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Identifying and Categorizing Adverse Events in Trials of Digital Mental Health Interventions: Narrative Scoping Review of Trials in the International Standard Randomized Controlled Trial Number Registry.

Background: To contextualize the benefits of an intervention, it is important that adverse events (AEs) are reported. This is potentially difficult in trials of digital mental health interventions, where delivery may be remote and the mechanisms of actions less understood. Objective: We aimed to explore the reporting of AEs in randomized controlled trials of digital mental health interventions. Methods: The International Standard Randomized Controlled Trial Number database was searched for trials registered before May 2022. Using advanced search filters, we identified 2546 trials in the category of mental and behavioral disorders. These trials were independently reviewed by 2 researchers against the eligibility criteria. Trials were included where digital mental health interventions for participants with a mental health disorder were evaluated through a completed randomized controlled trial (protocol and primary results publication published). Published protocols and primary results publications were then retrieved. Data were extracted independently by 3 researchers, with discussion to reach consensus when required. Results: Twenty-three trials met the eligibility criteria, of which 16 (69%) included a statement on AEs within a publication, but only 6 (26%) reported AEs within their primary results publication. Seriousness was referred to by 6 trials, relatedness by 4, and expectedness by 2. More interventions delivered with human support (9/11, 82%) than those with only remote or no support (6/12, 50%) included a statement on AEs, but they did not report more AEs. Several reasons for participant dropout were identified by trials that did not report AEs, of which some were identifiable or related to AEs, including serious AEs. Conclusions: There is significant variation in the reporting of AEs in trials of digital mental health interventions. This variation may reflect limited reporting processes and difficulty recognizing AEs related to digital mental health interventions. There is a need to develop guidelines specifically for these trials to improve future reporting.

JMIR mental health · review · 25 citationsread the source →

Lifestyle behaviour change for preventing the progression of chronic kidney disease: a systematic review.

Objectives: Modifying lifestyle can prevent the progression of chronic kidney disease (CKD) but the specific elements which lead to favourable behaviour change are not well understood. We aimed to identify and evaluate behaviour change techniques and functions in lifestyle interventions for preventing the progression of CKD. Design: Systematic review. Data sources: MEDLINE, EMBASE, CINAHL and PsycINFO. Eligibility criteria: Trials of lifestyle behaviour change interventions (including diet, physical activity, smoking and/or alcohol) published to September 2018 in adults with CKD stages 1-5. Data extraction and synthesis: Trial characteristics including population, sample size, study setting, intervention, comparator, outcomes and study duration, were extracted. Study quality was independently assessed by two reviewers using the Cochrane risk of bias tool. The Behaviour Change Technique Taxonomy v1 was used to identify behaviour change techniques (eg, goal setting) and the Health Behaviour Change Wheel was used to identify intervention functions (eg, education). Both were independently assessed by three reviewers. Results: In total, 26 studies involving 4263 participants were included. Risk of bias was high or unclear in most studies. Interventions involved diet (11), physical activity (8) or general lifestyle (7). Education was the most frequently used function (21 interventions), followed by enablement (18), training (12), persuasion (4), environmental restructuring (4), modelling (2) and incentivisation (2). The most common behaviour change techniques were behavioural instruction (23 interventions), social support (16), behavioural demonstration (13), feedback on behaviour (12) and behavioural practice/rehearsal (12). Eighteen studies (69%) showed a significant improvement in at least one primary outcome, all of which included education, persuasion, modelling and incentivisation. Conclusion: Lifestyle behaviour change interventions for CKD patients frequently used education, goal setting, feedback, monitoring and social support. The most promising interventions included education and used a variety of intervention functions (persuasion, modelling and incentivisation). Prospero registration number: CRD42019106053.

BMJ open · systematic review · 52 citationsread the source →

Cognitive behavioural therapy for adherence and depression in patients with HIV: a three-arm randomised controlled trial.

Background: Depression is highly prevalent in people with HIV and has consistently been associated with poor antiretroviral therapy (ART) adherence. Integrating cognitive behavioural therapy (CBT) for depression with adherence counselling using the Life-Steps approach (CBT-AD) has an emerging evidence base. The aim of this study was to test the efficacy of CBT-AD. Methods: In this three-arm randomised controlled trial in HIV-positive adults with depression, we compared CBT-AD with information and supportive psychotherapy plus adherence counselling using the Life-Steps approach (ISP-AD), and with enhanced treatment as usual (ETAU) including Life-Steps adherence counselling only. Participants were recruited from three sites in New England, USA (two hospital settings and one community health centre). Patients were randomly assigned (2:2:1) to receive CBT-AD (one Life-Steps session plus 11 weekly integrated sessions lasting up to 1 h each), ISP-AD (one Life-Steps session plus 11 weekly integrated sessions lasting up to 1 h each), or ETAU (one Life-Steps session and five assessment visits roughly every 2 weeks), randomisation was done with allocation software, in pairs, and stratified by three variables: study site, whether or not participants had been prescribed antidepressant medication, and whether or not participants had a history of injection drug use. The primary outcome was ART adherence at the end of treatment (4 month assessment) assessed via electronic pill caps (Medication Event Monitoring System [MEMS]) with correction for pocketed doses, analysed by intention to treat. Findings: Patients were recruited from Feb 26, 2009, to June 21, 2012. Patients who were assigned to CBT-AD (94 randomly assigned, 83 completed assessment) had greater improvements in adherence (estimated difference 1·00 percentage point per visit, 95% CI 0·34 to 1·66, p=0·003) and depression (Center for Epidemiological Studies depression [CESD] score estimated difference -0·41, -0·66 to -0·16, p=0·001; Montgomery-Asberg depression rating scale [MADRS] score -4·69, -8·09 to -1·28, p=0·007; clinical global impression [CGI] score -0·66, -1·11 to -0·21, p=0·005) than did patients who had ETAU (49 assigned, 46 completed assessment) after treatment (4 months). No significant differences in adherence were noted between CBT-AD and ISP-AD (97 assigned, 87 completed assessment). No study-related adverse events were reported. Interpretation: Integrating evidenced-based treatment for depression with evidenced-based adherence counselling is helpful for individuals living with HIV/AIDS and depression. Future efforts should examine how to best disseminate effective psychosocial depression treatments such as CBT-AD to people living with HIV/AIDS and examine the cost-effectiveness of such approaches. Funding: National Institute of Mental Health, National Institute of Allergy and Infectious Diseases.

The lancet. HIV · randomised controlled trial · 114 citationsread the source →

Interventions for the treatment of metastatic extradural spinal cord compression in adults.

Background: Metastatic extradural spinal cord compression (MESCC) is treated with radiotherapy, corticosteroids, and surgery, but there is uncertainty regarding their comparative effects. This is an updated version of the original Cochrane review published in theCochrane Database of Systematic Reviews (Issue 4, 2008). Objectives: To determine the efficacy and safety of radiotherapy, surgery and corticosteroids in MESCC. Search methods: In March 2015, we updated previous searches (July 2008 and December 2013) of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, LILACS, CANCERLIT, clinical trials registries, conference proceedings, and references, without language restrictions. We also contacted experts for relevant published, unpublished and ongoing trials. Selection criteria: Randomised controlled trials (RCTs) of radiotherapy, surgery and corticosteroids in adults with MESCC. Data collection and analysis: Three authors independently screened and selected trials, assessed risk of bias, and extracted data. We sought clarifications from trial authors. Where possible, we pooled relative risks with their 95% confidence intervals, using a random effects model if heterogeneity was significant. We assessed overall evidence-quality using the GRADE approach. Main results: This update includes seven trials involving 876 (723 evaluable) adult participants (19 to 87 years) in high-income countries. Most were free of the risk of bias. Different radiotherapy doses and schedulesTwo equivalence trials in people with MESCC and a poor prognosis evaluated different radiotherapy doses and schedules. In one, a single dose (8 Gray (Gy)) of radiotherapy (RT) was as effective as short-course RT (16 Gy in two fractions over one week) in enhancing ambulation in the short term (65% versus 69%; risk ratio (RR) was 0.93, (95% confidence interval (CI) 0.82 to 1.04); 303 participants; moderate quality evidence). The regimens were also equally effective in reducing analgesic and narcotic use (34% versus 40%; RR 0.85, 95% CI 0.62 to 1.16; 271 participants), and in maintaining urinary continence (90% versus 87%; RR 1.03, 95% CI 0.96 to 1.1; 303 participants) in the short term (moderate quality evidence). In the other trial, split-course RT (30 Gy in eight fractions over two weeks) was no different from short-course RT in enhancing ambulation (70% versus 68%; RR 1.02, 95% CI 0.9 to 1.15; 276 participants); reducing analgesic and narcotic use (49% versus 38%; RR 1.27, 95% CI 0.96 to 1.67; 262 participants); and in maintaining urinary continence (87% versus 90%; RR 0.97, 0.93 to 1.02; 275 participants) in the short term (moderate quality evidence). Median survival was similar with the three RT regimens (four months). Local tumour recurrence may be more common with single-dose compared to short-course RT (6% versus 3%; RR 2.21, 95% CI 0.69 to 7.01; 303 participants) and with short-course compared to split-course RT (4% versus 0%; RR 0.1, 95% CI 0.01 to 1.72; 276 participants), but these differences were not statistically significant (low quality evidence). Gastrointestinal adverse effects were infrequent with the three RT regimens (moderate quality evidence), and serious adverse events or post-radiotherapy myelopathy were not noted. We did not find trials comparing radiotherapy schedules in people with MESCC and a good prognosis. Surgery plus radiotherapy compared to radiotherapyLaminectomy plus RT offered no advantage over RT in one small trial with 29 participants (very low quality evidence). In another trial that was stopped early for apparent benefit, decompressive surgery plus RT resulted in better ambulatory rates (84% versus 57%; RR 1.48, 95% CI 1.16 to 1.90; 101 participants, low quality evidence). Narcotic use may also be lower, and bladder control may also be maintained longer than with than RT in selected patients (low quality evidence). Median survival was longer after surgery (126 days versus 100 days), but the proportions surviving at one month (94% versus 86%; RR 1.09, 95% CI 0.96 to 1.24; 101 participants) did not differ significantly (low quality evidence). Serious adverse events were not noted. Significant benefits with surgery occurred only in people younger than 65 years. High dose corticosteroids compared to moderate dose or no corticosteroidsData from three small trials suggest that high-dose steroids may not differ from moderate-dose or no corticosteroids in enhancing ambulation (60% versus 55%; RR 1.08, 95% CI 0.81 to 1.45; 3 RCTs, 105 participants); survival over two years (11% versus 10%; RR 1.11, 95% CI 0.24 to 5.05; 1 RCT, 57 participants); pain reduction (78% versus 91%; RR 0.86, 95% CI 0.62 to 1.20; 1 RCT, 25 participants); or urinary continence (63% versus 53%; RR 1.18, 95% CI 0.66 to 2.13; 1 RCT, 34 participants; low quality evidence). Serious adverse effects were more frequent with high-dose corticosteroids (17% versus 0%; RR 8.02, 95% CI 1.03 to 62.37; 2 RCTs, 77 participants; moderate quality evidence).None of the trials reported satisfaction with care or quality of life in participants. Authors' conclusions: Based on current evidence, ambulant adults with MESCC with stable spines and predicted survival of less than six months will probably benefit as much from one dose of radiation (8 Gy) as from two doses (16 Gy) or eight doses (30 Gy). We are unsure if a single dose is as effective as two or more doses in preventing local tumour recurrence. Laminectomy preceding radiotherapy may offer no benefits over radiotherapy alone. Decompressive surgery followed by radiotherapy may benefit ambulant and non-ambulant adults younger than 65 years of age, with poor prognostic factors for radiotherapy, a single area of compression, paraplegia for less than 48 hours, and a predicted survival of more than six months. We are uncertain whether high doses of corticosteroids offer any benefits over moderate doses or indeed no corticosteroids; but high-dose steroids probably significantly increases the risk of serious adverse effects. Early detection; and treatment based on neurological status, age and estimated survival, are crucial with all treatment modalities. Most of the evidence was of low quality. High-quality evidence from more trials is needed to clarify current uncertainties, and some studies are in progress.

The Cochrane database of systematic reviews · meta-analysis · 39 citationsread the source →

Physical activity interventions for disease-related physical and mental health during and following treatment in people with non-advanced colorectal cancer.

Background: Colorectal cancer is the third most commonly diagnosed cancer worldwide. A diagnosis of colorectal cancer and subsequent treatment can adversely affect an individuals physical and mental health. Benefits of physical activity interventions in alleviating treatment side effects have been demonstrated in other cancer populations. Given that regular physical activity can decrease the risk of colorectal cancer, and cardiovascular fitness is a strong predictor of all-cause and cancer mortality risk, physical activity interventions may have a role to play in the colorectal cancer control continuum. Evidence of the efficacy of physical activity interventions in this population remains unclear. Objectives: To assess the effectiveness and safety of physical activity interventions on the disease-related physical and mental health of individuals diagnosed with non-advanced colorectal cancer, staged as T1-4 N0-2 M0, treated surgically or with neoadjuvant or adjuvant therapy (i.e. chemotherapy, radiotherapy or chemoradiotherapy), or both. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 6), along with OVID MEDLINE, six other databases and four trial registries with no language or date restrictions. We screened reference lists of relevant publications and handsearched meeting abstracts and conference proceedings of relevant organisations for additional relevant studies. All searches were completed between 6 June and 14 June 2019. Selection criteria: We included randomised control trials (RCTs) and cluster-RCTs comparing physical activity interventions, to usual care or no physical activity intervention in adults with non-advanced colorectal cancer. Data collection and analysis: Two review authors independently selected studies, performed the data extraction, assessed the risk of bias and rated the quality of the studies using GRADE criteria. We pooled data for meta-analyses by length of follow-up, reported as mean differences (MDs) or standardised mean differences (SMDs) using random-effects wherever possible, or the fixed-effect model, where appropriate. If a meta-analysis was not possible, we synthesised studies narratively. Main results: We identified 16 RCTs, involving 992 participants; 524 were allocated to a physical activity intervention group and 468 to a usual care control group. The mean age of participants ranged between 51 and 69 years. Ten studies included participants who had finished active treatment, two studies included participants who were receiving active treatment, two studies included both those receiving and finished active treatment. It was unclear whether participants were receiving or finished treatment in two studies. Type, setting and duration of physical activity intervention varied between trials. Three studies opted for supervised interventions, five for home-based self-directed interventions and seven studies opted for a combination of supervised and self-directed programmes. One study did not report the intervention setting. The most common intervention duration was 12 weeks (7 studies). Type of physical activity included walking, cycling, resistance exercise, yoga and core stabilisation exercise. Most of the uncertainty in judging study bias came from a lack of clarity around allocation concealment and blinding of outcome assessors. Blinding of participants and personnel was not possible. The quality of the evidence ranged from very low to moderate overall. We did not pool physical function results at immediate-term follow-up due to considerable variation in results and inconsistency of direction of effect. We are uncertain whether physical activity interventions improve physical function compared with usual care. We found no evidence of effect of physical activity interventions compared to usual care on disease-related mental health (anxiety: SMD -0.11, 95% confidence interval (CI) -0.40 to 0.18; 4 studies, 198 participants; I2 = 0%; and depression: SMD -0.21, 95% CI -0.50 to 0.08; 4 studies, 198 participants; I2 = 0%; moderate-quality evidence) at short- or medium-term follow-up. Seven studies reported on adverse events. We did not pool adverse events due to inconsistency in reporting and measurement. We found no evidence of serious adverse events in the intervention or usual care groups. Minor adverse events, such as neck, back and muscle pain were most commonly reported. No studies reported on overall survival or recurrence-free survival and no studies assessed outcomes at long-term follow-up We found evidence of positive effects of physical activity interventions on the aerobic fitness component of physical fitness (SMD 0.82, 95% CI 0.34 to 1.29; 7 studies, 295; I2 = 68%; low-quality evidence), cancer-related fatigue (MD 2.16, 95% CI 0.18 to 4.15; 6 studies, 230 participants; I2 = 18%; low-quality evidence) and health-related quality of life (SMD 0.36, 95% CI 0.10 to 0.62; 6 studies, 230 participants; I2 = 0%; moderate-quality evidence) at immediate-term follow-up. These positive effects were also observed at short-term follow-up but not medium-term follow-up. Only three studies reported medium-term follow-up for cancer-related fatigue and health-related quality of life. Authors' conclusions: The findings of this review should be interpreted with caution due to the low number of studies included and the quality of the evidence. We are uncertain whether physical activity interventions improve physical function. Physical activity interventions may have no effect on disease-related mental health. Physical activity interventions may be beneficial for aerobic fitness, cancer-related fatigue and health-related quality of life up to six months follow-up. Where reported, adverse events were generally minor. Adequately powered RCTs of high methodological quality with longer-term follow-up are required to assess the effect of physical activity interventions on the disease-related physical and mental health and on survival of people with non-advanced colorectal cancer. Adverse events should be adequately reported.

The Cochrane database of systematic reviews · meta-analysis · 53 citationsread the source →

Self-management interventions including action plans for exacerbations versus usual care in patients with chronic obstructive pulmonary disease.

Background: Chronic Obstructive Pulmonary Disease (COPD) self-management interventions should be structured but personalised and often multi-component, with goals of motivating, engaging and supporting the patients to positively adapt their behaviour(s) and develop skills to better manage disease. Exacerbation action plans are considered to be a key component of COPD self-management interventions. Studies assessing these interventions show contradictory results. In this Cochrane Review, we compared the effectiveness of COPD self-management interventions that include action plans for acute exacerbations of COPD (AECOPD) with usual care. Objectives: To evaluate the efficacy of COPD-specific self-management interventions that include an action plan for exacerbations of COPD compared with usual care in terms of health-related quality of life, respiratory-related hospital admissions and other health outcomes. Search methods: We searched the Cochrane Airways Group Specialised Register of trials, trials registries, and the reference lists of included studies to May 2016. Selection criteria: We included randomised controlled trials evaluating a self-management intervention for people with COPD published since 1995. To be eligible for inclusion, the self-management intervention included a written action plan for AECOPD and an iterative process between participant and healthcare provider(s) in which feedback was provided. We excluded disease management programmes classified as pulmonary rehabilitation or exercise classes offered in a hospital, at a rehabilitation centre, or in a community-based setting to avoid overlap with pulmonary rehabilitation as much as possible. Data collection and analysis: Two review authors independently assessed trial quality and extracted data. We resolved disagreements by reaching consensus or by involving a third review author. Study authors were contacted to obtain additional information and missing outcome data where possible. When appropriate, study results were pooled using a random-effects modelling meta-analysis. The primary outcomes of the review were health-related quality of life (HRQoL) and number of respiratory-related hospital admissions. Main results: We included 22 studies that involved 3,854 participants with COPD. The studies compared the effectiveness of COPD self-management interventions that included an action plan for AECOPD with usual care. The follow-up time ranged from two to 24 months and the content of the interventions was diverse. Over 12 months, there was a statistically significant beneficial effect of self-management interventions with action plans on HRQoL, as measured by the St. George's Respiratory Questionnaire (SGRQ) total score, where a lower score represents better HRQoL. We found a mean difference from usual care of -2.69 points (95% CI -4.49 to -0.90; 1,582 participants; 10 studies; high-quality evidence). Intervention participants were at a statistically significant lower risk for at least one respiratory-related hospital admission compared with participants who received usual care (OR 0.69, 95% CI 0.51 to 0.94; 3,157 participants; 14 studies; moderate-quality evidence). The number needed to treat to prevent one respiratory-related hospital admission over one year was 12 (95% CI 7 to 69) for participants with high baseline risk and 17 (95% CI 11 to 93) for participants with low baseline risk (based on the seven studies with the highest and lowest baseline risk respectively).There was no statistically significant difference in the probability of at least one all-cause hospital admission in the self-management intervention group compared to the usual care group (OR 0.74, 95% CI 0.54 to 1.03; 2467 participants; 14 studies; moderate-quality evidence). Furthermore, we observed no statistically significant difference in the number of all-cause hospitalisation days, emergency department visits, General Practitioner visits, and dyspnoea scores as measured by the (modified) Medical Research Council questionnaire for self-management intervention participants compared to usual care participants. There was no statistically significant effect observed from self-management on the number of COPD exacerbations and no difference in all-cause mortality observed (RD 0.0019, 95% CI -0.0225 to 0.0263; 3296 participants; 16 studies; moderate-quality evidence). Exploratory analysis showed a very small, but significantly higher respiratory-related mortality rate in the self-management intervention group compared to the usual care group (RD 0.028, 95% CI 0.0049 to 0.0511; 1219 participants; 7 studies; very low-quality evidence).Subgroup analyses showed significant improvements in HRQoL in self-management interventions with a smoking cessation programme (MD -4.98, 95% CI -7.17 to -2.78) compared to studies without a smoking cessation programme (MD -1.33, 95% CI -2.94 to 0.27, test for subgroup differences: Chi² = 6.89, df = 1, P = 0.009, I² = 85.5%). The number of behavioural change techniques clusters integrated in the self-management intervention, the duration of the intervention and adaptation of maintenance medication as part of the action plan did not affect HRQoL. Subgroup analyses did not detect any potential variables to explain differences in respiratory-related hospital admissions among studies. Authors' conclusions: Self-management interventions that include a COPD exacerbation action plan are associated with improvements in HRQoL, as measured with the SGRQ, and lower probability of respiratory-related hospital admissions. No excess all-cause mortality risk was observed, but exploratory analysis showed a small, but significantly higher respiratory-related mortality rate for self-management compared to usual care. For future studies, we would like to urge only using action plans together with self-management interventions that meet the requirements of the most recent COPD self-management intervention definition. To increase transparency, future study authors should provide more detailed information regarding interventions provided. This would help inform further subgroup analyses and increase the ability to provide stronger recommendations regarding effective self-management interventions that include action plans for AECOPD. For safety reasons, COPD self-management action plans should take into account comorbidities when used in the wider population of people with COPD who have comorbidities. Although we were unable to evaluate this strategy in this review, it can be expected to further increase the safety of self-management interventions. We also advise to involve Data and Safety Monitoring Boards for future COPD self-management studies.

The Cochrane database of systematic reviews · meta-analysis · 187 citationsread the source →

Increased hippocampal noradrenaline is a biomarker for efficacy of vagus nerve stimulation in a limbic seizure model.

Vagus nerve stimulation (VNS) is an effective adjunctive treatment for medically refractory epilepsy. In this study, we measured VNS-induced changes in hippocampal neurotransmitter levels and determined their potential involvement in the anticonvulsive action of VNS, to elucidate the mechanism of action responsible for the seizure suppressing effect of VNS in an animal model for limbic seizures. We used in vivo intracerebral microdialysis to measure VNS-induced changes in hippocampal extracellular concentrations of noradrenaline, dopamine, serotonin and GABA in freely moving, male Wistar rats. During the same experiment, the effect of VNS on pilocarpine-induced limbic seizures was assessed using video-EEG monitoring. The involvement of VNS-induced increases in hippocampal noradrenaline in the mechanims of action of VNS was evaluated by blocking hippocampal α(2)-receptors. VNS produced a significant increase in hippocampal noradrenaline concentration (69 ± 16% above baseline levels). VNS also increased the latency between pilocarpine infusion and the onset of epileptiform discharges, and reduced the duration and severity of pilocarpine-induced limbic seizures. A strong positive correlation was found between the noradrenergic and anticonvulsive effects of VNS. Blockade of hippocampal α(2 -receptors reversed the seizure-suppressing effect of VNS. VNS induces increases in extracellular hippocampal noradrenaline, which are at least partly responsible for its seizure-suppressing effect in a model for limbic seizures, and constitute a potential biomarker for the efficacy of VNS in temporal lobe epilepsy.

Journal of neurochemistry · 189 citationsread the source →

Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis.

Background: Generalised anxiety disorder is a disease that can be associated with substantial dysfunction. Pharmacological treatment is often the first choice for clinicians because of the cost and resource constraints of psychological alternatives, but there is a paucity of comparative information for the multiple available drug choices. Methods: A systematic review and network meta-analysis was performed on randomised trials in adult outpatients with generalised anxiety disorder identified from MEDLINE, Web of Science, Cochrane Library, ClinicalTrials.gov, Chinese National Knowledge Infrastructure (CNKI), Wanfang data, Drugs@FDA and commercial pharmaceutical registries. Placebo and active control trials were included. Data were extracted from all manuscripts and reports. Primary outcomes were efficacy (mean difference [MD] in change in Hamilton Anxiety Scale Score) and acceptability (study discontinuations for any cause). We estimated summary mean treatment differences and odds ratios using network meta-analyses with random effects. This study is registered with PROSPERO, number CRD42018087106. Findings: Studies were published between Jan 1, 1994 and Aug 1, 2017, in which 1992 potential studies were screened for inclusion. This analysis is based on 89 trials, which included 25 441 patients randomly assigned to 22 different active drugs or placebo. Duloxetine (MD -3·13, 95% credible interval [CrI] -4·13 to -2·13), pregabalin (MD -2·79, 95% CrI -3·69 to -1·91), venlafaxine (MD -2·69, 95% CrI -3·50 to -1·89), and escitalopram (MD -2·45, 95% CrI -3·27 to -1·63) were more efficacious than placebo with relatively good acceptability. Mirtazapine, sertraline, fluoxetine, buspirone, and agomelatine were also found to be efficacious and well tolerated but these findings were limited by small sample sizes. Quetiapine (MD -3·60 95% CrI -4·83 to -2·39) had the largest effect on HAM-A but it was poorly tolerated (odds ratio 1·44, 95% CrI 1·16-1·80) when compared with placebo. Likewise, paroxetine and benzodiazepines were effective but also poorly tolerated when compared with placebo. Risk of reporting bias was considered low, and when possible all completed studies were included to avoid publication bias. Interpretation: To our knowledge, this is the largest contemporary review of pharmacological agents for the treatment of generalised anxiety disorder by use of network analysis. There are several effective treatment choices for generalised anxiety disorder across classes of medication. The failure of initial pharmacological therapy might not be a reason to abandon a pharmacological treatment strategy. Funding: No funding was received for this research.

Lancet (London, England) · systematic review · 217 citationsread the source →

School Closures During Social Lockdown and Mental Health, Health Behaviors, and Well-being Among Children and Adolescents During the First COVID-19 Wave: A Systematic Review.

Importance: School closures as part of broader social lockdown measures during the COVID-19 pandemic may be associated with the health and well-being of children and adolescents. Objective: To review published reports on the association of school closures during broader social lockdown with mental health, health behaviors, and well-being in children and adolescents aged 0 to 19 years, excluding associations with transmission of infection. Evidence review: Eleven databases were searched from inception to September 2020, and machine learning was applied for screening articles. A total of 16 817 records were screened, 151 were reviewed in full text, and 36 studies were included. Quality assessment was tailored to study type. A narrative synthesis of results was undertaken because data did not allow meta-analysis. Findings: A total of 36 studies from 11 countries were identified, involving a total of 79 781 children and adolescents and 18 028 parents, which occurred during the first wave of the COVID-19 pandemic (February to July 2020). All evaluated school closure as part of broader social lockdown during the first COVID-19 wave, and the duration of school closure ranged from 1 week to 3 months. Of those, 9 (25%) were longitudinal pre-post studies, 5 (14%) were cohort, 21 (58%) were cross-sectional, and 1 (3%) was a modeling study. Thirteen studies (36%) were high quality, 17 (47%) were medium quality, and 6 (17%) were low quality. Twenty-three studies (64%) were published, 8 (22%) were online reports, and 5 (14%) were preprints. Twenty-five studies (69%) concerning mental health identified associations across emotional, behavioral, and restlessness/inattention problems; 18% to 60% of children and adolescents scored above risk thresholds for distress, particularly anxiety and depressive symptoms, and 2 studies reported no significant association with suicide. Three studies reported that child protection referrals were lower than expected number of referrals originating in schools. Three studies suggested higher screen time usage, 2 studies reported greater social media use, and 6 studies reported lower physical activity. Studies on sleep (10 studies) and diet (5 studies) provided inconclusive evidence on harms. Conclusions and relevance: In this narrative synthesis of reports from the first wave of the COVID-19 pandemic, studies of short-term school closures as part of social lockdown measures reported adverse mental health symptoms and health behaviors among children and adolescents. Associations between school closure and health outcomes and behaviors could not be separated from broader lockdown measures.

JAMA pediatrics · systematic review · 426 citationsread the source →

Prevalence of Health Misinformation on Social Media: Systematic Review.

Background: Although at present there is broad agreement among researchers, health professionals, and policy makers on the need to control and combat health misinformation, the magnitude of this problem is still unknown. Consequently, it is fundamental to discover both the most prevalent health topics and the social media platforms from which these topics are initially framed and subsequently disseminated. Objective: This systematic review aimed to identify the main health misinformation topics and their prevalence on different social media platforms, focusing on methodological quality and the diverse solutions that are being implemented to address this public health concern. Methods: We searched PubMed, MEDLINE, Scopus, and Web of Science for articles published in English before March 2019, with a focus on the study of health misinformation in social media. We defined health misinformation as a health-related claim that is based on anecdotal evidence, false, or misleading owing to the lack of existing scientific knowledge. We included (1) articles that focused on health misinformation in social media, including those in which the authors discussed the consequences or purposes of health misinformation and (2) studies that described empirical findings regarding the measurement of health misinformation on these platforms. Results: A total of 69 studies were identified as eligible, and they covered a wide range of health topics and social media platforms. The topics were articulated around the following six principal categories: vaccines (32%), drugs or smoking (22%), noncommunicable diseases (19%), pandemics (10%), eating disorders (9%), and medical treatments (7%). Studies were mainly based on the following five methodological approaches: social network analysis (28%), evaluating content (26%), evaluating quality (24%), content/text analysis (16%), and sentiment analysis (6%). Health misinformation was most prevalent in studies related to smoking products and drugs such as opioids and marijuana. Posts with misinformation reached 87% in some studies. Health misinformation about vaccines was also very common (43%), with the human papilloma virus vaccine being the most affected. Health misinformation related to diets or pro-eating disorder arguments were moderate in comparison to the aforementioned topics (36%). Studies focused on diseases (ie, noncommunicable diseases and pandemics) also reported moderate misinformation rates (40%), especially in the case of cancer. Finally, the lowest levels of health misinformation were related to medical treatments (30%). Conclusions: The prevalence of health misinformation was the highest on Twitter and on issues related to smoking products and drugs. However, misinformation on major public health issues, such as vaccines and diseases, was also high. Our study offers a comprehensive characterization of the dominant health misinformation topics and a comprehensive description of their prevalence on different social media platforms, which can guide future studies and help in the development of evidence-based digital policy action plans.

Journal of medical Internet research · systematic review · 808 citationsread the source →

Effect of Varenicline Combined With Medical Management on Alcohol Use Disorder With Comorbid Cigarette Smoking: A Randomized Clinical Trial.

Importance: Individuals with alcohol use disorder have high rates of cigarette smoking. Varenicline tartrate, an approved treatment for smoking cessation, may reduce both drinking and smoking. Objectives: To test the efficacy of varenicline with medical management for patients with alcohol use disorder and comorbid smoking seeking alcohol treatment, and to evaluate the secondary effects on smoking abstinence. Design, setting, and participants: This phase 2, randomized, double-blind, parallel group, placebo-controlled trial was conducted at 2 outpatient clinics from September 19, 2012, to August 31, 2015. Eligible participants met alcohol-dependence criteria and reported heavy drinking (≥5 drinks for men and ≥4 drinks for women) 2 or more times per week and smoking 2 or more times per week; 131 participants were randomized to either varenicline or placebo stratified by sex and site. All analyses were of the intention-to-treat type. Data analysis was conducted from February 5, 2016, to September 29, 2017. Interventions: Varenicline tartrate, 1 mg twice daily, and matching placebo pills for 16 weeks. Medical management emphasized medication adherence for 4 weeks followed by support for changing drinking. Main outcomes and measures: Percentage of heavy drinking days (PHDD) weeks 9 to 16, no heavy drinking days (NHDD) weeks 9 to 16, and prolonged smoking abstinence weeks 13 to 16. Results: Of 131 participants, 39 (29.8%) were women and 92 (70.2%) were men, the mean (SD) age was 42.7 (11.7) years, and the race/ethnicity self-identified by most respondents was black (69 [52.7%]). Sixty-four participants were randomized to receive varenicline, and 67 to receive placebo. Mean change in PHDD between varenicline and placebo across sex and site was not significantly different. However, a significant treatment by sex by time interaction for PHDD (F1,106 = 4.66; P = .03) revealed that varenicline compared with placebo resulted in a larger decrease in log-transformed PHDD in men (least square [LS] mean difference in change from baseline, 0.54; 95% CI, -0.09 to 1.18; P = .09; Cohen d = 0.45) but a smaller decrease in women (LS mean difference, -0.69; 95% CI, -1.63 to 0.25; P = .15; Cohen d = -0.53). Thirteen of 45 men (29%) had NHDD taking varenicline compared with 3 of 47 men (6%) taking placebo (Cohen h = 0.64; 95% CI, 0.22-1.03), whereas 1 of 19 women (5%) had NHDD compared with 5 of 20 women (25%) taking placebo (Cohen h = -0.60; 95% CI, -1.21 to 0.04). Taking varenicline, 8 of 64 participants (13%) achieved prolonged smoking abstinence; no one (0 of 67) quit smoking taking placebo (P = .003; Cohen h = 0.72; 95% CI, 0.38-1.07). Conclusions and relevance: Varenicline with medical management resulted in decreased heavy drinking among men and increased smoking abstinence in the overall sample. Varenicline could be considered to promote improvements in men with these dual behavioral health risks. Trial registration: clinicaltrials.gov Identifier: NCT01553136.

JAMA psychiatry · randomised controlled trial · 77 citationsread the source →

Financial incentives for smoking cessation in pregnancy: randomised controlled trial.

Objective: To assess the efficacy of a financial incentive added to routine specialist pregnancy stop smoking services versus routine care to help pregnant smokers quit. Design: Phase II therapeutic exploratory single centre, individually randomised controlled parallel group superiority trial. Setting: One large health board area with a materially deprived, inner city population in the west of Scotland, United Kingdom. Participants: 612 self reported pregnant smokers in NHS Greater Glasgow and Clyde who were English speaking, at least 16 years of age, less than 24 weeks pregnant, and had an exhaled carbon monoxide breath test result of 7 ppm or more. 306 women were randomised to incentives and 306 to control. Interventions: The control group received routine care, which was the offer of a face to face appointment to discuss smoking and cessation and, for those who attended and set a quit date, the offer of free nicotine replacement therapy for 10 weeks provided by pharmacy services, and four, weekly support phone calls. The intervention group received routine care plus the offer of up to £400 of shopping vouchers: £50 for attending a face to face appointment and setting a quit date; then another £50 if at four weeks' post-quit date exhaled carbon monoxide confirmed quitting; a further £100 was provided for continued validated abstinence of exhaled carbon monoxide after 12 weeks; a final £200 voucher was provided for validated abstinence of exhaled carbon monoxide at 34-38 weeks' gestation. Main outcome measure: The primary outcome was cotinine verified cessation at 34-38 weeks' gestation through saliva (<14.2 ng/mL) or urine (<44.7 ng/mL). Secondary outcomes included birth weight, engagement, and self reported quit at four weeks. Results: Recruitment was extended from 12 to 15 months to achieve the target sample size. Follow-up continued until September 2013. Of the 306 women randomised, three controls opted out soon after enrolment; these women did not want their data to be used, leaving 306 intervention and 303 control group participants in the intention to treat analysis. No harms of financial incentives were documented. Significantly more smokers in the incentives group than control group stopped smoking: 69 (22.5%) versus 26 (8.6%). The relative risk of not smoking at the end of pregnancy was 2.63 (95% confidence interval 1.73 to 4.01) P<0.001. The absolute risk difference was 14.0% (95% confidence interval 8.2% to 19.7%). The number needed to treat (where financial incentives need to be offered to achieve one extra quitter in late pregnancy) was 7.2 (95% confidence interval 5.1 to 12.2). The mean birth weight was 3140 g (SD 600 g) in the incentives group and 3120 (SD 590) g in the control group (P=0.67). Conclusion: This phase II randomised controlled trial provides substantial evidence for the efficacy of incentives for smoking cessation in pregnancy; as this was only a single centre trial, incentives should now be tested in different types of pregnancy cessation services and in different parts of the United Kingdom. Trial registration: Current Controlled Trials ISRCTN87508788.

BMJ (Clinical research ed.) · randomised controlled trial · 143 citationsread the source →

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

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

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

Efficacy of Gabapentin for the Treatment of Alcohol Use Disorder in Patients With Alcohol Withdrawal Symptoms: A Randomized Clinical Trial.

Importance: Although an estimated 30 million people meet criteria for alcohol use disorder (AUD), few receive appropriate pharmacotherapy. A more personalized, symptom-specific, approach might improve efficacy and acceptance. Objective: To examine whether gabapentin would be useful in the treatment of AUD, especially in those with the most alcohol withdrawal symptoms. Design, setting, and participants: This double-blind randomized clinical trial conducted between November 2014 and June 2018 evaluated gabapentin vs placebo in community-recruited participants screened and treated in an academic outpatient setting over a 16-week treatment period. A total of 145 treatment-seeking individuals who met Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for AUD and were not receiving other AUD intervention were screened, and 96 who also met recent alcohol withdrawal criteria were randomized to treatment after 3 abstinent days. Daily drinking was recorded, and percentage of disialo carbohydrate-deficient transferrin in the blood, a heavy drinking marker, was collected at baseline and monthly during treatment. Interventions: Gabapentin up to 1200 mg/d, orally, vs placebo along with 9 medical management visits (20 minutes each). Main outcomes and measures: The percentage of individuals with no heavy drinking days and those with total abstinence were compared between treatment groups and further evaluated based on prestudy alcohol withdrawal symptoms. Results: Of 96 randomized individuals, 90 were evaluable (44 in the gabapentin arm and 46 in the placebo arm), with a mean (SD) age of 49.6 (10.1) years; 69 were men (77%) and 85 were white (94%). The evaluable participants had 83% baseline heavy drinking days (4 or more drinks/day for women, 5 or more for men) and met 4.5 alcohol withdrawal criteria from the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). More gabapentin-treated individuals had no heavy drinking days (12 of 44 participants [27%]) compared with placebo (4 of 46 participants [9%]), a difference of 18.6% (95% CI, 3.1-34.1; P = .02; number needed to treat [NNT], 5.4), and more total abstinence (8 of 44 [18%]) compared with placebo (2 of 46 [4%]), a difference of 13.8% (95% CI, 1.0-26.7; P = .04; NNT, 6.2). The prestudy high-alcohol withdrawal group had positive gabapentin effects on no heavy drinking days (P < .02; NNT, 3.1) and total abstinence (P = .003; NNT, 2.7) compared with placebo, while within the low-alcohol withdrawal group, there were no significant differences. These findings were similar for other drinking variables, where gabapentin was more efficacious than placebo in the high-alcohol withdrawal group only. Gabapentin caused more dizziness, but this did not affect efficacy. Conclusions and relevance: These data, combined with others, suggest gabapentin might be most efficacious in people with AUD and a history of alcohol withdrawal symptoms. Future studies should evaluate sleep changes and mood during early recovery as mediators of gabapentin efficacy. Trial registration: ClinicalTrials.gov Identifier: NCT02349477.

JAMA internal medicine · randomised controlled trial · 119 citationsread the source →

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

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

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

Dialectical behavior therapy for high suicide risk in individuals with borderline personality disorder: a randomized clinical trial and component analysis.

Importance: Dialectical behavior therapy (DBT) is an empirically supported treatment for suicidal individuals. However, DBT consists of multiple components, including individual therapy, skills training, telephone coaching, and a therapist consultation team, and little is known about which components are needed to achieve positive outcomes. Objective: To evaluate the importance of the skills training component of DBT by comparing skills training plus case management (DBT-S), DBT individual therapy plus activities group (DBT-I), and standard DBT which includes skills training and individual therapy. Design, setting, and participants: We performed a single-blind randomized clinical trial from April 24, 2004, through January 26, 2010, involving 1 year of treatment and 1 year of follow-up. Participants included 99 women (mean age, 30.3 years; 69 [71%] white) with borderline personality disorder who had at least 2 suicide attempts and/or nonsuicidal self-injury (NSSI) acts in the last 5 years, an NSSI act or suicide attempt in the 8 weeks before screening, and a suicide attempt in the past year. We used an adaptive randomization procedure to assign participants to each condition. Treatment was delivered from June 3, 2004, through September 29, 2008, in a university-affiliated clinic and community settings by therapists or case managers. Outcomes were evaluated quarterly by blinded assessors. We hypothesized that standard DBT would outperform DBT-S and DBT-I. Interventions: The study compared standard DBT, DBT-S, and DBT-I. Treatment dose was controlled across conditions, and all treatment providers used the DBT suicide risk assessment and management protocol. Main outcomes and measures: Frequency and severity of suicide attempts and NSSI episodes. Results: All treatment conditions resulted in similar improvements in the frequency and severity of suicide attempts, suicide ideation, use of crisis services due to suicidality, and reasons for living. Compared with the DBT-I group, interventions that included skills training resulted in greater improvements in the frequency of NSSI acts (F1,85 = 59.1 [P < .001] for standard DBT and F1,85 = 56.3 [P < .001] for DBT-S) and depression (t399 = 1.8 [P = .03] for standard DBT and t399 = 2.9 [P = .004] for DBT-S) during the treatment year. In addition, anxiety significantly improved during the treatment year in standard DBT (t94 = -3.5 [P < .001]) and DBT-S (t94 = -2.6 [P = .01]), but not in DBT-I. Compared with the DBT-I group, the standard DBT group had lower dropout rates from treatment (8 patients [24%] vs 16 patients [48%] [P = .04]), and patients were less likely to use crisis services in follow-up (ED visits, 1 [3%] vs 3 [13%] [P = .02]; psychiatric hospitalizations, 1 [3%] vs 3 [13%] [P = .03]). Conclusions and relevance: A variety of DBT interventions with therapists trained in the DBT suicide risk assessment and management protocol are effective for reducing suicide attempts and NSSI episodes. Interventions that include DBT skills training are more effective than DBT without skills training, and standard DBT may be superior in some areas. Trial registration: clinicaltrials.gov Identifier: NCT00183651.

JAMA psychiatry · randomised controlled trial · 325 citationsread the source →

The impact of a multilevel childhood obesity prevention intervention on healthful food acquisition, preparation, and fruit and vegetable consumption on African-American adult caregivers.

Objective: To evaluate the secondary impact of a multilevel, child-focused, obesity intervention on food-related behaviours (acquisition, preparation, fruit and vegetable (FV) consumption) on youths' primary caregivers. Design: B'More Healthy Communities for Kids (BHCK) group-randomized controlled trial promoted access to healthy foods and food-related behaviours through wholesaler and small store strategies, peer mentor-led nutrition education aimed at youths, and social media and text messaging targeting their adult caregivers. Measures included caregivers' (n 516) self-reported household food acquisition frequency for FV, snacks and grocery items over 30 d, and usual FV consumption in a sub-sample of 226 caregivers via the NCI FV Screener. Hierarchical models assessed average treatment effects (ATE). Treatment-on-the-treated-effect (TTE) analyses evaluated correlation between behavioural change and exposure to BHCK. Exposure scores at post-assessment were based on self-reported viewing of BHCK materials and participating in activities. Setting: Thirty Baltimore City low-income neighbourhoods, USA.ParticipantsAdult caregivers of youths aged 9-15 years. Results: Of caregivers, 90·89 % were female; mean age 39·31 (sd 9·31) years. Baseline mean (sd) intake (servings/d) was 1·30 (1·69) fruits and 1·35 (1·05) vegetables. In ATE, no significant intervention effect was found on caregivers' food-related behaviours. In TTE, each point increase in BHCK exposure score (range: 0-6·9) increased caregivers' daily fruit consumption by 0·2 servings (0·24 (se 0·11); 95 % CI 0·04, 0·47). Caregivers reporting greater social media exposure tripled their daily fruit intake (3·16 (se 0·92); 95 % CI 1·33, 4·99) and increased their frequency of unhealthy food purchasing v. baseline. Conclusions: Child-focused community-based nutrition interventions may also benefit family members' fruit intake. Child-focused interventions should involve adult caregivers and intervention effects on family members should be assessed. Future multilevel studies should consider using social media to improve reach and engage caregiver participants.

Public health nutrition · randomised controlled trial · 20 citationsread the source →

Interventions for treating femoral shaft fractures in children and adolescents.

Background: Fractures of the femoral shaft in children are relatively uncommon but serious injuries that disrupt the lives of children and their carers and can result in significant long-term disability. Treatment involves either surgical fixation, such as intramedullary nailing or external fixation, or conservative treatment involving prolonged immobilisation, often in hospital. Objectives: To assess the effects (benefits and harms) of interventions for treating femoral shaft fractures in children and adolescents. Search methods: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (accessed 16 August 2013), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2013 Issue 7), MEDLINE (1946 to August Week 1 2013), EMBASE (1980 to 2012 week 9), CINAHL (16 August 2013), clinical trials registries, conference proceedings and reference lists; and contacted trial authors and experts in the field. Selection criteria: Randomised and quasi-randomised controlled trials comparing conservative and surgical interventions for diaphyseal fractures of the femur in children under 18 years of age. Our primary outcomes were functional outcome measures, unacceptable malunion, and serious adverse events. Data collection and analysis: Two authors independently screened and selected trials, assessed risk of bias and extracted data. We assessed the overall quality of the evidence for each outcome for each comparison using the GRADE approach. We pooled data using a fixed-effect model. Main results: We included 10 trials (six randomised and four quasi-randomised) involving a total of 527 children (531 fractures). All trials were at some risk of bias, including performance bias as care provider blinding was not practical, but to a differing extent. Just one trial was at low risk of selection bias. Reflecting both the risk of bias and the imprecision of findings, we judged the quality of evidence to be 'low' for most outcomes, meaning that we are unsure about the estimates of effect. Most trials failed to report on self-assessed function or when children resumed their usual activities. The trials evaluated 10 different comparisons, belonging to three main categories. Surgical versus conservative treatment Four trials presenting data for 264 children aged 4 to 12 years made this comparison. Low quality evidence (one trial, 101 children) showed children had very similar function assessed using the RAND health status score at two years after surgery (external fixation) compared with conservative treatment (spica cast): mean 69 versus 68. The other three trials did not report on function. There was moderate quality evidence (four trials, 264 children, aged 4 to 12 years, followed up 3 to 24 months) that surgery reduced the risk of malunion (risk ratio (RR) 0.29, 95% confidence interval (CI) 0.15 to 0.59, 4 trials). Assuming an illustrative baseline risk of 115 malunions per 1000 in children treated conservatively, these data equate to 81 fewer (95% CI 47 to 97 fewer) malunions per 1000 in surgically-treated children. Conversely, low quality evidence indicated that there were more serious adverse events such as infections after surgery (RR 2.39, 95% CI 1.10 to 5.17, 4 trials). Assuming an illustrative baseline risk of 40 serious adverse events per 1000 for conservative treatment, these data equate to 56 more (95% CI 4 to 167 more) serious adverse events per 1000 children treated surgically. There was low quality evidence (one trial, 101 children) of similar satisfaction levels in children and parents with surgery involving external fixation and plaster cast only. However, there was low quality evidence (one trial, 46 children) that more parents were satisfied with intramedullary nailing than with traction followed by a cast, and that surgery reduced the time taken off from school. Comparisons of different methods of conservative treatmentThe three trials in this category made three different comparisons. We are very unsure if unacceptable malunion rates differ between immediate hip spica versus skeletal traction followed by spica in children aged 3 to 10 years followed up for six to eight weeks (RR 4.0, 95% CI 0.5 to 32.9; one trial, 42 children; very low quality evidence). Malunion rates at 5 to 10 years may not differ between traction followed by functional orthosis versus traction followed by spica cast in children aged 5 to 13 years (RR 0.98, 95% CI 0.46 to 2.12; one trial, 43 children; low quality evidence). We are very unsure (very low quality evidence) if either function or serious adverse events (zero events reported) differ between single-leg versus double-leg spica casts (one trial, 52 young children aged two to seven years). Low quality evidence on the same comparison indicates that single-leg casts are less awkward to manage by parents, more comfortable for the child and may require less time off work by the caregiver. Comparisons of different methods of surgical treatmentThe three trials in this category made three different comparisons. Very low quality evidence means that we are very unsure if the rates of malunion, serious adverse events, time to return to school or parental satisfaction actually differ in children whose fractures were fixed using elastic stable intramedullary nailing or external fixation (one trial, 19 children). The same applies to the rates of serious adverse events and time to resume full weight-bearing in children treated with dynamic versus static external fixation (one trial, 52 children). Very low quality evidence (one trial, 47 children) means that we do not know if malunion, serious adverse events and time to resume weight-bearing actually differ between intramedullary nailing versus submuscular plating. However, there could be more difficulties in plate removal subsequently. Authors' conclusions: There is insufficient evidence to determine if long-term function differs between surgical and conservative treatment. Surgery results in lower rates of malunion in children aged 4 to 12 years, but may increase the risk of serious adverse events. Elastic stable intramedullary nailing may reduce recovery time. There is insufficient evidence from comparisons of different methods of conservative treatment or of different methods of surgical treatment to draw conclusions on the relative effects of the treatments compared in the included trials.

The Cochrane database of systematic reviews · meta-analysis · 23 citationsread the source →

A Mobile Health Mindfulness Intervention for Women With Moderate to Moderately Severe Postpartum Depressive Symptoms: Feasibility Study.

Background: Approximately 20% of women suffer from postpartum depression (PPD). Due to barriers such as limited access to care, half of the women with PPD do not receive treatment. Therefore, it is critical to identify effective and scalable interventions. Traditional mindfulness programs have been effective in reducing depressive symptoms, however access remains a barrier. A self-paced mobile health (mHealth) mindfulness program may fit the lifestyle of busy mothers who are unable to attend in-person classes. However, little is known regarding the feasibility or efficacy of mHealth mindfulness interventions in postpartum women with depressive symptoms. Objective: This study aims to assess the feasibility, acceptability, and preliminary efficacy of an mHealth mindfulness intervention for postpartum women with moderate to moderately severe depressive symptoms. Methods: We conducted a single-arm feasibility trial of an mHealth mindfulness intervention within Kaiser Permanente Northern California (KPNC), a large integrated health care system. Participants were identified through clinician referral and electronic health records via KPNC's universal perinatal depression screening program and recruited by the study team. Inclusion criteria included the following: English-speaking, up to 6 months postpartum with a Patient Health Questionnaire (PHQ-8) score of 10 to 19, and no regular mindfulness/meditation practice. Participants were asked to use a mindfulness app, Headspace, 10 to 20 min/day for 6 weeks. Baseline and postintervention surveys captured data on patient-reported outcomes (depression and stress symptoms, sleep quality, and mindfulness). Semistructured interviews captured acceptability. Retention and adherence were used to assess feasibility. Results: Of the 115 women who were contacted and met the eligibility criteria or declined participation before eligibility assessment, 27 (23%) were enrolled. In addition, 70% (19/27) completed the study. The mean age of participants was 31 years (SD 5.2), 30% (8/27) were non-Hispanic White, and, on average, participants were 12.3 weeks postpartum (SD 5.7). Of the women who completed the study, 100% (19/19) used the Headspace app at least once, and nearly half (9/19, 47%) used the app on ≥50% of the days during the 6-week intervention period. Of the 16 participants who completed the postintervention interview, 69% (11/16) reported that they were very or extremely satisfied with the app. Interviews indicated that women appreciated the variety of meditations and felt that the program led to reduced anxiety and improved sleep. Significant improvements in pre- and postintervention scores were observed for depressive symptoms (PHQ-8: -3.8, P=.004), perceived stress (10-item Perceived Stress Scale: -6.0, P=.005), and sleep quality (Pittsburgh Sleep Quality Index: -2.1, P=.02, indicating less sleep disturbance). Improvements in mindfulness were also significant (Five Facet Mindfulness Questionnaire-Short Form: 10.9, P=.01). Conclusions: An mHealth mindfulness intervention for postpartum women with moderate to moderately severe depressive symptoms is feasible and acceptable. An efficacy trial is warranted.

JMIR mental health · 27 citationsread the source →

Effects of cortico-cortical paired associative stimulation based on multisensory integration to brain network connectivity in stroke patients: study protocol for a randomized doubled blind clinical trial.

Introduction: Brain has a spontaneous recovery after stroke, reflecting the plasticity of the brain. Currently, TMS is used for studies of single-target brain region modulation, which lacks consideration of brain networks and functional connectivity. Cortico-cortical paired associative stimulation (ccPAS) promotes recovery of motor function. Multisensory effects in primary visual cortex(V1) directly influence behavior and perception, which facilitate motor functional recovery in stroke patients. Therefore, in this study, dual-targeted precise stimulation of V1 and primary motor cortex(M1) on the affected hemisphere of stroke patients will be used for cortical visuomotor multisensory integration to improve motor function. Method: This study is a randomized, double-blind controlled clinical trial over a 14-week period. 69 stroke subjects will be enrolled and divided into sham stimulation group, ccPAS low frequency group, and ccPAS high frequency group. All groups will receive conventional rehabilitation. The intervention lasted for two weeks, five times a week. Assessments will be performed before the intervention, at the end of the intervention, and followed up at 6 and 14 weeks. The primary assessment indicator is the 'Fugl-Meyer Assessment of the Upper Extremity ', secondary outcomes were 'The line bisection test', 'Modified Taylor Complex Figure', 'NIHSS' and neuroimaging assessments. All adverse events will be recorded. Discussion: Currently, ccPAS is used for the modulation of neural circuits. Based on spike-timing dependent plasticity theory, we can precisely intervene in the connections between different cortices to promote the recovery of functional connectivity on damaged brain networks after stroke. We hope to achieve the modulation of cortical visuomotor interaction by combining ccPAS with the concept of multisensory integration. We will further analyze the correlation between analyzing visual and motor circuits and explore the alteration of neuroplasticity by the interactions between different brain networks. This study will provide us with a new clinical treatment strategy to achieve precise rehabilitation for patient with motor dysfunction after stroke. Trial registration: This trial was registered in the Chinese Clinical Trial Registry with code ChiCTR2300067422 and was approved on January 16, 2023.

BMC neurology · clinical trial · 3 citationsread the source →

Evaluation of the BALANCE Program as a Digital Therapeutic Solution for Type 2 Diabetes Management: Protocol for a Prospective Lifestyle Intervention Study.

Background: Type 2 diabetes mellitus (T2DM) is a growing global health concern. In 2016, 9.7% of Bruneian adults aged 18 to 69 years had diabetes, making it the third leading cause of death. Effective self-management can mitigate complications that require health care interventions and lower health care costs. Brunei Darussalam has deployed BruHealth, a national mobile health platform synced with the Brunei Health Information Management System, allowing patients to access health records, schedule appointments, and explore medical articles. A digital therapeutics module for T2DM (diabetes mellitus digital therapeutics [DM DTx]) has been developed, consisting of a digital lifestyle intervention module within BruHealth and a separate health care professional portal for health coaches. The 16-week BALANCE program aims to support self-management. This study explores the efficacy of DM DTx in managing T2DM through digital lifestyle interventions. Objective: The primary objective is to determine the proportion of participants who achieve at least a 0.6% reduction in glycated hemoglobin after 16 weeks. Secondary objectives include evaluating changes in glycated hemoglobin, fasting lipid profile, blood glucose, BMI, and waist circumference and analyzing participant feedback. Given the predominantly Muslim population, the study also aims to gain insight into fasting practices for Muslim participants with T2DM. Methods: This single-arm, nonrandomized intervention study involves adults aged 18 to 70 years with T2DM. Participants complete a fully online 16-week program via BruHealth that includes diabetes self-management education, personalized diet and exercise plans, self-monitoring tools (eg, glucometer and smartwatch), and support from health coaches through video consultations and instant messaging. Anthropometric and biochemical measures are collected at baseline and after the intervention. Data sources include the Brunei Health Information Management System, BruHealth app logs, and the health care professional portal. Descriptive statistics will summarize participant characteristics and outcomes. Paired 2-tailed t tests or Wilcoxon signed-rank tests will compare the results before and after the intervention. Subgroup analyses will explore outcomes based on glycemic changes, BMI, medication type, and program engagement. Participant feedback will be qualitatively analyzed. Fasting risk in Muslim participants will be stratified using the International Diabetes Federation-Diabetes and Ramadan Alliance Risk score. Results: Recruitment began on August 20, 2024, following project approval in July 2024, and continued until July 2025. By the end of data collection on November 12, 2025, a total of 459 participants had been enrolled, and 422 (91.9%) had completed the program. Data analysis is currently ongoing, with results expected in early 2026. Conclusions: Self-management mobile health apps are promising tools for chronic disease management, including T2DM. The BALANCE program is Brunei's first national-scale study evaluating a fully online T2DM intervention. Localization to a region's population may support improved health outcomes. International registered report identifier (irrid): DERR1-10.2196/73964.

JMIR research protocols · clinical trial · 1 citationsread the source →

Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study.

Background: Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression. Methods: In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin's effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797. Findings: Psilocybin's acute psychedelic effects typically became detectable 30-60 min after dosing, peaked 2-3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0-1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1 week (mean QIDS difference -11·8, 95% CI -9·15 to -14·35, p=0·002, Hedges' g=3·1) and 3 months (-9·2, 95% CI -5·69 to -12·71, p=0·003, Hedges' g=2) after high-dose treatment. Marked and sustained improvements in anxiety and anhedonia were also noted. Interpretation: This study provides preliminary support for the safety and efficacy of psilocybin for treatment-resistant depression and motivates further trials, with more rigorous designs, to better examine the therapeutic potential of this approach. Funding: Medical Research Council.

The lancet. Psychiatry · clinical trial · 998 citationsread the source →

Effectiveness of the Coping With Depression (CWD) course for older adults provided by the community-based mental health care system in the Netherlands: a randomized controlled field trial.

Background: The Dutch version of the Coping With Depression (CWD) course for older adults has been implemented in the prevention arm of the community-based mental health care system in the Netherlands. The study group included older adults with subclinical depression as well as those with a major depressive disorder; all were enrolled into the course by mental health care professionals. The effectiveness (immediate and long-term) of the course for this heterogeneous population was studied in an effectiveness trial. Method: Participants were self-referred, responding to media announcements. A total of 119 participants aged 55-85 years (69% female), with subclinical depression and major depression, were randomized to either the CWD course (N = 61) or the waiting list (N = 58). Results: Nine participants dropped out of the course. According to a diagnostic interview based on the DSM-IV, 39% had a major depressive disorder (MDD), 69% had had a previous MDD, and 45% had an anxiety disorder. Older adults in the intervention group showed a significant decrease in depression symptoms. Gains were maintained over 14 months. In the intervention condition 83% had a pre-treatment score > or = 16 on the Center for Epidemiologic Studies Depression Scale (CES-D); at post-treatment 62% still scored > or = 16. Conclusions: The course was beneficial for participants with mild or severe depression, and treatment acceptability was high. It should be fitted into a stepped-care protocol that varies intervention intensity according to clinical needs, using the post-treatment level of functioning as an indication for the next step.

International psychogeriatrics · randomised controlled trial · 41 citationsread the source →

Decentering as a potential common mechanism across two therapies for generalized anxiety disorder.

OBJECTIVE: The purpose of this study was to examine decentering as a potential mechanism of action across 2 treatments for generalized anxiety disorder: an acceptance-based behavioral therapy (ABBT) and applied relaxation (AR). METHOD: Sixty-four individuals who completed at least half of the 16 total sessions of either ABBT or AR (65.6% female; 79.7% identified as White; average age = 34.41 years) completed measures of decentering (Experiences Questionnaire) and of symptoms of anxiety (Depression Anxiety Stress Scale-Stress subscale) at 5 time points over the course of therapy, and a measure of worry (Penn State Worry Questionnaire) at pre- and posttreatment. RESULTS: Initial growth curve models showed that decentering increased significantly over therapy (z = 7.09), and this increase was associated with a decrease in worry symptoms (Penn State Worry Questionnaire) at posttreatment (z = -8.51). The rate of change did not significantly vary across treatments, Δχ2/Δdf = 0.16/1, p = .69. Further, a series of bivariate latent difference score models indicated that the best-fitting model was one in which decentering was a leading indicator of change in symptoms (DASS-Stress). Allowing this coupling to vary across treatments did not significantly improve the fit of the model, Δχ2/Δdf = 0.71/1, p = .40. CONCLUSIONS: In this sample, results suggest that increased decentering was associated with decreases in anxiety and that changes in decentering appear to precede changes in symptoms within both ABBT and AR, indicating that decentering may be an important common mechanism of action. (PsycINFO Database Record

Journal of Consulting and Clinical Psychology · randomised controlled trial · 82 citationsread the source →

'Conditional candour' and 'knowing me': an interpretive description study on patient preferences for physician behaviours during end-of-life communication.

Objective: To understand patients' preferences for physician behaviours during end-of-life communication. Methods: We used interpretive description methods to analyse data from semistructured, one-on-one interviews with patients admitted to general medical wards at three Canadian tertiary care hospitals. Study recruitment took place from October 2012 to August 2013. We used a purposive, maximum variation sampling approach to recruit hospitalised patients aged ≥55 years with a high risk of mortality within 6-12 months, and with different combinations of the following demographic variables: race (Caucasian vs non-Caucasian), gender and diagnosis (cancer vs non-cancer). Results: A total of 16 participants were recruited, most of whom (69%) were women and 70% had a non-cancer diagnosis. Two major concepts regarding helpful physician behaviour during end-of-life conversations emerged: (1) 'knowing me', which reflects the importance of acknowledging the influence of family roles and life history on values and priorities expressed during end-of-life communication, and (2) 'conditional candour', which describes a process of information exchange that includes an assessment of patients' readiness, being invited to the conversation, and sensitive delivery of information. Conclusions: Our findings suggest that patients prefer a nuanced approach to truth telling when having end-of-life discussions with their physician. This may have important implications for clinical practice and end-of-life communication training initiatives.

BMJ open · 44 citationsread the source →

Teclistamab Dosing Strategies in Relapsed/Refractory Myeloma: A Real-World Comparison of Weekly and Biweekly Versus Fixed Intervals.

Background/Objectives: Teclistamab is a bispecific antibody targeting BCMA and CD3, approved for relapsed/refractory multiple myeloma. It is administered continuously until progression or intolerance; however, prolonged use may increase infections and treatment burden. This study compares continuous versus fixed-duration teclistamab to determine whether treatment discontinuation after response is feasible without compromising outcomes. Methods: A multicenter retrospective study was conducted on adults with relapsed/refractory multiple myeloma treated with teclistamab between August 2022 and May 2024. Patients received step-up dosing followed by weekly administration. Those who achieved ≥VGPR and discontinued therapy due to deep response, toxicity, or preference were assigned to the fixed-duration group. Outcomes included response rates, progression-free survival (PFS), overall survival (OS), and adverse events. Results: Eighty-eight patients were included (continuous: n = 72; fixed: n = 16). The fixed group had higher complete response rates (69% vs. 44%) and shorter median time to best response (1 vs. 2 months). Median PFS was 16 months for continuous dosing versus 13 months for fixed-duration. Twelve-month PFS was similar (65% vs. 66%). Twelve-month OS was 83% vs. 81% in the continuous and fixed groups, respectively. Cytokine release syndrome and neurotoxicity rates were similar. Infections were more frequent and severe in the fixed cohort (75% any grade; 69% grade ≥ 3). Conclusions: Fixed-duration teclistamab after deep response appears feasible in appropriately selected patients, with comparable early survival outcomes to continuous treatment. Prospective studies are needed to define selection criteria, immune recovery markers, and optimal discontinuation timing.

Cancersread the source →

Urinary fistulae after partial nephrectomy.

Objective: To report the risk factors and natural history of urinary fistula (UF) after partial nephrectomy (PN), as their incidence has been reported to be 3-6% in large series of PN but there are few reports of the risk factors associated with the development of UF after PN, and the natural history of UF in a large group of patients. Patients and methods: This was a retrospective review of 1118 PN at one tertiary-care institution. Most patients had a drain placed in the perinephric space after surgery. Fifty-two patients were identified as having a UF if they had persistent flank drainage for >14 days after surgery, or presented with evidence of a UF after the drain had been removed. Risk factors for development and the course of the UF are reported. Results: Fifty-two patients developed a UF after PN (4.4%, 95% confidence interval, CI, 3.5-6.1%) The rate of a persistent urine leak (defined as drain fluid consistent with urine for >2 weeks after surgery) was 4.0 (95% CI 2.9-5.3)%. The overall rate of delayed UF presentation was only 0.4 (0.09-0.9)%. Patients who developed a UF had larger tumours (3.5 vs 2.6  cm, P= 0.03), a higher estimated blood loss (400 vs 300  mL, P < 0.001), and longer ischaemia time (50 vs 39  min, P < 0.001) than patients who did not develop a UF. Differences in tumour histology, laterality, multifocality, type of surgery (laparoscopic vs open), and intraoperative collecting system entry were not statistically different in patients who did or did not develop a UF. Patients with tumours of >2.5  cm were twice as likely to develop a UF than patients with tumours of <2.5  cm (P= 0.02). Most patients were managed conservatively with a percutaneous drain until the UF resolved, if they were asymptomatic. Overall, in 36 patients (69%) the fistula resolved with no intervention, while 16 (31%) required intervention. Stenting was the commonest intervention (15%). No patient required re-operative open surgery. Conclusion: The rate of development of UF after PN is low. Tumour size, blood loss and ischaemia time were all associated with the development of a UF. In most patients with a urine leak immediately after surgery the UF will resolve with no intervention, and can be managed conservatively with patience, in the absence of clinical symptoms.

BJU international · 37 citationsread the source →

Surrogate versus couple therapy in vaginismus.

Introduction: Women who do not have a cooperative partner cannot complete the usual therapeutic process in the treatment of vaginismus, because they cannot progress to the stage of practicing the insertion of the man partner's fingers and the insertion of a penis. Aim: To compare traditional couple therapy with therapy utilizing a surrogate partner. Methods: The study was controlled and retrospective. Data were obtained from the treatment charts of patients who had come to the clinic for treatment of vaginismus. Sixteen vaginismus patients who were treated with a man surrogate partner were compared with 16 vaginismus patients who were treated with their own partners. Main outcome measures: Successful pain-free intercourse upon completion of therapy. Results: One hundred percent of the surrogate patients succeeded in penile-vaginal intercourse compared with 75% in the couples group (P = 0.1). All surrogate patients ended the therapy because it was fully successful, compared with 69% in the couples group. Twelve percent of the couples group ended the therapy because it failed, and 19% because the couples decided to separate. Conclusions: Treating vaginismus with a man surrogate partner was at least as effective as couple therapy. Surrogate therapy may be considered for vaginismus patients who have no cooperative partner.

The journal of sexual medicine · cohort or longitudinal · 10 citationsread the source →

Diagnostic precision of PET imaging and functional MRI in disorders of consciousness: a clinical validation study.

Background: Bedside clinical examinations can have high rates of misdiagnosis of unresponsive wakefulness syndrome (vegetative state) or minimally conscious state. The diagnostic and prognostic usefulness of neuroimaging-based approaches has not been established in a clinical setting. We did a validation study of two neuroimaging-based diagnostic methods: PET imaging and functional MRI (fMRI). Methods: For this clinical validation study, we included patients referred to the University Hospital of Liège, Belgium, between January, 2008, and June, 2012, who were diagnosed by our unit with unresponsive wakefulness syndrome, locked-in syndrome, or minimally conscious state with traumatic or non-traumatic causes. We did repeated standardised clinical assessments with the Coma Recovery Scale-Revised (CRS-R), cerebral (18)F-fluorodeoxyglucose (FDG) PET, and fMRI during mental activation tasks. We calculated the diagnostic accuracy of both imaging methods with CRS-R diagnosis as reference. We assessed outcome after 12 months with the Glasgow Outcome Scale-Extended. Findings: We included 41 patients with unresponsive wakefulness syndrome, four with locked-in syndrome, and 81 in a minimally conscious state (48=traumatic, 78=non-traumatic; 110=chronic, 16=subacute). (18)F-FDG PET had high sensitivity for identification of patients in a minimally conscious state (93%, 95% CI 85-98) and high congruence (85%, 77-90) with behavioural CRS-R scores. The active fMRI method was less sensitive at diagnosis of a minimally conscious state (45%, 30-61) and had lower overall congruence with behavioural scores (63%, 51-73) than PET imaging. (18)F-FDG PET correctly predicted outcome in 75 of 102 patients (74%, 64-81), and fMRI in 36 of 65 patients (56%, 43-67). 13 of 41 (32%) of the behaviourally unresponsive patients (ie, diagnosed as unresponsive with CRS-R) showed brain activity compatible with (minimal) consciousness (ie, activity associated with consciousness, but diminished compared with fully conscious individuals) on at least one neuroimaging test; 69% of these (9 of 13) patients subsequently recovered consciousness. Interpretation: Cerebral (18)F-FDG PET could be used to complement bedside examinations and predict long-term recovery of patients with unresponsive wakefulness syndrome. Active fMRI might also be useful for differential diagnosis, but seems to be less accurate. Funding: The Belgian National Funds for Scientific Research (FNRS), Fonds Léon Fredericq, the European Commission, the James McDonnell Foundation, the Mind Science Foundation, the French Speaking Community Concerted Research Action, the University of Copenhagen, and the University of Liège.

Lancet (London, England) · cohort or longitudinal · 352 citationsread the source →

The psychiatric sequelae of the COVID-19 pandemic in adolescents, adults, and health care workers.

Background: The COVID-19 pandemic is the most serious global public health crisis since the 1918 influenza pandemic. This study is the first to assess its mental health impact across the lifespan in the United States in adolescents, adults, and health care workers. Methods: We recruited 4909 participants through an online survey advertising on Facebook and Instagram to assess exposure to COVID-19 and psychiatric symptoms from April 27 to July 13. We also recruited through the University of Pittsburgh, University of Pittsburgh Medical Center, and other health care systems around Pittsburgh. The primary outcomes were clinically significant depression, anxiety, and posttraumatic stress disorder (PTSD) symptoms, suicidal ideation or behavior, and grief reactions since COVID-19. Results: Adolescents were significantly more likely to report moderate to severe symptoms of depression (55% vs. 29%; χ2  = 122, df = 1; p < .001), anxiety (48% vs. 29%; χ2  = 73; df = 1; p < .001), PTSD (45% vs. 33%; χ2  = 12; df = 1; p < .001), suicidal ideation or behavior (38% vs. 16%; χ2  = 117; df = 1; p < .001), and sleep problems (69% vs. 57%; χ2  = 26; df = 1; p < .001) compared to adults. The rates of intense grief reactions among those who lost someone to COVID-19 was 55%. Loneliness was the most common predictor across outcomes and higher number of hours spent on social media and exposure to media about COVID-19 predicted depression symptoms and suicidal ideation or behavior in adolescents. Conclusions: The COVID-19 pandemic is associated with increased rates of clinically significant psychiatric symptoms. Loneliness could put individuals at increased risk for the onset of psychiatric disorders.

Depression and anxiety · 157 citationsread the source →

Developmental Coordination Disorder

For the last 100 years, poor motor coordination in children has been recognized as a developmental problem.1 As early as 1937, these children were classified as “clumsy.”1 Since then, other terms such as “motorically awkward,” “motor impaired,” and “physically awkward” have been used to describe these children, and the terms “developmental apraxia” and “perceptual motor difficulties” have been used to characterize this developmental problem.2,3 Since the 1994 International Consensus Conference on Children and Clumsiness, the term “developmental coordination disorder” (DCD) has been used to describe the condition of children with motor incoordination.1,4 The purpose of this article is to provide the following information about DCD: (1) definition, (2) prevalence, (3) etiology, (4) discussion regarding the difficulties in classifying these children, (5) common characteristics, (6) long-term prognosis, and (7) brief review of treatment approaches. Developmental coordination disorder, a chronic and usually permanent condition found in children, is characterized by motor impairment that interferes with the child's activities of daily living and academic achievement.3,5 In order for a child to be diagnosed with DCD, these motor impairments must negatively affect some other aspect of his or her life.6 Impairment alone, however, does not qualify a child for the diagnosis of DCD; the motor impairment must not be caused by or have the symptoms of an identifiable neurological problem.2,5 That is, the child must not have any disturbances of muscle tone (ataxia or spasticity), sensory loss, or involuntary movements. If mental retardation is present, the testable IQ of the child must be greater than 70 and the motor impairments must be greater than what would normally be expected for children with mental retardation.5 Finally, a child diagnosed with DCD must not meet the criteria for a diagnosis of pervasive developmental disorder.6 Developmental coordination disorder appears to be a fairly common disorder of childhood and is usually identified in children between 6 and 12 years of age. Ten years ago, researchers7,8 estimated that DCD occurred in 10% to 19% of school-aged children. With a more precise definition of DCD, the current prevalence is estimated to be between 5% and 8% of all school-aged children,5,9–11 with more boys than girls (2:1) being diagnosed with DCD.12 This difference may reflect higher referral rates for boys, because the behavior of boys with motor incoordination may be more difficult to manage at home and in the classroom.8 In addition, a higher incidence of DCD may be found among children with a history of prenatal or perinatal difficulties.3 Due to the heterogeneity of DCD, finding its cause has been difficult.3 Several theories speculate that the etiology of DCD is part of the continuum of cerebral palsy5,13; is secondary to prenatal, perinatal, or neonatal insult3; or is secondary to neuronal damage at the cellular level in the neurotransmitter or receptor systems.14 Hadders-Algra14 based her view that DCD is a result of damage at the cellular level on evidence that cerebral palsy is often caused by prenatal damage that cannot be identified by current diagnostic techniques. Developmental coordination disorder, a chronic and usually permanent condition found in children, is characterized by motor impairment that interferes with the child’s activities of daily living. Although both standard and nonstandard functional tests are available to identify the specific disabilities experienced by a child with DCD, relating the observed disabilities to the primary impairment(s) or any possible neuropathology is not easily accomplished. The problems experienced by children with DCD are believed to emanate from abnormalities in neurotransmitter or receptor systems rather than from damage to specific groups of neurons or brain regions.15 Children's difficulties with coordination can result from a combination of one or more impairments in proprioception, motor programming, timing, or sequencing of muscle activity. A number of theories have evolved in an attempt to shed light on the specific neuronal processing deficits that contribute to DCD. Current models used to explain the neural regulation of posture and movement during development can serve as a basis for the examination and management of individuals with DCD. Using these models, many of the deficits of motor control observed in these children can be described. A variety of theoretical models exist to explain the role of the nervous system in motor development. Forty years ago, the primitive reflex model was a generally accepted theory used to explain how the brain regulates early motor behavior.16 As development proceeded, the higher centers exerted increasing control over the lower reflexes.16 These earlier models were based on a hierarchy of motor control in which higher centers were capable of planning and executing a motor plan without external or internal feedback from lower centers of the central nervous system (CNS). The more recently proposed systems model suggests a more complex interaction among various levels of the CNS. In the systems model, sensory feedback is interpreted by the CNS, and the appropriate movement strategy is selected based on current experience, the state of the internal and external environment, and memory of similar movements. Edelman's neuronal group selection theory includes aspects of both of these models and proposes that functional groups of neurons exist at all levels of the CNS.17 These neuronal groups are determined by evolution, but their functional integrity is dependent on afferent information produced by movement and experience.17 In this regard, these genetically determined collections of interconnected neurons (neuronal groups) in both cortical and subcortical structures serve as an early repertoire for motor behavior or receipt of specific sensory information.14,17,18 According to neuronal group selection theory, motor development proceeds in 2 phases.15 The first, the phase of primary variability, is characterized by crude and erratic motor activity that does not require sensory information for its initiation or guidance. These self-generated movements give rise to afferent (visual, kinesthetic) inputs that reinforce more specific synaptic connections within each group. An intermediate period in which effective patterns are selected is followed by the secondary variability phase. In this phase, sensory and motor factors interact to establish the intercellular connections that produce the specific and complex muscle contraction patterns that characterize coordinated, goal-directed movement. Reciprocal connections between groups subserving movements in various body parts and representing different parts of visual space are reinforced with each repetition of a particular function. As the more efficient movement patterns are practiced, the appropriate synaptic circuits are reinforced and subsequently established.14,17,19,20 The literature includes a wide variation in terminology and criteria to describe DCD. This variation has made studying the causes of DCD and developing treatment approaches for the child with DCD difficult. In their analysis of clinical trial data, Macnab et al21 identified 5 different subtype profiles of DCD. The first subtype included children with better gross motor than fine motor skills, although both were still below normal while standing balance and visual-perceptual skills were both within normal ranges. Compared with children of the same age with DCD, children in the second subtype scored high on measures of upper-limb speed and dexterity, visuomotor integration, and visual-perception skills, but they demonstrated poor performance on measures of kinesthetic ability (accuracy in discriminating movement and position of the upper limbs) and balance. Children in subtype 3 demonstrated the greatest overall motor involvement and were the only subtype to have difficulty with both kinesthetic and visual skills. Compared with their peers with DCD, children in subtype 4 performed well on kinesthetic tasks but demonstrated poor performance on tasks requiring visual and dexterity skills. Children in subtype 5 demonstrated poor performance on measurements of running speed and agility compared with their peers with DCD; however, they performed well relative to their peers with DCD in the tasks involving visual-perception skills. The development of different classification systems for DCD may have been influenced by the design of motor tests.21 For example, items testing one motor skill may be influenced by a related motor skill (eg, ball-throwing skills cannot be separated from visuomotor skills). In addition, a test may have an over-representation of one skill that could unduly influence the child's performance on the test. For example, having a greater number of items testing gross motor rather than fine motor skills could either positively or negatively influence a child's score, depending on the child's specific strengths and weaknesses. Another difficulty in interpreting the literature on DCD is the lack of inclusion criteria. Geuze et al22 reviewed 164 publications on the study of DCD and found that only 60% of the studies had objective inclusion criteria. Because of this lack of inclusion criteria, Geuze et al recommended that a child scoring below the 15th percentile on standardized tests of motor skills and having an IQ score above 69 would qualify for a diagnosis of DCD. The inconsistency among standardized motor tests used to identify children with DCD is another problem. In one study,5 the Bruininks-Oseretsky Test of Motor Proficiency (BOTMP) and the Movement Assessment Battery for Children (M-ABC) were administered to 157 children with DCD and 155 children with no motor difficulties; the test results were in agreement 82% (kappa=.62) of the time in distinguishing children who had DCD from children who did not have DCD. This is considered a substantial level of agreement.23 In a study of 202 children (101 with DCD and 101 without DCD), the BOTMP and M-ABC agreed only 67% of the time (kappa=.41), which was considered a moderate level of agreement.24 Because the BOTMP and the M-ABC are 2 of the most commonly used tests for identifying children with DCD, the potential lack of agreement by these tests in identifying children who have DCD is a concern. Two primary factors may explain the difference in outcomes between the BOTMP and M-ABC when used to identify children with DCD.24 First, the BOTMP allows the tester to verbally prompt and correct the child during the testing procedure, allowing the child who is dependent on more external controls to do better on the BOTMP. The BOTMP tends to under-identify children with DCD. Second, the M-ABC requires more careful instruction on the part of the examiner and allows more opportunities for the examinee to practice, but does not allow any verbal or physical prompting by the examiner. Children with attention problems may have more difficulty with the careful instructions for the M-ABC. Another difficulty in classifying children with DCD is the overlap with other disorders. Approximately 41% of children with attention-deficit/hyperactivity disorder (ADHD) and 56% of children with learning disabilities also have DCD.5,21 Further confusing the classification scheme is that the terms “developmental coordination disorder,” for which no identifiable organic brain damage is present, and “apraxia,” which is caused by identifiable brain damage, have been used interchangeably.3 Children with DCD may have a wide range of dysfunctions. These dysfunctions can be grouped into 3 areas: gross motor, fine motor, and psychosocial. Many children with DCD have neurological soft signs such as hypotonia, persistence of primitive reflexes, and immature balance reactions that interfere with gross motor development.5,25 These children also may demonstrate an awkward running pattern, fall frequently, drop items, and have difficulty imitating body positions and following 2- to 3-step motor commands.8 Because of their gross motor problems, children with DCD also perform poorly in sporting events,2 possibly due, in part, to their slow reaction and movement times.7 Their decreased participation in sports may result in decreased muscle force.8 Difficulty with handwriting or drawing often is the first identifiable sign of a fine motor problem and is the most frequently mentioned motor problem experienced by children with DCD. Children with DCD frequently have difficulty planning and executing other fine motor skills such as gripping and dressing.26–29 Unfortunately, children with DCD may experience problems not limited to fine or gross motor areas. These children also may experience psychosocial problems at school. Children with DCD may have learning disabilities or reading problems and may be at increased risk for lower intelligence.5,8 They may act out in class more than other children,13 may be the class clown, and may exhibit less socially desirable means of gaining recognition and friends.8 Adolescents with DCD have been found to have fewer friends, and they have more feelings of low self-worth and more anxiety than peers without DCD and younger children with DCD.30 Historically, parents have been told not to worry about their child's clumsiness because the child will outgrow the problem.31 However, current researchers in the area of DCD report that the children do not outgrow clumsiness and that, without intervention, they will not improve.1,8,12,27,31 Losse et al31 tested 17 children aged 6 years and retested them at age 16 years. The children with motor difficulties at 6 years of age continued to exhibit problems at 16 years of age. In another study,32 818 children with DCD were tested for reading comprehension at age 7 years and then again at age 10 years. A positive correlation in poor reading comprehension existed for children with DCD at 7 and 10 years of age. A follow-up study was conducted on 22-year-old individuals (N=55) who at age 7 years had either DCD or attention-deficit/hyperactivity disorder (ADHD), or both.33 The children with DCD and those with both DCD and ADHD had poorer outcomes than their similarly aged peers without DCD and children with ADHD only. The children with DCD and those with both DCD and ADHD were found to have had more criminal offenses, more incidences of substance abuse and other psychiatric disorders, and lower levels of schooling. Treatment approaches used by occupational therapists and physical therapists can be broadly categorized into either bottom-up or top-down approaches (Tab. 1).10,12,34–36 Bottom-up approaches are based on hierarchical theories of motor control. These theories tend to explain the remediation of motor dysfunction through activation of higher levels of neuronal functioning in a child. The bottom-up approaches frequently used in managing children with DCD are sensory integration, the process-oriented treatment approach, and perceptual motor training.34 Summary of Bottom-Up Versus Top-Down Approaches Summary of Bottom-Up Versus Top-Down Approaches In sensory integration therapy, the child is provided sensory stimulation designed to promote motor development and higher cortical learning. A child undergoing sensory integration therapy may show some gains in motor development, but these gains often do not generalize to functional skills.34 Kinesthesia (the perception of one's own body parts, weight, and movement) is integral to the acquisition of motor skills in process-oriented treatment approaches. Therapeutic intervention with process-oriented treatment is based on specifically designed kinesthetic training activities. As described by Laszlo and Bairstow,37 this approach has an inherent reward system built into it through its use of positive reinforcement, presentation of desirable activities within the capabilities of the child, and judicious progression of the level of difficulty. The usefulness of the process-oriented treatment approach has been the subject of considerable study.9,10,37,38 Sims and colleagues35 suggested that much of the success of this approach can be attributed to a strong motivation effect, fostered by positive feedback and a sense of self-competence. Perceptual motor training, an eclectic approach, offers the child with DCD a wide range of motor experiences along with ample opportunities to practice these skills. Often, in outcome studies, children who receive perceptual motor training are compared with children who receive either sensory integration therapy or process-oriented treatment. Children perceptual motor training have been found to demonstrate motor to or greater than those of children either sensory integration therapy or process-oriented perceptual motor training, process-oriented may promote learning through positive feedback and reinforcement, these do not and to the that top-down approaches approaches use a approach to motor skill development and have been influenced by the systems approach to motor learning and control. This approach suggests that motor skills from an interaction of many both internal and external to the approaches also the in which motor behavior intervention and approaches or are the 2 most commonly intervention on of a The theoretical for intervention in a child's motor performance is the result of learning on a specific Motor tasks are into with each and then to the Children with this approach have demonstrated gains in motor skills.34 approaches to motor development problem The approach strategy the to to the and perform the well did plan The child verbal to the to motor learning. In this approach, the as a by the child out how to his or her motor performance on various motor intervention, the results of studies of approaches are In one 10 children with DCD who were with a approach to motor development were compared with 10 children who were with a bottom-up The children were for and groups on various standardized motor tests 10 treatment However, children in the approach group motor skill and to better than children who were the bottom-up and the approach both provide repetition and practice of specific motor skills, and the approach has the of problem The greater success of top-down when compared with bottom-up be a result of the top-down inclusion of both and motor learning with for attention to and memory as the child in activities. The results of these studies, in to outcome measures of the different approaches in children with DCD, would that approaches that systems theory on sensory information being only part of the and motor learning theory be most effective for these 2 a brief of clinical the of various treatment approaches used with children with of Treatment Approaches for Children With Developmental approach to daily occupational performance treatment approach treatment group integration, perceptual motor, gross and fine motor integration Assessment Battery for Test of Motor Test of for of Motor and of of Treatment Approaches for Children With Developmental approach to daily occupational performance treatment approach treatment group integration, perceptual motor, gross and fine motor integration Assessment Battery for Test of Motor Test of for of Motor and of The neuronal group selection theory can provide a for interpreting the in outcomes among the various approaches. children with moderate to cerebral palsy have a limited repertoire of primary neuronal which children with DCD are believed to experience difficulty at the level of secondary variability, that is, in and the most efficient and effective for a normal development, experience a primary role in the neuronal group selection that the for and According to the neuronal group selection theory, this of motor skill during the of secondary variability as a result of of neuronal selection of specific neurons within each repetition of synaptic within and among neuronal and sensory synaptic which act in and cortical and subcortical and following to a variety of motor of these connections is dependent on sensory Bottom-up approaches such as sensory integration, process-oriented and perceptual motor training sensory experience, with less on processing and motor Although an intervention based on information processing may provide the experience to the most effective neuronal bottom-up approaches may not provide for motor practice of and goal-directed tasks in order to reinforce and establish these approaches less on the specific impairments to decreased coordination and more on the of that is, the among a number of structures and systems and the within which the is Treatment based on a top-down approach that provide the child the to in problem while afferent subcortical structures the feedback and to identify and the most efficient movement for the Because integration, internal of motor and appropriate motor at the level of secondary the on sensory rather than factors by the bottom-up approaches in part, be for the observed in outcomes following treatment. A number of motor learning theories have been proposed in an attempt to explain the through which are into more complex According to the motor control and learning theory proposed by and motor circuits that the and following long-term these and functioning neuronal circuits through practice, the child is to motor into more complex movements. and proposed 2 to such the first of which on sensory to neuronal is during the second that the to the specific motor tasks through the and involving the and in the first of learning requires attention and The motor then in the of learning through repetition and top-down approaches meet both of these bottom-up approaches information processing only. the and of the neural in children with DCD is a not Motor control are complex and on functioning of and motor only are children with DCD a group in terms of functional disabilities the specific of the problems observed can from one child to the Because of these an approach to the management of children with DCD is Developmental coordination disorder is a complex disorder 5% to of school-aged children. intervention, these children will to exhibit poor motor skills and show deficits in other as for may (1) the most appropriate level of intervention (2) which produce results that generalize to the and provide long-term in motor (3) what have on the child's motor and (4) motor skills to the that to the

Physical Therapy · review · 472 citationsread the source →

Association of the Mediterranean Dietary Quality Index with handgrip strength and muscle endurance: A cross-sectional study.

Mediterranean diet is a healthy eating pattern associated with various health advantages. Different scoring methods of adherence to this diet have been used to investigate the association between the Mediterranean diet and muscle outcomes. The present study aimed to investigate the association of the Mediterranean Dietary Quality Index (Med-DQI) with handgrip strength (HS) and muscle endurance (ME). The current cross-sectional study involved 268 Iranian adults aged 18-70 years. Anthropometric measures were evaluated. We used the 168-item food frequency questionnaire (FFQ) to develop the Med-DQI score. The Med-DQI score ranges from 0 to 14 (lower score suggests higher adherence to Mediterranean diet). HS was measured by a digital handgrip dynamometer, and ME was the amount of time to reach a maximum of 50% of grip strength. Multiple regression analysis was used to determine the association of Med-DQI and its components with HS and ME. Med-DQI score was not associated with mean handgrip strength (MHS) (p = .34) and mean muscle endurance (MME) (p = .69) in the crude model. The associations remained insignificant after the adjustment of covariates (p = .16, .31, respectively). Among the components of Med-DQI, cholesterol, meats, fish, and cereals were positively correlated with MHS (p < .001 for all). Meats (p = .02), olive oil (p < .001), cereals (p = .04), fruits and vegetables (p < .001 for all) were also positively correlated with MME. According to our findings, Med-DQI score is not associated with MHS and MME in a population of Iranian adults. Further longitudinal studies are required to confirm these findings.

Food science & nutrition · 6 citationsread the source →

The impact of ART on union dissolution: a register-based study in Denmark 1994-2010.

Study question: Are couples initiating ART treatment at higher risk for future union dissolution compared to other couples? Summary answer: There is no effect of ART treatments in future marital dissolution over a period of 16 years when adjusting for all confounders. What is known already: Findings regarding marital stability and infertility treatments have been sparse and controversial. While there is data showing higher divorce rates among women who go through infertility treatments, there is also some evidence of this experience bringing couples closer by forcing them to communicate more and to deal with the surrounding stigma. Using a population-based study and couple-level data, we investigated the extent to which ART treatment increases the risk for divorce/marital dissolution during up to 16 years of follow-up. Study design size, duration: Register-based national cohort study including all women registered with ART treatment in Denmark between 1 January 1994 and 30 September 2009 (n = 42 845). Marital/cohabiting status was confirmed by matching these women to partners who they were married to or shared an address with. To account for having a significant relationship at baseline (2 years), marital/cohabiting status was confirmed by accessing this variable before the establishment of the cohort back to 1 January 1992. Participants/materials, setting, methods: A comparison group from the background population including five controls per case and matched to female age at baseline was prospectively sampled. Participants could change status during follow-up if they entered ART. The final sample had 148 972 couples, followed until marital dissolution, death of self/spouse, migration or until 31 December 2010. We used Cox regression models adjusting for female and male age, education, marriage, common child at baseline and live-born child during follow-up. Main results and the role of chance: At baseline, the majority of couples were married (69%). More non-ART couples opted for marriage (70% versus 64%; P < 0.0001) and already had common children at study entry (43% versus 9%; P < 0.0001). During the 16 years of follow-up the majority of couples had children with their baseline partners (56% non-ART versus 65% ART), and 22% ended up separated or divorced (20% ART versus 22% non-ART). Findings revealed a lower risk of break-up among ART couples (crude HR 0.84, 95% CI 0.82-0.86), even after adjusting for both partners' age, education, partnership status and having a common child at baseline (adj HR 0.83, 95% CI 0.80-0.86). However, when subsequent common children (time-dependent) was added to the model, no difference in the risk of dissolution was found (adj HR 1.00, 95% CI 0.99-1.01). A significant interaction between ART status and common children showed that the risk of break-up was attributed to childlessness regardless of having gone through ART treatment. Limitations reason for caution: This study did not control for involuntary childlessness, non-ART fertility care (ovulation induction, IUI) and biological parenthood. Additionally, there are important predictors of divorce that were not considered. We were unable to adjust for religion, existence of previous marital relationships, income, employment, health status of parents and child(ren), and quality of relationship. Wider implication of findings: The finding that going through ART does not increase the risk of break up per se is reassuring for couples who underwent ART and have children or are contemplating to start ART. Study funding/competing interest(s): This work was supported by FCT (Portuguese Foundation for Science and Technology), grant ref. SFRH/BPD/85789/2012. The authors have no conflicts of interest. Trial registration number: N/A.

Human reproduction (Oxford, England) · 11 citationsread the source →

Mental Health Specialist Video Consultations Versus Treatment-as-Usual for Patients With Depression or Anxiety Disorders in Primary Care: Randomized Controlled Feasibility Trial.

Background: Most people affected by depression or anxiety disorders are treated solely by their primary care physician. Access to specialized mental health care is impeded by patients' comorbidity and immobility in aging societies and long waiting times at the providers' end. Video-based integrated care models may leverage limited resources more efficiently and provide timely specialized care in primary care settings. Objective: The study aims to evaluate the feasibility of mental health specialist video consultations with primary care patients with depression or anxiety disorders. Methods: Participants were recruited by their primary care physicians during regular practice visits. Patients who had experienced at least moderate symptoms of depression and/or anxiety disorders were considered eligible for the study. Patients were randomized into 2 groups receiving either treatment-as-usual as provided by their general practitioner or up to 5 video consultations conducted by a mental health specialist. Video consultations focused on systematic diagnosis and proactive monitoring using validated clinical rating scales, the establishment of an effective working alliance, and a stepped-care algorithm within integrated care adjusting treatments based on clinical outcomes. Feasibility outcomes were recruitment, rate of loss to follow-up, acceptability of treatment, and attendance at sessions. Effectiveness outcomes included depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder-7), burden of specific somatic complaints (Somatic Symptom Disorder-B Criteria Scale-12), recovery (Recovery Assessment Scale-German [RAS-G]), and perception of chronic illness care (Patient Assessment of Chronic Illness Care), which were measured at baseline and 16 weeks postallocation by assessors blinded to the group allocation. Results: A total of 50 patients with depression and/or anxiety disorders were randomized, 23 in the intervention group and 27 in the treatment-as-usual group. The recruitment yield (number randomized per number screened) and the consent rate (number randomized per number eligible) were 69% (50/73) and 86% (50/58), respectively. Regarding acceptability, 87% (20/23) of the participants in the intervention group completed the intervention. Of the 108 planned video consultations, 102 (94.4%) were delivered. Follow-up rates were 96% (22/23) and 85% (23/27) for the intervention and control groups, respectively. The change from baseline scores at postmeasurement for the No Domination by Symptoms domain of recovery (RAS-G) was somewhat higher in the intervention group than in the control group (Mann-Whitney U test: rank-biserial r=0.19; 95% CI -0.09 to 0.46; P=.18). We did not detect any notable differences between the intervention and control groups in terms of other effectiveness outcomes. We did not observe any serious adverse events related to the trial. Conclusions: The intervention and study procedures were found to be feasible for patients, primary care practice staff, and mental health specialists. A sufficiently powered pragmatic trial on mental health specialist video consultations should be conducted to investigate their effectiveness in routine care. Trial registration: German Clinical Trials Register DRKS00015812; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00015812.

JMIR mental health · 25 citationsread the source →

Midlife contributors to socioeconomic differences in frailty during later life: a prospective cohort study.

Background: Health inequalities persist into old age. We aimed to investigate risk factors for socioeconomic differences in frailty that could potentially be modified through policy measures. Methods: In this multi-wave longitudinal cohort study (Whitehall II study), we assessed participants' socioeconomic status, behavioural and biomedical risk factors, and disease status at age 45-55 years, and frailty (defined according to the Fried phenotype) at baseline and at one or more of three clinic visits about 18 years later (mean age 69 years [SD 5·9]). We used logistic mixed models to examine the associations between socioeconomic status and risk factors at age 50 years and subsequent prevalence of frailty (adjusted for sex, ethnic origin, and age), with sensitivity analyses and multiple imputation for missing data. Findings: Between Sept 9, 2007, and Dec 8, 2016, 6233 middle-aged adults were measured for frailty. Frailty was present in 562 (3%) of 16 164 person-observations, and varied by socioeconomic status: 145 (2%) person-observations had high socioeconomic status, 241 (4%) had intermediate status, and 176 (7%) had low socioeconomic status, adjusting for sex and age. Risk factors for frailty included cardiovascular disease, depression, smoking, high or abstinent alcohol consumption, low fruit and vegetable consumption, physical inactivity, poor lung function, hypertension, and overweight or obesity. Cardiometabolic markers for future frailty were high ratio of total to high-density lipoprotein cholesterol, and raised interleukin-6 and C-reactive protein concentrations. The five most important factors contributing to the frailty gradient, assessed by percent attenuation of the association between socioeconomic status and frailty, were physical activity (13%), interleukin-6 (13%), body-mass index category (11%), C-reactive protein (11%), and poor lung function (10%). Overall, socioeconomic differences in frailty were reduced by 40% in the maximally-adjusted model compared with the minimally-adjusted model. Interpretation: Behavioural and cardiometabolic risk factors in midlife account for more than a third of socioeconomic differences in frailty. Our findings suggest that interventions targeting physical activity, obesity, smoking, and low-grade inflammation in middle age might reduce socioeconomic differences in later-life frailty. Funding: British Heart Foundation and British Medical Research Council.

The Lancet. Public health · 66 citationsread the source →

Combat sports and wellbeing: advancing health and inclusion in athletes and practitioners. An opinion paper

Historically, combat sports have been predominantly conceptualized within the framework of elite competition, emphasizing physical aptitude, technical proficiency, and strategic execution (1-3). Despite their traditional and peculiar constitutions and developments, disciplines such as judo, karate, taekwondo, wrestling, fencing, boxing, and mixed martial arts have commonly been associated with high-performance athletes striving for competitive excellence on national and international stages (1, 4-6). However, contemporary discourse increasingly recognizes their expansive role in contributing to physical and psychological well-being, and social inclusion of the practitioners (7, 8). This paradigmatic shift underscores the capacity of combat sports to function as inclusive and accessible modalities for fostering multidimensional health benefits across diverse populations, including individuals with disabilities and other marginalized groups (9-13).The interdisciplinary exploration of physical activity and health highlights the intricate interrelationship between structured sports engagement and holistic well-being (14). Whilst conventional team and individual sports have long been acknowledged for their physiological and psychosocial benefits, combat sports exhibit distinct characteristics that might amplify these advantages (15, 16). Within combat sports, the synergistic interplay of rigorous physical conditioning, the cognitive engagement, adherence to rules, competition dynamics, respect, externalizing emotions regulation, are intertwined with pedagogical and philosophical values, thus presenting a unique framework for enhancing psychological resilience, cognitive adaptability, and emotional control. Consequently, the systematic practice of combat sports has been increasingly examined as a way of promoting mental health, stress modulation, and social cohesion (17, 18).The inclusive nature of many combat sports programmes further accentuates their relevance in dismantling stereotypes, facilitating integration, and fostering equity and social integration (19-21). In fact, they demonstrated significant adaptability to accommodate individuals with disabilities (e.g., physical impairments, developmental, emotional, intellectual disorders), thereby ensuring equitable access and fostering empowerment (9, 22). Adapted judo, para-taekwondo, and other modified combat disciplines provide individuals with disabilities a structured platform to engage in physical activity, cultivate self-efficacy, and develop meaningful social connections within a supportive and adaptive environment (23). From a public health perspective, the integration of combat sports within community-based health initiatives offers a compelling opportunity to engage populations that may not traditionally participate in structured physical activity programmes (7, 8, 19). The distinctive accessibility of combat sports, which cater to practitioners of all skill levels (e.g., from novices to elite athletes) sets them apart from many other sports. While their structured progression, adaptability, and emphasis on holistic development make them a viable option for lifelong and intergenerational participation (19, 24, 25), the mentorship and pedagogical frameworks cultivate positive role modeling, discipline, and intrinsic motivation, which are integral for sustaining long-term adherence to health-promoting behaviors (8).Furthermore, the intersection between combat sports and mental health has increasingly emerged as a focal point within academic and clinical research (17) with empirical evidence suggesting an association between participation and enhanced self-regulation and self-efficacy, and reduction in anxiety and depressive symptomatology (8, 26, 27). In necessitating sustained focus, adaptability, and emotional equilibrium, combat sports inherently require cognitive and affective demands, which align closely with established psychological frameworks that underpin mental well-being (28, 29). Moreover, the integration of mindfulness techniques, stress management strategies, and resilience-building paradigms within combat sports training substantiates their potential as a non-pharmacological intervention for addressing various mental health challenges (e.g., autism spectrum and oppositional defiant disorders) (30, 31).Despite these advantages, the discourse surrounding combat sports and well-being necessitates a critical examination of inherent risks and potential challenges. Issues related to injury risk, hypercompetitive environments, eating disorders, sexual harassment, and the psychological stressors associated with high-intensity training warrant careful scrutiny (32-36). The implementation of evidence-based injury prevention protocols, the establishment of ethically responsible coaching methodologies, and the promotion of safe training environments are imperative to ensure that the benefits of combat sports are maximized while minimizing adverse outcomes. Against this backdrop, this opinion paper seeks to examine the role of combat sports in advancing health and social inclusion among athletes and practitioners. Through a synthesis of contemporary empirical findings, theoretical paradigms, and applied insights, this paper aims to contribute to the evolving discourse on the potential of combat sports as a catalyst for holistic well-being. By delineating the multidimensional impact of combat sports on physical, psychological, and social health, this paper endeavors to underscore their transformative potential as an instrument for fostering individual and community well-being within different populations. DiscussionWhilst an expanding body of research and an evolution in scholarly discourse is recognizing the combat sports’ broader implications for holistic well-being (30, 37), a rigorous evaluation of the investigation methodologies, the validity of hypotheses, and the translational potential of recent findings is necessary to contextualize their significance within the sports and public health sciences, considering their strengths, weaknesses, opportunities, and threats (Figure 1).----------------------------------------ADD FIGURE 1 ABOUT HERE----------------------------------------Empirical evidence robustly shows the positive impact of combat sports on physical fitness, motor coordination, and cardiovascular health (3, 38). These benefits are attributed to the high-intensity, intermittent nature of combat sports training, which enhances aerobic and anaerobic endurance, muscular strength, and neuromuscular control (39). However, concerns regarding injury risk, particularly in striking and contact-intensive disciplines such as boxing, taekwondo, and mixed martial arts, necessitate continued research into injury mitigation strategies, particularly those targeting concussion and repetitive head trauma (6, 35, 40, 41). Moreover, many combat sports have developed styles with reduced or simulated contact to minimize injury risk. For example, the French "boxe éducative" emphasizing technique and control, penalizing any violent behaviors (42) and the value and application of kata (i.e., forms; prearranged, pattern practices) to learning and adopting judo technique in a safe way educating the athlete culturally, to enrich her/him as a person (43).Beyond physical health, recent studies highlight the psychological benefits of combat sports, including reductions in anxiety and depression and improvements in self-efficacy, emotional regulation, resilience, and stress management (27, 44-47). Therefore, combat sports-based interventions for individuals with mental health conditions have yielded promising outcomes (23). Despite these encouraging findings, variability in study designs, participant demographics, and intervention protocols limits their external validity, underscoring the need for further rigorously controlled investigations. Furthermore, some authors claimed that combat sport athletes might present symptoms of low energy availability and high anxiety levels associated with competition- and injury-related psychological stressors, deficits in executive functions and neuropsychological impairments associated with occurrence of concussions, disordered eating and eating disorders associated with weight-loss, and might suffer offensive, frightening, hostile, degrading, humiliating experiences, or sexual harassment, which urge safeguarding actions (32-36).The role of combat sports in fostering social inclusion has gained empirical support, particularly in programmes aimed at individuals with disabilities and marginalized communities (25, 48). For instance, a recent systematic review shows that judo interventions adapted for intellectual disabilities help improve social integration and self-perception and enhance participants' quality of life (49). The development of para-combat sports demonstrates enhanced physical and motor abilities while providing psychosocial benefits to various populations with different disabilities, promoting social integration, self-perception, and community belonging (50, 51). However, longitudinal research is needed to assess the long-term retention rates and sustainability of these benefits. Furthermore, there is a need of studies focused on the most appropriate adapted rules to achieve a fairer competition for ensuring a sense of success in individuals with physical, emotional, mental, hearing or visual impairments participating in adapted sports competitions at local, national, and international levels. Methodological approaches in combat sports research encompass experimental, longitudinal, qualitative, and systematic review designs. While randomized controlled trials remain the gold standard for establishing causality, their application in combat sports research is constrained by ethical concerns, logistical challenges, and the inherently dynamic nature of training environments (52, 53). Consequently, many studies rely on observational designs, which, despite their value in identifying associations, are susceptible to confounding variables and biases (24, 54).Qualitative methodologies have provided critical insights into the lived experiences of combat sports practitioners, offering perspectives on psychological and social dimensions that are often overlooked in quantitative studies (28). Ethnographic research has been particularly instrumental in elucidating the role of combat sports in shaping identity, discipline, and personal development (55). However, limitations in reproducibility and generalizability highlight the need for mixed-methods approaches to generate a more comprehensive understanding of combat sports' impact (25, 56).Additionally, the incorporation of biometric and neurocognitive assessments, such as heart rate variability analysis, functional MRI, and salivary cortisol measurements, has advanced our understanding of the physiological and psychological mechanisms underlying combat sports participation (47, 57, 58). Despite their objective precision, these techniques often face challenges related to cost, accessibility, and limited sample sizes, necessitating the development of scalable and cost-effective methodologies for broader research application. Finally, recent studies show that virtual reality (VR) technology and digital platforms are increasingly becoming part of combat sports training methods. Due to COVID-19 restrictions, martial arts schools and organizations implemented hybrid or online training models, which allowed athletes to stay engaged. VR boxing programmes provide users with virtual sparring simulations to enhance their motor skills without needing physical interaction. Initial results indicate that VR training enhances response behavior in karate athletes (59). Digital adaptations offer great potential, especially for people with limited mobility or remote locations. However, further studies are necessary to prove their enduring effects on physical health and psychological and social aspects (59-61).Strengths and Weaknesses of Scientific HypothesesThe hypothesis that combat sports confer multidimensional health benefits is strongly supported by empirical evidence spanning physiological, psychological, and social domains (8, 62-64). The integration of physical exertion, cognitive engagement, and structured discipline inherent in combat sports aligns with established theories of exercise psychology, neuroplasticity, and social identity formation (65, 66). This multidimensional perspective provides a robust theoretical foundation for advocating combat sports as a health-promoting activity. Nevertheless, several limitations warrant consideration. The heterogeneity of disciplines, which vary highly in intensity, contact level, and training methodologies, is often inadequately addressed in research, leading to overgeneralized conclusions (17, 39). Often underexamined, individual differences in personality, motivation, and previous trauma history may strongly moderate the psychological outcomes of combat sports participation (35, 67, 68).Additionally, a research focus is needed on concerns regarding the potential for adverse psychological effects (e.g., anxiety, depression, disordered eating behaviors, burnout, and decreased self-esteem), particularly in competitive environments where performance pressure, extreme weight-cutting practices, and aggressive coaching styles are prevalent (69, 70). Indeed, a balanced perspective that considers both benefits and risks is essential for the development of evidence-based recommendations (10, 71).Future DirectionsTo enhance the field, future research should prioritize well-structured longitudinal studies that assess the long-term impact of combat sports participation on physical, psychological, and social health. Standardization of outcome measures, intervention protocols, and participant demographics would facilitate cross-study comparisons and strengthen the reliability of findings (72, 73). Moreover, interdisciplinary collaborations incorporating sports science, psychology, and sociology could provide a more holistic perspective on combat sports' broader implications on practitioners (74).From a policy perspective, to yield valuable insights into combat sports’ practical applications research should investigate their efficacy within public health, educational, and rehabilitation initiatives, particularly for underserved and vulnerable populations (23, 75, 76).Furthermore, while safety remains a primary concern, advancements in protective equipment, training methodologies, education for athletes, coaches, referees and tournament directors, and regulatory frameworks should be continually evaluated to optimize benefits while mitigating risks (40, 41, 58, 77, 78). Ethical considerations, particularly concerning athlete well-being and inclusive participation, should remain a central focus in both research and practical implementation (17, 34, 36).Therefore, key research challenges to be addressed are: 1. Injury risk and safety: a need for injury prevention strategies, especially for concussions and head trauma in striking sports. 2. Psychological wellbeing: risks of stress, anxiety, burnout, and negative self-perception in competitive environments. 3. Inclusion and accessibility: a need for more research on long-term social and psychological benefits for marginalized groups and individuals with disabilities. 4. Methodological limitations: lack of standardized protocols, variability in study designs, and limited reproducibility of findings. 5. Ethical and regulatory issues: concerns over coaching practices, extreme weight-cutting, and athlete wellbeing in high-pressure environments. 6. Technological innovations: more research required on the effectiveness of VR and digital training tools in combat sports. 7. Public health and policy: exploration of combat sports' role in health initiatives, rehabilitation, and educational programs. ConclusionThe evolving discourse on combat sports highlights their potential as a multidimensional tool for well-being promotion. While a substantial body of evidence supports their benefits, a critical examination of methodological limitations, scientific hypotheses, and practical applications is essential for further refine our understanding and enhance their effectiveness. Finally, this article makes a significant contribution not only to the field of martial arts but also to public health and sports psychology. Its interdisciplinary approach calls for scientific collaboration and methodological rigor, reinforces the need for evidence-based policies and can serve as a valuable guide for researchers and policymakers looking to integrate combat sports into strategies for promoting health and social inclusion.

Frontiers in Psychology · 12 citationsread the source →

Validation of the German Version of the Moral Injury Symptom and Support Scale for Health Professionals (G-MISS-HP) and Its Correlation to the Second Victim Phenomenon.

Introduction: Comparable to second victim phenomenon (SVP), moral injury (MI) affects health professionals (HP) working in stressful environments. Information on how MI and SVP intercorrelate and their part in a psychological trauma complex is limited. We tested and validated a German version of the Moral Injury Symptom and Support Scale for Health Professionals (G-MISS-HP) instrument, screening for MI and correlated it with the recently developed German version of the Second Victim Experience and Support Tool (G-SVESTR) instrument, testing for SVP. Methods: After translating Moral Injury Symptom and Support Scale for Health Professionals (MISS-HP), we conducted a cross-sectional online survey providing G-MISS-HP and G-SVEST-R to HP. Statistics included Pearson's interitem correlation, reliability analysis, principal axis factoring and principal components analysis with Promax rotation, confirmatory factor and ROC analyses. Results: A total of 244 persons responded, of whom 156 completed the survey (33% nurses, 16% physicians, 9% geriatric nurses, 7.1% speech and language therapists). Interitem and corrected item-scale correlations did not measure for one item sufficiently. It was, therefore, excluded from further analyses. The nine-item score revealed good reliability (Guttman's lambda 2 = 0.80; Cronbach's alpha = 0.79). Factor validity was demonstrated, indicating that a three-factor model from the original study might better represent the data compared with our two-factor model. Positive correlations between G-MISS-HP and G-SVESTR subscales demonstrated convergent validity. ROC revealed sensitivity of 89% and specificity of 63% for G-MISS-HP using a nine-item scale with cutoff value of 28.5 points. Positive and negative predictive values were 62% and 69%, respectively. Subgroup analyses did not reveal any differences. Conclusion: G-MISS-HP with nine items is a valid and reliable testing instrument for moral injury. However, strong intercorrelations of MI and SVP indicate the need for further research on the distinction of these phenomena.

International journal of environmental research and public health · 18 citationsread the source →

Temporal trends and patterns in atrial fibrillation incidence: A population-based study of 3·4 million individuals.

Background: Population-based studies of atrial fibrillation (AF) incidence are needed to inform health-service planning, but evidence is conflicting. We assessed trends of AF incidence in a large general population cohort from England. Methods: We used linked primary and secondary electronic health records of 3.4 million individuals. Eligible patients aged 16 years and older contributed data between Jan 2 1998 and Dec 31 2017. For patients with incident AF, we extracted baseline characteristics, comorbidities, socioeconomic status and geographic region. We calculated standardised rates by applying direct age and sex standardisation to the 2013 European Standard Population. We applied year-specific, age-specific and sex-specific incidence to UK census mid-year population estimates for yearly total incident AF. Findings: Comparing 2017 to 1998 standardised AF incidence increased by 30% (322 vs. 247 per 100 000 person-years; adjusted incidence ratio [IRR] 1·30, 95% CI 1·27-1·33). Absolute number of incident AF increased by 72% (202 333 vs. 117 880), due to an increasing number of older persons. Comorbidity burden at diagnosis of AF increased (3·74 [SD 2·29] vs 2·58 [1·83]; adjusted difference 1·26, 95% CI 1·14-1·39). The age of AF diagnosis declined in the most deprived individuals compared to the most affluent (adjusted difference 0·74 years, 0·62-0·88). Across the study period, age-standardised incidence was higher in men than women (IRR 1·49; 95% CI 1·46-1·52), and men were younger at diagnosis (adjusted difference 5·53 years; 95% CI 5·36 to 5·69). Socioeconomically deprived individuals had more comorbidities and a higher incidence of AF than the most affluent individuals (IRR 1·20; 95% CI 1·15-1·24). Interpretation: In England AF incidence has increased, and the socioeconomic gradient in age at diagnosis and comorbidity burden widened. This changing burden requires policy-based interventions to achieve health equity. Funding: British Heart Foundation and National Institute for Health Research.

The Lancet regional health. Europe · 80 citationsread the source →

The Role of Emotion Regulation and Loss-Related Coping Self-efficacy in an Internet Intervention for Grief: Mediation Analysis

BACKGROUND: Internet interventions for mental disorders and psychological problems such as prolonged grief have established their efficacy. However, little is known about how internet interventions work and the mechanisms through which they are linked to the outcomes. OBJECTIVE: As a first step in identifying mechanisms of change, this study aimed to examine emotion regulation and loss-related coping self-efficacy as putative mediators in a randomized controlled trial of a guided internet intervention for prolonged grief symptoms after spousal bereavement or separation or divorce. METHODS: The sample comprised older adults who reported prolonged grief or adaptation problems after bereavement, separation, or divorce and sought help from a guided internet intervention. They were recruited mainly via newspaper articles. The outcome variables were grief symptoms assessed using the Texas Revised Inventory of Grief and psychopathology symptoms assessed using the Brief Symptom Inventory. A total of 6 module-related items assessed loss-focused emotion regulation and loss-related coping self-efficacy. In the first step, path models were used to examine emotion regulation and loss-related coping self-efficacy as single mediators for improvements in grief and psychopathology symptoms. Subsequently, exploratory path models with the simultaneous inclusion of emotion regulation and self-efficacy were used to investigate the specificity and relative strength of these variables as parallel mediators. RESULTS: A total of 100 participants took part in the guided internet intervention. The average age was 51.11 (SD 13.60) years; 80% (80/100) were separated or divorced, 69% (69/100) were female, and 76% (76/100) were of Swiss origin. The internet intervention increased emotion regulation skills (β=.33; P=.001) and loss-related coping self-efficacy (β=.30; P=.002), both of which correlated with improvements in grief and psychopathology symptoms. Path models suggested that emotion regulation and loss-related coping self-efficacy were mediators for improvement in grief. Emotion regulation showed a significant indirect effect (β=.13; P=.009), whereas coping self-efficacy showed a trend (β=.07; P=.06). Both were confirmed as mediators for psychopathology (β=.12, P=.02; β=.10; P=.02, respectively). The path from the intervention to the improvement in grief remained significant when including the mediators (β=.26, P=.004; β=.32, P≤.001, respectively) in contrast to the path from the intervention to improvements in psychopathology (β=.15, P=.13; β=.16, P=.10, respectively). CONCLUSIONS: Emotion regulation and loss-related coping self-efficacy are promising therapeutic targets for optimizing internet interventions for grief. Both should be further examined as transdiagnostic or disorder-specific putative mediators in internet interventions for other disorders. TRIAL REGISTRATION: ClinicalTrials.gov NCT02900534; https://clinicaltrials.gov/ct2/show/NCT02900534. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-016-1759-5.

JMIR Mental Health · 19 citationsread the source →

Prevalence and correlates of substance use among trans female youth ages 16-24 years in the San Francisco Bay Area.

Background: Substance use is highly prevalent among transgender (trans*) females and has been associated with negative health outcomes, including HIV infection. Little is known about psychosocial risk factors that may influence the onset of substance use among trans*female youth, which can contribute to health disparities during adulthood. Methods: We conducted a secondary data analysis of a study on HIV risk and resilience among trans*female youth (N=292). Prevalence of substance use was assessed and multivariable logistic regression models were used to examine the relationship between posttraumatic stress disorder (PTSD), psychological distress, gender-related discrimination, parental drug or alcohol problems (PDAP) and multiple substance use outcomes. Results: Most (69%) of the trans*female youth reported recent drug use. In multivariable analyses, those with PTSD had increased odds of drug use [AOR=1.94 (95% CI=1.09-3.44)]. Those who experienced gender-related discrimination had increased odds of drug use [AOR=2.28 (95% CI=1.17-4.44)], drug use concurrent with sex [AOR=2.35 (95% CI=1.11-4.98)] and use of multiple drugs [AOR=3.24 (95% CI=1.52-6.88)]. Those with psychological distress had increased odds of using multiple heavy drugs [AOR=2.27 (95% CI=1.01-5.12)]. Those with PDAP had increased odds of drugs use [AOR=2.62 (95% CI=1.43-4.82)], drug use concurrent with sex [AOR=2.01 (95% CI, 1.15-3.51)] and use of multiple drugs [AOR=2.10 (95% CI=1.22-3.62)]. Conclusions: Substance use is highly prevalent among trans*female youth and was significantly associated with psychosocial risk factors. In order to effectively address substance use among trans*female youth, efforts must address coping related to gender-based discrimination and trauma. Furthermore, structural level interventions aiming to reduce stigma and gender-identity discrimination might also be effective.

Drug and alcohol dependence · 107 citationsread the source →

PATHOPHYSIOLOGY OF DEPRESSION: DO WE HAVE ANY SOLID EVIDENCE OF INTEREST TO CLINICIANS?

Major depressive disorder (MDD) is a common and costly disorder which is usually associated with severe and persistent symptoms leading to important social role impairment and increased mortality 1,2. It is one of the most important causes of disability worldwide 3. The high rate of inadequate treatment of the disorder remains a serious concern 1. This review is aimed at summarizing the solid evidence on the etiology and pathophysiology of MDD that is likely relevant for clinical psychiatry. Neurobiological findings are regarded as solid when they are consistent and convergent, i.e., they have been confirmed by several studies using the same method and fit into results from studies using different methodological approaches. Family, twin, and adoption studies provide very solid and consistent evidence that MDD is a familial disorder and that this familiality is mostly or entirely due to genetic factors 4. This important finding suggests that parental social behavior and other familial environmental risk factors are not as important in the pathogenesis of MDD as previously assumed and should not be the major focus of the treatment of the disorder. The above-mentioned studies consistently show that the influence of genetic factors is around 30–40% 4. Non-genetic factors, explaining the remaining 60–70% of the variance in susceptibility to MDD, are individual-specific environmental effects (including measurement error effects and gene-environment interactions). These effects are mostly adverse events in childhood and ongoing or recent stress due to interpersonal adversities, including childhood sexual abuse, other lifetime trauma, low social support, marital problems, and divorce 5,6. These results suggest that there is a huge potential in the prevention of MDD by means of psychosocial interventions (e.g., in schools, at workplace). In addition, these results mirror the clinical practice of empirically validated psychotherapies to treat depression 7,8,9, including interpersonal, psychodynamic and cognitive behavioral psychotherapies and cognitive behavioural analysis system of psychotherapy, which all focus directly or indirectly on interpersonal difficulties and skills. This does not exclude the fact that unidentified non-genetic, non-psychosocial risk factors may also play important roles in some patients (e.g., climatic change, medical conditions). Stress sensitivity in depression is partly gender-specific. While men and women are, in general, equally sensitive to the depressogenic effects of stressful life events, their responses vary depending upon the type of stressor. Specifically, men are more likely to have depressive episodes following divorce, separation, and work difficulties, whereas women are more sensitive to events in their proximal social network, such as difficulty getting along with an individual, serious illness, or death 10. These findings point to the importance of gender-sensitive psychosocial approaches in the prevention and treatment of MDD. In contrast to the very solid evidence from epidemiological studies on broad risk factor domains, there is no solid evidence for specific genes and specific gene-by-environment interactions in the pathogenesis of MDD. Genome-wide association studies have indicated that many genes with small effects are involved in complex diseases, increasing the difficulty in identifying such genes 11. While there has been progress in the search for risk genes for several complex diseases despite this methodological problem 12, psychiatric conditions have turned out to be very resistant to robust gene identification. For example, based on a community-based prospective study, it has been proposed that a specific genetic variation in the promoter region of the serotonin transporter (a target of antidepressant drugs) interacts with stressful life events in the pathogenesis of depression 13. Although there is high clinical and neurobiological plausibility of this interaction, a recent meta-analysis yielded no evidence that the serotonin transporter gene alone or in interaction with psychological stress was associated with the risk of depression 14. The limited success of genetic studies of depression has been related to use of current classification schemas including ICD-10 and DSM-IV. These diagnostic manuals are based on clusters of symptoms and characteristics of clinical course that do not necessarily describe homogenous disorders but instead reflect common final pathways of different pathophysiolgical processes 15,16. The clinician should be aware that family history will continue to be the most solid source of information to estimate the genetic risk of MDD. Corticotropin-releasing hormone (CRH) is released from the hypothalamus in response to the perception of psychological stress by cortical brain regions. This hormone induces the secretion of pituitary corticotropin, which stimulates the adrenal gland to release cortisol into the plasma. The physiologic response to stress is partly gender-specific: women show generally greater stress responsiveness than men, which is consistent with the greater incidence of major depression in women 17. Moreover, men show greater cortisol responses to achievement challenges, whereas women show greater cortisol responses to social rejection challenges 18. Although MDD is considered as a stress disorder, most subjects treated for MDD have no evidence of dysfunctions of the hypothalamic-pituitary-adrenal axis (HPA) 19. However, some subjects with MDD do show abnormalities of that axis and of the extrahypothalamic CRH system 20. Altered stress hormone secretion appeared to be most prominent in depressed subjects with a history of childhood trauma 21. Elevated cortisol may act as a mediator between major depression and its physical long-term consequences such as coronary heart disease, type II diabetes, and osteoporosis 22. The importance of HPA axis dysfunction for the efficacy of antidepressants is a matter of debate 23. This axis is regulated through a dual system of mineralocorticoid (MR) and glucocorticoid (GR) receptors. Decreased limbic GR receptor function 24,25 and increased functional activity of the MR system 26 suggest an imbalance in the MR/GR ratio in stress-related conditions such as MDD. Epigenetic regulation of the glucocorticoid receptors has been associated with childhood abuse 27. Such environmental programming of gene expression may represent one possible mechanism that links early life stress to abnormal HPA axis function and increased risk of MDD in adults. While the CRH stimulation test (dex/CRH test) 28 is a sensitive measure of the HPA axis dysfunction in depression, the specificity of this test for MDD is low. However, non-suppression in the dex/CRH test has consistently predicted increased risk for depressive relapse during clinical remission 23. Additionally, the measurement of waking salivary cortisol concentration has been shown to be a simple and sensitive test for HPA axis hyperactivity in depression 29. Hypercortisolemia is almost exclusively found in subjects with severe and psychotic depression, in whom glucocorticoid antagonists may have some therapeutic effect 30. There is convergent evidence for CRH to play a major role in the pathogenesis of certain types of depression. Levels of CRH in the cerebrospinal fluid are elevated in some depressed subjects 31. Post-mortem studies reported an increased number of CRH secreting neurons in limbic brain regions in depression 32, likely reflecting a compensatory response to increased CRH concentrations 33. In addition, CRH produces a number of physiological and behavioral alterations that resemble the symptoms of major depression, including decreased appetite, disrupted sleep, decreased libido, and psychomotor alterations 34. There is also preliminary evidence that CRH1 receptor antagonists reduce symptoms of depression and anxiety 35. “Sickness behavior” as a result of an activation of the inflammatory response system shares many symptoms with depression, including fatigue, anhedonia, psychomotor retardation, and cognitive impairment. Sickness is mediated by pro-inflammatory cytokines such as interleukin-1α, tumor necrosis factor-α, and interleukin-6, which activate the HPA axis and impair the central serotonin system 36. The prevalence of depression as an unwanted effect of recombinant interferons is around 30% 37. In animals, blocking pro-inflammatory cytokine-mediated signaling produces antidepressant-like effects 38. Clinical data suggest that cytokines may play a role in the pathophysiology of a subgroup of depressed subjects, particularly those with comorbid physical conditions 36. The antidepressant enhancing effect of acetylsalicylic acid 39 points to the possible clinical relevance of psychoneuroimmunology in clinical depression research. Taken together, the laboratory tests with the highest potential to be clinically useful in the care of depressed individuals are based on abnormalities of the neuroendocrine and neuroimmune systems. Despite the large amount of basic science data suggesting that the HPA axis is importantly involved in the pathophysiology of depression, the effect of pharmacological modulation of this neuroendocrine system as antidepressant therapy has been disappointing. The link between childhood trauma and a permanently altered physiologic stress system points to the use of specific psychotherapies in the treatment of depressed patients with a history of early life trauma 40. Most of the serotonergic, noradrenergic and dopaminergic neurons are located in midbrain and brainstem nuclei and project to large areas of the entire brain. This anatomy suggests that monoaminergic systems are involved in the regulation of a broad range of brain functions, including mood, attention, reward processing, sleep, appetite, and cognition. Almost every compound that inhibits monoamine reuptake, leading to an increased concentration of monoamines in the synaptic cleft, has been proven to be a clinically effective antidepressant 19. Inhibiting the enzyme monoamine oxidase, which induces an increased availability of monoamines in presynaptic neurons, also has antidepressant effects. These observations led to the pharmacologically most relevant theory of depression, referred to as the monoamine-deficiency hypothesis. The monoamine-deficiency theory posits that the underlying pathophysiological basis of depression is a depletion of the neurotransmitters serotonin, norepinephrine or dopamine in the central nervous system. Serotonin is the most extensively studied neurotransmitter in depression. The most direct evidence for an abnormally reduced function of central serotonergic system comes from studies using tryptophan depletion, which reduces central serotonin synthesis. Such a reduction leads to the development of depressive symptoms in subjects at increased risk of depression (subjects with MDD in full remission, healthy subjects with a family history of depression) 41,42, possibly mediated by increased brain metabolism in the ventromedial prefrontal cortex and subcortical brain regions 42. Experimentally reduced central serotonin has been associated with mood congruent memory bias, altered reward-related behaviors, and disruption of inhibitory affective processing 16, all of which add to the clinical plausibility of the serotonin deficiency hypothesis. There is also evidence for abnormalities of serotonin receptors in depression, with the most solid evidence pointing to the serotonin-1A receptor, which regulates serotonin function. Decreased availability of this receptor has been found in multiple brain areas of patients with MDD 43, although this abnormality is not highly specific for MDD and has been found in patients with panic disorder 44 and temporal lobe epilepsy 45, possibly contributing to the considerable comorbidity among these conditions. However, there is no explanation for the mechanism of serotonin loss in depressed patients, and studies of serotonin metabolites in plasma, urine and cerebrospinal fluid, as well as post-mortem research on the serotonergic system in depression, have yielded inconsistent results. There is preliminary evidence that an increased availability of the brain monoamine oxidase, which metabolizes serotonin, may cause serotonin deficiency 46. In addition, loss-of-function mutations in the gene coding for the brain-specific enzyme tryptophan hydroxylase-2 may explain the loss of serotonin production as a rare risk factor for depression 47. Dysfunction of the central noradrenergic system has been hypothesized to play a role in the pathophysiology of MDD, based upon evidence of decreased norepinephrine metabolism, increased activity of tyrosine hydroxylase, and decreased density of norepinephrine transporter in the locus coeruleus in depressed patients 48. In addition, decreased neuronal counts in the locus coeruleus, increased alpha-2 adrenergic receptor density, and decreased alpha-1 adrenergic receptor density have been found in the brains of depressed suicide victims post-mortem 49. Since there is no method to selectively deplete central norepinephrine and no imaging tool to study the central norepinephrine system, solid evidence for abnormalities of this system in depression is lacking. While the classical theories of the neurobiology of depression mainly focused on serotonin and norepinephrine, there is increasing interest in the role of dopamine 50. Dopamine reuptake inhibitors (e.g., nomifensine) and dopamine receptor agonists (e.g., pramipexole) had antidepressant effects in placebo-controlled studies of MDD 51. In the cerebrospinal fluid and jugular vein plasma, levels of dopamine metabolites were consistently reduced in depression, suggesting decreased dopamine turnover 52. Striatal dopamine transporter binding and dopamine uptake were reduced in MDD, consistent with a reduction in dopamine neurotransmission 53. Degeneration of dopamine projections to the striatum in Parkinson's disease was associated with a major depressive syndrome in about one half of cases, which usually preceded the appearance of motor signs 54. Experimentally reduced dopaminergic transmission into the accumbens has been associated with anhedonic symptoms and performance deficits on a reward processing task in subjects at increased risk of depression 55,56. These findings are consistent with the clinical observation that depressed patients have a blunted reaction to positive reinforcers and an abnormal response to negative feedback 57. Almost all established antidepressants target the monoamine systems 58. However, full and partial resistance to these drugs and their delayed onset of action suggest that dysfunctions of monoaminergic neurotransmitter systems found in MDD represent the downstream effects of other, more primary abnormalities. Despite this limitation, the monoamine-deficiency hypothesis has proved to be the most clinically relevant neurobiological theory of depression. New findings on the role of dopamine in depression emphasize the scientific potential of this theory, and promising reports of antidepressant effects of drugs that modulate the dopaminergic system (e.g., pramipexole, modafinil) in difficult-to-treat depression underline its clinical relevance 51,59. Although many historical attempts to localize mental functions have failed, they have considerably contributed to a modern neuroscientific understanding of mental disorders 60. The development of neuroimaging techniques has opened up the potential to investigate structural and functional abnormalities in living depressed patients. Unfortunately, the diversity of imaging techniques used, the relatively small and heterogeneous study samples studied, and the limited overlap of results across imaging paradigms 61 make it difficult to reliably identify neuronal regions or networks with consistently abnormal structure or function in MDD. Functional imaging studies have provided the most limited overlap of findings. This may be due to methodological limitations and/or the complexity of neurocircuitry involved in MDD. A recent meta-analytic study found the best evidence for abnormal brain activity in MDD in lateral frontal and temporal cortices, insula, and cerebellum. In these brain regions activity was decreased at rest, they showed a relative lack of activation during induction of negative emotions, and an increase in activity following treatment with serotonin reuptake inhibitors. Opposite changes may exist in ventromedial frontal areas, striatum and possibly other subcortical brain regions 61. More solid evidence has been provided by structural imaging and post-mortem studies. A recent meta-analytic study on brain volume abnormalities in MDD revealed relatively large volume reductions in the ventromedial prefrontal cortex, particularly in the left anterior cingulate and in the orbitofrontal cortex. Moderate volume reductions were found in the lateral prefrontal cortex, hippocampus and striatum 62. Post-mortem studies consistently identified a reduction in glia cell density in dorsal, orbital and subgenual prefrontal cortices, as well as in the amygdala 63,64. Overall, functional, structural and post-mortem studies suggest that structural and functional abnormalities in the left subgenual cingulate cortex are the most solid neuroanatomical finding in MDD. Volume reduction in this region was found early in illness and in young adults at high familial risk for MDD 65, suggesting a primary neurobiological abnormality associated with the etiology of the illness. Humans with lesions that include the subgenual prefrontal cortex showed abnormal autonomic responses to social stimuli 66, and rats with left-sided lesions in this region had increased sympathetic arousal and corticosterone responses to restraint stress 67. Most importantly, chronic deep brain stimulation to reduce the potentially elevated activity in the subgenual cingulated cortex produced clinical benefits in patients with treatment-resistant depression 68. In summary, despite the considerable heterogeneity of findings from neuroimaging studies, there is convergent evidence for the presence of abnormalities in the subgenual prefrontal cortex in some patients with MDD. Neuroanatomical research in depression is of great clinical interest, since novel antidepressant treatments such as deep brain stimulation can target specific brain regions. In addition, there are promising leads for neuroimaging findings to predict the likelihood of responses to specific treatments 69. Risk factors for depressive episodes change during the course of the illness. The first depressive episode is usually “reactive”, i.e., triggered by important psychosocial stressors, while subsequent episodes become increasingly “endogenous”, i.e., triggered by minor stressors or occurring spontaneously 70. There is consistent evidence that the volume loss of the hippocampus and other brain regions is related to the duration of depression 71, suggesting that untreated depression leads to hippocampal volume loss, possibly resulting in increased stress sensitivity 72 and increased risk of recurrence 73. Glucocorticoid neurotoxicity, glutamatergic toxicity, decreased neurotrophic factors, and decreased neurogenesis have been proposed as possible mechanisms explaining brain volume loss in depression. There is no solid evidence on of these since there are no imaging to directly and neurotrophic processes in neurotrophic factor has considerable Specifically, studies have shown between and in hippocampal as well as expression of following antidepressant treatment The clinician should be aware of the potentially effect of depression and treat depressed patients as early and as A of studies consistently showed reductions in acid concentrations in the prefrontal and cortex in depression This may reflect stress since psychological stress to presynaptic of prefrontal neurotransmission low concentration may reflect reduction in the density and of In addition, chronic stress may reduce receptor possibly through changes in evidence of the hypothesis of depression the lack of effects of drugs on depressive symptoms and prefrontal concentration in subjects with MDD of evidence suggest a dysfunction of the neurotransmitter system in a of the receptor produced and large antidepressant effects in patients with treatment-resistant MDD inhibitors of release (e.g., antidepressant abnormal levels were found in depressed subjects as by and there is evidence for abnormal signaling in post-mortem Since is the major neurotransmitter involved in almost every brain the of the specific role of in depression (e.g., there are promising leads that the receptor is involved in MDD and are diagnostic for MDD, suggesting regulation in depressed patients. In addition, some depressive symptoms may show psychomotor of of positive and negative and a subgroup of patients with MDD may have a disorder In healthy young subjects, changes in the of the had specific effects on subsequent mood In depressed patients, of can have antidepressant on these abnormalities have been hypothesized to be associated with MDD The association between of the and in cortisol in some subjects with and the effect of antidepressants on of and to the of this hypothesis Despite of the many promising the and genetic of this hypothesis are It remains to be antidepressant effects of such as directly to of on these abnormalities have been hypothesized to be associated with MDD The association between of the and in cortisol in some subjects with and the effect of antidepressants on of and to the of this hypothesis Despite of the many promising the and genetic of this hypothesis are It remains to be antidepressant effects of such as directly to of The and of the neurobiological of depression are in 1. The many theories of depression and the relatively low response rate of all antidepressant treatments a hypothesis of and suggest that depression is a clinically and heterogeneous disorder. This research on of the response to therapeutic interventions using such as neuroimaging and neuroendocrine tests in with for with to stress sensitivity and antidepressant The of of therapeutic will for the development of that has the potential to interventions and to up pathways in the of novel therapeutic approaches.

World Psychiatry · editorial or comment · 607 citationsread the source →

Mentalization based treatment for borderline personality disorder

Borderline personality disorder (BPD) is a complex and serious mental disorder characterized by a pervasive pattern of difficulties with emotion regulation and impulse control, and instability both in relationships and in selfimage 1. It represents a serious public health problem, because it is associated with suicide attempts and self harm, both of which are consistent targets of mental health services. Recurrent suicidal behaviour is reported in 69–80% of patients with BPD, and suicide rates are estimated to be up to 10% 2. BPD is a common condition that is thought to occur globally with a prevalence of 0.2–1.8% in the general population 3. Higher prevalence rates are found in clinical populations. Moran et al 4 found a prevalence rate of 4–6% among primary care attenders, suggesting that people with BPD are more likely to visit their general practitioner. Chanen et al 5 reported a prevalence rate of 11% in adolescent outpatients and 49% in adolescent inpatients. The highest prevalence has been found in people requiring the most intensive level of care, with a rate of 60–80% among patients in forensic services 6–7. The high prevalence and increased suicide rate in patients with BPD make an unassailable argument that effective treatment needs to be developed and that treatment has to be widely available. Whilst a number of treatments for BPD have been shown to be moderately effective in randomized controlled trials, it remains of considerable concern that most of them require extensive training, making them unavailable to most patients. Mentalization based treatment (MBT) was developed with this in mind. It requires relatively little additional training on top of general mental health training, and has been implemented in research studies by community mental health professionals, primarily nurses, with limited training given modest levels of supervision. The term mentalization grew out of the Ecole Psychosomatique de Paris and to some extent was operationalized by developmental researchers investigating theory of mind 8. It was first used by Fonagy in 1989 9 in a broader way and has since been developed in relation to understanding a number of mental disorders. Mentalization, or better mentalizing, is the process by which we make sense of each other and ourselves, implicitly and explicitly, in terms of subjective states and mental processes. It is a profoundly social construct in the sense that we are attentive to the mental states of those we are with, physically or psychologically. Given the generality of this definition, most mental disorders will inevitably involve some difficulties with mentalization. In fact, we can conceive of most mental disorder as the mind misinterpreting its own experience of itself, thus ultimately a disorder of mentalization. However, the key issue is whether the dysfunction is core to the disorder and/or a focus on mentalization is heuristically valid, i.e. provides an appropriate domain for therapeutic intervention. While mentalizing theory is being applied to a number of disorders (e.g., posttraumatic stress disorder 10, eating disorders 11 and depression 12), in a number of contexts (e.g., inpatient, partial hospital, and outpatient facilities), and in different groups of patients (e.g., adolescents, families, substance abusers), the treatment method is most clearly organized as a therapy for BPD 13. It is only in this condition that clear empirical support with randomized controlled trials 14–15 is available. In BPD, a fragile mentalizing capacity vulnerable to social and interpersonal interaction is considered a core feature of the disorder. If a treatment is to be successful, it must either have mentalization as its focus or at the very least stimulate development of mentalizing as an epiphenomenon. The failure of adult mental processing in borderline states had been apparent to most clinicians, but none had identified the primary difficulty as a loss of mentalizing arising from early development. The simple basic suggestion we made was that representing self and others as thinking, believing, wishing or desiring did not arrive at age 4 as a consequence of maturation, but rather was a developmental achievement that was profoundly rooted in the quality of early object relations. Its predictable vulnerability to disappearance under stress in borderline conditions was seen as an appropriate focus for psychodynamically oriented psychological intervention, even though concerns had been expressed over many decades about the use of psychodynamic therapy in the treatment of BPD. These began as long ago as 1938, when an American psychoanalyst, Adolph Stern, identified a group of patients, now considered to have had BPD, who did not respond to classical psychoanalytic treatment 16. He later described modifications of psychotherapy for his borderline group that remain relevant today 17. Mentalizing theory is rooted in Bowlby's attachment theory and its elaboration by contemporary developmental psychologists, whilst paying attention to constitutional vulnerabilities. There is suggestive evidence that borderline patients have a history of disorganized attachment, which leads to problems in affect regulation, attention and self control 18–19. It is our suggestion that these problems are mediated through a failure to develop a robust mentalizing capacity. Our understanding of others critically depends on whether as infants our own mental states were adequately understood by caring, attentive, non-threatening adults. The most important cause of disruption in mentalizing is psychological trauma early or late in childhood, which undermines the capacity to think about mental states or the ability to give narrative accounts of one's past relationships. Building on the accumulating evidence from developmental psychopathology, the mentalization theory of BPD first suggests that individuals are constitutionally vulnerable and/or exposed to psychological trauma; second, that both these factors can undermine the development of social/cognitive capacities necessary for mentalization via neglect in early relationships 20, especially where the contingency between their emotional experience and the caregiver's mirroring is non-congruent 21; third, that this results in an hypersensitive attachment system within interpersonal contexts; and fourth, that this leads to the development of an enfeebled ability to represent affect and effortfully control attentional capacity 22. Given the known continuity of attachment styles over time, residues of attachment problems of childhood might be expected to be apparent in adulthood. The adult attachment literature in relation to BPD has been reviewed by Levy 23. While the relationship between BPD diagnosis and a specific attachment category is not obvious, there is little doubt that BPD is strongly associated with insecure attachment (only 6–8% of BPD patients are coded as secure). It appears that early attachment insecurity is a relatively stable characteristic of BPD patients, particularly in conjunction with subsequent negative life events 24. The focus in treatment of BPD needs to be on stabilizing the sense of self and helping the patient maintain an optimal level of arousal in the context of a well-managed, i.e. not too intense and yet not too detached, attachment relationship between patient and therapist. The patient with BPD is exquisitely sensitive to all interpersonal interactions. So, the therapist needs to be aware that therapy, an interpersonal interaction, inevitably will provoke anxiety related to loss of a sense of self and that the ensuing emotional experiences will rapidly threaten to overwhelm the patient's mental capacities, leading to escalating emotions and inability to accurately understand others’ motives. Psychiatrists and other mental health professionals also need to be aware of this sensitivity if they are to avoid iatrogenic interactions with patients with BPD. Inpatient hospital admission, for example, is an intense emotional experience for all patients and, unless carefully managed, will make patients with BPD worse by overstimulating their attachment processes. This overstimulation in treatment may account for the poor long-term outcomes of patients with BPD when unmodified intensive treatments were offered (25). Patients with BPD have a vulnerability in regulating emotional responses and generating effective strategies for controlling their thoughts and feelings, which challenges their capacity for thinking about their own actions in terms of subtle understandings of their thoughts and feelings. They slip into what superficially could be described as a kind of mindless state, both in relation to others and to themselves. Of course, the story turns out to be more complicated than this, because these incapacities, palpable at certain times, are not always evident. But, at moments of emotional distress, particularly distress triggered by actual or threatened loss, the capacity for mentalization is most likely to apparently evaporate. The question is how this understanding and the clinical observations can usefully be translated into a therapeutic approach that could be helpful given the prevalence and severity of this clinical problem within a public healthcare system. To this end, we defined some core underpinning techniques to be used in the context of group and individual therapy and labeled them MBT 13–26. Only three important aspects of treatment will be considered here, namely the aim of interventions, the therapeutic stance, and mentalizing the transference. The initial task in MBT is to stabilize emotional expression, because without improved control of affect there can be no serious consideration of internal representations. Although the converse is also true, identification and expression of affect are targeted first because they represent an immediate threat to continuity of therapy as well as potentially to the patient's life. Uncontrolled affect leads to impulsivity, and only once this affect is under control is it possible to focus on internal representations and to strengthen the patient's sense of self. The aim and the actual outcome of an intervention are more important in MBT than the type of intervention itself. The primary aim of any intervention has to be to reinstate mentalizing when it is lost or to help to maintain it in circumstances when it might be lost or is being lost. Any intervention that succeeds in these aims may be used in MBT. As a result of this, MBT takes a more permissive approach to interventions than most other therapies, giving it a plurality in terms of technique which might account for its popularity and appeal to practitioners from different schools as well as the limited amount of training required before practitioners begin using it in their everyday practice. We do not ask that practitioners learn a new model of therapy from the beginning, but that they modify their current practice focussing on mentalizing rather than behaviours, cognitions, or insight. We do, however, ask that they undertake to develop a particular therapeutic stance and implement a series of steps to try to engage the patient in a process of mentalizing, firstly using some generic psychotherapy techniques such as empathy, support and clarification, and then moving on to other interventions specifically designed to “stress” the attachment relationship within controlled conditions, which includes a focus on the patienttherapist relationship through “mentalizing the transference”. The therapist's mentalizing therapeutic stance should include: a) humility deriving from a sense of “notknowing”; b) patience in taking time to identify differences in perspectives; c) legitimizing and accepting different perspectives; d) actively questioning the patient about his/her experience — asking for detailed descriptions of experience (“what questions”) rather than explanations (“why questions”); e) careful eschewing of the need to understand what makes no sense (i.e., saying explicitly that something is unclear). An important component of this stance is monitoring one's own mentalizing failures as a therapist. In this context, it is important to be aware that the therapist is constantly at risk of losing his/her capacity to mentalize in the face of a nonmentalizing patient. Consequently, we consider therapists’ occasional enactments as an acceptable concomitant of the therapeutic alliance, something that simply has to be owned up to. As with other instances of breaks in mentalizing, such incidents require that the process is “rewound and the incident explored”. Hence, in this collaborative patient-therapist relationship, the two partners involved have a joint responsibility to understand mental processes underpinning events both within and without therapy. We caution about the use of transference interpretation in the treatment of BPD because it assumes a level of mentalizing capacity of the patient that he/she often does not possess. This may have led to the suggestion that we “specifically eschew transference interpretation” (27). We do not. In fact we specifically employ transference interpretation, give indicators about when it can be used and carefully define six essential components. But equally we caution practitioners firstly about the commonly stated aim of transference interpretation, namely to provide insight, and secondly about genetic aspects, such as linking current experience to the past, because of their potential iatrogenic effects. Our first step is the validation of the transference feeling, that is establishing the patient's perspective. Of course this is not the same as agreeing with the patient, but it must be evident to the patient that the therapist has at least understood his/her point of view. The danger of the genetic approach to the transference is that it might implicitly invalidate the patient's experience. The second step is exploration. The events which generated the transference feelings must be identified. The behaviours that the thoughts or feelings are tied to need to be made explicit, sometimes in painful detail. The third step is accepting enactment on the part of the therapist. Most experiences of the patient in the transference are likely to be based on reality, even if on a very partial connection to it. Mostly this means that the therapist has been drawn into the transference and acted in some way consistent with the patient's perception of him/her. It may be easy to attribute this to the patient, but this would be completely unhelpful. On the contrary, the therapist should initially explicitly acknowledge even partial enactments of the transference as inexplicable voluntary actions that he/she accepts agency for, rather than identifying them as a distortion of the patient. Drawing attention to such therapist components may be particularly significant in modeling to the patient that one can accept agency for involuntary acts and that such acts do not invalidate the general attitude which the therapist tries to convey. Only then can distortions be explored. Step four is collaboration in arriving at an interpretation. Transference interpretations must be arrived at in the same spirit of collaboration as any other form of interpretive mentalizing. The metaphor we use in training is that the therapist must imagine sitting side-by-side with the patient, not opposite. They sit side-by-side looking at the patient's thoughts and feelings, where possible both adopting the inquisitive stance. The fifth step is for the therapist to present an alternative perspective and the final step is to monitor carefully the patient's reaction as well as one's own. We suggest these steps are taken in sequence and we talk about mentalizing the transference to distinguish the process from transference interpretation, which is commonly viewed as a technique to provide insight. Mentalizing the transference is a shorthand term for encouraging patients to think about the relationship they are in at the current moment (the therapist relationship) with the aim to focus their attention on another mind, the mind of a therapist, and to assist them in the task of contrasting their own perception of themselves with how they are perceived by another, by the therapist or indeed by members of a therapeutic group. Whilst we might point to similarities in patterns of relationships in the therapy and in childhood or currently outside of the therapy, the aim of this is not to provide the patients with an explanation (insight) that they might be able to use to control their behaviour pattern, but far more simply to highlight one other puzzling phenomenon that requires thought and contemplation, part of our general therapeutic stance aimed to facilitate the recovery of mentalization which we see as the overall aim of treatment. Our initial study of MBT 14 compared its effectiveness in the context of a partial hospital program with routine general psychiatric care for patients with BPD. Treatment took place within a routine clinical service and was implemented by mental health professionals without full psychotherapy training who were offered expert supervision. Results showed that patients in the partial hospital program showed a statistically significant decrease on all measures, in contrast with the control group, which showed limited change or deterioration over the same period. Improvement in depressive symptoms, decrease in suicidal and self-mutilatory acts, reduced inpatient days, and better social and interpersonal function began after 6 months and continued to the end of treatment at 18 months. The 44 patients who participated in the original study were assessed at 3 month intervals after of the using the same of outcome Results that patients who had partial hospital treatment not only their but also showed a statistically significant continued on most measures, in contrast with the control group of patients who showed only limited change the same period. of continued in social and interpersonal these suggest that were an was made to health care associated with partial hospital treatment compared with treatment within general psychiatric services care of all patients who participated in the was assessed using from and service were compared 6 months to 18 months of and at differences were found between the groups or treatment. the treatment the of partial hospital treatment were by psychiatric inpatient care and reduced treatment. The for to decrease in the group was not in the control group, suggesting that partial hospital treatment for BPD is no more than general psychiatric care and leads to considerable after the of treatment. patients who participated in the partial hospital treatment have now been up after initial The primary outcome for this study was number of suicide However, in the of the limited related to social in we were to whether the social and interpersonal found at the end of months had been and whether additional in the of achievement had been made in either group. Patients in the MBT program better than those treatment as their initial at the end of their general social function many more were in or full time than the group, and only for BPD compared to of the patients in the group who were for randomized controlled of MBT in an outpatient has been patients were to or clinical representing current practice. were in both conditions all outcome Patients randomized to showed a of both and significant suicide attempts and research studies are randomized controlled trials on patients with substance use disorders and patients with eating disorders. partial study of the original partial hospital has also been by an group in the that results are within mental health services from the of the treatment. MBT may not be different from other of intervention widely by and other mental health professionals in the contexts in which individuals with BPD are being We no for the intervention. MBT represents the relatively of a of developmental processes identified in all our a) the of an intense relationship based on attempts to engage the patients in a process of understanding their mental and b) the of their feelings and that patients are able to identify themselves as thinking and in the context of and high levels of emotional In the recovery of mentalization patients their thoughts and feelings, which then makes relationships and a Although we would to have identified a particular method that makes the of this therapeutic process we make no of can likely about and personality change by this and our of The of research is to identify effective and for generating change in this group.

World Psychiatry · editorial or comment · 663 citationsread the source →

Recreational drug use, polydrug use, and sexual behaviour in HIV-diagnosed men who have sex with men in the UK: results from the cross-sectional ASTRA study.

Background: Recreational drug use in men who have sex with men (MSM) is of concern because it might be linked to the transmission of HIV and other sexually transmitted infections. Evidence about drug use in HIV-diagnosed MSM in the UK is limited by representativeness of the study populations. We describe patterns of drug use and associations with sexual behaviours in HIV-diagnosed MSM in the UK. Methods: We used data from the cross-sectional ASTRA study, which recruited participants aged 18 years or older with HIV from eight HIV outpatient clinics in the UK between Feb 1, 2011, and Dec 31, 2012. We examined data for MSM, assessing the prevalence of recreational drug use and polydrug use in the previous 3 months and associations with sociodemographic and HIV-related factors. We examined the association of polydrug use with measures of condomless sex in the previous 3 months and with other sexual behaviours. Findings: Our analysis included data for 2248 MSM: 2136 (95%) were gay, 1973 (89%) were white, 1904 (85%) were on antiretroviral treatment (ART), and 1682 (76%) had a viral load of 50 copies per mL or lower. 1138 (51%) used recreational drugs in the previous 3 months; 608 (27%) used nitrites, 477 (21%) used cannabis, 460 (21%) used erectile dysfunction drugs, 453 (20%) used cocaine, 280 (13%) used ketamine, 258 (12%) used 3,4-methylenedioxy-N-methylamphetamine (MDMA), 221 (10%) used gamma-hydroxybutyrate or gamma-butyrolactone, 175 (8%) used methamphetamine, and 162 (7%) used mephedrone. In the 1138 individuals who used drugs, 529 (47%) used three or more drugs and 241 (21%) used five or more. Prevalence of injection drug use was 3% (n = 68). Drug use was independently associated with younger age (p < 0·0001), not being religious (p = 0·001), having an HIV-positive stable partner (p = 0·0008), HIV-serostatus disclosure (p = 0·009), smoking (p < 0·0001), evidence of harmful alcohol drinking (p = 0·0001), and ART non-adherence (p < 0·0001). Increasing polydrug use was associated with increasing prevalence of condomless sex (prevalence range from no drug use to use of five or more drugs was 24% to 78%), condomless sex with HIV-seroconcordant partners (17% to 69%), condomless sex with HIV-serodiscordant partners (10% to 25%), and higher-HIV-risk condomless sex after taking viral load into account (4% to 16%; p ≤ 0·005 for all). Associations were similar after adjustment for sociodemographic and HIV-related factors. Methamphetamine was more strongly associated with higher-HIV-risk condomless sex than were other commonly used drugs. Interpretation: Polydrug use is prevalent in HIV-diagnosed MSM and is strongly associated with condomless sex. Specialist support services for MSM with HIV who use recreational drugs might be beneficial in the reduction of harm and prevention of ongoing transmission of HIV and other sexually transmitted infections. Funding: National Institute for Health Research.

The lancet. HIV · 226 citationsread the source →

Prevalence and characteristics of tinnitus among US adults.

Background: Tinnitus is common; however, few risk factors for tinnitus are known. Methods: We examined cross-sectional relations between several potential risk factors and self-reported tinnitus in 14,178 participants in the 1999-2004 National Health and Nutrition Examination Surveys, a nationally representative database. We calculated the prevalence of any and frequent (at least daily) tinnitus in the overall US population and among subgroups. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) after adjusting for multiple potential confounders. Results: Approximately 50 million US adults reported having any tinnitus, and 16 million US adults reported having frequent tinnitus in the past year. The prevalence of frequent tinnitus increased with increasing age, peaking at 14.3% between 60 and 69 years of age. Non-Hispanic whites had higher odds of frequent tinnitus compared with other racial/ethnic groups. Hypertension and former smoking were associated with an increase in odds of frequent tinnitus. Loud leisure-time, firearm, and occupational noise exposure also were associated with increased odds of frequent tinnitus. Among participants who had an audiogram, frequent tinnitus was associated with low-mid frequency (OR 2.37; 95% CI, 1.76-3.21) and high frequency (OR 3.00; 95% CI, 1.78-5.04) hearing impairment. Among participants who were tested for mental health conditions, frequent tinnitus was associated with generalized anxiety disorder (OR 6.07; 95% CI, 2.33-15.78) but not major depressive disorder (OR 1.58; 95% CI, 0.54-4.62). Conclusions: The prevalence of frequent tinnitus is highest among older adults, non-Hispanic whites, former smokers, and adults with hypertension, hearing impairment, loud noise exposure, or generalized anxiety disorder. Prospective studies of risk factors for tinnitus are needed.

The American journal of medicine · 613 citationsread the source →

Decisions to limit life-sustaining treatment for critically ill patients who lack both decision-making capacity and surrogate decision-makers.

Objective: Many intensive care unit (ICU) physicians have withdrawn life-support from a patient who lacked decision-making capacity and a surrogate decision-maker, yet little is known about the decision-making practices for these patients. We sought to determine how often such patients are admitted to the ICU of a metropolitan hospital and how end-of-life decisions are made for them. Design: Prospective, observational cohort study. Patients and setting: Consecutive adult patients admitted to the medical ICU of a metropolitan West Coast hospital during a 7-month period in 2003 to 2004. Measurements: Attending physicians completed a questionnaire about the decision-making process for each patient for whom they considered limiting life-support who lacked decisional capacity and a legally recognized surrogate decision-maker. Main results: Of the 303 patients admitted during the study period, 49 (16%; 95% confidence interval [CI], 12-21%) lacked decision-making capacity and a surrogate during the entire ICU stay. Compared with all other ICU patients, these patients were more likely to be male (88% vs. 69%; p = .002), white (42% vs. 23%; p = .028), and > or =65 yrs old (29% vs. 13%; p = .007). Physicians considered withholding or withdrawing treatment from 37% (18) of the 49 patients who lacked both decision-making capacity and a surrogate decision-maker. For 56% (10) of these 18 patients, the opinion of another attending physician was obtained; for 33% (6 of 18), the ICU team made the decision independently, and for 11% (2 of 18), the input of the courts or the hospital ethics committee was obtained. Overall, 27% of deaths (13 of 49) during the study period were in incapacitated patients who lacked a surrogate (95% CI, 15-41%). Conclusions: Sixteen percent of patients admitted to the medical ICU of this hospital lacked both decision-making capacity and a surrogate decision-maker. Decisions to limit life support were generally made by physicians without judicial or institutional review. Further research and debate are needed to develop optimal decision-making strategies for these difficult cases.

Critical care medicine · 88 citationsread the source →

Impaired declarative memory consolidation during sleep in patients with primary insomnia: Influence of sleep architecture and nocturnal cortisol release.

Background: A central cognitive function of sleep is to consolidate newly acquired memories for long-term storage. Here, we investigated whether the overnight consolidation of declarative memory in patients with chronic sleep disturbances is impaired, owing to less slow wave sleep (SWS) and an increased cortisol release. Methods: Polysomnographic recordings, serum cortisol concentrations, and overnight memory consolidation in 16 patients with primary insomnia were compared with those of 13 healthy control subjects. Results: Patients displayed distinctly less overnight consolidation of declarative memory (p < .05), which was significantly correlated with SWS in the control subjects (r = .69) but with rapid eye movement (REM) sleep in the patients (r = .56), who had a diminished amount of SWS (p < .05). Increased cortisol levels in the middle of the night were associated with impaired retrieval of declarative memory after sleep for both control subjects (r = -.52) and patients (r = -.46). Conclusions: Primary insomnia is associated with a diminished sleep-related consolidation of declarative memory. Efficient overnight consolidation of declarative memory is associated with high amounts of SWS and low serum cortisol levels during the early part of the night. Where SWS is decreased, REM sleep might play a partly compensatory role in the consolidation of declarative memory.

Biological psychiatry · 171 citationsread the source →

Circumcision in Australia: prevalence and effects on sexual health.

The results from a telephone survey in 2001-02 of a probability sample of Australian households including 10,173 men aged 16-59 (response rate 69.4%) are used to assess the prevalence of circumcision across social groups in Australia and examine lifetime history of sexually transmissible infection (STI), sexual difficulties in the last year, sexual practices including masturbation, and sexual attitudes. More than half (59%) of the men were circumcised. Circumcision was less common among younger men (32% aged <20) and more common among the Australian born (69%). After correction for age, circumcision was unrelated to reporting STI, but appeared to protect against penile candidiasis. Circumcision was unrelated to most sexual difficulties, but circumcised men were less likely to report physical pain during intercourse or trouble keeping an erection; reasons for this are unknown. There were no significant differences in practices at last sexual encounter with a female partner or in masturbation alone. Circumcised men had somewhat more liberal sexual attitudes. Neonatal circumcision was routine in Australia until the 1970s. It appears not to be associated with significant protective or harmful sexual health outcomes. This study provides no evidence about the effects on sexual sensitivity.

International journal of STD & AIDS · 37 citationsread the source →

Interventions for treating femoral shaft fractures in children and adolescents.

Background: Fractures of the femoral shaft in children are relatively uncommon but serious injuries that disrupt the lives of children and their carers and can result in significant long-term disability. Treatment involves either surgical fixation, such as intramedullary nailing or external fixation, or conservative treatment involving prolonged immobilisation, often in hospital. Objectives: To assess the effects (benefits and harms) of interventions for treating femoral shaft fractures in children and adolescents. Search methods: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (accessed 16 August 2013), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2013 Issue 7), MEDLINE (1946 to August Week 1 2013), EMBASE (1980 to 2012 week 9), CINAHL (16 August 2013), clinical trials registries, conference proceedings and reference lists; and contacted trial authors and experts in the field. Selection criteria: Randomised and quasi-randomised controlled trials comparing conservative and surgical interventions for diaphyseal fractures of the femur in children under 18 years of age. Our primary outcomes were functional outcome measures, unacceptable malunion, and serious adverse events. Data collection and analysis: Two authors independently screened and selected trials, assessed risk of bias and extracted data. We assessed the overall quality of the evidence for each outcome for each comparison using the GRADE approach. We pooled data using a fixed-effect model. Main results: We included 10 trials (six randomised and four quasi-randomised) involving a total of 527 children (531 fractures). All trials were at some risk of bias, including performance bias as care provider blinding was not practical, but to a differing extent. Just one trial was at low risk of selection bias. Reflecting both the risk of bias and the imprecision of findings, we judged the quality of evidence to be 'low' for most outcomes, meaning that we are unsure about the estimates of effect. Most trials failed to report on self-assessed function or when children resumed their usual activities. The trials evaluated 10 different comparisons, belonging to three main categories. Surgical versus conservative treatment. Four trials presenting data for 264 children aged 4 to 12 years made this comparison. Low quality evidence (one trial, 101 children) showed children had very similar function assessed using the RAND health status score at two years after surgery (external fixation) compared with conservative treatment (spica cast): mean 69 versus 68. The other three trials did not report on function. There was moderate quality evidence (four trials, 264 children, aged 4 to 12 years, followed up 3 to 24 months) that surgery reduced the risk of malunion (risk ratio (RR) 0.29, 95% confidence interval (CI) 0.15 to 0.59, 4 trials). Assuming an illustrative baseline risk of 115 malunions per 1000 in children treated conservatively, these data equate to 81 fewer (95% CI 47 to 97 fewer) malunions per 1000 in surgically-treated children. Conversely, low quality evidence indicated that there were more serious adverse events such as infections after surgery (RR 2.39, 95% CI 1.10 to 5.17, 4 trials). Assuming an illustrative baseline risk of 40 serious adverse events per 1000 for conservative treatment, these data equate to 56 more (95% CI 4 to 167 more) serious adverse events per 1000 children treated surgically. There was low quality evidence (one trial, 101 children) of similar satisfaction levels in children and parents with surgery involving external fixation and plaster cast only. However, there was low quality evidence (one trial, 46 children) that more parents were satisfied with intramedullary nailing than with traction followed by a cast, and that surgery reduced the time taken off from school. Comparisons of different methods of conservative treatment. The three trials in this category made three different comparisons. We are very unsure if unacceptable malunion rates differ between immediate hip spica versus skeletal traction followed by spica in children aged 3 to 10 years followed up for six to eight weeks (RR 4.0, 95% CI 0.5 to 32.9; one trial, 42 children; very low quality evidence). Malunion rates at 5 to 10 years may not differ between traction followed by functional orthosis versus traction followed by spica cast in children aged 5 to 13 years (RR 0.98, 95% CI 0.46 to 2.12; one trial, 43 children; low quality evidence). We are very unsure (very low quality evidence) if either function or serious adverse events (zero events reported) differ between single-leg versus double-leg spica casts (one trial, 52 young children aged two to seven years). Low quality evidence on the same comparison indicates that single-leg casts are less awkward to manage by parents, more comfortable for the child and may require less time off work by the caregiver. Comparisons of different methods of surgical treatment. The three trials in this category made three different comparisons. Very low quality evidence means that we are very unsure if the rates of malunion, serious adverse events, time to return to school or parental satisfaction actually differ in children whose fractures were fixed using elastic stable intramedullary nailing or external fixation (one trial, 19 children). The same applies to the rates of serious adverse events and time to resume full weight-bearing in children treated with dynamic versus static external fixation (one trial, 52 children). Very low quality evidence (one trial, 47 children) means that we do not know if malunion, serious adverse events and time to resume weight-bearing actually differ between intramedullary nailing versus submuscular plating. However, there could be more difficulties in plate removal subsequently. Authors' conclusions: There is insufficient evidence to determine if long-term function differs between surgical and conservative treatment. Surgery results in lower rates of malunion in children aged 4 to 12 years, but may increase the risk of serious adverse events. Elastic stable intramedullary nailing may reduce recovery time. There is insufficient evidence from comparisons of different methods of conservative treatment or of different methods of surgical treatment to draw conclusions on the relative effects of the treatments compared in the included trials. Plain language summary: Different methods of treating fractures of the shaft of the thigh bone in children and adolescents Although uncommon, fractures of the femoral shaft (thigh bone) in children may require prolonged treatment in hospital and sometimes surgery. This can cause significant discomfort and can disrupt the lives of the children and their familles. This review compared different methods of treating these fractures. Surgical treatment comprises different methods of fixing the broken bones, such as internally-placed nails, or pins incorporated into an external frame (external fixation). Non-surgical or conservative treatment usually involves different types of plaster casts with or without traction (where a pulling force is applied to the leg). We searched for studies in the medical literature until August 2013. The review includes 10 randomised or quasi-randomised controlled trials that recruited 527 children. Four trials compared different surgical versus non-surgical treatments; three compared different methods of non-surgical treatment and three compared different methods of surgical treatment. Generally we are unsure about the results of these trials because some were at risk of bias, some results were contradictory and usually there was too little evidence to rule out chance findings. Most trials failed to report on self-assessed function or when children resumed their usual activities. Comparing surgical versus non-surgical treatment. Low quality evidence (one trial, 101 children) showed children had similar function at two years after having surgery, involving external fixation, compared with those treated with a plaster cast. The other three trials did not report this outcome. There was moderate quality evidence (four trials, 264 children, aged 4 to 12 years, followed up for 3 to 24 months) that surgery reduced the risk of malunion (the leg is deformed) compared with non-surgical treatment. However, low quality evidence (four trials) indicated that there were more serious adverse events such as infections after surgery. There was low quality evidence (one trial, 101 children) of similar satisfaction levels in children and parents with surgery involving external fixation and plaster cast only. However, there was low quality evidence (one trial, 46 children) that more parents were satisfied with surgery involving an internal nail than with traction followed by a cast and that surgery reduced the time taken off from school. Comparing various non-surgical treatments. Very low quality evidence means that we are very unsure if the rates of malunion differ or not between children treated with immediate plaster casts versus with traction followed by plaster cast (one trial, 42 children), or between children treated with traction followed by either a functional orthosis (a brace or cast that allows some movement) or a cast (one trial, 43 children). We are very unsure if either function or serious adverse events differ between young children (aged two to seven years) immobilised in single-leg versus double-leg casts (one trial, 52 children). However, single-leg casts appear to be easier to manage by parents and more comfortable for the child. Comparing various surgical treatments Very low quality evidence means that we are very unsure if the rates of malunion, serious adverse events, time to return to school or parental satisfaction actually differ in children whose fractures were fixed using internal nails or external fixation (one trial, 19 children). (ABSTRACT TRUNCATED)

Evidence-based child health : a Cochrane review journal · 16 citationsread the source →