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Use of a Comprehensive Geriatric Assessment for the Management of Elderly Patients With Advanced Non-Small-Cell Lung Cancer: The Phase III Randomized ESOGIA-GFPC-GECP 08-02 Study.

Purpose: Comprehensive geriatric assessment (CGA) is recommended to assess the vulnerability of elderly patients, but its integration in cancer treatment decision making has never been prospectively evaluated. Here, in elderly patients with advanced non-small-cell lung cancer (NSCLC), we compared a standard strategy of chemotherapy allocation on the basis of performance status (PS) and age with an experimental strategy on the basis of CGA. Patients and methods: In a multicenter, open-label, phase III trial, elderly patients ≥ 70 years old with a PS of 0 to 2 and stage IV NSCLC were randomly assigned between chemotherapy allocation on the basis of PS and age (standard arm: carboplatin-based doublet if PS ≤ 1 and age ≤ 75 years; docetaxel if PS = 2 or age > 75 years) and treatment allocation on the basis of CGA (CGA arm: carboplatin-based doublet for fit patients, docetaxel for vulnerable patients, and best supportive care for frail patients). The primary end point was treatment failure free survival (TFFS). Secondary end points were overall survival (OS), progression-free survival, tolerability, and quality of life. Results: Four hundred ninety-four patients were randomly assigned (standard arm, n = 251; CGA arm, n = 243). Median age was 77 years. In the standard and CGA arms, 35.1% and 45.7% of patients received a carboplatin-based doublet, 64.9% and 31.3% received docetaxel, and 0% and 23.0% received best supportive care, respectively. In the standard and CGA arms, median TFFS times were 3.2 and 3.1 months, respectively (hazard ratio, 0.91; 95% CI, 0.76 to 1.1), and median OS times were 6.4 and 6.1 months, respectively (hazard ratio, 0.92; 95% CI, 0.79 to 1.1). Patients in the CGA arm, compared with standard arm patients, experienced significantly less all grade toxicity (85.6% v 93.4%, respectively P = .015) and fewer treatment failures as a result of toxicity (4.8% v 11.8%, respectively; P = .007). Conclusion: In elderly patients with advanced NSCLC, treatment allocation on the basis of CGA failed to improve the TFFS or OS but slightly reduced treatment toxicity.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology · randomised controlled trial · 259 citationsread the source →

Effectiveness of a brief lay counsellor-delivered, problem-solving intervention for adolescent mental health problems in urban, low-income schools in India: a randomised controlled trial.

Background: Mental health problems are a leading cause of disability in adolescents worldwide. Problem solving is a well-tested mental health intervention in many populations. We aimed to investigate the effectiveness of a brief, transdiagnostic problem-solving intervention for common adolescent mental health problems when delivered by non-specialist school counsellors in New Delhi, India. Methods: This randomised trial was done in six government-run schools (three all-boys schools, two all-girls schools, and one co-educational school) that serve low-income communities. We recruited participants from grades 9 to 12 (ages 12-20 years) by selecting students with persistently elevated mental health symptoms accompanied by distress or functional impairment. Clinical eligibility criteria were assessed by research assistants using the Hindi-language version of the Strengths and Difficulties Questionnaire (SDQ), with reference to locally validated borderline cutoff scores of 19 or greater for boys and 20 or greater for girls on the SDQ Total Difficulties scale, an abnormal score of 2 or more on the SDQ Impact scale, and persistence of more than 1 month on the SDQ Chronicity index. Participants were randomly allocated (1:1) to problem solving delivered through a brief (2-3 week) counsellor-led intervention with supporting printed materials (intervention group), or problem solving delivered via printed booklets alone (control group). Primary outcomes were adolescent-reported mental health symptoms (SDQ Total Difficulties scale) and idiographic psychosocial problems (Youth Top Problems [YTP]) at 6 weeks. Primary analyses were done on an intention-to-treat basis at the 6-week endpoint. The trial is registered with ClinicalTrials.gov, NCT03630471. Findings: Participants were enrolled between Aug 20, and Dec 4, 2018. 283 eligible adolescents were referred to the trial, and 251 (89%) of these were enrolled (mean age 15·61 years; 174 [69%] boys). 125 participants were allocated to each group (after accounting for one participant in the intervention group who withdrew consent after randomisation). Primary outcome data were available for 245 (98%) participants. At 6 weeks, the mean YTP scores were 3·52 (SD 2·66) in the intervention group and 4·60 (2·75) in the control group (adjusted mean difference -1·01, 95% CI -1·63 to -0·38; adjusted effect size 0·36, 95% CI 0·11 to 0·61; p=0·0015). The mean SDQ Total Difficulties scores were 17·48 (5·45) in the intervention group and 18·33 (5·45) in the control group (-0·86, -2·14 to 0·41; 0·16, -0·09 to 0·41; p=0·18). We observed no adverse events. Interpretation: A brief lay counsellor-delivered problem-solving intervention combined with printed booklets seemed to have a modest effect on psychosocial outcomes among adolescents with diverse mental health problems compared with problem-solving booklets alone. This counsellor-delivered intervention might be a suitable first-line intervention in a stepped care approach, which is being evaluated in ongoing studies. Funding: Wellcome Trust.

The Lancet. Child & adolescent health · randomised controlled trial · 69 citationsread the source →

Inflammatory markers in post-traumatic stress disorder: a systematic review, meta-analysis, and meta-regression.

Background: Studies investigating inflammatory markers in post-traumatic stress disorder (PTSD) have yielded mixed results. The aim of our study was to compare concentrations of inflammatory markers in patients with PTSD compared with healthy controls. Methods: We did a meta-analysis and meta-regression of studies comparing inflammatory markers between patients with PTSD and healthy controls by searching PubMed, Embase, Scopus, Web of Science, and PsycINFO for articles published between Jan 1, 1960, and April 7, 2015. From eligible studies (ie, cross-sectional studies or baseline data from longitudinal studies of peripheral blood cytokine concentrations that compared adults with PTSD with healthy controls), we extracted outcomes of interest, such as mean and SD of peripheral blood cytokines, the time of day blood was collected, whether the study allowed patients with comorbid major depressive disorder in the PTSD group, whether patients were medication free, and severity of PTSD symptoms. We undertook meta-analyses whenever values of inflammatory markers were available in two or more studies. A random-effects model with restricted maximum-likelihood estimator was used to synthesise the effect size (assessed by standardised mean difference [SMD]) across studies. Findings: 8057 abstracts were identified and 20 studies were included. Interleukin 6 (SMD 0.88; p=0.0003), interleukin 1β (SMD 1.42; p=0.045), and interferon γ (SMD 0.49; p=0.002) levels were higher in the PTSD group than in healthy controls. Subgroup meta-analysis of patients who were not given medication showed higher tumour necrosis factor α (TNFα; SMD 0.69, 95% CI 0.35-1.02; p<0.0001) in the PTSD group than the control group in addition to the aforementioned cytokines. TNFα (SMD 1.32, 0.13-2.50; p=0.003), interleukin 1β (SMD 2.35, 0.01-4.68; p=0.048), and interleukin 6 (SMD 1.75, 0.97-2.53; p<0.0001) levels remained increased in the PTSD group in a subgroup meta-analysis of studies that excluded comorbid major depressive disorder. Illness duration was positively associated with interleukin 1β levels (b=0.33, p<0.0001) and severity with interleukin 6 (b=0.02, p=0.042). A model composed of several variables-presence of comorbid major depressive disorder, use of psychotropic medications, assay used, and time of day blood was collected-explained the large amount of heterogeneity between interleukin 1β, interleukin 6, and C-reactive protein studies. Egger's linear regression test revealed a potential publication bias for interleukin 1β. Additionally, for most inflammatory markers, study heterogeneity was reported to be high (I(2)>75%). Interpretation: PTSD is associated with increased interleukin 6, interleukin 1β, TNFα, and interferon γ levels. This information might be useful for consideration of chronic low-grade inflammation as a potential target or biomarker in PTSD treatment. Use of psychotropic medication and presence of comorbid major depressive disorder were important moderators that might explain the inconsistency between results of previous studies. Our search strategy used a range of databases and we made exhaustive effort to acquire data by contacting the authors. Notably, high levels of between-study heterogeneity were recorded for most cytokine variables measured in our analysis. However, meta-regression analysis could explain a large amount of this heterogeneity. Funding: None.

The lancet. Psychiatry · meta-analysis · 549 citationsread the source →

Telerehabilitation services for stroke.

Background: Telerehabilitation offers an alternate way of delivering rehabilitation services. Information and communication technologies are used to facilitate communication between the healthcare professional and the patient in a remote location. The use of telerehabilitation is becoming more viable as the speed and sophistication of communication technologies improve. However, it is currently unclear how effective this model of delivery is relative to rehabilitation delivered face-to-face or when added to usual care. Objectives: To determine whether the use of telerehabilitation leads to improved ability to perform activities of daily living amongst stroke survivors when compared with (1) in-person rehabilitation (when the clinician and the patient are at the same physical location and rehabilitation is provided face-to-face); or (2) no rehabilitation or usual care. Secondary objectives were to determine whether use of telerehabilitation leads to greater independence in self-care and domestic life and improved mobility, balance, health-related quality of life, depression, upper limb function, cognitive function or functional communication when compared with in-person rehabilitation and no rehabilitation. Additionally, we aimed to report on the presence of adverse events, cost-effectiveness, feasibility and levels of user satisfaction associated with telerehabilitation interventions. Search methods: We searched the Cochrane Stroke Group Trials Register (June 2019), the Cochrane Central Register of Controlled Trials (the Cochrane Library, Issue 6, 2019), MEDLINE (Ovid, 1946 to June 2019), Embase (1974 to June 2019), and eight additional databases. We searched trial registries and reference lists. Selection criteria: Randomised controlled trials (RCTs) of telerehabilitation in stroke. We included studies that compared telerehabilitation with in-person rehabilitation or no rehabilitation. In addition, we synthesised and described the results of RCTs that compared two different methods of delivering telerehabilitation services without an alternative group. We included rehabilitation programmes that used a combination of telerehabilitation and in-person rehabilitation provided that the greater proportion of intervention was provided via telerehabilitation. Data collection and analysis: Two review authors independently identified trials on the basis of prespecified inclusion criteria, extracted data and assessed risk of bias. A third review author moderated any disagreements. The review authors contacted investigators to ask for missing information. We used GRADE to assess the quality of the evidence and interpret findings. Main results: We included 22 trials in the review involving a total of 1937 participants. The studies ranged in size from the inclusion of 10 participants to 536 participants, and reporting quality was often inadequate, particularly in relation to random sequence generation and allocation concealment. Selective outcome reporting and incomplete outcome data were apparent in several studies. Study interventions and comparisons varied, meaning that, in many cases, it was inappropriate to pool studies. Intervention approaches included post-hospital discharge support programs, upper limb training, lower limb and mobility retraining and communication therapy for people with post-stroke language disorders. Studies were either conducted upon discharge from hospital or with people in the subacute or chronic phases following stroke. Primary outcome: we found moderate-quality evidence that there was no difference in activities of daily living between people who received a post-hospital discharge telerehabilitation intervention and those who received usual care (based on 2 studies with 661 participants (standardised mean difference (SMD) -0.00, 95% confidence interval (CI) -0.15 to 0.15)). We found low-quality evidence of no difference in effects on activities of daily living between telerehabilitation and in-person physical therapy programmes (based on 2 studies with 75 participants: SMD 0.03, 95% CI -0.43 to 0.48). Secondary outcomes: we found a low quality of evidence that there was no difference between telerehabilitation and in-person rehabilitation for balance outcomes (based on 3 studies with 106 participants: SMD 0.08, 95%CI -0.30 to 0.46). Pooling of three studies with 569 participants showed moderate-quality evidence that there was no difference between those who received post-discharge support interventions and those who received usual care on health-related quality of life (SMD 0.03, 95% CI -0.14 to 0.20). Similarly, pooling of six studies (with 1145 participants) found moderate-quality evidence that there was no difference in depressive symptoms when comparing post-discharge tele-support programs with usual care (SMD -0.04, 95% CI -0.19 to 0.11). We found no difference between groups for upper limb function (based on 3 studies with 170 participants: mean difference (MD) 1.23, 95% CI -2.17 to 4.64, low-quality evidence) when a computer program was used to remotely retrain upper limb function in comparison to in-person therapy. Evidence was insufficient to draw conclusions on the effects of telerehabilitation on mobility or participant satisfaction with the intervention. No studies evaluated the cost-effectiveness of telerehabilitation; however, five of the studies reported health service utilisation outcomes or costs of the interventions provided within the study. Two studies reported on adverse events, although no serious trial-related adverse events were reported. Authors' conclusions: While there is now an increasing number of RCTs testing the efficacy of telerehabilitation, it is hard to draw conclusions about the effects as interventions and comparators varied greatly across studies. In addition, there were few adequately powered studies and several studies included in this review were at risk of bias. At this point, there is only low or moderate-level evidence testing whether telerehabilitation is a more effective or similarly effective way to provide rehabilitation. Short-term post-hospital discharge telerehabilitation programmes have not been shown to reduce depressive symptoms, improve quality of life, or improve independence in activities of daily living when compared with usual care. Studies comparing telerehabilitation and in-person therapy have also not found significantly different outcomes between groups, suggesting that telerehabilitation is not inferior. Some studies reported that telerehabilitation was less expensive to provide but information was lacking about cost-effectiveness. Only two trials reported on whether or not any adverse events had occurred; these trials found no serious adverse events were related to telerehabilitation. The field is still emerging and more studies are needed to draw more definitive conclusions. In addition, while this review examined the efficacy of telerehabilitation when tested in randomised trials, studies that use mixed methods to evaluate the acceptability and feasibility of telehealth interventions are incredibly valuable in measuring outcomes.

The Cochrane database of systematic reviews · meta-analysis · 345 citationsread the source →

Effect of a smartphone application (Perx) on medication adherence and clinical outcomes: a 12-month randomised controlled trial.

Objective: To determine whether the Perx app improves medication adherence and clinical outcomes over 12 months compared with standard care in patients requiring polypharmacy. Design: Randomised controlled trial with 12-month follow-up. Setting: Outpatient clinics in three tertiary hospitals in Sydney, Australia. Participants: Eligible participants were aged 18-75 years, with at least one chronic condition, taking ≥3 different medications (oral medications or injections), with smartphone accessibility. Participants were randomised in a 1:1 ratio. Interventions: The intervention group used the Perx app that contained customised reminders and gamified interactions to reward verified medication adherence. Main outcome measures: The primary outcome was medication adherence over 12 months measured using pill counts. Secondary outcomes included clinical outcomes (haemoglobin A1c (HbA1c), cholesterol, blood glucose, triglycerides, creatinine, thyroid function, blood pressure and weight). Results: Of 1412 participants screened for eligibility, 124 participants were randomised; 45 in the Perx arm and 40 in the control arm completed the study. The average age was 59.5, 58.9% were women, chronic conditions were cardiovascular disease (78%), type 2 diabetes (75%), obesity (65%) or other endocrine disorders (18%). On average, participants were taking six medications daily. The Perx group had greater improvements in adherence at month 2 (Coef. 8%; 95% CI 0.01 to 0.15), month 3 (Coef. 7%; 95% CI 0.00 to 0.14) and month 12 (Coef. 7%; 95% CI 0.00 to 0.13). The probability of HbA1c ≤6.5% was greater in the Perx group at months 9 and 12 and cholesterol (total and low-density lipoprotein cholesterol) was lower in the Perx group at month 3. The intervention was particularly effective for those with obesity, taking medications for diabetes and taking ≤4 medications. Conclusions: This study provides evidence that app-based behavioural change interventions can increase medication adherence and produce longer-term improvements in some clinical outcomes in adults managing multimorbidity. More trials are needed to build the evidence base. Trial registration number: ACTRN12617001285347.

BMJ open · randomised controlled trial · 33 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 →

The effectiveness of manual-guided, problem-solving-based self-learning programme for family caregivers of people with recent-onset psychosis: A randomised controlled trial with 6-month follow-up.

Background: Family intervention for psychotic disorders is an integral part of psychiatric treatment with positive effects on patients' mental state and relapse rate. However, the effect of such family-based intervention on caregivers' psychological distress and well-being, especially in non-Western countries, has received comparatively much less attention. Objectives: To test the effects of guided problem-solving-based manual-guided self-learning programme for family caregivers of adults with recent-onset psychosis over a 6-month period of follow-up, when compared with those in usual family support service. Design: A single-centre randomised controlled trial, which was registered at ClinicalTrials.gov (NCT02391649), with a repeated-measures, two-arm (parallel-group) design. Settings: One main psychiatric outpatient clinic in the New Territories of Hong Kong. Participants: A random sample of 116 family caregiverss of adult outpatients with recent-onset psychosis. Methods: Following pre-test measurement, caregivers were assigned randomly to one of two study groups: a 5-month self-help, problem-solving-based manual-guided self-learning (or bibliotherapy) programme (in addition to usual care), or usual family support service only. Varieties of patient and caregiver health outcomes were assessed and compared at baseline and at 1-week and 6-month post-intervention. Results: One hundred and eleven (96%) caregivers completed the 6-month follow-up (two post-tests); 55 of them (95%) completed ≥4 modules and attended ≥2 review sessions (i.e., 75% of the intervention). The family participants' mean age was about 38 years and over 64% of them were female and patient's parent or spouse. Multivariate analyses of variance indicated that the manual-guided self-learning group reported significantly greater improvements than the usual care group in family burden [F(1,110)=6.21, p=0.006] and caregiving experience [F(1,110)=6.88, p=0.0004], and patients' psychotic symptoms [F(1,110)=6.25, p=0.0003], functioning [F(1,110)=7.01, p=0.0005] and number of hospitalisations [F(1,110)=5.71, p=0.005] over 6-month follow-up. Conclusions: Problem-solving-based, manual-guided self-learning programme for family caregivers of adults with recent-onset psychosis can be an effective self-help programme and provide medium-term benefits to patients' and caregivers' mental health and duration of patients' re-hospitalisations.

International journal of nursing studies · randomised controlled trial · 21 citationsread the source →

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

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

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

Sutureless Adult Voluntary Male Circumcision with Topical Anesthetic: A Randomized Field Trial of Unicirc, a Single-Use Surgical Instrument.

Introduction: The World Health Organization has solicited rapid and minimally invasive techniques to facilitate scale-up of voluntary medical male circumcision (VMMC). Study design: Non-blinded randomized controlled field trial with 2:1 allocation ratio. Participants: 75 adult male volunteers. Setting: Outpatient primary care clinic. Intervention: Open surgical circumcision under local anesthetic with suturing vs. Unicirc disposable instrument under topical anesthetic and wound sealing with cyanoacrylate tissue adhesive. Primary outcome: Intraoperative duration. Secondary outcomes: Intraoperative and postoperative pain; adverse events; time to healing; patient satisfaction; cosmetic result. Results: The intraoperative time was less with the Unicirc technique (median 12 vs. 25 min, p < 0.001). Wound healing and cosmetic results were superior in the Unicirc group. Adverse events were similar in both groups. Conclusions: VMMC with Unicirc under topical anesthetic and wound sealing with cyanoacrylate tissue adhesive is rapid, heals by primary intention with superior cosmetic results, and is potentially safer and more cost-effective than open surgical VMMC. Trial registration: Clinicaltrials.gov NCT02443792.

PloS one · randomised controlled trial · 10 citationsread the source →

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

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

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

Feasibility and Acceptability of a Positive Psychological Intervention for Patients With Type 2 Diabetes.

Objective: Positive psychological attributes (eg, optimism) have been associated with a healthier lifestyle and superior medical outcomes in patients with type 2 diabetes; however, there has been minimal study of behavioral interventions that target positive psychological constructs in this population. Accordingly, we developed a novel, telephone-based, 12-week positive psychology intervention and assessed its feasibility and short-term impact in adults with type 2 diabetes and suboptimal health behavior adherence. Method: This was a pilot and feasibility study in adult inpatients and outpatients at an urban academic medical center recruited between December 2013 and December 2014. Adult patients with (1) type 2 diabetes (meeting American Diabetes Association criteria, eg, glycated hemoglobin A1c [HbA1c] > 6.5% or fasting glucose > 126 mg/dL) and (2) suboptimal adherence (score < 15/18 on the Medical Outcomes Study Specific Adherence Scale items for medication, diet, and exercise) were eligible. Participants received a positive psychology manual, completed exercises (eg, writing a gratitude letter, performing acts of kindness), and reviewed these activities by phone with a study trainer over the 12-week study period. Feasibility and acceptability were assessed via exercise completion rates and postexercise ratings of ease/utility on 0-10 Likert scales. Longer-term efficacy was explored by examining changes in psychological states and health behaviors from baseline to 12 weeks using random-effects regression models and estimates of effect size. Results: A total of 15 participants enrolled; 12 participants provided complete baseline and follow-up data and were included in the analyses. Over 90% of these participants completed at least 2 exercises, and 75% completed a majority of the exercises. Participants rated the exercises as helpful (mean = 7.8/10) and easy to complete (mean = 7.1/10), and they reported improvements in optimism, gratitude, depression, anxiety, physical function, self-care, and health behaviors (Cohen d = 0.28-1.00). Conclusion: A positive psychology intervention for suboptimally adherent patients with type 2 diabetes was feasible, acceptable, and associated with broad pre-post psychological and health behavior improvement in a small initial study. Further testing of this promising intervention is warranted. Trial registration: ClinicalTrials.gov identifier: NCT02736084.

The primary care companion for CNS disorders · clinical trial · 28 citationsread the source →

The effect of walking and vitamin B supplementation on quality of life in community-dwelling adults with mild cognitive impairment: a randomized, controlled trial.

Objectives: To examine the effect of walking and vitamin B supplementation on quality-of-life (QoL) in community-dwelling adults with mild cognitive impairment. Methods: One year, double-blind, placebo-controlled trial. Participants were randomized to: (1) twice-weekly, group-based, moderate-intensity walking program (n = 77) or a light-intensity placebo activity program (n = 75); and (2) daily vitamin B pills containing 5 mg folic acid, 0.4 mg B12, 50 mg B6 (n = 78) or placebo pills (n = 74). QoL was measured at baseline, after six and 12 months using the population-specific Dementia Quality-of-Life (D-QoL) to assess overall QoL and the generic Short-Form 12 mental and physical component scales (SF12-MCS and SF12-PCS) to assess health-related QoL. Results: Baseline levels of QoL were relatively high. Modified intention-to-treat analyses revealed no positive main intervention effect of walking or vitamin supplementation. In both men and women, ratings of D-QoL-belonging and D-QoL-positive affect subscales improved with 0.003 (P = 0.04) and 0.002 points (P = 0.06) with each percent increase in attendance to the walking program. Only in men, SF12-MCS increased with 0.03 points with each percent increase in attendance (P = 0.08). Conclusion: Several small but significant improvements in QoL were observed with increasing attendance to the walking program. No effect of vitamin B supplementation was observed. Trial registration: International Standard Randomized Controlled Trial Number Register, 19227688, http://www.controlled-trials.com/isrctn/.

Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation · randomised controlled trial · 42 citationsread the source →

Patterns of therapeutic alliance: rupture-repair episodes in prolonged exposure for posttraumatic stress disorder.

Objective: To better understand the role of therapeutic alliance in posttraumatic stress disorder (PTSD) treatment, we examined patterns of and shifts in alliance. First, we identified individuals with repaired ruptures, unrepaired ruptures, and no ruptures in alliance. Then, we explored group differences in these alliance events for clients with common clinical correlates (i.e., co-occurring depression and childhood abuse history) and whether or not the presence of these events influenced treatment outcome. Method: At pretreatment, clients (N = 116)-76.1% female, 66% Caucasian, age M = 36.7 years (SD = 11.3)--completed measures assessing PTSD diagnosis and severity (PTSD Symptom Scale Interview and Self-Report), depression diagnosis and severity (Structured Clinical Interview for DSM-IV and Beck Depression Inventory), and trauma history. During 10 weeks of prolonged exposure therapy, alliance (California Psychotherapy Alliance Scale) measures were completed. At posttreatment, PTSD and depression were reassessed. Results: Ruptures in alliance were quite common (46%). No significant differences emerged in the frequency of repaired ruptures, unrepaired ruptures, or no ruptures between those with and without co-occurring major depressive disorder, χ²(2, N = 82) = 2.69, p = .26, or those with and without a history of childhood abuse, χ²(2, N = 81) = 0.57, p = .75. Unrepaired ruptures predicted worse treatment outcome (β = .44, p = .001). Conclusions: The current study underscores the importance of attending to discontinuities in alliance throughout treatment.

Journal of consulting and clinical psychology · randomised controlled trial · 47 citationsread the source →

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

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

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

Palliative Care in Heart Failure: The PAL-HF Randomized, Controlled Clinical Trial.

Background: Advanced heart failure (HF) is characterized by high morbidity and mortality. Conventional therapy may not sufficiently reduce patient suffering and maximize quality of life. Objectives: The authors investigated whether an interdisciplinary palliative care intervention in addition to evidence-based HF care improves certain outcomes. Methods: The authors randomized 150 patients with advanced HF between August 15, 2012, and June 25, 2015, to usual care (UC) (n = 75) or UC plus a palliative care intervention (UC + PAL) (n = 75) at a single center. Primary endpoints were 2 quality-of-life measurements, the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary and the Functional Assessment of Chronic Illness Therapy-Palliative Care scale (FACIT-Pal), assessed at 6 months. Secondary endpoints included assessments of depression and anxiety (measured via the Hospital Anxiety and Depression Scale [HADS]), spiritual well-being (measured via the FACIT-Spiritual Well-Being scale [FACIT-Sp]), hospitalizations, and mortality. Results: Patients randomized to UC + PAL versus UC alone had clinically significant incremental improvement in KCCQ and FACIT-Pal scores from randomization to 6 months (KCCQ difference = 9.49 points, 95% confidence interval [CI]: 0.94 to 18.05, p = 0.030; FACIT-Pal difference = 11.77 points, 95% CI: 0.84 to 22.71, p = 0.035). Depression improved in UC + PAL patients (HADS-depression difference = -1.94 points; p = 0.020) versus UC-alone patients, with similar findings for anxiety (HADS-anxiety difference = -1.83 points; p = 0.048). Spiritual well-being was improved in UC + PAL versus UC-alone patients (FACIT-Sp difference = 3.98 points; p = 0.027). Randomization to UC + PAL did not affect rehospitalization or mortality. Conclusions: An interdisciplinary palliative care intervention in advanced HF patients showed consistently greater benefits in quality of life, anxiety, depression, and spiritual well-being compared with UC alone. (Palliative Care in Heart Failure [PAL-HF]; NCT01589601).

Journal of the American College of Cardiology · randomised controlled trial · 386 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 →

The visual scoring of sleep and arousal in infants and children.

Age is probably the single most crucial factor determining how humans sleep. Age and level of vigilance significantly influence the electroencephalogram (EEG) and the polysomnogram (PSG). The Pediatric Task Force provide an evidence-based review of the age-related development of the polysomnographic features of sleep in neonates, infants, and children, assessing the reliability and validity of these features, and assessing alternative methods of measurement. We used this annotated supporting text to develop rules for scoring sleep and arousals in infants and children. A pediatric EEG or PSG can only be determined to be normal by assessing whether the EEG patterns are appropriate for maturational age. Sleep in infants at term can be scored as NREM and REM sleep because all the polysomnographic and EEG features of REM sleep are present and quiet sleep, if not NREM sleep, is at least "not REM sleep." The dominant posterior rhythm (DPR) of relaxed wakefulness increases in frequency with age: (1) 3.5-4.5 Hz in 75% of normal infants by 3-4 months post-term; (2) 5-6 Hz in most infants 5-6 months post-term; 3) 6 Hz in 70% of normal children by 2 months of age; and 3) 8 Hz (range 7.5-9.5 Hz) in 82% of normal children age 3 years, 9 Hz in 65% of 9-year-olds, and 10 Hz in 65% of 15-year-old controls. Sleep spindles in children occur independently at two different frequencies and two different scalp locations: 11.0-12.75 Hz over the frontal and 13.0-14.75 Hz over the centroparietal electrodes; these findings are most prominent in children younger than 13 years. Centroparietal spikes are often maximal over the vertex (Cz), less often maximal over the left central (C3) or right central (C4) EEG derivation. About 50% of sleep spindles within a particular infant's PSG are asynchronous before 6 months of age, 30% at 1 year. Based on this, we recommend that: (1) sleep spindles be scored as a polysomnographic signature of NREM stage 2 sleep (N2) at whatever age they are first seen in a PSG, typically present by 2 to 3 months post-term; (2) identify and score sleep spindles from the frontal and centroparietal EEG derivations, especially in infants and children younger than 13 years. NREM sleep in an infant or child can be scored if the dominant posterior rhythm occupies <50% of a 30-second epoch, and one or more of the following EEG patterns appear: (1) a diffuse lower voltage mixed frequency activity; (2) hypnagogic hypersynchrony; (3) rhythmic anterior theta of drowsiness; (4) diffuse high voltage occipital delta slowing; (5) runs or bursts of diffuse, frontal, frontocentral, or occipital maximal rhythmic 3-5 Hz slowing; (6) vertex sharp waves; and/or (7) post-arousal hypersynchrony. K complexes first appear 5 months post-term and are usually present by 6 months post-term, whereas clearly recognizable vertex sharp waves are most often seen 16 months post-term. Vertex sharp waves are best seen over the central (Cz, C3, C4) and K complexes over the frontal (Fz, F3, F4) electrodes. Slow wave activity (SWA) of slow wave sleep (SWS) is first seen as early as 2 to 3 months post-term and is usually present 4 to 4.5 months post-term. SWA of SWS in an infant or child often has a peak-to-peak amplitude of 100 to 400 microV. Based on consensus voting we recommended scoring N1, N2, and N3 corresponding to NREM 1, 2, and SWS whenever it was recognizable in an infant's PSG, usually by 4 to 4.5 months post-term (as early as 2-3 months post-term). Epochs of NREM sleep which contain no sleep spindles, K complexes, or SWA would be scored as N1; those which contain either K complexes or sleep spindles and <20% SWS as N2, and those in which >20% of the 30-second epoch contain 0.5 to 2 Hz >75 microV (usually 100-400 microV) activity as N3. The DPR should be scored in the EEG channel that is best observed, (typically occipital), but DPR reactive to eye opening can be seen in central electrodes. Because sleep spindles occur independently over the frontal and central regions in children, they should be scored whether they occur in the frontal or central regions. Because sleep spindles are asynchronous before age 2 years, simultaneous recording of left and right frontal and central activity may be warranted in children 1-2 years of age. Simultaneous recording of left, right, and midline central electrodes may be appropriate because of the asynchronous nature of sleep spindles before age 2 years, but reliability testing is needed. Evidence has shown that the PSG cannot reliably be used to identify neurological deficits or to predict behavior or outcome in infants because of significant diversity of results, even in normal infants. Normal sleep EEG patterns and architecture are present in the first year of life, even in infants with severe neurological compromise. Increasing evidence suggests that sleep and its disorders play critical roles in the development of healthy children and healthy adults thereafter. Reliability studies comparing head-to-head different scoring criteria, recording techniques, and derivations are needed so that future scoring recommendations can be based on evidence rather than consensus opinion. We need research comparing clinical outcomes with PSG measures to better inform clinicians and families exactly what meaning a PSG has in evaluating a child's suspected sleep disorder.

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · review · 206 citationsread the source →

Comparison of self-report measures for identifying late-life generalized anxiety in primary care.

This study evaluated the Penn State Worry Questionnaire, Penn State Worry Questionnaire-Abbreviated, and the Generalized Anxiety Disorder Questionnaire-IV for identifying generalized anxiety disorder in older medical patients. Participants were 191 of 281 patients screened for a clinical trial evaluating cognitive-behavior treatment, n = 110 with generalized anxiety disorder, 81 without. Participants completed the Penn State Worry Questionnaire and Generalized Anxiety Disorder Questionnaire-IV at pretreatment. Kappa coefficients estimated agreement with the Structured Clinical Interview for Diagnosis. Receiver operating characteristic curves compared sensitivity and specificity of self-report measures. The Penn State Worry Questionnaire (cutoff = 50) provided the strongest prediction of generalized anxiety disorder (sensitivity, 76%; specificity, 73%; 75% correctly classified; kappa = .49. Item 2 of the Generalized Anxiety Disorder Questionnaire-IV demonstrated comparable accuracy. The Penn State Worry Questionnaire, Generalized Anxiety Disorder Questionnaire-IV, and briefer versions of these measures may be useful in identifying late-life generalized anxiety disorder in medical settings.

Journal of geriatric psychiatry and neurology · cohort or longitudinal · 25 citationsread the source →

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

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

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

Physical activity and depressive symptoms in adolescents: a prospective study.

Background: The frequency of mental illness amongst adolescents and its potential long-term consequences make it an important topic to research in relation to risk and protective factors. Research on the relationship between physical activity and depressive symptoms in adolescents is limited. There is a particular lack of evidence from longitudinal studies. This study examines the relationship between depression and physical activity using the Research with East London Adolescents: Community Health Survey (RELACHS). Methods: This was a prospective cohort study. Participants were recruited from three Local Education Authority boroughs in East London in 2001 from year 7 (aged 11-12) and year 9 (aged 13-14) and were followed-up in 2003. All pupils in the 28 schools that took part were eligible for the study. Of the total 3,322 pupils eligible for the survey the overall response rate was 84% (2,789 pupils). A total of 2,093 (75%) pupils were also followed-up in 2003. The sample was multiethnic (73% of respondents were non-white) and deprived. Just under half of the sample was male (49%). Depressive symptoms were measured using the Short Moods and Feelings Questionnaire (SMFQ). Logistic regression analyses were used to examine the association between physical activity and depressive symptoms both cross-sectionally and longitudinally. Results: After adjustments, there was evidence for a cross-sectional association between physical activity and depressive symptoms for both boys and girls at baseline, with a decrease in the odds of depressive symptoms of about 8% for each additional hour of exercise undertaken per week (boys: odds ratio (OR) = 0.92, 95% CI 0.85 to 0.99; girls: OR = 0.92, 95% CI 0.85 to 1.00). There was no evidence for an association between a change in physical activity from baseline to follow-up and depressive symptoms at follow-up. Conclusions: This study provides some evidence for an association between level of physical activity and decreased depressive symptoms in adolescents. Further longitudinal research of these associations is required before physical activity can be recommended as an intervention for depression in adolescents.

BMC medicine · 105 citationsread the source →

Effectiveness of internet-based cognitive behavioural treatment for adolescents with chronic fatigue syndrome (FITNET): a randomised controlled trial.

Background: Chronic fatigue syndrome is characterised by persistent fatigue and severe disability. Cognitive behavioural therapy seems to be a promising treatment, but its availability is restricted. We developed Fatigue In Teenagers on the interNET (FITNET), the first dedicated internet-based therapeutic program for adolescents with this disorder, and compared its effectiveness with that of usual care. Methods: Adolescents aged 12-18 years with chronic fatigue syndrome were assigned to FITNET or usual care in a 1:1 ratio at one tertiary treatment centre in the Netherlands by use of a computer-generated blocked randomisation allocation schedule. The study was open label. Primary outcomes were school attendance, fatigue severity, and physical functioning, and were assessed at 6 months with computerised questionnaires. Analysis was by intention to treat. Thereafter, all patients were offered FITNET if needed. This trial is registered, number ISRCTN59878666. Findings: 68 of 135 adolescents were assigned to FITNET and 67 to usual care, and 67 and 64, respectively, were analysed. FITNET was significantly more effective than was usual care for all dichotomised primary outcomes at 6 months-full school attendance (50 [75%] vs 10 [16%], relative risk 4·8, 95% CI 2·7-8·9; p<0·0001), absence of severe fatigue (57 [85%] vs 17 [27%], 3·2, 2·1-4·9; p<0·0001), and normal physical functioning (52 [78%] vs 13 [20%], 3·8, 2·3-6·3; p<0·0001). No serious adverse events were reported. Interpretation: FITNET offers a readily accessible and highly effective treatment for adolescents with chronic fatigue syndrome. The results of this study justify implementation on a broader scale. Funding: Netherlands Organisation for Health Research and Development.

Lancet (London, England) · randomised controlled trial · 140 citationsread the source →

Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial.

Background: Obesity is associated with a reduction in life expectancy and an increase in mortality from cardiovascular diseases, cancer, and other causes. We therefore assessed the efficacy and safety of two doses of phentermine plus topiramate controlled-release combination as an adjunct to diet and lifestyle modification for weight loss and metabolic risk reduction in individuals who were overweight and obese, with two or more risk factors. Methods: In this 56-week phase 3 trial, we randomly assigned overweight or obese adults (aged 18-70 years), with a body-mass index of 27-45 kg/m(2) and two or more comorbidities (hypertension, dyslipidaemia, diabetes or prediabetes, or abdominal obesity) to placebo, once-daily phentermine 7·5 mg plus topiramate 46·0 mg, or once-daily phentermine 15·0 mg plus topiramate 92·0 mg in a 2:1:2 ratio in 93 centres in the USA. Drugs were administered orally. Patients were randomly assigned by use of a computer-generated algorithm that was implemented through an interactive voice response system, and were stratified by sex and diabetic status. Investigators, patients, and study sponsors were masked to treatment. Primary endpoints were the percentage change in bodyweight and the proportion of patients achieving at least 5% weight loss. Analysis was by intention to treat. This study is registered with Clinical Trials.gov, number NCT00553787. Findings: Of 2487 patients, 994 were assigned to placebo, 498 to phentermine 7·5 mg plus topiramate 46·0 mg, and 995 to phentermine 15·0 mg plus topiramate 92·0 mg; 979, 488, and 981 patients, respectively, were analysed. At 56 weeks, change in bodyweight was -1·4 kg (least-squares mean -1·2%, 95% CI -1·8 to -0·7), -8·1 kg (-7·8%, -8·5 to -7·1; p<0·0001), and -10·2 kg (-9·8%, -10·4 to -9·3; p<0·0001) in the patients assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus topiramate 92·0 mg, respectively. 204 (21%) patients achieved at least 5% weight loss with placebo, 303 (62%; odds ratio 6·3, 95% CI 4·9 to 8·0; p<0·0001) with phentermine 7·5 mg plus topiramate 46·0 mg, and 687 (70%; 9·0, 7·3 to 11·1; p<0·0001) with phentermine 15·0 mg plus topiramate 92·0 mg; for ≥10% weight loss, the corresponding numbers were 72 (7%), 182 (37%; 7·6, 5·6 to 10·2; p<0·0001), and 467 (48%; 11·7, 8·9 to 15·4; p<0·0001). The most common adverse events were dry mouth (24 [2%], 67 [13%], and 207 [21%] in the groups assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus topiramate 92·0 mg, respectively), paraesthesia (20 [2%], 68 [14%], and 204 [21%], respectively), constipation (59 [6%], 75 [15%], and 173 [17%], respectively), insomnia (47 [5%], 29 [6%], and 102 [10%], respectively), dizziness (31 [3%], 36 [7%], 99 [10%], respectively), and dysgeusia (11 [1%], 37 [7%], and 103 [10%], respectively). 38 (4%) patients assigned to placebo, 19 (4%) to phentermine 7·5 mg plus topiramate 46·0 mg, and 73 (7%) to phentermine 15·0 mg plus topiramate 92·0 mg had depression-related adverse events; and 28 (3%), 24 (5%), and 77 (8%), respectively, had anxiety-related adverse events. Interpretation: The combination of phentermine and topiramate, with office-based lifestyle interventions, might be a valuable treatment for obesity that can be provided by family doctors. Funding: Vivus.

Lancet (London, England) · randomised controlled trial · 667 citationsread the source →

Lifestyle changes for treating psoriasis.

Background: Psoriasis is an inflammatory skin disease that presents with itching, red, scaling plaques; its worsening has been associated with obesity, drinking, smoking, lack of sleep, and a sedentary lifestyle. Lifestyle changes may improve psoriasis. Objectives: To assess the effects of lifestyle changes for psoriasis, including weight reduction, alcohol abstinence, smoking cessation, dietary modification, exercise, and other lifestyle change interventions. Search methods: We searched the following databases up to July 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched the China National Knowledge Infrastructure, the Airiti Library, and five trials registers up to July 2018. We checked the references of included trials for further relevant trials, and we asked the authors of the included trials if they were aware of any relevant unpublished data. Selection criteria: We included randomised controlled trials (RCTs) of lifestyle changes (either alone or in combination) for treating psoriasis in people diagnosed by a healthcare professional. Treatment had to be given for at least 12 weeks. Eligible comparisons were no lifestyle changes or another active intervention. Data collection and analysis: We used standard methodological procedures expected by Cochrane. The primary outcome measures were 'Severity of psoriasis' and 'Adherence to the intervention'. Secondary outcomes were 'Quality of life', 'Time to relapse', and 'Reduction in comorbidities'. We used GRADE to assess the quality of the evidence for each outcome. Main results: We included 10 RCTs with 1163 participants (mean age: 43 to 61 years; 656 men and 478 women were reported). Six trials examined the effects of dietary intervention (low-calorie diet) in 499 obese participants (mean age: 44.3 to 61 years; where reported, 395 had moderate-to-severe psoriasis). One trial assessed a combined dietary intervention and exercise programme in 303 obese participants with moderate-to-severe psoriasis who had started a systemic therapy for psoriasis and had not achieved clearance after four weeks of continuous treatment (median age: 53 years). Another trial assessed a walking exercise and continuous health education in 200 participants (mean age: 43.1 years, severity not reported). Finally, two trials included education programmes promoting a healthy lifestyle in 161 participants (aged 18 to 78 years), with one trial on mild psoriasis and the other trial not reporting severity. Comparisons included information only; no intervention; medical therapy alone; and usual care (such as continuing healthy eating).All trials were conducted in hospitals and treated participants for between 12 weeks and three years. One trial did not report the treatment period. Seven trials measured the outcomes at the end of treatment and there was no additional follow-up. In two trials, there was follow-up after the treatment ended. Five trials had a high risk of performance bias, and four trials had a high risk of attrition bias. We found no trials assessing interventions for alcohol abstinence or smoking cessation. No trials assessed time to relapse. Only two trials assessed adverse events; in one trial these were caused by the add-on therapy ciclosporin (given in both groups). The trial comparing two dietary interventions to a no-treatment group observed no adverse events. The results presented in this abstract are based on trials of obese participants. Outcomes for dietary interventions versus usual care were measured 24 weeks to six months from baseline. Compared to usual care, dietary intervention (strict caloric restriction) may lead to 75% or greater improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) (risk ratio (RR) 1.66, 95% confidence interval (CI) 1.07 to 2.58; 2 trials, 323 participants; low-quality evidence). Adherence to the intervention may be greater with the dietary intervention than usual care, but the 95% CI indicates that the dietary intervention might also make little or no difference (RR 1.26, 95% CI 0.76 to 2.09; 2 trials, 105 participants; low-quality evidence). Dietary intervention probably achieves a greater improvement in dermatology quality-of-life index (DLQI) score compared to usual care (MD -12.20, 95% CI -13.92 to -10.48; 1 trial, 36 participants; moderate-quality evidence), and probably reduces the BMI compared to usual care (MD -4.65, 95% CI -5.93 to -3.36; 2 trials, 78 participants; moderate-quality evidence).Outcomes for dietary interventions plus exercise programme were measured 16 weeks from baseline and are based on one trial (303 participants). Compared to information only (on reducing weight to improve psoriasis), combined dietary intervention and exercise programme (dietetic plan and physical activities) probably improves psoriasis severity, but the 95% CI indicates that the intervention might make little or no difference (PASI 75: RR 1.28, 95% CI 0.83 to 1.98). This combined intervention probably results in a greater reduction in BMI (median change -1.10 kg/m², P = 0.002), but there is probably no difference in adherence (RR 0.95, 95% CI 0.89 to 1.01; 137/151 and 145/152 participants adhered in the treatment and control group, respectively). There were no data on quality of life. These outcomes are based on moderate-quality evidence. Authors' conclusions: Dietary intervention may reduce the severity of psoriasis (low-quality evidence) and probably improves quality of life and reduces BMI (moderate-quality evidence) in obese people when compared with usual care, while combined dietary intervention and exercise programme probably improves psoriasis severity and BMI when compared with information only (moderate-quality evidence). None of the trials measured quality of life. We did not detect a clear difference in treatment adherence between those in the combined dietary intervention and exercise programme group and those given information only (moderate-quality evidence). Adherence may be improved through dietary intervention compared with usual care (low-quality evidence). Participants generally adhered well to the lifestyle interventions assessed in the review. No trials assessed the time to relapse. Trial limitations included unblinded participants and high dropout rate. Future trials should reduce dropouts and include comprehensive outcome measures; they should examine whether dietary intervention with or without an exercise programme is effective in non-obese people with psoriasis, whether an additional exercise programme is more effective than dietary intervention alone, whether the time to relapse prolongs in people who receive dietary intervention with or without exercise programme, and whether smoking cessation and alcohol abstinence are effective in treating psoriasis.

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

Premature mortality attributable to socioeconomic inequality in England between 2003 and 2018: an observational study.

Background: Low socioeconomic position is consistently associated with increased risk of premature death. The aim of this study is to measure the aggregate scale of inequality in premature mortality for the whole population of England. Methods: We used mortality records from the UK Office for National Statistics to study all 2 465 285 premature deaths (defined as those before age 75 years) in England between Jan 1, 2003, and Dec 31, 2018. Socioeconomic position was defined using deciles of the Index of Multiple Deprivation: a measure of neighbourhood income, employment, education levels, crime, health, availability of services, and local environment. We calculated the number of expected deaths by applying mortality in the least deprived decile to other deciles, within the strata of age, sex, and time. The mortality attributable to socioeconomic inequality was defined as the difference between the observed and expected deaths. We also used life table modelling to estimate years-of-life lost attributable to socioeconomic inequality. Findings: 35·6% (95% CI 35·3-35·9) of premature deaths were attributable to socioeconomic inequality, equating to 877 082 deaths, or one every 10 min. The biggest contributors were ischaemic heart disease (152 171 excess deaths), respiratory cancers (111 083) and chronic obstructive pulmonary disease (83 593). The most unequal causes of death were tuberculosis, opioid use, HIV, psychoactive drugs use, viral hepatitis, and obesity, each with more than two-thirds attributable to inequality. Inequality was greater among men and peaked in early childhood and at age 40-49 years. The proportion of deaths attributable to inequality increased during the study period, particularly for women, because mortality rates among the most deprived women (excluding cardiovascular diseases) plateaued, and for some diseases increased. A mean of 14·4 months of life before age 75 years are lost due to socioeconomic inequality. Interpretation: One in three premature deaths are attributable to socioeconomic inequality, making this our most important public health challenge. Interventions that address upstream determinants of health should be prioritised. Funding: National Institute of Health Research; Wellcome Trust.

The Lancet. Public health · cohort or longitudinal · 143 citationsread the source →

Influence of diet on leukocyte telomere length, markers of inflammation and oxidative stress in individuals with varied glucose tolerance: a Chinese population study.

Objectives: To explore influence of carbohydrates/fat proportions, dietary ingredients on telomere length shortening, oxidative stress and inflammation in a Chinese population with different glucose tolerance status. Methods: Five hundred and fifty-six Chinese subjects without diabetes history underwent a 75 g, 2 h Oral Glucose Tolerance Test (OGTT). Subjects with diabetes (n = 159), pre-diabetes (n = 197), and normal glucose tolerance (n = 200) were screened. Dietary intakes were evaluated using a semi-quantitative food frequency questionnaire (FFQ). Peripheral blood leukocyte telomere length (LTL) was assessed using a real-time PCR assay. Blood lipid profile, levels of the oxidative stress indicators superoxide dismutase (SOD), glutathione reductase (GR), 8-oxo-2'-deoxyguanosine (8-oxo-dG) and inflammation indicators tumor necrosis factor (TNF-ɑ), interleukine-6 (IL-6) were measured. Levels of HbA1c, plasma glucose, insulin, and C peptide were also determined. Measurements were taken at 0 min, 30 min, 60 min, and 120 min after 75 g OGTT. Insulin sensitivity was evaluated by HOMA-IR. Basal insulin secretion index (HOMA-β), early phase disposition index (DI30) and total phase disposition index (DI120) indicate insulin levels at different phases of insulin secretion. Results: In patients with newly diagnosed diabetes, LTL adjusted by age was longer in HbA1c < 7 % group (log (LTL):1.93 ± 0.25) than in HbA1c ≥ 7 % group (log (LTL):1.82 ± 0.29). LTL was not associated with daily energy intake, diet fat, carbohydrates and protein proportions. Multiple linear regression analysis indicated that legumes, nuts, fish and seaweeds were protective factors for LTL shortening, and sweetened carbonated beverage was a risk factor for LTL shortening ( legumes: β = 0.105, p = 0.018; nuts: β = 0.110, p = 0.011; fish: β = 0.118, p = 0.007; seaweeds: β = 0.116, p = 0.009; sweetened carbonated beverage: β = -0.120, p = 0.004 ). Daily energy intake was positively associated with TNF-ɑ, IL-6 (TNF-ɑ: r = 0.125, p = 0.006;IL-6: r = 0.092, p =0.04). Fat, carbohydrate proportions were positively associated with TNF-ɑ (fat: r = 0.119, p = 0.008 ; carbohydrate: r = 0.094, p = 0.043). Seaweeds and dairy intake were negatively associated with 8-oxo-dG (seaweed: r = -0.496, p = 0.001;dairy: r = -0.246, p = 0.046 ), vegetables and fruits were positively associated with GR ( vegetables: r = 0.101, p = 0.034;fruits: r = 0.125, p = 0.045). Cereal, meat were positively associated with TNF-ɑ ( cereal: r = 0.091, p = 0.048 ; meat: r = 0.405, p = 0.009). Conclusion: Diabetes patients with better plasma glucose (HbA1c < 7 %) had longer LTL, LTL could reflect plasma glucose status in diabetes patients. LTL were probably not influenced by diet carbohydrates/fat proportions but was associated with diet ingredients. Diet ingredients significantly impacted on markers of inflammation and oxidative stress, which probably had an effect on LTL.

Nutrition journal · 58 citationsread the source →

Connection to Nature and Psychological Wellbeing: The Role of Mindfulness and Spirituality.

This study examined mindfulness and spirituality as potential explanatory mechanisms underlying the associations between connection to nature and young adults' psychological wellbeing (depression, anxiety, perceived stress, life satisfaction, and positive states of mind). Two studies employed structural equation modeling (SEM) to test these pathways using different conceptualizations and measures of mindfulness and spirituality. Participants (Study 1: N = 219, 69.4% female; Study 2: N = 180, 75% female) completed self-report measures of connection to nature, mindfulness, spirituality, and psychological wellbeing. In Study 1, mindful attention functioned as a significant mediating mechanism reducing anxiety and perceived stress, while mindful awareness mediated reductions in depression and increases in positive states of mind. Conversely, spirituality (life scheme and self-efficacy) was not a significant mediator. In Study 2, using alternative measures, spirituality (self-transcendence) significantly operated as a mediating mechanism across all wellbeing outcomes except anxiety, whereas none of the five facets of mindfulness acted as significant mediating mechanisms. Overall, these findings suggest that the roles of mindfulness and spirituality in linking connection to nature and psychological wellbeing may vary depending on how these constructs are conceptualized and measured, highlighting the need for greater conceptual clarity in future research.

International journal of environmental research and public healthread the source →

Impact of the 'Healthy Youngsters, Healthy Dads' program on physical activity and other health behaviours: a randomised controlled trial involving fathers and their preschool-aged children.

Background: Targeting fathers may be a key strategy to increase physical activity among their preschool-aged children, but limited research exists in this area. The primary study aim was to examine the impact of a lifestyle program for fathers and their preschool-aged children on child physical activity levels. Methods: A total of 125 fathers (aged: 38 ± 5.4 years, BMI: 28.1 ± 4.9 kg/m2) and 125 preschool-aged children (aged: 3.9 ± 0.8 years, BMI z-score: 0.3 ± 0.9, 39.2% girls) recruited from Newcastle, Australia, NSW were randomised to (i) the Healthy Youngsters, Healthy Dads (HYHD) program, or (ii) wait-list control group. The program included two fathers-only workshops (2 h each) and eight father-child weekly educational and practical sessions (75 min each), plus home-based activities targeting family physical activity and nutrition. Assessments took place at baseline, 10-weeks (post-intervention) and 9-months follow-up. The primary outcome was the children's mean steps/day at 10-weeks. Secondary outcomes included: co-physical activity, fathers' physical activity levels and parenting practices for physical activity and screen time behaviours, children's fundamental movement skill (FMS) proficiency, plus accelerometer based light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA), screen time and adiposity for fathers and children. Process measures included; attendance, satisfaction, fidelity and retention. Linear mixed models estimated the treatment effect at all time-points for all outcomes. Results: Intention-to-treat analyses revealed a significant group-by-time effect for steps per day at 10-weeks (+ 1417, 95%CI: 449, 2384) and 9-months follow-up (+ 1480, 95%CI: 493, 2467) in intervention children compared to control. There were also favourable group-by-time effects for numerous secondary outcomes including fathers' physical activity levels, children's FMS proficiency, and several parenting constructs. No effects were observed for both fathers' and children's accelerometer based LPA or MVPA, co-physical activity, screen-time and adiposity measures. Process evaluation data revealed very high levels of satisfaction, attendance, retention, and intervention fidelity. Conclusion: Engaging fathers in a lifestyle program is a promising strategy to increase physical activity among preschool-aged children. Additional benefits to fathers' physical activity levels, children's FMS proficiency and parenting practices further support the importance of engaging fathers to improve family health outcomes. Trial registration: Australian New Zealand Clinical Trials Registry: ACTRN12619000105145 . Registered 24/01/2019.

BMC public health · randomised controlled trial · 26 citationsread the source →

Mindfulness Meditation-Based Pain Relief Employs Different Neural Mechanisms Than Placebo and Sham Mindfulness Meditation-Induced Analgesia.

Mindfulness meditation reduces pain in experimental and clinical settings. However, it remains unknown whether mindfulness meditation engages pain-relieving mechanisms other than those associated with the placebo effect (e.g., conditioning, psychosocial context, beliefs). To determine whether the analgesic mechanisms of mindfulness meditation are different from placebo, we randomly assigned 75 healthy, human volunteers to 4 d of the following: (1) mindfulness meditation, (2) placebo conditioning, (3) sham mindfulness meditation, or (4) book-listening control intervention. We assessed intervention efficacy using psychophysical evaluation of experimental pain and functional neuroimaging. Importantly, all cognitive manipulations (i.e., mindfulness meditation, placebo conditioning, sham mindfulness meditation) significantly attenuated pain intensity and unpleasantness ratings when compared to rest and the control condition (p < 0.05). Mindfulness meditation reduced pain intensity (p = 0.032) and pain unpleasantness (p < 0.001) ratings more than placebo analgesia. Mindfulness meditation also reduced pain intensity (p = 0.030) and pain unpleasantness (p = 0.043) ratings more than sham mindfulness meditation. Mindfulness-meditation-related pain relief was associated with greater activation in brain regions associated with the cognitive modulation of pain, including the orbitofrontal, subgenual anterior cingulate, and anterior insular cortex. In contrast, placebo analgesia was associated with activation of the dorsolateral prefrontal cortex and deactivation of sensory processing regions (secondary somatosensory cortex). Sham mindfulness meditation-induced analgesia was not correlated with significant neural activity, but rather by greater reductions in respiration rate. This study is the first to demonstrate that mindfulness-related pain relief is mechanistically distinct from placebo analgesia. The elucidation of this distinction confirms the existence of multiple, cognitively driven, supraspinal mechanisms for pain modulation. Significance statement: Recent findings have demonstrated that mindfulness meditation significantly reduces pain. Given that the "gold standard" for evaluating the efficacy of behavioral interventions is based on appropriate placebo comparisons, it is imperative that we establish whether there is an effect supporting meditation-related pain relief above and beyond the effects of placebo. Here, we provide novel evidence demonstrating that mindfulness meditation produces greater pain relief and employs distinct neural mechanisms than placebo cream and sham mindfulness meditation. Specifically, mindfulness meditation-induced pain relief activated higher-order brain regions, including the orbitofrontal and cingulate cortices. In contrast, placebo analgesia was associated with decreased pain-related brain activation. These findings demonstrate that mindfulness meditation reduces pain through unique mechanisms and may foster greater acceptance of meditation as an adjunct pain therapy.

The Journal of neuroscience : the official journal of the Society for Neuroscience · randomised controlled trial · 222 citationsread the source →

TREAT AF (Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation): A Randomized Clinical Trial.

Objectives: This study was a sham-controlled, double-blind, randomized clinical trial to examine the effect of chronic low level tragus stimulation (LLTS) in patients with paroxysmal AF. Background: Low-level transcutaneous electrical stimulation of the auricular branch of the vagus nerve at the tragus (LLTS) acutely suppresses atrial fibrillation (AF) in humans, but the chronic effect remains unknown. Methods: LLTS (20 Hz, 1 mA below the discomfort threshold) was delivered using an ear clip attached to the tragus (active arm) (n = 26) or the ear lobe (sham control arm) (n = 27) for 1 h daily over 6 months. AF burden over 2-week periods was assessed by noninvasive continuous electrocardiogram monitoring at baseline, 3 months, and 6 months. Five-minute electrocardiography and serum were obtained at each visit to measure heart rate variability and inflammatory cytokines, respectively. Results: Baseline characteristics were balanced between the 2 groups. Adherence to the stimulation protocol (≤4 sessions lost per month) was 75% in the active arm and 83% in the control arm (p > 0.05). At 6 months, the median AF burden was 85% lower in the active arm compared with the control arm (ratio of medians: 0.15; 95% confidence interval: 0.03 to 0.65; p = 0.011). Tumor necrosis factor-alpha was significantly decreased by 23% in the active group relative to the control group (ratio of medians: 0.77; 95% confidence interval: 0.63 to 0.94; p = 0.0093). Frequency domain indices of heart rate variability were significantly altered with active versus control stimulation (p < 0.01). No device-related side effects were observed. Conclusions: Chronic, intermittent LLTS resulted in lower AF burden than did sham control stimulation, supporting its use to treat paroxysmal AF in selected patients. (Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation [TREAT-AF]; NCT02548754).

JACC. Clinical electrophysiology · randomised controlled trial · 184 citationsread the source →

State care in childhood and adult mortality: a systematic review and meta-analysis of prospective cohort studies.

Background: Removal from family of origin to state care can be a highly challenging childhood experience and is itself linked to an array of unfavourable outcomes in adult life. We aim to synthetise evidence on the risk of adult mortality in people with a history of state care in early life, and assess the association according to different contexts. Methods: In this systematic review and meta-analysis, we focused on four health outcomes hypothesised to be associated with exposure to early state care: total mortality, cardiovascular disease, cancer, and suicide. We searched the electronic databases PubMed and Embase from inception to Jan 21, 2022, for studies fulfilling the following criteria: it was a prospective study in which the assessment of care was made up to 18 years of age; it included an unexposed comparator group; the focus of the study was temporary out-of-home care and not adoption; mortality surveillance was extended into adulthood; standard estimates of association (eg, relative risk, odds ratios, or hazard ratios) and variance (eg, CIs and SE) were provided; the study appeared in a peer-reviewed journal; and the study was published in English. An adapted Cochrane Risk of Bias Tool was used to assess study quality. We extracted estimates of association and variance from qualifying studies and augmented these findings with analyses of unpublished data from individual participants in two UK birth cohorts-ie, the 1958 and 1970 studies (total n=21 936). We computed hazard ratios with accompanying 95% CIs for care and each health outcome separately for each study, and then pooled the results using a random-effects meta-analysis. This review is registered at PROSPERO, CRD42021254665. Findings: We identified 210 potentially eligible published articles, of which 14 met our inclusion criteria (two studies were unpublished). Of 3 223 580 individuals drawn from 13 studies, those who were exposed to care in childhood had twice the risk of total mortality in adulthood relative to those without a history of care in childhood (summary risk ratio 2·21 [95% CI 1·62-3·02]), with study-specific estimates varying between 1·04 and 5·77 (I2 =98%). Despite some attenuation, this association remained following adjustment for other measures of early-life adversity; extended into middle and older age; was stronger in higher-quality studies; and was of equal magnitude according to sex, geographical region, and birth year. There was some suggestion of sensitive periods of exposure to care, whereby individuals who entered state care for the first time in adolescence (2·47 [0·98-6·52]) had greater rates of mortality than those doing so early in the life course (1·75 [1·25-2·45]). In four studies including 534 890 people, children in care had more than three times the risk of completed suicide in adulthood relative to their unexposed peers (3·35 [2·41-4·68]), with study-specific estimates ranging between 2·42 and 5·85 (I2=72%). The magnitude of this association was weaker after adjustment for multiple covariates; in men than in women; and in lower-quality studies. Interpretation: Our results for adult mortality suggest child protection systems, social policy, and health services following care graduation are insufficient to mitigate the adverse experiences that might have preceded placement into care and those that might accompany it. Funding: None.

The Lancet. Public health · meta-analysis · 25 citationsread the source →

Interventions for promoting habitual exercise in people living with and beyond cancer.

Background: This is an updated version of the original Cochrane Review published in the Cochrane Library 2013, Issue 9. Despite good evidence for the health benefits of regular exercise for people living with or beyond cancer, understanding how to promote sustainable exercise behaviour change in sedentary cancer survivors, particularly over the long term, is not as well understood. A large majority of people living with or recovering from cancer do not meet current exercise recommendations. Hence, reviewing the evidence on how to promote and sustain exercise behaviour is important for understanding the most effective strategies to ensure benefit in the patient population and identify research gaps. Objectives: To assess the effects of interventions designed to promote exercise behaviour in sedentary people living with and beyond cancer and to address the following secondary questions: Which interventions are most effective in improving aerobic fitness and skeletal muscle strength and endurance? Which interventions are most effective in improving exercise behaviour amongst patients with different cancers? Which interventions are most likely to promote long-term (12 months or longer) exercise behaviour? What frequency of contact with exercise professionals and/or healthcare professionals is associated with increased exercise behaviour? What theoretical basis is most often associated with better behavioural outcomes? What behaviour change techniques (BCTs) are most often associated with increased exercise behaviour? What adverse effects are attributed to different exercise interventions? Search methods: We used standard methodological procedures expected by Cochrane. We updated our 2013 Cochrane systematic review by updating the searches of the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, Embase, AMED, CINAHL, PsycLIT/PsycINFO, SportDiscus and PEDro up to May 2018. We also searched the grey literature, trial registries, wrote to leading experts in the field and searched reference lists of included studies and other related recent systematic reviews. Selection criteria: We included only randomised controlled trials (RCTs) that compared an exercise intervention with usual care or 'waiting list' control in sedentary people over the age of 18 with a homogenous primary cancer diagnosis. Data collection and analysis: In the update, review authors independently screened all titles and abstracts to identify studies that might meet the inclusion criteria, or that could not be safely excluded without assessment of the full text (e.g. when no abstract is available). We extracted data from all eligible papers with at least two members of the author team working independently (RT, LS and RG). We coded BCTs according to the CALO-RE taxonomy. Risk of bias was assessed using the Cochrane's tool for assessing risk of bias. When possible, and if appropriate, we performed a fixed-effect meta-analysis of study outcomes. If statistical heterogeneity was noted, a meta-analysis was performed using a random-effects model. For continuous outcomes (e.g. cardiorespiratory fitness), we extracted the final value, the standard deviation (SD) of the outcome of interest and the number of participants assessed at follow-up in each treatment arm, to estimate the standardised mean difference (SMD) between treatment arms. SMD was used, as investigators used heterogeneous methods to assess individual outcomes. If a meta-analysis was not possible or was not appropriate, we narratively synthesised studies. The quality of the evidence was assessed using the GRADE approach with the GRADE profiler. Main results: We included 23 studies in this review, involving a total of 1372 participants (an addition of 10 studies, 724 participants from the original review); 227 full texts were screened in the update and 377 full texts were screened in the original review leaving 35 publications from a total of 23 unique studies included in the review. We planned to include all cancers, but only studies involving breast, prostate, colorectal and lung cancer met the inclusion criteria. Thirteen studies incorporated a target level of exercise that could meet current recommendations for moderate-intensity aerobic exercise (i.e.150 minutes per week); or resistance exercise (i.e. strength training exercises at least two days per week).Adherence to exercise interventions, which is crucial for understanding treatment dose, is still reported inconsistently. Eight studies reported intervention adherence of 75% or greater to an exercise prescription that met current guidelines. These studies all included a component of supervision: in our analysis of BCTs we designated these studies as 'Tier 1 trials'. Six studies reported intervention adherence of 75% or greater to an aerobic exercise goal that was less than the current guideline recommendations: in our analysis of BCTs we designated these studies as 'Tier 2 trials.' A hierarchy of BCTs was developed for Tier 1 and Tier 2 trials, with programme goal setting, setting of graded tasks and instruction of how to perform behaviour being amongst the most frequent BCTs. Despite the uncertainty surrounding adherence in some of the included studies, interventions resulted in improvements in aerobic exercise tolerance at eight to 12 weeks (SMD 0.54, 95% CI 0.37 to 0.70; 604 participants, 10 studies; low-quality evidence) versus usual care. At six months, aerobic exercise tolerance was also improved (SMD 0.56, 95% CI 0.39 to 0.72; 591 participants; 7 studies; low-quality evidence). Authors' conclusions: Since the last version of this review, none of the new relevant studies have provided additional information to change the conclusions. We have found some improved understanding of how to encourage previously inactive cancer survivors to achieve international physical activity guidelines. Goal setting, setting of graded tasks and instruction of how to perform behaviour, feature in interventions that meet recommendations targets and report adherence of 75% or more. However, long-term follow-up data are still limited, and the majority of studies are in white women with breast cancer. There are still a considerable number of published studies with numerous and varied issues related to high risk of bias and poor reporting standards. Additionally, the meta-analyses were often graded as consisting of low- to very low-certainty evidence. A very small number of serious adverse effects were reported amongst the studies, providing reassurance exercise is safe for this population.

The Cochrane database of systematic reviews · meta-analysis · 153 citationsread the source →

Non-pharmacological interventions for assisting the induction of anaesthesia in children.

Background: Induction of general anaesthesia can be distressing for children. Non-pharmacological methods for reducing anxiety and improving co-operation may avoid the adverse effects of preoperative sedation. Objectives: To assess the effects of non-pharmacological interventions in assisting induction of anaesthesia in children by reducing their anxiety, distress or increasing their co-operation. Search methods: In this updated review we searched CENTRAL (the Cochrane Library 2012, Issue 12) and searched the following databases from inception to 15 January 2013: MEDLINE, EMBASE, PsycINFO and Web of Science. We reran the search in August 2014. We will deal with the single study found to be of interest when we next update the review. Selection criteria: We included randomized controlled trials of a non-pharmacological intervention implemented on the day of surgery or anaesthesia. Data collection and analysis: At least two review authors independently extracted data and assessed risk of bias in trials. Main results: We included 28 trials (2681 children) investigating 17 interventions of interest; all trials were conducted in high-income countries. Overall we judged the trials to be at high risk of bias. Except for parental acupuncture (graded low), all other GRADE assessments of the primary outcomes of comparisons were very low, indicating a high degree of uncertainty about the overall findings. Parental presence: In five trials (557 children), parental presence at induction of anaesthesia did not reduce child anxiety compared with not having a parent present (standardized mean difference (SMD) 0.03, 95% confidence interval (CI) -0.14 to 0.20). In a further three trials (267 children) where we were unable to pool results, we found no clear differences in child anxiety, whether a parent was present or not. In a single trial, child anxiety showed no significant difference whether one or two parents were present, although parental anxiety was significantly reduced when both parents were present at the induction. Parental presence was significantly less effective than sedative premedication in reducing children's anxiety at induction in three trials with 254 children (we could not pool results). Child interventions (passive): When a video of the child's choice was played during induction, children were significantly less anxious than controls (median difference modified Yale Preoperative Anxiety Scale (mYPAS) 31.2, 95% CI 27.1 to 33.3) in a trial of 91 children. In another trial of 120 children, co-operation at induction did not differ significantly when a video fairytale was played before induction. Children exposed to low sensory stimulation were significantly less anxious than control children on introduction of the anaesthesia mask and more likely to be co-operative during induction in one trial of 70 children. Music therapy did not show a significant effect on children's anxiety in another trial of 51 children. Child interventions (mask introduction): We found no significant differences between a mask exposure intervention and control in a single trial of 103 children for child anxiety (risk ratio (RR) 0.59, 95% CI 0.31 to 1.11) although children did demonstrate significantly better co-operation in the mask exposure group (RR 1.27, 95% CI 1.06 to 1.51). Child interventions (interactive): In a three-arm trial of 168 children, preparation with interactive computer packages (in addition to parental presence) was more effective than verbal preparation, although differences between computer and cartoon preparation were not significant, and neither was cartoon preparation when compared with verbal preparation. Children given video games before induction were significantly less anxious at induction than those in the control group (mYPAS mean difference (MD) -9.80, 95% CI -19.42 to -0.18) and also when compared with children who were sedated with midazolam (mYPAS MD -12.20, 95% CI -21.82 to -2.58) in a trial of 112 children. When compared with parental presence only, clowns or clown doctors significantly lessened children's anxiety in the operating/induction room (mYPAS MD -24.41, 95% CI -38.43 to -10.48; random-effects, I² 75%) in three trials with a total of 133 children. However, we saw no significant differences in child anxiety in the operating room between clowns/clown doctors and sedative premedication (mYPAS MD -9.67, 95% CI -21.14 to 1.80, random-effects, I² 66%; 2 trials of 93 children). In a trial of hypnotherapy versus sedative premedication in 50 children, there were no significant differences in children's anxiety at induction (RR 0.59, 95% CI 0.33 to 1.04). Parental interventions: Children of parents having acupuncture compared with parental sham acupuncture were less anxious during induction (mYPAS MD -17, 95% CI -30.51 to -3.49) and were more co-operative (RR 1.59, 95% CI 1.01 to 2.53) in a single trial of 67 children. Two trials with 191 parents assessed the effects of parental video viewing but did not report any of the review's prespecified primary outcomes. Authors' conclusions: This review shows that the presence of parents during induction of general anaesthesia does not diminish their child's anxiety. Potentially promising non-pharmacological interventions such as parental acupuncture; clowns/clown doctors; playing videos of the child's choice during induction; low sensory stimulation; and hand-held video games need further investigation in larger studies.

The Cochrane database of systematic reviews · meta-analysis · 100 citationsread the source →

A meta-analysis of genetic effects associated with neurodevelopmental disorders and co-occurring conditions.

A systematic understanding of the aetiology of neurodevelopmental disorders (NDDs) and their co-occurrence with other conditions during childhood and adolescence remains incomplete. In the current meta-analysis, we synthesized the literature on (1) the contribution of genetic and environmental factors to NDDs, (2) the genetic and environmental overlap between different NDDs, and (3) the co-occurrence between NDDs and disruptive, impulse control and conduct disorders (DICCs). Searches were conducted across three platforms: Web of Science, Ovid Medline and Ovid Embase. Studies were included only if 75% or more of the sample consisted of children and/or adolescents and the studies had measured the aetiology of NDDs and DICCs using single-generation family designs or genomic methods. Studies that had selected participants on the basis of unrelated diagnoses or injuries were excluded. We performed multilevel, random-effects meta-analyses on 296 independent studies, including over four million (partly overlapping) individuals. We further explored developmental trajectories and the moderating roles of gender, measurement, geography and ancestry. We found all NDDs to be substantially heritable (family-based heritability, 0.66 (s.e. = 0.03); SNP heritability, 0.19 (s.e. = 0.03)). Meta-analytic genetic correlations between NDDs were moderate (grand family-based genetic correlation, 0.36 (s.e. = 0.12); grand SNP-based genetic correlation, 0.39 (s.e. = 0.19)) but differed substantially between pairs of disorders. The genetic overlap between NDDs and DICCs was strong (grand family-based genetic correlation, 0.62 (s.e. = 0.20)). While our work provides evidence to inform and potentially guide clinical and educational diagnostic procedures and practice, it also highlights the imbalance in the research effort that has characterized developmental genetics research.

Nature human behaviour · meta-analysis · 82 citationsread the source →

Interventions for fatigue in people with kidney failure requiring dialysis.

Background: Fatigue is a common and debilitating symptom in people receiving dialysis that is associated with an increased risk of death, cardiovascular disease and depression. Fatigue can also impair quality of life (QoL) and the ability to participate in daily activities. Fatigue has been established by patients, caregivers and health professionals as a core outcome for haemodialysis (HD). Objectives: We aimed to evaluate the effects of pharmacological and non-pharmacological interventions on fatigue in people with kidney failure receiving dialysis, including HD and peritoneal dialysis (PD), including any setting and frequency of the dialysis treatment. Search methods: We searched the Cochrane Kidney and Transplant Register of Studies up to 18 October 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. Selection criteria: Studies evaluating pharmacological and non-pharmacological interventions affecting levels of fatigue or fatigue-related outcomes in people receiving dialysis were included. Studies were eligible if fatigue or fatigue-related outcomes were reported as a primary or secondary outcome. Any mode, frequency, prescription, and duration of therapy were considered. Data collection and analysis: Three authors independently extracted data and assessed the risk of bias. Treatment estimates were summarised using random effects meta-analysis and expressed as a risk ratio (RR) or mean difference (MD), with a corresponding 95% confidence interval (CI) or standardised MD (SMD) if different scales were used. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Main results: Ninety-four studies involving 8191 randomised participants were eligible. Pharmacological and non-pharmacological interventions were compared either to placebo or control, or to another pharmacological or non-pharmacological intervention. In the majority of domains, risks of bias in the included studies were unclear or high. In low certainty evidence, when compared to control, exercise may improve fatigue (4 studies, 217 participants (Iowa Fatigue Scale, Modified Fatigue Impact Scale, Piper Fatigue Scale (PFS), or Haemodialysis-Related Fatigue scale score): SMD -1.18, 95% CI -2.04 to -0.31; I2 = 87%) in HD. In low certainty evidence, when compared to placebo or standard care, aromatherapy may improve fatigue (7 studies, 542 participants (Fatigue Severity Scale (FSS), Rhoten Fatigue Scale (RFS), PFS or Brief Fatigue Inventory score): SMD -1.23, 95% CI -1.96 to -0.50; I2 = 93%) in HD. In low certainty evidence, when compared to no intervention, massage may improve fatigue (7 studies, 657 participants (FSS, RFS, PFS or Visual Analogue Scale (VAS) score): SMD -1.06, 95% CI -1.47, -0.65; I2 = 81%) and increase energy (2 studies, 152 participants (VAS score): MD 4.87, 95% CI 1.69 to 8.06, I2 = 59%) in HD. In low certainty evidence, when compared to placebo or control, acupressure may reduce fatigue (6 studies, 459 participants (PFS score, revised PFS, or Fatigue Index): SMD -0.64, 95% CI -1.03 to -0.25; I2 = 75%) in HD. A wide range of heterogenous interventions and fatigue-related outcomes were reported for exercise, aromatherapy, massage and acupressure, preventing our capability to pool and analyse the data. Due to the paucity of studies, the effects of pharmacological and other non-pharmacological interventions on fatigue or fatigue-related outcomes, including non-physiological neutral amino acid, relaxation with or without music therapy, meditation, exercise with nandrolone, nutritional supplementation, cognitive-behavioural therapy, ESAs, frequent HD sections, home blood pressure monitoring, blood flow rate reduction, serotonin reuptake inhibitor, beta-blockers, anabolic steroids, glucose-enriched dialysate, or light therapy, were very uncertain. The effects of pharmacological and non-pharmacological treatments on death, cardiovascular diseases, vascular access, QoL, depression, anxiety, hypertension or diabetes were sparse. No studies assessed tiredness, exhaustion or asthenia. Adverse events were rarely and inconsistently reported. Authors' conclusions: Exercise, aromatherapy, massage and acupressure may improve fatigue compared to placebo, standard care or no intervention. Pharmacological and other non-pharmacological interventions had uncertain effects on fatigue or fatigue-related outcomes in people receiving dialysis. Future adequately powered, high-quality studies are likely to change the estimated effects of interventions for fatigue and fatigue-related outcomes in people receiving dialysis.

The Cochrane database of systematic reviews · meta-analysis · 16 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 →

Life course health consequences and associated annual costs of adverse childhood experiences across Europe and North America: a systematic review and meta-analysis.

Background: An increasing number of studies are identifying associations between adverse childhood experiences (ACEs) and ill health throughout the life course. We aimed to calculate the proportions of major risk factors for and causes of ill health that are attributable to one or multiple types of ACE and the associated financial costs. Methods: In this systematic review and meta-analysis, we searched for studies in which risk data in individuals with ACEs were compared with these data in those without ACEs. We searched six electronic databases (MEDLINE, CINAHL, PsycINFO, Applied Social Sciences Index and Abstracts, Criminal Justice Databases, and the Education Resources Information Center) for quantitative studies published between Jan 1, 1990, and July 11, 2018, that reported risks of health-related behaviours and causes of ill health in adults that were associated with cumulative measures of ACEs (ie, number of ACEs). We included studies in adults in populations that did not have a high risk of ACEs, that had sample sizes of at least 1000 people, and that provided ACE prevalence data. We calculated the pooled RR for risk factors (harmful alcohol use, illicit drug use, smoking, and obesity) and causes of ill health (cancer, diabetes, cardiovascular disease, respiratory disease, anxiety, and depression) associated with ACEs. RRs were used to estimate the population-attributable fractions (PAFs) of risk attributable to ACEs and the disability-adjusted life-years (DALYs) and financial costs associated with ACEs. This study was prospectively registered in PROSPERO (CRD42018090356). Findings: Of 4387 unique articles found following our initial search, after review of the titles (and abstracts, when the title was relevant), we assessed 880 (20%) full-text articles. We considered 221 (25%) full-text articles for inclusion, of which 23 (10%) articles met all selection criteria for our meta-analysis. We found a pooled prevalence of 23·5% of individuals (95% CI 18·7-28·5) with one ACE and 18·7% (14·7-23·2) with two or more ACEs in Europe (from ten studies) and of 23·4% of individuals (22·0-24·8) with one ACE and 35·0% (31·6-38·4) with two or more ACEs in north America (from nine studies). Illicit drug use had the highest PAFs associated with ACEs of all the risk factors assessed in both regions (34·1% in Europe; 41·1% in north America). In both regions, PAFs of causes of ill health were highest for mental illness outcomes: ACEs were attributed to about 30% of cases of anxiety and 40% of cases of depression in north America and more than a quarter of both conditions in Europe. Costs of cardiovascular disease attributable to ACEs were substantially higher than for most other causes of ill health because of higher DALYs for this condition. Total annual costs attributable to ACEs were estimated to be US$581 billion in Europe and $748 billion in north America. More than 75% of these costs arose in individuals with two or more ACEs. Interpretation: Millions of adults across Europe and north America live with a legacy of ACEs. Our findings suggest that a 10% reduction in ACE prevalence could equate to annual savings of 3 million DALYs or $105 billion. Programmes to prevent ACEs and moderate their effects are available. Rebalancing expenditure towards ensuring safe and nurturing childhoods would be economically beneficial and relieve pressures on health-care systems. Funding: World Health Organization Regional Office for Europe.

The Lancet. Public health · meta-analysis · 660 citationsread the source →

Efficacy of Psychosocial Interventions in Inducing and Maintaining Alcohol Abstinence in Patients With Chronic Liver Disease: A Systematic Review.

Background & aims: We conducted a systematic review of efficacy of psychosocial interventions in inducing or maintaining alcohol abstinence in patients with chronic liver disease (CLD) and alcohol use disorder (AUD). Methods: We performed structured keyword searches in PubMed, PsychINFO, and MEDLINE for original research articles that were published from January 1983 through November 2014 that evaluated the use of psychosocial interventions to induce or maintain alcohol abstinence in patients with CLD and AUD. Results: We identified 13 eligible studies that comprised 1945 patients; 5 were randomized controlled trials (RCTs). Delivered therapies included motivational enhancement therapy, cognitive behavioral therapy (CBT), motivational interviewing, supportive therapy, and psychoeducation either alone or in combination in the intervention group and general health education or treatment as usual in the control group. All studies of induction of abstinence (4 RCTs and 6 observational studies) reported an increase in abstinence among participants in the intervention and control groups. Only an integrated therapy that combined CBT and motivational enhancement therapy with comprehensive medical care, delivered during a period of 2 years, produced a significant increase in abstinence (74% increase in intervention group vs 48% increase in control group, P = .02), which was reported in 1 RCT. All studies of maintenance of abstinence (1 RCT and 2 observational studies) observed recidivism in the intervention and control groups. Only an integrated therapy that combined medical care with CBT produced a significantly smaller rate of recidivism (32.7% in integrated CBT group vs 75% in control group, P = .03), which was reported from 1 observational study. However, data were not collected for more than 2 years on outcomes of patients with CLD and AUD. Conclusions: In a systematic analysis of studies of interventions to induce or maintain alcohol abstinence in patients with CLD and AUD, integrated combination psychotherapy with CBT, motivational enhancement therapy, and comprehensive medical care increased alcohol abstinence. No psychosocial intervention was successful in maintaining abstinence, but an integrated therapy with CBT and medical care appears to reduce recidivism.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · systematic review · 140 citationsread the source →

Older Adults' Social Relationships and Health Care Utilization: A Systematic Review.

Background: Deficiencies in older people's social relationships (including loneliness, social isolation, and low social support) have been implicated as a cause of premature mortality and increased morbidity. Whether they affect service use is unclear. Objectives: To determine whether social relationships are associated with older adults' use of health services, independently of health-related needs. Search methods: We searched 8 electronic databases (MEDLINE, Embase, CINAHL, Web of Science, PsycINFO, Scopus, the Cochrane Library, and the Centre for Reviews and Dissemination) for data published between 1983 and 2016. We also identified relevant sources from scanning the reference lists of included studies and review articles, contacting authors to identify additional studies, and searching the tables of contents of key journals. Selection criteria: Studies met inclusion criteria if more than 50% of participants were older than 60 years or mean age was older than 60 years; they included a measure of social networks, received social support, or perceived support; and they reported quantitative data on the association between social relationships and older adults' health service utilization. Data collection and analysis: Two researchers independently screened studies for inclusion. They extracted data and appraised study quality by using standardized forms. In a narrative synthesis, we grouped the studies according to the outcome of interest (physician visits, hospital admissions, hospital readmissions, emergency department use, hospital length of stay, utilization of home- and community-based services, contact with general health services, and mental health service use) and the domain of social relationships covered (social networks, received social support, or perceived support). For each service type and social relationship domain, we assessed the strength of the evidence across studies according to the quantity and quality of studies and consistency of findings. Main results: The literature search retrieved 26 077 citations, 126 of which met inclusion criteria. Data were reported across 226 678 participants from 19 countries. We identified strong evidence of an association between weaker social relationships and increased rates of readmission to hospital (75% of high-quality studies reported evidence of an association in the same direction). In evidence of moderate strength, according to 2 high-quality and 3 medium-quality studies, smaller social networks were associated with longer hospital stays. When we considered received and perceived social support separately, they were not linked to health care use. Overall, the evidence did not indicate that older patients with weaker social relationships place greater demands on ambulatory care (including physician visits and community- or home-based services) than warranted by their needs. Authors' conclusions: Current evidence does not support the view that, independently of health status, older patients with lower levels of social support place greater demands on ambulatory care. Future research on social relationships would benefit from a consensus on clinically relevant concepts to measure. Public Health Implications. Our findings are important for public health because they challenge the notion that lonely older adults are a burden on all health and social care services. In high-income countries, interventions aimed at reducing social isolation and loneliness are promoted as a means of preventing inappropriate service use. Our review cautions against assuming that reductions in care utilization can be achieved by intervening to strengthen social relationships.

American journal of public health · systematic review · 128 citationsread the source →

Predictors of treatment resistance in patients with schizophrenia: a population-based cohort study.

Background: Identification of patients at high risk of treatment-resistant schizophrenia at the time of schizophrenia diagnosis would be of great clinical benefit in minimising the delay to clozapine treatment in patients unlikely to respond to non-clozapine antipsychotics. However, little is known about predictors of treatment resistance in this patient population. We used a treatment-based proxy for treatment-resistant schizophrenia to identify candidate predictors of treatment resistance at first hospital contact with a schizophrenia diagnosis. Methods: In this population-based cohort study, we obtained Danish national registry data for all adult patients (≥18 years) with incident schizophrenia diagnosed between Jan 1, 1996, and Dec 31, 2006, and followed up until Dec 31, 2010. Our main proxy definition of treatment-resistant schizophrenia was the earliest instance of either clozapine initiation or hospital admission for schizophrenia after having had two periods of different antipsychotic monotherapy. We did multivariable Cox proportional hazards regression analysis to estimate the association between baseline candidate predictors and treatment resistance. Findings: 8624 patients fulfilled the criteria for inclusion. In multivariable complete-case analyses, 1703 (21%) of 8044 patients fulfilled the main proxy definition of treatment-resistant schizophrenia during a median follow-up of 9·1 years (IQR 6·3-11·9). Younger age (hazard ratio 0·96 [95% CI 0·95-0·97]), living in a less urban area (provincial 1·38 [1·23-1·56], rural 1·44 [1·25-1·65]), primary education level (0·88 [0·79-0·98]), more than 30 bed-days in psychiatric hospital in the year before first schizophrenia diagnosis (1·54 [1·35-1·75]), inpatient at first schizophrenia diagnosis (2·07 [1·87-2·29]), paranoid subtype (1·24 [1·13-1·37]), comorbid personality disorder (1·24 [1·11-1·39]), psychotropic drug use (antipsychotics 1·51 [1·35-1·69], antidepressants 1·15 [1·03-1·29], and benzodiazepines 1·22 [1·10-1·37]), and previous suicide attempt (1·21 [1·07-1·39]) were all significantly associated with treatment-resistant schizophrenia. Interpretation: Our study identifies several candidate predictors that could potentially be included in future prediction models for treatment-resistant schizophrenia. Notably, established risk factors for schizophrenia did not predict treatment resistance, suggesting that treatment-resistant disease might be a distinct subtype of schizophrenia and not merely a more severe form. Funding: European Community's Seventh Framework Programme.

The lancet. Psychiatry · 127 citationsread the source →

Sexual dysfunction related to psychiatric disorders: a systematic review.

Background: Sexual dysfunction is thought to be highly prevalent in patients with psychiatric disorders. Factors such as the use of psychotropic substances (ie, psychopharmaceuticals and drugs), age, or somatic diseases may contribute to sexual problems, but the extent to which psychopathology itself affects sexual functioning is not well understood. Aim: The study sought to provide an overview of the literature on the prevalence of sexual dysfunction in psychotropic-free and somatic disease-free psychiatric patients. Method: A systematic review (PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analyses]) was conducted by 2 authors (TH and AWMP) independently, with the review process being monitored by a third author. Relevant articles on the relationship between sexual dysfunctions and psychopathology were searched in PubMed, Web of Science, and PsycINFO from inception until June 16, 2022. The study methods were entered in the international register of systematic reviews PROSPERO (2021, CRD42021223410). Outcomes: The main outcome measures were sexual dysfunction and sexual satisfaction. Results: Twenty-four studies were identified, including a total of 1199 patients. These studies focused on depressive disorders (n = 9 studies), anxiety disorders (n = 7), obsessive- compulsive disorder (OCD) (n = 5), schizophrenia (n = 4), and posttraumatic stress disorder (n = 2). No studies on bipolar disorder were found. Reported prevalence rates of sexual dysfunction in psychiatric disorders were 45% to 93% for depressive disorders, 33% to 75% for anxiety disorders, 25% to 81% for OCD, and 25% for schizophrenia. The most affected phase of the sexual response cycle was sexual desire, in both men and women with depressive disorders, posttraumatic stress disorder, and schizophrenia. Patients with OCD and anxiety disorders most frequently reported dysfunction in the orgasm phase, 24% to 44% and 7% to 48%, respectively. Clinical implications: The high prevalence of sexual dysfunction requires more clinical attention by means of psychoeducation, clinical guidance, sexual anamnesis, and additional sexological treatment. Strengths and limitations: This is the first systematic review on sexual dysfunction in psychotropic-free and somatic disease-free psychiatric patients. Limitations include the small number of studies, small sample sizes, the use of multiple questionnaires (some not validated), which may contribute to bias. Conclusion: A limited number of studies identified a high prevalence of sexual dysfunction in patients with a psychiatric disorder, with substantial variation between patient groups in frequency and phase of reported sexual dysfunction.

The journal of sexual medicine · systematic review · 33 citationsread the source →

MDMA-induced indifference to negative sounds is mediated by the 5-HT2A receptor.

Background: MDMA has been shown to induce feelings of sociability, a positive emotional bias and enhanced empathy. While previous research has used only visual emotional stimuli, communication entails more than that single dimension and it is known that auditory information is also crucial in this process. In addition, it is, however, unclear what the neurobiological mechanism underlying these MDMA effects on social behaviour is. Previously, studies have shown that MDMA-induced emotional excitability and positive mood are linked to the action on the serotonin (5-HT) 2A receptor. Aim: The present study aimed at investigating the effect of MDMA on processing of sounds (Processing of Affective Sounds Task (PAST)) and cognitive biases (Approach-Avoidance Task (AAT)) towards emotional and social stimuli and the role of 5-HT2A receptor in these effects. Methods: Twenty healthy recreational users entered a 2 × 2, placebo-controlled, within-subject study with ketanserin (40 mg) as pre-treatment and MDMA (75 mg) as treatment. Behavioural (PAST, AAT) measures were conducted 90 min after treatment with MDMA, respectively, 120 min after ketanserin. Self-report mood measures and oxytocin concentrations were taken at baseline and before and after behavioural tests. Results: Findings showed that MDMA reduced arousal elicited by negative sounds. This effect was counteracted by ketanserin pre-treatment, indicating involvement of the 5-HT2 receptor in this process. MDMA did not seem to induce a bias towards emotional and social stimuli. It increased positive and negative mood ratings and elevated oxytocin plasma concentrations. The reduction in arousal levels when listening to negative sounds was not related to the elevated subjective arousal. Conclusion: It is suggested that this decrease in arousal to negative stimuli reflects potentially a lowering of defences, a process that might play a role in the therapeutic process.

Psychopharmacology · randomised controlled trial · 17 citationsread the source →

Clinical effectiveness and patient perspectives of different treatment strategies for tics in children and adolescents with Tourette syndrome: a systematic review and qualitative analysis.

Background: Tourette syndrome (TS) is a neurodevelopmental condition characterised by chronic motor and vocal tics affecting up to 1% of school-age children and young people and is associated with significant distress and psychosocial impairment. Objective: To conduct a systematic review of the benefits and risks of pharmacological, behavioural and physical interventions for tics in children and young people with TS (part 1) and to explore the experience of treatment and services from the perspective of young people with TS and their parents (part 2). Data sources: For the systematic reviews (parts 1 and 2), mainstream bibliographic databases, The Cochrane Library, education, social care and grey literature databases were searched using subject headings and text words for tic* and Tourette* from database inception to January 2013. Review/research methods: For part 1, randomised controlled trials and controlled before-and-after studies of pharmacological, behavioural or physical interventions in children or young people (aged < 18 years) with TS or chronic tic disorder were included. Mixed studies and studies in adults were considered as supporting evidence. Risk of bias associated with each study was evaluated using the Cochrane tool. When there was sufficient data, random-effects meta-analysis was used to synthesize the evidence and the quality of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. For part 2, qualitative studies and survey literature conducted in populations of children/young people with TS or their carers or in health professionals with experience of treating TS were included in the qualitative review. Results were synthesized narratively. In addition, a national parent/carer survey was conducted via the Tourettes Action website. Participants included parents of children and young people with TS aged under 18 years. Participants (young people with TS aged 10-17 years) for the in-depth interviews were recruited via a national survey and specialist Tourettes clinics in the UK. Results: For part 1, 70 studies were included in the quantitative systematic review. The evidence suggested that for treating tics in children and young people with TS, antipsychotic drugs [standardised mean difference (SMD) -0.74, 95% confidence interval (CI) -1.08 to -0.41; n = 75] and noradrenergic agents [clonidine (Dixarit(®), Boehringer Ingelheim) and guanfacine: SMD -0.72, 95% CI -1.03 to -0.40; n = 164] are effective in the short term. There was little difference among antipsychotics in terms of benefits, but adverse effect profiles do differ. Habit reversal training (HRT)/comprehensive behavioural intervention for tics (CBIT) was also shown to be effective (SMD -0.64, 95% CI -0.99 to -0.29; n = 133). For part 2, 295 parents/carers of children and young people with TS contributed useable survey data. Forty young people with TS participated in in-depth interviews. Four studies were in the qualitative review. Key themes were difficulties in accessing specialist care and behavioural interventions, delay in diagnosis, importance of anxiety and emotional symptoms, lack of provision of information to schools and inadequate information regarding medication and adverse effects. Limitations: The number and quality of clinical trials is low and this downgrades the strength of the evidence and conclusions. Conclusions: Antipsychotics, noradrenergic agents and HRT/CBIT are effective in reducing tics in children and young people with TS. The balance of benefits and harms favours the most commonly used medications: risperidone (Risperdal(®), Janssen), clonidine and aripiprazole (Abilify(®), Otsuka). Larger and better-conducted trials addressing important clinical uncertainties are required. Further research is needed into widening access to behavioural interventions through use of technology including mobile applications ('apps') and video consultation. Study registration: This study is registered as PROSPERO CRD42012002059. Funding: The National Institute for Health Research Health Technology Assessment programme.

Health technology assessment (Winchester, England) · systematic review · 94 citationsread the source →

Caffeine effects on risky decision making after 75 hours of sleep deprivation.

Introduction: Recent research indicates that sleep deprivation impairs decision making. However, it is unknown to what extent such deficits are exacerbated in a dose-response manner by increasing levels of sleepiness, and the extent to which such sleep-loss-induced deficits can be reversed by caffeine. Methods: At three time points, 26 healthy subjects completed alternate forms of the Iowa Gambling Task (IGT): rested baseline, 51 h awake, and 75 h awake. Every 2 h each night, 12 volunteers also received 4 200-mg doses of caffeine, with the last dose occurring 3 h prior to the IGT. Results: At baseline, volunteers readily learned to avoid disadvantageous high-risk card decks while progressively choosing more frequently from advantageous low-risk card decks. When sleep deprived, however, these same subjects showed impaired performance, choosing more frequently from the disadvantageous high-risk card decks, particularly during the latter half of the game. Contrary to expectations, the severity of performance impairment did not increase significantly from 51 to 75 h of wakefulness, and caffeine had no significant effects on IGT performance during sleep deprivation. Discussion and conclusions: As a provisional extension of our previous study, these preliminary findings further suggest that the ability to integrate emotion with cognition to guide decision making, a capacity believed to be mediated by the ventromedial prefrontal cortex, may be particularly vulnerable to sleep loss. Moreover, these capacities may not be significantly improved by moderate doses of caffeine, suggesting that they may function separately from simple arousal and alertness systems.

Aviation, space, and environmental medicine · 51 citationsread the source →

Effects of exercise amount and intensity on abdominal obesity and glucose tolerance in obese adults: a randomized trial.

Background: Exercise reduces obesity and related glucose tolerance, but whether increasing exercise intensity offers additional benefit at fixed exercise amounts is unknown. Objective: To determine the separate effects of exercise amount and intensity on abdominal obesity and glucose tolerance. Design: 24-week, single-center, parallel-group trial from 2009 to 2013. (ClinicalTrials.gov: NCT00955071). Setting: Kingston, Ontario, Canada. Participants: 300 abdominally obese adults. Intervention: Control (no exercise) (n = 75) or 5 weekly sessions of low-amount, low-intensity exercise (LALI) (180 and 300 kcal/session for women and men, respectively, at 50% of maximum oxygen consumption [V̇o2peak]) (n = 73); high-amount, low-intensity exercise (HALI) (360 and 600 kcal/session, respectively, at 50% of V̇o2peak) (n = 76); or high-amount, high-intensity exercise (HAHI) (360 and 600 kcal/session, respectively, at 75% of V̇o2peak) (n = 76). Daily unsupervised physical activity and sedentary time were measured by accelerometer. Measurements: Waist circumference and 2-hour glucose level (primary outcomes) and cardiorespiratory fitness and measures of insulin action (secondary measurements). Results: 217 participants (72.3%) completed the intervention. Mean exercise time in minutes per session was 31 (SD, 4.4) for LALI, 58 (SD, 7.6) for HALI, and 40 (SD, 6.2) for HAHI. Daily unsupervised physical activity and sedentary time did not change in any exercise group versus control (P > 0.33). After adjustment for age and sex in a linear mixed model, reductions in waist circumference were greater in the LALI (-3.9 cm [95% CI, -5.6 to -2.3 cm]; P < 0.001), HALI (-4.6 cm [CI, -6.2 to -3.0 cm]; P < 0.001), and HAHI (-4.6 cm [CI, -6.3 to -2.9 cm]; P < 0.001) groups than the control group but did not differ among the exercise groups (P > 0.43). After adjustment for covariates, reductions in 2-hour glucose level were greater in the HAHI group (-0.7 mmol/L [-12.5 mg/dL] [CI, -1.3 to -0.1 mmol/L {-23.5 to -1.5 mg/dL}]; P = 0.027) than the control group but did not differ for the LALI or HALI group versus the control group (P > 0.159). Weight loss was greater in all exercise groups than the control group (P < 0.001); however, reduction in body weight did not differ among the exercise groups (P > 0.182). Limitation: The clinical importance of reducing 2-hour glucose level in nondiabetic adults remains undetermined. Conclusion: Fixed amounts of exercise independent of exercise intensity resulted in similar reductions in abdominal obesity. Reduction in 2-hour glucose level was restricted to high-intensity exercise.

Annals of internal medicine · randomised controlled trial · 127 citationsread the source →

Effect of Artificial Intelligence Tutoring vs Expert Instruction on Learning Simulated Surgical Skills Among Medical Students: A Randomized Clinical Trial.

Importance: To better understand the emerging role of artificial intelligence (AI) in surgical training, efficacy of AI tutoring systems, such as the Virtual Operative Assistant (VOA), must be tested and compared with conventional approaches. Objective: To determine how VOA and remote expert instruction compare in learners' skill acquisition, affective, and cognitive outcomes during surgical simulation training. Design, setting, and participants: This instructor-blinded randomized clinical trial included medical students (undergraduate years 0-2) from 4 institutions in Canada during a single simulation training at McGill Neurosurgical Simulation and Artificial Intelligence Learning Centre, Montreal, Canada. Cross-sectional data were collected from January to April 2021. Analysis was conducted based on intention-to-treat. Data were analyzed from April to June 2021. Interventions: The interventions included 5 feedback sessions, 5 minutes each, during a single 75-minute training, including 5 practice sessions followed by 1 realistic virtual reality brain tumor resection. The 3 intervention arms included 2 treatment groups, AI audiovisual metric-based feedback (VOA group) and synchronous verbal scripted debriefing and instruction from a remote expert (instructor group), and a control group that received no feedback. Main outcomes and measures: The coprimary outcomes were change in procedural performance, quantified as Expertise Score by a validated assessment algorithm (Intelligent Continuous Expertise Monitoring System [ICEMS]; range, -1.00 to 1.00) for each practice resection, and learning and retention, measured from performance in realistic resections by ICEMS and blinded Objective Structured Assessment of Technical Skills (OSATS; range 1-7). Secondary outcomes included strength of emotions before, during, and after the intervention and cognitive load after intervention, measured in self-reports. Results: A total of 70 medical students (41 [59%] women and 29 [41%] men; mean [SD] age, 21.8 [2.3] years) from 4 institutions were randomized, including 23 students in the VOA group, 24 students in the instructor group, and 23 students in the control group. All participants were included in the final analysis. ICEMS assessed 350 practice resections, and ICEMS and OSATS evaluated 70 realistic resections. VOA significantly improved practice Expertise Scores by 0.66 (95% CI, 0.55 to 0.77) points compared with the instructor group and by 0.65 (95% CI, 0.54 to 0.77) points compared with the control group (P < .001). Realistic Expertise Scores were significantly higher for the VOA group compared with instructor (mean difference, 0.53 [95% CI, 0.40 to 0.67] points; P < .001) and control (mean difference. 0.49 [95% CI, 0.34 to 0.61] points; P < .001) groups. Mean global OSATS ratings were not statistically significant among the VOA (4.63 [95% CI, 4.06 to 5.20] points), instructor (4.40 [95% CI, 3.88-4.91] points), and control (3.86 [95% CI, 3.44 to 4.27] points) groups. However, on the OSATS subscores, VOA significantly enhanced the mean OSATS overall subscore compared with the control group (mean difference, 1.04 [95% CI, 0.13 to 1.96] points; P = .02), whereas expert instruction significantly improved OSATS subscores for instrument handling vs control (mean difference, 1.18 [95% CI, 0.22 to 2.14]; P = .01). No significant differences in cognitive load, positive activating, and negative emotions were found. Conclusions and relevance: In this randomized clinical trial, VOA feedback demonstrated superior performance outcome and skill transfer, with equivalent OSATS ratings and cognitive and emotional responses compared with remote expert instruction, indicating advantages for its use in simulation training. Trial registration: ClinicalTrials.gov Identifier: NCT04700384.

JAMA network open · randomised controlled trial · 128 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 →

The effectiveness of case-based learning in health professional education. A BEME systematic review: BEME Guide No. 23.

Background: Case-based learning (CBL) is a long established pedagogical method, which is defined in a number of ways depending on the discipline and type of 'case' employed. In health professional education, learning activities are commonly based on patient cases. Basic, social and clinical sciences are studied in relation to the case, are integrated with clinical presentations and conditions (including health and ill-health) and student learning is, therefore, associated with real-life situations. Although many claims are made for CBL as an effective learning and teaching method, very little evidence is quoted or generated to support these claims. We frame this review from the perspective of CBL as a type of inquiry-based learning. Aim: To explore, analyse and synthesise the evidence relating to the effectiveness of CBL as a means of achieving defined learning outcomes in health professional prequalification training programmes. Method: Selection criteria: We focused the review on CBL for prequalification health professional programmes including medicine, dentistry, veterinary science, nursing and midwifery, social care and the allied health professions (physiotherapy, occupational therapy, etc.). Papers were required to have outcome data on effectiveness. Search strategies: The search covered the period from 1965 to week 4 September 2010 and the following databases: ASSIA, CINAHL, EMBASE, Education Research, Medline and Web of Knowledge (WoK). Two members of the topic review group (TRG) independently reviewed the 173 abstracts retrieved from Medline and compared findings. As there was good agreement on inclusion, one went onto review the WoK and ASSIA EndNote databases and the other the Embase, CINAHL and Education Research databases to decide on papers to submit for coding. Coding and data analysis: The TRG modified the standard best evidence medical education coding sheet to fit our research questions and assessed each paper for quality. After a preliminary reliability exercise, each full paper was read and graded by one reviewer with the papers scoring 3-5 (of 5) for strength of findings being read by a second reviewer. A summary of each completed coding form was entered into an Excel spread sheet. The type of data in the papers was not amenable to traditional meta-analysis because of the variability in interventions, information given, student numbers (and lack of) and timings. We, therefore, adopted a narrative synthesis method to compare, contrast, synthesise and interpret the data, working within a framework of inquiry-based learning. Results: The final number of coded papers for inclusion was 104. The TRG agreed that 23 papers would be classified as of higher quality and significance (22%). There was a wide diversity in the type, timing, number and length of exposure to cases and how cases were defined. Medicine was the most commonly included profession. Numbers of students taking part in CBL varied from below 50 to over 1000. The shortest interventions were two hours, and one case, whereas the longest was CBL through a whole year. Group sizes ranged from students working alone to over 30, with the majority between 2 and 15 students per group. The majority of studies involved single cohorts of students (61%), with 29% comparing multiple groups, 8% involving different year groups and 2% with historical controls. The outcomes evaluation was either carried out postintervention only (78 papers; 75%), preintervention and postintervention (23 papers; 22%) or during and postintervention (3 papers; <3%). Our analysis provided the basis for discussion of definitions of CBL, methods used and advocated, topics and learning outcomes and whether CBL is effective based on the evaluation data. Conclusion: Overwhelmingly, students enjoy CBL and think that it enhances their learning. The empirical data taken as a whole are inconclusive as to the effects on learning compared with other types of activity. Teachers enjoy CBL, partly because it engages, and is perceived to motivate, students. CBL seems to foster learning in small groups though whether this is the case delivery or the group learning effect is unclear.

Medical teacher · systematic review · 534 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 →

Testing the ego-depletion effect in optimized conditions.

The observation that exerting self-control in an initial task impairs subsequent self-control performance in a following task has been used to explain a wide range of phenomena. If evidence for this "ego-depletion" effect was initially believed to be strong, it is now questioned. Recent meta-analyses indicated that this effect was sensitive to publication bias and that it was greatly reduced after control for this bias. In a pre-registered replication attempt where an ego-depletion protocol was conducted in multiple independent laboratories, the effect was not distinguishable from zero. Here, a different approach is adopted to examine the validity of this effect by improving the experimental protocol with the addition of important methodological precautions: 1) a pre-test measurement, 2) a learning period, 3) a prolonged depleting task, 4) a similar control condition, and 5) valid indexes of self-control. Accordingly, a well-learned Simon task was done before and after 1h of continuous practice of a Stroop task in a high inhibition demands condition (75% of incongruent trials) or in a control condition (0% of incongruent trials). Datasets from between-subjects (Study 1, N = 82) and within-subjects (Study 2, N = 52) experiments were analyzed using generalized linear mixed models. A significant ego-depletion effect was found in Study 1 (greater interference effect and accuracy decline in high inhibition demands than in control condition) but not in Study 2. Because it is difficult to explain this difference in results, the findings suggest that, even in a context chosen to optimize the observation of an ego-depletion effect, it seems difficult to be conclusive about the existence of this effect.

PloS one · randomised controlled trial · 8 citationsread the source →

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

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

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

Efficacy of health coaching and a web-based program on physical activity, weight, and distress management among cancer survivors: A multi-centered randomised controlled trial.

Objectives: To investigate the efficacy of health coaching and a web-based program on survivor physical activity (PA), weight, and distress management among stomach, colon, lung and breast cancer patients. Methods: This randomised, controlled, 1-year trial conducted in five hospitals recruited cancer survivors within 2 months of completing primary cancer treatment who had not met ≥1 of these behavioural goals: (i) conducting moderate PA for at least 150 minutes/week or strenuous exercise for over 75 minutes per week or, in the case of lung cancer patients, low or moderate intensity exercise for over 12.5 MET per week, (ii) maintaining normal weight, and (iii) attaining a score >72 in the Post Traumatic Growth Inventory (PTGI). Participants were randomly assigned to one of three groups: the control group, a web-only group, or a health coaching + web group. The primary endpoint was based on a composite of PA, weight, and PTGI score at 12 months. Results: Patients in the health coaching + web group (difference = 6.6%, P = .010) and the web-only group (difference = 5.9%, P = .031) had greater overall improvements across the three-outcome composite than the control group. The health coaching + web group had greater overall improvement in PTGI (difference = 12.6%; P < .001) than the control group, but not in PA and weight. Conclusion: The web-based program, with or without health coaching, may improve health behaviours including PA, weight, and distress management among cancer survivors within 2 months of completing primary cancer treatment. The web-based program with health coaching was mainly effective for reducing psychological distress.

Psycho-oncology · randomised controlled trial · 40 citationsread the source →

Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study.

Background: Neurokinin 3 receptor antagonists are potential non-hormonal therapies for the treatment of vasomotor symptoms in menopausal women as options are scarce for those who cannot or do not want to take hormone therapy. Fezolinetant is one of the first non-hormonal neurokinin 3 receptor antagonists in development for the treatment of vasomotor symptoms due to menopause. This study investigated the safety and efficacy of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms associated with menopause. Methods: SKYLIGHT 1 is a randomised, double-blind, placebo-controlled, 12-week, phase 3 trial with a 40-week active treatment extension. This trial was done at 97 facilities across the USA, Canada, Czech Republic, Hungary, Poland, Spain, and the UK. Women aged 40-65 years with an average of seven or more moderate-to-severe hot flashes per day were randomly assigned (1:1:1) to once-daily exact-matched placebo, fezolinetant 30 mg, or fezolinetant 45 mg. Randomisation was done using a web-based interactive response system and investigators, project team members, clinical staff, and participants were masked to treatment assignment. Coprimary endpoints were mean change in frequency and severity of vasomotor symptoms from baseline to weeks 4 and 12. The efficacy and safety analyses comprised all randomly assigned participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov (NCT04003155) and is completed. Findings: Between July 11, 2019, and Aug 11, 2021, 2205 women were recruited of whom 175 were assigned to placebo, 176 to fezolinetant 30 mg, and 176 to fezolinetant 45 mg (175 in the placebo group, 174 in the fezolinetant 30 mg group, and 173 in the fezolinetant 45 mg received at least one dose [safety analysis set]). One participant randomly assigned to fezolinetant 45 mg received fezolinetant 30 mg in error, so the efficacy analysis set (full analysis set) consisted of 173 in the fezolinetant 30 mg group and 174 in the fezolinetant 45 mg group. 23 participants in the placebo group, 31 in the fezolinetant 30 mg group, and 13 in the fezolinetant 45 mg group discontinued treatment before week 12, mostly due to adverse events or participant withdrawal. Compared with placebo, fezolinetant 30 mg and fezolinetant 45 mg significantly reduced the frequency of vasomotor symptoms at week 4 (difference in change in least squares mean -1·87 [SE 0·42; p<0·001], -2·07 [SE 0·42; p<0·001]) and week 12 (-2·39 [SE 0·44; p<0·001], -2·55 [SE 0·43; p<0·001]). Compared with placebo, fezolinetant 30 mg and 45 mg significantly reduced the severity of vasomotor symptoms at week 4 (-0·15 [0·06; p=0·012], -0·19 [0·06; p=0·002]) and week 12 (-0·24 [0·08; p=0·002], -0·20 [0·08; p=0·007]). Improvements in frequency and severity of vasomotor symptoms were observed after 1 week and maintained over 52 weeks. During the first 12 weeks, treatment-emergent adverse events occurred in 65 (37%) of 174 women in the fezolinetant 30 mg group, 75 (43%) of 173 in the fezolinetant 45 mg group, and 78 (45%) of 175 in the placebo group. The incidence of liver enzyme elevations was low (placebo n=1; fezolinetant 30 mg n=2; fezolinetant 45 mg n=0) and these events were generally asymptomatic, transient, and resolved while on treatment or after treatment discontinuation. Interpretation: Data support the clinical use of fezolinetant as a non-hormonal treatment for vasomotor symptoms associated with menopause. The study was placebo-controlled for 12 weeks followed by a 40-week blinded extension to assess the maintenance of effect. Furthermore, the population studied was diverse and representative of the potential target population for fezolinetant therapy. Further characterisation of the benefit of fezolinetant on quality of life, including on symptoms of mood and sexual wellbeing, merits investigation. Funding: Astellas Pharma.

Lancet (London, England) · randomised controlled trial · 172 citationsread the source →

Timing of Resistance Training During Ramadan Fasting and Its Effects on Muscle Strength and Hypertrophy.

Purpose: During Ramadan month, Muslims often continue training to maintain their muscle performance. However, trainers should stress the importance of the time of day chosen for practicing resistance training (RT) during Ramadan fasting to avoid health and performance alteration. Thus, this study aimed to investigate the effects of the timing of RT during Ramadan intermittent fasting (RIF) on muscle strength and hypertrophy in healthy male adults. Methods: Forty men were randomly allocated to 2 matched groups: 20 practicing whole-body RT in the late afternoon in a fasted state and 20 training in the late evening in a fed state (FED). Both groups performed 4 days per week of whole-body RT (∼75%-85% 1-repetition maximum, 12 repetitions/3-4 sets) during RIF. Anthropometric measurements and 1-repetition-maximum test for the squats, deadlift, and bench press were measured. A cross-sectional area of the quadriceps and biceps brachii was examined using ultrasound scans. All measurements were taken at 4 time points: 24 hours before the start of Ramadan, on the 15th day of Ramadan, on the 29th day of Ramadan, and 21 days after Ramadan. Results: Post hoc tests indicated significant preimprovement to postimprovement in FED at the 29th day of Ramadan for the 1-repetition-maximum test for the squats (P = .02; effect size = 0.21) and deadlift (P = .03; effect size = 0.24) when compared to 24 hours before the start of Ramadan. No significant changes were observed in the fasted-state group or for cross-sectional area for both groups. Conclusions: Practicing RT during RIF appears not to have adverse effects on muscle hypertrophy and strength no matter whether it is practiced in FED or fasted state. However, RT had greater effects on muscle strength when applied in FED. Our findings suggest that training sessions should be scheduled after breaking the fast during Ramadan.

International journal of sports physiology and performance · randomised controlled trial · 6 citationsread the source →

Actissist: Proof-of-Concept Trial of a Theory-Driven Digital Intervention for Psychosis.

Background: Timely access to intervention for psychosis is crucial yet problematic. As such, health care providers are forming digital strategies for addressing mental health challenges. A theory-driven digital intervention that monitors distressing experiences and provides real-time active management strategies could improve the speed and quality of recovery in psychosis, over and above conventional treatments. This study assesses the feasibility and acceptability of Actissist, a digital health intervention grounded in the cognitive model of psychosis that targets key early psychosis domains. Methods: A proof-of-concept, single, blind, randomized controlled trial of Actissist, compared to a symptom-monitoring control. Thirty-six early psychosis patients were randomized on a 2:1 ratio to each arm of the trial. Actissist was delivered via a smartphone app over 12-weeks; clinical and functional assessment time-points were baseline, post-treatment and 22-weeks. Assessors' blind to treatment condition conducted the assessments. Acceptability was examined using qualitative methods. Results: Actissist was feasible (75% participants used Actissist at least once/day; uptake was high, 97% participants remained in the trial; high follow-up rates), acceptable (90% participants recommend Actissist), and safe (0 serious adverse events), with high levels of user satisfaction. Treatment effects were large on negative symptoms, general psychotic symptoms and mood. The addition of Actissist conferred benefit at post-treatment assessment over routine symptom-monitoring and treatment as usual. Conclusions: This is the first controlled proof-of-concept trial of a theory-driven digital health intervention for early psychosis. Actissist is feasible and acceptable to early psychosis patients, with a strong signal for treatment efficacy. Trial Registration: ISRCTN: 34966555.

Schizophrenia bulletin · randomised controlled trial · 143 citationsread the source →

Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis.

Background: Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis. Methods: In two randomized, placebo-controlled, phase 3 trials of identical design (SOLO 1 and SOLO 2), we enrolled adults with moderate-to-severe atopic dermatitis whose disease was inadequately controlled by topical treatment. Patients were randomly assigned in a 1:1:1 ratio to receive, for 16 weeks, subcutaneous dupilumab (300 mg) or placebo weekly or the same dose of dupilumab every other week alternating with placebo. The primary outcome was the proportion of patients who had both a score of 0 or 1 (clear or almost clear) on the Investigator's Global Assessment and a reduction of 2 points or more in that score from baseline at week 16. Results: We enrolled 671 patients in SOLO 1 and 708 in SOLO 2. In SOLO 1, the primary outcome occurred in 85 patients (38%) who received dupilumab every other week and in 83 (37%) who received dupilumab weekly, as compared with 23 (10%) who received placebo (P<0.001 for both comparisons with placebo). The results were similar in SOLO 2, with the primary outcome occurring in 84 patients (36%) who received dupilumab every other week and in 87 (36%) who received dupilumab weekly, as compared with 20 (8%) who received placebo (P<0.001 for both comparisons). In addition, in the two trials, an improvement from baseline to week 16 of at least 75% on the Eczema Area and Severity Index was reported in significantly more patients who received each regimen of dupilumab than in patients who received placebo (P<0.001 for all comparisons). Dupilumab was also associated with improvement in other clinical end points, including reduction in pruritus and symptoms of anxiety or depression and improvement in quality of life. Injection-site reactions and conjunctivitis were more frequent in the dupilumab groups than in the placebo groups. Conclusions: In two phase 3 trials of identical design involving patients with atopic dermatitis, dupilumab improved the signs and symptoms of atopic dermatitis, including pruritus, symptoms of anxiety and depression, and quality of life, as compared with placebo. Trials of longer duration are needed to assess the long-term effectiveness and safety of dupilumab. (Funded by Sanofi and Regeneron Pharmaceuticals; SOLO 1 ClinicalTrials.gov number, NCT02277743 ; SOLO 2 ClinicalTrials.gov number, NCT02277769 .).

The New England journal of medicine · randomised controlled trial · 1521 citationsread the source →

Exercise intervention improves quality of life in older adults after myocardial infarction: randomised clinical trial.

Objective: To establish the benefits of an early, tailored and low-cost exercise intervention in older patients hospitalised for acute coronary syndrome (ACS). Methods: The study was a multicentre, randomised assessment of an exercise intervention in patients with ACS ≥70 years with reduced physical performance (as defined by the short physical performance battery (SPPB), value 4-9). The exercise intervention included four supervised sessions (1, 2, 3, 4 months after discharge) and home-based exercises. The control group attended a health education programme only. The outcomes were the 6-month and 1-year effects on physical performance, daily activities, anxiety/depression and quality of life. Finally, 1-year occurrence of adverse events was recorded. Results: Overall, 235 patients with ACS (median age 76 (73-81) years) were randomised 1 month after ACS. Exercise and control groups were well balanced. Exercise intervention improved 6-month and 1-year grip strength and gait speed. Exercise intervention was associated with a better quality of life (as measured by EuroQol-visual analogue scale at 6 months 80 (70-90) vs 70 (50-80) points, p<0.001 and at 1 year 75 (70-87) vs 65 (50-80) points, p<0.001) and with a reduced perception of anxiety and/or depression (6 months: 21% vs 42%, p=0.001; 1 year 32% vs 47%, p=0.03). The occurrence of cardiac death and hospitalisation for cardiac cause was lower in the intervention group (7.5% vs 17%, p=0.04). Conclusions: The proposed early, tailored, low-cost exercise intervention improves mobility, daily activities, quality of life and outcomes in older patients with ACS. Larger studies are needed to confirm the clinical benefit. Trial registration number: NCT03021044.

Heart (British Cardiac Society) · randomised controlled trial · 61 citationsread the source →

Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression.

Background: Psilocybin is being studied for use in treatment-resistant depression. Methods: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits). Results: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; P<0.001) and between the 10-mg group and 1-mg group was -2.5 (95% CI, -6.2 to 1.2; P = 0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups. Conclusions: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. (Funded by COMPASS Pathfinder; EudraCT number, 2017-003288-36; ClinicalTrials.gov number, NCT03775200.).

The New England journal of medicine · randomised controlled trial · 786 citationsread the source →

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

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

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

Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or when this treatment is medically inadvisable: a placebo-controlled, randomized phase III clinical trial (LIBERTY AD CAFÉ).

Background: Atopic dermatitis is a chronic inflammatory skin disease that may require systemic therapy. Ciclosporin A (CsA) is a widely used, potent immunosuppressant but it is not effective in all patients with atopic dermatitis, and side-effects limit its use. Dupilumab, a fully human anti-interleukin 4 receptor-alpha monoclonal antibody, inhibits signaling of IL-4 and IL-13, key drivers of Type 2/Th2-mediated inflammation, and is approved in the U.S.A. and the European Union for the treatment of inadequately-controlled moderate-to-severe atopic dermatitis in adults. Objectives: To evaluate efficacy and safety of dupilumab with concomitant topical corticosteroids (TCS) in adults with atopic dermatitis with inadequate response to/intolerance of CsA, or for whom CsA treatment was medically inadvisable. Methods: In this 16-week, double-blind, randomized, placebo-controlled, phase III trial, patients were randomized 1 : 1 : 1 to subcutaneous dupilumab 300 mg weekly (qw) or every 2 weeks (q2w) or placebo. All received concomitant medium-potency TCS from Week -2 through Week 16; dosage could be tapered if lesions cleared, or stopped for adverse reactions to TCS. Results: In total, 390 patients were screened, 325 were randomized, and 318 completed the trial. Treatment groups had similar baseline characteristics. Significantly more patients in the dupilumab qw + TCS and q2w + TCS groups achieved ≥ 75% improvement from baseline in the Eczema Area and Severity Index at Week 16 vs. the placebo + TCS group (primary end point) (59·1% and 62·6% vs. 29·6%, respectively; P < 0·001 vs. placebo + TCS, both doses). Other clinical outcomes and atopic dermatitis symptoms were significantly improved in the dupilumab qw + TCS and q2w + TCS groups, including pruritus, pain, sleep disturbance, symptoms of anxiety and depression, and quality of life (QoL). Treatment groups had similar overall rates of adverse events (qw + TCS, q2w + TCS and placebo + TCS groups: 69·1%, 72·0% and 69·4%, respectively) and serious adverse events (1·8%, 1·9% and 1·9%, respectively). Conjunctivitis was more frequent with dupilumab + TCS; skin infections were more frequent with placebo + TCS. Conclusions: Dupilumab + TCS significantly improved signs and symptoms of atopic dermatitis and QoL in adults with a history of inadequate response to/intolerance of CsA, or for whom CsA treatment was medically inadvisable. No new safety signals were identified.

The British journal of dermatology · randomised controlled trial · 367 citationsread the source →

Effect of the INSIGHT Responsive Parenting Intervention on Rapid Infant Weight Gain and Overweight Status at Age 1 Year: A Randomized Clinical Trial.

Importance: Rapid infant weight gain is associated with later obesity, but interventions to prevent rapid infant growth and reduce risk for overweight status in infancy are lacking. Objective: To examine the effect of a responsive parenting (RP) intervention on infant weight gain between birth and 28 weeks and overweight status at age 1 year. Design, setting, and participants: The Intervention Nurses Start Infants Growing on Healthy Trajectories (INSIGHT) study is an ongoing randomized clinical trial comparing an RP intervention designed to prevent childhood obesity with a safety control. The study includes primiparous mother-newborn dyads (n = 291) and was conducted at the Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, in addition to home visits. Enrollment was initiated in January 2012, and evaluable population analyses for this study were conducted between April 2015 and November 2015. Interventions: At 2 weeks post partum, initial intervention materials appropriate to the assigned treatment group were mailed to the participant's home. Research nurses conducted home visits at 3 weeks, 16 weeks, 28 weeks, and 40 weeks, and a research center visit occurred at 1 year. The Intervention Nurses Start Infants Growing on Healthy Trajectories curriculum included messages about infant feeding, sleep hygiene, active social play, emotion regulation, and growth record education. The control group received a developmentally appropriate home safety intervention also delivered by nurse home visitors. Main outcomes and measures: Conditional weight gain from birth to 28 weeks was calculated. General linear models examined intervention effect on conditional weight gain. The intervention's effect on infant weight-for-length percentiles was tested using analysis of variance. Logistic regression compared the odds of overweight status (weight for length ≥95th percentile) at 1 year as a function of conditional weight gain. Results: Of the mothers included in the study, 246 were white (88%), 260 were non-Hispanic (93%), 210 were married (75%), and 201 were working full time (72%) at time of enrollment. The mean conditional weight gain score was lower among infants in the RP group compared with the control group (-0.18; 95% CI, -0.36 to -0.001), reflecting that the RP infants gained weight more slowly than control group infants (0.18; 95% CI, 0.02-0.34); this effect did not differ by feeding mode (predominantly fed breast milk or not). Infants in the RP group also had lower mean weight-for-length percentiles at 1 year than infants in the control group (57.5%; 95% CI, 52.56%-62.37% vs 64.4%; 95% CI, 59.94%-69.26%; P = .04) and were less likely to be overweight at age 1 year (5.5% vs 12.7%; P = .05). Conclusions and relevance: An RP intervention is associated with reduced rapid weight gain during the first 6 months after birth and overweight status at age 1 year. Trial registration: clinicaltrials.gov Identifier: NCT01167270.

JAMA pediatrics · randomised controlled trial · 192 citationsread the source →