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Association Between Palliative Care and Patient and Caregiver Outcomes: A Systematic Review and Meta-analysis.

Importance: The use of palliative care programs and the number of trials assessing their effectiveness have increased. Objective: To determine the association of palliative care with quality of life (QOL), symptom burden, survival, and other outcomes for people with life-limiting illness and for their caregivers. Data sources: MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL to July 2016. Study selection: Randomized clinical trials of palliative care interventions in adults with life-limiting illness. Data extraction and synthesis: Two reviewers independently extracted data. Narrative synthesis was conducted for all trials. Quality of life, symptom burden, and survival were analyzed using random-effects meta-analysis, with estimates of QOL translated to units of the Functional Assessment of Chronic Illness Therapy-palliative care scale (FACIT-Pal) instrument (range, 0-184 [worst-best]; minimal clinically important difference [MCID], 9 points); and symptom burden translated to the Edmonton Symptom Assessment Scale (ESAS) (range, 0-90 [best-worst]; MCID, 5.7 points). Main outcomes and measures: Quality of life, symptom burden, survival, mood, advance care planning, site of death, health care satisfaction, resource utilization, and health care expenditures. Results: Forty-three RCTs provided data on 12 731 patients (mean age, 67 years) and 2479 caregivers. Thirty-five trials used usual care as the control, and 14 took place in the ambulatory setting. In the meta-analysis, palliative care was associated with statistically and clinically significant improvements in patient QOL at the 1- to 3-month follow-up (standardized mean difference, 0.46; 95% CI, 0.08 to 0.83; FACIT-Pal mean difference, 11.36] and symptom burden at the 1- to 3-month follow-up (standardized mean difference, -0.66; 95% CI, -1.25 to -0.07; ESAS mean difference, -10.30). When analyses were limited to trials at low risk of bias (n = 5), the association between palliative care and QOL was attenuated but remained statistically significant (standardized mean difference, 0.20; 95% CI, 0.06 to 0.34; FACIT-Pal mean difference, 4.94), whereas the association with symptom burden was not statistically significant (standardized mean difference, -0.21; 95% CI, -0.42 to 0.00; ESAS mean difference, -3.28). There was no association between palliative care and survival (hazard ratio, 0.90; 95% CI, 0.69 to 1.17). Palliative care was associated consistently with improvements in advance care planning, patient and caregiver satisfaction, and lower health care utilization. Evidence of associations with other outcomes was mixed. Conclusions and relevance: In this meta-analysis, palliative care interventions were associated with improvements in patient QOL and symptom burden. Findings for caregiver outcomes were inconsistent. However, many associations were no longer significant when limited to trials at low risk of bias, and there was no significant association between palliative care and survival.

JAMA · meta-analysis · 799 citationsread the source →

A co-designed mHealth programme to support healthy lifestyles in Māori and Pasifika peoples in New Zealand (OL@-OR@): a cluster-randomised controlled trial.

Background: The OL@-OR@ mobile health programme was co-designed with Māori and Pasifika communities in New Zealand, to support healthy lifestyle behaviours. We aimed to determine whether use of the programme improved adherence to health-related guidelines among Māori and Pasifika communities in New Zealand compared with a control group on a waiting list for the programme. Methods: The OL@-OR@ trial was a 12-week, two-arm, cluster-randomised controlled trial. A cluster was defined as any distinct location or setting in New Zealand where people with shared interests or contexts congregated, such as churches, sports clubs, and community groups. Members of a cluster were eligible to participate if they were aged 18 years or older, had regular access to a mobile device or computer, and had regular internet access. Clusters of Māori and of Pasifika (separately) were randomly assigned (1:1) to either the intervention or control condition. The intervention group received the OL@-OR@ mHealth programme (smartphone app and website). The control group received a control version of the app that only collected baseline and outcome data. The primary outcome was self-reported adherence to health-related guidelines, which were measured with a composite health behaviour score (of physical activity, smoking, alcohol intake, and fruit and vegetable intake) at 12 weeks. The secondary outcomes were self-reported adherence to health-related behaviour guidelines at 4 weeks; self-reported bodyweight at 12 weeks; and holistic health and wellbeing status at 12 weeks, in all enrolled individuals in eligible clusters; and user engagement with the app, in individuals allocated to the intervention. Adverse events were not collected. This study is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12617001484336. Findings: Between Jan 24 and Aug 14, 2018, we enrolled 337 Māori participants from 19 clusters and 389 Pasifika participants from 18 clusters (n=726 participants) in the intervention group and 320 Māori participants from 15 clusters and 405 Pasifika participants from 17 clusters (n=725 participants) in the control group. Of these participants, 227 (67%) Māori participants and 347 (89%) Pasifika participants (n=574 participants) in the intervention group and 281 (88%) Māori participants and 369 (91%) Pasifika participants (n=650 participants) in the control group completed the 12-week follow-up and were included in the final analysis. Relative to baseline, adherence to health-related behaviour guidelines increased at 12 weeks in both groups (315 [43%] of 726 participants at baseline to 329 [57%] of 574 participants in the intervention group; 331 [46%] of 725 participants to 369 [57%] of 650 participants in the control group); however, there was no significant difference between intervention and control groups in adherence at 12 weeks (odds ratio [OR] 1·13; 95% CI 0·84-1·52; p=0·42). Furthermore, the proportion of participants adhering to guidelines on physical activity (351 [61%] of 574 intervention group participants vs 407 [63%] of 650 control group participants; OR 1·03, 95% CI 0·73-1·45; p=0·88), smoking (434 [76%] participants vs 501 [77%] participants; 1·12, 0·67-1·87; p=0·66), alcohol consumption (518 [90%] participants vs 596 [92%] participants; 0·73, 0·37-1·44; p=0·36), and fruit and vegetable intake (194 [34%] participants vs 196 [30%] participants; 1·08, 0·79-1·49; p=0·64) did not differ between groups. We found no significant differences between the intervention and control groups in any secondary outcome. 147 (26%) intervention group participants engaged with the OL@-OR@ programme (ie, set at least one behaviour change goal online). Interpretation: The OL@-OR@ mobile health programme did not improve adherence to health-related behaviour guidelines amongst Māori and Pasifika individuals. Funding: Healthier Lives He Oranga Hauora National Science Challenge.

The Lancet. Digital health · randomised controlled trial · 45 citationsread the source →

Long-term effects of cardiac rehabilitation after heart valve surgery - results from the randomised CopenHeartVR trial.

Aims. The CopenHeartVR trial found positive effects of cardiac rehabilitation (CR) on physical capacity at 4 months. The long-term effects of CR following valve surgery remains unclear, especially regarding readmission and mortality. Using data from he CopenHeartVR Trial we investigated long-term effects on physical capacity, mental and physical health and effect on mortality and readmission rates as prespecified in the original protocol. Methods. A total of 147 participants were included after heart valve surgery and randomly allocated 1:1 to 12-weeks exercise-based CR including a psycho-educational programme (intervention group) or control. Physical capacity was assessed as peak oxygen uptake (VO2 peak) measured by cardiopulmonary exercise testing, mental and physical health by Short Form-36 questionnaire, Hospital Anxiety and Depression Scale, and HeartQol. Mortality and readmission were obtained from hospital records and registers. Groups were compared using mixed regression model analysis and log rank test. Results. No differences in VO2 peak at 12 months or in self-assessed mental and physical health at 24 months (68% vs 75%, p = .120) was found. However, our data demonstrated reduction in readmissions in the intervention group at intermediate time points; after 3, 6 (43% vs 59%, p = .03), and 12 (53% vs 67%, p = .04) months, respectively, but no significant effect at 24 months. Conclusions. Exercise-based CR after heart valve surgery reduces combined readmissions and mortality up to 12 months despite lack of improvement in exercise capacity, physical and mental health long-term. Exercise-based CR can ensure short-term benefits in terms of physical capacity, and lower readmission within a year, but more research is needed to sustain these effects over a longer time period. These considerations should be included in the management of patients after heart valve surgery.

Scandinavian cardiovascular journal : SCJ · randomised controlled trial · 9 citationsread the source →

Effect of Telephone Cognitive Behavioral Therapy for Insomnia in Older Adults With Osteoarthritis Pain: A Randomized Clinical Trial.

Importance: Scalable delivery models of cognitive behavioral therapy for insomnia (CBT-I), an effective treatment, are needed for widespread implementation, particularly in rural and underserved populations lacking ready access to insomnia treatment. Objective: To evaluate the effectiveness of telephone CBT-I vs education-only control (EOC) in older adults with moderate to severe osteoarthritis pain. Design, setting, and participants: This is a randomized clinical trial of 327 participants 60 years and older who were recruited statewide through Kaiser Permanente Washington from September 2016 to December 2018. Participants were double screened 3 weeks apart for moderate to severe insomnia and osteoarthritis (OA) pain symptoms. Blinded assessments were conducted at baseline, after 2 months posttreatment, and at 12-month follow-up. Interventions: Six 20- to 30-minute telephone sessions provided over 8 weeks. Participants submitted daily diaries and received group-specific educational materials. The CBT-I instruction included sleep restriction, stimulus control, sleep hygiene, cognitive restructuring, and homework. The EOC group received information about sleep and OA. Main outcomes and measures: The primary outcome was score on the Insomnia Severity Index (ISI) at 2 months posttreatment and 12-month follow-up. Secondary outcomes included pain (score on the Brief Pain Inventory-short form), depression (score on the 8-item Patient Health Questionnaire), and fatigue (score on the Flinders Fatigue Scale). Results: Of the 327 participants, the mean (SD) age was 70.2 (6.8) years, and 244 (74.6%) were women. In the 282 participants with follow-up ISI data, the total 2-month posttreatment ISI scores decreased 8.1 points in the CBT-I group and 4.8 points in the EOC group, an adjusted mean between-group difference of -3.5 points (95% CI, -4.4 to -2.6 points; P < .001). Results were sustained at 12-month follow-up (adjusted mean difference, -3.0 points; 95% CI, -4.1 to -2.0 points; P < .001). At 12-month follow-up, 67 of 119 (56.3%) participants receiving CBT-I remained in remission (ISI score, ≤7) compared with 33 of 128 (25.8%) participants receiving EOC. Fatigue was also significantly reduced in the CBT-I group compared with the EOC group at 2 months posttreatment (mean between-group difference, -2.0 points; 95% CI, -3.1 to -0.9 points; P = <.001) and 12-month follow-up (mean between-group difference, -1.8 points; 95% CI, -3.1 to -0.6 points; P = .003). Posttreatment significant differences were observed for pain, but these differences were not sustained at 12-month follow-up. Conclusions and relevance: In this randomized clinical trial, telephone CBT-I was effective in improving sleep, fatigue, and, to a lesser degree, pain among older adults with comorbid insomnia and OA pain in a large statewide health plan. Results support provision of telephone CBT-I as an accessible, individualized, effective, and scalable insomnia treatment. Trial registration: Clinical Trials.gov Identifier: NCT02946957.

JAMA internal medicine · randomised controlled trial · 69 citationsread the source →

Tenofovir-diphosphate in peripheral blood mononuclear cells during low, medium and high adherence to emtricitabine/ tenofovir alafenamide vs. emtricitabine/ tenofovir disoproxil fumarate.

Objective: Tenofovir alafenamide (TAF) preferentially loads peripheral blood mononuclear cells (PBMCs), resulting in higher PBMC tenofovir-diphosphate (TFV-DP) vs. tenofovir disoproxil fumarate (TDF). No studies have yet compared TFV-DP in PBMC from lower than daily dosing between prodrugs, which has potential implications for event-driven preexposure prophylaxis and pharmacologic forgiveness. Design: Two separate randomized, directly observed therapy (DOT) crossover studies (DOT-DBS and TAF-DBS) were conducted to mimic low, medium and high adherence. Methods: HIV-negative adults were randomized to two 12-week DOT regimens of 33, 67 or 100% of daily dosing with emtricitabine (F)/TAF 200 mg/25 mg (TAF-DBS) or F/TDF 200 mg/300 mg (DOT-DBS), separated by a 12-week washout. PBMC steady-state concentrations (Css) of TFV-DP and FTC-TP were estimated using nonlinear mixed models and compared between F/TAF and F/TDF. Results: Thirty-five participants contributed to 33% (n = 23), 67% (n = 23) and 100% (n = 23) of daily F/TAF regimens. Forty-four contributed to 33% (n = 15), 67% (n = 16) and 100% (n = 32) of daily F/TDF regimens. PBMC TFV-DP Css were 7.3 [95% confidence interval (95% CI): 6.4-8.2], 7.1 (5.9-8.2) and 6.7- (4.4-8.9) fold higher (P < 0.0001) following F/TAF vs. F/TDF; 593 vs. 81.7, 407 vs. 57.4, and 215 vs. 32.3 fmol/106 cells, respectively. TFV-DP was 2.6 (2.1-3.1) fold higher with 33% F/TAF vs. 100% F/TDF. Estimated half-lives (95% CI) of TFV-DP in PBMC were 2.9 (1.5-5.5) days for F/TAF and 2.1 (1.5-2.9) days for F/TDF. FTC-TP was similar in both studies (P = 0.119). Conclusion: F/TAF produced 6.7 to 7.3-fold higher TFV-DP in PBMC vs. F/TDF across adherence levels, supporting increased potency and pharmacologic forgiveness with F/TAF in the PBMC compartment.

AIDS (London, England) · randomised controlled trial · 27 citationsread the source →

Effectiveness and cost-effectiveness of referral to a commercial open group behavioural weight management programme in adults with overweight and obesity: 5-year follow-up of the WRAP randomised controlled trial.

Background: There is evidence that commercially available behavioural weight management programmes can lead to short-term weight loss and reductions in glycaemia. Here, we aimed to provide the 5-year impact and cost-effectiveness of these interventions compared with a brief intervention. Methods: WRAP was a non-blinded, parallel-group randomised controlled trial (RCT). We recruited from primary care practices in England and randomly assigned participants to one of three interventions (brief intervention, 12-week open-group behavioural programme [WW, formerly Weight Watchers], or a 52-week open-group WW behavioural programme) in an uneven (2:5:5) allocation. Participants were followed up 5 years after randomisation using data from measurement visits at primary care practices or a research centre, review of primary care electronic medical notes, and self-report questionnaires. The primary outcome was change in weight at 5 years follow-up, assessed using analysis of covariance. We also estimated cost-effectiveness of the intervention. This study is registered at Current Controlled Trials, ISRCTN64986150. Findings: Between Oct 18, 2012, and Feb 10, 2014, we recruited 1269 eligible participants (two participants were randomly assigned but not eligible and therefore excluded) and 1040 (82%) consented to be approached about additional follow-up and to have their medical notes reviewed at 5 years. The primary outcome (weight) was ascertained for 871 (69%) of 1267 eligible participants. Mean duration of follow-up was 5·1 (SD 0·3) years. Mean weight change from baseline to 5 years was -0·46 (SD 8·31) kg in the brief intervention group, -1·95 (9·55) kg in the 12-week programme group, and -2·67 (9·81) kg in the 52-week programme. The adjusted difference in weight change was -1·76 (95% CI -3·68 to 0·17) kg between the 52-week programme and the brief intervention; -0·80 (-2·13 to 0·54) kg between the 52-week and the 12-week programme; and -0·96 (-2·90 to 0·97) kg between the 12-week programme and the brief intervention. During the trial, the 12-week programme incurred the lowest cost and produced the highest quality-adjusted life-years (QALY). Simulations beyond 5 years suggested that the 52-week programme would deliver the highest QALYs at the lowest cost and would be the most cost-effective. No participants reported adverse events related to the intervention. Interpretation: Although the difference in weight change between groups was not statistically significant, some weight loss was maintained at 5 years after an open-group behavioural weight management programme. Health economic modelling suggests that this could have important implications to reduce the incidence of weight-related disease and these interventions might be cost-saving. Funding: The UK National Institute for Health and Care Research Programme Grants for Applied Research and the Medical Research Council.

The Lancet. Public health · randomised controlled trial · 25 citationsread the source →

CollAborative care for Screen-Positive EldeRs with major depression (CASPER plus): a multicentred randomised controlled trial of clinical effectiveness and cost-effectiveness.

Background: Depression in older adults is common and is associated with poor quality of life, increased morbidity and early mortality, and increased health and social care use. Collaborative care, a low-intensity intervention for depression that is shown to be effective in working-age adults, has not yet been evaluated in older people with depression who are managed in UK primary care. The CollAborative care for Screen-Positive EldeRs (CASPER) plus trial fills the evidence gap identified by the most recent guidelines on depression management. Objectives: To establish the clinical effectiveness and cost-effectiveness of collaborative care for older adults with major depressive disorder in primary care. Design: A pragmatic, multicentred, two-arm, parallel, individually randomised controlled trial with embedded qualitative study. Participants were automatically randomised by computer, by the York Trials Unit Randomisation Service, on a 1 : 1 basis using simple unstratified randomisation after informed consent and baseline measures were collected. Blinding was not possible. Setting: Sixty-nine general practices in the north of England. Participants: A total of 485 participants aged ≥ 65 years with major depressive disorder. Interventions: A low-intensity intervention of collaborative care, including behavioural activation, delivered by a case manager for an average of six sessions over 7-8 weeks, alongside usual general practitioner (GP) care. The control arm received only usual GP care. Main outcome measures: The primary outcome measure was Patient Health Questionnaire-9 items score at 4 months post randomisation. Secondary outcome measures included depression severity and caseness at 12 and 18 months, the EuroQol-5 Dimensions, Short Form questionnaire-12 items, Patient Health Questionnaire-15 items, Generalised Anxiety Disorder-7 items, Connor-Davidson Resilience Scale-2 items, a medication questionnaire, objective data and adverse events. Participants were followed up at 12 and 18 months. Results: In total, 485 participants were randomised (collaborative care, n = 249; usual care, n = 236), with 390 participants (80%: collaborative care, 75%; usual care, 86%) followed up at 4 months, 358 participants (74%: collaborative care, 70%; usual care, 78%) followed up at 12 months and 344 participants (71%: collaborative care, 67%; usual care, 75%) followed up at 18 months. A total of 415 participants were included in primary analysis (collaborative care, n = 198; usual care, n = 217), which revealed a statistically significant effect in favour of collaborative care at the primary end point at 4 months [8.98 vs. 10.90 score points, mean difference 1.92 score points, 95% confidence interval (CI) 0.85 to 2.99 score points; p  < 0.001], equivalent to a standard effect size of 0.34. However, treatment differences were not maintained in the longer term (at 12 months: 0.19 score points, 95% CI -0.92 to 1.29 score points; p = 0.741; at 18 months: < 0.01 score points, 95% CI -1.12 to 1.12 score points; p = 0.997). The study recorded details of all serious adverse events (SAEs), which consisted of 'unscheduled hospitalisation', 'other medically important condition' and 'death'. No SAEs were related to the intervention. Collaborative care showed a small but non-significant increase in quality-adjusted life-years (QALYs) over the 18-month period, with a higher cost. Overall, the mean cost per incremental QALY for collaborative care compared with usual care was £26,016; however, for participants attending six or more sessions, collaborative care appears to represent better value for money (£9876/QALY). Limitations: Study limitations are identified at different stages: design (blinding unfeasible, potential contamination), process (relatively low overall consent rate, differential attrition/retention rates) and analysis (no baseline health-care resource cost or secondary/social care data). Conclusion: Collaborative care was effective for older people with case-level depression across a range of outcomes in the short term though the reduction in depression severity was not maintained over the longer term of 12 or 18 months. Participants who received six or more sessions of collaborative care did benefit substantially more than those who received fewer treatment sessions but this difference was not statistically significant. Future work recommendations: Recommendations for future research include investigating the longer-term effect of the intervention. Depression is a recurrent disorder and it would be useful to assess its impact on relapse and the prevention of future case-level depression. Trial registration: Current Controlled Trials ISRCTN45842879. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 67. See the NIHR Journals Library website for further project information.

Health technology assessment (Winchester, England) · randomised controlled trial · 33 citationsread the source →

Healthy strategies for successful weight loss and weight maintenance: a systematic review.

The rates of overweight and obesity are rising in Canada and worldwide, and there is a need for effective methods for weight loss and weight maintenance to empower individuals to make changes. The purpose of this systematic review was to examine the evidence available for successful diet strategies for weight loss and weight maintenance among adults. A search was conducted of the following databases: CAB Abstracts, Central Register of Controlled Trials, EMBASE, MEDLINE, Food Science and Technology Abstracts, and Web of Knowledge. The studies investigated had participants who were overweight or obese and between 18 and 65 years of age. A successful study was defined as one that reported an intervention that created ≥5% weight loss from baseline and a maintenance phase during which the ≥5% weight loss was maintained from baseline to 12 months. After exclusions, the search resulted in 67 papers. Overall, for significant safe weight loss, an energy deficit was required, which was commonly achieved by reduced fat intake. Increased dietary fibre was also a component of 21% of successful interventions. Physical activity was included in 88% of successful interventions, and behaviour training such as self-monitoring was part of 92% of successful interventions. The same combination of energy and fat restriction, regular physical activity, and behavioural strategies was also required for successful weight maintenance. This review confirmed previous knowledge about weight loss and weight maintenance in adults. A comprehensive approach, including reduced dietary intake, regular physical activity, and behavioural strategies, is warranted and is supported by the research evidence.

Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme · systematic review · 111 citationsread the source →

Suicide prevention strategies revisited: 10-year systematic review.

Background: Many countries are developing suicide prevention strategies for which up-to-date, high-quality evidence is required. We present updated evidence for the effectiveness of suicide prevention interventions since 2005. Methods: We searched PubMed and the Cochrane Library using multiple terms related to suicide prevention for studies published between Jan 1, 2005, and Dec 31, 2014. We assessed seven interventions: public and physician education, media strategies, screening, restricting access to suicide means, treatments, and internet or hotline support. Data were extracted on primary outcomes of interest, namely suicidal behaviour (suicide, attempt, or ideation), and intermediate or secondary outcomes (treatment-seeking, identification of at-risk individuals, antidepressant prescription or use rates, or referrals). 18 suicide prevention experts from 13 European countries reviewed all articles and rated the strength of evidence using the Oxford criteria. Because the heterogeneity of populations and methodology did not permit formal meta-analysis, we present a narrative analysis. Findings: We identified 1797 studies, including 23 systematic reviews, 12 meta-analyses, 40 randomised controlled trials (RCTs), 67 cohort trials, and 22 ecological or population-based investigations. Evidence for restricting access to lethal means in prevention of suicide has strengthened since 2005, especially with regard to control of analgesics (overall decrease of 43% since 2005) and hot-spots for suicide by jumping (reduction of 86% since 2005, 79% to 91%). School-based awareness programmes have been shown to reduce suicide attempts (odds ratio [OR] 0·45, 95% CI 0·24-0·85; p=0·014) and suicidal ideation (0·5, 0·27-0·92; p=0·025). The anti-suicidal effects of clozapine and lithium have been substantiated, but might be less specific than previously thought. Effective pharmacological and psychological treatments of depression are important in prevention. Insufficient evidence exists to assess the possible benefits for suicide prevention of screening in primary care, in general public education and media guidelines. Other approaches that need further investigation include gatekeeper training, education of physicians, and internet and helpline support. The paucity of RCTs is a major limitation in the evaluation of preventive interventions. Interpretation: In the quest for effective suicide prevention initiatives, no single strategy clearly stands above the others. Combinations of evidence-based strategies at the individual level and the population level should be assessed with robust research designs. Funding: The Expert Platform on Mental Health, Focus on Depression, and the European College of Neuropsychopharmacology.

The lancet. Psychiatry · systematic review · 1070 citationsread the source →

Spiritual needs of patients with chronic pain diseases and cancer - validation of the spiritual needs questionnaire.

Purpose: For many patients confronted with chronic diseases, spirituality/religiosity is a relevant resource to cope. While most studies on patients' spiritual needs refer to the care of patients at the end of life, our intention was to develop an instrument to measure spiritual, existential and psychosocial need of patients with chronic diseases. Methods: In an anonymous cross-sectional survey, we applied the Spiritual Needs Questionnaire (SpNQ version 1.2.) to 210 patients (75% women, mean age 54 +/- 12 years) with chronic pain conditions (67%), cancer (28%), other chronic conditions (5%). Patients were recruited at the Community Hospital Herdecke, the Institute for Complementary Medicine (University of Bern), and at a conference of a cancer support group in Herten. Results: Factor analysis of the 19-item instrument (Cronbach's alpha +/- .93) pointed to 4 factors which explain 67% of variance: Religious Needs, Need for Inner Peace, Existentialistic Needs (Reflection / Meaning), and Actively Giving. Within the main sample of patients with chronic pain and cancer, Needs for Inner Peace had the highest scores, followed by Self competent Attention; Existentialistic Needs had low scores, while the Religious Needs scores indicate no interest. Patients with cancer had significantly higher SpNQ scores than patients with chronic pain conditions. There were just some weak associations between Actively Giving and life satisfaction (r +/- .17; p +/- .012), and negatively with the symptom score (r +/- -.29; p < .0001); Need for Inner Peace was weakly associated with satisfaction with treatment efficacy (r +/- .24; p < .0001). Regression analyses reveal that the underlying disease (i.e., cancer) was of outstanding relevance for the patients' spiritual needs. Conclusion: The preliminary results indicate that spiritual needs are conceptually different from life satisfaction, and can be interpreted as the patients' longing for spiritual well-being. Methods how health care professionals may meet their patients' spiritual needs remain to be explored.

European journal of medical research · cohort or longitudinal · 87 citationsread the source →

Clinically significant improved fitness and weight loss among overweight persons with serious mental illness.

Objective: The objective of this study was to evaluate the effectiveness of a fitness health mentor program (In SHAPE) in improving physical fitness and weight loss among overweight and obese adults with serious mental illness. Methods: A randomized controlled trial was conducted with 133 persons with serious mental illness and a body mass index (BMI) >25 who were assigned either to the In SHAPE program (one year of weekly sessions with a fitness trainer plus a fitness club membership) or to one year of fitness club membership and education. Assessments were conducted at baseline and three, six, nine, and 12 months later. Results: Participants had a mean baseline weight of 231.8±54.8 pounds and a mean BMI of 37.6±8.2. At 12-month follow-up, In SHAPE (N=67) compared with fitness club membership and education (N=66) was associated with three times greater fitness club attendance, twice as much participation in physical exercise, greater engagement in vigorous physical activity, and improvement in diet. Twice the proportion of participants (40% versus 20%) achieved clinically significant improvement in cardiorespiratory fitness (>50 m on the six-minute walk test). Weight loss and BMI did not differ between groups. Among In SHAPE participants, 49% achieved either clinically significant increased fitness or weight loss (5% or greater), and 24% achieved both clinically significant improved fitness and weight loss. Conclusions: The In SHAPE program achieved clinically significant reduction in cardiovascular risk for almost one-half of participants at 12 months. Although the intervention showed promise in improving fitness, optimizing weight loss may require additional intensive, multicomponent dietary interventions.

Psychiatric services (Washington, D.C.) · randomised controlled trial · 134 citationsread the source →

Self- and proxy reports of quality of life among adolescents living in residential youth care compared to adolescents in the general population and mental health services.

Background: Child welfare services are aimed at providing care and protection, fostering well-being and prosocial behaviour. Thus, Quality of Life (QoL) should be an important outcome measure in Residential Youth Care (RYC) institutions. However, the dearth of research in this area gives rise to serious concern. The present study is the first large scale, nationwide study assessing QoL among adolescents living in RYC. To provide a reference frame, adolescent self- and primary contact proxy reports were compared to the general population and to adolescent outpatients in Child and Adolescent Mental Health Service (CAMHS). Also, we investigated the association between self-report of QoL in adolescents living in RYC and proxy reports of their primary contacts at the institution. Methods: All residents between the ages of 12-23 years living in RYC in Norway were the inclusion criteria. Eighty-six RYC institutions (with 601 eligible youths) were included, 201 youths/ parents did not give their consent. Finally, 400 youths aged 12-20 years participated, yielding a response rate of 67%. As a reference frame for comparison, a general population (N = 1444) and an outpatient sample of adolescents in CAMHS (N = 68) were available. We used the Questionnaire for Measuring Health-related Quality of Life in Children and Adolescents (KINDL-R). General Linear Model analyses (ANCOVA) were conducted with five KINDL life domains as dependent variables and group as independent variable. Results: Self- and proxy reports of QoL in adolescents living in RYC revealed a significantly (p < 0.001) poorer QoL compared to the general population on the life domains Physical- and Emotional well-being, Self-esteem, and relationship with Friends. Adolescents evaluated their physical well-being as worse compared to adolescents in CAHMS. Self- and proxy reports in RYC differed significantly on two of five life domains, but correlated low to moderate with each other. Conclusions: The results in this study raise major concerns about the poor QoL of the adolescents living in RYC, thereby challenging the child welfare system and decision makers to take action to improve the QoL of this group. The use of QoL as outcome measures is highly recommended.

Health and quality of life outcomes · cohort or longitudinal · 16 citationsread the source →

Reduction in saturated fat intake for cardiovascular disease.

Background: Reducing saturated fat reduces serum cholesterol, but effects on other intermediate outcomes may be less clear. Additionally, it is unclear whether the energy from saturated fats eliminated from the diet are more helpfully replaced by polyunsaturated fats, monounsaturated fats, carbohydrate or protein. Objectives: To assess the effect of reducing saturated fat intake and replacing it with carbohydrate (CHO), polyunsaturated (PUFA), monounsaturated fat (MUFA) and/or protein on mortality and cardiovascular morbidity, using all available randomised clinical trials. Search methods: We updated our searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid) and Embase (Ovid) on 15 October 2019, and searched Clinicaltrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) on 17 October 2019. Selection criteria: Included trials fulfilled the following criteria: 1) randomised; 2) intention to reduce saturated fat intake OR intention to alter dietary fats and achieving a reduction in saturated fat; 3) compared with higher saturated fat intake or usual diet; 4) not multifactorial; 5) in adult humans with or without cardiovascular disease (but not acutely ill, pregnant or breastfeeding); 6) intervention duration at least 24 months; 7) mortality or cardiovascular morbidity data available. Data collection and analysis: Two review authors independently assessed inclusion, extracted study data and assessed risk of bias. We performed random-effects meta-analyses, meta-regression, subgrouping, sensitivity analyses, funnel plots and GRADE assessment. Main results: We included 15 randomised controlled trials (RCTs) (16 comparisons, 56,675 participants), that used a variety of interventions from providing all food to advice on reducing saturated fat. The included long-term trials suggested that reducing dietary saturated fat reduced the risk of combined cardiovascular events by 17% (risk ratio (RR) 0.83; 95% confidence interval (CI) 0.70 to 0.98, 12 trials, 53,758 participants of whom 8% had a cardiovascular event, I² = 67%, GRADE moderate-quality evidence). Meta-regression suggested that greater reductions in saturated fat (reflected in greater reductions in serum cholesterol) resulted in greater reductions in risk of CVD events, explaining most heterogeneity between trials. The number needed to treat for an additional beneficial outcome (NNTB) was 56 in primary prevention trials, so 56 people need to reduce their saturated fat intake for ~four years for one person to avoid experiencing a CVD event. In secondary prevention trials, the NNTB was 53. Subgrouping did not suggest significant differences between replacement of saturated fat calories with polyunsaturated fat or carbohydrate, and data on replacement with monounsaturated fat and protein was very limited. We found little or no effect of reducing saturated fat on all-cause mortality (RR 0.96; 95% CI 0.90 to 1.03; 11 trials, 55,858 participants) or cardiovascular mortality (RR 0.95; 95% CI 0.80 to 1.12, 10 trials, 53,421 participants), both with GRADE moderate-quality evidence. There was little or no effect of reducing saturated fats on non-fatal myocardial infarction (RR 0.97, 95% CI 0.87 to 1.07) or CHD mortality (RR 0.97, 95% CI 0.82 to 1.16, both low-quality evidence), but effects on total (fatal or non-fatal) myocardial infarction, stroke and CHD events (fatal or non-fatal) were all unclear as the evidence was of very low quality. There was little or no effect on cancer mortality, cancer diagnoses, diabetes diagnosis, HDL cholesterol, serum triglycerides or blood pressure, and small reductions in weight, serum total cholesterol, LDL cholesterol and BMI. There was no evidence of harmful effects of reducing saturated fat intakes. Authors' conclusions: The findings of this updated review suggest that reducing saturated fat intake for at least two years causes a potentially important reduction in combined cardiovascular events. Replacing the energy from saturated fat with polyunsaturated fat or carbohydrate appear to be useful strategies, while effects of replacement with monounsaturated fat are unclear. The reduction in combined cardiovascular events resulting from reducing saturated fat did not alter by study duration, sex or baseline level of cardiovascular risk, but greater reduction in saturated fat caused greater reductions in cardiovascular events.

The Cochrane database of systematic reviews · meta-analysis · 98 citationsread the source →

Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial.

Background: The antiviral efficacy of remdesivir against SARS-CoV-2 is still controversial. We aimed to evaluate the clinical efficacy of remdesivir plus standard of care compared with standard of care alone in patients admitted to hospital with COVID-19, with indication of oxygen or ventilator support. Methods: DisCoVeRy was a phase 3, open-label, adaptive, multicentre, randomised, controlled trial conducted in 48 sites in Europe (France, Belgium, Austria, Portugal, Luxembourg). Adult patients (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and illness of any duration were eligible if they had clinical evidence of hypoxaemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzymes, severe chronic kidney disease, any contraindication to one of the studied treatments or their use in the 29 days before random assignment, or use of ribavirin, as well as pregnancy or breastfeeding. Participants were randomly assigned (1:1:1:1:1) to receive standard of care alone or in combination with remdesivir, lopinavir-ritonavir, lopinavir-ritonavir and interferon beta-1a, or hydroxychloroquine. Randomisation used computer-generated blocks of various sizes; it was stratified on severity of disease at inclusion and on European administrative region. Remdesivir was administered as 200 mg intravenous infusion on day 1, followed by once daily, 1-h infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. The primary outcome was the clinical status at day 15 measured by the WHO seven-point ordinal scale, assessed in the intention-to-treat population. Safety was assessed in the modified intention-to-treat population and was one of the secondary outcomes. This trial is registered with the European Clinical Trials Database, EudraCT2020-000936-23, and ClinicalTrials.gov, NCT04315948. Findings: Between March 22, 2020, and Jan 21, 2021, 857 participants were enrolled and randomly assigned to remdesivir plus standard of care (n=429) or standard of care only (n=428). 15 participants were excluded from analysis in the remdesivir group, and ten in the control group. At day 15, the distribution of the WHO ordinal scale was: (1) not hospitalised, no limitations on activities (61 [15%] of 414 in the remdesivir group vs 73 [17%] of 418 in the control group); (2) not hospitalised, limitation on activities (129 [31%] vs 132 [32%]); (3) hospitalised, not requiring supplemental oxygen (50 [12%] vs 29 [7%]); (4) hospitalised, requiring supplemental oxygen (76 [18%] vs 67 [16%]); (5) hospitalised, on non-invasive ventilation or high flow oxygen devices (15 [4%] vs 14 [3%]); (6) hospitalised, on invasive mechanical ventilation or extracorporeal membrane oxygenation (62 [15%] vs 79 [19%]); (7) death (21 [5%] vs 24 [6%]). The difference between treatment groups was not significant (odds ratio 0·98 [95% CI 0·77-1·25]; p=0·85). There was no significant difference in the occurrence of serious adverse events between treatment groups (remdesivir, 135 [33%] of 406 vs control, 130 [31%] of 418; p=0·48). Three deaths (acute respiratory distress syndrome, bacterial infection, and hepatorenal syndrome) were considered related to remdesivir by the investigators, but only one by the sponsor's safety team (hepatorenal syndrome). Interpretation: No clinical benefit was observed from the use of remdesivir in patients who were admitted to hospital for COVID-19, were symptomatic for more than 7 days, and required oxygen support. Funding: European Union Commission, French Ministry of Health, Domaine d'intérêt majeur One Health Île-de-France, REACTing, Fonds Erasme-COVID-Université Libre de Bruxelles, Belgian Health Care Knowledge Centre, Austrian Group Medical Tumor, European Regional Development Fund, Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation. Translation: For the French translation of the abstract see Supplementary Materials section.

The Lancet. Infectious diseases · randomised controlled trial · 264 citationsread the source →

Does low intensity extracorporeal shock wave therapy have a physiological effect on erectile function? Short-term results of a randomized, double-blind, sham controlled study.

Purpose: We investigated the clinical and physiological effect of low intensity extracorporeal shock wave therapy on men with organic erectile dysfunction who are phosphodiesterase type 5 inhibitor responders. Materials and methods: After a 1-month phosphodiesterase type 5 inhibitor washout period, 67 men were randomized in a 2:1 ratio to receive 12 sessions of low intensity extracorporeal shock wave therapy or sham therapy. Erectile function and penile hemodynamics were assessed before the first treatment (visit 1) and 1 month after the final treatment (followup 1) using validated sexual function questionnaires and venoocclusive strain gauge plethysmography. Results: Clinically we found a significantly greater increase in the International Index of Erectile Function-Erectile Function domain score from visit 1 to followup 1 in the treated group than in the sham treated group (mean ± SEM 6.7 ± 0.9 vs 3.0 ± 1.4, p = 0.0322). There were 19 men in the treated group who were initially unable to achieve erections hard enough for penetration (Erection Hardness Score 2 or less) who were able to achieve erections sufficiently firm for penetration (Erection Hardness Score 3 or greater) after low intensity extracorporeal shock wave therapy, compared to none in the sham group. Physiologically penile hemodynamics significantly improved in the treated group but not in the sham group (maximal post-ischemic penile blood flow 8.2 vs 0.1 ml per minute per dl, p <0.0001). None of the men experienced discomfort or reported any adverse effects from the treatment. Conclusions: This is the first randomized, double-blind, sham controlled study to our knowledge that shows that low intensity extracorporeal shock wave therapy has a positive short-term clinical and physiological effect on the erectile function of men who respond to oral phosphodiesterase type 5 inhibitor therapy. The feasibility and tolerability of this treatment, coupled with its potential rehabilitative characteristics, make it an attractive new therapeutic option for men with erectile dysfunction.

The Journal of urology · randomised controlled trial · 158 citationsread the source →

A comparison of efficacy between cognitive behavioral therapy (CBT) and CBT combined with medication in adults with attention-deficit/hyperactivity disorder (ADHD).

The study aimed to explore whether cognitive behavioral therapy (CBT) combined with medication is superior to CBT alone in core symptoms, emotional symptoms, self-esteem as well as social and cognitive functions of adult attention-deficit/hyperactivity disorder (ADHD) patients. Samples from a previous RCT study and outpatient participants were all included. A total of 124 patients received 12 weeks of manualized CBT sessions, either with (n = 57) or without (n = 67) medication. Efficacy variables were evaluated at baseline and each week. Mixed linear models (MLM) were used to compare differences between the two groups in all of the above domains. Within-group comparisons showed that both groups had robust improvements in core ADHD symptoms, emotional symptoms and social functional outcomes. The CBT + M group presented more domains of improvement in executive functions than the CBT group. However, comparisons between groups didn't indicate the superiority of CBT + M in core symptoms, emotional symptoms and self-esteem. Instead, the CBT group showed a greater improvement in the physical domain of the WHOQOL-BREF than the CBT + M group. This study further indicated that CBT is an effective treatment for adults with ADHD. A combination of CBT and medication presented broader improvements in executive functions, but not in clinical symptoms, than CBT alone.

Psychiatry research · randomised controlled trial · 31 citationsread the source →

Towards a consensus definition of allostatic load: a multi-cohort, multi-system, multi-biomarker individual participant data (IPD) meta-analysis.

Background: Allostatic load (AL) is a multi-system composite index for quantifying physiological dysregulation caused by life course stressors. For over 30 years, an extensive body of research has drawn on the AL framework but has been hampered by the lack of a consistent definition. Methods: This study analyses data for 67,126 individuals aged 40-111 years participating in 13 different cohort studies and 40 biomarkers across 12 physiological systems: hypothalamic-pituitary-adrenal (HPA) axis, sympathetic-adrenal-medullary (SAM) axis, parasympathetic nervous system functioning, oxidative stress, immunological/inflammatory, cardiovascular, respiratory, lipidemia, anthropometric, glucose metabolism, kidney, and liver. We use individual-participant-data meta-analysis and exploit natural heterogeneity in the number and type of biomarkers that have been used across studies, but a common set of health outcomes (grip strength, walking speed, and self-rated health), to determine the optimal configuration of parameters to define the concept. Results: There was at least one biomarker within 9/12 physiological systems that was reliably and consistently associated in the hypothesised direction with the three health outcomes in the meta-analysis of these cohorts: dehydroepiandrosterone sulfate (DHEAS), low frequency-heart rate variability (LF-HRV), C-reactive protein (CRP), resting heart rate (RHR), peak expiratory flow (PEF), high density lipoprotein cholesterol (HDL-C), waist-to-height ratio (WtHR), HbA1c, and cystatin C. An index based on five biomarkers (CRP, RHR, HDL-C, WtHR and HbA1c) available in every study was found to predict an independent outcome - mortality - as well or better than more elaborate sets of biomarkers. Discussion: This study has identified a brief 5-item measure of AL that arguably represents a universal and efficient set of biomarkers for capturing physiological 'wear and tear' and a further biomarker (PEF) that could usefully be included in future data collection.

Psychoneuroendocrinology · meta-analysis · 60 citationsread the source →

Self-Transcendence: Association with Spirituality in an Italian Sample of Terminal Cancer Patients.

Terminally ill cancer patients often experience demoralization and loss of dignity, which undermines their spiritual wellbeing, which could, however, be supported by the presence of other factors such as self-transcendence and religious coping strategies. To assess self-transcendence and religious coping strategies and how they influence spirituality, we studied 141 end-stage cancer patients (64.3% male; mean age 68.6 ± 14.6) with a Karnofsky Performance Status ≤ 50 and a life expectancy ≤ 4 months using the Self-Transcendence Scale, the Demoralization Scale, the Functional Assessment of Chronic Illness Therapy-Spiritual Wellbeing (FACIT-Sp-12), the Brief Religious COPE, and the Patient Dignity Inventory. To understand the effects of these variables on spirituality, hierarchical multiple regression was performed on FACIT-Sp-12. The final model predicted 67% of the variance in spiritual wellbeing. Demoralization was the strongest influencing factor (β = -0.727, p < 0.001), followed by self-transcendence (β = 0.256, p < 0.001), and positive religious coping (β = 0.148, p < 0.05). This study suggests that self-transcendence and positive religious coping may be protective factors for spirituality in terminal cancer patients. These factors should be considered in treatment to promote spiritual wellbeing and improve patients' quality of life at the end of life.

Behavioral sciences (Basel, Switzerland) · 10 citationsread the source →

Self-Compassion as a prospective predictor of PTSD symptom severity among trauma-exposed U.S. Iraq and Afghanistan war veterans.

U.S. combat veterans of the Iraq and Afghanistan wars have elevated rates of posttraumatic stress disorder (PTSD) compared to the general population. Self-compassion, characterized by self-kindness, a sense of common humanity when faced with suffering, and mindful awareness of suffering, is a potentially modifiable factor implicated in the development and maintenance of PTSD. We examined the concurrent and prospective relationship between self-compassion and PTSD symptom severity after accounting for level of combat exposure and baseline PTSD severity in 115 Iraq and Afghanistan war veterans exposed to 1 or more traumatic events during deployment. PTSD symptoms were assessed using the Clinician Administered PTSD Scale for DSM-IV (CAPS-IV) at baseline and 12 months (n =101). Self-compassion and combat exposure were assessed at baseline via self-report. Self-compassion was associated with baseline PTSD symptoms after accounting for combat exposure (β = -.59; p < .001; ΔR(2) = .34; f(2) = .67; large effect) and predicted 12-month PTSD symptom severity after accounting for combat exposure and baseline PTSD severity (β = -.24; p = .008; ΔR(2) = .03; f(2) = .08; small effect). Findings suggest that interventions that increase self-compassion may be beneficial for treating chronic PTSD symptoms among some Iraq and Afghanistan war veterans.

Journal of traumatic stress · 41 citationsread the source →

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

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

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

Cognitive behavioural therapy (CBT), third-wave CBT and interpersonal therapy (IPT) based interventions for preventing depression in children and adolescents.

Background: Depression is common in young people. It has a marked negative impact and is associated with self-harm and suicide. Preventing its onset would be an important advance in public health. This is an update of a Cochrane review that was last updated in 2011. Objectives: To determine whether evidence-based psychological interventions (including cognitive behavioural therapy (CBT), interpersonal therapy (IPT) and third wave CBT)) are effective in preventing the onset of depressive disorder in children and adolescents. Search methods: We searched the specialised register of the Cochrane Common Mental Disorders Group (CCMDCTR to 11 September 2015), which includes relevant randomised controlled trials from the following bibliographic databases: The Cochrane Library (all years), EMBASE (1974 to date), MEDLINE (1950 to date) and PsycINFO (1967 to date). We searched conference abstracts and reference lists of included trials and reviews, and contacted experts in the field. Selection criteria: We included randomised controlled trials of an evidence-based psychological prevention programme compared with any comparison control for young people aged 5 to 19 years, who did not currently meet diagnostic criteria for depression. Data collection and analysis: Two authors independently assessed trials for inclusion and rated their risk of bias. We adjusted sample sizes to take account of cluster designs and multiple comparisons. We contacted trial authors for additional information where needed. We assessed the quality of evidence for the primary outcomes using GRADE. Main results: We included 83 trials in this review. The majority of trials (67) were carried out in school settings with eight in colleges or universities, four in clinical settings, three in the community and four in mixed settings. Twenty-nine trials were carried out in unselected populations and 53 in targeted populations. For the primary outcome of depression diagnosis at medium-term follow-up (up to 12 months), there were 32 trials with 5965 participants and the risk of having a diagnosis of depression was reduced for participants receiving an intervention compared to those receiving no intervention (risk difference (RD) -0.03, 95% confidence interval (CI) -0.05 to -0.01; P value = 0.01). We rated this evidence as moderate quality according to the GRADE criteria. There were 70 trials (73 trial arms) with 13,829 participants that contributed to the analysis for the primary outcome of depression symptoms (self-rated) at the post-intervention time point, with results showing a small but statistically significant effect (standardised mean difference (SMD) -0.21, 95% CI -0.27 to -0.15; P value < 0.0001). This effect persisted to the short-term assessment point (up to three months) (SMD -0.31, 95% CI -0.45 to -0.17; P value < 0.0001; 16 studies; 1558 participants) and medium-term (4 to 12 months) assessment point (SMD -0.12, 95% CI -0.18 to -0.05; P value = 0.0002; 53 studies; 11,913 participants); however, the effect was no longer evident at the long-term follow-up. We rated this evidence as low to moderate quality according to the GRADE criteria. The evidence from this review is unclear with regard to whether the type of population modified the overall effects; there was statistically significant moderation of the overall effect for depression symptoms (P value = 0.0002), but not for depressive disorder (P value = 0.08). For trials implemented in universal populations there was no effect for depression diagnosis (RD -0.01, 95% CI -0.03 to 0.01) and a small effect for depression symptoms (SMD -0.11, 95% CI -0.17 to -0.05). For trials implemented in targeted populations there was a statistically significantly beneficial effect of intervention (depression diagnosis RD -0.04, 95% CI -0.07 to -0.01; depression symptoms SMD -0.32, 95% CI -0.42 to -0.23). Of note were the lack of attention placebo-controlled trials in targeted populations (none for depression diagnosis and four for depression symptoms). Among trials implemented in universal populations a number used an attention placebo comparison in which the intervention consistently showed no effect. Authors' conclusions: Overall the results show small positive benefits of depression prevention, for both the primary outcomes of self-rated depressive symptoms post-intervention and depression diagnosis up to 12 months (but not beyond). Estimates of numbers needed to treat to benefit (NNTB = 11) compare well with other public health interventions. However, the evidence was of moderate to low quality using the GRADE framework and the results were heterogeneous. Prevention programmes delivered to universal populations showed a sobering lack of effect when compared with an attention placebo control. Interventions delivered to targeted populations, particularly those selected on the basis of depression symptoms, had larger effect sizes, but these seldom used an attention placebo comparison and there are practical difficulties inherent in the implementation of targeted programmes. We conclude that there is still not enough evidence to support the implementation of depression prevention programmes. Future research should focus on current gaps in our knowledge. Given the relative lack of evidence for universal interventions compared with attention placebo controls and the poor results from well-conducted effectiveness trials of universal interventions, in our opinion any future such trials should test a depression prevention programme in an indicated targeted population using a credible attention placebo comparison group. Depressive disorder as the primary outcome should be measured over the longer term, as well as clinician-rated depression. Such a trial should consider scalability as well as the potential for the intervention to do harm.

The Cochrane database of systematic reviews · meta-analysis · 136 citationsread the source →

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

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

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

Effectiveness of brief alcohol interventions in primary care populations.

Background: Excessive drinking is a significant cause of mortality, morbidity and social problems in many countries. Brief interventions aim to reduce alcohol consumption and related harm in hazardous and harmful drinkers who are not actively seeking help for alcohol problems. Interventions usually take the form of a conversation with a primary care provider and may include feedback on the person's alcohol use, information about potential harms and benefits of reducing intake, and advice on how to reduce consumption. Discussion informs the development of a personal plan to help reduce consumption. Brief interventions can also include behaviour change or motivationally-focused counselling. This is an update of a Cochrane Review published in 2007. Objectives: To assess the effectiveness of screening and brief alcohol intervention to reduce excessive alcohol consumption in hazardous or harmful drinkers in general practice or emergency care settings. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and 12 other bibliographic databases to September 2017. We searched Alcohol and Alcohol Problems Science Database (to December 2003, after which the database was discontinued), trials registries, and websites. We carried out handsearching and checked reference lists of included studies and relevant reviews. Selection criteria: We included randomised controlled trials (RCTs) of brief interventions to reduce hazardous or harmful alcohol consumption in people attending general practice, emergency care or other primary care settings for reasons other than alcohol treatment. The comparison group was no or minimal intervention, where a measure of alcohol consumption was reported. 'Brief intervention' was defined as a conversation comprising five or fewer sessions of brief advice or brief lifestyle counselling and a total duration of less than 60 minutes. Any more was considered an extended intervention. Digital interventions were not included in this review. Data collection and analysis: We used standard methodological procedures expected by Cochrane. We carried out subgroup analyses where possible to investigate the impact of factors such as gender, age, setting (general practice versus emergency care), treatment exposure and baseline consumption. Main results: We included 69 studies that randomised a total of 33,642 participants. Of these, 42 studies were added for this update (24,057 participants). Most interventions were delivered in general practice (38 studies, 55%) or emergency care (27 studies, 39%) settings. Most studies (61 studies, 88%) compared brief intervention to minimal or no intervention. Extended interventions were compared with brief (4 studies, 6%), minimal or no intervention (7 studies, 10%). Few studies targeted particular age groups: adolescents or young adults (6 studies, 9%) and older adults (4 studies, 6%). Mean baseline alcohol consumption was 244 g/week (30.5 standard UK units) among the studies that reported these data. Main sources of bias were attrition and lack of provider or participant blinding. The primary meta-analysis included 34 studies (15,197 participants) and provided moderate-quality evidence that participants who received brief intervention consumed less alcohol than minimal or no intervention participants after one year (mean difference (MD) -20 g/week, 95% confidence interval (CI) -28 to -12). There was substantial heterogeneity among studies (I² = 73%). A subgroup analysis by gender demonstrated that both men and women reduced alcohol consumption after receiving a brief intervention. We found moderate-quality evidence that brief alcohol interventions have little impact on frequency of binges per week (MD -0.08, 95% CI -0.14 to -0.02; 15 studies, 6946 participants); drinking days per week (MD -0.13, 95% CI -0.23 to -0.04; 11 studies, 5469 participants); or drinking intensity (-0.2 g/drinking day, 95% CI -3.1 to 2.7; 10 studies, 3128 participants).We found moderate-quality evidence of little difference in quantity of alcohol consumed when extended and no or minimal interventions were compared (-14 g/week, 95% CI -37 to 9; 6 studies, 1296 participants). There was little difference in binges per week (-0.08, 95% CI -0.28 to 0.12; 2 studies, 456 participants; moderate-quality evidence) or difference in days drinking per week (-0.45, 95% CI -0.81 to -0.09; 2 studies, 319 participants; moderate-quality evidence). Extended versus no or minimal intervention provided little impact on drinking intensity (9 g/drinking day, 95% CI -26 to 9; 1 study, 158 participants; low-quality evidence).Extended intervention had no greater impact than brief intervention on alcohol consumption, although findings were imprecise (MD 2 g/week, 95% CI -42 to 45; 3 studies, 552 participants; low-quality evidence). Numbers of binges were not reported for this comparison, but one trial suggested a possible drop in days drinking per week (-0.5, 95% CI -1.2 to 0.2; 147 participants; low-quality evidence). Results from this trial also suggested very little impact on drinking intensity (-1.7 g/drinking day, 95% CI -18.9 to 15.5; 147 participants; very low-quality evidence).Only five studies reported adverse effects (very low-quality evidence). No participants experienced any adverse effects in two studies; one study reported that the intervention increased binge drinking for women and two studies reported adverse events related to driving outcomes but concluded they were equivalent in both study arms. Sources of funding were reported by 67 studies (87%). With two exceptions, studies were funded by government institutes, research bodies or charitable foundations. One study was partly funded by a pharmaceutical company and a brewers association, another by a company developing diagnostic testing equipment. Authors' conclusions: We found moderate-quality evidence that brief interventions can reduce alcohol consumption in hazardous and harmful drinkers compared to minimal or no intervention. Longer counselling duration probably has little additional effect. Future studies should focus on identifying the components of interventions which are most closely associated with effectiveness.

The Cochrane database of systematic reviews · meta-analysis · 409 citationsread the source →

Integrated disease management interventions for patients with chronic obstructive pulmonary disease.

Background: People with chronic obstructive pulmonary disease (COPD) show considerable variation in symptoms, limitations, and well-being; this often complicates medical care. A multi-disciplinary and multi-component programme that addresses different elements of care could improve quality of life (QoL) and exercise tolerance, while reducing the number of exacerbations. Objectives: To compare the effectiveness of integrated disease management (IDM) programmes versus usual care for people with chronic obstructive pulmonary disease (COPD) in terms of health-related quality of life (QoL), exercise tolerance, and exacerbation-related outcomes. Search methods: We searched the Cochrane Airways Group Register of Trials, CENTRAL, MEDLINE, Embase, and CINAHL for potentially eligible studies. Searches were current as of September 2020. Selection criteria: Randomised controlled trials (RCTs) that compared IDM programmes for COPD versus usual care were included. Interventions consisted of multi-disciplinary (two or more healthcare providers) and multi-treatment (two or more components) IDM programmes of at least three months' duration. Data collection and analysis: Two review authors independently assessed trial quality and extracted data. If required, we contacted study authors to request additional data. We performed meta-analyses using random-effects modelling. We carried out sensitivity analyses for the quality of included studies and performed subgroup analyses based on setting, study design, dominant intervention components, and region. Main results: Along with 26 studies included in the 2013 Cochrane Review, we added 26 studies for this update, resulting in 52 studies involving 21,086 participants for inclusion in the meta-analysis. Follow-up periods ranged between 3 and 48 months and were classified as short-term (up to 6 months), medium-term (6 to 15 months), and long-term (longer than 15 months) follow-up. Studies were conducted in 19 different countries. The mean age of included participants was 67 years, and 66% were male. Participants were treated in all types of healthcare settings, including primary (n =15), secondary (n = 22), and tertiary care (n = 5), and combined primary and secondary care (n = 10). Overall, the level of certainty of evidence was moderate to high. We found that IDM probably improves health-related QoL as measured by St. George's Respiratory Questionnaire (SGRQ) total score at medium-term follow-up (mean difference (MD) -3.89, 95% confidence interval (CI) -6.16 to -1.63; 18 RCTs, 4321 participants; moderate-certainty evidence). A comparable effect was observed at short-term follow-up (MD -3.78, 95% CI -6.29 to -1.28; 16 RCTs, 1788 participants). However, the common effect did not exceed the minimum clinically important difference (MCID) of 4 points. There was no significant difference between IDM and control for long-term follow-up and for generic QoL. IDM probably also leads to a large improvement in maximum and functional exercise capacity, as measured by six-minute walking distance (6MWD), at medium-term follow-up (MD 44.69, 95% CI 24.01 to 65.37; 13 studies, 2071 participants; moderate-certainty evidence). The effect exceeded the MCID of 35 metres and was even greater at short-term (MD 52.26, 95% CI 32.39 to 72.74; 17 RCTs, 1390 participants) and long-term (MD 48.83, 95% CI 16.37 to 80.49; 6 RCTs, 7288 participants) follow-up. The number of participants with respiratory-related admissions was reduced from 324 per 1000 participants in the control group to 235 per 1000 participants in the IDM group (odds ratio (OR) 0.64, 95% CI 0.50 to 0.81; 15 RCTs, median follow-up 12 months, 4207 participants; high-certainty evidence). Likewise, IDM probably results in a reduction in emergency department (ED) visits (OR 0.69, 95%CI 0.50 to 0.93; 9 RCTs, median follow-up 12 months, 8791 participants; moderate-certainty evidence), a slight reduction in all-cause hospital admissions (OR 0.75, 95%CI 0.57 to 0.98; 10 RCTs, median follow-up 12 months, 9030 participants; moderate-certainty evidence), and fewer hospital days per person admitted (MD -2.27, 95% CI -3.98 to -0.56; 14 RCTs, median follow-up 12 months, 3563 participants; moderate-certainty evidence). Statistically significant improvement was noted on the Medical Research Council (MRC) Dyspnoea Scale at short- and medium-term follow-up but not at long-term follow-up. No differences between groups were reported for mortality, courses of antibiotics/prednisolone, dyspnoea, and depression and anxiety scores. Subgroup analysis of dominant intervention components and regions of study suggested context- and intervention-specific effects. However, some subgroup analyses were marked by considerable heterogeneity or included few studies. These results should therefore be interpreted with caution. Authors' conclusions: This review shows that IDM probably results in improvement in disease-specific QoL, exercise capacity, hospital admissions, and hospital days per person. Future research should evaluate which combination of IDM components and which intervention duration are most effective for IDM programmes, and should consider contextual determinants of implementation and treatment effect, including process-related outcomes, long-term follow-up, and cost-effectiveness analyses.

The Cochrane database of systematic reviews · meta-analysis · 48 citationsread the source →

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

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

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

Determinants of breastfeeding initiation and cessation among employed mothers: a prospective cohort study.

Background: The U.S. continues to have one of the lowest breastfeeding rates in the industrialized world. Studies have shown that full-time employment and early return to work decreased breastfeeding duration, but little is known about the relationship between leave policies and breastfeeding initiation and cessation. This study aimed to identify workplace-related barriers and facilitators associated with breastfeeding initiation and cessation in the first 6 months postpartum. Methods: A prospective cohort study design was utilized to recruit 817 Minnesota women aged 18 and older while hospitalized for childbirth. Selection criteria included English-speaking, employed mothers with a healthy, singleton birth. These women were followed up using telephone interviews at 6 weeks, 12 weeks, and 6 months after childbirth. The main study outcomes were breastfeeding initiation, measured during hospital enrollment, and breastfeeding cessation by 6 months postpartum. Results: Women were 30 years old; 86 % were White, and 73 % were married. Breastfeeding rates were 81 % at childbirth, 67 % at 6 weeks, 49 % at 12 weeks, and 33 % at 6 months postpartum. Logistic regression revealed the odds of breastfeeding initiation were higher for women who: held professional jobs, were primiparae, had graduate degree, did not smoke prenatally, had no breastfeeding problems, and had family or friends who breastfeed. Survival analyses showed the hazard for breastfeeding cessation by 6 months was: higher for women who returned to work at any time during the 6 months postpartum versus those who did not return, lower for professional workers, higher among single than married women, higher for every educational category compared to graduate school, and higher for those with no family or friends who breastfeed. Conclusions: While employer paid leave policy did not affect breastfeeding initiation or cessation, women who took shorter leaves were more likely to stop breastfeeding in the first 6 months postpartum. Future research should examine women's awareness of employer policies regarding paid and unpaid leave.

BMC pregnancy and childbirth · 89 citationsread the source →

Pharmacological and electronic cigarette interventions for smoking cessation in adults: component network meta-analyses.

Background: Tobacco smoking is the leading preventable cause of death and disease worldwide. Stopping smoking can reduce this harm and many people would like to stop. There are a number of medicines licenced to help people quit globally, and e-cigarettes are used for this purpose in many countries. Typically treatments work by reducing cravings to smoke, thus aiding initial abstinence and preventing relapse. More information on comparative effects of these treatments is needed to inform treatment decisions and policies. Objectives: To investigate the comparative benefits, harms and tolerability of different smoking cessation pharmacotherapies and e-cigarettes, when used to help people stop smoking tobacco. Search methods: We identified studies from recent updates of Cochrane Reviews investigating our interventions of interest. We updated the searches for each review using the Cochrane Tobacco Addiction Group (TAG) specialised register to 29 April 2022. Selection criteria: We included randomised controlled trials (RCTs), cluster-RCTs and factorial RCTs, which measured smoking cessation at six months or longer, recruited adults who smoked combustible cigarettes at enrolment (excluding pregnant people) and randomised them to approved pharmacotherapies and technologies used for smoking cessation worldwide (varenicline, cytisine, nortriptyline, bupropion, nicotine replacement therapy (NRT) and e-cigarettes) versus no pharmacological intervention, placebo (control) or another approved pharmacotherapy. Studies providing co-interventions (e.g. behavioural support) were eligible if the co-intervention was provided equally to study arms. Data collection and analysis: We followed standard Cochrane methods for screening, data extraction and risk of bias (RoB) assessment (using the RoB 1 tool). Primary outcome measures were smoking cessation at six months or longer, and the number of people reporting serious adverse events (SAEs). We also measured withdrawals due to treatment. We used Bayesian component network meta-analyses (cNMA) to examine intervention type, delivery mode, dose, duration, timing in relation to quit day and tapering of nicotine dose, using odds ratios (OR) and 95% credibility intervals (CrIs). We calculated an effect estimate for combination NRT using an additive model. We evaluated the influence of population and study characteristics, provision of behavioural support and control arm rates using meta-regression. We evaluated certainty using GRADE. Main results: Of our 332 eligible RCTs, 319 (835 study arms, 157,179 participants) provided sufficient data to be included in our cNMA. Of these, we judged 51 to be at low risk of bias overall, 104 at high risk and 164 at unclear risk, and 118 reported pharmaceutical or e-cigarette/tobacco industry funding. Removing studies at high risk of bias did not change our interpretation of the results. Benefits We found high-certainty evidence that nicotine e-cigarettes (OR 2.37, 95% CrI 1.73 to 3.24; 16 RCTs, 3828 participants), varenicline (OR 2.33, 95% CrI 2.02 to 2.68; 67 RCTs, 16,430 participants) and cytisine (OR 2.21, 95% CrI 1.66 to 2.97; 7 RCTs, 3848 participants) were associated with higher quit rates than control. In absolute terms, this might lead to an additional eight (95% CrI 4 to 13), eight (95% CrI 6 to 10) and seven additional quitters per 100 (95% CrI 4 to 12), respectively. These interventions appeared to be more effective than the other interventions apart from combination NRT (patch and a fast-acting form of NRT), which had a lower point estimate (calculated additive effect) but overlapping 95% CrIs (OR 1.93, 95% CrI 1.61 to 2.34). There was also high-certainty evidence that nicotine patch alone (OR 1.37, 95% CrI 1.20 to 1.56; 105 RCTs, 37,319 participants), fast-acting NRT alone (OR 1.41, 95% CrI 1.29 to 1.55; 120 RCTs, 31,756 participants) and bupropion (OR 1.43, 95% CrI 1.26 to 1.62; 71 RCTs, 14,759 participants) were more effective than control, resulting in two (95% CrI 1 to 3), three (95% CrI 2 to 3) and three (95% CrI 2 to 4) additional quitters per 100 respectively. Nortriptyline is probably associated with higher quit rates than control (OR 1.35, 95% CrI 1.02 to 1.81; 10 RCTs, 1290 participants; moderate-certainty evidence), resulting in two (CrI 0 to 5) additional quitters per 100. Non-nicotine/placebo e-cigarettes (OR 1.16, 95% CrI 0.74 to 1.80; 8 RCTs, 1094 participants; low-certainty evidence), equating to one additional quitter (95% CrI -2 to 5), had point estimates favouring the intervention over control, but CrIs encompassed the potential for no difference and harm. There was low-certainty evidence that tapering the dose of NRT prior to stopping treatment may improve effectiveness; however, 95% CrIs also incorporated the null (OR 1.14, 95% CrI 1.00 to 1.29; 111 RCTs, 33,156 participants). This might lead to an additional one quitter per 100 (95% CrI 0 to 2). Harms There were insufficient data to include nortriptyline and non-nicotine EC in the final SAE model. Overall rates of SAEs for the remaining treatments were low (average 3%). Low-certainty evidence did not show a clear difference in the number of people reporting SAEs for nicotine e-cigarettes, varenicline, cytisine or NRT when compared to no pharmacotherapy/e-cigarettes or placebo. Bupropion may slightly increase rates of SAEs, although the CrI also incorporated no difference (moderate certainty). In absolute terms bupropion may cause one more person in 100 to experience an SAE (95% CrI 0 to 2). Authors' conclusions: The most effective interventions were nicotine e-cigarettes, varenicline and cytisine (all high certainty), as well as combination NRT (additive effect, certainty not rated). There was also high-certainty evidence for the effectiveness of nicotine patch, fast-acting NRT and bupropion. Less certain evidence of benefit was present for nortriptyline (moderate certainty), non-nicotine e-cigarettes and tapering of nicotine dose (both low certainty). There was moderate-certainty evidence that bupropion may slightly increase the frequency of SAEs, although there was also the possibility of no increased risk. There was no clear evidence that any other tested interventions increased SAEs. Overall, SAE data were sparse with very low numbers of SAEs, and so further evidence may change our interpretation and certainty. Future studies should report SAEs to strengthen certainty in this outcome. More head-to-head comparisons of the most effective interventions are needed, as are tests of combinations of these. Future work should unify data from behavioural and pharmacological interventions to inform approaches to combined support for smoking cessation.

The Cochrane database of systematic reviews · systematic review · 114 citationsread the source →

Cortisol response to stress in female youths exposed to childhood maltreatment: results of the youth mood project.

Background: Few studies have examined stress reactivity and its relationship to major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) among maltreated youth. We examined differences between maltreated and control participants in heart rate and cortisol resting and reactivity levels in response to a psychosocial stressor. Methods: We recruited 67 female youths aged 12 to 16 with no prior history of depression from child protection agencies and a control group of 25 youths matched on age and postal code. Child maltreatment was measured with two self-report instruments. Psychiatric status was assessed using the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. Results: Piecewise multilevel growth curve analysis was used to model group differences in resting and reactivity cortisol levels and heart rate in response to the Trier Social Stress Test (TSST). During the resting period, both the maltreated and control groups showed a similar decline in levels of cortisol. During the reactivity phase, youth in the control group showed an increase in cortisol levels following the TSST and a gradual flattening over time; maltreated youth exhibited an attenuated response. This blunted reactivity was not associated with current symptoms of MDD or PTSD. There were no group differences in resting and reactivity levels of heart rate. Conclusions: These findings provide further support for hypothalamic-pituitary-adrenal axis dysregulation among maltreated youth. Since the ability to respond to acute stressors by raising cortisol is important for health, these findings may assist in understanding the vulnerability of maltreated youth to experience physical and mental health problems.

Biological psychiatry · 190 citationsread the source →

Behavioral Experiments for Intolerance of Uncertainty: A Randomized Clinical Trial for Adults With Generalized Anxiety Disorder.

Sophisticated multicomponent treatments for adults with generalized anxiety disorder (GAD) have been developed over the past three decades. Although these comprehensive treatments have produced encouraging results, they appear to be less efficacious than treatments for other anxiety disorders. The goal of this randomized controlled trial is to test a newly developed, highly focused treatment for adults with GAD: Behavioral Experiments for Intolerance of Uncertainty. Sixty (60) participants (51 women, 9 men), with a mean age of 34.60 years (range: 19 to 67 years), were randomized to either treatment (n = 30) or wait-list control (n = 30). Treatment consisted of 12 weekly 1-hour sessions in which participants learned to use behavioral experiments to test their catastrophic beliefs about uncertainty. Assessments were conducted at pre-, mid- and postcondition, and at 6- and 12-month follow-up. The primary outcome was the severity of GAD, and secondary outcomes were worry, depression, somatic anxiety, and intolerance of uncertainty. Using growth curve modeling, we found that (1) the treatment group was superior to the wait-list group in terms of change from pre- to posttest on all outcomes; (2) the combined sample (once wait-listed participants received treatment) evidenced large and significant decreases on all outcomes; and (3) treatment gains were either maintained or increased over the 12-month follow-up period of the study. The new treatment is a promising treatment option for adults with GAD considering that it may be as efficacious as more comprehensive evidence-based psychological treatments for GAD.

Behavior therapy · randomised controlled trial · 38 citationsread the source →

Web-based acceptance and commitment therapy for depressive symptoms with minimal support: a randomized controlled trial.

Low-intensity interventions for people suffering from depressive symptoms are highly desirable. The aim of the present study was to investigate the outcomes of a web-based acceptance and commitment therapy (ACT)-based intervention without face-to-face contact for people suffering from depressive symptoms. Participants (N = 39) with depressive symptoms were randomly assigned to an Internet-delivered acceptance and commitment therapy (iACT) intervention or a waiting list control condition (WLC). Participants were evaluated with standardized self-reporting measures (Beck Depression Inventory [BDI-II], Symptom Checklist-90 [SCL-90], Acceptance and Action Questionnaire [AAQ-2], Five Facet Mindfulness Questionnaire [FFMQ], Automatic Thoughts Questionnaire [ATQ], and White Bear Suppression Inventory [WBSI]) at pre- and post-measurement. Long-term effects in the iACT group were examined using a 12-month follow-up. The iACT program comprised home assignments, online feedback given by master's-level students of psychology over a 7-week intervention period, and automated email-based reminders. Significant effects were observed in favor of the iACT group on depression symptomatology (between effect sizes [ESs] at post-treatment, iACT/WLC, g = .83), psychological and physiological symptoms (g = .60), psychological flexibility (g = .67), mindfulness skills (g = .53), and frequency of automatic thoughts (g = .57) as well as thought suppression (g = .53). The treatment effects in the iACT group were maintained over the 12-month follow-up period (within-iACT ES: BDI-II, g = 1.33; SCL-90, g = 1.04; ATQF/B [Frequency/Believability], FFMQ, WBSI, AAQ-II, g = .74-1.08). The iACT participants stated that they would be happy to recommend the same intervention to others with depressive symptoms. We conclude that an ACT-based guided Internet-delivered treatment with minimal contact can be effective for people with depressive symptoms.

Behavior modification · randomised controlled trial · 65 citationsread the source →

A randomised controlled trial of dietary improvement for adults with major depression (the 'SMILES' trial).

Background: The possible therapeutic impact of dietary changes on existing mental illness is largely unknown. Using a randomised controlled trial design, we aimed to investigate the efficacy of a dietary improvement program for the treatment of major depressive episodes. Methods: 'SMILES' was a 12-week, parallel-group, single blind, randomised controlled trial of an adjunctive dietary intervention in the treatment of moderate to severe depression. The intervention consisted of seven individual nutritional consulting sessions delivered by a clinical dietician. The control condition comprised a social support protocol to the same visit schedule and length. Depression symptomatology was the primary endpoint, assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) at 12 weeks. Secondary outcomes included remission and change of symptoms, mood and anxiety. Analyses utilised a likelihood-based mixed-effects model repeated measures (MMRM) approach. The robustness of estimates was investigated through sensitivity analyses. Results: We assessed 166 individuals for eligibility, of whom 67 were enrolled (diet intervention, n = 33; control, n = 34). Of these, 55 were utilising some form of therapy: 21 were using psychotherapy and pharmacotherapy combined; 9 were using exclusively psychotherapy; and 25 were using only pharmacotherapy. There were 31 in the diet support group and 25 in the social support control group who had complete data at 12 weeks. The dietary support group demonstrated significantly greater improvement between baseline and 12 weeks on the MADRS than the social support control group, t(60.7) = 4.38, p < 0.001, Cohen's d = -1.16. Remission, defined as a MADRS score <10, was achieved for 32.3% (n = 10) and 8.0% (n = 2) of the intervention and control groups, respectively (χ 2 (1) = 4.84, p = 0.028); number needed to treat (NNT) based on remission scores was 4.1 (95% CI of NNT 2.3-27.8). A sensitivity analysis, testing departures from the missing at random (MAR) assumption for dropouts, indicated that the impact of the intervention was robust to violations of MAR assumptions. Conclusions: These results indicate that dietary improvement may provide an efficacious and accessible treatment strategy for the management of this highly prevalent mental disorder, the benefits of which could extend to the management of common co-morbidities. Trial registration: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000251820 . Registered on 29 February 2012.

BMC medicine · randomised controlled trial · 586 citationsread the source →

Targeted smoking cessation for dual users of combustible and electronic cigarettes: a randomised controlled trial.

Background: Although many smokers use electronic cigarettes (e-cigarettes) to quit smoking, most continue to smoke while vaping. This dual use might delay cessation and increase toxicant exposure. We aimed to test the efficacy of a self-help intervention designed to help dual users to quit smoking. Methods: In this three-arm randomised controlled trial we recruited individuals in the USA using Facebook and multimedia advertisements. Included participants were 18 years or older, smoked at least weekly in the preceding year, and vaped at least weekly in the preceding month. We used computer generated randomisation with balanced-permuted blocks (block size 10, with 2-4-4 ratio) to allocate participants to assessment only (ASSESS group), generic smoking cessation self-help booklets (GENERIC group), or booklets targeting dual users (eTARGET group). Individuals in the generic or targeted intervention groups received monthly cessation materials for 18 months, with assessments every 3 months for 24 months. The main outcome was self-reported 7-day point-prevalence smoking abstinence at each assessment point. All randomly allocated participants were included in primary analyses using generalised estimating equations for each of 20 datasets created by multiple imputation. Analysis of the χ2s produced an F test. The trial is registered with ClinicalTrials.gov, NCT02416011, and is now closed. Findings: Between July 12, 2016, and June 30, 2017, we randomly assigned 2896 dual users (575 to assessment, 1154 to generic intervention, and 1167 to targeted self-help). 7-day point-prevalence smoking abstinence increased from 14% at 3 months to 42% at 24 months (F7,541·7=67·1, p<0·0001) in the overall sample. Targeted self-help resulted in higher smoking abstinence than did assessment alone throughout the treatment period (F1,973·8=10·20, p=0·0014 [α=0·017]). The generic intervention group had abstinence rates between those of the assessment and targeted groups, but did not significantly differ from either when adjusted for multiple comparisons (GENERIC vs eTARGET F1,1102·5=1·79, p=0·18 [α=0·05]; GENERIC vs ASSESS F1,676·7=4·29, p=0·039 [α=0·025]). Differences between study groups attenuated after the interventions ended. Interpretation: A targeted self-help intervention with high potential for dissemination could be efficacious in promoting smoking cessation among dual users of combustible cigarettes and e-cigarettes. Funding: National Institute on Drug Abuse, National Cancer Institute.

The Lancet. Public health · randomised controlled trial · 45 citationsread the source →

Uptake of antiretroviral therapy and male circumcision after community-based HIV testing and strategies for linkage to care versus standard clinic referral: a multisite, open-label, randomised controlled trial in South Africa and Uganda.

Background: Male circumcision decreases HIV acquisition by 60%, and antiretroviral therapy (ART) almost eliminates HIV transmission from HIV-positive people who are virally suppressed; however, coverage of these interventions has lagged behind targets. We aimed to assess whether community-based HIV testing with counsellor support and point-of-care CD4 cell count testing would increase uptake of ART and male circumcision. Methods: We did this multisite, open-label, randomised controlled trial in six research-naive communities in rural South Africa and Uganda. Eligible HIV-positive participants (aged ≥16 years) were randomly assigned (1:1:1) in a factorial design to receive lay counsellor clinic linkage facilitation, lay counsellor follow-up home visits, or standard-of-care clinic referral, and then (1:1) either point-of-care CD4 cell count testing or referral for CD4 testing. HIV-negative uncircumcised men (aged 16-49 years) who could receive secure mobile phone text messages were randomly assigned (1:1:1) to receive text message reminders, lay counsellor visits, or standard clinic referral. The study biostatistician generated the randomisation schedule via a computer-generated random number program with varying block sizes (multiples of six or three) stratified by country. Primary outcomes for HIV-positive people were obtaining a CD4 cell count, linkage to an HIV clinic, ART initiation, and viral suppression at 9 months, and for HIV-negative uncircumcised men were visiting a circumcision facility and uptake of male circumcision at 3 months. We assessed social harms as a safety outcome throughout the study. We did the primary analyses by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02038582. Findings: Between June 6, 2013, and March 11, 2015, 15 332 participants were tested. 2339 (15%) participants tested HIV positive, of whom 1325 (57%) were randomly assigned to receive lay counsellor clinic linkage facilitation (n=437), lay counsellor follow-up home visits (n=449), or standard clinic referral (n=439), and then point-of-care CD4 cell testing (n=206, n=220, and n=213, respectively) or referral for CD4 testing (n=231, n=229, and n=226, respectively). 12 993 (85%) participants tested HIV negative, of whom 750 (6%) uncircumcised men were randomly assigned to receive clinic referral (n=230), text message reminders (n=288), or lay counsellor follow-up visits (n=232). 1218 (93%) of 1303 HIV-positive participants were linked to care, but only 488 (37%) participants initiated ART. Overall, 635 (50%) of 1272 HIV-positive individuals achieved viral suppression at 9 months: 219 (52%) of 419 participants in the clinic facilitation group, 202 (47%) of 431 participants in the lay counsellor follow-up group, and 214 (51%) of 422 participants in the clinic referral group, with no significant differences between groups (p=0·668 for clinic facilitation and p=0·273 for lay counsellor follow-up vs clinic referral). 523 (72%) of 734 HIV-negative men visited a circumcision facility, with no difference between groups. 62 (28%) of 224 men were circumcised in the male circumcision clinic referral group compared with 137 (48%) of 284 men in the text message reminder group (relative risk 1·72, 95% CI 1·36-2·17; p<0·0001) and 106 (47%) of 226 men in the lay counsellor follow-up group (1·67, 1·29-2·14; p=0·0001). No cases of study-related social harm were reported, including probing about partnership separation, unintended disclosure, gender-based violence, and stigma. Interpretation: All the community-based strategies achieved high rates of linkage of HIV-positive people to HIV clinics, roughly a third of whom initiated ART, and of those more than 80% were virally suppressed at 9 months. Uptake of male circumcision was almost two-times higher in men who received text message reminders or lay counsellor visits than in those who received standard-of-care clinic referral. Clinic barriers to ART initiation should be addressed in future strategies to increase the proportion of HIV-positive people accessing treatment and achieving viral suppression. Funding: National Institute of Allergy and Infectious Diseases, National Institutes of Health.

The lancet. HIV · randomised controlled trial · 65 citationsread the source →

Effects of digital cognitive behavioural therapy for insomnia on insomnia severity: a large-scale randomised controlled trial.

Background: Although several large-scale randomised controlled trials have shown the efficacy of digital cognitive behavioural therapy for insomnia (dCBT-I), there is a need to validate widespread dissemination of dCBT-I using recommended key outcomes for insomnia. We investigated the effect of a fully automated dCBT-I programme on insomnia severity, sleep-wake patterns, sleep medication use, and daytime impairment. Methods: We did a parallel-group superiority randomised controlled trial comparing dCBT-I with online patient education about sleep. The interventions were available through a free-to-access website, publicised throughout Norway, which incorporated automated screening, informed consent, and randomisation procedures, as well as outcome assessments. Adults (age ≥18 years) who had regular internet access and scored 12 or higher on the Insomnia Severity Index (ISI) were eligible for inclusion, and were allocated (1:1) to receive dCBT-I (consisting of six core interactive sessions to be completed over 9 weeks) or patient education (control group). Participants were masked to group assignment and had no contact with researchers during the intervention period. The primary outcome was the change in ISI score from baseline to 9-week follow-up, assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02558647) and is ongoing, with 2-year follow-up assessments planned. Findings: Between Feb 26, 2016, and July 1, 2018, 5349 individuals commenced the online screening process, of which 1497 were ineligible or declined to participate, 2131 discontinued the screening process, and 1721 were randomly allocated (868 to receive dCBT-I and 853 to receive patient education). At 9-week follow-up, 584 (67%) participants in the dCBT-I group and 534 (63%) in the patient education group completed the ISI assessment. The latent growth model showed that participants in the dCBT-I group had a significantly greater reduction in ISI scores from baseline (mean score 19·2 [SD 3·9]) to 9-week follow-up (10·4 [6·2]) than those in the patient education group (from 19·6 [4·0] to 15·2 [5·3]; estimated mean difference -4·7 (95% CI -5·4 to -4·1; Cohen's d -1·21; p<0·001). Compared with patient education, the number needed to treat with dCBT-I was 2·7 (95% CI 2·4 to 3·2) for treatment response (ISI score reduction ≥8) and 3·2 (2·8 to 3·8) for insomnia remission (ISI score <8). No adverse events were reported to the trial team. Interpretation: dCBT-I is effective in reducing the severity of symptoms associated with the insomnia disorder. These findings support the widespread dissemination of dCBT-I. Future research is needed to identify the moderators of response and to improve targeting. Funding: Norwegian Research Council; Liaison Committee for Education, Research and Innovation in Central Norway.

The Lancet. Digital health · randomised controlled trial · 95 citationsread the source →

An Ecological Momentary Intervention for weight loss and healthy eating via smartphone and Internet: study protocol for a randomised controlled trial.

Background: Long-term weight loss maintenance is difficult to achieve. Effectiveness of obesity interventions could be increased by providing extended treatment, and by focusing on person-environment interactions. Ecological Momentary Intervention (EMI) can account for these two factors by allowing an indefinite extension of a treatment protocol in everyday life. EMI relies on observations in daily life to intervene by providing appropriate in-the-moment treatment. The Think Slim intervention is an EMI based on the principles of cognitive behavioural therapy (CBT), and its effectiveness will be investigated in the current study. Methods: A randomised controlled trial (RCT) will be conducted. At least 134 overweight adults (body mass index (BMI) above 25 kg/m(2)) will be randomly assigned to an 8-week immediate intervention group (Diet + Think Slim intervention, n = 67) or to an 8-week diet-only control group (followed by the Think Slim intervention, n = 67). The Think Slim intervention consists of (1) an app-based EMI that estimates and intervenes when people are likely to overeat, based on Ecological Momentary Assessment data, and (2) ten online computerised CBT sessions which work in conjunction with an EMI module in the app. The primary outcome is BMI. Secondary outcomes include (1) scores on self-report questionnaires for dysfunctional thinking, eating styles, eating disorder pathology, general psychological symptomatology, and self-esteem, and (2) eating patterns, investigated via network analysis. Primary and secondary outcomes will be obtained at pre- and post-intervention measurements, and at 3- and 12-month follow-up measurements. Discussion: This is the first EMI aimed at treating obesity via a cognitive approach, provided via a smartphone app and the Internet, in the context of an RCT. Trial registration: This trial has been registered at the Netherlands Trial Register, part of the Dutch Cochrane Centre ( NTR5473 ; registration date: 26 October 2015).

Trials · randomised controlled trial · 21 citationsread the source →

Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial.

Importance: Major depressive disorder (MDD) is a substantial public health burden, but current treatments have limited effectiveness and adherence. Recent evidence suggests that 1 or 2 administrations of psilocybin with psychological support produces antidepressant effects in patients with cancer and in those with treatment-resistant depression. Objective: To investigate the effect of psilocybin therapy in patients with MDD. Design, setting, and participants: This randomized, waiting list-controlled clinical trial was conducted at the Center for Psychedelic and Consciousness Research at Johns Hopkins Bayview Medical Center in Baltimore, Maryland. Adults aged 21 to 75 years with an MDD diagnosis, not currently using antidepressant medications, and without histories of psychotic disorder, serious suicide attempt, or hospitalization were eligible to participate. Enrollment occurred between August 2017 and April 2019, and the 4-week primary outcome assessments were completed in July 2019. A total of 27 participants were randomized to an immediate treatment condition group (n = 15) or delayed treatment condition group (waiting list control condition; n = 12). Data analysis was conducted from July 1, 2019, to July 31, 2020, and included participants who completed the intervention (evaluable population). Interventions: Two psilocybin sessions (session 1: 20 mg/70 kg; session 2: 30 mg/70 kg) were given (administered in opaque gelatin capsules with approximately 100 mL of water) in the context of supportive psychotherapy (approximately 11 hours). Participants were randomized to begin treatment immediately or after an 8-week delay. Main outcomes and measures: The primary outcome, depression severity was assessed with the GRID-Hamilton Depression Rating Scale (GRID-HAMD) scores at baseline (score of ≥17 required for enrollment) and weeks 5 and 8 after enrollment for the delayed treatment group, which corresponded to weeks 1 and 4 after the intervention for the immediate treatment group. Secondary outcomes included the Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR). Results: Of the randomized participants, 24 of 27 (89%) completed the intervention and the week 1 and week 4 postsession assessments. This population had a mean (SD) age of 39.8 (12.2) years, was composed of 16 women (67%), and had a mean (SD) baseline GRID-HAMD score of 22.8 (3.9). The mean (SD) GRID-HAMD scores at weeks 1 and 4 (8.0 [7.1] and 8.5 [5.7]) in the immediate treatment group were statistically significantly lower than the scores at the comparable time points of weeks 5 and 8 (23.8 [5.4] and 23.5 [6.0]) in the delayed treatment group. The effect sizes were large at week 5 (Cohen d = 2.5; 95% CI, 1.4-3.5; P < .001) and week 8 (Cohen d = 2.6; 95% CI, 1.5-3.7; P < .001). The QIDS-SR documented a rapid decrease in mean (SD) depression score from baseline to day 1 after session 1 (16.7 [3.5] vs 6.3 [4.4]; Cohen d = 2.6; 95% CI, 1.8-3.5; P < .001), which remained statistically significantly reduced through the week 4 follow-up (6.0 [5.7]; Cohen d = 2.3; 95% CI, 1.5-3.0; P < .001). In the overall sample, 17 participants (71%) at week 1 and 17 (71%) at week 4 had a clinically significant response to the intervention (≥50% reduction in GRID-HAMD score), and 14 participants (58%) at week 1 and 13 participants (54%) at week 4 were in remission (≤7 GRID-HAMD score). Conclusions and relevance: Findings suggest that psilocybin with therapy is efficacious in treating MDD, thus extending the results of previous studies of this intervention in patients with cancer and depression and of a nonrandomized study in patients with treatment-resistant depression. Trial registration: ClinicalTrials.gov Identifier: NCT03181529.

JAMA psychiatry · randomised controlled trial · 900 citationsread the source →

Acceptance and commitment therapy as a web-based intervention for depressive symptoms: randomised controlled trial.

Background: Depression is a highly prevalent disorder, causing a large burden of disease and substantial economic costs. Web-based self-help interventions seem promising in promoting mental health. Aims: To compare the efficacy of a guided web-based intervention based on acceptance and commitment therapy (ACT) with an active control (expressive writing) and a waiting-list control condition (Netherlands Trial Register NTR1296). Method: Adults with depressive symptoms from the general population were randomised to ACT (n = 82), expressive writing (n = 67) or waiting-list control (n = 87). The main outcome was reduction in depressive symptoms assessed with the Center for Epidemiological Studies - Depression scale. Results: Significant reductions in depressive symptoms were found following the ACT intervention, compared with the control group (Cohen's d = 0.56) and the expressive writing intervention (d = 0.36). The effects were sustained at 6-month and 12-month follow-up. Conclusions: Acceptance and commitment therapy as a web-based public mental health intervention for adults with depressive symptoms can be effective and applicable.

The British journal of psychiatry : the journal of mental science · randomised controlled trial · 66 citationsread the source →

Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial.

Background: Vascular-targeted photodynamic therapy, a novel tissue-preserving treatment for low-risk prostate cancer, has shown favourable safety and efficacy results in single-arm phase 1 and 2 studies. We compared this treatment with the standard of care, active surveillance, in men with low-risk prostate cancer in a phase 3 trial. Methods: This randomised controlled trial was done in 47 European university centres and community hospitals. Men with low-risk, localised prostate cancer (Gleason pattern 3) who had received no previous treatment were randomly assigned (1:1) to vascular-targeted photodynamic therapy (4 mg/kg padeliporfin intravenously over 10 min and optical fibres inserted into the prostate to cover the desired treatment zone and subsequent activation by laser light 753 nm with a fixed power of 150 mW/cm for 22 min 15 s) or active surveillance. Randomisation was done by a web-based allocation system stratified by centre with balanced blocks of two or four patients. Best practice for active surveillance at the time of study design was followed (ie, biopsy at 12-month intervals and prostate-specific antigen measurement and digital rectal examination at 3-month intervals). The co-primary endpoints were treatment failure (histological progression of cancer from low to moderate or high risk or death during 24 months' follow-up) and absence of definite cancer (absence of any histology result definitely positive for cancer at month 24). Analysis was by intention to treat. Treatment was open-label, but investigators assessing primary efficacy outcomes were masked to treatment allocation. This trial is registered with ClinicalTrials.gov, number NCT01310894. Findings: Between March 8, 2011, and April 30, 2013, we randomly assigned 206 patients to vascular-targeted photodynamic therapy and 207 patients to active surveillance. Median follow-up was 24 months (IQR 24-25). The proportion of participants who had disease progression at month 24 was 58 (28%) of 206 in the vascular-targeted photodynamic therapy group compared with 120 (58%) of 207 in the active surveillance group (adjusted hazard ratio 0·34, 95% CI 0·24-0·46; p<0·0001). 101 (49%) men in the vascular-targeted photodynamic therapy group had a negative prostate biopsy result at 24 months post treatment compared with 28 (14%) men in the active surveillance group (adjusted risk ratio 3·67, 95% CI 2·53-5·33; p<0·0001). Vascular-targeted photodynamic therapy was well tolerated. The most common grade 3-4 adverse events were prostatitis (three [2%] in the vascular-targeted photodynamic therapy group vs one [<1%] in the active surveillance group), acute urinary retention (three [2%] vs one [<1%]) and erectile dysfunction (two [1%] vs three [1%]). The most common serious adverse event in the vascular-targeted photodynamic therapy group was retention of urine (15 patients; severe in three); this event resolved within 2 months in all patients. The most common serious adverse event in the active surveillance group was myocardial infarction (three patients). Interpretation: Padeliporfin vascular-targeted photodynamic therapy is a safe, effective treatment for low-risk, localised prostate cancer. This treatment might allow more men to consider a tissue-preserving approach and defer or avoid radical therapy. Funding: Steba Biotech.

The Lancet. Oncology · randomised controlled trial · 236 citationsread the source →

Computer-based diabetes self-management interventions for adults with type 2 diabetes mellitus.

Background: Diabetes is one of the commonest chronic medical conditions, affecting around 347 million adults worldwide. Structured patient education programmes reduce the risk of diabetes-related complications four-fold. Internet-based self-management programmes have been shown to be effective for a number of long-term conditions, but it is unclear what are the essential or effective components of such programmes. If computer-based self-management interventions improve outcomes in type 2 diabetes, they could potentially provide a cost-effective option for reducing the burdens placed on patients and healthcare systems by this long-term condition. Objectives: To assess the effects on health status and health-related quality of life of computer-based diabetes self-management interventions for adults with type 2 diabetes mellitus. Search methods: We searched six electronic bibliographic databases for published articles and conference proceedings and three online databases for theses (all up to November 2011). Reference lists of relevant reports and reviews were also screened. Selection criteria: Randomised controlled trials of computer-based self-management interventions for adults with type 2 diabetes, i.e. computer-based software applications that respond to user input and aim to generate tailored content to improve one or more self-management domains through feedback, tailored advice, reinforcement and rewards, patient decision support, goal setting or reminders. Data collection and analysis: Two review authors independently screened the abstracts and extracted data. A taxonomy for behaviour change techniques was used to describe the active ingredients of the intervention. Main results: We identified 16 randomised controlled trials with 3578 participants that fitted our inclusion criteria. These studies included a wide spectrum of interventions covering clinic-based brief interventions, Internet-based interventions that could be used from home and mobile phone-based interventions. The mean age of participants was between 46 to 67 years old and mean time since diagnosis was 6 to 13 years. The duration of the interventions varied between 1 to 12 months. There were three reported deaths out of 3578 participants. Computer-based diabetes self-management interventions currently have limited effectiveness. They appear to have small benefits on glycaemic control (pooled effect on glycosylated haemoglobin A1c (HbA1c): -2.3 mmol/mol or -0.2% (95% confidence interval (CI) -0.4 to -0.1; P = 0.009; 2637 participants; 11 trials). The effect size on HbA1c was larger in the mobile phone subgroup (subgroup analysis: mean difference in HbA1c -5.5 mmol/mol or -0.5% (95% CI -0.7 to -0.3); P < 0.00001; 280 participants; three trials). Current interventions do not show adequate evidence for improving depression, health-related quality of life or weight. Four (out of 10) interventions showed beneficial effects on lipid profile. One participant withdrew because of anxiety but there were no other documented adverse effects. Two studies provided limited cost-effectiveness data - with one study suggesting costs per patient of less than $140 (in 1997) or 105 EURO and another study showed no change in health behaviour and resource utilisation. Authors' conclusions: Computer-based diabetes self-management interventions to manage type 2 diabetes appear to have a small beneficial effect on blood glucose control and the effect was larger in the mobile phone subgroup. There is no evidence to show benefits in other biological outcomes or any cognitive, behavioural or emotional outcomes.

The Cochrane database of systematic reviews · meta-analysis · 213 citationsread the source →

Towards universal voluntary HIV testing and counselling: a systematic review and meta-analysis of community-based approaches.

Background: Effective national and global HIV responses require a significant expansion of HIV testing and counselling (HTC) to expand access to prevention and care. Facility-based HTC, while essential, is unlikely to meet national and global targets on its own. This article systematically reviews the evidence for community-based HTC. Methods and findings: PubMed was searched on 4 March 2013, clinical trial registries were searched on 3 September 2012, and Embase and the World Health Organization Global Index Medicus were searched on 10 April 2012 for studies including community-based HTC (i.e., HTC outside of health facilities). Randomised controlled trials, and observational studies were eligible if they included a community-based testing approach and reported one or more of the following outcomes: uptake, proportion receiving their first HIV test, CD4 value at diagnosis, linkage to care, HIV positivity rate, HTC coverage, HIV incidence, or cost per person tested (outcomes are defined fully in the text). The following community-based HTC approaches were reviewed: (1) door-to-door testing (systematically offering HTC to homes in a catchment area), (2) mobile testing for the general population (offering HTC via a mobile HTC service), (3) index testing (offering HTC to household members of people with HIV and persons who may have been exposed to HIV), (4) mobile testing for men who have sex with men, (5) mobile testing for people who inject drugs, (6) mobile testing for female sex workers, (7) mobile testing for adolescents, (8) self-testing, (9) workplace HTC, (10) church-based HTC, and (11) school-based HTC. The Newcastle-Ottawa Quality Assessment Scale and the Cochrane Collaboration's "risk of bias" tool were used to assess the risk of bias in studies with a comparator arm included in pooled estimates. 117 studies, including 864,651 participants completing HTC, met the inclusion criteria. The percentage of people offered community-based HTC who accepted HTC was as follows: index testing, 88% of 12,052 participants; self-testing, 87% of 1,839 participants; mobile testing, 87% of 79,475 participants; door-to-door testing, 80% of 555,267 participants; workplace testing, 67% of 62,406 participants; and school-based testing, 62% of 2,593 participants. Mobile HTC uptake among key populations (men who have sex with men, people who inject drugs, female sex workers, and adolescents) ranged from 9% to 100% (among 41,110 participants across studies), with heterogeneity related to how testing was offered. Community-based approaches increased HTC uptake (relative risk [RR] 10.65, 95% confidence interval [CI] 6.27-18.08), the proportion of first-time testers (RR 1.23, 95% CI 1.06-1.42), and the proportion of participants with CD4 counts above 350 cells/µl (RR 1.42, 95% CI 1.16-1.74), and obtained a lower positivity rate (RR 0.59, 95% CI 0.37-0.96), relative to facility-based approaches. 80% (95% CI 75%-85%) of 5,832 community-based HTC participants obtained a CD4 measurement following HIV diagnosis, and 73% (95% CI 61%-85%) of 527 community-based HTC participants initiated antiretroviral therapy following a CD4 measurement indicating eligibility. The data on linking participants without HIV to prevention services were limited. In low- and middle-income countries, the cost per person tested ranged from US$2-US$126. At the population level, community-based HTC increased HTC coverage (RR 7.07, 95% CI 3.52-14.22) and reduced HIV incidence (RR 0.86, 95% CI 0.73-1.02), although the incidence reduction lacked statistical significance. No studies reported any harm arising as a result of having been tested. Conclusions: Community-based HTC achieved high rates of HTC uptake, reached people with high CD4 counts, and linked people to care. It also obtained a lower HIV positivity rate relative to facility-based approaches. Further research is needed to further improve acceptability of community-based HTC for key populations. HIV programmes should offer community-based HTC linked to prevention and care, in addition to facility-based HTC, to support increased access to HIV prevention, care, and treatment. Review registration: International Prospective Register of Systematic Reviews CRD42012002554 Please see later in the article for the Editors' Summary.

PLoS medicine · meta-analysis · 313 citationsread the source →

The WHO Health Promoting School framework for improving the health and well-being of students and their academic achievement.

Background: The World Health Organization's (WHO's) Health Promoting Schools (HPS) framework is an holistic, settings-based approach to promoting health and educational attainment in school. The effectiveness of this approach has not been previously rigorously reviewed. Objectives: To assess the effectiveness of the Health Promoting Schools (HPS) framework in improving the health and well-being of students and their academic achievement. Search methods: We searched the following electronic databases in January 2011 and again in March and April 2013: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL, Campbell Library, ASSIA, BiblioMap, CAB Abstracts, IBSS, Social Science Citation Index, Sociological Abstracts, TRoPHI, Global Health Database, SIGLE, Australian Education Index, British Education Index, Education Resources Information Centre, Database of Education Research, Dissertation Express, Index to Theses in Great Britain and Ireland, ClinicalTrials.gov, Current controlled trials, and WHO International Clinical Trials Registry Platform. We also searched relevant websites, handsearched reference lists, and used citation tracking to identify other relevant articles. Selection criteria: We included cluster-randomised controlled trials where randomisation took place at the level of school, district or other geographical area. Participants were children and young people aged four to 18 years, attending schools or colleges. In this review, we define HPS interventions as comprising the following three elements: input to the curriculum; changes to the school's ethos or environment or both; and engagement with families or communities, or both. We compared this intervention against schools that implemented either no intervention or continued with their usual practice, or any programme that included just one or two of the above mentioned HPS elements. Data collection and analysis: At least two review authors identified relevant trials, extracted data, and assessed risk of bias in the trials. We grouped different types of interventions according to the health topic targeted or the approach used, or both. Where data permitted, we performed random-effects meta-analyses to provide a summary of results across studies. Main results: We included 67 eligible cluster trials, randomising 1443 schools or districts. This is made up of 1345 schools and 98 districts. The studies tackled a range of health issues: physical activity (4), nutrition (12), physical activity and nutrition combined (18), bullying (7), tobacco (5), alcohol (2), sexual health (2), violence (2), mental health (2), hand-washing (2), multiple risk behaviours (7), cycle-helmet use (1), eating disorders (1), sun protection (1), and oral health (1). The quality of evidence overall was low to moderate as determined by the GRADE approach. 'Risk of bias' assessments identified methodological limitations, including heavy reliance on self-reported data and high attrition rates for some studies. In addition, there was a lack of long-term follow-up data for most studies. We found positive effects for some interventions for: body mass index (BMI), physical activity, physical fitness, fruit and vegetable intake, tobacco use, and being bullied. Intervention effects were generally small but have the potential to produce public health benefits at the population level. We found little evidence of effectiveness for standardised body mass index (zBMI) and no evidence of effectiveness for fat intake, alcohol use, drug use, mental health, violence and bullying others; however, only a small number of studies focused on these latter outcomes. It was not possible to meta-analyse data on other health outcomes due to lack of data. Few studies provided details on adverse events or outcomes related to the interventions. In addition, few studies included any academic, attendance or school-related outcomes. We therefore cannot draw any clear conclusions as to the effectiveness of this approach for improving academic achievement. Authors' conclusions: The results of this review provide evidence for the effectiveness of some interventions based on the HPS framework for improving certain health outcomes but not others. More well-designed research is required to establish the effectiveness of this approach for other health topics and academic achievement.

The Cochrane database of systematic reviews · meta-analysis · 382 citationsread the source →

Mindfulness-based therapy: a comprehensive meta-analysis.

Background: Mindfulness-based therapy (MBT) has become a popular form of intervention. However, the existing reviews report inconsistent findings. Objective: To clarify these inconsistencies in the literature, we conducted a comprehensive effect-size analysis to evaluate the efficacy of MBT. Data sources: A systematic review of studies published in journals or in dissertations in PubMED or PsycINFO from the first available date until May 10, 2013. Review methods: A total of 209 studies (n=12,145) were included. Results: Effect-size estimates suggested that MBT is moderately effective in pre-post comparisons (n=72; Hedge's g=.55), in comparisons with waitlist controls (n=67; Hedge's g=.53), and when compared with other active treatments (n=68; Hedge's g=.33), including other psychological treatments (n=35; Hedge's g=.22). MBT did not differ from traditional CBT or behavioral therapies (n=9; Hedge's g=-.07) or pharmacological treatments (n=3; Hedge's g=.13). Conclusion: MBT is an effective treatment for a variety of psychological problems, and is especially effective for reducing anxiety, depression, and stress.

Clinical psychology review · meta-analysis · 819 citationsread the source →

A randomized trial of a Facebook-based physical activity intervention for young adult cancer survivors.

Purpose: Over half of young adult cancer survivors do not meet physical activity (PA) guidelines. PA interventions can enhance health and quality of life among young adult cancer survivors. However, few exercise interventions have been designed and tested in this population. This study evaluated the feasibility and preliminary efficacy of a 12-week, Facebook-based intervention (FITNET) aimed at increasing moderate-to-vigorous intensity PA compared with a Facebook-based self-help comparison (SC) condition. Methods: Young adult cancer survivors (n = 86) were randomly assigned to the FITNET or SC group. All participants were asked to complete self-administered online questionnaires at baseline and after 12 weeks. Results: Seventy-seven percent of participants completed postintervention assessments, and most participants reported using intervention components as intended. Participants in both groups would recommend the program to other young adult cancer survivors (FITNET, 46.9 vs. SC, 61.8 %; p = 0.225). Over 12 weeks, both groups increased self-reported weekly minutes of moderate-to-vigorous PA (FITNET, 67 min/week (p = 0.009) vs. SC, 46 min/week (p = 0.045)), with no significant difference between groups. Increases in light PA were 135 min/week greater in the FITNET group relative to the SC group (p = 0.032), and the FITNET group reported significant weight loss over time (-2.1 kg, p = 0.004; p = 0.083 between groups). Conclusion: Facebook-based intervention approaches demonstrated potential for increasing PA in young adult cancer survivors. Implications for cancer survivors: Social networking sites may be a feasible way for young adult cancer survivors to receive health information and support to promote PA and healthy behaviors.

Journal of cancer survivorship : research and practice · randomised controlled trial · 208 citationsread the source →

A randomized, multicentre, open-label, comparative trial of disulfiram, naltrexone and acamprosate in the treatment of alcohol dependence.

Aim: To compare the effects in alcohol-dependent patients of three pharmacotherapies, disulfiram (DIS), naltrexone (NTX), and acamprosate (ACA), when used with a brief manual-based cognitive-behavioural intervention. Method: We conducted a randomized, open label, multicentre naturalistic study in two phases; first, a 12-week continuously supervised medication, followed by targeted medication (TM) up to 52 weeks in addition to a 67-week follow-up period; altogether 119 weeks (2.5 years), in 243 voluntary treatment-seeking alcohol-dependent adult outpatients. Subjects were randomized 1:1:1 to receive supervised NTX, ACA or DIS, 50, 1998, or 200 mg, respectively, per day, plus a brief manual-based cognitive-behavioural intervention. The patients were met in the second and sixth weeks, and then after 3, 6, and 12 months. The primary outcome measures were the time (days) to first heavy drinking day (HDD), and time during the first 3 months to the first drinking day after medication started. Secondary variables were abstinent days/week (0 drinks/day), average weekly alcohol intake, Alcohol Use Disorder Identification Test (AUDIT), Severity of Alcohol Dependence Data (SADD), and quality of life (QL) measures. Results: All three study groups showed marked reduction in drinking, from baseline to the end of the study. During the continuous medication phase, treatment with DIS was more effective in reducing HDDs and average weekly alcohol consumption, and increasing time to the first drink, as well as the number of abstinent days. During the TM period, there were no significant differences between the groups in time to first HDD and days to first drinking, but the abstinence days were significantly more frequent in the DIS group than ACA and NTX. There were no differences between the NTX and ACA groups in either phase of the study of drinking outcomes. However, SADD scores improved more in the NTX group than the ACA group. Conclusions: Patients allocated to ACA, NTX and DIS combined with brief manual-based cognitive behavioural intervention significantly reduce their alcohol consumption and report improved QL. Supervised DIS appeared superior, especially during the continuous medication period, to NTX and ACA.

Alcohol and alcoholism (Oxford, Oxfordshire) · randomised controlled trial · 80 citationsread the source →

Effects of a palliative care intervention on clinical outcomes in patients with advanced cancer: the Project ENABLE II randomized controlled trial.

Context: There are few randomized controlled trials on the effectiveness of palliative care interventions to improve the care of patients with advanced cancer. Objective: To determine the effect of a nursing-led intervention on quality of life, symptom intensity, mood, and resource use in patients with advanced cancer. Design, setting, and participants: Randomized controlled trial conducted from November 2003 through May 2008 of 322 patients with advanced cancer in a rural, National Cancer Institute-designated comprehensive cancer center in New Hampshire and affiliated outreach clinics and a VA medical center in Vermont. Interventions: A multicomponent, psychoeducational intervention (Project ENABLE [Educate, Nurture, Advise, Before Life Ends]) conducted by advanced practice nurses consisting of 4 weekly educational sessions and monthly follow-up sessions until death or study completion (n = 161) vs usual care (n = 161). Main outcome measures: Quality of life was measured by the Functional Assessment of Chronic Illness Therapy for Palliative Care (score range, 0-184). Symptom intensity was measured by the Edmonton Symptom Assessment Scale (score range, 0-900). Mood was measured by the Center for Epidemiological Studies Depression Scale (range, 0-60). These measures were assessed at baseline, 1 month, and every 3 months until death or study completion. Intensity of service was measured as the number of days in the hospital and in the intensive care unit (ICU) and the number of emergency department visits recorded in the electronic medical record. Results: A total of 322 participants with cancer of the gastrointestinal tract (41%; 67 in the usual care group vs 66 in the intervention group), lung (36%; 58 vs 59), genitourinary tract (12%; 20 vs 19), and breast (10%; 16 vs 17) were randomized. The estimated treatment effects (intervention minus usual care) for all participants were a mean (SE) of 4.6 (2) for quality of life (P = .02), -27.8 (15) for symptom intensity (P = .06), and -1.8 (0.81) for depressed mood (P = .02). The estimated treatment effects in participants who died during the study were a mean (SE) of 8.6 (3.6) for quality of life (P = .02), -24.2 (20.5) for symptom intensity (P = .24), and -2.7 (1.2) for depressed mood (P = .03). Intensity of service did not differ between the 2 groups. Conclusion: Compared with participants receiving usual oncology care, those receiving a nurse-led, palliative care-focused intervention addressing physical, psychosocial, and care coordination provided concurrently with oncology care had higher scores for quality of life and mood, but did not have improvements in symptom intensity scores or reduced days in the hospital or ICU or emergency department visits. Trial registration: clinicaltrials.gov Identifier: NCT00253383.

JAMA · randomised controlled trial · 1314 citationsread the source →

Exercise for health: a randomized, controlled trial evaluating the impact of a pragmatic, translational exercise intervention on the quality of life, function and treatment-related side effects following breast cancer.

Exercise for Health was a randomized, controlled trial designed to evaluate two modes of delivering (face-to-face [FtF] and over-the-telephone [Tel]) an 8-month translational exercise intervention, commencing 6-weeks post-breast cancer surgery (PS). Outcomes included quality of life (QoL), function (fitness and upper body) and treatment-related side effects (fatigue, lymphoedema, body mass index, menopausal symptoms, anxiety, depression and pain). Generalised estimating equation modelling determined time (baseline [5 weeks PS], mid-intervention [6 months PS], post-intervention [12 months PS]), group (FtF, Tel, Usual Care [UC]) and time-by-group effects. 194 women representative of the breast cancer population were randomised to the FtF (n = 67), Tel (n = 67) and UC (n = 60) groups. There were significant (p < 0.05) interaction effects on QoL, fitness and fatigue with differences being observed between the treatment groups and the UC group. Trends observed for the treatment groups were similar. The treatment groups reported improved QoL, fitness and fatigue over time and changes observed between baseline and post-intervention were clinically relevant. In contrast, the UC group experienced no change, or worsening QoL, fitness and fatigue, mid-intervention. Although improvements in the UC group occurred by 12-months post-surgery, the change did not meet the clinically relevant threshold. There were no differences in other treatment-related side effects between groups. This translational intervention trial, delivered either FtF or Tel, supports exercise as a form of adjuvant breast cancer therapy that can prevent declines in fitness and function during treatment and optimise recovery post-treatment.

Breast cancer research and treatment · randomised controlled trial · 141 citationsread the source →

A randomized controlled comparison of guided self-help cognitive behavioral therapy and behavioral weight loss for binge eating disorder.

We performed a randomized controlled study to test the relative efficacy of guided self-help (gsh) cognitive-behavioral therapy (CBTgsh) and behavioral weight loss treatment (BWLgsh) treatments for binge eating disorder (BED). To provide an additional partial control for non-specific influences of attention, a third control (CON) treatment condition was included. We tested the treatments using a guided self-help approach given the promising results from initial studies using minimal therapist guidance. Ninety consecutive overweight patients (19 males, 71 females) with BED were randomly assigned (5:5:2 ratio) to one of three treatments: CBTgsh (N=37), BWLgsh (N=38), or CON (N=15). The three 12-week treatment conditions were administered individually following guided self-help protocols. Overall, 70 (78%) completed treatments; CBTgsh (87%) and CON (87%) had significantly higher completion rates than BWLgsh (67%). Intent-to-treat analyses revealed that CBTgsh had significantly higher remission rates (46%) than either BWLgsh (18%) or CON (13%). Weight loss was minimal and differed little across treatments. The findings suggest that CBT, administered via guided self-help, demonstrates efficacy for BED, but not for obesity. The findings support CBT administered via guided self-help as a first step in the treatment of BED and provide evidence for its specific effects.

Behaviour research and therapy · randomised controlled trial · 124 citationsread the source →

Randomized controlled multicentre trial of cognitive behaviour therapy in the early initial prodromal state: effects on social adjustment post treatment.

Aim: Improvement of social adjustment is a major aim of indicated prevention in young people at risk of developing psychosis. The present study explores the effect of specific cognitive behaviour therapy (CBT) as compared with supportive counselling (SC) on social adjustment in people in a potential early initial prodromal state of psychosis (EIPS) primarily defined by self-experienced cognitive thought and perception deficits (basic symptoms). Methods: A total of 128 help-seeking outpatients in the EIPS were randomized to receive either specific CBT or SC for 12 months. Social adjustment was assessed with the Social Adjustment Scale II (SAS II) at baseline, time of transition or post treatment Results: From 113 patients, who completed the SAS II at intake, 67 (59.3%) completed the SAS assessments at time of transition or post treatment. Both specific CBT and SC resulted in improvements in scales of SAS II, with no significant between-group differences post treatment. Conclusions: Although treatment in specially designed early detection and intervention centres improves functioning of people in the EIPS, specific CBT was not superior to SC. One could hypothesize that additional vocational rehabilitation, case management and involvement of multidisciplinary teams are needed to further improve short-term outcome of specific interventions on this dimension.

Early intervention in psychiatry · randomised controlled trial · 38 citationsread the source →

Fewer emergency readmissions and better quality of life for older adults at risk of hospital readmission: a randomized controlled trial to determine the effectiveness of a 24-week exercise and telephone follow-up program.

Objectives: To evaluate the effect of an exercise-based model of hospital and in-home follow-up care for older people at risk of hospital readmission on emergency health service utilization and quality of life. Design: Randomized controlled trial. Setting: Tertiary metropolitan hospital in Australia. Participants: One hundred twenty-eight patients (64 intervention, 64 control) with an acute medical admission, aged 65 and older and with at least one risk factor for readmission (multiple comorbidities, impaired functionality, aged >or=75, recent multiple admissions, poor social support, history of depression). Intervention: Comprehensive nursing and physiotherapy assessment and individualized program of exercise strategies and nurse-conducted home visit and telephone follow-up commencing in the hospital and continuing for 24 weeks after discharge. Measurements: Emergency health service utilization (emergency hospital readmissions and visits to emergency department, general practitioner (GP), or allied health professional) and health-related quality of life (Medical Outcomes Study 12-item Short Form Survey (SF-12v2) collected at baseline and 4, 12, and 24 weeks after discharge. Results: The intervention group required significantly fewer emergency hospital readmissions (22% of intervention group, 47% of control group, P=.007) and emergency GP visits (25% of intervention group, 67% of control group, P<.001). The intervention group also reported significantly greater improvements in quality of life than the control group as measured using SF-12v2 Physical Component Summary scores (F (3, 279)=30.43, P<.001) and Mental Component Summary scores (F (3, 279)=7.20, P<.001). Conclusion: Early introduction of an individualized exercise program and long-term telephone follow-up may reduce emergency health service utilization and improve quality of life of older adults at risk of hospital readmission.

Journal of the American Geriatrics Society · randomised controlled trial · 161 citationsread the source →

Low-income depressed older adults with psychiatric comorbidity: secondary analyses of response to psychotherapy and case management.

Objective: This study examined the influence of comorbid anxiety and personality disorders on depression treatment response in 67 low-income older adults. Methods: Participants were randomized to clinical case management, cognitive-behavioral group therapy, or both for 6 months. Outcomes were assessed at baseline, post-treatment, and 6 and 12 months after treatment. Results: Dropout and depression diagnoses were similar across groups. Participants with comorbidity had more depressive and anxiety symptoms at most time points; degree of improvement did not differ significantly. Of participants with personality disorder, none met criteria at post-treatment (three relapsed by 12-month follow-up). Conclusions: Findings suggest depressed low-income elders with anxiety or personality disorders can be retained and benefit from depression treatment, but may require additional interventions to achieve similar levels of depressive symptoms.

International journal of geriatric psychiatry · randomised controlled trial · 21 citationsread the source →

Role of home visiting in improving parenting and health in families at risk of abuse and neglect: results of a multicentre randomised controlled trial and economic evaluation.

Objectives: To evaluate the effectiveness and cost effectiveness of an intensive home visiting programme in improving outcomes for vulnerable families. Design: Multicentre randomised controlled trial in which eligible women were allocated to receive home visiting (n = 67) or standard services (n = 64). Incremental cost analysis. Setting: 40 general practitioner practices across 2 counties in the UK. Participants: 131 vulnerable pregnant women. Intervention: Selected health visitors were trained in the Family Partnership Model to provide a weekly home visiting service from 6 months antenatally to 12 months postnatally. Main outcome measures: Mother-child interaction, maternal psychological health attitudes and behaviour, infant functioning and development, and risk of neglect or abuse. Results: At 12 months, differences favouring the home-visited group were observed on an independent assessment of maternal sensitivity (p<0.04) and infant cooperativeness (p<0.02). No differences were identified on any other measures. A non-significant increase in the likelihood of intervention group infants being the subject of child protection proceedings, or being removed from the home, and one death in the control group were found. The mean incremental cost per infant of the home visiting intervention was 3246 pounds sterling (bootstrapped 95% CI for the difference 1645-4803 pounds sterling). Conclusion: This intervention may have the potential to improve parenting and increase the identification of infants at risk of abuse and neglect in vulnerable families. Further investigation is needed, along with long-term follow-up to assess possible sleeper effects.

Archives of disease in childhood · randomised controlled trial · 89 citationsread the source →

Electroacupuncture for fatigue, sleep, and psychological distress in breast cancer patients with aromatase inhibitor-related arthralgia: a randomized trial.

Background: Although fatigue, sleep disturbance, depression, and anxiety are associated with pain in breast cancer patients, it is unknown whether acupuncture can decrease these comorbid symptoms in cancer patients with pain. The objective of this study was to evaluate the effect of electroacupuncture (EA) on fatigue, sleep, and psychological distress in breast cancer survivors who experience joint pain related to aromatase inhibitors (AIs). Methods: The authors performed a randomized controlled trial of an 8-week course of EA compared with a waitlist control (WLC) group and a sham acupuncture (SA) group in postmenopausal women with breast cancer who self-reported joint pain attributable to AIs. Fatigue, sleep disturbance, anxiety, and depression were measured using the Brief Fatigue Inventory (BFI), the Pittsburgh Sleep Quality Index (PSQI), and the Hospital Anxiety and Depression Scale (HADS). The effects of EA and SA versus WLC on these outcomes were evaluated using mixed-effects models. Results: Of the 67 randomly assigned patients, baseline pain interference was associated with fatigue (Pearson correlation coefficient [r]=0.75; P < .001), sleep disturbance (r=0.38; P=.0026), and depression (r=0.58; P < .001). Compared with the WLC condition, EA produced significant improvements in fatigue (P=.0095), anxiety (P=.044), and depression (P=.015) and a nonsignificant improvement in sleep disturbance (P=.058) during the 12-week intervention and follow-up period. In contrast, SA did not produce significant reductions in fatigue or anxiety symptoms but did produce a significant improvement in depression compared with the WLC condition (P=.0088). Conclusions: Compared with usual care, EA produced significant improvements in fatigue, anxiety, and depression; whereas SA improved only depression in women experiencing AI-related arthralgia.

Cancer · randomised controlled trial · 122 citationsread the source →

Effect of transcutaneous electrical muscle stimulation on muscle volume in patients with septic shock.

Objective: Intensive care unit admission is associated with muscle wasting and impaired physical function. We investigated the effect of early transcutaneous electrical muscle stimulation on quadriceps muscle volume in patients with septic shock. Design: Randomized interventional study using a single-legged exercise design with the contralateral leg serving as a paired control. Setting: A mixed 18-bed intensive care unit at a tertiary care university hospital. Patients: Eight adult male intensive care unit patients with septic shock included within 72 hrs of diagnosis. Interventions: After randomization of the quadriceps muscles, transcutaneous electrical muscle stimulation was applied on the intervention side for 7 consecutive days and for 60 mins per day. All patients underwent computed tomographic scans of both thighs immediately before and after the 7-day treatment period. The quadriceps muscle was manually delineated on the computed tomography slices, and muscle volumes were calculated after three-dimensional reconstruction. Measurements and main results: Median age and Acute Physiology and Chronic Health Evaluation II score were 67 years (interquartile range, 64-72 years) and 25 (interquartile range, 20-29), respectively. During the 7-day study period, the volume of the quadriceps muscle on the control thigh decreased by 16% (4-21%, p=.03) corresponding to a rate of 2.3% per day. The volume of the stimulated muscle decreased by 20% (3-25%, p=.04) corresponding to a rate of 2.9% per day (p=.12 for the difference in decrease). There was no difference in muscle volume between the stimulated and nonstimulated thigh at baseline (p=.10) or at day 7 (p=.12). The charge delivered to the muscle tissue per training session (0.82 [0.66-1.18] coulomb) correlated with the maximum sequential organ failure assessment score. Conclusions: We observed a marked decrease in quadriceps volume within the first week of intensive care for septic shock. This loss of muscle mass was unaffected by transcutaneous electrical muscle stimulation applied for 60 mins per day for 7 days.

Critical care medicine · randomised controlled trial · 88 citationsread the source →

Effect of creatine supplementation and resistance-exercise training on muscle insulin-like growth factor in young adults.

The purpose of this study was to compare changes in muscle insulin-like growth factor-I (IGF-I) content resulting from resistance-exercise training (RET) and creatine supplementation (CR). Male (n=24) and female (n=18) participants with minimal resistance-exercise-training experience (=1 year) who were participating in at least 30 min of structured physical activity (i.e., walking, jogging, cycling) 3-5 x/wk volunteered for the study. Participants were randomly assigned in blocks (gender) to supplement with creatine (CR: 0.25 g/kg lean-tissue mass for 7 days; 0.06 g/kg lean-tissue mass for 49 days; n=22, 12 males, 10 female) or isocaloric placebo (PL: n=20, 12 male, 8 female) and engage in a whole-body RET program for 8 wk. Eighteen participants were classified as vegetarian (lacto-ovo or vegan; CR: 5 male, 5 female; PL: 3 male, 5 female). Muscle biopsies (vastus lateralis) were taken before and after the intervention and analyzed for IGF-I using standard immunohistochemical procedures. Stained muscle cross-sections were examined microscopically and IGF-I content quantified using image-analysis software. Results showed that RET increased intramuscular IGF-I content by 67%, with greater accumulation from CR (+78%) than PL (+54%; p=.06). There were no differences in IGF-I between vegetarians and nonvegetarians. These findings indicate that creatine supplementation during resistance-exercise training increases intramuscular IGF-I concentration in healthy men and women, independent of habitual dietary routine.

International journal of sport nutrition and exercise metabolism · randomised controlled trial · 52 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 →

Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report.

Objective: This report describes the participants and compares the acute and longer-term treatment outcomes associated with each of four successive steps in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. Method: A broadly representative adult outpatient sample with nonpsychotic major depressive disorder received one (N=3,671) to four (N=123) successive acute treatment steps. Those not achieving remission with or unable to tolerate a treatment step were encouraged to move to the next step. Those with an acceptable benefit, preferably symptom remission, from any particular step could enter a 12-month naturalistic follow-up phase. A score of <or=5 on the Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR(16)) (equivalent to <or=7 on the 17-item Hamilton Rating Scale for Depression [HRSD(17)]) defined remission; a QIDS-SR(16) total score of >or=11 (HRSD(17)>or=14) defined relapse. Results: The QIDS-SR(16) remission rates were 36.8%, 30.6%, 13.7%, and 13.0% for the first, second, third, and fourth acute treatment steps, respectively. The overall cumulative remission rate was 67%. Overall, those who required more treatment steps had higher relapse rates during the naturalistic follow-up phase. In addition, lower relapse rates were found among participants who were in remission at follow-up entry than for those who were not after the first three treatment steps. Conclusions: When more treatment steps are required, lower acute remission rates (especially in the third and fourth treatment steps) and higher relapse rates during the follow-up phase are to be expected. Studies to identify the best multistep treatment sequences for individual patients and the development of more broadly effective treatments are needed.

The American journal of psychiatry · randomised controlled trial · 3740 citationsread the source →

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

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

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

Cognitive behavioural treatment for women who have menopausal symptoms after breast cancer treatment (MENOS 1): a randomised controlled trial.

Background: Hot flushes and night sweats (HFNS) affect 65-85% of women after breast cancer treatment; they are distressing, causing sleep problems and decreased quality of life. Hormone replacement therapy is often either undesirable or contraindicated. Safe, effective non-hormonal treatments are needed. We investigated whether cognitive behavioural therapy (CBT) can help breast cancer survivors to effectively manage HFNS. Methods: In this randomised controlled trial, we recruited women from breast clinics in London, UK, who had problematic HFNS (minimum ten problematic episodes a week) after breast-cancer treatment. Participants were randomly allocated to receive either usual care or usual care plus group CBT (1:1). Randomisation was done in blocks of 12-20 participants, stratifying by age (younger than 50 years, 50 years or older), and was done with a computer-generated sequence. The trial statistician and researchers collecting outcome measures were masked to group allocation. Group CBT comprised one 90 min session a week for 6 weeks, and included psycho-education, paced breathing, and cognitive and behavioural strategies to manage HFNS. Assessments were done at baseline, 9 weeks, and 26 weeks after randomisation. The primary outcome was the adjusted mean difference in HFNS problem rating (1-10) between CBT and usual care groups at 9 weeks after randomisation. Analysis of the primary endpoint was done by modified intention to treat. The trial is registered, ISRCTN13771934, and was closed March 15, 2011. Findings: Between May 5, 2009, and Aug 27, 2010, 96 women were randomly allocated to group CBT (n=47) or usual care (n=49). Group CBT significantly reduced HFNS problem rating at 9 weeks after randomisation compared with usual care (mean difference -1·67, 95% CI -2·43 to -0·91; p<0·0001) and improvements were maintained at 26 weeks (mean difference -1·76, -2·54 to -0·99; p<0·0001). We recorded no CBT-related adverse events. Interpretation: Group CBT seems to be a safe and effective treatment for women who have problematic HFNS after breast cancer treatment with additional benefits to mood, sleep, and quality of life. The treatment could be incorporated into breast cancer survivorship programmes and delivered by trained breast cancer nurses. Funding: Cancer Research UK.

The Lancet. Oncology · randomised controlled trial · 190 citationsread the source →

Clinical outcomes on B/F/TAF and dolutegravir-based regimens at 12 months following regimen switch: an observational cohort study.

Background: This retrospective observational study evaluated the clinical use and treatment outcomes in virologically suppressed people with HIV (PWH) switching to either bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir (DTG)-based regimens (single- and multi-tablet formulations (STR and MTR)). Methods: We analyzed electronic medical and dispensing records from Trio Health HIV Research Network for treatment-experienced PWH ≥ 18 years suppressed (viral load [VL] < 200 copies/mL) at switch to B/F/TAF, DTG STR (DTG/3TC, DTG/RPV, DTG/3TC/ABC) or most common DTG MTRs with VL at 12 months (+/-3) since switch between April 2019 and December 2024. Univariate comparisons: chi-square or t-test; characteristics associated with virologic suppression at 12 months: multivariable logistic regression [LR], controlling for age, gender, race, baseline CD4 count, regimen, and adherence (proportion days covered [PDC] ≥ 80%). Results: Of 3141 PWH, 66% switched to B/F/TAF, 27% to DTG STR, and 7% to DTG MTRs. Baseline characteristics differed significantly between groups: B/F/TAF group had a higher proportion of males (81% vs. 67% DTG MTR) and Black individuals (40% vs. 31% DTG STR), while the DTG STR and MTR groups had higher proportions of PWH with cardiovascular disease (35% and 39% respectively vs. 32% on B/F/TAF) and eGFR < 60 mL/min/1.73 m² (18% and 22% respectively vs. 8% on B/F/TAF). At 12 months post switch, proportion of individuals with PDC ≥ 80% was higher in the DTG STR group (76%) compared to DTG MTR (67%) and B/F/TAF (69%) with similar virologic suppression across groups (98%, 98%, and 97% respectively). In multivariable LR, there was an association of White race, PDC ≥ 80%, and CD4 ≥ 200 cells/mm3 with greater probability of suppression at 12 months. Conclusions: Despite differences in baseline characteristics and regimen adherence between individuals switched to B/F/TAF, DTG STRs, and MTRs, both B/F/TAF and DTG-based regimens were associated with high rates of virologic suppression. This data strongly supports the inclusion of these simple and safe regimens as switch options in virologically suppressed PWH. Baseline differences in patient demographics and characteristics may have impacted the adherence on B/F/TAF compared to DTG STR, however virologic outcomes were preserved, demonstrating the forgiveness of B/F/TAF in populations potentially facing adherence challenges.

AIDS research and therapy · cohort or longitudinalread the source →

Association Between Choice of Radical Prostatectomy, External Beam Radiotherapy, Brachytherapy, or Active Surveillance and Patient-Reported Quality of Life Among Men With Localized Prostate Cancer.

Importance: Patients diagnosed with localized prostate cancer have to decide among treatment strategies that may differ in their likelihood of adverse effects. Objective: To compare quality of life (QOL) after radical prostatectomy, external beam radiotherapy, and brachytherapy vs active surveillance. Design, setting, and participants: Population-based prospective cohort of 1141 men (57% participation among eligible men) with newly diagnosed prostate cancer were enrolled from January 2011 through June 2013 in collaboration with the North Carolina Central Cancer Registry. Median time from diagnosis to enrollment was 5 weeks, and all men were enrolled with written informed consent prior to treatment. Final follow-up date for current analysis was September 9, 2015. Exposures: Treatment with radical prostatectomy, external beam radiotherapy, brachytherapy, or active surveillance. Main outcomes and measures: Quality of life using the validated instrument Prostate Cancer Symptom Indices was assessed at baseline (pretreatment) and 3, 12, and 24 months after treatment. The instrument contains 4 domains-sexual dysfunction, urinary obstruction and irritation, urinary incontinence, and bowel problems-each scored from 0 (no dysfunction) to 100 (maximum dysfunction). Propensity-weighted mean domain scores were compared between each treatment group vs active surveillance at each time point. Results: Of 1141 enrolled men, 314 pursued active surveillance (27.5%), 469 radical prostatectomy (41.1%), 249 external beam radiotherapy (21.8%), and 109 brachytherapy (9.6%). After propensity weighting, median age was 66 to 67 years across groups, and 77% to 80% of participants were white. Across groups, propensity-weighted mean baseline scores were 41.8 to 46.4 for sexual dysfunction, 20.8 to 22.8 for urinary obstruction and irritation, 9.7 to 10.5 for urinary incontinence, and 5.7 to 6.1 for bowel problems. Compared with active surveillance, mean sexual dysfunction scores worsened by 3 months for patients who received radical prostatectomy (36.2 [95% CI, 30.4-42.0]), external beam radiotherapy (13.9 [95% CI, 6.7-21.2]), and brachytherapy (17.1 [95% CI, 7.8-26.6]). Compared with active surveillance at 3 months, worsened urinary incontinence was associated with radical prostatectomy (33.6 [95% CI, 27.8-39.2]); acute worsening of urinary obstruction and irritation with external beam radiotherapy (11.7 [95% CI, 8.7-14.8]) and brachytherapy (20.5 [95% CI, 15.1-25.9]); and worsened bowel symptoms with external beam radiotherapy (4.9 [95% CI, 2.4-7.4]). By 24 months, mean scores between treatment groups vs active surveillance were not significantly different in most domains. Conclusions and relevance: In this cohort of men with localized prostate cancer, each treatment strategy was associated with distinct patterns of adverse effects over 2 years. These findings can be used to promote treatment decisions that incorporate individual preferences.

JAMA · cohort or longitudinal · 229 citationsread the source →