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Physical activity, diet and other behavioural interventions for improving cognition and school achievement in children and adolescents with obesity or overweight.

Background: The global prevalence of childhood and adolescent obesity is high. Lifestyle changes towards a healthy diet, increased physical activity and reduced sedentary activities are recommended to prevent and treat obesity. Evidence suggests that changing these health behaviours can benefit cognitive function and school achievement in children and adolescents in general. There are various theoretical mechanisms that suggest that children and adolescents with excessive body fat may benefit particularly from these interventions. Objectives: To assess whether lifestyle interventions (in the areas of diet, physical activity, sedentary behaviour and behavioural therapy) improve school achievement, cognitive function (e.g. executive functions) and/or future success in children and adolescents with obesity or overweight, compared with standard care, waiting-list control, no treatment, or an attention placebo control group. Search methods: In February 2017, we searched CENTRAL, MEDLINE and 15 other databases. We also searched two trials registries, reference lists, and handsearched one journal from inception. We also contacted researchers in the field to obtain unpublished data. Selection criteria: We included randomised and quasi-randomised controlled trials (RCTs) of behavioural interventions for weight management in children and adolescents with obesity or overweight. We excluded studies in children and adolescents with medical conditions known to affect weight status, school achievement and cognitive function. We also excluded self- and parent-reported outcomes. Data collection and analysis: Four review authors independently selected studies for inclusion. Two review authors extracted data, assessed quality and risks of bias, and evaluated the quality of the evidence using the GRADE approach. We contacted study authors to obtain additional information. We used standard methodological procedures expected by Cochrane. Where the same outcome was assessed across different intervention types, we reported standardised effect sizes for findings from single-study and multiple-study analyses to allow comparison of intervention effects across intervention types. To ease interpretation of the effect size, we also reported the mean difference of effect sizes for single-study outcomes. Main results: We included 18 studies (59 records) of 2384 children and adolescents with obesity or overweight. Eight studies delivered physical activity interventions, seven studies combined physical activity programmes with healthy lifestyle education, and three studies delivered dietary interventions. We included five RCTs and 13 cluster-RCTs. The studies took place in 10 different countries. Two were carried out in children attending preschool, 11 were conducted in primary/elementary school-aged children, four studies were aimed at adolescents attending secondary/high school and one study included primary/elementary and secondary/high school-aged children. The number of studies included for each outcome was low, with up to only three studies per outcome. The quality of evidence ranged from high to very low and 17 studies had a high risk of bias for at least one item. None of the studies reported data on additional educational support needs and adverse events. Compared to standard practice, analyses of physical activity-only interventions suggested high-quality evidence for improved mean cognitive executive function scores. The mean difference (MD) was 5.00 scale points higher in an after-school exercise group compared to standard practice (95% confidence interval (CI) 0.68 to 9.32; scale mean 100, standard deviation 15; 116 children, 1 study). There was no statistically significant beneficial effect in favour of the intervention for mathematics, reading, or inhibition control. The standardised mean difference (SMD) for mathematics was 0.49 (95% CI -0.04 to 1.01; 2 studies, 255 children, moderate-quality evidence) and for reading was 0.10 (95% CI -0.30 to 0.49; 2 studies, 308 children, moderate-quality evidence). The MD for inhibition control was -1.55 scale points (95% CI -5.85 to 2.75; scale range 0 to 100; SMD -0.15, 95% CI -0.58 to 0.28; 1 study, 84 children, very low-quality evidence). No data were available for average achievement across subjects taught at school. There was no evidence of a beneficial effect of physical activity interventions combined with healthy lifestyle education on average achievement across subjects taught at school, mathematics achievement, reading achievement or inhibition control. The MD for average achievement across subjects taught at school was 6.37 points lower in the intervention group compared to standard practice (95% CI -36.83 to 24.09; scale mean 500, scale SD 70; SMD -0.18, 95% CI -0.93 to 0.58; 1 study, 31 children, low-quality evidence). The effect estimate for mathematics achievement was SMD 0.02 (95% CI -0.19 to 0.22; 3 studies, 384 children, very low-quality evidence), for reading achievement SMD 0.00 (95% CI -0.24 to 0.24; 2 studies, 284 children, low-quality evidence), and for inhibition control SMD -0.67 (95% CI -1.50 to 0.16; 2 studies, 110 children, very low-quality evidence). No data were available for the effect of combined physical activity and healthy lifestyle education on cognitive executive functions. There was a moderate difference in the average achievement across subjects taught at school favouring interventions targeting the improvement of the school food environment compared to standard practice in adolescents with obesity (SMD 0.46, 95% CI 0.25 to 0.66; 2 studies, 382 adolescents, low-quality evidence), but not with overweight. Replacing packed school lunch with a nutrient-rich diet in addition to nutrition education did not improve mathematics (MD -2.18, 95% CI -5.83 to 1.47; scale range 0 to 69; SMD -0.26, 95% CI -0.72 to 0.20; 1 study, 76 children, low-quality evidence) and reading achievement (MD 1.17, 95% CI -4.40 to 6.73; scale range 0 to 108; SMD 0.13, 95% CI -0.35 to 0.61; 1 study, 67 children, low-quality evidence). Authors' conclusions: Despite the large number of childhood and adolescent obesity treatment trials, we were only able to partially assess the impact of obesity treatment interventions on school achievement and cognitive abilities. School and community-based physical activity interventions as part of an obesity prevention or treatment programme can benefit executive functions of children with obesity or overweight specifically. Similarly, school-based dietary interventions may benefit general school achievement in children with obesity. These findings might assist health and education practitioners to make decisions related to promoting physical activity and healthy eating in schools. Future obesity treatment and prevention studies in clinical, school and community settings should consider assessing academic and cognitive as well as physical outcomes.

The Cochrane database of systematic reviews · meta-analysis · 77 citationsread the source →

Evaluation of Nutritional Status of Patients with Depression.

Aims and objectives: Our goal was to determine nutritional status, body composition, and biochemical parameters of patients diagnosed with depression based on DSM-IV-TR criteria. Methods: A total of 59 individuals, aged 18-60 years admitted to Mental Health Centre of Kayseri Education and Research Hospital, were included in the study. The participants were randomly assigned to two groups; depression group (n = 29) and control group (n = 30). Anthropometric measurements, some biochemical parameters, demographic data, and 24-hour dietary recall were evaluated. Results: 65.5% of depression and 60.0% of control group were female. Intake of vitamins A, thiamine, riboflavin, B6, folate, C, Na, K, Mg, Ca, P, Fe, Zn, and fibre (p < 0.05) were lower in depression group. Median levels of body weight, waist circumference, hip circumference, waist-to-hip ratio (p < 0.05) were significantly higher in depression group. Fasting blood glucose levels, serum vitamins B12, and folic acid (p < 0.05) in depression group were lower than controls. Serum insulin and HOMA levels of two groups were similar. Conclusion: Some vitamin B consumption and serum vitamin B12 and folic acid levels were low while signs of abdominal obesity were high among patients with depression. Future research exploring nutritional status of individuals with depression is warranted.

BioMed research international · randomised controlled trial · 37 citationsread the source →

Coached Mobile App Platform for the Treatment of Depression and Anxiety Among Primary Care Patients: A Randomized Clinical Trial.

Importance: Depression and anxiety are common and disabling. Primary care is the de facto site for treating these mental health problems but is typically underresourced to meet the burden of these demands. Objective: To evaluate the efficacy of a mobile intervention platform, IntelliCare, for addressing depression and anxiety among primary care patients. Design, setting, and participants: Two-arm randomized clinical trial at internal medicine clinics at the University of Arkansas for Medical Sciences. Adult primary care patients (N = 146) who screened positive for depression on the Patient Health Questionnaire-8 (PHQ; score  ≥ 10) or anxiety on the Generalized Anxiety Disorder-7 (GAD-7; score ≥ 8) were recruited between July 17, 2018, and December 14, 2018. Interventions: The coach-supported platform composed of a suite of apps, was delivered over 8 weeks. Wait list control participants received treatment as usual for 8 weeks, then the mobile platform. Main outcomes and measures: Primary outcomes were changes in depression (PHQ-9) and anxiety (GAD-7) during the intervention period. Secondary outcomes were differences in the proportion of patients who achieved recovery (PHQ-9/GAD-7 <5 or 50% improvement from baseline), sustainment of intervention effects during 2-month follow-up, and app use during the intervention period. Results: One hundred forty-six patients were included (119 of 146 were women [81.5%]; mean [SD] age, 42.3 [13.8] years). Of the 146 patients, 122 (83.6%) were diagnosed as having depression and 131 (89.7%) were diagnosed as having anxiety. A greater proportion of intervention vs wait list control participants achieved recovery from depression (n = 38 of 64 [59%] vs n = 18 of 58 [31%]; odds ratio, 3.25; 95% CI, 1.54-6.86) and anxiety (n = 37 of 65 [57%] vs n = 25 of 66 [38%]; odds ratio, 2.17; 95% CI, 1.08-4.36). Sustained effects were observed for depression (slope, 0.01; 95% CI, -0.09 to 0.10; P = .92) and anxiety scores (slope, 0.02; 95% CI, -0.08 to 0.12; P = .67) during follow-up. App use was high, with a median of 93 and 98 sessions among participants with depression and anxiety, respectively. Conclusions and relevance: In this trial, a mobile intervention app was effective for depression and anxiety among primary care patients. Findings also support designing digital mental health interventions as platforms containing simple, brief apps that can be bundled by users to meet their needs. Trial registration: ClinicalTrials.gov Identifier: NCT03500536.

JAMA psychiatry · randomised controlled trial · 122 citationsread the source →

Mindfulness-Based Stress Reduction vs Escitalopram for the Treatment of Adults With Anxiety Disorders: A Randomized Clinical Trial.

Importance: Anxiety disorders are common, highly distressing, and impairing conditions. Effective treatments exist, but many patients do not access or respond to them. Mindfulness-based interventions, such as mindfulness-based stress reduction (MBSR) are popular and can decrease anxiety, but it is unknown how they compare to standard first-line treatments. Objective: To determine whether MBSR is noninferior to escitalopram, a commonly used first-line psychopharmacological treatment for anxiety disorders. Design, setting, and participants: This randomized clinical trial (Treatments for Anxiety: Meditation and Escitalopram [TAME]) included a noninferiority design with a prespecified noninferiority margin. Patients were recruited between June 2018 and February 2020. The outcome assessments were performed by blinded clinical interviewer at baseline, week 8 end point, and follow-up visits at 12 and 24 weeks. Of 430 individuals assessed for inclusion, 276 adults with a diagnosed anxiety disorder from 3 urban academic medical centers in the US were recruited for the trial, and 208 completed the trial. Interventions: Participants were 1:1 randomized to 8 weeks of the weekly MBSR course or the antidepressant escitalopram, flexibly dosed from 10 to 20 mg. Main outcomes and measures: The primary outcome measure was anxiety levels as assessed with the Clinical Global Impression of Severity scale (CGI-S), with a predetermined noninferiority margin of -0.495 points. Results: The primary noninferiority sample consisted of 208 patients (102 in MBSR and 106 in escitalopram), with a mean (SD) age of 33 (13) years; 156 participants (75%) were female; 32 participants (15%) were African American, 41 (20%) were Asian, 18 (9%) were Hispanic/Latino, 122 (59%) were White, and 13 (6%) were of another race or ethnicity (including Native American or Alaska Native, more than one race, or other, consolidated owing to low numbers). Baseline mean (SD) CGI-S score was 4.44 (0.79) for the MBSR group and 4.51 (0.78) for the escitalopram group in the per-protocol sample and 4.49 (0.77) vs 4.54 (0.83), respectively, in the randomized sample. At end point, the mean (SD) CGI-S score was reduced by 1.35 (1.06) for MBSR and 1.43 (1.17) for escitalopram. The difference between groups was -0.07 (0.16; 95% CI, -0.38 to 0.23; P = .65), where the lower bound of the interval fell within the predefined noninferiority margin of -0.495, indicating noninferiority of MBSR compared with escitalopram. Secondary intent-to-treat analyses using imputed data also showed the noninferiority of MBSR compared with escitalopram based on the improvement in CGI-S score. Of patients who started treatment, 10 (8%) dropped out of the escitalopram group and none from the MBSR group due to adverse events. At least 1 study-related adverse event occurred for 110 participants randomized to escitalopram (78.6%) and 21 participants randomized to MBSR (15.4%). Conclusions and relevance: The results from this randomized clinical trial comparing a standardized evidence-based mindfulness-based intervention with pharmacotherapy for the treatment of anxiety disorders found that MBSR was noninferior to escitalopram. Trial registration: ClinicalTrials.gov Identifier: NCT03522844.

JAMA psychiatry · randomised controlled trial · 97 citationsread the source →

The effectiveness of a home care program for supporting caregivers of persons with dementia in developing countries: a randomised controlled trial from Goa, India.

Objectives: To develop and evaluate the effectiveness of a home based intervention in reducing caregiver burden, promoting caregiver mental health and reducing behavioural problems in elderly persons with dementia. Methodology and principal findings: This was a randomised controlled trial in which the person with dementia-caregiver dyad was randomly allocated either to receive the intervention immediately or to a waiting list group which received the intervention after 6 months. It was carried out in communities based in two talukas (administrative blocks) in Goa, India. Mild to moderate cases with dementia (diagnosed using the DSM IV criteria and graded using the Clinical Dementia Rating scale) and their caregivers were included in the trial. Community based intervention provided by a team consisting of Home Care Advisors who were supervised by a counselor and a psychiatrist, focusing on supporting the caregiver through information on dementia, guidance on behaviour management, a single psychiatric assessment and psychotropic medication if needed. We measured caregiver mental health (General Health Questionnaire), caregiver burden (Zarit Burden Score), distress due to behavioural disturbances (NPI-D), behavioural problems in the subject (NPI-S) and activities of daily living in the elder with dementia (EASI). Outcome evaluations were masked to the allocation status. We analysed each outcome with a mixed effects model. 81 families enrolled in the trial; 41 were randomly allocated to the intervention. 59 completed the trial and 18 died during the trial. The intervention led to a significant reduction of GHQ (-1.12, 95% CI -2.07 to -0.17) and NPI-D scores (-1.96, 95%CI -3.51 to -0.41) and non-significant reductions in the ZBS, EASI and NPI-S scores. We also observed a non-significant reduction in the total number of deaths in people with dementia in the intervention arm (OR 0.34, 95% CI 0.01 to 1.03). Conclusion: Home based support for caregivers of persons with dementia, which emphasizes the use of locally available, low-cost human resources, is feasible, acceptable and leads to significant improvements in caregiver mental health and burden of caring. ClinicalTrials.gov NCT00479271.

PloS one · randomised controlled trial · 138 citationsread the source →

Physical activity, diet and other behavioural interventions for improving cognition and school achievement in children and adolescents with obesity or overweight.

Background: The global prevalence of childhood and adolescent obesity is high. Lifestyle changes towards a healthy diet, increased physical activity and reduced sedentary activities are recommended to prevent and treat obesity. Evidence suggests that changing these health behaviours can benefit cognitive function and school achievement in children and adolescents in general. There are various theoretical mechanisms that suggest that children and adolescents with excessive body fat may benefit particularly from these interventions. Objectives: To assess whether lifestyle interventions (in the areas of diet, physical activity, sedentary behaviour and behavioural therapy) improve school achievement, cognitive function (e.g. executive functions) and/or future success in children and adolescents with obesity or overweight, compared with standard care, waiting-list control, no treatment, or an attention placebo control group. Search methods: In February 2017, we searched CENTRAL, MEDLINE and 15 other databases. We also searched two trials registries, reference lists, and handsearched one journal from inception. We also contacted researchers in the field to obtain unpublished data. Selection criteria: We included randomised and quasi-randomised controlled trials (RCTs) of behavioural interventions for weight management in children and adolescents with obesity or overweight. We excluded studies in children and adolescents with medical conditions known to affect weight status, school achievement and cognitive function. We also excluded self- and parent-reported outcomes. Data collection and analysis: Four review authors independently selected studies for inclusion. Two review authors extracted data, assessed quality and risks of bias, and evaluated the quality of the evidence using the GRADE approach. We contacted study authors to obtain additional information. We used standard methodological procedures expected by Cochrane. Where the same outcome was assessed across different intervention types, we reported standardised effect sizes for findings from single-study and multiple-study analyses to allow comparison of intervention effects across intervention types. To ease interpretation of the effect size, we also reported the mean difference of effect sizes for single-study outcomes. Main results: We included 18 studies (59 records) of 2384 children and adolescents with obesity or overweight. Eight studies delivered physical activity interventions, seven studies combined physical activity programmes with healthy lifestyle education, and three studies delivered dietary interventions. We included five RCTs and 13 cluster-RCTs. The studies took place in 10 different countries. Two were carried out in children attending preschool, 11 were conducted in primary/elementary school-aged children, four studies were aimed at adolescents attending secondary/high school and one study included primary/elementary and secondary/high school-aged children. The number of studies included for each outcome was low, with up to only three studies per outcome. The quality of evidence ranged from high to very low and 17 studies had a high risk of bias for at least one item. None of the studies reported data on additional educational support needs and adverse events. Compared to standard practice, analyses of physical activity-only interventions suggested high-quality evidence for improved mean cognitive executive function scores. The mean difference (MD) was 5.00 scale points higher in an after-school exercise group compared to standard practice (95% confidence interval (CI) 0.68 to 9.32; scale mean 100, standard deviation 15; 116 children, 1 study). There was no statistically significant beneficial effect in favour of the intervention for mathematics, reading, or inhibition control. The standardised mean difference (SMD) for mathematics was 0.49 (95% CI -0.04 to 1.01; 2 studies, 255 children, moderate-quality evidence) and for reading was 0.10 (95% CI -0.30 to 0.49; 2 studies, 308 children, moderate-quality evidence). The MD for inhibition control was -1.55 scale points (95% CI -5.85 to 2.75; scale range 0 to 100; SMD -0.15, 95% CI -0.58 to 0.28; 1 study, 84 children, very low-quality evidence). No data were available for average achievement across subjects taught at school. There was no evidence of a beneficial effect of physical activity interventions combined with healthy lifestyle education on average achievement across subjects taught at school, mathematics achievement, reading achievement or inhibition control. The MD for average achievement across subjects taught at school was 6.37 points lower in the intervention group compared to standard practice (95% CI -36.83 to 24.09; scale mean 500, scale SD 70; SMD -0.18, 95% CI -0.93 to 0.58; 1 study, 31 children, low-quality evidence). The effect estimate for mathematics achievement was SMD 0.02 (95% CI -0.19 to 0.22; 3 studies, 384 children, very low-quality evidence), for reading achievement SMD 0.00 (95% CI -0.24 to 0.24; 2 studies, 284 children, low-quality evidence), and for inhibition control SMD -0.67 (95% CI -1.50 to 0.16; 2 studies, 110 children, very low-quality evidence). No data were available for the effect of combined physical activity and healthy lifestyle education on cognitive executive functions. There was a moderate difference in the average achievement across subjects taught at school favouring interventions targeting the improvement of the school food environment compared to standard practice in adolescents with obesity (SMD 0.46, 95% CI 0.25 to 0.66; 2 studies, 382 adolescents, low-quality evidence), but not with overweight. Replacing packed school lunch with a nutrient-rich diet in addition to nutrition education did not improve mathematics (MD -2.18, 95% CI -5.83 to 1.47; scale range 0 to 69; SMD -0.26, 95% CI -0.72 to 0.20; 1 study, 76 children, low-quality evidence) and reading achievement (MD 1.17, 95% CI -4.40 to 6.73; scale range 0 to 108; SMD 0.13, 95% CI -0.35 to 0.61; 1 study, 67 children, low-quality evidence). Authors' conclusions: Despite the large number of childhood and adolescent obesity treatment trials, we were only able to partially assess the impact of obesity treatment interventions on school achievement and cognitive abilities. School and community-based physical activity interventions as part of an obesity prevention or treatment programme can benefit executive functions of children with obesity or overweight specifically. Similarly, school-based dietary interventions may benefit general school achievement in children with obesity. These findings might assist health and education practitioners to make decisions related to promoting physical activity and healthy eating in schools. Future obesity treatment and prevention studies in clinical, school and community settings should consider assessing academic and cognitive as well as physical outcomes.

The Cochrane database of systematic reviews · meta-analysis · 69 citationsread the source →

Rare disease diagnosis: A review of web search, social media and large-scale data-mining approaches.

Physicians and the general public are increasingly using web-based tools to find answers to medical questions. The field of rare diseases is especially challenging and important as shown by the long delay and many mistakes associated with diagnoses. In this paper we review recent initiatives on the use of web search, social media and data mining in data repositories for medical diagnosis. We compare the retrieval accuracy on 56 rare disease cases with known diagnosis for the web search tools google.com, pubmed.gov, omim.org and our own search tool findzebra.com. We give a detailed description of IBM's Watson system and make a rough comparison between findzebra.com and Watson on subsets of the Doctor's dilemma dataset. The recall@10 and recall@20 (fraction of cases where the correct result appears in top 10 and top 20) for the 56 cases are found to be be 29%, 16%, 27% and 59% and 32%, 18%, 34% and 64%, respectively. Thus, FindZebra has a significantly (p < 0.01) higher recall than the other 3 search engines. When tested under the same conditions, Watson and FindZebra showed similar recall@10 accuracy. However, the tests were performed on different subsets of Doctors dilemma questions. Advances in technology and access to high quality data have opened new possibilities for aiding the diagnostic process. Specialized search engines, data mining tools and social media are some of the areas that hold promise.

Rare diseases (Austin, Tex.) · review · 49 citationsread the source →

Non-specialist psychosocial interventions for children and adolescents with intellectual disability or lower-functioning autism spectrum disorders: a systematic review.

Background: The development of effective treatments for use by non-specialists is listed among the top research priorities for improving the lives of people with mental illness worldwide. The purpose of this review is to appraise which interventions for children with intellectual disabilities or lower-functioning autism spectrum disorders delivered by non-specialist care providers in community settings produce benefits when compared to either a no-treatment control group or treatment-as-usual comparator. Methods and findings: We systematically searched electronic databases through 24 June 2013 to locate prospective controlled studies of psychosocial interventions delivered by non-specialist providers to children with intellectual disabilities or lower-functioning autism spectrum disorders. We screened 234 full papers, of which 34 articles describing 29 studies involving 1,305 participants were included. A majority of the studies included children exclusively with a diagnosis of lower-functioning autism spectrum disorders (15 of 29, 52%). Fifteen of twenty-nine studies (52%) were randomized controlled trials and just under half of all effect sizes (29 of 59, 49%) were greater than 0.50, of which 18 (62%) were statistically significant. For behavior analytic interventions, the best outcomes were shown for development and daily skills; cognitive rehabilitation, training, and support interventions were found to be most effective for improving developmental outcomes, and parent training interventions to be most effective for improving developmental, behavioral, and family outcomes. We also conducted additional subgroup analyses using harvest plots. Limitations include the studies' potential for performance bias and that few were conducted in lower- and middle-income countries. Conclusions: The findings of this review support the delivery of psychosocial interventions by non-specialist providers to children who have intellectual disabilities or lower-functioning autism spectrum disorders. Given the scarcity of specialists in many low-resource settings, including many lower- and middle-income countries, these findings may provide guidance for scale-up efforts for improving outcomes for children with developmental disorders or lower-functioning autism spectrum disorders. Protocol registration: PROSPERO CRD42012002641

PLoS medicine · systematic review · 80 citationsread the source →

Two-Year Clinical Results of Lateral Collagen Meniscus Implant: A Multicenter Study.

Purpose: To present the 2-year results of the use of the lateral Collagen Meniscus Implant (CMI) for the treatment of irreparable lateral meniscal lesions or partial lateral meniscal defects, to investigate the potential predictors of clinical results, and to monitor device safety. Methods: Forty-three patients with a mean age of 30.1 ± 12.0 years were clinically evaluated 24 months after treatment of partial lateral meniscal defects with the CMI (Ivy Sports Medicine, Gräfelfing, Germany). We used the Lysholm score, the Tegner Activity Scale, a visual analog scale for pain (during strenuous activity, during routine activity, and at rest), a functional questionnaire, and a satisfaction questionnaire for the evaluation. All demographic and surgical parameters were used for multiple regression analysis to find outcome predictors. Serious adverse events and reoperations were monitored. Results: All clinical scores significantly improved from preoperatively to final evaluation at 24.2 ± 1.9 months' follow-up. The Lysholm score improved significantly from 64.3 ± 18.4 preoperatively to 93.2 ± 7.2 at final follow-up (P = .0001). Functional improvement was detected from 6 months after surgery, whereas strenuous activities and knee swelling reached optimal results after 12 months. The highest pain ratings experienced during strenuous activity, during routine activity, and at rest significantly improved from 59 ± 29, 29 ± 25, and 20 ± 25, respectively, preoperatively to 14 ± 18, 3 ± 5, and 2 ± 6, respectively, at 2 years' follow-up (P = .0001). At final follow-up, 58% of patients reported activity levels similar to their preinjury values whereas 95% of patients reported that they were satisfied with the procedure. A higher body mass index, the presence of concomitant procedures, and a chronic injury pattern seemed to negatively affect the final outcomes. Serious adverse events with a known or unknown relation to the scaffold, such as pain, swelling, and scaffold resorption, were reported in 6% of patients, leading to CMI explantation, debridement, or synovectomy. Conclusions: The lateral CMI scaffold could be considered a potentially effective and safe procedure to treat both irreparable lateral meniscal tears and post-meniscectomy syndrome in appropriately selected patients. Chronic injury, high body mass index, and concomitant procedures have been shown to negatively affect the short-term results; however, the results appeared to slowly improve through the 24-month follow-up period. Thus patience is needed when evaluating the expectations for and results of the described procedure. Level of evidence: Level IV, therapeutic case series.

Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association · randomised controlled trial · 28 citationsread the source →

Pre-migration and post-migration factors associated with mental health in humanitarian migrants in Australia and the moderation effect of post-migration stressors: findings from the first wave data of the BNLA cohort study.

Background: The process of becoming a humanitarian migrant is potentially damaging to mental health. We examined the association between pre-migration and post-migration potentially traumatic events and stressors and mental health, and assessed the moderating effect of post-migration stressors in humanitarian migrants in Australia. Methods: In this study, we used the first wave of data between 2013 and 2014 from the Building a New Life in Australia survey. The survey included 2399 migrants who had arrived in Australia holding a permanent humanitarian visa 3-6 months preceding the survey, with 77% and 23% of participants being granted visas through offshore and onshore humanitarian programmes, respectively. Post-traumatic stress disorder (PTSD) was measured with the Post-traumatic Stress Disorder 8 items (PTSD-8) and severe mental illness was measured with the Kessler Screening Scale for Psychological Distress (K6). Pre-migration potentially traumatic events and post-migration stressors related to asylum process and resettlement were measured with a self-reported questionnaire. Findings: Of the 2399 participants, 762 (31%; 95% CI 29·4-33·2) had PTSD and 394 (16%; 95% CI 14·2-17·2) had severe mental illness. The mean number of pre-migration potentially traumatic events was 2·1 (SD 1·4). 64%, 59%, 49%, and 18% of participants reported poor social integration, economic problems, worrying about family or friends overseas, and loneliness as post-migration stressors. Pre-migration potentially traumatic events and post-migration stressors were positively associated with PTSD and severe mental illness. Factors significantly modifying the association between pre-migration potentially traumatic events and mental health after controlling for confounding factors were resettlement related stressors, including loneliness (odds ratio 1·17, 95% CI 1·05-1·28 for PTSD and 1·28, 1·16-1·41 for severe mental illness) and the number of social integration stressors (1·10, 1·05-1·16 for PTSD). Interpretation: Our data suggest that post-migration resettlement-related stressors were the most important correlates of mental health in humanitarian migrants, accounting for both direct and indirect associations. Targeting resettlement-related stressors through augmenting psychosocial care programmes and social integration would be a key approach to improve humanitarian migrants' mental health. Funding: None.

The lancet. Psychiatry · 192 citationsread the source →

Out-of-home placement in early childhood and psychiatric diagnoses and criminal convictions in young adulthood: a population-based propensity score-matched study.

Background: To ensure their protection and healthy development, children exposed to adverse family circumstances might be placed in foster homes, institutions, or kinship care (out-of-home placement). We aimed to compare the rates of psychiatric diagnoses and criminal convictions in young adulthood (ages 18-25 years) among children who were first placed at ages 2-6 years with those of children who were not placed and who had similar sociodemographic and family characteristics. Method: We did a population-wide cohort study using the 1987 Finnish Birth Cohort, which collects longitudinal data linking nationwide child welfare, medical, and criminal registers for all 59 476 livebirths in Finland in 1987. The exposure was the first out-of-home placement at ages 2-6 years. Outcomes were rates of psychiatric diagnoses, criminal convictions, and prescriptions for psychotropic medication filled at ages 18-25 years. We matched cases to non-placed controls using propensity score matching on parental characteristics (eg, age, psychiatric diagnoses, education, family structure) and child characteristics (eg, neurodevelopmental problems, prematurity). Differences in adult outcomes between children placed and matched controls were assessed by use of logistic regression on the matched cohort. Findings: Of 54 814 individuals with complete data, 388 (1%) were first placed at ages 2-6 years; matched controls were identified for 386 of these children. At ages 18-25 years, those who had been placed as children had greater odds than never-placed controls of substance-related disorders (odds ratio 2·10, 95% CI 1·27-3·48), psychotic or bipolar disorders (3·98, 1·80-8·80), depression or anxiety (2·15, 1·46-3·18), neurodevelopmental disorders (3·59, 1·17-11·02), or other disorders (2·06, 1·25-3·39). Participants who were placed had more psychotropic medication prescriptions (1·96, 1·38-2·80) and higher rates of criminal convictions (violent offences, 2·43, 1·61-3·68; property offences, 1·86, 1·17-2·97). Interpretation: Preschool children who are placed out-of-home are at risk of adverse outcomes as adults, even accounting for their initial circumstances. It is important to explore which conditions lead to more or less favourable outcomes in child protection. Funding: Academy of Finland.

The Lancet. Child & adolescent health · 18 citationsread the source →

Sleeping when the world locks down: Correlates of sleep health during the COVID-19 pandemic across 59 countries.

Objectives: COVID-19 escalated into a global pandemic affecting countries around the world. As communities shut down to reduce disease spread, all aspects of life have been altered, including sleep. This study investigated changes in sleep patterns and correlates of sleep health in a global sample and examined relationships between sleep health and psychological distress. Design: Cross-sectional. Settings: Online survey distributed between April 19 and May 3, 2020. Participants: Total 6882 participants (18-94 years) across 59 countries. Measurements: Sleep health (RU-SATED), demographics, pandemic-related factors, mood. Results: More than half the sample shifted their sleep toward later bed- and wake-times, and more than a third reported increased sleep disturbances during the pandemic. Older age, being partnered, and living in a higher income country were associated with better sleep health, while a stricter level of quarantine and pandemic-related factors (being laid off from job, financial strain, or difficulties transitioning to working from home) were associated with poorer sleep health. Domestic conflict was the strongest correlate of poorer sleep health. Poorer sleep health was strongly associated with greater depression and anxiety symptoms. Participants from Latin America reported the lowest sleep health scores. Conclusions: COVID-19-associated factors have impacted sleep health on a global level. While our data are correlational, sleep health is strongly linked with mental health and could play a protective role against developing mental distress during pandemic-related isolation. Sleep health should be incorporated into public health messages aimed at helping people cope with the effects of a pandemic to maintain optimal mental and physical health.

Sleep health · 95 citationsread the source →

Divorce among physicians and other healthcare professionals in the United States: analysis of census survey data.

Objectives: To estimate the prevalence and incidence of divorce among US physicians compared with other healthcare professionals, lawyers, and non-healthcare professionals, and to analyze factors associated with divorce among physicians. Design: Retrospective analysis of nationally representative surveys conducted by the US census, 2008-13. Setting: United States. Participants: 48,881 physicians, 10,086 dentists, 13,883 pharmacists, 159,044 nurses, 18,920 healthcare executives, 59,284 lawyers, and 6,339,310 other non-healthcare professionals. Main outcome measures: Logistic models of divorce adjusted for age, sex, race, annual income, weekly hours worked, number of years since marriage, calendar year, and state of residence. Divorce outcomes included whether an individual had ever been divorced (divorce prevalence) or became divorced in the past year (divorce incidence). Results: After adjustment for covariates, the probability of being ever divorced (or divorce prevalence) among physicians evaluated at the mean value of other covariates was 24.3% (95% confidence interval 23.8% to 24.8%); dentists, 25.2% (24.1% to 26.3%); pharmacists, 22.9% (22.0% to 23.8%); nurses, 33.0% (32.6% to 33.3%); healthcare executives, 30.9% (30.1% to 31.8%); lawyers, 26.9% (26.4% to 27.4%); and other non-healthcare professionals, 35.0% (34.9% to 35.1%). Similarly, physicians were less likely than those in most other occupations to divorce in the past year. In multivariable analysis among physicians, divorce prevalence was greater among women (odds ratio 1.51, 95% confidence interval 1.40 to 1.63). In analyses stratified by physician sex, greater weekly work hours were associated with increased divorce prevalence only for female physicians. Conclusions: Divorce among physicians is less common than among non-healthcare workers and several health professions. Female physicians have a substantially higher prevalence of divorce than male physicians, which may be partly attributable to a differential effect of hours worked on divorce.

BMJ (Clinical research ed.) · 35 citationsread the source →

Psychological and Psychosomatic Symptoms of Second Victims of Adverse Events: a Systematic Review and Meta-Analysis.

Objectives: Despite growing interest in the second-victim phenomenon and greater awareness of its consequences, there has not been a meta-analysis quantifying the negative impact of adverse events on providers involved in adverse events. This study systematically reviewed the types and prevalence of psychological and psychosomatic symptoms among second victims. Methods: We conducted a systematic review of nine electronic databases up to February 2017, without restrictions to publication date or language, examining also additional sources (e.g., gray literature, volumes of journals). Two reviewers performed the search, selection process, quality assessment, data extraction, and synthesis. We resolved disagreements by consensus and/or involving a third reviewer. Quantitative studies on the prevalence of psychological and psychosomatic symptoms of second victims were eligible for inclusion. We used random effects modeling to calculate the overall prevalence rates and the I statistic. Results: Of 7210 records retrieved, 98 potentially relevant studies were identified. Full-text evaluation led to a final selection of 18 studies, based on the reports of 11,649 healthcare providers involved in adverse events. The most prevalent symptoms were troubling memories (81%, 95% confidence interval [CI] = 46-95), anxiety/concern (76%, 95% CI = 33-95), anger toward themselves (75%, 95% CI = 59-86), regret/remorse (72%, 95% CI = 62-81), distress (70%, 95% CI = 60-79), fear of future errors (56%, 95% CI = 34-75), embarrassment (52%, 95% CI = 31-72), guilt (51%, 95% CI = 41-62), and sleeping difficulties (35%, 95% CI = 22-51). Conclusions: Second victims report a high prevalence and wide range of psychological symptoms. More than two-thirds of providers reported troubling memories, anxiety, anger, remorse, and distress. Preventive and therapeutic programs should aim to decrease second victims' emotional distress.

Journal of patient safety · meta-analysis · 134 citationsread the source →

Mindfulness-based interventions for weight loss: a systematic review and meta-analysis.

Background: An increasing number of studies are investigating the efficacy of mindfulness-based interventions (MBIs) for weight loss and obesity-related eating behaviours. However, the results of past reviews are inconsistent. Objective: To clarify these inconsistencies, we conducted a comprehensive effect-size analysis to evaluate the efficacy of MBIs on weight loss and eating behaviours. Data source: Data sources were identified through a systematic review of studies published in journals or as dissertations in PsychINFO, PubMed, CINAHL, Web of Science, Medline and Scopus, ProQuest or OATD from the first available date to March 10, 2017. Review methods: A total of 18 publications (19 studies, n = 1,160) were included. Results: Mean weight loss for MBIs at post-treatment was 6.8 and 7.5 lb at follow-up. In pre-post comparisons, effect-size estimates suggest that MBIs are moderately effective for weight loss (n = 16; Hedge's g = .42; 95% CI [.26, .59], p < .000001) and largely effective in reducing obesity-related eating behaviours (n = 10; Hedge's g = .70; CI 95% [.36, 1.04], p < .00005). Larger effects on weight loss were found in studies that used a combination of informal and formal meditation practice (n = 6; Hedge's g = .55; CI 95% [.32, .77], p < .00001) compared with formal meditation practice alone (n = 4; Hedge's g = .46; CI [.10, .83], p < .05). Conclusion: Results suggest that MBIs are effective in reducing weight and improving obesity-related eating behaviours among individuals with overweight and obesity. Further research is needed to examine their efficacy for weight loss maintenance.

Obesity reviews : an official journal of the International Association for the Study of Obesity · meta-analysis · 118 citationsread the source →

Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: a systematic review and meta-analysis.

Background: Medicinal cannabinoids, including medicinal cannabis and pharmaceutical cannabinoids and their synthetic derivatives, such as tetrahydrocannabinol (THC) and cannabidiol (CBD), have been suggested to have a therapeutic role in certain mental disorders. We analysed the available evidence to ascertain the effectiveness and safety of all types of medicinal cannabinoids in treating symptoms of various mental disorders. Methods: For this systematic review and meta-analysis we searched MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Clinical Trials, and the Cochrane Database of Systematic Reviews for studies published between Jan 1, 1980, and April 30, 2018. We also searched for unpublished or ongoing studies on ClinicalTrials.gov, the EU Clinical Trials Register, and the Australian and New Zealand Clinical Trials Registry. We considered all studies examining any type and formulation of a medicinal cannabinoid in adults (≥18 years) for treating depression, anxiety, attention-deficit hyperactivity disorder (ADHD), Tourette syndrome, post-traumatic stress disorder, or psychosis, either as the primary condition or secondary to other medical conditions. We placed no restrictions on language, publication status, or study type (ie, both experimental and observational study designs were included). Primary outcomes were remission from and changes in symptoms of these mental disorders. The safety of medicinal cannabinoids for these mental disorders was also examined. Evidence from randomised controlled trials was synthesised as odds ratios (ORs) for disorder remission, adverse events, and withdrawals and as standardised mean differences (SMDs) for change in symptoms, via random-effects meta-analyses. The quality of the evidence was assessed with the Cochrane risk of bias tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. This study is registered with PROSPERO (CRD42017059372, CRD42017059373, CRD42017059376, CRD42017064996, and CRD42018102977). Findings: 83 eligible studies (40 randomised controlled trials, n=3067) were included: 42 for depression (23 randomised controlled trials; n=2551), 31 for anxiety (17 randomised controlled trials; n=605), eight for Tourette syndrome (two randomised controlled trials; n=36), three for ADHD (one randomised controlled trial; n=30), 12 for post-traumatic stress disorder (one randomised controlled trial; n=10), and 11 for psychosis (six randomised controlled trials; n=281). Pharmaceutical THC (with or without CBD) improved anxiety symptoms among individuals with other medical conditions (primarily chronic non-cancer pain and multiple sclerosis; SMD -0·25 [95% CI -0·49 to -0·01]; seven studies; n=252), although the evidence GRADE was very low. Pharmaceutical THC (with or without CBD) worsened negative symptoms of psychosis in a single study (SMD 0·36 [95% CI 0·10 to 0·62]; n=24). Pharmaceutical THC (with or without CBD) did not significantly affect any other primary outcomes for the mental disorders examined but did increase the number of people who had adverse events (OR 1·99 [95% CI 1·20 to 3·29]; ten studies; n=1495) and withdrawals due to adverse events (2·78 [1·59 to 4·86]; 11 studies; n=1621) compared with placebo across all mental disorders examined. Few randomised controlled trials examined the role of pharmaceutical CBD or medicinal cannabis. Interpretation: There is scarce evidence to suggest that cannabinoids improve depressive disorders and symptoms, anxiety disorders, attention-deficit hyperactivity disorder, Tourette syndrome, post-traumatic stress disorder, or psychosis. There is very low quality evidence that pharmaceutical THC (with or without CBD) leads to a small improvement in symptoms of anxiety among individuals with other medical conditions. There remains insufficient evidence to provide guidance on the use of cannabinoids for treating mental disorders within a regulatory framework. Further high-quality studies directly examining the effect of cannabinoids on treating mental disorders are needed. Funding: Therapeutic Goods Administration, Australia; Commonwealth Department of Health, Australia; Australian National Health and Medical Research Council; and US National Institutes of Health.

The lancet. Psychiatry · meta-analysis · 309 citationsread the source →

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 →

Diet, physical activity, and behavioural interventions for the treatment of overweight or obesity in preschool children up to the age of 6 years.

Background: Child overweight and obesity has increased globally, and can be associated with short- and long-term health consequences. Objectives: To assess the effects of diet, physical activity, and behavioural interventions for the treatment of overweight or obesity in preschool children up to the age of 6 years. Search methods: We performed a systematic literature search in the databases Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, and LILACS, as well as in the trial registers ClinicalTrials.gov and ICTRP Search Portal. We also checked references of identified trials and systematic reviews. We applied no language restrictions. The date of the last search was March 2015 for all databases. Selection criteria: We selected randomised controlled trials (RCTs) of diet, physical activity, and behavioural interventions for treating overweight or obesity in preschool children aged 0 to 6 years. Data collection and analysis: Two review authors independently assessed risk of bias, evaluated the overall quality of the evidence using the GRADE instrument, and extracted data following the Cochrane Handbook for Systematic Reviews of Interventions. We contacted trial authors for additional information. Main results: We included 7 RCTs with a total of 923 participants: 529 randomised to an intervention and 394 to a comparator. The number of participants per trial ranged from 18 to 475. Six trials were parallel RCTs, and one was a cluster RCT. Two trials were three-arm trials, each comparing two interventions with a control group. The interventions and comparators in the trials varied. We categorised the comparisons into two groups: multicomponent interventions and dietary interventions. The overall quality of the evidence was low or very low, and six trials had a high risk of bias on individual 'Risk of bias' criteria. The children in the included trials were followed up for between six months and three years. In trials comparing a multicomponent intervention with usual care, enhanced usual care, or information control, we found a greater reduction in body mass index (BMI) z score in the intervention groups at the end of the intervention (6 to 12 months): mean difference (MD) -0.3 units (95% confidence interval (CI) -0.4 to -0.2); P < 0.00001; 210 participants; 4 trials; low-quality evidence, at 12 to 18 months' follow-up: MD -0.4 units (95% CI -0.6 to -0.2); P = 0.0001; 202 participants; 4 trials; low-quality evidence, and at 2 years' follow-up: MD -0.3 units (95% CI -0.4 to -0.1); 96 participants; 1 trial; low-quality evidence. One trial stated that no adverse events were reported; the other trials did not report on adverse events. Three trials reported health-related quality of life and found improvements in some, but not all, aspects. Other outcomes, such as behaviour change and parent-child relationship, were inconsistently measured. One three-arm trial of very low-quality evidence comparing two types of diet with control found that both the dairy-rich diet (BMI z score change MD -0.1 units (95% CI -0.11 to -0.09); P < 0.0001; 59 participants) and energy-restricted diet (BMI z score change MD -0.1 units (95% CI -0.11 to -0.09); P < 0.0001; 57 participants) resulted in greater reduction in BMI than the comparator at the end of the intervention period, but only the dairy-rich diet maintained this at 36 months' follow-up (BMI z score change in MD -0.7 units (95% CI -0.71 to -0.69); P < 0.0001; 52 participants). The energy-restricted diet had a worse BMI outcome than control at this follow-up (BMI z score change MD 0.1 units (95% CI 0.09 to 0.11); P < 0.0001; 47 participants). There was no substantial difference in mean daily energy expenditure between groups. Health-related quality of life, adverse effects, participant views, and parenting were not measured. No trial reported on all-cause mortality, morbidity, or socioeconomic effects. All results should be interpreted cautiously due to their low quality and heterogeneous interventions and comparators. Authors' conclusions: Muticomponent interventions appear to be an effective treatment option for overweight or obese preschool children up to the age of 6 years. However, the current evidence is limited, and most trials had a high risk of bias. Most trials did not measure adverse events. We have identified four ongoing trials that we will include in future updates of this review. The role of dietary interventions is more equivocal, with one trial suggesting that dairy interventions may be effective in the longer term, but not energy-restricted diets. This trial also had a high risk of bias.

The Cochrane database of systematic reviews · meta-analysis · 119 citationsread the source →

Psychological therapies for the management of chronic pain (excluding headache) in adults.

Background: Chronic non-cancer pain, a disabling and distressing condition, is common in adults. It is a global public health problem and economic burden on health and social care systems and on people with chronic pain. Psychological treatments aim to reduce pain, disability and distress. This review updates and extends its previous version, published in 2012. Objectives: To determine the clinical efficacy and safety of psychological interventions for chronic pain in adults (age > 18 years) compared with active controls, or waiting list/treatment as usual (TAU). Search methods: We identified randomised controlled trials (RCTs) of psychological therapies by searching CENTRAL, MEDLINE, Embase and PsycINFO to 16 April 2020. We also examined reference lists and trial registries, and searched for studies citing retrieved trials. Selection criteria: RCTs of psychological treatments compared with active control or TAU of face-to-face therapies for adults with chronic pain. We excluded studies of headache or malignant disease, and those with fewer than 20 participants in any arm at treatment end. Data collection and analysis: Two or more authors rated risk of bias, extracted data, and judged quality of evidence (GRADE). We compared cognitive behavioural therapy (CBT), behavioural therapy (BT), and acceptance and commitment therapy (ACT) with active control or TAU at treatment end, and at six month to 12 month follow-up. We did not analyse the few trials of other psychological treatments. We assessed treatment effectiveness for pain intensity, disability, and distress. We extracted data on adverse events (AEs) associated with treatment. Main results: We added 41 studies (6255 participants) to 34 of the previous review's 42 studies, and now have 75 studies in total (9401 participants at treatment end). Most participants had fibromyalgia, chronic low back pain, rheumatoid arthritis, or mixed chronic pain. Most risk of bias domains were at high or unclear risk of bias, with selective reporting and treatment expectations mostly at unclear risk of bias. AEs were inadequately recorded and/or reported across studies. CBT The largest evidence base was for CBT (59 studies). CBT versus active control showed very small benefit at treatment end for pain (standardised mean difference (SMD) -0.09, 95% confidence interval (CI) -0.17 to -0.01; 3235 participants; 23 studies; moderate-quality evidence), disability (SMD -0.12, 95% CI -0.20 to -0.04; 2543 participants; 19 studies; moderate-quality evidence), and distress (SMD -0.09, 95% CI -0.18 to -0.00; 3297 participants; 24 studies; moderate-quality evidence). We found small benefits for CBT over TAU at treatment end for pain (SMD -0.22, 95% CI -0.33 to -0.10; 2572 participants; 29 studies; moderate-quality evidence), disability (SMD -0.32, 95% CI -0.45 to -0.19; 2524 participants; 28 studies; low-quality evidence), and distress (SMD -0.34, 95% CI -0.44 to -0.24; 2559 participants; 27 studies; moderate-quality evidence). Effects were largely maintained at follow-up for CBT versus TAU, but not for CBT versus active control. Evidence quality for CBT outcomes ranged from moderate to low. We rated evidence for AEs as very low quality for both comparisons. BT We analysed eight studies (647 participants). We found no evidence of difference between BT and active control at treatment end (pain SMD -0.67, 95% CI -2.54 to 1.20, very low-quality evidence; disability SMD -0.65, 95% CI -1.85 to 0.54, very low-quality evidence; or distress SMD -0.73, 95% CI -1.47 to 0.01, very low-quality evidence). At follow-up, effects were similar. We found no evidence of difference between BT and TAU (pain SMD -0.08, 95% CI -0.33 to 0.17, low-quality evidence; disability SMD -0.02, 95% CI -0.24 to 0.19, moderate-quality evidence; distress SMD 0.22, 95% CI -0.10 to 0.54, low-quality evidence) at treatment end. At follow-up, we found one to three studies with no evidence of difference between BT and TAU. We rated evidence for all BT versus active control outcomes as very low quality; for BT versus TAU. Evidence quality ranged from moderate to very low. We rated evidence for AEs as very low quality for BT versus active control. No studies of BT versus TAU reported AEs. ACT We analysed five studies (443 participants). There was no evidence of difference between ACT and active control for pain (SMD -0.54, 95% CI -1.20 to 0.11, very low-quality evidence), disability (SMD -1.51, 95% CI -3.05 to 0.03, very low-quality evidence) or distress (SMD -0.61, 95% CI -1.30 to 0.07, very low-quality evidence) at treatment end. At follow-up, there was no evidence of effect for pain or distress (both very low-quality evidence), but two studies showed a large benefit for reducing disability (SMD -2.56, 95% CI -4.22 to -0.89, very low-quality evidence). Two studies compared ACT to TAU at treatment end. Results should be interpreted with caution. We found large benefits of ACT for pain (SMD -0.83, 95% CI -1.57 to -0.09, very low-quality evidence), but none for disability (SMD -1.39, 95% CI -3.20 to 0.41, very low-quality evidence), or distress (SMD -1.16, 95% CI -2.51 to 0.20, very low-quality evidence). Lack of data precluded analysis at follow-up. We rated evidence quality for AEs to be very low. We encourage caution when interpreting very low-quality evidence because the estimates are uncertain and could be easily overturned. Authors' conclusions: We found sufficient evidence across a large evidence base (59 studies, over 5000 participants) that CBT has small or very small beneficial effects for reducing pain, disability, and distress in chronic pain, but we found insufficient evidence to assess AEs. Quality of evidence for CBT was mostly moderate, except for disability, which we rated as low quality. Further trials may provide more precise estimates of treatment effects, but to inform improvements, research should explore sources of variation in treatment effects. Evidence from trials of BT and ACT was of moderate to very low quality, so we are very uncertain about benefits or lack of benefits of these treatments for adults with chronic pain; other treatments were not analysed. These conclusions are similar to our 2012 review, apart from the separate analysis of ACT.

The Cochrane database of systematic reviews · meta-analysis · 349 citationsread the source →

Sociodemographic and Clinical Characteristics of Patients attending Psychotherapy in a Tertiary Care Hospital in Oman.

Objectives: There is significant evidence that psychotherapy is a pivotal treatment for persons diagnosed with Axis I clinical psychiatric conditions; however, a psychotherapy service has only recently been established in the Omani health care system. This study aimed to investigate the sociodemographic and clinical characteristics of attendees at a psychotherapy clinic at a tertiary care hospital. Methods: An analysis was carried out of 133 new referrals to the Psychotherapy Service at Sultan Qaboos University Hospital, a tertiary care hospital. Results: The majority of referrals were females (59%), aged 18-34 years, employed (38%), had ≤12 years of formal education (51%), and were single (54%). A total of 43% were treated for anxiety disorders (including obsessive compulsive disorder), while 22% were treated for depression. A total of 65% were prescribed psychotropic medications. The utilisation of the Psychotherapy Service and its user characteristics are discussed within the context of a culturally diverse Omani community which has unique personal belief systems such as in supernatural powers (Jinn), contemptuous envy (Hassad), evil eye (Ain) and sorcery (Sihr) which are often used to explain the aetiology of mental illness and influence personal decisions on utilising medical and psychological treatments. Conclusion: Despite the low number of referrals to the Psychotherapy Service, there is reason to believe that psychotherapy would be an essential tool to come to grips with the increasing number of mental disorders in Oman.

Sultan Qaboos University medical journal · 3 citationsread the source →

Organisational interventions for improving wellbeing and reducing work-related stress in teachers.

Background: The teaching profession is an occupation with a high prevalence of work-related stress. This may lead to sustained physical and mental health problems in teachers. It can also negatively affect the health, wellbeing and educational attainment of children, and impose a financial burden on the public budget in terms of teacher turnover and sickness absence. Most evaluated interventions for the wellbeing of teachers are directed at the individual level, and so do not tackle the causes of stress in the workplace. Organisational-level interventions are a potential avenue in this regard. Objectives: To evaluate the effectiveness of organisational interventions for improving wellbeing and reducing work-related stress in teachers. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, ASSIA, AEI, BEI, BiblioMap, DARE, DER, ERIC, IBSS, SSCI, Sociological Abstracts, a number of specialist occupational health databases, and a number of trial registers and grey literature sources from the inception of each database until January 2015. Selection criteria: Randomised controlled trials (RCTs), cluster-RCTs, and controlled before-and-after studies of organisational-level interventions for the wellbeing of teachers. Data collection and analysis: We used standard methodological procedures expected by Cochrane. Main results: Four studies met the inclusion criteria. They were three cluster-randomised controlled trials and one with a stepped-wedge design. Changing task characteristicsOne study with 961 teachers in eight schools compared a task-based organisational change intervention along with stress management training to no intervention. It found a small reduction at 12 months in 10 out of 14 of the subscales in the Occupational Stress Inventory, with a mean difference (MD) varying from -3.84 to 0.13, and a small increase in the Work Ability Index (MD 2.27; 95% confidence interval (CI) 1.64 to 2.90; 708 participants, low-quality evidence).Changing organisational characteristicsTwo studies compared teacher training combined with school-wide coaching support to no intervention. One study with 59 teachers in 43 schools found no significant effects on job-related anxiety (MD -0.25 95% CI -0.61 to 0.11, very low-quality evidence) or depression (MD -0.26 95% CI -0.57 to 0.05, very low-quality evidence) after 24 months. The other study with 77 teachers in 18 schools found no significant effects on the Maslach Burnout Inventory subscales (e.g. emotional exhaustion subscale: MD -0.05 95% CI -0.52 to 0.42, low-quality evidence) or the Teacher Perceived Emotional Ability subscales (e.g. regulating emotions subscale: MD 0.11 95% CI -0.11 to 0.33, low-quality evidence) after six months. Multi-component interventionOne study with 1102 teachers in 34 schools compared a multi-component intervention containing performance bonus, job promotion opportunities and mentoring support to a matched-comparison group consisting of 300 schools. It found moderately higher teacher retention rates (MD 11.50 95% CI 3.25 to 19.75 at 36 months follow-up, very low-quality evidence). However, the authors reported results only from one cohort out of four (eight schools), demonstrating a high risk of reporting bias. Authors' conclusions: We found low-quality evidence that organisational interventions lead to improvements in teacher wellbeing and retention rates. We need further evaluation of the effects of organisational interventions for teacher wellbeing. These studies should follow a complex-interventions framework, use a cluster-randomised design and have large sample sizes.

The Cochrane database of systematic reviews · systematic review · 75 citationsread the source →

The effectiveness of smoking cessation, physical activity/diet and alcohol reduction interventions delivered by mobile phones for the prevention of non-communicable diseases: A systematic review of randomised controlled trials.

Background: We conducted a systematic review to assess the effectiveness of smoking cessation, physical activity (PA), diet, and alcohol reduction interventions delivered by mobile technology to prevent non-communicable diseases (NCDs). Methods: We searched for randomised controlled trials (RCTs) of mobile-based NCD prevention interventions using MEDLINE, EMBASE, Global Health, CINAHL (Jan 1990-Jan 2016). Two authors extracted data. Findings: 71 trials were included: smoking cessation (n = 18); PA (n = 15), diet (n = 3), PA and diet (n = 25); PA, diet, and smoking cessation (n = 2); and harmful alcohol consumption (n = 8). 4 trials had low risk of bias. The effect of SMS-based smoking cessation support on biochemically verified continuous abstinence was pooled relative risk [RR] 2.19 [95% CI 1.80-2.68], I2 = 0%) and on verified 7 day point prevalence of smoking cessation was pooled RR 1.51 [95% CI 1.06-2.15], I2 = 0%, with no reported adverse events. There was no difference in peak oxygen intake at 3 months in a trial of an SMS-based PA intervention. The effect of SMS-based diet and PA interventions on: incidence of diabetes was pooled RR 0.67 [95% CI 0.49, 0.90], I2 = 0.0%; end-point weight was pooled MD -0.99Kg [95% CI -3.63, 1.64] I2 = 29.4%; % change in weight was pooled MD -3.1 [95%CI -4.86- -1.3] I2 0.3%; and on triglyceride levels was pooled MD -0.19 mmol/L [95% CI -0.29, -0.08], I2 = 0.0%. The results of other pooled analyses of the effect of SMS-based diet and PA interventions were heterogenous (I2 59-90%). The effects of alcohol reduction interventions were inconclusive. Conclusions: Smoking cessation support delivered by SMS increases quitting rates. Trials of PA interventions reporting outcomes ≥3 months showed no benefits. There were at best modest benefits of diet and PA interventions. The effects of the most promising SMS-based smoking, diet and PA interventions on morbidity and mortality in high-risk groups should be established in adequately powered RCTs.

PloS one · systematic review · 69 citationsread the source →

Treatment-related changes in bone mineral density as a surrogate biomarker for fracture risk reduction: meta-regression analyses of individual patient data from multiple randomised controlled trials.

Background: The validation of bone mineral density (BMD) as a surrogate outcome for fracture would allow the size of future randomised controlled osteoporosis registration trials to be reduced. We aimed to determine the association between treatment-related changes in BMD, assessed by dual-energy x-ray absorptiometry, and fracture outcomes, including the proportion of treatment effect explained by BMD changes. Methods: We did a pooled analysis of individual patient data from multiple randomised placebo-controlled clinical trials. We included data from multicentre, randomised, placebo-controlled, double-blind trials of osteoporosis medications that included women and men at increased osteoporotic fracture risk. Using individual patient data for each trial we calculated mean 24-month BMD percent change together with fracture reductions and did a meta-regression of the association between treatment-related differences in BMD changes (percentage difference, active minus placebo) and fracture risk reduction. We also used individual patient data to determine the proportion of anti-fracture treatment effect explained by BMD changes and the BMD change needed in future trials to ensure fracture reduction efficacy. Findings: Individual patient data from 91 779 participants of 23 randomised, placebo-controlled trials were included. The trials had 1-9 years of follow-up and included 12 trials of bisphosphonate, one of odanacatib, two of hormone therapy (one of conjugated equine oestrogen and one of conjugated equine oestrogen plus medroxyprogesterone acetate), three of PTH receptor agonists, one of denosumab, and four of selective oestrogen receptor modulator trials. The meta-regression revealed significant associations between treatment-related changes in hip, femoral neck, and spine BMD and reductions in vertebral (r2 0·73, p<0·0001; 0·59, p=0·0005; 0·61, p=0·0003), hip (0·41, p=0·014; 0·41, p=0·0074; 0·34, p=0·023) and non-vertebral fractures (0·53, p=0·0021; 0·65, p<0·0001; 0·51, p=0·0019). Minimum 24-month percentage changes in total hip BMD providing almost certain fracture reductions in future trials ranged from 1·42% to 3·18%, depending on fracture site. Hip BMD changes explained substantial proportions (44-67%) of treatment-related fracture risk reduction. Interpretation: Treatment-related BMD changes are strongly associated with fracture reductions across randomised trials of osteoporosis therapies with differing mechanisms of action. These analyses support BMD as a surrogate outcome for fracture outcomes in future randomised trials of new osteoporosis therapies and provide an important demonstration of the value of public access to individual patient data from multiple trials. Funding: Foundation for National Institutes of Health.

The lancet. Diabetes & endocrinology · systematic review · 165 citationsread the source →

Clinician-led, peer-led, and internet-delivered dissonance-based eating disorder prevention programs: Effectiveness of these delivery modalities through 4-year follow-up.

Objective: Independent trials have found that the dissonance-based Body Project eating disorder prevention program is efficacious and effective; the present trial provided the first test of whether delivery could be task-shifted from clinician-delivery to peer educator-delivery or Internet-delivery without loss of effectiveness through 4-year follow-up. Method: Young women at high-risk for eating disorders because of body image concerns (N = 680, Mage = 22.2) recruited at 3 colleges were randomized to clinician-led Body Project groups, peer-led Body Project groups, the Internet-based eBody Project, or educational video control. Results: Participants in clinician- and peer-led Body Project groups and the eBody Project generally showed larger reductions in risk factors and eating disorder symptoms versus controls through 1- and 2-year follow-up (d = .16-.59), with some effects persisting through 3- and 4-year follow-ups (d = .28-.58). Peer-led Body Project participants showed greater reductions in some risk factors than eBody Project participants (d = .18-.19), but no other contrasts between Body Project interventions differed. Eating disorder onset over 4-year follow-up was significantly lower for peer-led Body Project participants (8.1%) than control participants (17.6%) and clinician-led Body Project participants (19.3%), and marginally lower than eBody Project participants (15.5%). Conclusions: The evidence that all three Body Project interventions outperformed educational video controls, peer-led groups outperformed the Internet-based intervention, and peer-led groups showed lower eating disorder onset over 4-year follow-up than the other conditions are novel. Results imply that it might be optimal to task-shift Body Project delivery to peer-leaders to address implementation barriers associated with clinician-led delivery. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Journal of consulting and clinical psychology · randomised controlled trial · 68 citationsread the source →

Effects of a parenting intervention to address maternal psychological wellbeing and child development and growth in rural Uganda: a community-based, cluster randomised trial.

Background: Parenting interventions have been implemented to improve the compromised developmental potential among 39% of children younger than 5 years living in low-income and middle-income countries. Maternal wellbeing is important for child development, especially in children younger than 3 years who are vulnerable and dependent on their mothers for nutrition and stimulation. We assessed an integrated, community-based parenting intervention that targeted both child development and maternal wellbeing in rural Uganda. Methods: In this community-based, cluster randomised trial, we assessed the effectiveness of a manualised, parenting intervention in Lira, Uganda. We selected and randomly assigned 12 parishes (1:1) to either parenting intervention or control (inclusion on a waitlist with a brief message on nutrition) groups using a computer-generated list of random numbers. Within each parish, we selected two to three eligible communities that had a parish office or a primary school in which a preschool could be established, more than 75 households with children younger than 6 years, and at least 15 socially disadvantaged families (ie, maternal education of primary school level or lower) with at least one child younger than 36 months. Participants within communities were mother-child dyads, where the child was 12-36 months of age at enrollment, and the mother had low maternal education. In the parenting intervention group, participants attended 12 fortnightly peer-led group sessions focusing on child care and maternal wellbeing. The primary outcomes were cognitive and receptive language development, as measured with the Bayley Scales of Infant Development, 3rd edn. Secondary outcomes included self-reported maternal depressive symptoms, using the Center for Epidemiologic Studies Depression Scale, and child growth. Theoretically-relevant parenting practices, including the Home Observation for Measurement of the Environment inventory, and mother-care variables, such as perceived spousal support, were also assessed as potential mediators. Baseline assessments were done in January, 2013, and endline assessments were done in November, 2013, 3 months after completion of the programme. Ethics approval was received from Mbarara and McGill universities. This trial is registered with ClinicalTrials.gov, NCT01906606. Findings: Between December, 2012, and January, 2013, 13 communities (194 dyads) were randomly assigned to receive intervention, and 12 communities (154 dyads) were assigned to a waitlist control. 319 dyads completed baseline measures (171 in the intervention group and 148 in the control group), and 291 dyads completed endline measures (160 in the intervention group and 131 in the control group). At endline, children in the intervention group had significantly higher cognitive scores (58·90 vs 55·65, effect size 0·36, 95% CI 0·12-0·59) and receptive language scores (23·86 vs 22·40, 0·27, 0·03-0·50) than did children in the control group. Mothers in the intervention group reported significantly fewer depressive symptoms (15·36 vs 18·61, -0·391, 95% CI -0·62 to -0·16) than did mothers in the control group. However, no differences were found in child growth between groups. Interpretation: The 12 session integrated parenting intervention delivered by non-professional community members improved child development and maternal wellbeing in rural Uganda. Because this intervention was largely managed and implemented by a local organisation, using local community members and minimal resources, such a programme has the potential to be replicated and scaled up in other low-resource, village-based settings. Funding: Plan Uganda via Plan Finland (Ministry of Foreign Affairs) and Plan Australia (Australian Aid).

The Lancet. Global health · randomised controlled trial · 208 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 →

Gaining traction: Promising shifts in gender norms and intimate partner violence in the context of a community-based HIV prevention trial in South Africa.

Background: HIV and violence prevention programs increasingly seek to transform gender norms among participants, yet how to do so at the community level, and subsequent pathways to behavior change, remain poorly understood. We assessed shifts in endorsement of equitable gender norms, and intimate partner violence (IPV), during the three-year community-based trial of Tsima, an HIV 'treatment as prevention' intervention in rural South Africa. Methods: Cross-sectional household surveys were conducted with men and women ages 18-49 years, in 8 intervention and 7 control communities, at 2014-baseline (n = 1,149) and 2018-endline (n = 1,189). Endorsement of equitable gender norms was measured by the GEM Scale. Intent-to-treat analyses assessed intervention effects and change over time. Qualitative research with 59 community members and 38 staff examined the change process. Results: Nearly two-thirds of men and half of women in intervention communities had heard of the intervention/seen the logo; half of these had attended a two-day workshop. Regression analyses showed a 15% improvement in GEM Scale score over time, irrespective of the intervention, among men (p<0.001) and women (p<0.001). Younger women (ages 18-29) had a decreased odds of reporting IPV in intervention vs. control communities (aOR 0.53; p<0.05). Qualitative data suggest that gender norms shifts may be linked to increased media access (via satellite TV/smartphones) and consequent exposure to serial dramas modeling equitable relationships and negatively portraying violence. Tsima's couple communication/conflict resolution skills-building activities, eagerly received by intervention participants, appear to have further supported IPV reductions. Conclusions: There was a population-level shift towards greater endorsement of equitable gender norms between 2014-2018, potentially linked with rapid escalation in media access. There was also an intervention effect on reported IPV among young women, likely owing to improved couple communication. Societal-level gender norm shifts may create enabling environments for interventions to find new traction for violence and HIV-related behavior change.

PloS one · randomised controlled trial · 19 citationsread the source →

Efficacy and Safety of Transcranial Direct Current Stimulation as an Add-on Treatment for Bipolar Depression: A Randomized Clinical Trial.

Importance: More effective, tolerable interventions for bipolar depression treatment are needed. Transcranial direct current stimulation (tDCS) is a novel therapeutic modality with few severe adverse events that showed promising results for unipolar depression. Objective: To determine the efficacy and safety of tDCS as an add-on treatment for bipolar depression. Design, setting, and participants: A randomized, sham-controlled, double-blind trial (the Bipolar Depression Electrical Treatment Trial [BETTER]) was conducted from July 1, 2014, to March 30, 2016, at an outpatient, single-center academic setting. Participants included 59 adults with type I or II bipolar disorder in a major depressive episode and receiving a stable pharmacologic regimen with 17-item Hamilton Depression Rating Scale (HDRS-17) scores higher than 17. Data were analyzed in the intention-to-treat sample. Interventions: Ten daily 30-minute, 2-mA, anodal-left and cathodal-right prefrontal sessions of active or sham tDCS on weekdays and then 1 session every fortnight until week 6. Main outcomes and measures: Change in HDRS-17 scores at week 6. Results: Fifty-nine patients (40 [68%] women), with a mean (SD) age of 45.9 (12) years participated; 36 (61%) with bipolar I and 23 (39%) with bipolar II disorder were randomized and 52 finished the trial. In the intention-to-treat analysis, patients in the active tDCS condition showed significantly superior improvement compared with those receiving sham (βint = -1.68; number needed to treat, 5.8; 95% CI, 3.3-25.8; P = .01). Cumulative response rates were higher in the active vs sham groups (67.6% vs 30.4%; number needed to treat, 2.69; 95% CI, 1.84-4.99; P = .01), but not remission rates (37.4% vs 19.1%; number needed to treat, 5.46; 95% CI, 3.38-14.2; P = .18). Adverse events, including treatment-emergent affective switches, were similar between groups, except for localized skin redness that was higher in the active group (54% vs 19%; P = .01). Conclusions and relevance: In this trial, tDCS was an effective, safe, and tolerable add-on intervention for this small bipolar depression sample. Further trials should examine tDCS efficacy in a larger sample. Trial registration: clinicaltrials.gov Identifier: NCT02152878.

JAMA psychiatry · randomised controlled trial · 103 citationsread the source →

Effects of Fecal Microbiome Transfer in Adolescents With Obesity: The Gut Bugs Randomized Controlled Trial.

Importance: Treatment of pediatric obesity is challenging. Preclinical studies in mice indicated that weight and metabolism can be altered by gut microbiome manipulation. Objective: To assess efficacy of fecal microbiome transfer (FMT) to treat adolescent obesity and improve metabolism. Design, setting, and participants: This randomized, double-masked, placebo-controlled trial (October 2017-March 2019) with a 26-week follow-up was conducted among adolescents aged 14 to 18 years with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 30 or more in Auckland, New Zealand. A total of 87 individuals took part-565 individuals responded to advertisements, 328 were ineligible, and 150 declined participation. Clinical data were analyzed from September 2019 to May 2020. Interventions: Single course of oral encapsulated fecal microbiome from 4 healthy lean donors of the same sex or saline placebo. Main outcomes and measures: Primary outcome was BMI standard deviation score at 6 weeks using intention-to-treat analysis. Secondary outcomes included body composition, cardiometabolic parameters, well-being, and gut microbiome composition. Results: Eighty-seven participants (59% female adolescents, mean [SD] age 17.2 [1.4] years) were randomized 1:1, in groups stratified by sex, to FMT (42 participants) or placebo (45 participants). There was no effect of FMT on BMI standard deviation score at 6 weeks (adjusted mean difference [aMD] -0.026; 95% CI -0.074, 0.022). Reductions in android-to-gynoid-fat ratio in the FMT vs placebo group were observed at 6, 12, and 26 weeks, with aMDs of -0.021 (95% CI, -0.041 to -0.001), -0.023 (95% CI, -0.043 to -0.003), and -0.029 (95% CI, -0.049 to -0.008), respectively. There were no observed effects on insulin sensitivity, liver function, lipid profile, inflammatory markers, blood pressure, total body fat percentage, gut health, and health-related quality of life. Gut microbiome profiling revealed a shift in community composition among the FMT group, maintained up to 12 weeks. In post-hoc exploratory analyses among participants with metabolic syndrome at baseline, FMT led to greater resolution of this condition (18 to 4) compared with placebo (13 to 10) by 26 weeks (adjusted odds ratio, 0.06; 95% CI, 0.01-0.45; P = .007). There were no serious adverse events recorded throughout the trial. Conclusions and relevance: In this randomized clinical trial of adolescents with obesite, there was no effect of FMT on weight loss in adolescents with obesity, although a reduction in abdominal adiposity was observed. Post-hoc analyses indicated a resolution of undiagnosed metabolic syndrome with FMT among those with this condition. Further trials are needed to confirm these results and identify organisms and mechanisms responsible for mediating the observed benefits. Trial registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12615001351505.

JAMA network open · randomised controlled trial · 120 citationsread the source →

Internet-Based Exposure and Behavioral Activation for Complicated Grief and Rumination: A Randomized Controlled Trial.

This study examined the effectiveness and feasibility of therapist-guided Internet-delivered exposure (EX) and behavioral activation (BA) for complicated grief and rumination. Forty-seven bereaved individuals with elevated levels of complicated grief and grief rumination were randomly assigned to three conditions: EX (N=18), BA (N=17), or a waiting-list (N=12). Treatment groups received 6 homework assignments over 6 to 8weeks. Intention-to-treat analyses showed that EX reduced complicated grief, posttraumatic stress, depression, grief rumination, and brooding levels relative to the control group at posttreatment (d=0.7-1.2). BA lowered complicated grief, posttraumatic stress, and grief rumination levels at posttreatment (d=0.8-0.9). At 3-month follow-up, effects of EX were maintained on complicated grief and grief rumination (d=0.6-1.2), and for BA on complicated grief, posttraumatic stress, and grief rumination (d=0.8-0.9). EX reduced depression more strongly than BA (d=0.6). Completers analyses corroborated results for EX, and partially those for BA, but no group differences were detected. BA suffered from high dropout (59%), relative to EX (33%) and the waiting-list (17%). Feasibility appeared higher for EX than BA. Results supported potential applicability of online exposure but not behavioral activation to decrease complicated grief and rumination.

Behavior therapy · randomised controlled trial · 109 citationsread the source →

An Interactive Text Message Intervention to Reduce Binge Drinking in Young Adults: A Randomized Controlled Trial with 9-Month Outcomes.

Background: Binge drinking is associated with numerous negative consequences. The prevalence and intensity of binge drinking is highest among young adults. This randomized trial tested the efficacy of a 12-week interactive text message intervention to reduce binge drinking up to 6 months after intervention completion among young adults. Methods and findings: Young adult participants (18-25 y; n = 765) drinking above the low-risk limits (AUDIT-C score >3/4 women/men), but not seeking alcohol treatment, were enrolled from 4 Emergency Departments (EDs) in Pittsburgh, PA. Participants were randomized to one of three conditions in a 2:1:1 allocation ratio: SMS Assessments + Feedback (SA+F), SMS Assessments (SA), or control. For 12 weeks, SA+F participants received texts each Thursday querying weekend drinking plans and prompting drinking limit goal commitment and each Sunday querying weekend drinking quantity. SA+F participants received tailored feedback based on their text responses. To contrast the effects of SA+F with self-monitoring, SA participants received texts on Sundays querying drinking quantity, but did not receive alcohol-specific feedback. The control arm received standard care. Follow-up outcome data collected through web-based surveys were provided by 78% of participants at 3- months, 63% at 6-months and 55% at 9-months. Multiple imputation-derived, intent-to-treat models were used for primary analysis. At 9-months, participants in the SA+F group reported greater reductions in the number of binge drinking days than participants in the control group (incident rate ratio [IRR] 0.69; 95% CI .59 to.79), lower binge drinking prevalence (odds ratio [OR] 0.52; 95% CI 0.26 to 0.98]), less drinks per drinking day (beta -.62; 95% CI -1.10 to -0.15) and lower alcohol-related injury prevalence (OR 0.42; 95% CI 0.21 to 0.88). Participants in the SA group did not reduce drinking or alcohol-related injury relative to controls. Findings were similar using complete case analyses. Conclusions: An interactive text-message intervention was more effective than self-monitoring or controls in reducing alcohol consumption and alcohol-related injury prevalence up to 6 months after intervention completion. These findings, if replicated, suggest a scalable approach to help achieve sustained reductions in binge drinking and accompanying injuries among young adults. Trial registration: ClinicalTrials.gov NCT01688245.

PloS one · randomised controlled trial · 95 citationsread the source →

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

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

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

A telehealth lifestyle intervention to reduce excess gestational weight gain in pregnant women with overweight or obesity (GLOW): a randomised, parallel-group, controlled trial.

Background: Excess gestational weight gain (GWG) among women with overweight or obesity synergistically increases their already elevated risk of having gestational diabetes, a caesarean delivery, a large for gestational age infant, and post-partum weight retention, and increases their child's risk of obesity. We investigated whether a primarily telehealth lifestyle intervention reduced excess GWG among women with overweight or obesity. Methods: We did a randomised controlled trial in five antenatal clinics of Kaiser Permanente; Oakland, San Leandro, Walnut Creek, Fremont, and Santa Clara, CA, USA. Women at 8-15 weeks' gestation with singletons, pre-pregnancy BMI 25·0-40·0 kg/m2, and aged 18 years or older were randomly assigned (1:1) to receive the telehealth lifestyle intervention or usual antenatal care. Randomisation was adaptively balanced for age, BMI, and race and ethnicity. Data collectors and investigators were masked to group assignments. The core lifestyle intervention consisted of two in-person and 11 telephone sessions on behavioural strategies to improve weight, diet, and physical activity, and stress management to help women meet a trial goal of gaining at the lower limit of the Institute of Medicine (IOM) guidelines range for total GWG: 7 kg for women with overweight and 5 kg for women with obesity. Usual antenatal care included an antenatal visit at 7-10 weeks' gestation, an additional seven antenatal visits, on average, and periodic health education newsletters, including the IOM GWG guidelines and information on healthy eating and physical activity in pregnancy. The primary outcome was weekly rate of GWG expressed as excess GWG, per Institute of Medicine guidelines and mean assessed in the intention-to-treat population. The trial is registered at ClinicalTrials.gov, NCT02130232. Findings: Between March 24, 2014, and Sept 26, 2017, 5329 women were assessed for eligibility and 200 were randomly assigned to the lifestyle intervention group and 198 to the usual care group. Analyses included 199 women in the lifestyle intervention group (one lost to follow-up) and 195 in the usual care group (three lost to follow-up). 96 (48%) women in the lifestyle intervention group and 134 (69%) women in the usual care group exceeded Institute of Medicine guidelines for rate of GWG per week (relative risk 0·70, 95% CI 0·59 to 0·83). Compared with usual care, women in the lifestyle intervention had reduced weekly rate of GWG (mean 0·26 kg per week [SD 0·15] vs 0·32 kg per week [0·13]; mean between-group difference -0·07 kg per week, 95% CI -0·09 to -0·04). No between-group differences in perinatal complications were observed. Interpretation: Our evidence-based programme showed that health-care delivery systems could further adapt to meet the needs of their clinical settings to prevent excess GWG and improve healthy behaviours and markers of insulin resistance among women with overweight or obesity by using telehealth lifestyle interventions. Funding: US National Institutes of Health.

The lancet. Diabetes & endocrinology · randomised controlled trial · 122 citationsread the source →

A mindfulness-based intervention to increase resilience to stress in university students (the Mindful Student Study): a pragmatic randomised controlled trial.

Background: The rising number of young people going to university has led to concerns about an increasing demand for student mental health services. We aimed to assess whether provision of mindfulness courses to university students would improve their resilience to stress. Methods: We did this pragmatic randomised controlled trial at the University of Cambridge, UK. Students aged 18 years or older with no severe mental illness or crisis (self-assessed) were randomly assigned (1:1), via remote survey software using computer-generated random numbers, to receive either an 8 week mindfulness course adapted for university students (Mindfulness Skills for Students [MSS]) plus mental health support as usual, or mental health support as usual alone. Participants and the study management team were aware of group allocation, but allocation was concealed from the researchers, outcome assessors, and study statistician. The primary outcome was self-reported psychological distress during the examination period, as measured with the Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM), with higher scores indicating more distress. The primary analysis was by intention to treat. This trial is registered with the Australia and New Zealand Clinical Trials Registry, number ACTRN12615001160527. Findings: Between Sept 28, 2015, and Jan 15, 2016, we randomly assigned 616 students to the MSS group (n=309) or the support as usual group (n=307). 453 (74%) participants completed the CORE-OM during the examination period and 182 (59%) MSS participants completed at least half of the course. MSS reduced distress scores during the examination period compared with support as usual, with mean CORE-OM scores of 0·87 (SD 0·50) in 237 MSS participants versus 1·11 (0·57) in 216 support as usual participants (adjusted mean difference -0·14, 95% CI -0·22 to -0·06; p=0·001), showing a moderate effect size (β -0·44, 95% CI -0·60 to -0·29; p<0·0001). 123 (57%) of 214 participants in the support as usual group had distress scores above an accepted clinical threshold compared with 88 (37%) of 235 participants in the MSS group. On average, six students (95% CI four to ten) needed to be offered the MSS course to prevent one from experiencing clinical levels of distress. No participants had adverse reactions related to self-harm, suicidality, or harm to others. Interpretation: Our findings show that provision of mindfulness training could be an effective component of a wider student mental health strategy. Further comparative effectiveness research with inclusion of controls for non-specific effects is needed to define a range of additional, effective interventions to increase resilience to stress in university students. Funding: University of Cambridge and National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care East of England.

The Lancet. Public health · randomised controlled trial · 217 citationsread the source →

Habit formation following routine-based versus time-based cue planning: A randomized controlled trial.

Objectives: Habit formation has been identified as one of the key determinants of behaviour change. To initiate habit formation, self-regulation interventions can support individuals to form a cue-behaviour plan and to repeatedly enact the plan in the same context. This randomized controlled trial aimed to model habit formation of an everyday nutrition behaviour and examined whether habit formation and plan enactment differ when individuals plan to enact their behaviour in response to a routine-based versus time-based cue. Design: Following a baseline assessment, N = 192 adults (aged 18-77 years) were randomly assigned to a routine-based cue or a time-based cue planning intervention, in which they selected an everyday nutrition behaviour and linked it to a daily routine or a time cue. Methods: Participants responded to daily questionnaires over 84 days assessing plan enactment and the behaviour's automaticity (as an indicator of habit formation). Multilevel models with days nested in participants were fitted. Results: As indicated by asymptotic curves, it took a median of 59 days for participants who successfully formed habits to reach peak automaticity. Group-level analyses revealed that both routine-based and time-based cue planning led to increases in automaticity and plan enactment, but no between-condition differences were found. Repeated plan enactment was a key predictor for automaticity. Conclusions: Linking one's nutrition behaviour to a daily routine or a specific time was similarly effective for habit formation. Interventions should encourage persons to repeatedly carry out their planned behaviour in response to the planned cue to facilitate habit formation.

British journal of health psychology · randomised controlled trial · 57 citationsread the source →

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

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

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

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 →

What makes adults with hearing impairment take up hearing AIDS or communication programs and achieve successful outcomes?

Objectives: Client involvement in health decision making, or shared decision making, is increasingly being advocated. For example, rehabilitation interventions such as hearing aids and communication programs can be presented as options to adults with hearing impairment seeking help for the first time. Our previous research focused on the predictors of intervention decisions when options were presented with a decision aid. However, not all participants took up the intervention they initially decided upon. Although it is interesting to understand what informs adults with hearing impairment's intervention decisions, it is their intervention uptake and outcomes which best represent the ultimate end result of the rehabilitation process. This prospective study investigated the predictors of uptake and of successful outcomes of hearing aids and communication programs in middle-aged and older adults with hearing impairment seeking help for the first time. Design: Using shared decision making, 153 participants with hearing impairment (average of air conduction thresholds at 0.5, 1, 2, and 4 kHz greater than 25 dB HL in at least one ear) aged 50 yr and older were presented with intervention options: hearing aids, communication programs (group or individual), and no intervention. Each participant received a decision aid and had at least 1 wk to consider intervention options before the intervention decision was made. Outcome measures for both hearing aids and communication programs at 3 mo after intervention completion were benefit (measured with the Client-Oriented Scale of Improvement), composite outcomes (measured with the International Outcome Inventory), and reduction in self-reported hearing disability (measured with the Hearing Handicap Questionnaire). Multivariate analysis (logistic and linear regression) identified predictors of intervention uptake and of successful outcomes when all other variables were held constant. Results: Almost a quarter of the 153 participants (24%) did not take up the intervention they initially decided upon: 6 mo after making their intervention decision, 66 participants (43%) obtained hearing aids, 28 participants (18%) completed communication programs, and 59 participants (39%) did not complete an intervention. Seven intervention uptake predictors were identified: (1) application for subsidized hearing services (participants more likely to obtain hearing aids and less likely to complete no intervention); (2) higher socioeconomic status (no intervention less likely); (3) greater communication self-efficacy (hearing aids less likely); (4) greater contemplation stage of change (no intervention less likely); (5) greater hearing disability perceived by others and self (communication programs less likely); (6) greater perceived communication program effectiveness (communication programs more likely); and (7) greater perceived suitability of individual communication program (hearing aids less likely and communication programs more likely). Six predictors of successful intervention outcomes were identified: (1) higher socioeconomic status; (2) greater initial self-reported hearing disability; (3) lower precontemplation stage of change; (4) greater action stage of change; (5) lower chance locus of control; and (6) greater hearing disability perceived by others and self. Conclusions: Self-reported hearing disability and stages of change are the two most robust predictors of intervention uptake and successful outcomes. Clinicians should offer intervention options and should discuss these predictors when helping adults with hearing impairment make optimal decisions.

Ear and hearing · 76 citationsread the source →

Early intervention for psychosis.

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

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

Internet-based interventions to promote mental health help-seeking in elite athletes: an exploratory randomized controlled trial.

Background: Mental disorders are more common in young adults than at any other life stage. Despite this, young people have low rates of seeking professional help for mental health problems. Young elite athletes have less positive attitudes toward seeking help than nonathletes and thus may be particularly unlikely to seek help. Interventions aimed at increasing help-seeking in young elite athletes are warranted. Objective: To test the feasibility and efficacy of three Internet-based interventions designed to increase mental health help-seeking attitudes, intentions, and behavior in young elite athletes compared with a control condition. Methods: We conducted a randomized controlled trial (RCT) of three brief fully automated Internet-based mental health help-seeking interventions with 59 young elite athletes recruited online in a closed trial in Australia. The interventions consisted of a mental health literacy and destigmatization condition, a feedback condition providing symptom levels, and a minimal content condition comprising a list of help-seeking resources, compared with a control condition (no intervention). We measured help-seeking attitudes, intentions and behavior using self-assessed surveys. Participation was open to elite athletes regardless of their mental health status or risk of mental illness. Results: Of 120 athletes initially agreeing to participate, 59 (49%) submitted a preintervention or postintervention survey, or both, and were included in the present study. Adherence was satisfactory, with 48 (81%) participants visiting both weeks of assigned intervention material. None of the interventions yielded a significant increase in help-seeking attitudes, intentions, or behavior relative to control. However, at postintervention, there was a trend toward a greater increase in help-seeking behavior from formal sources for the mental health literacy/destigmatization condition compared with control (P = .06). This intervention was also associated with increased depression literacy (P = .003, P = .005) and anxiety literacy (P = .002, P = .001) relative to control at postintervention and 3-month follow-up, respectively, and a reduction in depression stigma relative to control at postintervention (P = .01, P = .12) and anxiety stigma at 3-month follow-up (P = .18, P = .02). The feedback and help-seeking list interventions did not improve depression or anxiety literacy or decrease stigmatizing attitudes to these conditions. However, the study findings should be treated with caution. Due to recruitment challenges, the achieved sample size fell significantly short of the target size and the study was underpowered. Accordingly, the results should be considered as providing preliminary pilot data only. Conclusions: This is the first RCT of an Internet-based mental health help-seeking intervention for young elite athletes. The results suggest that brief mental health literacy and destigmatization improves knowledge and may decrease stigma but does not increase help-seeking. However, since the trial was underpowered, a larger trial is warranted. Trial registration: 2009/373 (www.clinicaltrials.gov ID: NCT00940732), cited at http://www.webcitation.org/5ymsRLy9r.

Journal of medical Internet research · randomised controlled trial · 126 citationsread the source →

Efficacy of classification-based cognitive functional therapy in patients with non-specific chronic low back pain: a randomized controlled trial.

Background: Non-specific chronic low back pain disorders have been proven resistant to change, and there is still a lack of clear evidence for one specific treatment intervention being superior to another. Methods: This randomized controlled trial aimed to investigate the efficacy of a behavioural approach to management, classification-based cognitive functional therapy, compared with traditional manual therapy and exercise. Linear mixed models were used to estimate the group differences in treatment effects. Primary outcomes at 12-month follow-up were Oswestry Disability Index and pain intensity, measured with numeric rating scale. Inclusion criteria were as follows: age between 18 and 65 years, diagnosed with non-specific chronic low back pain for >3 months, localized pain from T12 to gluteal folds, provoked with postures, movement and activities. Oswestry Disability Index had to be >14% and pain intensity last 14 days >2/10. A total of 121 patients were randomized to either classification-based cognitive functional therapy group n = 62) or manual therapy and exercise group (n > = 59). Results: The classification-based cognitive functional therapy group displayed significantly superior outcomes to the manual therapy and exercise group, both statistically (p < 0.001) and clinically. For Oswestry Disability Index, the classification-based cognitive functional therapy group improved by 13.7 points, and the manual therapy and exercise group by 5.5 points. For pain intensity, the classification-based cognitive functional therapy improved by 3.2 points, and the manual therapy and exercise group by 1.5 points. Conclusions: The classification-based cognitive functional therapy produced superior outcomes for non-specific chronic low back pain compared with traditional manual therapy and exercise.

European journal of pain (London, England) · randomised controlled trial · 291 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 →

Phase III pilot study of dose escalation using conformal radiotherapy in prostate cancer: PSA control and side effects.

Radical radiotherapy is a standard form of management of localised prostate cancer. Conformal treatment planning spares adjacent normal tissues reducing treatment-related side effects and may permit safe dose escalation. We have tested the effects on tumour control and side effects of escalating radiotherapy dose and investigated the appropriate target volume margin. After an initial 3-6 month period of androgen suppression, 126 men were randomised and treated with radiotherapy using a 2 by 2 factorial trial design. The initial radiotherapy tumour target volume included the prostate and base of seminal vesicles (SV) or complete SV depending on SV involvement risk. Treatments were randomised to deliver a dose of 64 Gy with either a 1.0 or 1.5 cm margin around the tumour volume (1.0 and 1.5 cm margin groups) and also to treat either with or without a 10 Gy boost to the prostate alone with no additional margin (64 and 74 Gy groups). Tumour control was monitored by prostate-specific antigen (PSA) testing and clinical examination with additional tests as appropriate. Acute and late side effects of treatment were measured using the Radiation Treatment and Oncology Groups (RTOG) and LENT SOM systems. The results showed that freedom from PSA failure was higher in the 74 Gy group compared to the 64 Gy group, but this did not reach conventional levels of statistical significance with 5-year actuarial control rates of 71% (95% CI 58-81%) in the 74 Gy group vs 59% (95% CI 45-70%) in the 64 Gy group. There were 23 failures in the 74 Gy group and 33 in the 64 Gy group (Hazard ratio 0.64, 95% CI 0.38-1.10, P=0.10). No difference in disease control was seen between the 1.0 and 1.5 cm margin groups (5-year actuarial control rates 67%, 95% CI 53-77% vs 63%, 95% CI 50-74%) with 28 events in each group (Hazard ratio 0.97, 95% CI 0.50-1.86, P=0.94). Acute side effects were generally mild and 18 weeks after treatment, only four and five of the 126 men had persistent > or =Grade 1 bowel or bladder side effects, respectively. Statistically significant increases in acute bladder side effects were seen after treatment in the men receiving 74 Gy (P=0.006), and increases in both acute bowel side effects during treatment (P=0.05) and acute bladder sequelae (P=0.002) were recorded for men in the 1.5 cm margin group. While statistically significant, these differences were of short duration and of doubtful clinical importance. Late bowel side effects (RTOG> or =2) were seen more commonly in the 74 Gy and 1.5 cm margin groups (P=0.02 and P=0.05, respectively) in the first 2 years after randomisation. Similar results were found using the LENT SOM assessments. No significant differences in late bladder side effects were seen between the randomised groups using the RTOG scoring system. Using the LENT SOM instrument, a higher proportion of men treated in the 74 Gy group had Grade > or =3 urinary frequency at 6 and 12 months. Compared to baseline scores, bladder symptoms improved after 6 months or more follow-up in all groups. Sexual function deteriorated after treatment with the number of men reporting some sexual dysfunction (Grade> or =1) increasing from 38% at baseline to 66% at 6 months and 1 year and 81% by year 5. However, no consistent differences were seen between the randomised groups. In conclusion, dose escalation from 64 to 74 Gy using conformal radiotherapy may improve long-term PSA control, but a treatment margin of 1.5 cm is unnecessary and is associated with increased acute bowel and bladder reactions and more late rectal side effects. Data from this randomised pilot study informed the Data Monitoring Committee of the Medical Research Council RT 01 Trial and the two studies will be combined in subsequent meta-analysis.

British journal of cancer · randomised controlled trial · 155 citationsread the source →

Randomised controlled trial and parallel economic evaluation of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR).

Objectives: To determine the comparative effectiveness and cost-effectiveness of conventional ventilatory support versus extracorporeal membrane oxygenation (ECMO) for severe adult respiratory failure. Design: A multicentre, randomised controlled trial with two arms. Setting: The ECMO centre at Glenfield Hospital, Leicester, and approved conventional treatment centres and referring hospitals throughout the UK. Participants: Patients aged 18-65 years with severe, but potentially reversible, respiratory failure, defined as a Murray lung injury score > or = 3.0, or uncompensated hypercapnoea with a pH < 7.20 despite optimal conventional treatment. Interventions: Participants were randomised to conventional management (CM) or to consideration of ECMO. Main outcome measures: The primary outcome measure was death or severe disability at 6 months. Secondary outcomes included a range of hospital indices: duration of ventilation, use of high frequency/oscillation/jet ventilation, use of nitric oxide, prone positioning, use of steroids, length of intensive care unit stay, and length of hospital stay - and (for ECMO patients only) mode (venovenous/veno-arterial), duration of ECMO, blood flow and sweep flow. Results: A total of 180 patients (90 in each arm) were randomised from 68 centres. Three patients in the conventional arm did not give permission to be followed up. Of the 90 patients randomised to the ECMO arm, 68 received that treatment. ECMO was not given to three patients who died prior to transfer, two who died in transit, 16 who improved with conventional treatment given by the ECMO team and one who required amputation and could not therefore be heparinised. Ninety patients entered the CM (control) arm, three patients later withdrew and refused follow-up (meaning that they were alive), leaving 87 patients for whom primary outcome measures were available. CM consisted of any treatment deemed appropriate by the patient's intensivist with the exception of extracorporeal gas exchange. No CM patients received ECMO, although one received a form of experimental extracorporeal arteriovenous carbon dioxide removal support (a clear protocol violation). Fewer patients in the ECMO arm than in the CM arm had died or were severely disabled 6 months after randomisation, [33/90 (36.7%) versus 46/87 (52.9%) respectively]. This equated to one extra survivor for every six patients treated. Only one patient (in the CM arm) was known to be severely disabled at 6 months. Patients allocated to ECMO incurred average total costs of 73,979 pounds compared with 33,435 pounds for those undergoing CM (UK prices, 2005). A lifetime model predicted the cost per quality-adjusted life-year (QALY) of ECMO to be 19,252 pounds (95% confidence interval 7622 pounds to 59,200 pounds) at a discount rate of 3.5%. Lifetime QALYs gained were 10.75 for the ECMO group compared with 7.31 for the conventional group. Costs to patients and their relatives, including out of pocket and time costs, were higher for patients allocated to ECMO. Conclusions: Compared with CM, transferring adult patients with severe but potentially reversible respiratory failure to a single centre specialising in the treatment of severe respiratory failure for consideration of ECMO significantly increased survival without severe disability. Use of ECMO in this way is likely to be cost-effective when compared with other technologies currently competing for health resources. Trial registration: Current Controlled Trials ISRCTN47279827.

Health technology assessment (Winchester, England) · randomised controlled trial · 113 citationsread the source →

Final analysis of the prospective WSG-AGO EC-Doc versus FEC phase III trial in intermediate-risk (pN1) early breast cancer: efficacy and predictive value of Ki67 expression.

Background: Taxane-based adjuvant chemotherapy is standard in node-positive (N+) early breast cancer (BC). The magnitude of benefit in intermediate-risk N+ early BC is still unclear. WSG-AGO epiribicine and cyclophosphamide (EC)-Doc is a large trial evaluating modern taxane-based chemotherapy in patients with 1-3 positive lymph nodes (LNs) only. Patients and methods: A total of 2011 BC patients (18-65 years, pN1) were entered into a randomized phase III trial comparing 4 × E90C600 q3w followed by 4 × docetaxel 100 q3w (n = 1008) with the current standard: 6 × F500E100C500 q3w (n = 828) or C600M40F600 d1, 8× q4w (n = 175). Primary end point was event-free survival (EFS); secondary end points were overall survival (OS), toxicity, translational research, and quality of life. Central tumor bank samples were evaluable in a representative collective (n = 772; 40%). Ki-67 was assessed centrally in hormone receptor-positive disease as a surrogate marker for the distinction of luminal A/B-like tumors. Results: Baseline characteristics were well balanced between study arms in both main study and central tumor bank subset. At 59-month median follow-up, superior efficacy of EC-Doc [versus FEC (a combination of 5-fluorouracil, epirubicin, and cyclophosphamide)] was seen in EFS and OS: 5-year EFS: 89.8% versus 87.3% (P = 0.038); 5-year OS: 94.5% versus 92.8% (P = 0.034); both tests one-tailed. EC-Doc caused more toxicity. In hormone receptor-positive (HR)+ disease, only high-Ki-67 tumors (≥ 20%) derived significant benefit from taxane-based therapy: hazard ratio = 0.39 (95% CI 0.18-0.82) for EC-Doc versus FEC (test for interaction; P = 0.01). Conclusion: EC-Doc significantly improved EFS and OS versus FEC in intermediate-risk BC (1-3 LNs) within all subgroups as defined by local pathology. In HR+ disease, patients with luminal A-like tumors may be potentially over-treated by taxane-based chemotherapy. Clinical trial number: ClinicalTrials.gov, NCT02115204.

Annals of oncology : official journal of the European Society for Medical Oncology · randomised controlled trial · 40 citationsread the source →

A peer intervention reduces loneliness and improves social well-being in low-income older adults: A mixed-methods study.

Background: Evidence-based interventions addressing loneliness and social isolation are needed, including among low-income, community-dwelling older adults of diverse racial and ethnic backgrounds. Our objective was to assess the effect of a peer intervention in addressing loneliness, isolation, and behavioral health needs in this population. Methods: We conducted a mixed-method, two-year longitudinal study of a peer-outreach intervention in 74 low-income older adults recruited via an urban senior center in San Francisco. Structured participant surveys were conducted at baseline and every 6 months for up to 2 years. Outcomes included loneliness (3-item UCLA loneliness scale), social interaction (10-item Duke index), self-perceived socializing barriers (range: 0-10), and depression (PHQ-2 screen). Data were analyzed using mixed-effects linear and logistic regression adjusted for age and gender. Qualitative, semi-structured interviews with participants (N = 15) and peers (N = 6) were conducted in English and Spanish and analyzed thematically. Results: Participants were on average 71 years old (range: 59-96 years), with 58% male, 15% LGBT, 18% African American, 19% Latinx, 8% Asian, 86% living alone, and 36% with an ADL impairment. On average, 43 contact visits (IQR: 31-97 visits) between participants and peers occurred over the first year. Loneliness scores decreased by, on average, 0.8 points over 24 months (p = 0.015). Participants reported reduced depression (38%-16%, p < 0.001) and fewer barriers to socializing (1.5 fewer, p < 0.001). Because of the longitudinal relationship and matching of characteristics of peers to participants, participants reported strong feelings of kinship, motivations to reach out in other areas of life, and improved mood. Conclusion: Diverse older adults in an urban setting participating in a longitudinal peer program experienced reduced loneliness, depression, and barriers to socializing. Matching by shared backgrounds facilitated rapport and bonding between participants and peers.

Journal of the American Geriatrics Society · 34 citationsread the source →

Food insecurity among graduate students: prevalence and association with depression, anxiety and stress.

Objective: The impact of food insecurity on mental health has not yet been examined in graduate students, a population widely considered at elevated risk for financial strain and negative mental health outcomes. This study aimed to derive initial prevalence estimates of food insecurity in a sample of current graduate students at a large state university and to elucidate the relationship between food insecurity and depression, anxiety and stress in this sample. Design: Cross-sectional online survey including the US Household Food Security Survey Module: Six-Item Short Form and the Depression, Anxiety, and Stress Scales (DASS-21). Setting: University in the northeastern region of the USA. Participants: Two hundred sixty-three graduate students. Results: In the present sample, 59·7 % of participants reported high/marginal food security, 18·5 % reported low food security and 21·8 % reported very low food security. Graduate students with very low food security reported significantly greater depression (η2 = 0·09), anxiety (η2 = 0·10) and stress (η2 = 0·10), compared with those with low food security and high food security (all P's < 0·001). Conclusions: Food insecurity occurred in nearly half of the graduate students surveyed, and very low food security was associated with elevated levels of depression, anxiety and stress. Findings highlight the need to address food insecurity and associated elevated mental health problems present among graduate students.

Public health nutrition · 37 citationsread the source →

Burden of disease and costs of aneurysmal subarachnoid haemorrhage (aSAH) in the United Kingdom.

Background: To estimate life years and quality-adjusted life years (QALYs) lost and the economic burden of aneurysmal subarachnoid haemorrhage (aSAH) in the United Kingdom including healthcare and non-healthcare costs from a societal perspective. Methods: All UK residents in 2005 with aSAH (International Classification of Diseases 10th revision (ICD-10) code I60). Sex and age-specific abridged life tables were generated for a general population and aSAH cohorts. QALYs in each cohort were calculated adjusting the life tables with health-related quality of life (HRQL) data. Healthcare costs included hospital expenditure, cerebrovascular rehabilitation, primary care and community health and social services. Non-healthcare costs included informal care and productivity losses arising from morbidity and premature death. Results: A total of 80,356 life years and 74,807 quality-adjusted life years were estimated to be lost due to aSAH in the UK in 2005. aSAH costs the National Health Service (NHS) pound168.2 million annually with hospital inpatient admissions accounting for 59%, community health and social services for 18%, aSAH-related operations for 15% and cerebrovascular rehabilitation for 6% of the total NHS estimated costs. The average per patient cost for the NHS was estimated to be pound23,294. The total economic burden (including informal care and using the human capital method to estimate production losses) of a SAH in the United Kingdom was estimated to be pound510 million annually. Conclusion: The economic and disease burden of aSAH in the United Kingdom is reported in this study. Decision-makers can use these results to complement other information when informing prevention policies in this field and to relate health care expenditures to disease categories.

Cost effectiveness and resource allocation : C/E · 99 citationsread the source →

Socio-environmental correlates of physical activity in patients with chronic obstructive pulmonary disease (COPD).

Background: Study of the causes of the reduced levels of physical activity in patients with COPD has been scarce and limited to biological factors. Aim: To assess the relationship between novel socio-environmental factors, namely dog walking, grandparenting, neighbourhood deprivation, residential surrounding greenness and residential proximity to green or blue spaces, and amount and intensity of physical activity in COPD patients. Methods: This cross-sectional study recruited 410 COPD patients from five Catalan municipalities. Dog walking and grandparenting were assessed by questionnaire. Neighbourhood deprivation was assessed using the census Urban Vulnerability Index, residential surrounding greenness by the satellite-derived Normalized Difference Vegetation Index, and residential proximity to green or blue spaces as living within 300 m of such a space. Physical activity was measured during 1 week by accelerometer to assess time spent on moderate-to-vigorous physical activity (MVPA) and vector magnitude units (VMU) per minute. Findings: Patients were 85% male, had a mean (SD) age of 69 (9) years, and post-bronchodilator FEV1 of 56 (17) %pred. After adjusting for age, sex, socio-economic status, dyspnoea, exercise capacity and anxiety in a linear regression model, both dog walking and grandparenting were significantly associated with an increase both in time in MVPA (18 min/day (p<0.01) and 9 min/day (p<0.05), respectively) and in physical activity intensity (76 VMU/min (p=0.05) and 59 VMUs/min (p<0.05), respectively). Neighbourhood deprivation, surrounding greenness and proximity to green or blue spaces were not associated with physical activity. Conclusions: Dog walking and grandparenting are associated with a higher amount and intensity of physical activity in COPD patients. Trial registration number: Pre-results, NCT01897298.

Thorax · cohort or longitudinal · 39 citationsread the source →

Identification, Evaluation, and Management of Children With Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder with reported prevalence in the United States of 1 in 59 children (approximately 1.7%). Core deficits are identified in 2 domains: social communication/interaction and restrictive, repetitive patterns of behavior. Children and youth with ASD have service needs in behavioral, educational, health, leisure, family support, and other areas. Standardized screening for ASD at 18 and 24 months of age with ongoing developmental surveillance continues to be recommended in primary care (although it may be performed in other settings), because ASD is common, can be diagnosed as young as 18 months of age, and has evidenced-based interventions that may improve function. More accurate and culturally sensitive screening approaches are needed. Primary care providers should be familiar with the diagnostic criteria for ASD, appropriate etiologic evaluation, and co-occurring medical and behavioral conditions (such as disorders of sleep and feeding, gastrointestinal tract symptoms, obesity, seizures, attention-deficit/hyperactivity disorder, anxiety, and wandering) that affect the child's function and quality of life. There is an increasing evidence base to support behavioral and other interventions to address specific skills and symptoms. Shared decision making calls for collaboration with families in evaluation and choice of interventions.  This single clinical report updates the 2007 American Academy of Pediatrics clinical reports on the evaluation and treatment of ASD in one publication with an online table of contents and section view available through the American Academy of Pediatrics Gateway to help the reader identify topic areas within the report.

Pediatrics · review · 809 citationsread the source →

Deconstructing the Complexities of Advance Care Planning Outcomes: What Do We Know and Where Do We Go? A Scoping Review.

Background/objectives: Advance care planning (ACP) has shown benefit in some, but not all, studies. It is important to understand the utility of ACP. We conducted a scoping review to identify promising interventions and outcomes. Design: Scoping review. Measurements: We searched MEDLINE/PubMed, EMBASE, CINAHL, PsycINFO, and Web of Science for ACP randomized controlled trials from January 1, 2010, to March 3, 2020. We used standardized Preferred Reporting Items for Systematic Review and Meta-Analyses methods to chart study characteristics, including a standardized ACP Outcome Framework: Process (e.g., readiness), Action (e.g., communication), Quality of Care (e.g., satisfaction), Health Status (e.g., anxiety), and Healthcare Utilization. Differences between arms of P < .05 were deemed positive. Results: Of 1,464 articles, 69 met eligibility; 94% were rated high quality. There were variable definitions, age criteria (≥18 to ≥80 years), diseases (e.g., dementia and cancer), and settings (e.g., outpatient and inpatient). Interventions included facilitated discussions (42%), video only (20%), interactive, multimedia (17%), written only (12%), and clinician training (9%). For written only, 75% of primary outcomes were positive, as were 69% for multimedia programs; 67% for facilitated discussions, 59% for video only, and 57% for clinician training. Overall, 72% of Process and 86% of Action outcomes were positive. For Quality of Care, 88% of outcomes were positive for patient-surrogate/clinician congruence, 100% for patients/surrogate/clinician satisfaction with communication, and 75% for surrogate satisfaction with patients' care, but not for goal concordance. For Health Status outcomes, 100% were positive for reducing surrogate/clinician distress, but not for patient quality of life. Healthcare Utilization data were mixed. Conclusion: ACP is complex, and trial characteristics were heterogeneous. Outcomes for all ACP interventions were predominantly positive, as were Process and Action outcomes. Although some Quality of Care and Health Status outcomes were mixed, increased patient/surrogate satisfaction with communication and care and decreased surrogate/clinician distress were positive. Further research is needed to appropriately tailor interventions and outcomes for local contexts, set appropriate expectations of ACP outcomes, and standardize across studies.

Journal of the American Geriatrics Society · review · 381 citationsread the source →

Social capital, trust in the health-care system and self-rated health: the role of access to health care in a population-based study.

This paper investigates the relationship between institutional trust in the health-care system, i.e. an institutional aspect of social capital, and self-rated health, and whether the strength of this association is affected by access to health-care services. The 2004 public health survey in the Scania region of Sweden is a cross-sectional study; a total of 27,963 respondents aged 18-80 years answered a postal questionnaire, which represents 59% of the random sample. Logistic regression model was used to investigate the association between institutional trust and self-rated health. Multivariate analyses of self-rated health were performed in order to investigate the importance of possible confounders (age, country of origin, education, economic stress, generalized trust in other people, and care-seeking behaviour) on this association. A 28.7% proportion of the men and 33.2% of the women reported poor self-rated health. A total of 15.0% and 58.3% of the respondents reported "very high" and "rather high" trust in the health-care system, respectively. Almost one-third of all respondents reported low institutional trust. Respondents born outside Sweden, with low/medium education, low generalized trust and low institutional trust had significantly higher odds ratios of poor self-rated health. Multiple adjustments for age, country of origin, education, economic stress, and horizontal trust had some effect on the significant relationship between institutional trust and poor self-rated health, for both men and women, but the additional introduction of care-seeking behaviour in the model substantially reduced the odds ratios. In conclusion, low trust in the health-care system is associated with poor self-rated health. This association may be partly mediated by "not seeking health care when needed". However, this is a cross-sectional exploratory study and the causality may go in both directions.

Social science & medicine (1982) · 128 citationsread the source →

Marital status, social capital, material conditions and self-rated health: a population-based study.

Aims: Associations between marital status and self-rated health were investigated, adjusting for material conditions and trust (social capital). Methods: The 2004 public-health survey in Skåne is a cross-sectional study. A total of 27,757 persons aged 18-80 years answered a postal questionnaire, which represents 59% of the random sample. A logistic regression model was used to investigate associations between marital status and self-rated health, adjusting for economic problems and trust. Results: The prevalence of poor self-rated health was 28.7% among men and 33.2% among women. Older respondents, respondents born abroad, with medium/low education, low emotional support, low instrumental support, economic problems, low trust, never married and divorced had significantly higher odds ratios of poor self-rated health than their respective reference group. Low trust was significantly higher among the divorced and unmarried compared to the married/cohabitating. Adjustment for economic problems but not for trust reduced the odds ratios of poor self-rated health among the divorced, which became not significant among men. Conclusions: Never married and the divorced have significantly higher age-adjusted odds ratios of poor self-rated health than the married/cohabitating group. Economic problems but not trust seem to affect the association between marital status and poor self-rated health.

Health policy (Amsterdam, Netherlands) · 65 citationsread the source →

Heart rate variability

IN FOCUSHeart rate variabilityHarald M. StaussHarald M. StaussDepartment of Exercise Science, University of Iowa, Iowa City, Iowa 52242Published Online:01 Nov 2003https://doi.org/10.1152/ajpregu.00452.2003MoreSectionsPDF (59 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations the rhythm of the heart has not only fascinated cardiologists but also inspired poets and musicians. Indeed, the periodic beat of the heart was used to define the speed of music. In music notation, the traditional Italian term "moderato" originally referred to one beat of the measure per walking pace (76-80 paces/min) or heartbeat (∼72 beats/min). The use of the heartbeat to define the speed of music may imply that the periodicity of the beat of the heart is very constant. However, this is not necessarily the case. In fact, loss of heart rate variability can indicate severe cardiovascular diseases and reliably predict poor outcome of such conditions (18, 22, 27, 47a). This In Focus article reviews sources of heart rate variability, its role as a prognostic marker for cardiovascular diseases, and its application in estimation of cardiac autonomic nervous system activity. All of these topics have been addressed intensely in articles published in the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology during the last two years. In healthy subjects, the sinoatrial node located at the posterior wall of the right atrium initiates each beat of the heart. Due to the unstable membrane potential of the myocytes located in this region, action potentials are generated periodically at a fairly constant frequency. This relatively constant frequency generated by the autorhythmicity of the sinoatrial node is modulated by many factors that add variability to the heart rate signal at different frequencies. According to the Task Force of The European Society of Cardiology and The North American Society of Pacing and Electrophysiology (47a) these frequencies are classified into 1) ultra-low frequencies (ULF; >5-h cycle length) that include the circadian rhythm (6, 9, 34, 54); 2) very low frequencies (VLF; >25-s cycle length) that are supposed to be affected by temperature regulation (1, 7, 34, 52, 54) and humoral systems (9, 36); 3) low frequencies (LF; >6-s cycle length in humans) that are sensitive to changes in cardiac sympathetic (and presumably parasympathetic) nerve activity (27, 30); and 4) high frequencies (HF; 2.5- to 6.0-s cycle length in humans) that are synchronized to the respiratory rhythm (5) and are primarily modulated by cardiac parasympathetic innervation (38).The most prominent oscillation in the ULF band of the heart rate spectrum is the circadian rhythm. The autonomic nervous system contributes significantly to circadian heart rate variability. Using long-term recordings in conscious rabbits, Barrett et al. (6) demonstrated a strong circadian rhythm in heart rate, mean arterial blood pressure, renal blood flow, and renal sympathetic nerve activity. The importance of this study is that it clearly demonstrates that sympathetic nerve discharges exhibit a strong circadian rhythmicity. The paraventricular nucleus of the hypothalamus (PVN) appears to play a central role in mediating the circadian rhythm of autonomic nervous system activity. First, GABAergic and glutamatergic neurons project from the suprachiasmatic nuclei of the hypothalamus (SCN) to spinal-projecting neurons of the PVN (12). The SCN is the major central oscillator that triggers the day/night cycle. It receives photic input from the retina (47) and drives many neuroendocrine, metabolic, autonomic, and behavioral circadian rhythms (14, 16, 21, 31, 35, 44, 46, 50). In addition, microinjections of the inhibitory neurotransmitter GABA into the PVN of anesthetized rats elicit dose-dependent decreases in renal sympathetic nerve activity, whereas bicuculline (a GABA antagonist) increases renal sympathetic nerve activity (56). Second, from the PVN, neurons project to the nucleus of the solitary tract (that integrates inputs from the baroreceptors), the nucleus ambiguus (origin of preganglionic parasympathetic neurons to the heart), the rostroventrolateral medulla (location of sympathetic premotor neurons), and the intermediolateral cell column of the thoracolumbar spinal cord (location of preganglionic sympathetic neurons). Thus PVN neurons can modulate autonomic nervous system activity by sending inputs to major sites of autonomic nervous system regulation. As an example, a pivotal role of the PVN for sympathoexcitation during parturition was recently demonstrated in sheep. The increase in sympathetic nerve activity that accompanies birth in maternal animals was prevented by stereotactic lesioning of the PVN (43). Taken together, a major component of the circadian heart rate variability is elicited by diurnal fluctuations in autonomic nervous system activity, generated by corresponding fluctuations of neuronal activity within the PVN, which depend on circadian inputs originating from the SCN.It has been suggested that thermoregulation affects VLF heart rate variability (10, 26). Cooling the heart causes bradycardia, a mechanism used in heart surgeries. Conversely, fever is known to increase heart rate. Raising body core temperature from 36.0 to 36.6°C caused an increase in heart rate by almost 40 beats/min in male subjects (1), whereas acutely reducing ambient temperature from thermoneutral conditions (35°C) to 29, 23, and 17°C, reduced heart rate from 400 to 250 beats/min in 8-day-old rats (7). In addition, lowering temperature in the isolated working rat heart from 37 to 31°C reduced heart rate from 332 to 215 beats/min and markedly increased heart rate variability (28), indicating that parts of the temperature effects on heart rate and heart rate variability are independent from the autonomic nervous system. In contrast to the tachycardia that accompanies acute elevations in temperature, chronically raising ambient temperature in adult rodents from a standard housing temperature of 21-23°C to thermoneutral conditions (29-30°C) reduced heart rate by roughly 50 beats/min in rats (34) and by 200-300 beats/min in mice (54). The authors of these articles (34, 54) suggested that standard housing temperatures are associated with cold stress that causes parallel activation of brown adipose tissue, cardiac, and vasomotor sympathetic drives that elicits nonshivering thermogenesis and tonically elevates heart rate and arterial blood pressure. These and other studies indicate that both direct effects of temperature on pacemaker activity of the sinus node (28) and indirect effects mediated via the autonomic nervous system (11, 25, 51, 55) mediate temperature effects on heart rate and heart rate variability. Thus fluctuation in temperature is an important source of heart rate variability that should not be underestimated. In a more recent study, this was taken into account by core body temperature correction of heart rate variability (3).Endocrine factors affecting heart rate variability include thyroxine, reproductive hormones, the renin-angiotensin system, steroids, and others. Chronic subcutaneous infusion of angiotensin II in rats markedly increased blood pressure and heart rate variability, expressed as standard deviation (9). In contrast, chronic corticosterone treatment is likely to reduce baroreflex-mediated heart rate variability, because baroreceptor-heart rate (39) and baroreceptor-renal sympathetic nerve activity reflex sensitivity (41) were blunted in chronically corticosterone-treated rats. Furthermore, an interaction between angiotensin II and glucocorticoids was recently described. Intracerebro-ventricular microinjections of angiotensin II AT1 receptor antagonists caused marked decreases in mean blood pressure and heart rate in rats chronically treated with corticosterone but not in control animals (40). This interaction is likely to take place in the central nervous system, because peripheral angiotensin II AT1 receptor blockade did not alter the effects of betamethasone treatment on blood pressure, heart rate, and baroreceptor-heart rate reflex sensitivity in newborn lambs (42).Adenosine is a substance less known to affect heart rate variability. It is produced locally in the heart (53) and binds to A1-adenosinergic receptors, which are among the earliest expressed G protein-coupled receptors in the heart (36). The A1-adenosinergic agonist N6-cyclopentyladenosine dose dependently reduced heart rate in murine embryos, whereas 1,3-dipropyl-8-cyclopentylxanthine, an A1-adenosinergic antagonist, increased heart rate (36). Adenosine also exerts central nervous system effects in various brain areas (15, 20). Microinjections of adenosine into the nucleus of the solitary tract of awake rats caused dose-dependent changes in heart rate: low doses (0.01 nmol) produced a bradycardic response, whereas high doses (2.5-5.0 nmol) elicited a tachycardic response (15). Thus adenosine may indeed be involved in the regulation of heart rate and modulate heart rate variability via local cardiac and central nervous system effects. It has been proposed that the intrinsic cardiac nervous system plays an active role in regulating cardiac function (4, 37, 45, 57). This nervous system consists of sympathetic and parasympathetic neurons and interconnecting local circuits (37). Neurons in the canine right atrial ganglionated plexus (RAGP) spontaneously generate activity even after chronic cardiac autonomic denervation (45). Right atrial neurons in patients undergoing coronary artery bypass surgery generated spontaneous activity that was unrelated to the cardiac cycle but sensitive to changes in systemic arterial pressure, indicating that these neurons receive pressure-sensitive sensory inputs (4). In addition, it has been suggested that substance P acts as a neuromodulator and neurotransmitter in intracardiac ganglia of the guinea pig, modulates the response to vagal inputs, and triggers action potentials at the site of parasympathetic ganglia independent of acetylcholine (57). Furthermore, the right atrial (RAGP) and the posterior atrial ganglionated plexus (PAGP) appear to have different functions. Ablation of the PAGP reduced vagally mediated bradycardia by 26%, whereas RAGP ablation completely abolished this response. Inhibition of sympathetically mediated tachycardia by vagal stimulation was attenuated by ablation of either plexus (37). Thus parasympathetic efferent neurons are primarily located in the RAGP, whereas prejunctional parasympathetic-sympathetic interactions also involve neurons within the PAGP (37). The spontaneous activity of neurons in the intrinsic cardiac nervous system, even after cardiac denervation (45), suggests an active role of this system in regulating heart rate. However, the impact of the intrinsic cardiac nervous system on heart rate variability remains to be elucidated. The importance of the autonomic nervous system for heart rate variability in humans becomes apparent in patients following cardiac transplantation, in whom heart rate variability is markedly reduced (49). Although reinnervation is possible after months and years, initially transplanted hearts can be considered to be denervated. Thus the reduced heart rate variability in cardiac transplanted patients (49) underlines the importance of an intact autonomic innervation for spontaneously occurring heart rate variability. A major component of the chronotropic effect of the autonomic nervous system is linked to cAMP. Intracellular cAMP increases the inward current of Na+ (funny current, If), which determines the rate of the slow diastolic depolarization that precedes each action potential. The activity of adenylate cyclase and thus intracellular cAMP levels are increased by stimulation of sympathetic β1-adrenergic receptors and decreased (via a Gi protein) by stimulation of parasympathetic muscarinic receptors. Thus cardiac sympathetic innervation increases the rate of the slow diastolic depolarization and accelerates heart rate, while cardiac parasympathetic innervation elicits opposite effects. Interestingly, parasympathetic-mediated changes in heart rate occur much faster than sympathetic-mediated effects on heart rate (27, 30, 47a). As a result, cardiac sympathetic nervous system activity can only affect LF components of heart rate variability, whereas the parasympathetic nervous system can also modulate HF components. A hitherto unsolved question in this context is if the rapid heart rate response to parasympathetic stimulation compared with the slow effect of sympathetic inputs is due to 1) different kinetics of β1-adrenergic vs. muscarinic receptors, 2) different kinetics of adenylate cyclase vs. phosphodiesterase, the enzyme that cleaves cAMP, or 3) fast parasympathetic-mediated opening of KACh channels (via muscarinic receptors and a GK protein). Support for the latter possibility comes from experiments in the rabbit sinoatrial node that demonstrated that activation of KACh channels contributes to the initial slowing of heart rate as a result of vagal stimulation (8).On the basis of the different frequency response characteristics of sympathetic and parasympathetic modulation of heart rate, frequency analysis of heart rate variability is often used as a tool to determine "autonomic balance" or sympathetic and parasympathetic nervous system activity (27, 47a). As an example, the wavelet transform was recently used to determine cardiac autonomic responses to reperfusion in patients with thrombolysis after coronary thrombosis. Depending on the location of the infarct, marked alterations in LF or HF spectral power of heart rate or in the LF/HF ratio was observed in all successful reperfusions (48).The HF component corresponds to the frequency of respiration and is driven by the vagus as indicated by the strong respiratory pattern of cardiac vagal motoneurons in the nucleus ambiguus (38). The LF component has been ascribed to sympathetic modulation of cardiac pacemaker activity, because a variety of studies demonstrated that acute interventions that increase sympathetic nervous system activity, such as orthostatic perturbations (17, 19, 33), mental stress (32), or handgrip exercise (13, 24) increases LF spectral power of heart rate (27, 30). In addition to acute perturbations of cardiac sympathetic nerve activity, feedback oscillations generated by the baroreceptor reflex also appear to contribute to LF spectral power of heart rate as it was demonstrated that sinoaortic denervation markedly reduces the LF component (27, 30). Despite the strong modulation of heart rate by the autonomic nervous system, the LF and HF spectral components of heart rate variability may not always be very reliable markers for cardiac sympathetic and parasympathetic "tone" (30). In a recent study, muscle sympathetic nerve activity was recorded together with heart rate variability during application of lower body negative pressure that is known to increase muscle sympathetic nerve activity (17, 33). At higher levels of lower body negative pressure (-15 mmHg), both muscle sympathetic nerve activity and relative LF spectral power of heart rate increased significantly, whereas HF spectral power decreased (17). These findings suggest that LF spectral power reflects cardiac sympathetic "tone." However, no correlation within subjects was found between changes in LF/HF ratio and muscle sympathetic nerve activity (17). Thus heart rate variability does not reliably reflect the sympathetic response to orthostatic stress. Respiration-related fluctuation of heart rate (respiratory sinus arrhythmia) is probably the most often investigated component of heart rate variability, as it is believed that this component reflects respiration-driven vagal modulation of sinus arrhythmia (27). In a recent study, Rentero et al. (38) recorded the electrical activity from cardiac vagal motoneurons in the nucleus ambiguus. Firing of these neurons was modulated by the central respiratory cycle. This and other studies support the view that respiratory sinus arrhythmia is generated by central coupling of the respiratory oscillator with autonomic centers in the brain stem. However, a mechanical cardiopulmonary coupling as a source of respiration-related heart rate variability has also been suggested (5). The Bainbridge reflex causes a tachycardia in response to hypervolemia. This reflex is initiated by atrial mechanoreceptors and uses efferent sympathetic and parasympathetic pathways to modulate heart rate in response to changes in central venous pressure (23). Thus respiratory changes in central blood volume cause corresponding respiratory fluctuations in cardiac autonomic nervous system activity via the Bainbridge reflex. Only the parasympathetic component of the efferent pathway of the reflex can contribute to respiratory sinus arrhythmia, because sympathetic actions on heart rate are too damped to follow the respiratory frequency. The gain and phase of the transfer function between respiratory changes in lung volume and R-R intervals of the ECG were calculated in human subjects during graded changes in central blood volume (5). At the respiratory frequency, the phase was -180 degree, indicating that an inspiratory increase in central blood volume was associated with a decrease in R-R interval (increase in heart rate). Furthermore, the gain of the transfer function at the respiratory frequency steadily increased with increasing central volumes (except at the highest volume). Both of these findings confirm the presence of the Bainbridge reflex in humans (5). Thus, in addition to the central coupling of respiratory oscillators with cardiovascular centers, the Bainbridge reflex may contribute to respiration-related heart rate variability by mechanical cardiopulmonary coupling. There is general agreement that low heart rate variability is an unfavorable prognostic marker for cardiovascular diseases, such as diabetic autonomic neuropathy, hypertension, myocardial infarction, and heart failure (18, 22, 27, 29, 47a). Heart rate variability (variance of R-R intervals) was reduced in patients with mild hypertension (29) compared with normal values (1,134 ± 202 vs. 3,466 ± 1,018 ms2) provided by the Task Force (47a). In the rat model of myocardial infarction-induced congestive heart failure, Francis and colleagues (18) reported loss of spontaneous heart rate variability 6 wk after coronary artery ligation. Interestingly, reduced heart rate variability was also observed in a rat model of depression that is based on chronic (4 wk) mild stress application (22). Because depression is an independent risk factor for coronary artery disease, this finding may realistically model a human disease process. The reduction in heart rate variability was abolished by β-adrenergic receptor blockade, indicating that the reduced heart rate variability in this model of depression is related to elevated cardiac sympathetic tone (22).In summary, heart rate variability is generated by multiple factors not exclusively limited to the autonomic nervous system. Specific frequency components of heart rate variability mirror acute perturbations of the autonomic nervous system but do not always reflect autonomic nervous system activity. Simple statistics of heart rate variability, such as the standard deviation of R-R intervals in the ECG, can reliably predict the prognosis of cardiovascular diseases.I thank Dr. R. McAllen for critically reviewing the manuscript. References 1 Aoki K, Stephens DP, and Johnson JM. Diurnal variation in cutaneous vasodilator and vasoconstrictor systems during heat stress. Am J Physiol Regul Integr Comp Physiol 281: R591-R595, 2001.Link | ISI | Google Scholar3 Aoyagi N, Ohashi K, and Yamamoto Y. Frequency characteristics of long-term heart rate variability during constant-routine protocol. Am J Physiol Regul Integr Comp Physiol 285: R171-R176, 2003.Link | ISI | Google Scholar4 Arora RC, Hirsch GM, Johnson Hirsch K, Hancock Friesen C, and Armour JA. Function of human intrinsic cardiac neurons in situ. Am J Physiol Regul Integr Comp Physiol 280: R1736-R1740, 2001.Link | ISI | Google Scholar5 Barbieri R, Triedman JK, and Saul JP. Heart rate control and mechanical cardiopulmonary coupling to assess central volume: a systems analysis. Am J Physiol Regul Integr Comp Physiol 283: R1210-R1220, 2002.Link | ISI | Google Scholar6 Barrett CJ, Navakatikyan MA, and Malpas SC. Long-term control of renal blood flow: what is the role of the renal nerves? Am J Physiol Regul Integr Comp Physiol 280: R1534-R1545, 2001.Link | ISI | Google Scholar7 Blumberg MS, Knoot TG, and Kirby RF. Neural and hormonal control of arterial pressure during cold exposure in un-anesthetized week-old rats. Am J Physiol Regul Integr Comp Physiol 281: R1514-R1521, 2001.Link | ISI | Google Scholar8 Boyett MR, Kodama I, Honjo H, Arai A, Suzuki R, and Toyama J. Ionic basis of the chronotropic effect of acetylcholine on the rabbit sinoatrial node. Cardiovasc Res 29: 867-878, 1995.Crossref | PubMed | ISI | Google Scholar9 Braga and of on fluctuations and changes in blood pressure. Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google and elicited of heart rate variability. J Physiol | ISI | Google and modulation of sympathetic nerve activity to muscle in Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google and and GABA mediate suprachiasmatic nucleus inputs to spinal-projecting paraventricular Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and is not associated with of the exercise reflex in Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google C, and Y. The effect of on the circadian control of human core body temperature is Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and of adenosine receptors in the does not affect the in awake rats. Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google JK, A, and circadian and during two Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and sympathetic nerve and heart rate spectral effects of lower body negative pressure. Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google Francis Johnson and of heart failure after myocardial in the Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google A, and of lower body pressure on muscle sympathetic nerve activity response to Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and Adenosine initial depression of in the rat in Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google R, and and circadian phase in a diurnal the Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and Johnson alterations and autonomic in an model of Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google MA, and The interaction of the Bainbridge and in the conscious Res | ISI | Google A, and handgrip exercise arterial control of sympathetic in Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and nerve regulation to is in rats. Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and in heart rate variability. J Physiol | ISI | Google and function and cardiovascular interactions and Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and interval variability in isolated working rat hearts at various conditions and Res | PubMed | Google A, A, and and autonomic of in patients with mild Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google Malpas SC. Neural on cardiovascular and Am J Physiol Heart Physiol 2002.Link | ISI | Google and thermoregulation in and rats in a Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and effects on reflex responses to mental stress in Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and reflex during orthostatic in Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and and responses to and are in rats. Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and and in a by cycle. Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and of humoral heart rate regulation in the Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google Armour and within the intrinsic cardiac nervous system contribute to chronotropic regulation. Am J Physiol Regul Integr Comp Physiol 285: 2003.Link | ISI | Google Rentero N, A, and McAllen of cardiac vagal motoneurons in rat nucleus ambiguus. Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and modulate control of heart rate in conscious rats. Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google and central actions of angiotensin to increase arterial pressure. Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and modulate control of renal sympathetic nerve activity. Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and modulation of cardiovascular and autonomic function in role of Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and Inhibition of sympathetic responses at birth in by of the paraventricular Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and JP. pattern of during acute and chronic in conscious adult rats. Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google Armour and of chronic cardiac on of canine intracardiac neurons in Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and levels and circadian rhythm of activity in the a model of Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and nerve response of suprachiasmatic nucleus and Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google

American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · review · 309 citationsread the source →

A global assessment of the gender gap in self-reported health with survey data from 59 countries.

Background: While surveys in high-income countries show that women generally have poorer self-reported health than men, much less is known about gender differences in other regions of the world. Such data can be used to examine the determinants of sex differences. Methods: We analysed data on respondents 18 years and over from the World Health Surveys 2002-04 in 59 countries, which included multiple measures of self-reported health, eight domains of functioning and presumptive diagnoses of chronic conditions. The age-standardized female excess fraction was computed for all indicators and analysed for five regional groups of countries. Multivariate regression models were used to examine the association between country gaps in self-reported health between the sexes with societal and other background characteristics. Results: Women reported significantly poorer health than men on all self-reported health indicators. The excess fraction was 15 % for the health score based on the eight domains, 28 % for "poor" or "very poor" self-rated health on the single question, and 26 % for "severe" or "extreme" on a single question on limitations. The excess female reporting of poorer health occurred at all ages, but was smaller at ages 60 and over. The female excess was observed in all regions, and was smallest in the European high-income countries. Women more frequently reported problems in specific health domains, with the excess fraction ranging from 25 % for vision to 35 % for mobility, pain and sleep, and with considerable variation between regions. Angina, arthritis and depression had female excess fractions of 33, 32 and 42 % respectively. Higher female prevalence of the presumptive diagnoses was observed in all regional country groups. The main factors affecting the size of the gender gap in self-reported health were the female-male gaps in the prevalence of chronic conditions, especially arthritis and depression and gender characteristics of the society. Conclusions: Large female-male differences in self-reported health and functioning, equivalent to a decade of growing older, consistently occurred in all regions of the world, irrespective of differences in mortality levels or societal factors. The multi-country study suggests that a mix of biological factors and societal gender inequalities are major contributing factors to gender gap in self-reported measures of health.

BMC public health · 169 citationsread the source →

"There Was a Sense That Our Load Had Been Lightened": Evaluating Outcomes of Virtual Ethics Rounds for Veterinary Team Members.

Clinical ethics support services (CESS) are employed in healthcare to improve patient care and help team members develop skills to recognize and navigate ethically challenging situations (ECS). The objective of this study was to evaluate the impact of ethics rounds, one form of CESS, on veterinary team members. An anonymous, online mixed-methods survey incorporating a 15-item instrument designed to assess the outcomes of moral case deliberation originally developed for human healthcare workers (the Euro-MCD 2.0), was developed. The survey was administered to veterinary team members prior to and following participation in a 90-min virtual ethics rounds session. A total of 23 sessions of virtual ethics rounds were held. In total, 213 individuals participated, and 89 completed both surveys (response rate 41.8%). Most respondents were female (n = 70, 81%). Most were veterinarians (n = 51, 59%), followed by other veterinary team members (practice manager, animal attendant) (n = 18, 21%), veterinary nurses or animal health technicians (n = 10, 12%) and veterinary students (n = 8, 9%). Age ranged from 20 to 73 (median 41, IQR 32-52, n = 87). While there was no statistically significant difference between overall modified Euro-MCD 2.0 scores between T1 and T2, there were statistically significant changes in 7 out of 15 Euro-MCD 2.0 items in the domains of moral competence and moral teamwork. Reflexive thematic analysis of free-text responses identified themes including the types, impact and barriers to resolving ECS, the impacts of ethics rounds on veterinary team members and constraints preventing veterinary team members from speaking up in the face of ECS. While participants largely described the impact of ethics rounds as beneficial (for example, by facilitating clarification of thinking about ECS, allowing participants to see ECS from the perspective of others and providing a safe space for discussion), reflecting on ECS could be stressful for participants. Active participation in ethics rounds may be inhibited in the context of power imbalance, or in settings where bullying occurs. Overall, carefully facilitated ethics rounds has the potential to improve the ability of veterinary team members to identify and navigate ECS, and potentially mitigate moral distress.

Frontiers in veterinary science · 8 citationsread the source →

Neuroticism, acculturation and the cortisol awakening response in Mexican American adults.

Neuroticism is associated with greater susceptibility to the adverse effects of stress and greater exposure to the stressors associated with acculturation in U.S. born Mexican Americans. Neuroticism and acculturation have been associated with injury to crucial stress response systems and are known risk factors for certain mood and anxiety disorders. The purpose of the current study was to examine the effects of neuroticism, and acculturation on the cortisol awakening response (CAR) in healthy Mexican-American adults. Salivary cortisol samples were collected at awakening and 30, 45, and 60 min thereafter, on two consecutive weekdays from 59 healthy Mexican American adult males (26) and females (33), ages 18 to 38 years. Participants were assessed for level of neuroticism and acculturation. Data were analyzed using a mixed effects regression model with repeated measures at four time points. Results showed a significant Neuroticism×Acculturation×Time interaction. The CAR was virtually eliminated in highly acculturated Mexican Americans with greater Anglo orientation and high neuroticism compared with less acculturated Mexican Americans with greater Mexican orientation and lower neuroticism. Findings suggest that some Mexican Americans with high levels of neuroticism may be particularly susceptible to certain challenges and stressors associated with acculturation leading over time to the development of allostatic load, desensitization of the Hypothalamic CRF system and attenuation of the CAR.

Hormones and behavior · 24 citationsread the source →

Racial differences in legal socialization models across adolescence and emerging adulthood.

Objective: White and non-White adolescents report different experiences in the legal system. This disparity impacts their evaluations of, and attitudes toward, legal authorities such that non-White and older adolescents tend to perceive the legal system more negatively. Yet, many researchers assume that the process of legal socialization, which involves internalizing norms and information about the law and the legal system, is universal for all ages and races. Hypotheses: We hypothesized that legal socialization models would change over the course of adolescent development and would differ by race. Method: We used data from two longitudinal studies to examine racial differences in the integrated legal socialization model in early, middle, and late adolescence. Study 1 included 140 young adolescents (59% White, 41% non-White), and Study 2 included 296 midadolescents (82% White, 18% non-White) followed into late adolescence/emerging adulthood. Results: Study 1 identified differences in the integrated legal socialization model for young White and non-White adolescents. Normative status predicted rule-violating behavior for White participants, whereas no predictors or mediators related to rule-violating behavior for non-White participants. In Study 2, legal and moral reasoning during midadolescence became relevant in the model for both groups. Enforcement status predicted rule-violating behavior for non-White youth, whereas normative status continued to predict rule-violating behavior for White youth. In late adolescence/emerging adulthood, differences in the model shifted toward the relation between reasoning and legal attitudes. Conclusions: Our findings suggest that legal socialization is a developmental process occurring and changing throughout adolescence and that this developmental process differs for White and non-White youth. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Law and human behaviorread the source →

Acculturation, childhood trauma and the cortisol awakening response in Mexican-American adults.

Exposure to chronic and traumatic stress has been associated with the dysregulation of crucial stress response systems. Acculturation has been associated with unique forms of chronic psychosocial stress. The purpose of this study was to examine the effects of exposure to early traumatic stress and acculturation on dysregulation of the cortisol awakening response (CAR) in Mexican-American adults. Salivary cortisol samples were collected at awakening and 30, 45, and 60 min thereafter, on two consecutive weekdays from 59 healthy Mexican-American adult males (26) and females (33), ages 18-38 years. Participants were assessed for level of acculturation and exposure to early trauma. Data were analyzed using a mixed effects regression model with repeated measures at four time points. Mixed effects regression results indicated a significant Early Trauma x Time interaction (p=.0029) and a significant Acculturation x Time interaction (p=.0015), after controlling for age and sex. Subsequent analyses of the interaction of Trauma x Acculturation x Time showed that more than minimal exposure to either risk factor was associated with attenuation of the awakening cortisol response (p=.0002). Higher levels of acculturation with greater Anglo-orientation were associated with attenuation of the CAR in Mexican-American adults. Both moderate and higher levels of exposure to early trauma were associated with an attenuated CAR. However, greater exposure to both risk factors was only incrementally worse than exposure to either one.

Hormones and behavior · 44 citationsread the source →

Adverse childhood experiences in the children of the Avon Longitudinal Study of Parents and Children (ALSPAC).

Background: Exposure to adverse childhood experiences (ACEs) is a risk factor for poor later life health. Here, we describe the ACE variables measured in the children of the Avon Longitudinal Study of Parents and Children (ALSPAC) study, and a method used to derive summary measures and deal with missing data in them.    Methods: The ALSPAC data catalogue (59 608 variables) was searched in September 2017 for measures on adversity exposure between birth and 18 years. 6140 adversity questions were then screened for conforming to our ACE definitions and suitability for dichotomisation. This screening identified 541 questions on ten 'classic' ACEs (sexual, physical or emotional abuse, emotional neglect, substance abuse by the parents, parental mental illness or suicide attempt, violence between parents, parental separation, bullying and parental criminal conviction) and nine additional ACEs (bond between parent and child, satisfaction with neighbourhood, social support for the parent, social support for the child, physical illness of a parent, physical illness of the child, financial difficulties, low social class and violence between child and partner). These were used to derive a binary construct for exposure to each ACE. Finally, as cumulative measures of childhood adversity, different combinations of the 19 ACE constructs were summed to give total adversity scores. An appropriate strategy for multiple imputation was developed to deal with the complex patterns of missing data. Results: The ACE constructs and ACE-scores for exposure between birth and 16 years had prevalence estimates that were comparable to previous reports (for instance 4% sexual abuse, 18% physical abuse, 25% bullied, 32% parental separation). Conclusions: ACE constructs, derived using a pragmatic approach to handle the high dimensional ALSPAC data, can be used in future analyses on childhood adversity in ALSPAC children.

Wellcome open research · 84 citationsread the source →