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

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

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

Evaluation of the Effectiveness of Digital Technology Interventions to Reduce Loneliness in Older Adults: Systematic Review and Meta-analysis.

Background: Loneliness is a serious public health issue, and its burden is increasing in many countries. Loneliness affects social, physical, and mental health, and it is associated with multimorbidity and premature mortality. In addition to social interventions, a range of digital technology interventions (DTIs) are being used to tackle loneliness. However, there is limited evidence on the effectiveness of DTIs in reducing loneliness, especially in adults. The effectiveness of DTIs in reducing loneliness needs to be systematically assessed. Objective: The objective of this study is to assess the effectiveness of DTIs in reducing loneliness in older adults. Methods: We conducted electronic searches in PubMed, MEDLINE, CINAHL, Embase, and Web of Science for empirical studies published in English from January 1, 2010, to July 31, 2019. The study selection criteria included interventional studies that used any type of DTIs to reduce loneliness in adults (aged ≥18 years) with a minimum intervention duration of 3 months and follow-up measurements at least 3 months after the intervention. Two researchers independently screened articles and extracted data using the PICO (participant, intervention, comparator, and outcome) framework. The primary outcome measure was loneliness. Loneliness scores in both the intervention and control groups at baseline and at follow-up at 3, 4, 6, and 12 months after the intervention were extracted. Data were analyzed via narrative synthesis and meta-analysis using RevMan (The Cochrane Collaboration) software. Results: A total of 6 studies were selected from 4939 screened articles. These studies included 1 before and after study and 5 clinical trials (4 randomized clinical trials and 1 quasi-experimental study). All of these studies enrolled a total of 646 participants (men: n=154, 23.8%; women: n=427, 66.1%; no gender information: n=65, 10.1%) with an average age of 73-78 years (SD 6-11). Five clinical trials were included in the meta-analysis, and by using the random effects model, standardized mean differences (SMDs) were calculated for each trial and pooled across studies at the 3-, 4-, and 6-month follow-ups. The overall effect estimates showed no statistically significant difference in the effectiveness of DTIs compared with that of usual care or non-DTIs at follow-up at 3 months (SMD 0.02; 95% CI -0.36 to 0.40; P=.92), 4 months (SMD -1.11; 95% CI -2.60 to 0.38; P=.14), and 6 months (SMD -0.11; 95% CI -0.54 to 0.32; P=.61). The quality of evidence was very low to moderate in these trials. Conclusions: Our meta-analysis shows no evidence supporting the effectiveness of DTIs in reducing loneliness in older adults. Future research may consider randomized controlled trials with larger sample sizes and longer durations for both the interventions and follow-ups. International registered report identifier (irrid): RR2-10.1136/bmjopen-2019-032455.

Journal of medical Internet research · meta-analysis · 78 citationsread the source →

Digital Cognitive Behavioral Therapy for Insomnia Using a Smartphone Application in China: A Pilot Randomized Clinical Trial.

Importance: Digital cognitive behavioral therapy for insomnia (DCBT-I) requires adaptation to different sociocultural contexts. Moreover, studies comparing DCBT-I and sleep education in the same operating interface are lacking. Objective: To investigate the efficacy of a smartphone-based Chinese culture-adapted DCBT-I application (app) for insomnia compared with sleep education using the same app. Design, setting, and participants: This was a single-blinded, randomized clinical trial conducted from March 2021 to January 2022. Screening and randomization were conducted at Peking University First Hospital. Follow-up visits were performed online or in the same hospital. After assessing for eligibility, eligible participants were enrolled and allocated (1:1) to DCBT-I or sleep education groups. Data were analyzed from January to February 2022. Interventions: A Chinese smartphone-based app with the same interface was used in both DCBT-I and sleep education groups over 6 weeks, with 1-, 3-, and 6-month follow-ups. Main outcomes and measures: The primary outcome was Insomnia Severity Index (ISI) scores with the intention-to-treat principle. Secondary and exploratory outcomes included sleep diary measures; self-reported scales assessing dysfunctional beliefs about sleep, mental health, and quality of life; and smart bracelet measures. Results: Of 82 participants (mean [SD] age, 49.67 [14.49] years; 61 [74.4%] females), with 41 randomized to sleep education and 41 randomized to DCBT-I; 77 participants completed the 6-week intervention (39 participants in the sleep education group and 38 participants in the DCBT-I group; full analysis data set) and 73 completed the 6-month follow-up (per protocol data set). Mean (SD) ISI scores in the DCBT-I group were significantly lower than those in the sleep education group after the 6-week intervention (12.7 [4.8] points vs 14.9 [5.0] points; Cohen d = 0.458; P = .048) and at the 3-month follow-up (12.1 [5.4] points vs 14.8 [5.5] points; Cohen d = 0.489; P = .04). There were significant improvements from before to after the intervention for both the sleep education and DCBT-I groups, with large effect sizes(sleep education: d = 1.13; DCBT-I: d = 1.71). Some of the sleep diary measures and self-reported scales showed more improvements in the DCBT-I group than sleep education group, such as total sleep time (mean [SD]: 3 months, 403.9 [57.6] minutes vs 363.2 [72.3] minutes; 6 months, 420.3 [58.0] minutes vs 389.7 [59.4] minutes) and sleep efficiency (mean [SD]: 3 months, 87.4% [8.3%] vs 76.7% [12.1%]; 6 months, 87.5% [8.2%] vs 78.1% [10.9%]). Conclusions and relevance: In this randomized clinical trial, the smartphone-based Chinese culture-adapted DCBT-I improved insomnia severity compared with sleep education. Future multicenter clinical trials with large sample sizes are needed to validate its effectiveness in the Chinese population. Trial registration: ClinicalTrials.gov Identifier: NCT04779372.

JAMA network open · randomised controlled trial · 36 citationsread the source →

What Are the Minimal and Substantial Improvements in the HOOS and KOOS and JR Versions After Total Joint Replacement?

Background: Patient-reported outcome measures (PROMs) are a gold standard for measuring therapeutic outcomes in research. Extending their use to inform clinical care decisions, determine the appropriateness of therapeutic choices, and assess healthcare quality is attractive but will require our professional community to establish valid estimates of minimal and substantial clinical improvements. Questions/purposes: The purposes of this study were (1) to assess the validity of estimates for the minimal clinically important difference (MCID) calculated using distribution- and anchor-based methods by determining whether they exceed the minimal detectable change (MDC) for the Hip Disability and Osteoarthritis Outcome Score (HOOS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) domains, the HOOS, joint replacement (JR) and the KOOS, JR among patients who underwent THA or TKA; (2) to determine substantial clinical benefit thresholds for the HOOS and KOOS domains, the HOOS, JR, and the KOOS, JR among patients who underwent THA or TKA; and (3) to assess the proportions of patients who underwent THA or TKA who achieved an MCID for the HOOS and KOOS domains, HOOS, JR, and KOOS, JR based on distribution-based and anchor-based methods as well as the percentages of patients who achieved substantial clinical benefit using the anchor-based method. Methods: Medicare patients enrolled in our institutional joint replacement registry who subsequently underwent THA (n = 2323) or TKA (n = 2630) between 2007 and 2012 completed HOOS or KOOS preoperatively and 2 years postoperatively. Short-form joint replacement (JR) versions of each PROM were derived from the full PROMs. Of all eligible patients, 78% (3161 of 4080) of THAs and 74% of TKAs (3815 of 5156) consented to join the registry and completed a baseline survey, 88% (2796 of 3161) of THAs and 85% (3230 of 3815) of TKAs were eligible for followup survey administration, and 83% of THAs (2323 of 2796) and 81% (2630 of 3230) of TKAs returned 2-year surveys. For each HOOS domain, KOOS domain, HOOS, JR, and KOOS, JR, we calculated the calibration variation of the instrument (MDC) with confidence intervals (CIs) reflecting 80% (MDC80), 90% (MDC90), and 95% (MDC95) certainty; we calculated the smallest difference joint health patients might detect (MCID) using distribution- and anchor-based approaches and the difference that can be considered a large improvement in joint health (substantial clinical benefit) using an anchor-based approach. Results: Patients undergoing THA were 57% female with a mean (± SD) age of 73 ± 6 years, whereas patients undergoing TKA were 63% female with a mean age of 74 ± 6 years. Depending on the CI chosen for the MDC, values ranged from 7 to 16 for the HOOS and KOOS domains and the JRs. The MCIDs ranged from 6 to 9 for the distribution-based approach and 7 to 36 for the anchor-based approach. All HOOS and KOOS domains and all JR scores are scores from 0 (worst joint health) to 100 (best joint health). The MCIDs calculated using the distribution-based approach were not valid, because they were lower than the MDC for all HOOS/KOOS domains and both JRs at every confidence level. The anchor-based receiver operating characteristic approach, on the other hand, resulted in MCIDs exceeding MDC80 for seven of eight HOOS/KOOS domains and MDC95 for both JR scores. For all domains and JR versions, substantial clinical benefits ranged from 15 to 36, exceeding MDC95 in all domains and JR scores. Across HOOS and KOOS domains as well as the JR, the proportion of patients undergoing THA who achieved an MCID ranged from 77% to 95% with the distribution-based method and from 67% to 96% using the anchor-based method. The proportion achieving substantial clinical benefit ranged from 67% to 85%. Conclusions: The MDC and MCID differ greatly based on assumptions and methods used. The MCID anchor-based approach had superior construct and face validity compared with the MCID distribution-based approach, which never exceeded even small MDCs. Achieving consensus about standard definitions of meaningful improvement will be necessary to maximize utility of these PROMs to inform clinical care or performance measurement. Level of evidence: Level III, diagnostic study.

Clinical orthopaedics and related research · cohort or longitudinal · 400 citationsread the source →

Longer Nap Duration During Ramadan Observance Positively Impacts 5-m Shuttle Run Test Performance Performed in the Afternoon.

It is well-documented that changes in the rhythm of life during Ramadan affect sleep schedules (i.e., interruption of night sleep patterns) and are likely to have negative effects on physical and cognitive performances. The aim of the present study was to examine the effect of different naps opportunities' durations during Ramadan on performance of short-duration repetitive maximal exercise and perception of effort. Fifteen physically active men (age: 21 ± 3 years, height: 177 ± 6 cm, body-mass: 73 ± 10 kg) performed a 6 × 30-s shuttle run test after a 25-min nap (N25), a 45-min nap (N45), and in a no-nap condition (NN) during three experimental periods: ∼2 weeks before Ramadan (BR), the last ten days of Ramadan (ER), and ∼3 weeks after Ramadan (AR). During the shuttle run test performed in the late afternoon, the greatest distance (GD), the total distance (TD) and a fatigue index (FI) were assessed. Rating of perceived exertion (RPE) was determined after each 30-s effort. Dietary intake and sleep quality were assessed in each of the three periods. Compared to BR, GD and TD were lower in the ER testing period (p = 0.005; d = 0.54) but returned to BR levels in the AR period. During ER, carbohydrate intake was lower (p = 0.04; d = 0.2), and sleep duration and sleep quality were reduced (d = 0.27 and 0.54, respectively), although other aspects of dietary intake and sleep pattern were not affected. Compared to NN, GD and TD were higher after N25 (d = 0.57 and 0.34, respectively) and N45 (d = 0.93 and 0.88 respectively). RPE was lower in N45 (p = 0.035, d = 0.84). N45 resulted in higher TD (p = 0.021, d = 0.13) and lower RPE (p = 0.004; d = 0.57) compared to N25 during ER. Taking a daytime nap benefits subsequent performance in a shuttle run test, whether sleep the previous night was normal (as in BR) or compromised (as in ER). The benefits of napping were greater after a 45-min nap opportunity than after a 25-min nap opportunity.

Frontiers in physiology · 5 citationsread the source →

Generativity and Social Well-Being in Older Women: Expectations Regarding Aging Matter.

Objectives: Beliefs about aging can contribute to health and well-being in older adults. Feeling generative, or that one is caring for and contributing to the well-being of others, can also impact health and well-being. In this study, we hypothesized that those with more positive expectations regarding aging (ERA) in the mental health domain would report greater levels of perceived social support (PSS) and lower levels of loneliness in response to a generativity intervention (vs control condition). Method: Participants in this study (n = 73, 100% female) were randomly assigned to a 6-week generativity condition, which involved writing about life experiences and sharing advice with others, or to a control condition, which involved writing about neutral topics. Pre- and postintervention, PSS, and feelings of loneliness were measured. Results: Those in the generativity condition with more positive ERA in the mental health domain reported greater PSS and lower loneliness postintervention. Discussion: These results highlight the importance of psychological factors, such as ERA, in moderating the efficacy of interventions to promote social well-being in older adults.

The journals of gerontology. Series B, Psychological sciences and social sciences · randomised controlled trial · 15 citationsread the source →

Do brief measures of readiness to change predict alcohol consumption and consequences in primary care patients with unhealthy alcohol use?

Background: Assessing readiness to change is recommended as part of brief interventions for patients with unhealthy alcohol use. However, the utility and predictive validity of readiness measures have not been well established. Methods: In a prospective cohort study, we assessed primary care patients with unhealthy alcohol use (past-month drinking of risky amounts, or any amount and an affirmative response to CAGE alcohol screening questionnaire) and reassessed them 6 months later. At study entry, we assessed readiness to change using 1 multi-item measure of stage of change, and 5 single-item measures (readiness per se, importance of changing, confidence in ability to change, intention to cut down, intention to abstain). Outcomes included alcohol consumption and alcohol-related consequences. Multivariable regression models were fit for each measure of readiness and each outcome. Results: Of 312 patients with unhealthy alcohol use, 228 (73%) were assessed at study entry and 6 months later and had complete data. Among readiness measures, only confidence and intention to abstain (1 point changes on single-item measures) were associated with consumption 6 months later: less heavy episodic drinking [adjusted odds ratio (AOR) 0.88, 95% CI 0.80-0.98 and AOR 0.79, 0.64-0.98, respectively], and less drinking of risky amounts (AOR 0.89, 0.79-1.00 and AOR 0.78, 0.62-0.98, respectively). Intention to abstain was also associated with more abstinence (AOR 1.43, 1.09-1.88). Single-item measures of readiness, importance, and intention to cut down were significantly associated with higher odds of alcohol consequences. Greater confidence (single item) was associated with a lower odds of any consequences (AOR 0.88, 0.79-0.98). Conclusions: Greater readiness, as measured by several brief assessments, was associated with more consequences and was not predictive of consumption. However, assessing confidence in the ability to change one's alcohol use may have a role in predicting subsequent decreases in both consumption and consequences in primary care patients.

Alcoholism, clinical and experimental research · randomised controlled trial · 50 citationsread the source →

Centralized, stepped, patient preference-based treatment for patients with post-acute coronary syndrome depression: CODIACS vanguard randomized controlled trial.

Importance: Controversy remains about whether depression can be successfully managed after acute coronary syndrome (ACS) and the costs and benefits of doing so. Objective: To determine the effects of providing post-ACS depression care on depressive symptoms and health care costs. Design: Multicenter randomized controlled trial. Setting: Patients were recruited from 2 private and 5 academic ambulatory centers across the United States. Participants: A total of 150 patients with elevated depressive symptoms (Beck Depression Inventory [BDI] score ≥10) 2 to 6 months after an ACS, recruited between March 18, 2010, and January 9, 2012. Interventions: Patients were randomized to 6 months of centralized depression care (patient preference for problem-solving treatment given via telephone or the Internet, pharmacotherapy, both, or neither), stepped every 6 to 8 weeks (active treatment group; n = 73), or to locally determined depression care after physician notification about the patient's depressive symptoms (usual care group; n = 77). Main outcome measures: Change in depressive symptoms during 6 months and total health care costs. Results: Depressive symptoms decreased significantly more in the active treatment group than in the usual care group (differential change between groups, -3.5 BDI points; 95% CI, -6.1 to -0.7; P = .01). Although mental health care estimated costs were higher for active treatment than for usual care, overall health care estimated costs were not significantly different (difference adjusting for confounding, -$325; 95% CI, -$2639 to $1989; P = .78). Conclusions: For patients with post-ACS depression, active treatment had a substantial beneficial effect on depressive symptoms. This kind of depression care is feasible, effective, and may be cost-neutral within 6 months; therefore, it should be tested in a large phase 3 pragmatic trial. Trial registration: clinicaltrials.gov Identifier: NCT01032018.

JAMA internal medicine · randomised controlled trial · 107 citationsread the source →

Trajectory of post-traumatic stress following traumatic injury: 6-year follow-up.

Background: Traumatic injuries affect millions of patients each year, and resulting post-traumatic stress disorder (PTSD) significantly contributes to subsequent impairment. Aims: To map the distinctive long-term trajectories of PTSD responses over 6 years by using latent growth mixture modelling. Method: Randomly selected injury patients (n = 1084) admitted to four hospitals around Australia were assessed in hospital, and at 3, 12, 24 and 72 months. Lifetime psychiatric history and current PTSD severity and funxctioning were assessed. Results: Five trajectories of PTSD response were noted across the 6 years: (a) chronic (4%), (b) recovery (6%), (c) worsening/recovery (8%), (d) worsening (10%) and (e) resilient (73%). A poorer trajectory was predicted by female gender, recent life stressors, presence of mild traumatic brain injury and admission to intensive care unit. Conclusions: These findings demonstrate the long-term PTSD effects that can occur following traumatic injury. The different trajectories highlight that monitoring a subset of patients over time is probably a more accurate means of identifying PTSD rather than relying on factors that can be assessed during hospital admission.

The British journal of psychiatry : the journal of mental science · cohort or longitudinal · 136 citationsread the source →

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

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

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

Allopregnanolone and depression and anxiety symptoms across the peripartum: an exploratory study.

Recent research has implicated allopregnanolone (ALLO), a neuroactive steroid and metabolite of progesterone, in perinatal mood and anxiety symptoms. We sought to add to the limited literature examining ALLO and mood and anxiety at multiple time points across the peripartum. We measured mood and anxiety symptoms and ALLO levels by ELISA at the second and third trimester (T2 and T3) and week 6 postpartum (W6) in N = 73 women with prior histories of mood and/or anxiety disorders and N = 38 healthy controls. Analytic methods included multivariate and logistic regressions with linear mixed effect models. Among all participants (N = 111), higher ALLO levels at W6 were associated with higher depression and anxiety scores: each one unit increase in log ALLO at W6 was associated with a 2.54 point increase on the Edinburgh Postnatal Depression Scale (EPDS) (95% CI: 0.73 to 4.33) and an 8.0 point increase on the Perinatal Anxiety Screening Scale (PASS) (95% CI: 3.82 to 12.6). In addition, the nature of the relationship between log ALLO level and psychological measures changed across time; from T2 to W6 for EPDS, β = 3.73 (95% CI:1.16, 6.30), p = 0.0045; for PASS β = 9.78 (95% CI:3.77, 15.79), p = 0.0014); from T3 to W6, for (EPDS, β = 2.52 (95% CI:0.08, 4.96), p = 0.043; for PASS β = 7.33 (95% CI:1.63, 13.02), p = 0.018). The relationship of log ALLO to mood and anxiety symptoms was the same among women with and without psychiatric histories. Our exploratory findings indicate that the relationship between ALLO and mood and anxiety symptoms may change across the peripartum.

Archives of women's mental health · 17 citationsread the source →

Changes in energy and macronutrient intakes during Ramadan fasting: a systematic review, meta-analysis, and meta-regression.

Context: Ramadan fasting (RF) is associated with various physiological and metabolic changes among fasting Muslims. However, it remains unclear whether these effects are attributable to changes in meal timing or changes in dietary energy and macronutrient intakes. Furthermore, the literature on the associations between RF, meal timing, and energy and macronutrient intakes is inconclusive. Objectives: This systematic review aimed to estimate the effect sizes of RF on energy and macronutrient intakes (carbohydrates, protein, fats, dietary fiber, and water) and determine the effect of different moderators on the examined outcomes. Data sources: The Cochrane, CINAHL, EMBASE, EBSCOhost, Google Scholar, PubMed/MEDLINE, ProQuest Medical, Scopus, ScienceDirect, and Web of Science databases were searched from inception to January 31, 2022. Data extraction: The studies that assessed energy, carbohydrate, protein, fat, fiber, and water intakes pre- and post-fasting were extracted. Data analysis: Of the 4776 identified studies, 85 relevant studies (n = 4594 participants aged 9-85 y) were selected. The effect sizes for the studied variables were as follows: energy (number of studies [K] = 80, n = 3343 participants; mean difference [MD]: -142.45; 95% confidence interval [CI]: -215.19, -69.71), carbohydrates (K = 75, n = 3111; MD: -23.90; 95% CI: -36.42, -11.38), protein (K = 74, n = 3108; MD: -4.21; 95% CI: -7.34, -1.07), fats (K = 73, n = 3058; MD: -2.03; 95% CI: -5.73, 1.67), fiber (K = 16, n = 1198; MD: 0.47; 95% CI: -1.44, 2.39), and water (K = 17, n = 772; MD: -350.80; 95% CI: -618.09, 83.50). Subgroup analyses showed age significantly moderated the 6 dietary outcomes, and physical activity significantly moderated water intake. There were significant reductions in energy, carbohydrate, and protein intakes during RF. Conclusions: The change in meal timing rather than quantitative dietary intake may explain various physiological and health effects associated with RF.

Nutrition reviews · meta-analysis · 12 citationsread the source →

Interventions for reducing sedentary behaviour in community-dwelling older adults.

Background: Older adults are the most sedentary segment of society, often spending in excess of 8.5 hours a day sitting. Large amounts of time spent sedentary, defined as time spend sitting or in a reclining posture without spending energy, has been linked to an increased risk of chronic diseases, frailty, loss of function, disablement, social isolation, and premature death. Objectives: To evaluate the effectiveness of interventions aimed at reducing sedentary behaviour amongst older adults living independently in the community compared to control conditions involving either no intervention or interventions that do not target sedentary behaviour. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, PsycINFO, PEDro, EPPI-Centre databases (Trials Register of Promoting Health Interventions (TRoPHI) and the Obesity and Sedentary behaviour Database), WHO ICTRP, and ClinicalTrials.gov up to 18 January 2021. We also screened the reference lists of included articles and contacted authors to identify additional studies. Selection criteria: We included randomised controlled trials (RCTs) and cluster-RCTs. We included interventions purposefully designed to reduce sedentary time in older adults (aged 60 or over) living independently in the community. We included studies if some of the participants had multiple comorbidities, but excluded interventions that recruited clinical populations specifically (e.g. stroke survivors). Data collection and analysis: Two review authors independently screened titles and abstracts and full-text articles to determine study eligibility. Two review authors independently extracted data and assessed risk of bias. We contacted authors for additional data where required. Any disagreements in study screening or data extraction were settled by a third review author. Main results: We included seven studies in the review, six RCTs and one cluster-RCT, with a total of 397 participants. The majority of participants were female (n = 284), white, and highly educated. All trials were conducted in high-income countries. All studies evaluated individually based behaviour change interventions using a combination of behaviour change techniques such as goal setting, education, and behaviour monitoring or feedback. Four of the seven studies also measured secondary outcomes. The main sources of bias were related to selection bias (N = 2), performance bias (N = 6), blinding of outcome assessment (N = 2), and incomplete outcome data (N = 2) and selective reporting (N=1). The overall risk of bias was judged as unclear. Primary outcomes The evidence suggests that interventions to change sedentary behaviour in community-dwelling older adults may reduce sedentary time (mean difference (MD) -44.91 min/day, 95% confidence interval (CI) -93.13 to 3.32; 397 participants; 7 studies; I2 = 73%; low-certainty evidence). We could not pool evidence on the effect of interventions on breaks in sedentary behaviour or time spent in specific domains such as TV time, as data from only one study were available for these outcomes. Secondary outcomes We are uncertain whether interventions to reduce sedentary behaviour have any impact on the physical or mental health outcomes of community-dwelling older adults. We were able to pool change data for the following outcomes. • Physical function (MD 0.14 Short Physical Performance Battery (SPPB) score, 95% CI -0.38 to 0.66; higher score is favourable; 98 participants; 2 studies; I2 = 26%; low-certainty evidence). • Waist circumference (MD 1.14 cm, 95% CI -1.64 to 3.93; 100 participants; 2 studies; I2 = 0%; low-certainty evidence). • Fitness (MD -5.16 m in the 6-minute walk test, 95% CI -36.49 to 26.17; higher score is favourable; 80 participants; 2 studies; I2 = 29%; low-certainty evidence). • Blood pressure: systolic (MD -3.91 mmHg, 95% CI -10.95 to 3.13; 138 participants; 3 studies; I2 = 73%; very low-certainty evidence) and diastolic (MD -0.06 mmHg, 95% CI -5.72 to 5.60; 138 participants; 3 studies; I2 = 97%; very low-certainty evidence). • Glucose blood levels (MD 2.20 mg/dL, 95% CI -6.46 to 10.86; 100 participants; 2 studies; I2 = 0%; low-certainty evidence). No data were available on cognitive function, cost-effectiveness or adverse effects. Authors' conclusions: It is not clear whether interventions to reduce sedentary behaviour are effective at reducing sedentary time in community-dwelling older adults. We are uncertain if these interventions have any impact on the physical or mental health of community-dwelling older adults. There were few studies, and the certainty of the evidence is very low to low, mainly due to inconsistency in findings and imprecision. Future studies should consider interventions aimed at modifying the environment, policy, and social and cultural norms. Future studies should also use device-based measures of sedentary time, recruit larger samples, and gather information about quality of life, cost-effectiveness, and adverse event data.

The Cochrane database of systematic reviews · meta-analysis · 70 citationsread the source →

Effectiveness of behavioural and psychological interventions for managing obesity in children and adolescents: A systematic review and meta-analysis framed using minimal important difference estimates based on GRADE guidance to inform a clinical practice guideline.

Objective: Conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) of behavioural and psychological interventions for managing paediatric obesity. Methods: Eligible studies, published between 1985 and 2022, included 0 to 18 year olds with outcomes reported ≥3 months post-baseline, including patient-reported outcome measures (PROMs), cardiometabolic and anthropometric outcomes, and adverse events (AEs). We pooled data using a random effects model and assessed certainty of evidence (CoE) related to minimally important difference estimates for outcomes using GRADE. Results: We included 73 unique RCTs (n = 6305 participants, 53% female). Intervention types included physical activity (n = 1437), nutrition (n = 447), psychological (n = 1336), technology-based (n = 901) or multicomponent (≥2 intervention types, n = 2184). Physical activity had a small effect on health-related quality of life (HRQoL), varying effects ranging from moderate to very large on blood pressure, lipids and insulin resistance, and a small effect on BMIz. Nutrition had a small effect on lipids, insulin resistance and BMIz. Psychological interventions showed a small effect on HRQoL and triglycerides and moderate benefits on depressive symptoms, while technology interventions showed small benefits on blood pressure and BMIz. Multicomponent interventions had a large benefit on anxiety, small benefit on depressive symptoms, with large to very large benefits on lipids, and small benefits for diastolic blood pressure, insulin resistance and BMIz. AEs were reported infrequently, and when reported, were described as mild. Conclusion: Physical activity and multicomponent interventions showed improvements in PROMs, cardiometabolic and anthropometric outcomes. Future trials should consistently measure PROMs, evaluate outcomes beyond the intervention period, and study children <6 years of age.

Pediatric obesity · meta-analysis · 18 citationsread the source →

Age at onset of mental disorders worldwide: large-scale meta-analysis of 192 epidemiological studies.

Promotion of good mental health, prevention, and early intervention before/at the onset of mental disorders improve outcomes. However, the range and peak ages at onset for mental disorders are not fully established. To provide robust, global epidemiological estimates of age at onset for mental disorders, we conducted a PRISMA/MOOSE-compliant systematic review with meta-analysis of birth cohort/cross-sectional/cohort studies, representative of the general population, reporting age at onset for any ICD/DSM-mental disorders, identified in PubMed/Web of Science (up to 16/05/2020) (PROSPERO:CRD42019143015). Co-primary outcomes were the proportion of individuals with onset of mental disorders before age 14, 18, 25, and peak age at onset, for any mental disorder and across International Classification of Diseases 11 diagnostic blocks. Median age at onset of specific disorders was additionally investigated. Across 192 studies (n = 708,561) included, the proportion of individuals with onset of any mental disorders before the ages of 14, 18, 25 were 34.6%, 48.4%, 62.5%, and peak age was 14.5 years (k = 14, median = 18, interquartile range (IQR) = 11-34). For diagnostic blocks, the proportion of individuals with onset of disorder before the age of 14, 18, 25 and peak age were as follows: neurodevelopmental disorders: 61.5%, 83.2%, 95.8%, 5.5 years (k = 21, median=12, IQR = 7-16), anxiety/fear-related disorders: 38.1%, 51.8%, 73.3%, 5.5 years (k = 73, median = 17, IQR = 9-25), obsessive-compulsive/related disorders: 24.6%, 45.1%, 64.0%, 14.5 years (k = 20, median = 19, IQR = 14-29), feeding/eating disorders/problems: 15.8%, 48.1%, 82.4%, 15.5 years (k = 11, median = 18, IQR = 15-23), conditions specifically associated with stress disorders: 16.9%, 27.6%, 43.1%, 15.5 years (k = 16, median = 30, IQR = 17-48), substance use disorders/addictive behaviours: 2.9%, 15.2%, 48.8%, 19.5 years (k = 58, median = 25, IQR = 20-41), schizophrenia-spectrum disorders/primary psychotic states: 3%, 12.3%, 47.8%, 20.5 years (k = 36, median = 25, IQR = 20-34), personality disorders/related traits: 1.9%, 9.6%, 47.7%, 20.5 years (k = 6, median = 25, IQR = 20-33), and mood disorders: 2.5%, 11.5%, 34.5%, 20.5 years (k = 79, median = 31, IQR = 21-46). No significant difference emerged by sex, or definition of age of onset. Median age at onset for specific mental disorders mapped on a time continuum, from phobias/separation anxiety/autism spectrum disorder/attention deficit hyperactivity disorder/social anxiety (8-13 years) to anorexia nervosa/bulimia nervosa/obsessive-compulsive/binge eating/cannabis use disorders (17-22 years), followed by schizophrenia, personality, panic and alcohol use disorders (25-27 years), and finally post-traumatic/depressive/generalized anxiety/bipolar/acute and transient psychotic disorders (30-35 years), with overlap among groups and no significant clustering. These results inform the timing of good mental health promotion/preventive/early intervention, updating the current mental health system structured around a child/adult service schism at age 18.

Molecular psychiatry · meta-analysis · 2420 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 →

The impact of occupational shift work and working hours during pregnancy on health outcomes: a systematic review and meta-analysis.

Backgroud: An increasing number of original studies suggest that exposure to shift work and long working hours during pregnancy could be associated with the risk of adverse pregnancy outcomes, but the results remain conflicting and inconclusive. Objective: To examine the influences of shift work and longer working hours during pregnancy on maternal and fetal health outcomes. Data sources: Five electronic databases and 3 gray literature sources were searched up to March 15, 2019. Methods of study selection: Studies of all designs (except case studies and reviews) were included, which contained information on the relevant population (women who engaged in paid work during pregnancy); exposure (rotating shift work [shifts change according to a set schedule], fixed night shift [typical working period is between 11:00 pm and 11:00 am] or longer working hours [>40 hours per week]);comparator (fixed day shift [typical working period is between 8:00 am and 6:00 pm] or standard working hours [≤40 hours per week]); and outcomes (preterm delivery, low birthweight [birthweight <2500 g], small for gestational age, miscarriage, gestational hypertension, preeclampsia, intrauterine growth restriction, stillbirth, and gestational diabetes mellitus). Tabulation, integration, and results: From 3305 unique citations, 62 observational studies (196,989 women) were included. "Low" to "very low" certainty evidence from these studies revealed that working rotating shifts was associated with an increased odds of preterm delivery (odds ratio, 1.13; 95% confidence interval, 1.00-1.28, I2 = 31%), an infant small for gestational age (odds ratio, 1.18, 95% confidence interval, 1.01-1.38, I2 = 0%), preeclampsia (odds ratio, 1.75, 95% confidence interval, 1.01-3.01, I2 = 75%), and gestational hypertension (odds ratio, 1.19, 95% confidence interval, 1.10-1.29, I2 = 0%), compared to those who worked a fixed day shift. Working fixed night shifts was associated with an increased odds of preterm delivery (odds ratio, 1.21; 95% confidence interval, 1.03-1.42; I2 = 36%) and miscarriage (odds ratio, 1.23; 95% confidence interval, 1.03-1.47; I2 = 37%). Compared with standard hours, working longer hours was associated with an increased odds of miscarriage (odds ratio, 1.38; 95% confidence interval, 1.08-1.77; I2 = 73%), preterm delivery (odds ratio, 1.21; 95% confidence interval, 1.11-1.33; I2 = 30%), an infant of low birthweight (odds ratio, 1.43; 95% confidence interval, 1.11-1.84; I2 = 0%), or an infant small for gestational age (odds ratio, 1.16, 95% confidence interval, 1.00-1.36, I2 = 57%). Dose-response analysis showed that women working more than 55.5 hours (vs 40 hours) per week had a 10% increase in the odds of having a preterm delivery. Conclusion: Pregnant women who work rotating shifts, fixed night shifts, or longer hours have an increased risk of adverse pregnancy outcomes.

American journal of obstetrics and gynecology · meta-analysis · 219 citationsread the source →

Social isolation and diurnal cortisol patterns in an ageing cohort.

Background: Social isolation may operate as a psychosocial stressor which disrupts functioning of the hypothalamic-pituitary-adrenocortical axis. Methods: Using data from the MRC National Survey of Health and Development, we tested whether living alone, not being married and social network size were associated with diurnal cortisol patterns at 60-64 years. We hypothesised that recent onset compared with long-term isolation would be more strongly associated with cortisol awakening response, cortisol decline over the day and evening cortisol. Models were adjusted for sex, smoking, body mass index, alcohol intake, psychological distress and financial difficulties. Results: Those widowed within the last three years had a 36% (95%CI 6%, 73%) higher night time cortisol than those who were currently married. Those newly living alone also had a higher night time cortisol and flatter diurnal slope than those living with others. Conclusion: Independently of multiple behavioural and psychosocial correlates, recent onset of social isolation is related to diurnal cortisol patterns that increase the risk of morbidity and mortality.

Psychoneuroendocrinology · 34 citationsread the source →

Socio-economic patterning of food consumption and dietary diversity among Indian children: evidence from NFHS-4.

Background/objectives: Most interventions to foster child growth and development in India focus on improving food quality and quantity. We aimed to assess the pattern in food consumption and dietary diversity by socioeconomic status (SES) among Indian children. Subjects/methods: The most recent nationally representative, cross-sectional data from the National Family Health Survey (NFHS-4, 2015-16) was used for analysis of 73,852-74,038 children aged 6-23 months. Consumption of 21 food items, seven food groups, and adequately diversified dietary intake (ADDI) was collected through mother's 24-h dietary recall. Logistic regression models were conducted to assess the association between household wealth and maternal education with food consumption and ADDI, after controlling for covariates. Results: Overall, the mean dietary diversity score was low (2.26; 95% CI:2.24-2.27) and the prevalence of ADDI was only 23%. Both household wealth and maternal education were significantly associated with ADDI (OR:1.28; 95% CI:1.18-1.38 and OR:1.75; 95% CI:1.63-1.90, respectively), but the SES gradient was not particularly strong. Furthermore, the associations between SES and consumption of individual food items and food groups were not consistent. Maternal education was more strongly associated with consumption of essential food items and all food groups, but household wealth was found to have significant influence on intake of dairy group only. Conclusions: Interventions designed to improve food consumption and diversified dietary intake among Indian children need to be universal in their targeting given the overall high prevalence of inadequate dietary diversity and the relatively small differentials by SES.

European journal of clinical nutrition · 61 citationsread the source →

Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors.

Background: Persistent infection with high-risk human papillomaviruses (hrHPV) types is causally linked with the development of cervical precancer and cancer. HPV types 16 and 18 cause approximately 70% of cervical cancers worldwide. Objectives: To evaluate the harms and protection of prophylactic human papillomaviruses (HPV) vaccines against cervical precancer and HPV16/18 infection in adolescent girls and women. Search methods: We searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and Embase (June 2017) for reports on effects from trials. We searched trial registries and company results' registers to identify unpublished data for mortality and serious adverse events. Selection criteria: Randomised controlled trials comparing efficacy and safety in females offered HPV vaccines with placebo (vaccine adjuvants or another control vaccine). Data collection and analysis: We used Cochrane methodology and GRADE to rate the certainty of evidence for protection against cervical precancer (cervical intraepithelial neoplasia grade 2 and above [CIN2+], CIN grade 3 and above [CIN3+], and adenocarcinoma-in-situ [AIS]), and for harms. We distinguished between the effects of vaccines by participants' baseline HPV DNA status. The outcomes were precancer associated with vaccine HPV types and precancer irrespective of HPV type. Results are presented as risks in control and vaccination groups and risk ratios (RR) with 95% confidence intervals in brackets. Main results: We included 26 trials (73,428 participants). Ten trials, with follow-up of 1.3 to 8 years, addressed protection against CIN/AIS. Vaccine safety was evaluated over a period of 6 months to 7 years in 23 studies. Studies were not large enough or of sufficient duration to evaluate cervical cancer outcomes. All but one of the trials was funded by the vaccine manufacturers. We judged most included trials to be at low risk of bias. Studies involved monovalent (N = 1), bivalent (N = 18), and quadrivalent vaccines (N = 7). Most women were under 26 years of age. Three trials recruited women aged 25 and over. We summarize the effects of vaccines in participants who had at least one immunisation. Efficacy endpoints by initial HPV DNA statushrHPV negativeHPV vaccines reduce CIN2+, CIN3+, AIS associated with HPV16/18 compared with placebo in adolescent girls and women aged 15 to 26. There is high-certainty evidence that vaccines lower CIN2+ from 164 to 2/10,000 (RR 0.01 (0 to 0.05)) and CIN3+ from 70 to 0/10,000 (RR 0.01 (0.00 to 0.10). There is moderate-certainty evidence that vaccines reduce the risk of AIS from 9 to 0/10,000 (RR 0.10 (0.01 to 0.82).HPV vaccines reduce the risk of any CIN2+ from 287 to 106/10,000 (RR 0.37 (0.25 to 0.55), high certainty) and probably reduce any AIS lesions from 10 to 0/10,000 (RR 0.1 (0.01 to 0.76), moderate certainty). The size of reduction in CIN3+ with vaccines differed between bivalent and quadrivalent vaccines (bivalent: RR 0.08 (0.03 to 0.23), high certainty; quadrivalent: RR 0.54 (0.36 to 0.82), moderate certainty). Data in older women were not available for this comparison.HPV16/18 negativeIn those aged 15 to 26 years, vaccines reduce CIN2+ associated with HPV16/18 from 113 to 6 /10,000 (RR 0.05 (0.03 to 0.10). In women 24 years or older the absolute and relative reduction in the risk of these lesions is smaller (from 45 to 14/10,000, (RR 0.30 (0.11 to 0.81), moderate certainty). HPV vaccines reduce the risk of CIN3+ and AIS associated with HPV16/18 in younger women (RR 0.05 (0.02 to 0.14), high certainty and RR 0.09 (0.01 to 0.72), moderate certainty, respectively). No trials in older women have measured these outcomes. Vaccines reduce any CIN2+ from 231 to 95/10,000, (RR 0.41 (0.32 to 0.52)) in younger women. No data are reported for more severe lesions. Regardless of HPV DNA statusIn younger women HPV vaccines reduce the risk of CIN2+ associated with HPV16/18 from 341 to 157/10,000 (RR 0.46 (0.37 to 0.57), high certainty). Similar reductions in risk were observed for CIN3+ associated with HPV16/18 (high certainty). The number of women with AIS associated with HPV16/18 is reduced from 14 to 5/10,000 with HPV vaccines (high certainty).HPV vaccines reduce any CIN2+ from 559 to 391/10,000 (RR 0.70 (0.58 to 0.85, high certainty) and any AIS from 17 to 5/10,000 (RR 0.32 (0.15 to 0.67), high certainty). The reduction in any CIN3+ differed by vaccine type (bivalent vaccine: RR 0.55 (0.43 to 0.71) and quadrivalent vaccine: RR 0.81 (0.69 to 0.96)).In women vaccinated at 24 to 45 years of age, there is moderate-certainty evidence that the risks of CIN2+ associated with HPV16/18 and any CIN2+ are similar between vaccinated and unvaccinated women (RR 0.74 (0.52 to 1.05) and RR 1.04 (0.83 to 1.30) respectively). No data are reported in this age group for CIN3+ or AIS.Adverse effectsThe risk of serious adverse events is similar between control and HPV vaccines in women of all ages (669 versus 656/10,000, RR 0.98 (0.92 to 1.05), high certainty). Mortality was 11/10,000 in control groups compared with 14/10,000 (9 to 22) with HPV vaccine (RR 1.29 [0.85 to 1.98]; low certainty). The number of deaths was low overall but there is a higher number of deaths in older women. No pattern in the cause or timing of death has been established. Pregnancy outcomesAmong those who became pregnant during the studies, we did not find an increased risk of miscarriage (1618 versus 1424/10,000, RR 0.88 (0.68 to 1.14), high certainty) or termination (931 versus 838/10,000 RR 0.90 (0.80 to 1.02), high certainty). The effects on congenital abnormalities and stillbirths are uncertain (RR 1.22 (0.88 to 1.69), moderate certainty and (RR 1.12 (0.68 to 1.83), moderate certainty, respectively). Authors' conclusions: There is high-certainty evidence that HPV vaccines protect against cervical precancer in adolescent girls and young women aged 15 to 26. The effect is higher for lesions associated with HPV16/18 than for lesions irrespective of HPV type. The effect is greater in those who are negative for hrHPV or HPV16/18 DNA at enrolment than those unselected for HPV DNA status. There is moderate-certainty evidence that HPV vaccines reduce CIN2+ in older women who are HPV16/18 negative, but not when they are unselected by HPV DNA status. We did not find an increased risk of serious adverse effects. Although the number of deaths is low overall, there were more deaths among women older than 25 years who received the vaccine. The deaths reported in the studies have been judged not to be related to the vaccine. Increased risk of adverse pregnancy outcomes after HPV vaccination cannot be excluded, although the risk of miscarriage and termination are similar between trial arms. Long-term of follow-up is needed to monitor the impact on cervical cancer, occurrence of rare harms and pregnancy outcomes.

The Cochrane database of systematic reviews · systematic review · 290 citationsread the source →

Ginkgo biloba for tinnitus.

Background: Tinnitus is a symptom defined as the perception of sound in the absence of an external source. In England alone there are an estimated ¾ million general practice consultations every year where the primary complaint is tinnitus, equating to a major burden on healthcare services. Clinical management strategies include education and advice, relaxation therapy, tinnitus retraining therapy (TRT), cognitive behavioural therapy (CBT), sound enrichment using ear-level sound generators or hearing aids, and drug therapies to manage co-morbid symptoms such as insomnia, anxiety or depression.  OBJECTIVES: To assess the effects of Ginkgo biloba for tinnitus in adults and children. Search methods: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; CENTRAL (2022, Issue 6); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 7 June 2022. Selection criteria: Randomised controlled trials (RCTs) recruiting adults and children with acute or chronic subjective tinnitus. We included studies where the intervention involved Ginkgo biloba and this was compared to placebo, no intervention, or education and information. Concurrent use of other medication or other treatment was acceptable if used equally in each group. Where an additional intervention was used equally in both groups, we analysed this as a separate comparison. The review included all courses of Ginkgo biloba, regardless of dose regimens or formulations, and for any duration of treatment. Data collection and analysis: We used standard Cochrane methods. Our primary outcomes were tinnitus symptom severity measured as a global score on a multi-item tinnitus questionnaire and serious adverse effects (bleeding, seizures). Our secondary outcomes were tinnitus loudness (change in subjective perception), tinnitus intrusiveness, generalised depression, generalised anxiety, health-related quality of life and other adverse effects (gastrointestinal upset, headache, allergic reaction). We used GRADE to assess the certainty of the evidence for each outcome. Main results: This review included 12 studies (with a total of  1915 participants). Eleven studies compared the effects of Ginkgo biloba with placebo and one study compared the effects of Ginkgo biloba with hearing aids to hearing aids alone. All included studies were parallel-group RCTs. In general, risk of bias was high or unclear due to selection bias and poor reporting of allocation concealment and blinding of participants, personnel and outcome assessments. Due to heterogeneity in the outcomes measured and measurement methods used, only limited data pooling was possible.  Ginkgo biloba versus placebo When we pooled data from two studies for the primary outcome tinnitus symptom severity, we found that Ginkgo biloba may have little to no effect (Tinnitus Handicap Inventory scores) at three to six months compared to placebo, but the evidence is very uncertain (mean difference (MD) -1.35 (scale 0 to 100), 95% confidence interval (CI) -8.26 to 5.55; 2 studies; 85 participants) (very low-certainty). Ginkgo biloba may result in little to no difference in the risk of bleeding or seizures, with no serious adverse effects reported in either group (4 studies; 1154 participants; low-certainty). For the secondary outcomes, one study found that there may be little to no difference between the effects of Ginkgo biloba and placebo on tinnitus loudness measured with audiometric loudness matching at 12 weeks, but the evidence is very uncertain (MD -4.00 (scale -10 to 140 dB), 95% CI -13.33 to 5.33; 1 study; 73 participants) (very low-certainty). One study found that there may be little to no difference between the effects of Ginkgo biloba and placebo on health-related quality of life measured with the Glasgow Health Status Inventory at three months (MD -0.58 (scale 0 to 100), 95% CI -4.67 to 3.51; 1 study; 60 participants) (low-certainty). Ginkgo biloba may not increase the frequency of other adverse effects (gastrointestinal upset, headache, allergic reaction) at three months compared to placebo (risk ratio 0.91, 95% CI 0.52 to 1.60; 4 studies; 1175 participants) (low-certainty). None of the studies reported the other secondary outcomes of tinnitus intrusiveness or changes in depressive symptoms or depression, anxiety symptoms or generalised anxiety. Gingko biloba with concurrent intervention versus concurrent intervention only One study compared Ginkgo biloba with hearing aids to hearing aids only. It assessed the mean difference in the change in Tinnitus Handicap Inventory scores and tinnitus loudness using a 10-point visual analogue scale (VAS) at three months. The study did not report adverse effects, tinnitus intrusiveness, changes in depressive symptoms or depression, anxiety symptoms or generalised anxiety, or health-related quality of life. This was a single, very small study (22 participants) and for all outcomes the certainty of the evidence was very low. We were unable to draw meaningful conclusions from the numerical results. Authors' conclusions: There is uncertainty about the benefits and harms of Ginkgo biloba for the treatment of tinnitus when compared to placebo. We were unable to draw meaningful conclusions regarding the benefits and harms of Ginkgo biloba when used with concurrent intervention (hearing aids). The certainty of the evidence for the reported outcomes, assessed using GRADE, ranged from low to very low. Future research into the effectiveness of Ginkgo biloba in patients with tinnitus should use rigorous methodology. Randomisation and blinding should be of the highest quality, given the subjective nature of tinnitus and the strong likelihood of a placebo response. The CONSORT statement should be used in the design and reporting of future studies. We also recommend the use of validated, patient-centred outcome measures for research in the field of tinnitus.

The Cochrane database of systematic reviews · systematic review · 22 citationsread the source →

Attitudes and beliefs about deceased organ donation in the Arabic-speaking community in Australia: a focus group study.

Objectives: To describe the beliefs and attitudes to organ donation in the Arabic-speaking community. Design: Arabic-speaking participants were purposively recruited to participate in 6 focus groups. Transcripts were analysed thematically. Participants: 53 participants, aged 19-77 years, and originating from 8 countries, participated in 1 of 6 focus groups. Participants identified as Christian (73%), Islam (26%), Buddhist (2%) or did not identify with any religion (2%). Results: 6 themes (with subthemes) were identified; religious conviction; invisibility of organ donation; medical suspicion; owning the decision; and reciprocal benefit. Conclusions: Although organ donation is considered a generous life-saving 'gift', representative members of the Arabic-speaking community in Australia were unfamiliar with, unnerved by and sceptical about the donation process. Making positive decisions about organ donation would likely require resolving tensions between respecting family, community and religious values versus their individual autonomy. Providing targeted education about the process and benefits of organ donation within the Arabic community may clarify ambiguities surrounding cultural and religious-based views on organ donation, reduce taboos and suspicion towards donation, and in turn, lead to increased organ donation rates.

BMJ open · 26 citationsread the source →

Childhood eating disorders: British national surveillance study.

Background: The incidence of eating disorders appears stable overall, but may be increasing in younger age groups. Data on incidence, clinical features and outcome of early-onset eating disorders are sparse. Aims: To identify new cases of early-onset eating disorders (<13 years) presenting to secondary care over 1 year and to describe clinical features, management and 1-year outcomes. Method: Surveillance over 14 months through the established British Paediatric Surveillance System, and a novel child and adolescent psychiatry surveillance system set up for this purpose. Results: Overall incidence was 3.01/100,000 (208 individuals). In total, 37% met criteria for anorexia nervosa; 1.4% for bulimia nervosa; and 43% for eating disorder not otherwise specified. Nineteen per cent showed determined food avoidance and underweight without weight/shape concerns. Rates of comorbidity were 41%; family history of psychiatric disorder 44%; and early feeding difficulties 21%. Time to presentation was >8 months. A total of 50% were admitted to hospital, typically soon after diagnosis. Outcome data were available for 76% of individuals. At 1 year, 73% were reported improved, 6% worse and 10% unchanged (11% unknown). Most were still in treatment, and seven were hospital in-patients for most of the year. Conclusions: Childhood eating disorders represent a significant clinical burden to paediatric and mental health services. Efforts to improve early detection are needed. These data provide a baseline to monitor changing trends in incidence.

The British journal of psychiatry : the journal of mental science · 174 citationsread the source →

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

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

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

Longitudinal associations between formal volunteering and well-being among retired older people: follow-up results from a randomized controlled trial.

Volunteering has been identified as a potential mechanism for improving the psychosocial health of older adults. Utilizing a randomized controlled trial approach, the present study assessed the extent to which commencing volunteering can improve psychosocial health outcomes for older people. Fully retired Australian adults aged 60+ years (N= 445) were assessed at baseline and allocated to either the intervention or control arms of the trial. Those in the intervention condition were asked to participate in at least 60 min of formal volunteering per week for 6 months. Per-protocol analyses were conducted comparing psychosocial outcomes for those who complied with the intervention condition (n= 73) to outcomes for those who complied with the control condition (n= 112). Those who complied with the intervention condition demonstrated significant improvements in life satisfaction, purpose in life, and personal growth scores over a 12-month period relative to those in the control condition who did no volunteering. Findings provide evidence of a causal relationship between commencing volunteering and improvements in psychosocial health among older adults and indicate that encouraging participation in this activity could constitute an effective healthy aging intervention.

Aging & mental health · randomised controlled trial · 17 citationsread the source →

Collaborative Care for Opioid and Alcohol Use Disorders in Primary Care: The SUMMIT Randomized Clinical Trial.

Importance: Primary care offers an important and underutilized setting to deliver treatment for opioid and/or alcohol use disorders (OAUD). Collaborative care (CC) is effective but has not been tested for OAUD. Objective: To determine whether CC for OAUD improves delivery of evidence-based treatments for OAUD and increases self-reported abstinence compared with usual primary care. Design, setting, and participants: A randomized clinical trial of 377 primary care patients with OAUD was conducted in 2 clinics in a federally qualified health center. Participants were recruited from June 3, 2014, to January 15, 2016, and followed for 6 months. Interventions: Of the 377 participants, 187 were randomized to CC and 190 were randomized to usual care; 77 (20.4%) of the participants were female, of whom 39 (20.9%) were randomized to CC and 38 (20.0%) were randomized to UC. The mean (SD) age of all respondents at baseline was 42 (12.0) years, 41(11.7) years for the CC group, and 43 (12.2) yearsfor the UC group. Collaborative care was a system-level intervention, designed to increase the delivery of either a 6-session brief psychotherapy treatment and/or medication-assisted treatment with either sublingual buprenorphine/naloxone for opioid use disorders or long-acting injectable naltrexone for alcohol use disorders. Usual care participants were told that the clinic provided OAUD treatment and given a number for appointment scheduling and list of community referrals. Main outcomes and measures: The primary outcomes were use of any evidence-based treatment for OAUD and self-reported abstinence from opioids or alcohol at 6 months. The secondary outcomes included the Healthcare Effectiveness Data and Information Set (HEDIS) initiation and engagement measures, abstinence from other substances, heavy drinking, health-related quality of life, and consequences from OAUD. Results: At 6 months, the proportion of participants who received any OAUD treatment was higher in the CC group compared with usual care (73 [39.0%] vs 32 [16.8%]; logistic model adjusted OR, 3.97; 95% CI, 2.32-6.79; P < .001). A higher proportion of CC participants reported abstinence from opioids or alcohol at 6 months (32.8% vs 22.3%); after linear probability model adjustment for covariates (β = 0.12; 95% CI, 0.01-0.23; P = .03). In secondary analyses, the proportion meeting the HEDIS initiation and engagement measures was also higher among CC participants (initiation, 31.6% vs 13.7%; adjusted OR, 3.54; 95% CI, 2.02-6.20; P < .001; engagement, 15.5% vs 4.2%; adjusted OR, 5.89; 95% CI, 2.43-14.32; P < .001) as was abstinence from opioids, cocaine, methamphetamines, marijuana, and any alcohol (26.3% vs 15.6%; effect estimate, β = 0.13; 95% CI, 0.03-0.23; P = .01). Conclusions and relevance: Among adults with OAUD in primary care, the SUMMIT collaborative care intervention resulted in significantly more access to treatment and abstinence from alcohol and drugs at 6 months, than usual care. Trial registration: clinicaltrials.gov Identifier: NCT01810159.

JAMA internal medicine · randomised controlled trial · 174 citationsread the source →

Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: a randomised controlled, open-label, multicentre trial.

Background: Treatment of patients with ileocaecal Crohn's disease who have not responded to conventional therapy is commonly scaled up to biological agents, but surgery can also offer excellent short-term and long-term results. We compared laparoscopic ileocaecal resection with infliximab to assess how they affect health-related quality of life. Methods: In this randomised controlled, open-label trial, in 29 teaching hospitals and tertiary care centres in the Netherlands and the UK, adults with non-stricturing, ileocaecal Crohn's disease, in whom conventional therapy has failed were randomly allocated (1:1) by an internet randomisation module with biased-coin minimisation for participating centres and perianal fistula to receive laparoscopic ileocaecal resection or infliximab. Eligible patients were aged 18-80 years, had active Crohn's disease of the terminal ileum, and had not responded to at least 3 months of conventional therapy with glucocorticosteroids, thiopurines, or methotrexate. Patients with diseased terminal ileum longer than 40 cm or abdominal abscesses were excluded. The primary outcome was quality of life on the Inflammatory Bowel Disease Questionnaire (IBDQ) at 12 months. Secondary outcomes were general quality of life, measured by the Short Form-36 (SF-36) health survey and its physical and mental component subscales, days unable to participate in social life, days on sick leave, morbidity (additional procedures and hospital admissions), and body image and cosmesis. Analyses of the primary outcome were done in the intention-to-treat population, and safety analyses were done in the per-protocol population. This trial is registered at the Dutch Trial Registry (NTR1150). Findings: Between May 2, 2008, and October 14, 2015, 73 patients were allocated to have resection and 70 to receive infliximab. Corrected for baseline differences, the mean IBDQ score at 12 months was 178·1 (95% CI 171·1-185·0) in the resection group versus 172·0 (164·3-179·6) in the infliximab group (mean difference 6·1 points, 95% CI -4·2 to 16·4; p=0·25). At 12 months, the mean SF-36 total score was 112·1 (95% CI 108·0-116·2) in the resection group versus 106·5 (102·1-110·9) in the infliximab group (mean difference 5·6, 95% CI -0·4 to 11·6), the mean physical component score was 47·7 (45·7-49·7) versus 44·6 (42·5-46·8; mean difference 3·1, 4·2 to 6·0), and the mean mental component score was 49·5 (47·0-52·1) versus 46·1 (43·3-48·9; mean difference 3·5, -0·3 to 7·3). Mean numbers of days of sick leave were 3·4 days (SD 7·1) in the resection group versus 1·4 days (4·7) in the infliximab group (p<0·0001), days not able to take part in social life were 1·8 days (6·3) versus 1·1 days (4·5; p=0·20), days of scheduled hospital admission were 6·5 days (3·8) versus 6·8 days (3·2; p=0·84), and the number of patients who had unscheduled hospital admissions were 13 (18%) of 73 versus 15 (21%) of 70 (p=0·68). Body-image scale mean scores in the patients who had resection were 16·0 (95% CI 15·2-16·8) at baseline versus 17·8 (17·1-18·4) at 12 months, and cosmetic scale mean scores were 17·6 (16·6-18·6) versus 18·6 (17·6-19·6). Surgical intervention-related complications classified as IIIa or worse on the Clavien-Dindo scale occurred in four patients in the resection group. Treatment-related serious adverse events occurred in two patients in the infliximab group. During a median follow-up of 4 years (IQR 2-6), 26 (37%) of 70 patients in the infliximab group had resection, and 19 (26%) of 73 patients in the resection group received anti-TNF. Interpretation: Laparoscopic resection in patients with limited (diseased terminal ileum <40 cm), non-stricturing, ileocaecal Crohn's disease in whom conventional therapy has failed could be considered a reasonable alternative to infliximab therapy. Funding: Netherlands Organisation for Health Research and Development.

The lancet. Gastroenterology & hepatology · randomised controlled trial · 228 citationsread the source →

Effect of Fractional Carbon Dioxide vs Sham Laser on Sexual Function in Survivors of Breast Cancer Receiving Aromatase Inhibitors for Genitourinary Syndrome of Menopause: The LIGHT Randomized Clinical Trial.

Importance: Survivors of breast cancer present more severe symptoms of genitourinary syndrome of menopause (GSM) than patients without history of breast cancer. Recently, new treatments, such as vaginal laser therapy, have appeared, but evidence of their efficacy remains scarce. Objective: To assess the safety and efficacy of carbon dioxide (CO2) vs sham vaginal laser therapy after 6 months of follow-up in survivors of breast cancer with GSM receiving aromatase inhibitors. Design, setting, and participants: This prospective double-blind sham-controlled randomized clinical trial with two parallel study groups was performed during October 2020 to March 2022 in a tertiary referral hospital. Survivors of breast cancer using aromatase inhibitors were assessed for eligibility, and eligible patients were randomized into the 2 treatment groups. Follow-up was conducted at 6 months. Data were analyzed in July 2022. Interventions: All patients from both groups were instructed to use the first-line treatment (FLT) based on nonhormonal moisturizers and vaginal vibrator stimulation. Patients for each group were allocated to 5 monthly sessions of fractional CO2 laser therapy (CLT) or sham laser therapy (SLT). Main outcomes and measures: The primary outcome was sexual function, evaluated through Female Sexual Function Index (FSFI) score. Other subjective measures of efficacy included a visual analog scale of dyspareunia, vaginal pH, a Vaginal Health Index, quality of life (assessed via Short-Form 12), and body image (assessed with the Spanish Body Image Scale). Objective measures of efficacy included vaginal maturation index, vaginal epithelial elasticity (measured in Pascals) and vaginal epithelial thickness (measured in millimeters). Measures were assessed before and after the intervention. Tolerance (measured on a Likert scale), adverse effects, and estradiol levels were recorded. Results: Among 211 survivors of breast cancer assessed, 84 women were deemed eligible and 72 women (mean [SD] age, 52.6 [8.3] years) were randomized to CLT (35 participants) or SLT (37 participants) and analyzed. There were no statistically significant differences between groups at baseline. At 6 months, both groups showed improvement in FSFI (mean [SD] score at baseline vs 6 months: CLT, 14.8 [8.8] points vs 20.0 [9.5] points; SLT, 15.6 [7.0] points vs 23.5 [6.5] points), but there was no significant difference between CLT and SLT groups in the improvement of sexual function evaluated through the FSFI test overall (mean [SD] difference, 5.2 [1.5] points vs 7.9 [1.2] points; P = .15) or after excluding women who were not sexually active (mean [SD] difference, 2.9 [1.4] points vs 5.5 [1.1] points; P = .15). There were also no differences between improvement of the 2 groups at 6 months of follow-up in the other assessed subjective outcomes, including dyspareunia (mean [SD] difference, -4.3 [3.4] vs -4.5 [2.3]; P = .73), Vaginal Health Index (mean [SD] difference, 3.3 [4.1] vs 5.0 [4.5]; P = .17), body image (mean [SD] difference, -3.7 [4.5] vs -2.7 [4.8]; P = .35), and quality of life (mean [SD] difference, -0.3 [3.6] vs -0.7 [3.2]; P = .39). Similarly, there were no differences in improvements in objective outcomes, including vaginal pH (mean [SD] difference, -0.6 [0.9] vs -0.8 [1.2]; P = .29), vaginal maturation index (mean [SD] difference, 10.2 [17.4] vs 14.4 [17.1]; P = .15), vaginal epithelial thickness (mean [SD] difference, 0.021 [0.014] mm vs 0.013 [0.012] mm; P = .30), vaginal epithelial elasticity (mean [SD] difference, -1373 [3197] Pascals vs -2103 [3771] Pascals; P = .64). There were significant improvements in the overall analysis regardless of group in many outcomes. The 2 interventions were well tolerated, but tolerance was significantly lower in the CLT group than the SLT group (mean [SD] Likert scale score, 3.3 [1.3] vs 4.1 [1.0]; P = .007). No differences were observed in complications or serum estradiol levels. Conclusions and relevance: In this randomized clinical trial, vaginal laser treatment was found to be safe after 6 months of follow-up, but no statistically significant differences in efficacy were observed between CLT and SLT. Trial registration: ClinicalTrials.gov identifier: NCT04619485.

JAMA network open · randomised controlled trial · 62 citationsread the source →

Symptoms and Distress in Children With Advanced Cancer: Prospective Patient-Reported Outcomes From the PediQUEST Study.

Purpose: Thousands of children are living with advanced cancer; yet patient-reported outcomes (PROs) have rarely been used to describe their experiences. We aimed to describe symptom distress in 104 children age 2 years or older with advanced cancer enrolled onto the Pediatric Quality of Life and Evaluation of Symptoms Technology (PediQUEST) Study (multisite clinical trial evaluating an electronic PRO system). Methods: Symptom data were collected using age- and respondent-adapted versions of the PediQUEST Memorial Symptom Assessment Scale (PQ-MSAS) at most once per week. Clinical and treatment data were obtained from medical records. Individual symptom scores were dichotomized into high/low distress. Determinants of PQ-MSAS scores were explored using linear mixed-effects models. Results: During 9 months of follow-up, PQ-MSAS was administered 920 times: 459 times in teens (99% self-report), 249 times in children ages 7 to 12 years (96% child/parent report), and 212 times in those ages 2 to 6 years (parent reports). Common symptoms included pain (48%), fatigue (46%), drowsiness (39%), and irritability (37%); most scores indicated high distress. Among the 73 PQ-MSAS surveys administered in the last 12 weeks of life, pain was highly prevalent (62%; 58% with high distress). Being female, having a brain tumor, experiencing recent disease progression, and receiving moderate- or high-intensity cancer-directed therapy in the prior 10 days were associated with worse PQ-MSAS scores. In the final 12 weeks of life, receiving mild cancer-directed therapy was associated with improved psychological PQ-MSAS scores. Conclusion: Children with advanced cancer experience high symptom distress. Strategies to promote intensive symptom management are indicated, especially with disease progression or administration of intensive treatments.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology · randomised controlled trial · 212 citationsread the source →

Promoting resilience in adolescents and young adults with cancer: Results from the PRISM randomized controlled trial.

Background: Adolescents and young adults (AYAs) with cancer are at risk for poor psychosocial outcomes. This study aimed to determine whether a novel intervention targeting resilience resources would improve patient-reported resilience, quality of life, and psychological distress. Methods: In this parallel, phase 2 randomized controlled trial, English-speaking AYAs (12-25 years old) with cancer were randomized to the Promoting Resilience in Stress Management (PRISM) intervention or usual care (UC). PRISM is a brief, skills-based intervention targeting stress management, goal setting, cognitive reframing, and meaning making. Participants completed surveys at enrollment and 6 months. Mixed effects regression models evaluated associations between PRISM and the primary outcome (10-item Connor-Davidson Resilience Scale scores) and secondary outcomes (generic and cancer-related quality of life [Pediatric Quality of Life modules], psychological distress [Kessler-6], and anxiety/depression [Hospital Anxiety and Depression]) at 6 months. Results: Ninety-two AYAs were enrolled, were randomized, and completed baseline surveys (48 in the PRISM group and 44 in the UC group); 73% were 12 to 17 years old, and 62% had leukemia or lymphoma. Attrition was primarily due to medical complications and/or death; 36 PRISM participants and 38 UC participants completed 6-month surveys. PRISM was associated with improved resilience (+3.0 points; 95% confidence interval [CI], 0.5-5.4; P = .02) and cancer-specific quality of life (+9.6; 95% CI, 2.6-16.7; P = .01) and reduced psychological distress (-2.1; 95% CI, -4.1 to -0.2; P = .03) but not generic quality of life (+7.2; 95% CI, -0.8 to 15.2; P = .08). Although anxiety was similar between the groups, 2 PRISM participants (6%) and 8 UC participants (21%) met the criteria for depression at 6 months (odds ratio, 0.09; 95% CI, 0.01-1.09; P = .06). Conclusions: PRISM was associated with improved psychosocial outcomes in comparison with UC, suggesting that brief, skills-based interventions for AYAs may provide a benefit.

Cancer · randomised controlled trial · 143 citationsread the source →

Motivational interviewing targeting diet and physical activity improves adherence to paediatric obesity treatment: results from the MI Values randomized controlled trial.

Background: Adherence is a challenge in obesity treatment. Motivational interviewing (MI) may promote patient adherence. MI Values is a randomized controlled trial of MI implemented as an adjunct to an adolescent obesity treatment [Teaching Encouragement Exercise Nutrition Support (T.E.E.N.S.)]. Objective: Assess effects of MI Values on T.E.E.N.S. attrition and adherence. Methods: Participants were randomized to MI (n = 58) or control (n = 41). At weeks 1 and 10, MI participants had brief MI sessions; controls viewed health education videos. All participants continued with T.E.E.N.S. (biweekly dietitian and behavioural support visits; 3 times per week supervised physical activity). Assessments were repeated at baseline, 3 and 6 months. T-tests and chi-square analyses examined T.E.E.N.S. attrition and adherence by group. Results: Adolescents (N = 99) were primarily African-American (73%) females (74%); age = 13.8 ± 1.8 years, body mass index percentile = 98.0 ± 1.2. Compared with controls, MI participants had greater 3-month adherence overall (89.2% vs. 81.0%, P = 0.040), and to dietitian (91.3% vs. 84.0%; P = 0.046) and behavioural support (92.9% vs. 85.2%; P = 0.041) visits, and greater 6-month adherence overall (84.4% vs. 76.2%, P = 0.026) and to behavioural support visits (87.5% vs. 78.8%, P = 0.011). Conclusions: MI enhanced adherence to this obesity intervention. MI Values is the first study to examine the impact of MI on treatment adherence among obese, primarily African-American adolescents.

Pediatric obesity · randomised controlled trial · 54 citationsread the source →

The efficacy of Internet-based cognitive behavioral therapy for severely fatigued survivors of breast cancer compared with care as usual: A randomized controlled trial.

Background: Severe fatigue is a common and distressing symptom affecting approximately one in four survivors of breast cancer. The current study examined the efficacy of Internet-based cognitive behavioral therapy (ICBT) for severe fatigue in survivors of breast cancer compared with care as usual (CAU). Methods: The authors conducted a parallel-group randomized controlled trial. Severely fatigued, disease-free survivors of breast cancer who had completed cancer treatment at least 3 months previously were eligible. Participants were randomly allocated to ICBT or CAU using computer-generated stratified block randomization. The primary outcome of fatigue severity was assessed at baseline and after 6 months, as were the secondary outcomes of functional impairment, psychological distress, and quality of life. Statistical effects were tested with analyses of covariance (intention-to-treat analysis). Results: Participants were recruited between January 2014 and March 2016 and assigned to ICBT (66 patients) or CAU (66 patients). Compared with the participants who had received CAU, those who had received ICBT reported lower fatigue scores at 6 months (mean difference [Δ], 11.5; 95% confidence interval [95% CI], 7.7-15.3) and a large effect size (Cohen d = 1.0), with the majority of patients (73%) demonstrating clinically significant improvement. ICBT also was found to lead to lower functional impairment (Δ, 297.8; 95% CI, 145.5-450.1) and psychological distress scores (Δ, 5.7; 95% CI, 3.4-7.9) and higher quality-of-life scores (Δ, 11.7; 95% CI, 5.8-17.7) compared with CAU, with medium to large effect sizes (Cohen d = 0.6-0.8). Conclusions: ICBT appears to be effective in reducing severe fatigue and related symptoms and meets the current need for easy accessible and more efficient evidence-based treatment options for severely fatigued survivors of breast cancer. Cancer 2017;123:3825-34. © 2017 American Cancer Society.

Cancer · randomised controlled trial · 115 citationsread the source →

Impact of motivational interviewing on outcomes of an adolescent obesity treatment: results from the MI Values randomized controlled pilot trial.

The aim of this study is to examine outcomes from MI Values, a motivational interviewing (MI) intervention implemented adjunctive to obesity treatment. Adolescents (n = 99; 73% African American; 74% female; mean body mass index [BMI] percentile = 98.9 ± 1.2) were randomized to receive two MI sessions or education control. All adolescents participated in structured behavioural weight management treatment. Baseline, 3- and 6-month assessments of anthropometrics, dietary intake and physical activity were obtained. Both groups had significant reductions in BMI z-scores and energy intake and increased physical activity at 3 and 6 months (P < 0.05). MI participants reported greater reductions in 3-month energy intake compared with controls. Participation in MI is associated with reduction in energy intake, consistent with better adherence to dietitian visits previously reported from MI Values. MI might be an effective adjunct to adolescent obesity treatment; future research is needed to determine if motivational interviewing can enhance BMI outcomes, via greater adherence to behavioural intervention.

Clinical obesity · randomised controlled trial · 27 citationsread the source →

Home-based health promotion for older people with mild frailty: the HomeHealth intervention development and feasibility RCT.

Background: Mild frailty or pre-frailty is common and yet is potentially reversible. Preventing progression to worsening frailty may benefit individuals and lower health/social care costs. However, we know little about effective approaches to preventing frailty progression. Objectives: (1) To develop an evidence- and theory-based home-based health promotion intervention for older people with mild frailty. (2) To assess feasibility, costs and acceptability of (i) the intervention and (ii) a full-scale clinical effectiveness and cost-effectiveness randomised controlled trial (RCT). Design: Evidence reviews, qualitative studies, intervention development and a feasibility RCT with process evaluation. Intervention development: Two systematic reviews (including systematic searches of 14 databases and registries, 1990-2016 and 1980-2014), a state-of-the-art review (from inception to 2015) and policy review identified effective components for our intervention. We collected data on health priorities and potential intervention components from semistructured interviews and focus groups with older people (aged 65-94 years) (n = 44), carers (n = 12) and health/social care professionals (n = 27). These data, and our evidence reviews, fed into development of the 'HomeHealth' intervention in collaboration with older people and multidisciplinary stakeholders. 'HomeHealth' comprised 3-6 sessions with a support worker trained in behaviour change techniques, communication skills, exercise, nutrition and mood. Participants addressed self-directed independence and well-being goals, supported through education, skills training, enabling individuals to overcome barriers, providing feedback, maximising motivation and promoting habit formation. Feasibility rct: Single-blind RCT, individually randomised to 'HomeHealth' or treatment as usual (TAU). Setting: Community settings in London and Hertfordshire, UK. Participants: A total of 51 community-dwelling adults aged ≥ 65 years with mild frailty. Main outcome measures: Feasibility - recruitment, retention, acceptability and intervention costs. Clinical and health economic outcome data at 6 months included functioning, frailty status, well-being, psychological distress, quality of life, capability and NHS and societal service utilisation/costs. Results: We successfully recruited to target, with good 6-month retention (94%). Trial procedures were acceptable with minimal missing data. Individual randomisation was feasible. The intervention was acceptable, with good fidelity and modest delivery costs (£307 per patient). A total of 96% of participants identified at least one goal, which were mostly exercise related (73%). We found significantly better functioning (Barthel Index +1.68; p = 0.004), better grip strength (+6.48 kg; p = 0.02), reduced psychological distress (12-item General Health Questionnaire -3.92; p = 0.01) and increased capability-adjusted life-years [+0.017; 95% confidence interval (CI) 0.001 to 0.031] at 6 months in the intervention arm than the TAU arm, with no differences in other outcomes. NHS and carer support costs were variable but, overall, were lower in the intervention arm than the TAU arm. The main limitation was difficulty maintaining outcome assessor blinding. Conclusions: Evidence is lacking to inform frailty prevention service design, with no large-scale trials of multidomain interventions. From stakeholder/public perspectives, new frailty prevention services should be personalised and encompass multiple domains, particularly socialising and mobility, and can be delivered by trained non-specialists. Our multicomponent health promotion intervention was acceptable and delivered at modest cost. Our small study shows promise for improving clinical outcomes, including functioning and independence. A full-scale individually RCT is feasible. Future work: A large, definitive RCT of the HomeHealth service is warranted. Study registration: This study is registered as PROSPERO CRD42014010370 and Current Controlled Trials ISRCTN11986672. 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. 73. See the NIHR Journals Library website for further project information.

Health technology assessment (Winchester, England) · randomised controlled trial · 64 citationsread the source →

A psychosocial intervention for stroke survivors and carers: 12-month outcomes of a randomized controlled trial.

Background and Purpose: Stroke can have a devastating impact on the mental and physical health of stroke survivors and their carers. We aimed to evaluate the effectiveness of a novel psychosocial intervention designed to improve health outcomes in both groups. Methods: We conducted a randomized controlled trial of a personalized psychosocial intervention (eight 1-hour weekly sessions plus one booster) compared to usual care for adult stroke survivors and carers. Participants recruited from hospital services and community referrals completed questionnaires at baseline, 3, 6, and 12 months. Primary outcomes were quality of life and self-efficacy; secondary outcomes were depressive and anxiety symptoms, coping, illness perception, work and social adjustment, carer strain, and carer satisfaction. Mixed-effect model repeated measures analysis between groups and across time was conducted. Results: Of the 173 participants recruited (89 stroke survivors; 84 carers), a total of 137 participants - 73 stroke survivors (intervention n = 42; usual care n = 31) and 64 carers (intervention n = 35; usual care n = 29) - underwent analysis up to 12 months. No statistically significant differences were found in the primary outcomes between groups over time, though a significant improvement in carer satisfaction was found at 6 months in the intervention group compared to the usual care group. Conclusion: A personalized psychosocial intervention resulted in a significant improvement in carer satisfaction at 6 months but in no other outcomes. A lack of available services and barriers to social engagement may have impeded the effectiveness of this intervention.

Topics in stroke rehabilitation · randomised controlled trial · 31 citationsread the source →

Longitudinal DNA methylation in parent-infant pairs impacted by intergenerational social adversity: An RCT of the Michigan Model of Infant Mental Health Home Visiting.

Introduction: Early childhood development is a strong predictor of long-term health outcomes, potentially mediated via epigenetics (DNA methylation). The aim of the current study was to examine how childhood experiences, punitive parenting, and an intergenerational psychotherapeutic intervention may impact DNA methylation in young children and their mothers. Methods: Mothers and their infants/toddlers between 0 and 24 months were recruited at baseline (n = 146, 73 pairs) to participate in a randomized control trial evaluating the effectiveness of The Michigan Model of Infant Mental Health Home Visiting (IMH-HV) parent-infant psychotherapy compared to treatment as usual. Baseline and 12-month post-enrollment data were collected in the family's home and included self-report questionnaires, biological saliva samples, home environment observation, video-taped parent-child interaction, and audio-recorded interviews. Saliva DNA methylation was measured at the genes, nuclear receptor subfamily 3 group C member 1 (NR3C1), solute carrier family 6 member 4 (SLC6A4), brain-derived neurotrophic factor (BDNF), and the genetic element, long interspersed nuclear element-1 (LINE1). Results: For mothers, baseline methylation of BDNF, SLC6A4, NR3C1, or LINE1 was largely not associated with baseline measures of their childhood adversity, adverse life experiences, demographic characteristics related to structurally driven inequities, or to IMH-HV treatment effect. In infants, there were suggestions that methylation in SLC6A4 and LINE1 was associated with parenting attitudes. Infant BDNF methylation suggested an overall decrease in response to IMH-HV psychotherapy over 12 months. Conclusions: Overall, our findings suggest that the epigenome in infants and young children may be sensitive to both early life experiences and parent-infant psychotherapy.

Brain and behavior · randomised controlled trial · 1 citationsread the source →

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

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

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

An online breathing and wellbeing programme (ENO Breathe) for people with persistent symptoms following COVID-19: a parallel-group, single-blind, randomised controlled trial.

Background: There are few evidence-based interventions for long COVID; however, holistic approaches supporting recovery are advocated. We assessed whether an online breathing and wellbeing programme improves health related quality-of-life (HRQoL) in people with persisting breathlessness following COVID-19. Methods: We conducted a parallel-group, single-blind, randomised controlled trial in patients who had been referred from one of 51 UK-based collaborating long COVID clinics. Eligible participants were aged 18 years or older; were recovering from COVID-19 with ongoing breathlessness, with or without anxiety, at least 4 weeks after symptom onset; had internet access with an appropriate device; and were deemed clinically suitable for participation by one of the collaborating COVID-19 clinics. Following clinical assessment, potential participants were given a unique online portal code. Participants were randomly assigned (1:1) to either immediate participation in the English National Opera (ENO) Breathe programme or to usual care. Randomisation was done by the research team using computer-generated block randomisation lists, with block size 10. The researcher responsible for randomisation was masked to responses. Participants in the ENO Breathe group participated in a 6-week online breathing and wellbeing programme, developed for people with long COVID experiencing breathlessness, focusing on breathing retraining using singing techniques. Those in the deferred group received usual care until they exited the trial. The primary outcome, assessed in the intention-to-treat population, was change in HRQoL, assessed using the RAND 36-item short form survey instrument mental health composite (MHC) and physical health composite (PHC) scores. Secondary outcome measures were the chronic obstructive pulmonary disease assessment test score, visual analogue scales (VAS) for breathlessness, and scores on the dyspnoea-12, the generalised anxiety disorder 7-item scale, and the short form-6D. A thematic analysis exploring participant experience was also conducted using qualitative data from focus groups, survey responses, and email correspondence. This trial is registered with ClinicalTrials.gov, NCT04830033. Findings: Between April 22 and May 25, 2021, 158 participants were recruited and randomly assigned. Of these, eight (5%) individuals were excluded and 150 participants were allocated to a treatment group (74 in the ENO Breathe group and 76 in the usual care group). Compared with usual care, ENO Breathe was associated with an improvement in MHC score (regression coefficient 2·42 [95% CI 0·03 to 4·80]; p=0·047), but not PHC score (0·60 [-1·33 to 2·52]; p=0·54). VAS for breathlessness (running) favoured ENO Breathe participation (-10·48 [-17·23 to -3·73]; p=0·0026). No other statistically significant between-group differences in secondary outcomes were observed. One minor self-limiting adverse event was reported by a participant in the ENO Breathe group who felt dizzy using a computer for extended periods. Thematic analysis of ENO Breathe participant experience identified three key themes: (1) improvements in symptoms; (2) feeling that the programme was complementary to standard care; and (3) the particular suitability of singing and music to address their needs. Interpretation: Our findings suggest that an online breathing and wellbeing programme can improve the mental component of HRQoL and elements of breathlessness in people with persisting symptoms after COVID-19. Mind-body and music-based approaches, including practical, enjoyable, symptom-management techniques might have a role supporting recovery. Funding: Imperial College London.

The Lancet. Respiratory medicine · randomised controlled trial · 74 citationsread the source →

Effect of Lactobacillus rhamnosus HN001 in Pregnancy on Postpartum Symptoms of Depression and Anxiety: A Randomised Double-blind Placebo-controlled Trial.

Background: Probiotics may help to prevent symptoms of anxiety and depression through several putative mechanisms. Objective: The aim of this study was to evaluate the effect of Lactobacillus rhamnosus HN001 (HN001) given in pregnancy and postpartum on symptoms of maternal depression and anxiety in the postpartum period. This was a secondary outcome, the primary outcome being eczema in the offspring at 12months of age. Design, setting, participants: A randomised, double-blind, placebo-controlled trial of the effect of HN001 on postnatal mood was conducted in 423 women in Auckland and Wellington, New Zealand. Women were recruited at 14-16weeks gestation. Intervention: Women were randomised to receive either placebo or HN001 daily from enrolment until 6months postpartum if breastfeeding. Outcome measures: Modified versions of the Edinburgh Postnatal Depression Scale and State Trait Anxiety Inventory were used to assess symptoms of depression and anxiety postpartum. Trial registration: Australia NZ Clinical Trials Registry: ACTRN12612000196842. Findings: 423 women were recruited between December 2012 and November 2014. 212 women were randomised to HN001 and 211 to placebo. 380 women (89.8%) completed the questionnaire on psychological outcomes, 193 (91.0%) in the treatment group and 187 (88.6%) in the placebo group. Mothers in the probiotic treatment group reported significantly lower depression scores (HN001 mean=7·7 (SD=5·4), placebo 9·0 (6·0); effect size -1·2, (95% CI -2·3, -0·1), p=0·037) and anxiety scores (HN001 12·0 (4·0), placebo 13·0 (4·0); effect size -1·0 (-1·9, -0·2), p=0·014) than those in the placebo group. Rates of clinically relevant anxiety on screening (score>15) were significantly lower in the HN001 treated mothers (OR=0·44 (0·26, 0·73), p=0·002). Interpretation: Women who received HN001 had significantly lower depression and anxiety scores in the postpartum period. This probiotic may be useful for the prevention or treatment of symptoms of depression and anxiety postpartum. Funding source: Health Research Council of New Zealand (11/318) and Fonterra Co-operative Group Ltd.

EBioMedicine · randomised controlled trial · 275 citationsread the source →

Post-deployment screening for mental disorders and tailored advice about help-seeking in the UK military: a cluster randomised controlled trial.

Background: The effectiveness of post-deployment screening for mental disorders has not been assessed in a randomised controlled trial. We aimed to assess whether post-deployment screening for post-traumatic stress disorder (PTSD), depression, anxiety, or alcohol misuse was effective. We defined screening as the presumptive identification of a previously unrecognised disorder using tests to distinguish those who probably had the disorder from those who probably did not so that those people with a probable disorder could be referred appropriately, and assessed effectiveness and consequences for help-seeking by the odds ratio at follow-up between those receiving tailored help-seeking advice and those who received general mental health advice. Methods: We did a cluster randomised controlled trial among Royal Marines and Army personnel in the UK military after deployment to Afghanistan. Platoons were randomly assigned (1:1 initially, then 2:1) by stratified block randomisation with randomly varying block sizes of two and four to the screening group, which received tailored help-seeking advice, or the control group, which received general mental health advice. Initial assessment took place 6-12 weeks after deployment; follow-up assessments were done 10-24 months later. Follow-up measures were the PTSD Checklist-Civilian Version, Patient Health Questionnaire-9, Generalised Anxiety Disorder-7 scale, Alcohol Use Disorder Identification Test (AUDIT), and self-reported help-seeking from clinical and welfare providers comparing those receiving tailored advice and those receiving only general advice. All participants and all investigators other than the person who analysed the data were masked to allocation. The primary outcomes were PTSD, depression or generalised anxiety disorder, and alcohol misuse at follow-up. A key secondary outcome was assessment of whether post-deployment screening followed by tailored advice would modify help-seeking behaviour. Comparisons were made between screening and control groups, with primary analyses by intention to treat. This trial is registered with the ISRCTN Registry, number ISRCTN19965528. Findings: Between Oct 24, 2011, and Oct 31, 2014, 434 platoons comprising 10 190 personnel were included: 274 (6350 personnel) in the screening group and 160 (3840 personnel) in the control group. 5577 (88%) of 6350 personnel received screening and 3996 (63%) completed follow-up, whereas 3149 (82%) of 3840 received the control questionnaire and 2369 (62%) completed follow-up. 1958 (35%) of 5577 personnel in the screening group declined to see the tailored advice, but those with PTSD (83%) or anxiety or depression (84%) were more likely than non-cases (64%) to view the advice (both p<0·0001). At follow-up, there were no significant differences in prevalence between groups for PTSD (adjusted odds ratio 0·92, 95% CI 0·75-1·14), depression or anxiety (0·91, 0·71-1·16), alcohol misuse (0·88, 0·73-1·06), or seeking support for mental disorders (0·92, 0·78-1·08). Interpretation: Post-deployment screening for mental disorders based on tailored advice was not effective at reducing prevalence of mental health disorders nor did it increase help-seeking. Countries that have implemented post-deployment screening programmes for mental disorders should consider monitoring the outcomes of their programmes. Funding: The US Army Medical Research and Materiel Command-Military Operational Medicine Research Program (USAMRMC-MOMRP).

Lancet (London, England) · randomised controlled trial · 38 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 →

Promoting school climate and health outcomes with the SEHER multi-component secondary school intervention in Bihar, India: a cluster-randomised controlled trial.

Background: School environments affect health and academic outcomes. With increasing secondary school retention in low-income and middle-income countries, promoting quality school social environments could offer a scalable opportunity to improve adolescent health and wellbeing. Methods: We did a cluster-randomised trial to assess the effectiveness of a multi-component whole-school health promotion intervention (SEHER) with integrated economic and process evaluations in grade 9 students (aged 13-14 years) at government-run secondary schools in the Nalanda district of Bihar state, India. Schools were randomly assigned (1:1:1) to three groups: the SEHER intervention delivered by a lay counsellor (the SEHER Mitra [SM] group), the SEHER intervention delivered by a teacher (teacher as SEHER Mitra [TSM] group), and a control group in which only the standard government-run classroom-based life-skills Adolescence Education Program was implemented. The primary outcome was school climate measured with the Beyond Blue School Climate Questionnaire (BBSCQ). Students were assessed at the start of the academic year (June, 2015) and again 8 months later at the end of the academic year (March, 2016) via self-completed questionnaires. This study is registered with ClinicalTrials.gov, number NCT02484014. Findings: Of the 112 eligible schools in the Nalanda district, 75 were randomly selected to participate in the trial. We randomly assigned 25 schools to each of the three groups. One school subsequently dropped out of the TSM group, leaving 24 schools in this group. The baseline survey included a total of 13 035 participants, and the endpoint survey included 14 414 participants. Participants in the SM-delivered intervention schools had substantially higher school climate scores at endpoint survey than those in the control group (BBSCQ baseline-adjusted mean difference [aMD] 7·57 [95% CI 6·11-9·03]; effect size 1·88 [95% CI 1·44-2·32], p<0·0001) and the TSM-delivered intervention (aMD 7·57 [95% CI 6·06-9·08]; effect size 1·88 [95% CI 1·43-2·34], p<0·0001). There was no effect of the TSM-delivered intervention compared with control (aMD -0·009 [95% CI -1·53 to 1·51], effect size 0·00 [95% CI -0·45 to 0·44], p=0·99). Compared with the control group, participants in the SM-delivered intervention schools had moderate to large improvements in the secondary outcomes of depression (aMD -1·23 [95% CI -1·89 to -0·57]), bullying (aMD -0·91 [95% CI -1·15 to -0·66]), violence victimisation (odds ratio [OR] 0·62 [95% CI 0·46-0·84]), violence perpetration (OR 0·68 [95% CI 0·48-0·96]), attitude towards gender equity (aMD 0·41 [95% CI 0·21-0·61]), and knowledge of reproductive and sexual health (aMD 0·29 [95% CI 0·06-0·53]). Similar results for these secondary outcomes were noted for the comparison between SM-delivered intervention schools and TSM-delivered intervention schools (depression: aMD -1·23 [95% CI -1·91 to -0·55]; bullying: aMD -0·83 [95% CI -1·08 to -0·57]; violence victimisation: OR 0·49 [95% CI 0·35-0·67]; violence perpetration: OR 0·49 [95% CI 0·34-0·71]; attitude towards gender equity: aMD 0·23 [95% CI 0·02-0·44]; and knowledge of reproductive and sexual health: aMD 0·22 [95% CI -0·02 to 0·47]). However, no effects on these secondary outcomes were observed for the TSM-delivered intervention schools compared with the control group (depression: aMD -0·03 [95% CI -0·70 to 0·65]; bullying: aMD -0·08 [95% CI -0·34 to 0·18]; violence victimisation: OR 1·27 [95% CI 0·93-1·73]; violence perpetration: OR 1·37 [95% CI 0·95-1·95]; attitude towards gender equity: aMD 0·17 [95% CI -0·09 to 0·38]; and knowledge of reproductive and sexual health: aMD 0·06 [95% CI -0·18 to 0·32]). Interpretation: The multi-component whole-school SEHER health promotion intervention had substantial beneficial effects on school climate and health-related outcomes when delivered by lay counsellors, but no effects when delivered by teachers. Future research should focus on the evaluation of the scaling up of the SEHER intervention in diverse contexts and delivery agents. Funding: John D. and Catherine T. MacArthur Foundation, USA and the United Nations Population Fund India Office.

Lancet (London, England) · randomised controlled trial · 121 citationsread the source →

The benefit of minocycline on negative symptoms of schizophrenia in patients with recent-onset psychosis (BeneMin): a randomised, double-blind, placebo-controlled trial.

Background: The antibiotic minocycline has neuroprotective and anti-inflammatory properties that could prevent or reverse progressive neuropathic changes implicated in recent-onset schizophrenia. In the BeneMin study, we aimed to replicate the benefit of minocycline on negative symptoms reported in previous pilot studies, and to understand the mechanisms involved. Methods: In this randomised, double-blind, placebo-controlled trial, we recruited people with a schizophrenia-spectrum disorder that had begun within the past 5 years with continuing positive symptoms from 12 National Health Service (NHS) trusts. Participants were randomly assigned according to an automated permuted blocks algorithm, stratified by pharmacy, to receive minocycline (200 mg per day for 2 weeks, then 300 mg per day for the remainder of the 12-month study period) or matching placebo, which were added to their continuing treatment. The primary clinical outcome was the negative symptom subscale score of the Positive and Negative Syndrome Scales (PANSS) across follow-ups at months 2, 6, 9, and 12. The primary biomarker outcomes were medial prefrontal grey-matter volume, dorsolateral prefrontal cortex activation during a working memory task, and plasma concentration of interleukin 6. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN49141214, and the EU Clinical Trials register (EudraCT) number is 2010-022463-35I. Findings: Between April 16, 2013, and April 30, 2015, we recruited 207 people and randomly assigned them to receive minocycline (n=104) or placebo (n=103). Compared with placebo, the addition of minocycline had no effect on ratings of negative symptoms (treatment effect difference -0·19, 95% CI -1·23 to 0·85; p=0·73). The primary biomarker outcomes did not change over time and were not affected by minocycline. The groups did not differ in the rate of serious adverse events (n=11 in placebo group and n=18 in the minocycline group), which were mostly due to admissions for worsening psychiatric state (n=10 in the placebo group and n=15 in the minocycline group). The most common adverse events were gastrointestinal (n=12 in the placebo group, n=19 in the minocycline group), psychiatric (n=16 in placebo group, n=8 in minocycline group), nervous system (n=8 in the placebo group, n=12 in the minocycline group), and dermatological (n=10 in the placebo group, n=8 in the minocycline group). Interpretation: Minocycline does not benefit negative or other symptoms of schizophrenia over and above adherence to routine clinical care in first-episode psychosis. There was no evidence of a persistent progressive neuropathic or inflammatory process underpinning negative symptoms. Further trials of minocycline in early psychosis are not warranted until there is clear evidence of an inflammatory process, such as microgliosis, against which minocycline has known efficacy. Funding: National Institute for Health Research Efficacy and Mechanism Evaluation (EME) programme, an MRC and NIHR partnership.

The lancet. Psychiatry · randomised controlled trial · 137 citationsread the source →

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

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

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

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 →

Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials.

Importance: Several studies have reported antidepressant effects of anti-inflammatory treatment; however, the results have been conflicting and detrimental adverse effects may contraindicate the use of anti-inflammatory agents. Objective: To systematically review the antidepressant and possible adverse effects of anti-inflammatory interventions. Data sources: Trials published prior to December, 31, 2013, were identified searching Cochrane Central Register of Controlled Trials, PubMed, EMBASE, PsychINFO, Clinicaltrials.gov, and relevant review articles. Study selection: Randomized placebo-controlled trials assessing the efficacy and adverse effects of pharmacologic anti-inflammatory treatment in adults with depressive symptoms, including those who fulfilled the criteria for depression. Data extraction and synthesis: Data were extracted by 2 independent reviewers. Pooled standard mean difference (SMD) and odds ratios (ORs) were calculated. Main outcomes and measures: Depression scores after treatment and adverse effects. Results: Ten publications reporting on 14 trials (6262 participants) were included: 10 trials evaluated the use of nonsteroidal anti-inflammatory drugs (NSAIDs) (n=4,258) and 4 investigated cytokine inhibitors (n=2,004). The pooled effect estimate suggested that anti-inflammatory treatment reduced depressive symptoms (SMD, -0.34; 95% CI, -0.57 to -0.11; I2=90%) compared with placebo. This effect was observed in studies including patients with depression (SMD, -0.54; 95% CI, -1.08 to -0.01; I2=68%) and depressive symptoms (SMD, -0.27; 95% CI, -0.53 to -0.01; I2=68%). The heterogeneity of the studies was not explained by differences in inclusion of clinical depression vs depressive symptoms or use of NSAIDs vs cytokine inhibitors. Subanalyses emphasized the antidepressant properties of the selective cyclooxygenase 2 inhibitor celecoxib (SMD, -0.29; 95% CI, -0.49 to -0.08; I2=73%) on remission (OR, 7.89; 95% CI, 2.94 to 21.17; I2=0%) and response (OR, 6.59; 95% CI, 2.24 to 19.42; I2=0%). Among the 6 studies reporting on adverse effects, we found no evidence of an increased number of gastrointestinal or cardiovascular events after 6 weeks or infections after 12 weeks of anti-inflammatory treatment compared with placebo. All trials were associated with a high risk of bias owing to potentially compromised internal validity. Conclusions and relevance: Our analysis suggests that anti-inflammatory treatment, in particular celecoxib, decreases depressive symptoms without increased risks of adverse effects. However, a high risk of bias and high heterogeneity made the mean estimate uncertain. This study supports a proof-of-concept concerning the use of anti-inflammatory treatment in depression. Identification of subgroups that could benefit from such treatment might be warranted.

JAMA psychiatry · meta-analysis · 666 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 →

Modifiable risk factors of maternal postpartum weight retention: an analysis of their combined impact and potential opportunities for prevention.

Background/objectives: Pregnancy triggers a physiological change in weight status. Postpartum weight retention in the childbearing years can substantially alter a woman's weight gain trajectory, with several potential contributing factors identified. Most research has relied on women's recall of pre-pregnancy weight during pregnancy or later, and not considered risk factors in combination. Using measured pre-pregnancy weight, this study aimed to examine the associations of maternal postpartum weight retention with parity, pre-pregnancy BMI, excessive gestational weight gain (GWG), maternal serum vitamin D concentration and dietary Glycaemic Index in early and late pregnancy, and breastfeeding duration, including analysis of the combined impact of potentially modifiable risk factors. Subjects/methods: Prospective cohort study of 12 583 non-pregnant women aged 20-34 years in Southampton (UK) who were assessed prior to pregnancy, with those who subsequently became pregnant followed up in early and late gestation, and after delivery (n=2559 in the final sample). Linear regression models examined potential predictors of weight retention in adjusted individual and multivariate analyses, and as a risk factor score. Results: Compared with pre-pregnancy weight, 73% of women retained some weight at 6 months postpartum (mean (s.d.): 3.5 (6.2) kg). In the adjusted multivariate model, women who were primiparous, had a lower pre-pregnancy BMI, excessive GWG, a lower early pregnancy vitamin D concentration and breastfed for <6 months had greater weight retention 6 months postpartum (P<0.05 for all variables). For each additional modifiable risk factor (excessive GWG, low vitamin D concentration in early pregnancy and short breastfeeding duration; scale 0-3), women retained an additional 2.49 kg (95% CI: 2.16, 2.82; P<0.001). Conclusions: Having a greater number of modifiable risk factors was associated with greater weight retention 6 months postpartum. Initiatives supporting women to target these risk factors in the years prior to, during and after pregnancy could impact on their weight gain trajectory and later risk of adverse weight-related outcomes.

International journal of obesity (2005) · 47 citationsread the source →

Rumination in posttraumatic stress disorder.

Recent studies have shown that rumination is a powerful predictor of persistent posttraumatic stress disorder (PTSD). However, to date, the mechanisms by which rumination maintains PTSD symptoms are little understood. Two studies of assault survivors, a cross-sectional (N = 81) and a 6-month prospective longitudinal study (N = 73), examined several facets of ruminative thinking to establish which aspects of rumination provide the link to PTSD. The current investigation showed that rumination is not only used as a strategy to cope with intrusive memories but it also triggers such memories. Certain characteristics of rumination, such as compulsion to continue ruminating, occurrence of unproductive thoughts, and "why" and "what if" type questions, as well as negative emotions before and after rumination, were significantly associated with PTSD, concurrently and prospectively. These characteristics explained significantly more variance in PTSD severity than the mere presence of rumination, thereby indicating that not all ways of ruminative thinking are equally maladaptive.

Depression and anxiety · 213 citationsread the source →

Cognitive behavioural therapy as an adjunct to pharmacotherapy for primary care based patients with treatment resistant depression: results of the CoBalT randomised controlled trial.

Background: Only a third of patients with depression respond fully to antidepressant medication but little evidence exists regarding the best next-step treatment for those whose symptoms are treatment resistant. The CoBalT trial aimed to examine the effectiveness of cognitive behavioural therapy (CBT) as an adjunct to usual care (including pharmacotherapy) for primary care patients with treatment resistant depression compared with usual care alone. Methods: This two parallel-group multicentre randomised controlled trial recruited 469 patients aged 18-75 years with treatment resistant depression (on antidepressants for ≥6 weeks, Beck depression inventory [BDI] score ≥14 and international classification of diseases [ICD]-10 criteria for depression) from 73 UK general practices. Participants were randomised, with a computer generated code (stratified by centre and minimised according to baseline BDI score, whether the general practice had a counsellor, previous treatment with antidepressants, and duration of present episode of depression) to one of two groups: usual care or CBT in addition to usual care, and were followed up for 12 months. Because of the nature of the intervention it was not possible to mask participants, general practitioners, CBT therapists, or researchers to the treatment allocation. Analyses were by intention to treat. The primary outcome was response, defined as at least 50% reduction in depressive symptoms (BDI score) at 6 months compared with baseline. This trial is registered, ISRCTN38231611. Findings: Between Nov 4, 2008, and Sept 30, 2010, we assigned 235 patients to usual care, and 234 to CBT plus usual care. 422 participants (90%) were followed up at 6 months and 396 (84%) at 12 months, finishing on Oct 31, 2011. 95 participants (46%) in the intervention group met criteria for response at 6 months compared with 46 (22%) in the usual care group (odds ratio 3·26, 95% CI 2·10-5·06, p<0·001). Interpretation: Before this study, no evidence from large-scale randomised controlled trials was available for the effectiveness of augmentation of antidepressant medication with CBT as a next-step for patients whose depression has not responded to pharmacotherapy. Our study has provided robust evidence that CBT as an adjunct to usual care that includes antidepressants is an effective treatment, reducing depressive symptoms in this population. Funding: National Institute for Health Research Health Technology Assessment.

Lancet (London, England) · randomised controlled trial · 215 citationsread the source →

Internet-delivered targeted group intervention for body dissatisfaction and disordered eating in adolescent girls: a randomized controlled trial.

This study evaluated a targeted intervention designed to alleviate body image and eating problems in adolescent girls that was delivered over the internet so as to increase access to the program. The program consisted of six, 90-minute weekly small group, synchronous on-line sessions and was facilitated by a therapist and manual. Participants were 73 girls (mean age=14.4 years, SD=1.48) who self-identified as having body image or eating problems and were randomly assigned to an intervention group (n=36) (assessed at baseline, post-intervention and at 2- and 6-months follow-up) or a delayed treatment control group (n=37) (assessed at baseline and 6-7 weeks later). Clinically significant improvements in body dissatisfaction, disordered eating, and depression were observed at post-intervention and maintained at follow-up. Internet delivery was enthusiastically endorsed. The program offers a promising approach to improve body image and eating problems that also addresses geographic access problems.

Journal of abnormal child psychology · randomised controlled trial · 65 citationsread the source →

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

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

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

Hunter DBT project: randomized controlled trial of dialectical behaviour therapy in women with borderline personality disorder.

Objective: Deliberate self-harm (DSH), general hospital admission and psychiatric hospital admission are common in women meeting criteria for borderline personality disorder (BPD). Dialectical behaviour therapy (DBT) has been reported to be effective in reducing DSH and hospitalization. Method: A randomized controlled trial of 73 female subjects meeting criteria for BPD was carried out with intention-to-treat analyses and per-protocol analyses. The intervention was DBT and the control condition was treatment as usual plus waiting list for DBT (TAU+WL), with outcomes measured after 6 months. Primary outcomes were differences in proportions and event rates of: any DSH; general hospital admission for DSH and any psychiatric admission; and mean difference in length of stay for any hospitalization. Secondary outcomes were disability and quality of life measures. Results: Both groups showed a reduction in DSH and hospitalizations, but there were no significant differences in DSH, hospital admissions or length of stay in hospital between groups. Disability (days spent in bed) and quality of life (Physical, Psychological and Environmental domains) were significantly improved for the DBT group. Conclusion: DBT produced non-significant reductions in DSH and hospitalization when compared to the TAU+WL control, due in part to the lower than expected rates of hospitalization in the control condition. Nevertheless, DBT showed significant benefits for the secondary outcomes of improved disability and quality of life scores, a clinically useful result that is also in keeping with the theoretical constructs of the benefits of DBT.

The Australian and New Zealand journal of psychiatry · randomised controlled trial · 71 citationsread the source →

Worry Exposure versus Applied Relaxation in the Treatment of Generalized Anxiety Disorder

BACKGROUND: Worry exposure (WE) is a core element of cognitive-behavioral treatment for generalized anxiety disorder (GAD). Its efficacy as a stand-alone treatment method (without further cognitive-behavioral therapy interventions) has never been tested. We aimed to examine whether WE alone is as efficacious as the empirically supported stand-alone treatment for GAD, applied relaxation (AR). METHODS: In a randomized controlled study, 73 outpatients meeting DSM-IV criteria for GAD as primary diagnosis were allocated to either WE or AR or a waiting list control group; in a 2nd randomization procedure the waiting list subjects were reallocated to WE or AR. The treatment was manualized (15 sessions with WE or AR), included 6-month and 1-year follow-ups, as well as last observation carried forward and completer analyses, and was controlled for allegiance effects. The Hamilton Anxiety Rating Scale and the State-Trait Anxiety Scale were used as primary outcome measures. Self-report scales of anxiety, worrying and depression including negative metacognition about worrying and thought suppression served as secondary outcome measures. RESULTS: The dropout rate was moderate. The pre-/posttreatment effects were high for the Hamilton Anxiety Rating Scale (standardized mean difference >1) and for the State-Trait Anxiety Inventory (standardized mean difference >0.87). The proportion of patients reaching high end state functioning was 48% (WE) and 56% (AR). WE and AR did not differ with regard to dropout rate or treatment effects. The treatment effects were stable at 6 month and 1 year follow-up. CONCLUSION: This is the first study to show that a stand-alone exposure in sensu technique--WE--is efficacious in the treatment of GAD. Both AR and WE seem to represent effective principles of change in GAD.

Psychotherapy and Psychosomatics · randomised controlled trial · 148 citationsread the source →

Telemedicine-Based Collaborative Care for Posttraumatic Stress Disorder

IMPORTANCE: Posttraumatic stress disorder (PTSD) is prevalent, persistent, and disabling. Although psychotherapy and pharmacotherapy have proven efficacious in randomized clinical trials, geographic barriers impede rural veterans from engaging in these evidence-based treatments. OBJECTIVE: To test a telemedicine-based collaborative care model designed to improve engagement in evidence-based treatment of PTSD. DESIGN, SETTING, AND PARTICIPANTS: The Telemedicine Outreach for PTSD (TOP) study used a pragmatic randomized effectiveness trial design with intention-to-treat analyses. Outpatients were recruited from 11 Department of Veterans Affairs (VA) community-based outpatient clinics serving predominantly rural veterans. Inclusion required meeting diagnostic criteria for current PTSD according to the Clinician-Administered PTSD Scale. Exclusion criteria included receiving PTSD treatment at a VA medical center or a current diagnosis of schizophrenia, bipolar disorder, or substance dependence. Two hundred sixty-five veterans were enrolled from November 23, 2009, through September 28, 2011, randomized to usual care (UC) or the TOP intervention, and followed up for 12 months. INTERVENTIONS: Off-site PTSD care teams located at VA medical centers supported on-site community-based outpatient clinic providers. Off-site PTSD care teams included telephone nurse care managers, telephone pharmacists, telepsychologists, and telepsychiatrists. Nurses conducted care management activities. Pharmacists reviewed medication histories. Psychologists delivered cognitive processing therapy via interactive video. Psychiatrists supervised the team and conducted interactive video psychiatric consultations. MAIN OUTCOMES AND MEASURES: The primary outcome was PTSD severity as measured by the Posttraumatic Diagnostic Scale. Process-of-care outcomes included medication prescribing and regimen adherence and initiation of and adherence to cognitive processing therapy. RESULTS: During the 12-month follow-up period, 73 of the 133 patients randomized to TOP (54.9%) received cognitive processing therapy compared with 16 of 132 randomized to UC (12.1%) (odds ratio, 18.08 [95% CI, 7.96-41.06]; P < .001). Patients in the TOP arm had significantly larger decreases in Posttraumatic Diagnostic Scale scores (from 35.0 to 29.1) compared with those in the UC arm (from 33.5 to 32.1) at 6 months (β = -3.81; P = .002). Patients in the TOP arm also had significantly larger decreases in Posttraumatic Diagnostic Scale scores (from 35.0 to 30.1) compared with those in the UC arm (from 33.5 to 31.7) at 12 months (β = -2.49; P=.04). There were no significant group differences in the number of PTSD medications prescribed and adherence to medication regimens were not significant. Attendance at 8 or more sessions of cognitive processing therapy significantly predicted improvement in Posttraumatic Diagnostic Scale scores (β = -3.86 [95% CI, -7.19 to -0.54]; P = .02) and fully mediated the intervention effect at 12 months. CONCLUSIONS AND RELEVANCE: Telemedicine-based collaborative care can successfully engage rural veterans in evidence-based psychotherapy to improve PTSD outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00821678.

JAMA Psychiatry · randomised controlled trial · 277 citationsread the source →

An exercise and education program improves well-being of new mothers: a randomized controlled trial.

Objective: The purpose of this study was to evaluate the effect of a physical therapy exercise and health care education program on the psychological well-being of new mothers. Design: This was a randomized controlled trial. Participants: Primiparous and multiparous English-speaking women ready for discharge from The Angliss Hospital postnatal ward were eligible for this study. Women who were receiving psychiatric care were excluded. One hundred sixty-one women were randomized into the trial. Intervention: The experimental group (n=62) received an 8-week "Mother and Baby" (M&B) program, including specialized exercise provided by a women's health physical therapist combined with parenting education. The other group (education only [EO], n=73) received only the same educational material as the experimental group. Main outcome measures: Psychological well-being (Positive Affect Balance Scale), depressive symptoms (Edinburgh Postnatal Depression Scale), and physical activity levels were assessed at baseline, after 8 weeks (post-program), and then 4 weeks later. Results: There was significant improvement in well-being scores and depressive symptoms of the M&B group compared with the EO group over the study period. More specifically, there was a significant positive effect on well-being scores and depressive symptoms at 8 weeks, and this effect was maintained 4 weeks after completion of the program. The number of women identified as "at risk" for postnatal depression pre-intervention was reduced by 50% by the end of the intervention. Limitations: Although this study provides promising short-term (4-week) outcomes, further work is needed to explore whether the intervention effects are maintained as sustained psychological and behavioral benefits at 6 months. Conclusions: A physical therapy exercise and health education program is effective in improving postnatal well-being. Routine use of this program may reduce longer-term problems such as postnatal depression.

Physical therapy · randomised controlled trial · 80 citationsread the source →

Development and Validation of a Smartphone-Based Visual Acuity Test (Peek Acuity) for Clinical Practice and Community-Based Fieldwork.

Importance: Visual acuity is the most frequently performed measure of visual function in clinical practice and most people worldwide living with visual impairment are living in low- and middle-income countries. Objective: To design and validate a smartphone-based visual acuity test that is not dependent on familiarity with symbols or letters commonly used in the English language. Design, setting, and participants: Validation study conducted from December 11, 2013, to March 4, 2014, comparing results from smartphone-based Peek Acuity to Snellen acuity (clinical normal) charts and the Early Treatment Diabetic Retinopathy Study (ETDRS) logMAR chart (reference standard). This study was nested within the 6-year follow-up of the Nakuru Eye Disease Cohort in central Kenya and included 300 adults aged 55 years and older recruited consecutively. Main outcomes and measures: Outcome measures were monocular logMAR visual acuity scores for each test: ETDRS chart logMAR, Snellen acuity, and Peek Acuity. Peek Acuity was compared, in terms of test-retest variability and measurement time, with the Snellen acuity and ETDRS logMAR charts in participants' homes and temporary clinic settings in rural Kenya in 2013 and 2014. Results: The 95% CI limits for test-retest variability of smartphone acuity data were ±0.033 logMAR. The mean differences between the smartphone-based test and the ETDRS chart and the smartphone-based test and Snellen acuity data were 0.07 (95% CI, 0.05-0.09) and 0.08 (95% CI, 0.06-0.10) logMAR, respectively, indicating that smartphone-based test acuities agreed well with those of the ETDRS and Snellen charts. The agreement of Peek Acuity and the ETDRS chart was greater than the Snellen chart with the ETDRS chart (95% CI, 0.05-0.10; P = .08). The local Kenyan community health care workers readily accepted the Peek Acuity smartphone test; it required minimal training and took no longer than the Snellen test (77 seconds vs 82 seconds; 95% CI, 71-84 seconds vs 73-91 seconds, respectively; P = .13). Conclusions and relevance: The study demonstrated that the Peek Acuity smartphone test is capable of accurate and repeatable acuity measurements consistent with published data on the test-retest variability of acuities measured using 5-letter-per-line retroilluminated logMAR charts.

JAMA ophthalmology · cohort or longitudinal · 251 citationsread the source →

Mental Health Outcomes in Transgender and Nonbinary Youths Receiving Gender-Affirming Care.

Importance: Transgender and nonbinary (TNB) youths are disproportionately burdened by poor mental health outcomes owing to decreased social support and increased stigma and discrimination. Although gender-affirming care is associated with decreased long-term adverse mental health outcomes among these youths, less is known about its association with mental health immediately after initiation of care. Objective: To investigate changes in mental health over the first year of receiving gender-affirming care and whether initiation of puberty blockers (PBs) and gender-affirming hormones (GAHs) was associated with changes in depression, anxiety, and suicidality. Design, setting, and participants: This prospective observational cohort study was conducted at an urban multidisciplinary gender clinic among TNB adolescents and young adults seeking gender-affirming care from August 2017 to June 2018. Data were analyzed from August 2020 through November 2021. Exposures: Time since enrollment and receipt of PBs or GAHs. Main outcomes and measures: Mental health outcomes of interest were assessed via the Patient Health Questionnaire 9-item (PHQ-9) and Generalized Anxiety Disorder 7-item (GAD-7) scales, which were dichotomized into measures of moderate or severe depression and anxiety (ie, scores ≥10), respectively. Any self-report of self-harm or suicidal thoughts over the previous 2 weeks was assessed using PHQ-9 question 9. Generalized estimating equations were used to assess change from baseline in each outcome at 3, 6, and 12 months of follow-up. Bivariate and multivariable logistic models were estimated to examine temporal trends and investigate associations between receipt of PBs or GAHs and each outcome. Results: Among 104 youths aged 13 to 20 years (mean [SD] age, 15.8 [1.6] years) who participated in the study, there were 63 transmasculine individuals (60.6%), 27 transfeminine individuals (26.0%), 10 nonbinary or gender fluid individuals (9.6%), and 4 youths who responded "I don't know" or did not respond to the gender identity question (3.8%). At baseline, 59 individuals (56.7%) had moderate to severe depression, 52 individuals (50.0%) had moderate to severe anxiety, and 45 individuals (43.3%) reported self-harm or suicidal thoughts. By the end of the study, 69 youths (66.3%) had received PBs, GAHs, or both interventions, while 35 youths had not received either intervention (33.7%). After adjustment for temporal trends and potential confounders, we observed 60% lower odds of depression (adjusted odds ratio [aOR], 0.40; 95% CI, 0.17-0.95) and 73% lower odds of suicidality (aOR, 0.27; 95% CI, 0.11-0.65) among youths who had initiated PBs or GAHs compared with youths who had not. There was no association between PBs or GAHs and anxiety (aOR, 1.01; 95% CI, 0.41, 2.51). Conclusions and relevance: This study found that gender-affirming medical interventions were associated with lower odds of depression and suicidality over 12 months. These data add to existing evidence suggesting that gender-affirming care may be associated with improved well-being among TNB youths over a short period, which is important given mental health disparities experienced by this population, particularly the high levels of self-harm and suicide.

JAMA network open · cohort or longitudinal · 346 citationsread the source →

Effectiveness and safety of vagus nerve stimulation for severe treatment-resistant major depression in clinical practice after FDA approval: outcomes at 1 year.

Objective: To describe the outcomes of a consecutive series of depressed patients treated with vagus nerve stimulation (VNS) following US Food and Drug Administration (FDA) approval of this intervention. Method: We implanted a VNS device in 15 consecutive outpatients with treatment-resistant major depressive episodes, including 10 with major depressive disorder and 5 with bipolar disorder (DSM-IV criteria), between November 2005 and August 2006. Existing antidepressant treatment remained fixed as far as clinically possible. The primary outcome was change from baseline in the Beck Depression Inventory (BDI) score. Outcomes were assessed at 6 and 12 months postimplant and compared to those of the VNS pivotal efficacy trial that led to FDA approval of VNS. Results: The BDI score decreased significantly compared to baseline at 6 months (P < .05) and 12 months (P < .01), from a mean of 37.8 (SD = 7.8) before VNS activation to a mean of 24.6 (SD = 11.4) at 12 months. By 1 year, 28.6% (n = 4) of the sample responded to VNS and 7.1% (n = 1) remitted according to the BDI. Secondary outcomes on the Hamilton Depression Rating Scale 24-Item showed similar improvement at 1 year, with a 43% response rate (n = 6) and 14.3% remission rate (n = 2). No obvious predictors of response were detected. Side effects of VNS included hoarseness (73%), dyspnea (47%), nausea (40%), pain (33%), and anxiety (20%); no patient terminated treatment due to intolerable side effects. Conclusions: We found that a substantial minority of patients with extremely difficult-to-treat depressive disorders benefited from VNS in an ambulatory clinical practice, with outcomes comparable to those observed in previous VNS efficacy studies and with a similar side effect profile.

The Journal of clinical psychiatry · clinical trial · 93 citationsread the source →

Effects of 12-month tadalafil therapy for erectile dysfunction on couple relationships: results from the DETECT study.

Introduction: Erectile dysfunction (ED) is distressing and can affect a couple's relationship. Aim: To investigate partner awareness of ED, relationship problems, and the effects of tadalafil treatment over 12 months. Methods: The Determinants of Continued Use of Tadalafil study is a prospective 12-month European observational study in patients with ED initiating or changing treatment to on-demand tadalafil. A total of 1,900 patients were enrolled in eight countries. Assessments were made on predefined treatment outcomes in a routine clinical setting. Main outcome measures: At baseline, 1, 6, and 12 months, patients were asked about relationship problems (unspecified), partner awareness and support of consultation, and partner sexual problems. Data were analyzed for patients continuing tadalafil at 12 months. Results: At baseline, 96% of patients had a partner, 80% of partners supported an ED consult, and 73% were aware of the consultation. Relationship problems were reported by 17% of patients at baseline. At 12 months, 84% of patients were still taking tadalafil. Of these, 19% reported relationship problems at baseline. After 12 months of treatment with tadalafil, 4% of patients still reported perceived problems. Factors associated with no relationship problems at 12 months were: at baseline, no previous ED treatment, partner in poor health; and at 12 months a lower ED severity. If the partner was felt to have a sexual problem at 12 months, relationship improvement was less likely. Further, 3% of patients developed relationship problems during treatment. Factors associated with developing a relationship problem were: a history of pelvic surgery at baseline, a different partner at 12 months than at baseline, and a partner with a sexual problem at 12 months. Conclusions: Improvement of ED with tadalafil was associated with reduced relationship problems, suggesting that problems were associated with ED and resolved with treatment.

The journal of sexual medicine · clinical trial · 4 citationsread the source →

The Efficacy of Emotionally Focused Couples Therapy and Behavioral Couples Therapy: A Meta‐Analysis

RCT-only: g=.73 post, g=.66 at 6 months; no significant difference from BCT.

Journal of Marital and Family Therapyread the source →