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Diurnal variations to proinflammatory markers in individuals with diabetes compared to healthy controls: protocol for a systematic review and meta-analysis

Por: Reid · A. G. · Wu · C. Y. · Nguyen · T. H. O. · Symons · R. C. A. · Britten-Jones · A. C. · Downie · L. E.
Introduction

Diabetes mellitus is a highly prevalent metabolic disorder associated with chronic, low-grade inflammation. Of recent interest is the association between diabetes and circadian rhythm disruption. The aim of this review is to evaluate and synthesise clinical evidence for whether diabetes affects homeostatic diurnal patterns to proinflammatory markers in the human body. This could inform the optimal timing of immune-targeted therapies over the course of the day.

Methods and analysis

This systematic review will include primary clinical research studies reporting on diurnal variations, defined as an afternoon/evening (PM) minus a morning (AM) value, within a timeframe of 12±4 hours, for predefined proinflammatory markers, in individuals with diabetes (type 1 or type 2) compared with healthy controls. A search of online databases (Cochrane CENTRAL, Ovid MEDLINE and Ovid Embase) will be performed. Grey literature searches will be performed in clinical trial registries. Two review authors will independently screen retrieved citation records at the title/abstract and full-text levels. Study quality will be assessed using an appropriate National Institute of Health quality assessment tool. A meta-analysis will be performed if more than one study reports equivalent data for any outcome. Statistical heterogeneity will be assessed using the 2 test. Where a meta-analysis is not possible or unlikely to be meaningful, a narrative synthesis of the findings will be provided.

Ethics and dissemination

Ethics approval is not required for this systematic review as no original data will be collected. The results will be disseminated through peer-reviewed publication and conference presentations.

PROSPERO registration number

CRD420251115780.

Clustering socio-demographic of Indonesian adolescents and their associations with depression: a cross-sectional study

Por: Murti · F. A. K. · Nursalam · N. · Kustanti · C. Y. · McKenna · L. · Sutrisno · S. · Pradipta · R. O. · Saleh · A. · Efendi · F.
Objectives

To identify socio-demographic subgroups of adolescents through cluster analysis and examine the extent to which these clusters are associated with depression.

Design

This cross-sectional study used cluster analysis and logistic regression.

Setting

The Indonesian Health Survey 2023 is a nationally representative survey of Indonesia.

Participants

A total of 89,866 adolescents aged 15–24 years were included.

Primary and secondary outcome measures

Depression was assessed using the Mini International Neuropsychiatric Interview. Logistic regression models were applied to estimate the association between cluster membership and depression risk, adjusting for behavioural factors (smoking and alcohol use), and geographical distribution.

Results

Five discrete socio-demographic clusters were identified in this study. Two clusters showed a significantly elevated risk of depression compared with the socioeconomically disadvantaged rural male cluster (Cluster 1). Cluster 2 (older, poor, rural females) had an OR 1.58 (95% CI 1.18 to 2.12), while Cluster 3 (younger, urban, affluent females) had an OR 2.60 (95% CI 1.92 to 3.52).

Conclusions

Adolescent depression risk factors are shaped by intersecting socio-demographic vulnerabilities, particularly among females in disadvantaged rural and socioeconomically privileged urban settings. Gender-responsive and context-specific mental health interventions are required.

Transfer of faeces in ulcerative colitis 2: improving efficacy - study protocol for a multicentre randomised controlled trial (TURN2 study)

Por: Benard · M. V. · Van Der Spek · M. J. · Davids · M. · Visser · C. E. · Zoetendal · E. G. · Rethans · B. · Zwezerijnen-Jiwa · F. H. · Visschedijk · M. C. · Oldenburg · B. · Weersma · R. K. · Ponsioen · C. Y.
Introduction

The interaction between the gut microbiota and the host immune system is implicated in the pathogenesis of inflammatory bowel disease, including ulcerative colitis (UC). Targeting the gut microbiota with faecal microbiota transplantation (FMT) from a healthy donor has shown promise in inducing remission in patients with active UC. However, mixed results and protocol heterogeneity have limited its practical application. Our previous Transfer of Faeces in Ulcerative Colitis; Restoring Homeostasis (TURN) trial found a correlation of clinical response with specific strains and butyrate production. Since most gut microbes, including many butyrate producers, are anaerobes, anoxic processing of donor stool may be essential to increase efficacy of FMT in UC. This trial aims to enhance FMT efficacy by applying strict anoxic processing, selecting donors based on microbial composition and using repetitive dual-route administration.

Methods and analysis

This randomised, double-blind, placebo-controlled, multicentre study evaluates the efficacy of strictly anoxic prepared donor FMT compared with anoxic prepared autologous FMT in patients with mild to moderate active UC. An open-label extension option is available for non-responders in the autologous arm. Included patients will receive 4 weekly FMTs, comprising two double-route administrations (nasoduodenal administration combined with enema) and two single enemas. Donors are selected based on their microbiota profile, informed by our previous TURN trial and literature. A total of 76 patients evaluable for the primary endpoint will be included. The primary endpoint is steroid-free clinical and endoscopic remission at week 8, assessed by the adapted Mayo score. An interim analysis will be conducted midway through the study by a Data Safety Monitoring Board to monitor efficacy and safety. Other outcomes of this study include the evaluation of clinical, endoscopic and histological response. In addition to clinical results, this study aims to provide valuable insights into specific microbial strains, metabolites and mechanisms correlated with response, aiding in the development of future microbial therapies.

Ethics and dissemination

Ethics approval was obtained from the medical ethics committee of the Amsterdam University Medical Centre in the Netherlands (reference number 2018_057). All participants will provide written informed consent. The results of the trial will be disseminated through publication in a peer-reviewed journal and presentations at (inter)national conferences.

Trial registration number

Prospectively registered in May 2018 in the Dutch Trial Register (NTR/LTR) as NL7770. Assigned NL-OMON52507 following the transition of the Dutch Trial Register to the Overview of Medical Research in the Netherlands. Also registered at ClinicalTrials.gov (NCT05998213).

Developing a framework to guide intervention planning to reduce heat exposure and poor air quality in school classrooms: a scoping review protocol

Por: Naidoo · N. · Kapwata · T. · Bulani · M. · Bidassey-Manilal · S. · Reddy · P. · Ruthanam · M. · Wright · C. Y.
Introduction

Poor indoor air quality and heat, individually and together, cause serious health impacts on children. Thus, there is a growing interest in creating school classroom environments that reduce health risks associated with these indoor environmental conditions. However, it is unclear if the existing evidence provides effective, practical and reliable interventions or strategies that can be implemented in classrooms. Additionally, the pertinence of these strategies for low-income communities needs to be elucidated. This scoping review will, therefore, document the findings of studies that have analysed interventions and strategies to improve school classroom conditions by reducing heat exposure and poor air quality to protect the health and well-being of children. This scoping review will consider: (1) interventions or adaptation strategies that have reduced heat exposure in classrooms; (2) interventions or adaptation strategies that have reduced air pollutant exposure in classrooms; (3) classroom building modifications that reduce exposure to heat and poor air quality and (4) improved health outcomes in children due to reduced heat and air pollutants. Studies that report reductions in heat or air pollutant exposure and show significant improvements in learner health outcomes will be prioritised for deeper analysis and considered particularly valuable for informing evidence-based recommendations.

Methods and analysis

We will explore original and review articles from both high-income and low-income settings that evaluate interventions and strategies for preventing or reducing heat exposure and poor air quality, to safeguard the health and well-being of children in classrooms. A comprehensive literature search will be conducted on Ovid MEDLINE, Ovid Global Health, PubMed, Scopus, ScienceDirect and Web of Science. Searches will be limited to literature published in the last 10 years (2015–2025). Results will be exported to EndNote for deduplication and to Abstrackr software for screening. Four reviewers will do abstract screening to ensure consistency. Data from included papers will be presented in tables with a narrative commentary.

Ethics and dissemination

No ethical approval is required for this study as primary data collection will not be conducted. A manuscript detailing the findings from this review will be published in a peer-reviewed journal.

Examining the implementation of home-based palliative care for patients with end-stage liver disease (HoPE): a protocol for a feasibility study

Por: Nah · C. Y. · Yip · W. · Kaliyaperumal · K. · Yung · S. H. · Chia · S. C. · Hum · A.
Introduction

Cirrhosis is a major cause of morbidity and mortality. Patients with decompensated cirrhosis, or end-stage liver disease (ESLD), have a high symptom burden and an increased mortality risk. Yet, the uptake of palliative care in patients with ESLD remains low and variable. Despite robust evidence of the value of home palliative care in other advanced diseases, this has not been well studied in patients with ESLD. Hence, the primary aim of this study is to explore the implementation, feasibility and acceptability of home palliative care in patients with ESLD and healthcare professionals. We also aim to describe its impact on the quality of life (QoL), mood, symptom burden, caregiver burden and healthcare utilisation of patients with ESLD.

Methods and analysis

The study is a single-centre, mixed-methods feasibility study. Eligible patients include those with decompensated liver cirrhosis who are admitted under the gastroenterology and hepatology service and fulfil the Supportive and Palliative Care Indicator Tools (SPICT) criteria. Recruited patients will be followed up by a multi-disciplinary homecare team led by a palliative care physician for 6 months. Both qualitative and quantitative measures will be used to evaluate the primary aim and include the uptake of the service by both eligible patients and physicians. Semistructured interviews with key stakeholder groups will be conducted to determine their perspectives and experiences. Secondary outcome measures include changes in health-related QoL using the Chronic Liver Disease Questionnaire, depression severity, goals of care discussions, patient symptom burden, caregiver burden and healthcare utilisation.

Ethics and dissemination

This study will adhere to the Declaration of Helsinki and has been approved by the research ethics committee of the National Healthcare Group (DSRB (Domain Specific Review Board) reference: 2023/00852). Results will be submitted for publication in international peer-reviewed journals.

Effectiveness of a centrally designed, large-scale, multisite undergraduate medical simulation programme: student-reported confidence across eight London hospitals in a UK medical school setting

Por: Fung · C. Y. · Wraith · C. · Houghton · N. · Woods · B. · Brown · C. · Dharmarajah · A. · Sam · A. H.
Objectives

Simulation is well established in medical education. However, with rising numbers of medical students globally, provision of high-quality, equitable simulation teaching on a large, multisite scale is increasingly challenging. We sought to explore whether a centrally designed, multisite simulation programme could enhance student confidence equitably across multiple clinical sites with differing resources.

Design

An evaluative study on the changes in medical student confidence on defined intended learning outcomes (ILOs) in 3 undergraduate year groups across 11 simulation sessions delivered at eight different clinical sites with variable resources and facilitators.

Setting

Eight hospitals affiliated with Imperial College School of Medicine.

Outcomes

Students’ self-reported confidence in achieving the ILOs via a questionnaire at the end of each session. Changes in confidence following each session were analysed and compared across sites.

Results

522 students responded to the survey over 3 academic years. Students’ mean confidence in achieving ILOs increased in all sessions. Nine out of 10 sessions showed no statistically significant difference in the confidence increases between sites.

Conclusion

Our study suggests it is possible to deliver an equitable, centrally designed, large-scale simulation teaching programme to medical students across multiple clinical sites with different facilitator teams. The programme is sustainable, easily facilitated by new teaching fellows each year and is likely adaptable to other healthcare professions and settings.

Assessment of adverse childhood experiences in women: a study of reliability and predictive validity of self-reporting versus medical records abstraction in an American population

Por: Rocca · W. A. · Gazzuola Rocca · L. · Smith · C. Y. · Esterov · D. · Kapoor · E. · Geske · J. R. · Bailey · K. R. · Mielke · M. M. · Kantarci · K.
Objective

To study the reliability and validity of adverse childhood experiences (ACE) scores measured using a questionnaire versus abstraction of medical records, and to test whether the scores vary by history of bilateral oophorectomy, or by age and presence of anxiety or depressive symptoms at the time of questionnaire administration.

Design

The study involved a reliability component and a predictive validity component.

Setting

A population-based sample in Olmsted County, Minnesota, was derived from the Mayo Clinic Cohort Study of Oophorectomy and Aging-2.

Participants

We included 198 women who underwent premenopausal bilateral oophorectomy for a non-malignant indication between 1988 and 2007 and 174 referent women of the same age randomly sampled from the general population (total of 372 women). At a later time (median of 22.7 years later), the women were contacted and invited to self-administer the ACE questionnaire during an inperson visit. Independent of the visit, their medical records were abstracted for ACE by a physician.

Interventions

Questionnaire and abstraction-based ACE scores.

Main outcome measures

Agreement between the two ACE scores (reliability; weighted kappa statistics) and comparison of incidence of multimorbidity in women with ACE scores ≥1 vs 0 (predictive validity; survival analyses). Data were analysed in March and April 2024.

Results

The 372 women in the study had a median age of 65 years at the time of ACE questionnaire self-administration (IQR, 62–69). Questionnaire-based ACE scores showed moderate agreement with abstracted ACE scores (weighted kappa 0.44 (95% CI 0.34 to 0.54)). The cut-off score of ACE ≥1 showed an overall fair agreement between the two scores (kappa 0.33 (95% CI 0.24 to 0.43)). A comparison of the cumulative incidence of multimorbidity in women with an ACE score ≥1 versus women with ACE score of 0 yielded a HR of 1.13 (95% CI 1.00 to 1.27) for abstracted ACE and 1.13 (95% CI 1.01 to 1.27) for questionnaire-based ACE. The best predictive validity was for ACE measured by both methods combined (either or) with a HR of 1.29 (95% CI 1.13 to 1.46).

Conclusions and relevance

Questionnaire-based ACE scores have moderate agreement with medical records abstracted ACE scores. However, both sets of ACE scores are predictive of the accumulation of multimorbidity at older age and should be considered complementary.

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