Eating disorders in weight-related therapy (EDIT): Protocol for a systematic review with individual participant data meta-analysis of eating disorder risk in behavioural weight management

The Eating Disorders In weight-related Therapy (EDIT) Collaboration brings together data from randomised controlled trials of behavioural weight management interventions to identify individual participant risk factors and intervention strategies that contribute to eating disorder risk. We present a protocol for a systematic review and individual participant data (IPD) meta-analysis which aims to identify participants at risk of developing eating disorders, or related symptoms, during or after weight management interventions conducted in adolescents or adults with overweight or obesity. We systematically searched four databases up to March 2022 and clinical trials registries to May 2022 to identify randomised controlled trials of weight management interventions conducted in adolescents or adults with overweight or obesity that measured eating disorder risk at pre- and post-intervention or follow-up. Authors from eligible trials have been invited to share their deidentified IPD. Two IPD meta-analyses will be conducted. The first IPD meta-analysis aims to examine participant level factors associated with a change in eating disorder scores during and following a weight management intervention. To do this we will examine baseline variables that predict change in eating disorder risk within intervention arms. The second IPD meta-analysis aims to assess whether there are participant level factors that predict whether participation in an intervention is more or less likely than no intervention to lead to a change in eating disorder risk. To do this, we will examine if there are differences in predictors of eating disorder risk between intervention and no-treatment control arms. The primary outcome will be a standardised mean difference in global eating disorder score from baseline to immediately post-intervention and at 6- and 12- months follow-up. Identifying participant level risk factors predicting eating disorder risk will inform screening and monitoring protocols to allow early identification and intervention for those at risk

A randomised placebo-controlled multicentre trial of intravenous semapimod HCl for moderate to severe Crohn's disease

Objective Semapimod, a small molecule known to inhibit proinflammatory cytokine activity, was studied to determine the optimal dose necessary to achieve a response in patients with moderate to severe Crohn's disease (CD). Methods A randomised, double-blind, placebo-controlled trial (CD04) was carried out followed by an open-label extension study (CD05). The trial was conducted in international multicentre outpatient clinics and included patients with moderate to severe CD (Crohn's Disease Activity Index (CDAI) 250-400). Placebo was administered for 3 days; 60 mg semapimod intravenously for 1 day with placebo for 2 days; or 60 mg semapimod intravenously for 3 days. Participants who completed CD04 could participate in the open-label extension study, CD05, to receive up to five additional semapimod HCl 60 mg daily doses three times every 6-8 weeks. The main outcome measures were CDAI, Inflammatory Bowel Disease Questionnaire (IBDQ), Crohn's Disease Endoscopic Inflammation Score (CDEIS) and serum C-reactive protein (CRP) concentration. Results 152 patients were randomised in CD04. Responses for 1 and 3 day regimens were similar to placebo for CDAI (p=0.82), IBDQ (p=0.85), CDEIS (p=0.57) and CRP (p=0.40). The only noteworthy treatment-related safety finding was infusion reaction (phlebitis): 7.3, 34.8 and 62.7% for the placebo and 1 and 3 day semapimod treatment groups, respectively (p= 360 mg was associated with decreased CDAI in a limited number of patients.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Digital cognitive-behavioural therapy to reduce suicidal ideation and behaviours: A systematic review and meta-analysis of individual participant data

© 2022 Author(s). Published by BMJ.Question Digital interventions based on cognitive-behavioural therapy (iCBT) is associated with reductions in suicidal ideation. However, fine-grained analyses of effects and potential effect-moderating variables are missing. This study aimed to investigate the effectiveness of iCBT on suicidal ideation, effect moderators, effects on suicide attempts and predictors of adherence. Study selection and analysis We systematically searched CENTRAL, PsycINFO, Embase and PubMed for randomised controlled trials that investigated iCBT for suicidal ideation or behaviours. Participants reporting baseline suicidal ideation were eligible. We conducted a one-stage individual participant data (IPD) meta-analysis. Suicidal ideation was the primary outcome, analysed as three indices: Severity of suicidal ideation, reliable changes and treatment response. Findings We included IPD from nine out of ten eligible trials (2037 participants). iCBT showed significant reductions of suicidal ideation compared with control conditions across all indices (severity: B=-0.247, 95% CI-0.322 to-0.173; reliable changes: B=0.633, 95% CI 0.408 to 0.859; treatment response: B=0.606, 95% CI 0.410 to 0.801). In iCBT, the rate of reliable improvement was 40.5% (controls: 27.3%); the deterioration rate was 2.8% (controls: 5.1%). No participant-level moderator effects were identified. The effects on treatment response were higher for trials with waitlist-controls compared with active controls. There were insufficient data on suicide attempts. Human support and female gender predicted treatment adherence. The main source of potential bias was missing outcome data. Conclusions The current evidence indicates that iCBT is effective in reducing suicidal ideation irrespective of age, gender and previous suicide attempts. Future studies should rigorously assess suicidal behaviour and drop-out reasons

Observations of continuum depression in warm dense matter with X-ray thomson scattering

Detailed measurements of the electron densities, temperatures, and ionization states of compressed CH shells approaching pressures of 50 Mbar are achieved with spectrally resolved x-ray scattering. Laser-produced 9 keV x-rays probe the plasma during the transient state of three-shock coalescence. High signal-to-noise x-ray scattering spectra show direct evidence of continuum depression in highly degenerate warm dense matter states with electron densities ne>1024cm-3. The measured densities and temperatures agree well with radiation-hydrodynamic modeling when accounting for continuum lowering in calculations that employ detailed configuration accounting

Antifungal Activity against Candida Biofilms

Candida species have two distinct lifestyles: planktonic, and surface-attached communities called biofilms. Mature C. albicans biofilms show a complex three-dimensional architecture with extensive spatial heterogeneity, and consist of a dense network of yeast, hyphae, and pseudohyphae encased within a matrix of exopolymeric material. Several key processes are likely to play vital roles at the dif- ferent stages of biofilm development, such as cell-substrate and cell-cell adherence, hyphal devel- opment, and quorum sensing. Biofilm formation is a survival strategy, since biofilm yeasts are more resistant to antifungals and environmental stress. Antifungal resistance is a multifactorial process that includes multidrug efflux pumps, target proteins of the ergosterol biosynthetic pathway. Most studies agree in presenting azoles as agents with poor activity against Candida spp. biofilms. However, recent studies have demonstrated that echinocandins and amphotericin B exhibit remarkable activity against C. albicans and Candida non-albicans biofilms. The association of Candida species with biofilm for- mation increases the therapeutic complexity of foreign body-related yeast infections. The traditional approach to the management of these infections has been to explant the affected device. There is a strong medical but also economical motivation for the development of novel anti-fungal biofilm strate- gies due to the constantly increasing resistance of Candida biofilms to conventional antifungals, and the high mortality caused by related infections. A better description of the extent and role of yeast in biofilms may be critical for developing novel therapeutic strategies in the clinical setting