2014, 33 consecutive patients received SABR to a total of 50 oligometastases and were followed for 2 yr. The median age was 70 yr. The Gleason score was ≥8 in 15 patients (45%). Twenty patients had bone only, 12 had node only, and one had mixed disease. SABR was feasible and delivered as planned in 97% of cases. There was one grade 3 adverse event (3.0%, vertebral fracture). No patient died. The 1 and 2-yr LPFS was 97% (95% confidence interval [CI]: 91-100) and 93% (95% CI: 84-100), and DPFS was 58% (95% CI: 43-77) and 39% (95% CI: 25-60), respectively. In those not on androgen deprivation therapy (ADT; n=22), the 2-yr freedom from ADT was 48%. There was no significant difference from baseline QoL observed. Limitations include small sample size, limited duration of follow-up, and lack of a control arm. Conclusions: A single SABR session was feasible and associated with low morbidity in this cohort. Over one-third of patients did not progress and were free from ADT at 2-yr. QoL measures were maintained with this treatment strategy. Patient summary: This clinical trial investigated single treatment stereotactic radiotherapy for low volume advanced prostate cancer. The approach was found to be safe with avoidance of hormone therapy in almost half of the participants at 2 yr.

European urology · clinical trial · 222 citationsread the source →

Intranasal oxytocin attenuates the cortisol response to physical stress: a dose-response study.

Introduction: Intranasal oxytocin attenuates cortisol levels during social stress inductions. However, no research to date has documented the dose-response relation between intranasal oxytocin administration and cortisol, and researchers examining intranasal oxytocin have not examined the cortisol response to physical stress. We therefore examined the effects of 24IU and 48IU of intranasal oxytocin on the cortisol response to vigorous exercise. Method: Seventeen males participated in a randomized, placebo-controlled, double-blind, and within-subject experiment. Participants engaged in vigorous exercise for 60min following the administration of placebo or intranasal oxytocin on three occasions. Saliva samples and mood ratings were collected at eight intervals across each session. Results: Salivary cortisol concentrations changed over time, peaking after 60min of exercise (quadratic: F(1,16)=7.349, p=.015, partial η(2)=.32). The 24IU dose of oxytocin attenuated cortisol levels relative to placebo (F(1,16)=4.496, p=.05, partial η(2)=.22) and the 48IU dose, although the latter fell just short of statistical significance (F(1,16)=3.054, p=.10, partial η(2)=.16). There was no difference in the cortisol response to exercise in participants who were administered 48IU of intranasal oxytocin relative to placebo. Intranasal oxytocin had no effect on mood. Conclusion: This is the first study to demonstrate that the effect of intranasal oxytocin on salivary cortisol is dose-dependent, and that intranasal oxytocin attenuates cortisol levels in response to physical stress. Future research using exogenous oxytocin will need to consider the possibility of dose-response relations.

Psychoneuroendocrinology · randomised controlled trial · 144 citationsread the source →

Increased placebo analgesia over time in irritable bowel syndrome (IBS) patients is associated with desire and expectation but not endogenous opioid mechanisms.

A study was conducted to determine whether changes in expected pain levels, desire for pain relief, or anxiety contribute to an increase in placebo analgesia over time as well as to determine whether placebo analgesic effects of IBS patients are related to endogenous opioid mechanisms. Twenty-six women with IBS were exposed to rectal stimulation (35 or 55 mmHg for 30 s) and tested under natural history (NH), rectal placebo (RP) and rectal lidocaine (RL) conditions. During all conditions, 16 patients were given saline intravenously (to test for a placebo effect) and 10 patients were given naloxone intravenously (to test naloxone antagonism of the placebo effect) on a double blind basis. Patients rated expected pain level, desire for pain relief and anxiety at 2 and 22 min after the onset of NH, RP, and RL conditions and they rated actual pain intensity at 5-min intervals for 40 min. There was a large and significant placebo effect (P<0.001) that increased over time. Ratings of expected pain levels, desire for pain relief and anxiety decreased over time and contributed to more variance in placebo and lidocaine responses during the last half of the session. These changes suggest that a reduction in negative emotions may be central to placebo effects. There was no significant difference between psychological mediators (desire, expectation, anxiety) or the placebo effect in the saline and naloxone groups, indicating that neither the psychological mediators nor the placebo analgesic effect were associated with endogenous opioids in this clinically related paradigm.

Pain · randomised controlled trial · 219 citationsread the source →

Five-year follow-up of harms and benefits of behavioral infant sleep intervention: randomized trial.

Background and objectives: Randomized trials have demonstrated the short- to medium-term effectiveness of behavioral infant sleep interventions. However, concerns persist that they may harm children's emotional development and subsequent mental health. This study aimed to determine long-term harms and/or benefits of an infant behavioral sleep program at age 6 years on (1) child, (2) child-parent, and (3) maternal outcomes. Methods: Three hundred twenty-six children (173 intervention) with parent-reported sleep problems at age 7 months were selected from a population sample of 692 infants recruited from well-child centers. The study was a 5-year follow-up of a population-based cluster-randomized trial. Allocation was concealed and researchers (but not parents) were blinded to group allocation. Behavioral techniques were delivered over 1 to 3 individual nurse consultations at infant age 8 to 10 months, versus usual care. The main outcomes measured were (1) child mental health, sleep, psychosocial functioning, stress regulation; (2) child-parent relationship; and (3) maternal mental health and parenting styles. Results: Two hundred twenty-five families (69%) participated. There was no evidence of differences between intervention and control families for any outcome, including (1) children's emotional (P = .8) and conduct behavior scores (P = .6), sleep problems (9% vs 7%, P = .2), sleep habits score (P = .4), parent- (P = .7) and child-reported (P = .8) psychosocial functioning, chronic stress (29% vs 22%, P = .4); (2) child-parent closeness (P = .1) and conflict (P = .4), global relationship (P = .9), disinhibited attachment (P = .3); and (3) parent depression, anxiety, and stress scores (P = .9) or authoritative parenting (63% vs 59%, P = .5). Conclusions: Behavioral sleep techniques have no marked long-lasting effects (positive or negative). Parents and health professionals can confidently use these techniques to reduce the short- to medium-term burden of infant sleep problems and maternal depression.

Pediatrics · randomised controlled trial · 69 citationsread the source →

Effect of nightly versus on-demand vardenafil on recovery of erectile function in men following bilateral nerve-sparing radical prostatectomy.

Background: To date, no data have been available from large, well-designed trials comparing on demand and nightly dosing of phosphodiesterase type 5 (PDE5) inhibitors on recovery of erectile function in postprostatectomy patients with erectile dysfunction (ED). Objective: To investigate the effect of early postoperative dosing with vardenafil, administered either nightly or on demand, compared with placebo on recovery of erectile function in men with ED following bilateral nerve-sparing radical prostatectomy (NSRP) surgery. Design, setting, and participants: A randomised, double-blind, double-dummy, multicentre, parallel group study conducted at 87 centres across Europe, Canada, South Africa, and the United States. For inclusion, patients had to be scheduled to undergo bilateral NSRP within 1 mo of screening and have a normal International Index of Erectile Function erectile function domain (IIEF-EF) score of > or =26 at screening. A total of 628 men, aged 18-64 yr, were randomised to treatment. Study design consisted of a 9-mo double-blind treatment period, a 2-mo single-blind washout period, and an optional 2-mo open-label period. Intervention: Patients received placebo, nightly vardenafil, or on demand vardenafil. Measurements: Primary outcome measure was the percentage of subjects with an IIEF-EF score of > or =22 after the 2-mo washout period. Secondary variables included mean per-patient success rates for Sexual Encounter Profile (SEP) questions 2 and 3. Results and limitations: No statistically significant differences were observed among treatment groups in the proportion of patients with an IIEF-EF score of > or =22 or in SEP3 success rates after the washout period. On-demand vardenafil treatment resulted in significantly greater IIEF-EF scores and better SEP3 response rates than placebo over the entire treatment period. Conclusions: In this study of men with ED following bilateral NSRP, vardenafil was efficacious when used on demand, supporting a paradigm shift towards on demand dosing with PDE5 inhibitors in this patient group. Trial registration: European clinical trials database (EudraCT; available at http://eudract.emea.europa.eu/). Trial registration number: 11336.

European urology · randomised controlled trial · 258 citationsread the source →

Lack of efficacy of psychological and pharmacological treatments of disorders of eating behavior: neurobiological background.

Background: Treatments of eating disorders result too often in partial psychological and physical remission, chronicization, dropout, relapse and death, with no fully known explanations for this failure. In order to clarify this problem, we conducted three studies to identify the biochemical background of cognitive-behavioural psychotherapy (CBT), individual psychology brief psychotherapy (IBPP), and psychotherapy-pharmacotherapy with CBT + olanzapine in anorexics (AN) and bulimics (BN) by measuring the levels of plasma homovanillic acid (HVA) for dopamine secretion, plasma 3-methoxy-4-hydroxy-phenylglycol (MHPG) for noradrenalin secretion, and platelet [3H]-Paroxetin-binding Bmax and Kd for serotonin transporter function. The data were then compared with psychopathological and physical alterations. Methods: Study 1 investigated the effects of 4 months of CBT on plasma HVA, MHPG and [3H]-Par-binding in 14 AN-restricted, 14 AN-bingeing/purging, and 22 BN inpatients. Study 2 investigated the effects of 4 months of IBPP on plasma HVA in 15 AN and 17 BN outpatients. Study 3 investigated the effect of 3 months of CBT + olanzapine (5 mg/day) in 30 AN outpatients. The data were analyzed using one-way ANOVA for repeated measures for the changes between basal and post-treatment biological and psychological parameters, two-way ANOVA for repeated measures for the differences in the psychobiological data in the 3 groups, Spearman's test for the correlations between basal and final changes in the psychological and biological scores. Results: Study 1 revealed significant amelioration of the psychopathology in the AN and BN patients, no effects on HVA, MHPG or Paroxetin binding Kd, and a significant increase in Par-binding Bmax only in the BN patients. Study 2 revealed a significant effect of IBPP on psychopathology in the AN and BN patients, and a significant increase in HVA only in the BN patients. Study 3 revealed a significant positive effect of CBT + olanzapine therapy on the psychopathology and increased HVA values. No correlations were observed in the 3 groups between biological and psychological effects of the three treatments. Conclusions: Our data advance suggestions on the mechanism of action of the three therapies; however, the lack of correlations between biochemical and psychological effects casts doubt on their significance. Clinical Trials.gov. Identifier NCT01990755 .

BMC psychiatry · randomised controlled trial · 11 citationsread the source →

International standards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project.

Background: In 2006, WHO produced international growth standards for infants and children up to age 5 years on the basis of recommendations from a WHO expert committee. Using the same methods and conceptual approach, the Fetal Growth Longitudinal Study (FGLS), part of the INTERGROWTH-21(st) Project, aimed to develop international growth and size standards for fetuses. Methods: The multicentre, population-based FGLS assessed fetal growth in geographically defined urban populations in eight countries, in which most of the health and nutritional needs of mothers were met and adequate antenatal care was provided. We used ultrasound to take fetal anthropometric measurements prospectively from 14 weeks and 0 days of gestation until birth in a cohort of women with adequate health and nutritional status who were at low risk of intrauterine growth restriction. All women had a reliable estimate of gestational age confirmed by ultrasound measurement of fetal crown-rump length in the first trimester. The five primary ultrasound measures of fetal growth--head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length--were obtained every 5 weeks (within 1 week either side) from 14 weeks to 42 weeks of gestation. The best fitting curves for the five measures were selected using second-degree fractional polynomials and further modelled in a multilevel framework to account for the longitudinal design of the study. Findings: We screened 13,108 women commencing antenatal care at less than 14 weeks and 0 days of gestation, of whom 4607 (35%) were eligible. 4321 (94%) eligible women had pregnancies without major complications and delivered live singletons without congenital malformations (the analysis population). We documented very low maternal and perinatal mortality and morbidity, confirming that the participants were at low risk of adverse outcomes. For each of the five fetal growth measures, the mean differences between the observed and smoothed centiles for the 3rd, 50th, and 97th centiles, respectively, were small: 2·25 mm (SD 3·0), 0·02 mm (3·0), and -2·69 mm (3·2) for head circumference; 0·83 mm (0·9), -0·05 mm (0·8), and -0·84 mm (1·0) for biparietal diameter; 0·63 mm (1·2), 0·04 mm (1·1), and -1·05 mm (1·3) for occipitofrontal diameter; 2·99 mm (3·1), 0·25 mm (3·2), and -4·22 mm (3·7) for abdominal circumference; and 0·62 mm (0·8), 0·03 mm (0·8), and -0·65 mm (0·8) for femur length. We calculated the 3rd, 5th 10th, 50th, 90th, 95th and 97th centile curves according to gestational age for these ultrasound measures, representing the international standards for fetal growth. Interpretation: We recommend these international fetal growth standards for the clinical interpretation of routinely taken ultrasound measurements and for comparisons across populations. Funding: Bill & Melinda Gates Foundation.

Lancet (London, England) · cohort or longitudinal · 589 citationsread the source →

Global patterns of mortality in international migrants: a systematic review and meta-analysis.

Background: 258 million people reside outside their country of birth; however, to date no global systematic reviews or meta-analyses of mortality data for these international migrants have been done. We aimed to review and synthesise available mortality data on international migrants. Methods: In this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Library, and Google Scholar databases for observational studies, systematic reviews, and randomised controlled trials published between Jan 1, 2001, and March 31, 2017, without language restrictions. We included studies reporting mortality outcomes for international migrants of any age residing outside their country of birth. Studies that recruited participants exclusively from intensive care or high dependency hospital units, with an existing health condition or status, or a particular health exposure were excluded. We also excluded studies limited to maternal or perinatal outcomes. We screened studies using systematic review software and extracted data from published reports. The main outcomes were all-cause and International Classification of Diseases, tenth revision (ICD-10) cause-specific standardised mortality ratios (SMRs) and absolute mortality rates. We calculated summary estimates using random-effects models. This study is registered with PROSPERO, number CRD42017073608. Findings: Of the 12 480 articles identified by our search, 96 studies were eligible for inclusion. The studies were geographically diverse and included data from all global regions and for 92 countries. 5464 mortality estimates for more than 15·2 million migrants were included, of which 5327 (97%) were from high-income countries, 115 (2%) were from middle-income countries, and 22 (<1%) were from low-income countries. Few studies included mortality estimates for refugees (110 estimates), asylum seekers (144 estimates), or labour migrants (six estimates). The summary estimate of all-cause SMR for international migrants was lower than one when compared with the general population in destination countries (0·70 [95% CI 0·65-0·76]; I2=99·8%). All-cause SMR was lower in both male migrants (0·72 [0·63-0·81]; I2=99·8%) and female migrants (0·75 [0·67-0·84]; I2=99·8%) compared with the general population. A mortality advantage was evident for refugees (SMR 0·50 [0·46-0·54]; I2=89·8%), but not for asylum seekers (1·05 [0·89-1·24]; I2=54·4%), although limited data was available on these groups. SMRs for all causes of death were lower in migrants compared with the general populations in the destination country across all 13 ICD-10 categories analysed, with the exception of infectious diseases and external causes. Heterogeneity was high across the majority of analyses. Point estimates of all-cause age-standardised mortality in migrants ranged from 420 to 874 per 100 000 population. Interpretation: Our study showed that international migrants have a mortality advantage compared with general populations, and that this advantage persisted across the majority of ICD-10 disease categories. The mortality advantage identified will be representative of international migrants in high-income countries who are studying, working, or have joined family members in these countries. However, our results might not reflect the health outcomes of more marginalised groups in low-income and middle-income countries because little data were available for these groups, highlighting an important gap in existing research. Our results present an opportunity to reframe the public discourse on international migration and health in high-income countries. Funding: Wellcome Trust, National Institute for Health Research, Medical Research Council, Alliance for Health Policy and Systems Research, Department for International Development, Fogarty International Center, Grand Challenges Canada, International Development Research Centre Canada, Inter-American Institute for Global Change Research, National Cancer Institute, National Heart, Lung and Blood Institute, National Institute of Mental Health, Swiss National Science Foundation, World Diabetes Foundation, UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, and European Society for Clinical Microbiology and Infectious Diseases (ESCMID) Study Group Research Funding for the ESCMID Study Group for Infections in Travellers and Migrants.

Lancet (London, England) · meta-analysis · 198 citationsread the source →

Exploring the relationship between absolute and relative position and late-life depression: evidence from 10 European countries.

Purpose: Socioeconomic inequality has been associated with higher levels of morbidity and mortality. This study explores the role of absolute and relative deprivation in predicting late-life depression on both individual and country levels. Design and methods: Country- and individual-level inequality indicators were used in multivariate logistic regression and in relative indexes of inequality. Data obtained from the Survey of Health, Ageing and Retirement in Europe (SHARE, Wave 1, Release 2) included 22,777 men and women (aged 50-104 years) from 10 European countries. Late-life depression was measured using the EURO-D scale and corresponding clinical cut point. Absolute deprivation was measured using gross domestic product and median household income at the country level and socioeconomic status at the individual level. Relative deprivation was measured by Gini coefficients at the country level and educational attainment at the individual level. Results: Rates of depression ranged from 18.10% in Denmark to 36.84% in Spain reflecting a clear north-south gradient. Measures of absolute and relative deprivation were significant in predicting depression at both country and individual levels. Findings suggest that the adverse impact of societal inequality cannot be overcome by increased individual-level or country-level income. Increases in individual-level income did not mitigate the effect of country-level relative deprivation. Implications: Mental health disparities persist throughout later life whereby persons exposed to higher levels of country-level inequality suffer greater morbidity compared with those in countries with less inequality. Cross-national variation in the relationship between inequality and depression illuminates the need for further research.

The Gerontologist · cohort or longitudinal · 35 citationsread the source →

SARS-CoV-2 in Spanish Intensive Care Units: Early experience with 15-day survival in Vitoria.

Purpose: Community transmission of SARS-CoV-2 was detected in Spain in February 2020, with 216% intensive care unit (ICU) capacity expanded in Vitoria by March 18th, 2020. Methods: We identified patients from the two public hospitals in Vitoria who were admitted to ICU with confirmed infection by SARS-CoV-2. Data reported here were available in April 6th, 2020. Mortality was assessed in those who completed 15-days of ICU stay. Results: We identified 48 patients (27 males) with confirmed SARS-CoV-2. Median [interquartile range (IQR)] age of patients was 63 [51-75] years. Symptoms began a median of 7 [5-12] days before ICU admission. The most common comorbidities identified were obesity (48%), arterial hypertension (44%) and chronic lung disease (37%). All patients were admitted by hypoxemic respiratory failure and none received non-invasive mechanical ventilation. Forty-five (94%) underwent intubation, 3 (6%) high flow nasal therapy (HFNT), 1 (2%) extracorporeal membrane oxygenation (ECMO) and 22 (46%) required prone position. After 15 days, 14/45 (31%) intubated patients died (13% within one week), 10/45 (22%) were extubated, and 21/45 (47%) underwent mechanical ventilation. Six patients had documented super-infection. Procalcitonin plasma above 0.5μg/L was associated with 16% vs. 19% (p=0.78) risk of death after 7 days. Conclusion: This early experience with SARS-CoV-2 in Spain suggests that a strategy of right oxygenation avoiding non-invasive mechanical ventilation was life-saving. Seven-day mortality in SARS-CoV-2 requiring intubation was lower than 15%, with 80% of patients still requiring mechanical ventilation. After 15 days of ICU admission, half of patients remained intubated, whereas one third died.

Anaesthesia, critical care & pain medicine · cohort or longitudinal · 156 citationsread the source →

Experiential virtual scenarios with real-time monitoring (interreality) for the management of psychological stress: a block randomized controlled trial.

Background: The recent convergence between technology and medicine is offering innovative methods and tools for behavioral health care. Among these, an emerging approach is the use of virtual reality (VR) within exposure-based protocols for anxiety disorders, and in particular posttraumatic stress disorder. However, no systematically tested VR protocols are available for the management of psychological stress. Objective: Our goal was to evaluate the efficacy of a new technological paradigm, Interreality, for the management and prevention of psychological stress. The main feature of Interreality is a twofold link between the virtual and the real world achieved through experiential virtual scenarios (fully controlled by the therapist, used to learn coping skills and improve self-efficacy) with real-time monitoring and support (identifying critical situations and assessing clinical change) using advanced technologies (virtual worlds, wearable biosensors, and smartphones). Methods: The study was designed as a block randomized controlled trial involving 121 participants recruited from two different worker populations-teachers and nurses-that are highly exposed to psychological stress. Participants were a sample of teachers recruited in Milan (Block 1: n=61) and a sample of nurses recruited in Messina, Italy (Block 2: n=60). Participants within each block were randomly assigned to the (1) Experimental Group (EG): n=40; B1=20, B2=20, which received a 5-week treatment based on the Interreality paradigm; (2) Control Group (CG): n=42; B1=22, B2=20, which received a 5-week traditional stress management training based on cognitive behavioral therapy (CBT); and (3) the Wait-List group (WL): n=39, B1=19, B2=20, which was reassessed and compared with the two other groups 5 weeks after the initial evaluation. Results: Although both treatments were able to significantly reduce perceived stress better than WL, only EG participants reported a significant reduction (EG=12% vs. CG=0.5%) in chronic "trait" anxiety. A similar pattern was found for coping skills: both treatments were able to significantly increase most coping skills, but only EG participants reported a significant increase (EG=14% vs CG=0.3%) in the Emotional Support skill. Conclusions: Our findings provide initial evidence that the Interreality protocol yields better outcomes than the traditionally accepted gold standard for psychological stress treatment: CBT. Consequently, these findings constitute a sound foundation and rationale for the importance of continuing future research in technology-enhanced protocols for psychological stress management. Trial registration: ClinicalTrials.gov: NCT01683617; http://clinicaltrials.gov/show/NCT01683617 (Archived by WebCite at http://www.webcitation.org/6QnziHv3h).

Journal of medical Internet research · randomised controlled trial · 68 citationsread the source →

Association between physical exercise and mental health in 1·2 million individuals in the USA between 2011 and 2015: a cross-sectional study.

Background: Exercise is known to be associated with reduced risk of all-cause mortality, cardiovascular disease, stroke, and diabetes, but its association with mental health remains unclear. We aimed to examine the association between exercise and mental health burden in a large sample, and to better understand the influence of exercise type, frequency, duration, and intensity. Methods: In this cross-sectional study, we analysed data from 1 237 194 people aged 18 years or older in the USA from the 2011, 2013, and 2015 Centers for Disease Control and Prevention Behavioral Risk Factors Surveillance System survey. We compared the number of days of bad self-reported mental health between individuals who exercised and those who did not, using an exact non-parametric matching procedure to balance the two groups in terms of age, race, gender, marital status, income, education level, body-mass index category, self-reported physical health, and previous diagnosis of depression. We examined the effects of exercise type, duration, frequency, and intensity using regression methods adjusted for potential confounders, and did multiple sensitivity analyses. Findings: Individuals who exercised had 1·49 (43·2%) fewer days of poor mental health in the past month than individuals who did not exercise but were otherwise matched for several physical and sociodemographic characteristics (W=7·42 × 1010, p<2·2 × 10-16). All exercise types were associated with a lower mental health burden (minimum reduction of 11·8% and maximum reduction of 22·3%) than not exercising (p<2·2 × 10-16 for all exercise types). The largest associations were seen for popular team sports (22·3% lower), cycling (21·6% lower), and aerobic and gym activities (20·1% lower), as well as durations of 45 min and frequencies of three to five times per week. Interpretation: In a large US sample, physical exercise was significantly and meaningfully associated with self-reported mental health burden in the past month. More exercise was not always better. Differences as a function of exercise were large relative to other demographic variables such as education and income. Specific types, durations, and frequencies of exercise might be more effective clinical targets than others for reducing mental health burden, and merit interventional study. Funding: Cloud computing resources were provided by Microsoft.

The lancet. Psychiatry · 681 citationsread the source →

The Role of Spirituality and Religiosity in Healthcare During the COVID-19 Pandemic: An Integrative Review of the Scientific Literature

The pandemic caused by the new coronavirus SARS-CoV-2 has been affecting populations globally since the end of 2019. Previous studies have indicated that spirituality in these times of crisis serves as a source of hope and well-being that helps people get through the day. This study investigated the role of spirituality and religiosity in healthcare during the COVID-19 pandemic. An integrative review of the scientific literature available on PubMed, Scopus, and Web of Science databases and a review of the gray literature in the Information System on Gray Literature in Europe (OpenGrey) were carried out. From a total of 1,338 articles searched; 25 articles were included in this review (22 quantitative observational, 2 qualitative and one randomized controlled trial). Our findings revealed the importance of including spirituality in clinical practice for both health professionals and patients. On the one hand, spirituality can be considered a good coping strategy used by healthcare professionals to promote mental health and well-being during the COVID-19 pandemic and resulting in greater patient satisfaction with the care given. On the other hand, addressing spiritual needs of individuals leads to a reduction in stress, anxiety, depression, and an increase in resilience and hope among patients.

Journal of Religion and Health · review · 63 citationsread the source →

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

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

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

Effectiveness of an online insomnia program (SHUTi) for prevention of depressive episodes (the GoodNight Study): a randomised controlled trial.

Background: In view of the high co-occurrence of depression and insomnia, a novel way to reduce the risk of escalating depression might be to offer an insomnia intervention. We aimed to assess whether an online self-help insomnia program could reduce depression symptoms. Methods: We did this randomised controlled trial at the Australian National University in Canberra, Australia. Internet users (aged 18-64 years) with insomnia and depression symptoms, but who did not meet criteria for major depressive disorder, were randomly assigned (1:1), via computer-generated randomisation, to receive SHUTi, a 6 week, modular, online insomnia program based on cognitive behavioural therapy for insomnia, or HealthWatch, an interactive, attention-matched, internet-based placebo control program. Randomisation was stratified by age and sex. Telephone-based interviewers, statisticians, and chief investigators were masked to group allocation. The primary outcome was depression symptoms at 6 months, as measured with the Patient Health Questionnaire (PHQ-9). The primary analysis was by intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000121965. Findings: Between April 30, 2013, and June 9, 2014, we randomly assigned 1149 participants to receive SHUTi (n=574) or HealthWatch (n=575), of whom 581 (51%) participants completed the study program assessments at 6 weeks and 504 (44%) participants completed 6 months' follow-up. SHUTi significantly lowered depression symptoms on the PHQ-9 at 6 weeks and 6 months compared with HealthWatch (F[degrees of freedom 2,640·1]=37·2, p<0·0001). Major depressive disorder was diagnosed in 22 (4%) participants at 6 months (n=9 in the SHUTi group and n=13 in the HealthWatch group), with no superior effect of SHUTi versus HealthWatch (Fisher's exact test=0·52; p=0·32). No adverse events were reported. Interpretation: Online cognitive behaviour therapy for insomnia treatment is a practical and effective way to reduce depression symptoms and could be capable of reducing depression at the population level by use of a fully automatised system with the potential for wide dissemination. Funding: Australian National Health and Medical Research Council.

The lancet. Psychiatry · randomised controlled trial · 272 citationsread the source →

Seroprevalence of SARS-CoV-2 Antibodies Among Children in School and Day Care in Montreal, Canada.

Importance: Quebec prioritized in-person learning after the first wave of the COVID-19 pandemic, with school closures being implemented temporarily in selected schools or in hot-spot areas. Quebec's decision to keep most schools open was controversial, especially in Montreal, which was the epicenter of Canada's first and second waves; therefore, understanding the extent to which children were infected with SARS-CoV-2 provides important information for decisions about school closures. Objective: To estimate the seroprevalence of SARS-CoV-2 antibodies in children and teenagers in 4 neighborhoods of Montreal, Canada. Design, setting, and participants: This cohort study (the Enfants et COVID-19: Étude de séroprévalence [EnCORE] study) enrolled a convenience sample of children aged 2 to 17 years between October 22, 2020, and March 22, 2021, in Montreal, Canada. Exposures: Potential exposure to SARS-CoV-2. Main outcomes and measures: The main outcome was seroprevalence of SARS-CoV-2 antibodies, collected using dried blood spots (DBSs) and analyzed with a research-based enzyme-linked immunosorbent assay (ELISA). Parents also completed an online questionnaire that included questions on self-reported COVID-19 symptoms and tests, along with sociodemographic questions. Results: This study included 1632 participants who provided a DBS sample from 30 day cares, 22 primary schools, and 11 secondary schools. The mean (SD) age of the children who provided a DBS sample was 9.0 (4.4) years; 801 (49%) were female individuals, with 354 participants (22%) from day cares, 725 (44%) from primary schools, and 553 (34%) from secondary schools. Most parents had at least a bachelor's degree (1228 [75%]), and 210 (13%) self-identified as being a racial or ethnic minority. The mean seroprevalence was 5.8% (95% CI, 4.6%-7.0%) but increased over time from 3.2% (95% CI, 0.7%-5.8%) in October to November 2020 to 8.4% (95% CI, 4.4%-12.4%) in March to April 2021. Of the 95 children with positive SARS-CoV-2 antibody results, 78 (82%) were not tested or tested negative with reverse transcription-polymerase chain reaction (RT-PCR) testing, and all experienced mild (49 [52%]) or no clinical symptoms (46 [48%]). The children of parents who self-identified as belonging to a racial and ethnic minority group were more likely to be seropositive compared with children of White parents (adjusted seroprevalence ratio, 1.9; 95% CI, 1.1-2.6). Conclusions and relevance: These results provide a benchmark of the seroprevalence status in Canadian children. The findings suggest that there was more transmission occurring in children compared with what was being detected by RT-PCR, although children experienced few or mild symptoms. It will be important to continue monitoring the serological status of children, particularly in the context of new COVID-19 variants of concern and in the absence of mass vaccination campaigns targeting young children.

JAMA network open · 39 citationsread the source →

Cardiovascular, Metabolic and Endocrine, Cancer, Mortality, Derma, and Other Outcomes of Olive Oil and Oleic Acid: An Umbrella Review.

The research on health effects of olive oil and oleic acid remains variable. This umbrella review aimed to synthesize evidence from systematic reviews (with or without meta-analyses) regarding the health outcomes of oleic acid and olive oil, clarify the validity and strength of the evidence, and finally help to make dietary recommendations for different people. We conducted a comprehensive search of the Cochrane, PubMed, Web of Science, Medline, and Embase databases. These studies were assessed using AMSTAR 2 and GRADE tools. 19 out of 741 eligible studies were included, and the majority were prospective studies. Topical application of olive oil is suggested to prevent pressure ulcers and acute radiation dermatitis; only a few adverse reactions (e.g., occupational allergic contact dermatitis and lichen planus pigmentosus) have been reported. Consumption of olive oil reduced the risk of Type 2 diabetes and cardiovascular disease by 22% and 18%, respectively. Especially, olive oil improved glycemic control in reducing fasting blood glucose (MD: -0.44, 95% CI: -0.66, -0.22), HbA1c (MD = -0.27, 95% CI: -0.37, -0.17), insulin (SMD = -0.28, 95% CI: -0.51, -0.05), and homeostatic model assessment for insulin resistance (HOMA-IR) (SMD = -0.19, 95% CI: -0.35, -0.03). Every 25 g/day OO intake was associated with an 11% lower relative risk of all-cause mortality (95% CI: 0.85, 0.93). Additionally, each 10 g/day olive oil intake increased 0.22 mg/dL HDL and improved endothelial function. However, the quality of 77% of the evidence was low to moderate, as assessed by GRADE. The methodological quality of 69% of the studies was low and critically low. Olive oil is proven to be a healthy dietary option for Type 2 diabetes and cardiovascular disease populations, a superior topical application choice for the immobilized. With the major evidence not being high, further standardized research is needed to explore the optimal dosage and the effects of oleic acid in olive oil.

Food science & nutrition · reviewread the source →

Impacts of shift work on sleep and circadian rhythms.

Shift work comprises work schedules that extend beyond the typical "nine-to-five" workday, wherein schedules often comprise early work start, compressed work weeks with 12-hour shifts, and night work. According to recent American and European surveys, between 15 and 30% of adult workers are engaged in some type of shift work, with 19% of the European population reportedly working at least 2 hours between 22:00 and 05:00. The 2005 International Classification of Sleep Disorders estimates that a shift work sleep disorder can be found in 2-5% of workers. This disorder is characterized by excessive sleepiness and/or sleep disruption for at least one month in relation with the atypical work schedule. Individual tolerance to shift work remains a complex problem that is affected by the number of consecutive work hours and shifts, the rest periods, and the predictability of work schedules. Sleepiness usually occurs during night shifts and is maximal at the end of the night. Impaired vigilance and performance occur around times of increased sleepiness and can seriously compromise workers' health and safety. Indeed, workers suffering from a shift work sleep-wake disorder can fall asleep involuntarily at work or while driving back home after a night shift. Working on atypical shifts has important socioeconomic impacts as it leads to an increased risk of accidents, workers' impairment and danger to public safety, especially at night. The aim of the present review is to review the circadian and sleep-wake disturbances associated with shift work as well as their medical impacts.

Pathologie-biologie · review · 340 citationsread the source →

Effects of COVID-19 Mental Health Interventions Among Children, Adolescents, and Adults Not Quarantined or Undergoing Treatment Due to COVID-19 Infection: A Systematic Review of Randomised Controlled Trials.

Objectives: Our objective was to assess the effects of mental health interventions for children, adolescents, and adults not quarantined or undergoing treatment due to COVID-19 infection. Methods: We searched 9 databases (2 Chinese-language) from December 31, 2019, to March 22, 2021. We included randomised controlled trials of interventions to address COVID-19 mental health challenges among people not hospitalised or quarantined due to COVID-19 infection. We synthesized results descriptively due to substantial heterogeneity of populations and interventions and risk of bias concerns. Results: We identified 9 eligible trials, including 3 well-conducted, well-reported trials that tested interventions designed specifically for COVID-19 mental health challenges, plus 6 other trials with high risk of bias and reporting concerns, all of which tested standard interventions (e.g., individual or group therapy, expressive writing, mindfulness recordings) minimally adapted or not specifically adapted for COVID-19. Among the 3 well-conducted and reported trials, 1 (N  =  670) found that a self-guided, internet-based cognitive-behavioural intervention targeting dysfunctional COVID-19 worry significantly reduced COVID-19 anxiety (standardized mean difference [SMD] 0.74, 95% confidence interval [CI], 0.58 to 0.90) and depression symptoms (SMD 0.38, 95% CI, 0.22 to 0.55) in Swedish general population participants. A lay-delivered telephone intervention for homebound older adults in the United States (N  =  240) and a peer-moderated education and support intervention for people with a rare autoimmune condition from 12 countries (N  =  172) significantly improved anxiety (SMD 0.35, 95% CI, 0.09 to 0.60; SMD 0.31, 95% CI, 0.03 to 0.58) and depressive symptoms (SMD 0.31, 95% CI, 0.05 to 0.56; SMD 0.31, 95% CI, 0.07 to 0.55) 6-week post-intervention, but these were not significant immediately post-intervention. No trials in children or adolescents were identified. Conclusions: Interventions that adapt evidence-based strategies for feasible delivery may be effective to address mental health in COVID-19. More well-conducted trials, including for children and adolescents, are needed.

Canadian journal of psychiatry. Revue canadienne de psychiatrie · systematic review · 23 citationsread the source →

The Impact of Parental and Medical Leave Policies on Socioeconomic and Health Outcomes in OECD Countries: A Systematic Review of the Empirical Literature.

Policy Points: Historically, reforms that have increased the duration of job-protected paid parental leave have improved women's economic outcomes. By targeting the period around childbirth, access to paid parental leave also appears to reduce rates of infant mortality, with breastfeeding representing one potential mechanism. The provision of more generous paid leave entitlements in countries that offer unpaid or short durations of paid leave could help families strike a balance between the competing demands of earning income and attending to personal and family well-being. Context: Policies legislating paid leave from work for new parents, and to attend to individual and family illness, are common across Organisation for Economic Co-operation and Development (OECD) countries. However, there exists no comprehensive review of their potential impacts on economic, social, and health outcomes. Methods: We conducted a systematic review of the peer-reviewed literature on paid leave and socioeconomic and health outcomes. We reviewed 5,538 abstracts and selected 85 published papers on the impact of parental leave policies, 22 papers on the impact of medical leave policies, and 2 papers that evaluated both types of policies. We synthesized the main findings through a narrative description; a meta-analysis was precluded by heterogeneity in policy attributes, policy changes, outcomes, and study designs. Findings: We were able to draw several conclusions about the impact of parental leave policies. First, extensions in the duration of paid parental leave to between 6 and 12 months were accompanied by attendant increases in leave-taking and longer durations of leave. Second, there was little evidence that extending the duration of paid leave had negative employment or economic consequences. Third, unpaid leave does not appear to confer the same benefits as paid leave. Fourth, from a population health perspective, increases in paid parental leave were consistently associated with better infant and child health, particularly in terms of lower mortality rates. Fifth, paid paternal leave policies of adequate length and generosity have induced fathers to take additional time off from work following the birth of a child. How medical leave policies for personal or family illness influence health has not been widely studied. Conclusions: There is substantial quasi-experimental evidence to support expansions in the duration of job-protected paid parental leave as an instrument for supporting women's labor force participation, safeguarding women's incomes and earnings, and improving child survival. This has implications, in particular, for countries that offer shorter durations of job-protected paid leave or lack a national paid leave entitlement altogether.

The Milbank quarterly · systematic review · 83 citationsread the source →

The epidemiology of trauma and post-traumatic stress disorder in a representative cohort of young people in England and Wales.

Background: Despite the emphasis placed on childhood trauma in psychiatry, comparatively little is known about the epidemiology of trauma and trauma-related psychopathology in young people. We therefore aimed to evaluate the prevalence, clinical features, and risk factors associated with trauma exposure and post-traumatic stress disorder (PTSD) in young people. Methods: We carried out a comprehensive epidemiological study based on participants from the Environmental Risk Longitudinal Twin Study, a population-representative birth-cohort of 2232 children born in England and Wales in 1994-95. At the follow-up home visit at age 18 years, participants were assessed with structured interviews for trauma exposure, PTSD, other psychopathology, risk events, functional impairment, and service use. Risk factors for PTSD were measured prospectively over four previous assessments between age 5 and 12 years. The key outcomes were the prevalence, clinical features, and risk factors associated with trauma exposure and PTSD. We also derived and tested the internal validity of a PTSD risk calculator. Findings: We found that 642 (31·1%) of 2064 participants reported trauma exposure and 160 (7·8%) of 2063 experienced PTSD by age 18 years. Trauma-exposed participants had high rates of psychopathology (187 [29·2%] of 641 for major depressive episode, 146 [22·9%] of 638 for conduct disorder, and 102 [15·9%] of 641 for alcohol dependence), risk events (160 [25·0%] of 641 for self-harm, 53 [8·3%] of 640 for suicide attempt, and 42 [6·6%] of 640 for violent offence), and functional impairment. Participants with lifetime PTSD had even higher rates of psychopathology (87 [54·7%] of 159 for major depressive episode, 43 [27·0%] of 159 for conduct disorder, and 41 [25·6%] of 160 for alcohol dependence), risk events (78 [48·8%] of 160 for self-harm, 32 [20·1%] of 159 for suicide attempt, and 19 [11·9%] of 159 for violent offence), and functional impairment. However, only 33 (20·6%) of 160 participants with PTSD received help from mental health professionals. The PTSD risk calculator had an internally validated area under the receiver operating characteristic curve of 0·74, indicating adequate discrimination of trauma-exposed participants with and without PTSD, and internally validated calibration-in-the-large of -0·10 and calibration slope of 0·90, indicating adequate calibration. Interpretation: Trauma exposure and PTSD are associated with complex psychiatric presentations, high risk, and significant impairment in young people. Improved screening, reduced barriers to care provision, and comprehensive clinical assessment are needed to ensure that trauma-exposed young people and those with PTSD receive appropriate treatment. Funding: The Medical Research Council, the National Institute of Child Health and Development, the Jacobs Foundation, the Nuffield Foundation, the National Society for Prevention of Cruelty to Children, the Economic and Social Research Council, the National Institute for Health Research, MQ, and Canadian Institutes for Advanced Research.

The lancet. Psychiatry · cohort or longitudinal · 287 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 →

Prevalence of depression, anxiety, and insomnia among healthcare workers during the COVID-19 pandemic: A systematic review and meta-analysis.

Background: COVID-19 pandemic has the potential to significantly affect the mental health of healthcare workers (HCWs), who stand in the frontline of this crisis. It is, therefore, an immediate priority to monitor rates of mood, sleep and other mental health issues in order to understand mediating factors and inform tailored interventions. The aim of this review is to synthesize and analyze existing evidence on the prevalence of depression, anxiety and insomnia among HCWs during the Covid-19 outbreak. Methods: A systematic search of literature databases was conducted up to April 17th, 2020. Two reviewers independently assessed full-text articles according to predefined criteria. Risk of bias for each individual study was assessed and data pooled using random-effects meta-analyses to estimate the prevalence of specific mental health problems. The review protocol is registered in PROSPERO and is available online. Findings: Thirteen studies were included in the analysis with a combined total of 33,062 participants. Anxiety was assessed in 12 studies, with a pooled prevalence of 23·2% and depression in 10 studies, with a prevalence rate of 22·8%. A subgroup analysis revealed gender and occupational differences with female HCPs and nurses exhibiting higher rates of affective symptoms compared to male and medical staff respectively. Finally, insomnia prevalence was estimated at 38·9% across 5 studies. Interpretation: Early evidence suggests that a considerable proportion of HCWs experience mood and sleep disturbances during this outbreak, stressing the need to establish ways to mitigate mental health risks and adjust interventions under pandemic conditions.

Brain, behavior, and immunity · meta-analysis · 2357 citationsread the source →

Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010.

Background: We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to estimate the burden of disease attributable to mental and substance use disorders in terms of disability-adjusted life years (DALYs), years of life lost to premature mortality (YLLs), and years lived with disability (YLDs). Methods: For each of the 20 mental and substance use disorders included in GBD 2010, we systematically reviewed epidemiological data and used a Bayesian meta-regression tool, DisMod-MR, to model prevalence by age, sex, country, region, and year. We obtained disability weights from representative community surveys and an internet-based survey to calculate YLDs. We calculated premature mortality as YLLs from cause of death estimates for 1980-2010 for 20 age groups, both sexes, and 187 countries. We derived DALYs from the sum of YLDs and YLLs. We adjusted burden estimates for comorbidity and present them with 95% uncertainty intervals. Findings: In 2010, mental and substance use disorders accounted for 183·9 million DALYs (95% UI 153·5 million-216·7 million), or 7·4% (6·2-8·6) of all DALYs worldwide. Such disorders accounted for 8·6 million YLLs (6·5 million-12·1 million; 0·5% [0·4-0·7] of all YLLs) and 175·3 million YLDs (144·5 million-207·8 million; 22·9% [18·6-27·2] of all YLDs). Mental and substance use disorders were the leading cause of YLDs worldwide. Depressive disorders accounted for 40·5% (31·7-49·2) of DALYs caused by mental and substance use disorders, with anxiety disorders accounting for 14·6% (11·2-18·4), illicit drug use disorders for 10·9% (8·9-13·2), alcohol use disorders for 9·6% (7·7-11·8), schizophrenia for 7·4% (5·0-9·8), bipolar disorder for 7·0% (4·4-10·3), pervasive developmental disorders for 4·2% (3·2-5·3), childhood behavioural disorders for 3·4% (2·2-4·7), and eating disorders for 1·2% (0·9-1·5). DALYs varied by age and sex, with the highest proportion of total DALYs occurring in people aged 10-29 years. The burden of mental and substance use disorders increased by 37·6% between 1990 and 2010, which for most disorders was driven by population growth and ageing. Interpretation: Despite the apparently small contribution of YLLs--with deaths in people with mental disorders coded to the physical cause of death and suicide coded to the category of injuries under self-harm--our findings show the striking and growing challenge that these disorders pose for health systems in developed and developing regions. In view of the magnitude of their contribution, improvement in population health is only possible if countries make the prevention and treatment of mental and substance use disorders a public health priority. Funding: Queensland Department of Health, National Health and Medical Research Council of Australia, National Drug and Alcohol Research Centre-University of New South Wales, Bill & Melinda Gates Foundation, University of Toronto, Technische Universität, Ontario Ministry of Health and Long Term Care, and the US National Institute of Alcohol Abuse and Alcoholism.

Lancet (London, England) · review · 3758 citationsread the source →

Probiotic Bifidobacterium longum NCC3001 Reduces Depression Scores and Alters Brain Activity: A Pilot Study in Patients With Irritable Bowel Syndrome.

Background & aims: Probiotics can reduce symptoms of irritable bowel syndrome (IBS), but little is known about their effects on psychiatric comorbidities. We performed a prospective study to evaluate the effects of Bifidobacterium longum NCC3001 (BL) on anxiety and depression in patients with IBS. Methods: We performed a randomized, double-blind, placebo-controlled study of 44 adults with IBS and diarrhea or a mixed-stool pattern (based on Rome III criteria) and mild to moderate anxiety and/or depression (based on the Hospital Anxiety and Depression scale) at McMaster University in Canada, from March 2011 to May 2014. At the screening visit, clinical history and symptoms were assessed and blood samples were collected. Patients were then randomly assigned to groups and given daily BL (n = 22) or placebo (n = 22) for 6 weeks. At weeks 0, 6, and 10, we determined patients' levels of anxiety and depression, IBS symptoms, quality of life, and somatization using validated questionnaires. At weeks 0 and 6, stool, urine and blood samples were collected, and functional magnetic resonance imaging (fMRI) test was performed. We assessed brain activation patterns, fecal microbiota, urine metabolome profiles, serum markers of inflammation, neurotransmitters, and neurotrophin levels. Results: At week 6, 14 of 22 patients in the BL group had reduction in depression scores of 2 points or more on the Hospital Anxiety and Depression scale, vs 7 of 22 patients in the placebo group (P = .04). BL had no significant effect on anxiety or IBS symptoms. Patients in the BL group had a mean increase in quality of life score compared with the placebo group. The fMRI analysis showed that BL reduced responses to negative emotional stimuli in multiple brain areas, including amygdala and fronto-limbic regions, compared with placebo. The groups had similar fecal microbiota profiles, serum markers of inflammation, and levels of neurotrophins and neurotransmitters, but the BL group had reduced urine levels of methylamines and aromatic amino acids metabolites. At week 10, depression scores were reduced in patients given BL vs placebo. Conclusion: In a placebo-controlled trial, we found that the probiotic BL reduces depression but not anxiety scores and increases quality of life in patients with IBS. These improvements were associated with changes in brain activation patterns that indicate that this probiotic reduces limbic reactivity. ClinicalTrials.gov no. NCT01276626.

Gastroenterology · randomised controlled trial · 587 citationsread the source →

Dietary inflammatory index, cardiometabolic conditions and depression in the Seguimiento Universidad de Navarra cohort study.

Only one prospective study has analysed the relationship between the inflammatory properties of diet and risk of depression thus far. The aim of this study was to assess the association between the dietary inflammatory index (DII) and the incidence of depression. In a cohort study of 15 093 university graduates, participants completed a validated FFQ at baseline and after 10 years of follow-up. The DII was calculated based on the FFQ. Each of the twenty-eight nutrients or foods received a score based on findings from the peer-reviewed literature reporting on the relationships between diet and inflammatory biomarkers (IL-1β, IL-4, IL-6, IL-10, TNF-α and C-reactive protein). Participants were classified as having depression if they reported a new clinical diagnosis of depression by a physician, antidepressant drugs, or both. Multivariable Cox regression models were used to estimate hazard ratios (HR) of depression according to quintiles of the DII. After a median 8·5 years of follow-up, we observed 1051 incident cases of depression. The HR for participants in the highest quintile of DII (strongly pro-inflammatory) was 1·47 (95% CI 1·17, 1·85) compared with those in the bottom quintile, with a significant dose-response relationship (P trend=0·01). In the subgroup analyses, the association between DII and depression was stronger among participants >55 years and among those with cardiometabolic comorbidities (HR 2·70; 95% CI 1·22, 5·97 and HR 1·80; 95% CI 1·27, 2·57, respectively). A pro-inflammatory diet was associated with a significantly higher risk of depression in a Mediterranean population. This association was stronger among older subjects and subjects with cardiometabolic diseases.

The British journal of nutrition · 90 citationsread the source →

Extended and standard duration weight-loss programme referrals for adults in primary care (WRAP): a randomised controlled trial.

Background: Evidence exist that primary care referral to an open-group behavioural programme is an effective strategy for management of obesity, but little evidence on optimal intervention duration is available. We aimed to establish whether 52-week referral to an open-group weight-management programme would achieve greater weight loss and improvements in a range of health outcomes and be more cost-effective than the current practice of 12-week referrals. Methods: In this non-blinded, parallel-group, randomised controlled trial, we recruited participants who were aged 18 years or older and had body-mass index (BMI) of 28 kg/m2 or higher from 23 primary care practices in England. Participants were randomly assigned (2:5:5) to brief advice and self-help materials, a weight-management programme (Weight Watchers) for 12 weeks, or the same weight-management programme for 52 weeks. We followed-up participants over 2 years. The primary outcome was weight at 1 year of follow-up, analysed with mixed-effects models according to intention-to-treat principles and adjusted for centre and baseline weight. In a hierarchical closed-testing procedure, we compared combined behavioural programme arms with brief intervention, then compared the 12-week programme and 52-week programme. We did a within-trial cost-effectiveness analysis using person-level data and modelled outcomes over a 25-year time horizon using microsimulation. This study is registered with Current Controlled Trials, number ISRCTN82857232. Findings: Between Oct 18, 2012, and Feb 10, 2014, we enrolled 1269 participants. 1267 eligible participants were randomly assigned to the brief intervention (n=211), the 12-week programme (n=528), and the 52-week programme (n=528). Two participants in the 12-week programme had been found to be ineligible shortly after randomisation and were excluded from the analysis. 823 (65%) of 1267 participants completed an assessment at 1 year and 856 (68%) participants at 2 years. All eligible participants were included in the analyses. At 1 year, mean weight changes in the groups were -3·26 kg (brief intervention), -4·75 kg (12-week programme), and -6·76 kg (52-week programme). Participants in the behavioural programme lost more weight than those in the brief intervention (adjusted difference -2·71 kg, 95% CI -3·86 to -1·55; p<0·0001). The 52-week programme was more effective than the 12-week programme (-2·14 kg, -3·05 to -1·22; p<0·0001). Differences between groups were still significant at 2 years. No adverse events related to the intervention were reported. Over 2 years, the incremental cost-effectiveness ratio (ICER; compared with brief intervention) was £159 per kg lost for the 52-week programme and £91 per kg for the 12-week programme. Modelled over 25 years after baseline, the ICER for the 12-week programme was dominant compared with the brief intervention. The ICER for the 52-week programme was cost-effective compared with the brief intervention (£2394 per quality-adjusted life-year [QALY]) and the 12-week programme (£3804 per QALY). Interpretation: For adults with overweight or obesity, referral to this open-group behavioural weight-loss programme for at least 12 weeks is more effective than brief advice and self-help materials. A 52-week programme produces greater weight loss and other clinical benefits than a 12-week programme and, although it costs more, modelling suggests that the 52-week programme is cost-effective in the longer term. Funding: National Prevention Research Initiative, Weight Watchers International (as part of an UK Medical Research Council Industrial Collaboration Award).

Lancet (London, England) · randomised controlled trial · 156 citationsread the source →

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

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

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

Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.

Background: Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. Methods: The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. Findings: Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, -1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, -1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. Interpretation: Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI. Funding: Bill & Melinda Gates Foundation.

Lancet (London, England) · 4695 citationsread the source →

Neuropsychiatric phenotypes in children with Noonan syndrome.

Aim: We investigated neuropsychiatric outcomes in children with Noonan syndrome and addressed limitations in previous research with a focus on prepubertal children, comparison to typically developing children, comprehensive neuropsychiatric evaluation, and controlling for overall cognitive abilities. Method: Forty-five children with Noonan syndrome (mean = 8 years 6 months, SD = 2 years 2 months; 29 females) and 40 typically developing children (mean = 8 years 9 months, SD = 2 years; 22 females) were evaluated with objective, parent-report, and psychiatric interview measures. Results: Children with Noonan syndrome demonstrated elevated symptoms across attention-deficit/hyperactivity disorder (ADHD) (attention, hyperactivity, and inhibition), autism spectrum disorder (ASD) (maintaining social relationships, behavioral rigidity, and sensory sensitivity), and oppositional defiant disorder (ODD) (aggression) symptom clusters relative to typically developing children (all p < 0.05). Group differences in nearly all parent-report measures were significant after accounting for variations in intellectual functioning, suggesting that increased neurodevelopmental symptoms are not simply driven by overall intelligence. Twenty out of 42 children with Noonan syndrome met criteria for ADHD, eight out of 42 for ODD, and 11 out of 43 demonstrated clinically significant symptoms seen in children with ASD. Interpretation: Children with Noonan syndrome are at increased risk for a range of ADHD, ASD, and ODD associated symptoms. A dimensional approach reveals significant ASD symptoms in Noonan syndrome that do not emerge when using the currently accepted categorical diagnostic approach. What this paper adds: Neuropsychiatric disorders occur in more than half of children with Noonan syndrome. Children with Noonan syndrome demonstrate highly variable neurodevelopmental symptom profiles. Children with Noonan syndrome display variable impairments in attention, hyperactivity, and inhibition. Specific social concerns include behavioral rigidity, transitions, and difficulties maintaining social relationships. Children with Noonan syndrome display variably elevated levels of aggression and emotional dysregulation.

Developmental medicine and child neurology · 34 citationsread the source →

Mind-Body Interventions for Individuals With Heart Failure: A Systematic Review of Randomized Trials.

Background: The effects of mind-body interventions (MBIs) (eg, Tai Chi, yoga, meditation) for individuals with heart failure (HF) have not been systematically evaluated. Methods and results: We performed a systematic review of randomized controlled trials (RCTs) examining the effects of MBIs in HF. We extracted participant characteristics, MBI procedure, outcomes assessed, and main results of English-language RCTs before October 2016. We identified 24 RCTs (n = 1314 participants) of 9 MBI types: Tai Chi (n = 7), yoga (n = 4), relaxation (n = 4), meditation (n = 2), acupuncture (n = 2), biofeedback (n = 2), stress management (n = 1), Pilates (n = 1), and reflexology (n = 1). Most (n = 22, 95.8%) reported small-to-moderate improvements in quality of life (14/14 studies), exercise capacity (8/9 studies), depression (5/5 studies), anxiety and fatigue (4/4 studies), blood pressure (3/5 studies), heart rate (5/6 studies), heart rate variability (7/9 studies), and B-type natriuretic peptide (3/4 studies). Studies ranged from 4 minutes to 26 weeks and group sizes ranged from 8 to 65 patients per study arm. Conclusions: Although wide variability exists in the types and delivery, RCTs of MBIs have demonstrated small-to-moderate positive effects on HF patients' objective and subjective outcomes. Future research should examine the mechanisms by which different MBIs exert their effects.

Journal of cardiac failure · systematic review · 29 citationsread the source →

Effectiveness of a bite-sized web-based intervention to improve healthcare worker wellbeing: A randomized clinical trial of WISER.

Importance: Problems with the wellbeing of healthcare workers (HCWs) are widespread and associated with detrimental consequences for the workforce, organizations, and patients. Objective: This study tested the effectiveness of the Web-based Implementation for the Science of Enhancing Resilience (WISER) intervention, a positive psychology program, to improve six dimensions of the wellbeing of HCWs. Design: We conducted a randomized controlled trial of HCWs between 1 April 2018 and 22 July 2019. Cohort 1 received WISER daily for 10 days. Cohort 2 acted as a waitlist control before receiving WISER. Setting: Web-based intervention for actively employed HCWs across the United States. Participants: Eligibility criteria included being ≥18 years old and working as a HCW. Each participant was randomized to start the intervention or serve as a waitlist control for 14 days before starting the intervention. Interventions: Cohorts received links via 10 texts exposing them to introductory videos and positive psychology exercises (3 good things, cultivating awe, random acts of kindness, cultivating relationships, and gratitude letters). Main outcomes and measures: The primary outcome was emotional exhaustion; secondary outcomes included depressive symptoms, work-life integration, happiness, emotional thriving, and emotional recovery. All outcomes were assessed at baseline, 1-week post-intervention (primary endpoint), and 1, 6, and 12-month post-intervention. Outcomes were measured using six validated wellbeing instruments, rescaled to 100-point scales for comparison. Six items assessed participants' WISER experience. The analysis employed mixed-effects models. Results: In cohorts 1 and 2, 241 and 241 initiated WISER, and 178 (74%) and 186 (77%) completed the 6-month follow-up, respectively. Cohort populations were similar at baseline, mostly female (81; 76%) and nurses (34; 32%) or physicians (22; 23%), with 1-10 years of experience in their current position (54; 52%). Relative to control, WISER significantly improved depressive symptoms [-7.5 (95%CI: -11.0, -4.0), p < 0.001], work-life integration [6.5 (95%CI: 4.1, 8.9), p < 0.001], happiness [5.7 (95%CI: 3.0, 8.4), p < 0.001], emotional thriving [6.4 (95%CI: 2.5, 10.3), p = 0.001], and emotional recovery [5.3 (95%CI: 1.7, 8.9), p = 0.004], but not emotional exhaustion [-3.7 (95%CI: -8.2, 0.8), p = 0.11] at 1 week. Combined cohort results at 1, 6, and 12 months showed that all six wellbeing outcomes were significantly improved relative to baseline (p < 0.05 for all). Favorable impressions of WISER were reported by 87% of participants at the 6-month post-assessment. Conclusion and relevance: WISER improved HCW depressive symptoms, work-life integration, happiness, emotional thriving, and emotional recovery. Improvements in all HCW wellbeing outcomes endured at the 1-, 6-, and 12-month follow-ups. HCW's impressions of WISER were positive. Clinical trials number: https://clinicaltrials.gov/ct2/show/, identifier: NCT02603133. Web-based Implementation for the Science of Enhancing Resilience Study (WISER).

Frontiers in public health · randomised controlled trial · 17 citationsread the source →

Intimate partner violence during pregnancy and perinatal mental disorders in low and lower middle income countries: A systematic review of literature, 1990-2017.

Mental health consequences of intimate partner violence (IPV) against pregnant and postpartum women are poorly understood in low and lower-middle-income countries (LLMIC). We systematically reviewed the evidence from 24 studies (1990-2017) selected via a comprehensive search strategy with 14 inclusion, exclusion, and quality-control criteria to assess the extent to which intimate partner violence during pregnancy adversely affects perinatal mental disorders among participants in 10 LLMIC across 4 economic regions. Mostly cross-sectional, studies included 61-1369 participants selected randomly (88%) or non-randomly (12%) from purposively selected 1-6 clinics or 1-50 communities. Multivariate logistic regression was most frequently used (68%) for association estimates, adjusting for 3-16 socio-demographic variables pertinent to: women; husbands; and/or households. The prevalence of physical IPV ranged 2-35% among participants; sexual IPV ranged 9-40%; and psychological IPV ranged 22-65%. The prevalence of antenatal and postnatal depression ranged 15-65% and 5-35% among participants, respectively. Suicidal ideation ranged 5-11% during pregnancy and 2-22% during the postpartum period. Study participants who had experienced IPV had 1.69-3.76 and 1.46-7.04 higher odds of antenatal and postnatal depression compared to those who had not, depending on country, and IPV type and severity. Considering the strong association between IPV and mental disorders, efforts should focus on developing IPV interventions aimed at preventing pregnancy during IPV and promoting mental health resilience among pregnancy and postpartum women in low and lower-middle-income countries.

Clinical psychology review · systematic review · 106 citationsread the source →

Randomized, Controlled Trial of an Advance Care Planning Video Decision Support Tool for Patients With Advanced Heart Failure.

Background: Conversations about goals of care and cardiopulmonary resuscitation (CPR)/intubation for patients with advanced heart failure can be difficult. This study examined the impact of a video decision support tool and patient checklist on advance care planning for patients with heart failure. Methods: This was a multisite, randomized, controlled trial of a video-assisted intervention and advance care planning checklist versus a verbal description in 246 patients ≥64 years of age with heart failure and an estimated likelihood of death of >50% within 2 years. Intervention participants received a verbal description for goals of care (life-prolonging care, limited care, and comfort care) and CPR/intubation plus a 6-minute video depicting the 3 levels of care, CPR/intubation, and an advance care planning checklist. Control subjects received only the verbal description. The primary analysis compared the proportion of patients preferring comfort care between study arms immediately after the intervention. Secondary outcomes were CPR/intubation preferences and knowledge (6-item test; range, 0-6) after intervention. Results: In the intervention group, 27 (22%) chose life-prolonging care, 31 (25%) chose limited care, 63 (51%) selected comfort care, and 2 (2%) were uncertain. In the control group, 50 (41%) chose life-prolonging care, 27 (22%) selected limited care, 37 (30%) chose comfort care, and 8 (7%) were uncertain (P<0.001). Intervention participants (compared with control subjects) were more likely to forgo CPR (68% versus 35%; P<0.001) and intubation (77% versus 48%; P<0.001) and had higher mean knowledge scores (4.1 versus 3.0; P<0.001). Conclusions: Patients with heart failure who viewed a video were more informed, more likely to select a focus on comfort, and less likely to desire CPR/intubation compared with patients receiving verbal information only. Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01589120.

Circulation · randomised controlled trial · 88 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 →

Real-Time Psychophysiological and Writing Correlates of Expressive Writing.

Concealing memories and emotions associated with a traumatic event seems to have negative effects on health. Re-enacting those events through writing is an opportunity to disclose such memories and emotions, and especially for emotion regulation. To study this, 57 university students were randomly assigned to one of two groups. They either completed an expressive writing or a neutral writing task. Real-time writing and psychophysiological data were recorded throughout the experiment to examine writing dynamics associated with emotion regulation and its psychophysiological correlates (electrodermal activity and electrocardiography measures). The results showed that the expressive group (EG) paused for longer than the control group (CG) denoting a positive and medium effect size ( η p 2 = .10 ) . Furthermore, during and after writing, the EG showed a higher low frequency/high frequency ratio than the CG, evidencing a positive and large effect size ( η p 2 = .22 ) . These real-time findings are interpreted as signs of emotion regulation happening during writing.

Experimental psychology · 1 citationsread the source →

Changes in social connection during COVID-19 social distancing: It's not (household) size that matters, it's who you're with.

To slow the transmission of COVID-19, countries around the world have implemented social distancing and stay-at-home policies-potentially leading people to rely more on household members for their sense of closeness and belonging. To understand the conditions under which people felt the most connected, we examined whether changes in overall feelings of social connection varied by household size and composition. In two pre-registered studies, undergraduates in Canada (NStudy 1 = 548) and adults primarily from the U.S. and U.K. (NStudy 2 = 336) reported their perceived social connection once before and once during the pandemic. In both studies, living with a partner robustly and uniquely buffered shifts in social connection during the first phases of the pandemic (βStudy 1 = .22, βStudy 2 = .16). In contrast, neither household size nor other aspects of household composition predicted changes in connection. We discuss implications for future social distancing policies that aim to balance physical health with psychological health.

PloS one · 57 citationsread the source →

The Psychomotor Vigilance Test as a measure of alertness and sleep inertia in people with central disorders of hypersomnolence.

Study objectives: The central disorders of hypersomnolence (CDH) manifest with daytime sleepiness, often accompanied by cognitive symptoms. Objective tests characterizing cognitive dysfunction may have diagnostic utility. Further, because some people with CDH report worsening cognition upon awakening, cognitive testing before and after napping may provide additional diagnostic information. Methods: Patients with CDH with idiopathic hypersomnia (n = 76), narcolepsy type 1 (n = 19), narcolepsy type 2 (n = 22), and self-reported excessive daytime sleepiness not meeting current diagnostic criteria (n = 76) and nonsleepy controls (n = 33) underwent testing with the Psychomotor Vigilance Test (PVT), a 10-minute reaction-time test. A subset of participants underwent repeat testing during a Multiple Sleep Latency Test, before and immediately after naps 2 and 4. Results: Most PVT metrics were significantly better in controls than in patients with CDH. Minimal group differences in PVT performance were observed by CDH diagnosis. PVT performance was weakly correlated to Epworth Sleepiness Scale and Multiple Sleep Latency Test mean sleep latency in the CDH group. Before and after naps, PVT metrics were minimally different for controls, while PVT performance generally worsened following naps in the CDH group, with significant worsening compared with controls for nap 2 mean, median, lapses, and fastest 10% of responses and nap 4 lapses and slowest 10% of responses. Change in performance did not differ based on CDH diagnostic group for any metric on either nap. Conclusions: The PVT, at baseline and following a short nap, may provide adjunctive diagnostic utility in separating individuals with CDH from controls. Citation: Trotti LM, Saini P, Bremer E, et al. The Psychomotor Vigilance Test as a measure of alertness and sleep inertia in people with central disorders of hypersomnolence. J Clin Sleep Med. 2022;18(5):1395-1403.

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 25 citationsread the source →

Psychological responses, mental health, and sense of agency for the dual challenges of climate change and the COVID-19 pandemic in young people in the UK: an online survey study.

Background: The COVID-19 pandemic and climate change are both significant and pressing global challenges, posing threats to public health and wellbeing. Young people are particularly vulnerable to the distress both crises can cause, but understanding of the varied psychological responses to both issues is poor. We aimed to investigate these responses and their links with mental health conditions and feelings of agency. Methods: We conducted an online survey between Aug 5 and Oct 26, 2020, targeting a diverse sample of young people (aged 16-24 years, n=530) in the UK. The survey was distributed using a combination of a survey panel (panel sample) and direct approaches to youth groups and schools who shared the survey with young people in their networks (community sample). We collected data on respondents' psychological responses to both climate change and the COVID-19 pandemic, their sense of agency to respond to each crisis, and the range of impacts on their lives. We also collected demographics data and screened for mental health and wellbeing indicators. We used non-parametric tests for most statistical comparisons. For paired samples, we used Wilcoxon's signed-rank test, and used Mann-Whitney U-tests or Kruskal-Wallis tests for two or more independent samples. Summed scale scores were considered as interval-level data and analysed with Student's t tests and ANOVAs. Effect sizes are reported as Cohen's d and partial eta-squared (η·2p), respectively. Findings: After excluding 18 suspected bots and 94 incomplete responses, 530 responses were retained for analysis. Of the 518 respondents who provided demographic data, 63% were female, 71·4% were White, and the mean family affluence score was 8·22 (SD 2·29). Most participants (n=343; 70%) did not report a history of diagnosis or treatment for a mental health disorder, but mental health scores indicated a common experience of (relatively mild) symptoms of anxiety, depression, and stress. Although UK youth reported more life disruption and concern for their future due to the COVID-19 pandemic, climate change was associated with significantly greater distress overall, particularly for individuals with low levels of generalised anxiety. The COVID-19 pandemic was more associated with feelings of anxiety, isolation, disconnection, and frustration; distress around loss and grief; and effects on quality of life. Climate change was more likely to evoke emotions such as interest and engagement, guilt, shame, anger, and disgust. The greater distress attributed to climate change overall was due, in particular, to higher levels of guilt, sense of personal responsibility, and greater distress triggered by upsetting media coverage. Agency to address climate change was associated with greater climate distress, but pandemic-related distress and agency were unrelated. Interpretation: The COVID-19 pandemic and climate change are affecting the wellbeing of UK young people in distinct ways, with implications for health service, policy, and research responses. There is a need for mental health practitioners, policy makers, and other societal actors to account for the complex relationship between climate agency, distress, and mental wellbeing in young people. Funding: Imperial College London.

The Lancet. Planetary health · 47 citationsread the source →

The profile of psychiatric symptoms exacerbated by methamphetamine use.

Background: Methamphetamine use can produce symptoms almost indistinguishable from schizophrenia. Distinguishing between the two conditions has been hampered by the lack of a validated symptom profile for methamphetamine-induced psychiatric symptoms. We use data from a longitudinal cohort study to examine the profile of psychiatric symptoms that are acutely exacerbated by methamphetamine use. Methods: 164 methamphetamine users, who did not meet DSM-IV criteria for a lifetime primary psychotic disorder, were followed monthly for one year to assess the relationship between days of methamphetamine use and symptom severity on the 24-item Brief Psychiatric Rating Scale. Exacerbation of psychiatric symptoms with methamphetamine use was quantified using random coefficient models. The dimensions of symptom exacerbation were examined using principal axis factoring and a latent profile analysis. Results: Symptoms exacerbated by methamphetamine loaded on three factors: positive psychotic symptoms (suspiciousness, unusual thought content, hallucinations, bizarre behavior); affective symptoms (depression, suicidality, guilt, hostility, somatic concern, self-neglect); and psychomotor symptoms (tension, excitement, distractibility, motor hyperactivity). Methamphetamine use did not significantly increase negative symptoms. Vulnerability to positive psychotic and affective symptom exacerbation was shared by 28% of participants, and this vulnerability aligned with a past year DSM-IV diagnosis of substance-induced psychosis (38% vs. 22%, χ(2)(df1)=3.66, p=0.056). Conclusion: Methamphetamine use produced a symptom profile comprised of positive psychotic and affective symptoms, which aligned with a diagnosis of substance-induced psychosis, with no evidence of a negative syndrome.

Drug and alcohol dependence · 55 citationsread the source →

A systematic review of the relationships among psychosocial factors and coping in adults with type 2 diabetes mellitus.

Type 2 diabetes mellitus contributes to poor health outcomes including mortality, yet there is a gap in the literature when seeking to understand the influence of psychosocial factors on coping in this population. The paper presents a systematic review of quantitative studies that examined relationships among psychosocial determinants and coping in adults with type 2 diabetes. This review is the second layer of knowledge discovery for the concept, "Taking on a life-altering change is a rhythmical journey of experiencing ups and downs on the way to acceptance." The life-altering change was determined to be a diagnosis of type 2 diabetes, the journey is the ups and downs of coping with the diagnosis as people work toward acceptance of type 2 diabetes. The review includes a synthesis of findings from 22 quantitative studies of psychosocial factors and coping in adults with type 2 diabetes. Anxiety, depression, stress, and diabetes distress were identified as key influential psychosocial factors. Increased social support was inversely related to emotional distress and coping styles were related to social well-being, psychological health, and physical health outcomes. The positive coping style of problem-focused coping was linked to improved psychological and physical health. Emotional responses to diagnosis were related to depression and anxiety. Negative coping styles of resignation, protest, or isolation were higher in women and linked to poorer quality of life, while avoidance was linked to increased diabetes-related distress and depressive symptoms.

International journal of nursing sciences · review · 53 citationsread the source →

Tetrahydrobiopterin augments endothelium-dependent dilatation in sedentary but not in habitually exercising older adults.

Endothelium-dependent dilatation (EDD) is impaired with ageing in sedentary, but not in regularly exercising adults. We tested the hypotheses that differences in tetrahydrobiopterin (BH(4)) bioactivity are key mechanisms explaining the impairment in EDD with sedentary ageing, and the maintenance of EDD with ageing in regularly exercising adults. Brachial artery flow-mediated dilatation (FMD), normalized for local shear stress, was measured after acute oral placebo or BH(4) in young sedentary (YS) (n = 10; 22 +/- 1 years, mean +/- s.e.m.), older sedentary (OS) (n = 9; 62 +/- 2), and older habitually aerobically trained (OT) (n = 12; 66 +/- 1) healthy men. At baseline, FMD was approximately 50% lower in OS versus YS (1.12 +/- 0.09 versus 0.57 +/- 0.09 (Deltamm (dyn cm(-2))) x 10(-2), P < 0.001; 1 dyn = 10(-5) N), but was preserved in OT (0.93 +/- 0.08 (Deltamm (dyn cm(-2))) x 10(-2)). BH4 administration improved FMD by approximately 45% in OS (1.00 +/- 0.10 (Deltamm (dyn cm(-2))) x 10(-2), P < 0.01 versus baseline), but did not affect FMD in YS or OT. Endothelium-independent dilatation neither differed between groups at baseline nor changed with BH4 administration. These results suggest that BH4 bioactivity may be a key mechanism involved in the impairment of conduit artery EDD with sedentary ageing, and the EDD-preserving effect of habitual exercise.

The Journal of physiology · randomised controlled trial · 136 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 →

Impact of breastfeeding interventions among United States minority women on breastfeeding outcomes: a systematic review.

Background: In the U.S., strong ethnic/racial, socioeconomic, demographic, and geographic breastfeeding (BF) inequities persist, and African American and Hispanic women are less likely to meet their breastfeeding goals compared to White women. This systematic review (SR) was designed to answer the question: What is the impact of breastfeeding interventions targeting ethnic/racial minority women in the U.S. on improving BF initiation, duration and exclusivity rates? Methods: The SR was conducted following the Institute of Medicine Guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. The study protocol was developed and registered a priori in PROSPERO (ID#CRD42020177764). The electronical databases searched was MEDLINE All (Ovid). Search strategies were led by the team's expert public health librarian using both controlled vocabulary and free text queries and were tested against a validated set of relevant papers included in existing reviews. The GRADE methodology was used to assess the quality of the studies. Results: We included 60 studies that had randomized (n = 25), observational (n = 24), quasi-experimental (n = 9), or cross-sectional (n = 2) designs. The studies focused on populations that were multi-ethnic/racial (n = 22), only Hispanic (n = 24), only Black (n = 13), and only American Indian (n = 1). The study interventions were classified following the socioecological model: macrosystem/policy level (n = 6); community level (n=51), which included healthcare organizations (n = 34), The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) (n = 9), and community organizations/public health institutions (n = 8); and  interpersonal level (n = 3). Conclusions: Policy and community level interventions delivered through WIC, healthcare facilities, and community agencies) are likely to improve BF outcomes among women of color. The combination of interventions at different levels of the socioecological model has not been studied among minority women in the U.S. Implementation science research is needed to learn how best to scale up and sustain effective BF interventions, taking into account the needs and wants of minority women. Thus, it is strongly recommended  to conduct large scale implementation research studies addressesing how to strengthen the different health and social environments surrounding women of color in the U.S. to improving their BF outcomes.

International journal for equity in health · systematic review · 97 citationsread the source →

Exceptional longevity in men: modifiable factors associated with survival and function to age 90 years.

Background: Prospective data on nongenetic determinants of exceptional longevity are limited, and information on long-lived men and their functional status is particularly sparse. We examined modifiable factors associated with a life span of 90 or more years and late-life function in men. Methods: In this prospective cohort study of 2357 healthy men (mean age, 72 years) within the Physicians' Health Study (1981-2006), biological and lifestyle factors and comorbid conditions were assessed by self-report with baseline and annual questionnaires. Mortality and incidence of major diseases were confirmed by medical record review. Late-life function was assessed 16 years after baseline by the Medical Outcomes Study 36-Item Short-Form Health Survey. Results: A total of 970 men (41%) survived to at least age 90 years. Smoking was associated with increased risk of mortality before age 90 years (hazard ratio [HR]; 2.10; 95% confidence interval [CI], 1.75-2.51), and similar associations were observed with diabetes (HR, 1.86; 95% CI, 1.52-2.26), obesity (HR, 1.44; 95% CI, 1.10-1.90), and hypertension (HR, 1.28; 95% CI, 1.15-1.43). Regular exercise was associated with a nearly 30% lower mortality risk (HR, 0.72; 95% CI, 0.62-0.83). The probability of a 90-year life span at age 70 years was 54% in the absence of smoking, diabetes, obesity, hypertension, or sedentary lifestyle. It ranged from 36% to 22% with 2 adverse factors and was negligible (4%) with 5. Compared with nonsurvivors, men with exceptional longevity had a healthier lifestyle (67% vs 53% had <or=1 adverse factor), had a lower incidence of chronic diseases, and were 3 to 5 years older at disease onset. They had better late-life physical function (mean +/- SD score [maximum 100], 73 +/- 23 vs 62 +/- 30; P < .001) and mental well-being (mean score, 84 +/- 14 vs 81 +/- 17; P = .03). More than 68% (vs 45%) rated their late-life health as excellent or very good, and less than 8% (vs 22%) reported fair or poor health (P < .001 for trend). Regular exercise was associated with significantly better-and smoking and overweight with significantly worse-late-life physical function. Smoking also was associated with a significant decrement in mental function. Conclusion: Modifiable healthy behaviors during early elderly years, including smoking abstinence, weight management, blood pressure control, and regular exercise, are associated not only with enhanced life span in men but also with good health and function during older age.

Archives of internal medicine · editorial or comment · 143 citationsread the source →

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

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

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

Building extended families through embryo donation: the experiences of donors and recipients.

Study question: How do embryo donors and recipients understand and experience embryo donation (ED)? Summary answer: Donors and recipients regard the genetic link between donors and donor-conceived child as significant, and draw on metaphors of ED as adoption and as building extended family networks in order to manage the complex interplay of genetic, gestational and social aspects of reproduction and family-building. What is known already: The uptake of embryo donation internationally is relatively low and there has been little research into the outcomes and experiences of ED for donor and recipient families. Study design, size, duration: Embryo donors and recipients in New Zealand were interviewed between March and October 2012 as to their understandings and experiences of embryo donation. Participants/materials, setting, methods: Participants were recruited from across New Zealand and interviews were conducted with 22 donors (10 couples, 2 individuals) and 15 recipients (5 couples, 5 individuals). Interview data were analysed thematically to identify factors that influenced their perspectives and affected their experiences. Main results and the role of chance: The genetic link between donors and offspring is regarded as bestowing immutable social ties by both donors and recipients. This makes ED a difficult choice for both donors, who experience a sense of ongoing responsibility for offspring welfare, and for recipients, who may have concerns about the donor-offspring bond. Disclosure of genetic background is regarded as critical for the welfare of both the donor-conceived child as well as siblings in the donor family. Both donors and recipients draw parallels between ED and open adoption practices, and draw on extended family constructs in order to describe their relationship to each other. Limitations, reasons for caution: Donors and recipients were interviewed at various stages of the ED process, and experiences may change over time. Wider implications of the findings: The comparison of ED with open adoption practice and the metaphor of extended family-building both help make sense of and complicate the ED experience. These concepts help to structure expectations for the assessment for ED, the disclosure of donor conception, and the nature of relationships, information-exchange and contact. Study funding/competing interests: This study was funded by an AUT University Faculty of Health Environmental Sciences research grant.

Human reproduction (Oxford, England) · 30 citationsread the source →