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AnteayerBMJ Open

Protocol for the Gut Bugs in Autism Trial: a double-blind randomised placebo-controlled trial of faecal microbiome transfer for the treatment of gastrointestinal symptoms in autistic adolescents and adults

Por: Tweedie-Cullen · R. Y. · Leong · K. · Wilson · B. C. · Derraik · J. G. B. · Albert · B. B. · Monk · R. · Vatanen · T. · Creagh · C. · Depczynski · M. · Edwards · T. · Beck · K. · Thabrew · H. · O'Sullivan · J. M. · Cutfield · W. S.
Introduction

Autism (formally autism spectrum disorder) encompasses a group of complex neurodevelopmental conditions, characterised by differences in communication and social interactions. Co-occurring chronic gastrointestinal symptoms are common among autistic individuals and can adversely affect their quality of life. This study aims to evaluate the efficacy of oral encapsulated faecal microbiome transfer (FMT) in improving gastrointestinal symptoms and well-being among autistic adolescents and adults.

Methods and analysis

This double-blind, randomised, placebo-controlled trial will recruit 100 autistic adolescents and adults aged 16–45 years, who have mild to severe gastrointestinal symptoms (Gastrointestinal Symptoms Rating Scale (GSRS) score ≥2.0). We will also recruit eight healthy donors aged 18–32 years, who will undergo extensive clinical screening. Recipients will be randomised 1:1 to receive FMT or placebo, stratified by biological sex. Capsules will be administered over two consecutive days following an overnight bowel cleanse with follow-up assessments at 6, 12 and 26 weeks post-treatment. The primary outcome is GSRS score at 6 weeks. Other assessments include anthropometry, body composition, hair cortisol concentration, gut microbiome profile, urine/plasma gut-derived metabolites, plasma markers of gut inflammation/permeability and questionnaires on general well-being, sleep quality, physical activity, food diversity and treatment tolerability. Adverse events will be recorded and reviewed by an independent data monitoring committee.

Ethics and dissemination

Ethics approval for the study was granted by the Central Health and Disability Ethics Committee on 24 August 2021 (reference number: 21/CEN/211). Results will be published in peer-reviewed journals and presented to both scientific and consumer group audiences.

Trial registration number

ACTRN12622000015741.

Fibre-rich Foods to Treat Obesity and Prevent Colon Cancer trial study protocol: a randomised clinical trial of fibre-rich legumes targeting the gut microbiome, metabolome and gut transit time of overweight and obese patients with a history of noncancerou

Por: Hartman · T. J. · Christie · J. · Wilson · A. · Ziegler · T. R. · Methe · B. · Flanders · W. D. · Rolls · B. J. · Loye Eberhart · B. · Li · J. V. · Huneault · H. · Cousineau · B. · Perez · M. R. · O'Keefe · S. J. D.
Introduction

Recently published studies support the beneficial effects of consuming fibre-rich legumes, such as cooked dry beans, to improve metabolic health and reduce cancer risk. In participants with overweight/obesity and a history of colorectal polyps, the Fibre-rich Foods to Treat Obesity and Prevent Colon Cancer randomised clinical trial will test whether a high-fibre diet featuring legumes will simultaneously facilitate weight reduction and suppress colonic mucosal biomarkers of colorectal cancer (CRC).

Methods/design

This study is designed to characterise changes in (1) body weight; (2) biomarkers of insulin resistance and systemic inflammation; (3) compositional and functional profiles of the faecal microbiome and metabolome; (4) mucosal biomarkers of CRC risk and (5) gut transit. Approximately 60 overweight or obese adults with a history of noncancerous adenomatous polyps within the previous 3 years will be recruited and randomised to one of two weight-loss diets. Following a 1-week run-in, participants in the intervention arm will receive preportioned high-fibre legume-rich entrées for two meals/day in months 1–3 and one meal/day in months 4–6. In the control arm, entrées will replace legumes with lean protein sources (eg, chicken). Both groups will receive in-person and written guidance to include nutritionally balanced sides with energy intake to lose 1–2 pounds per week.

Ethics and dissemination

The National Institutes of Health fund this ongoing 5-year study through a National Cancer Institute grant (5R01CA245063) awarded to Emory University with a subaward to the University of Pittsburgh. The study protocol was approved by the Emory Institutional Review Board (IRB approval number: 00000563).

Trial registration number

NCT04780477.

Development and application of simulation modelling for orthopaedic elective resource planning in England

Por: Harper · A. · Monks · T. · Wilson · R. · Redaniel · M. T. · Eyles · E. · Jones · T. · Penfold · C. · Elliott · A. · Keen · T. · Pitt · M. · Blom · A. · Whitehouse · M. R. · Judge · A.
Objectives

This study aimed to develop a simulation model to support orthopaedic elective capacity planning.

Methods

An open-source, generalisable discrete-event simulation was developed, including a web-based application. The model used anonymised patient records between 2016 and 2019 of elective orthopaedic procedures from a National Health Service (NHS) Trust in England. In this paper, it is used to investigate scenarios including resourcing (beds and theatres) and productivity (lengths of stay, delayed discharges and theatre activity) to support planning for meeting new NHS targets aimed at reducing elective orthopaedic surgical backlogs in a proposed ring-fenced orthopaedic surgical facility. The simulation is interactive and intended for use by health service planners and clinicians.

Results

A higher number of beds (65–70) than the proposed number (40 beds) will be required if lengths of stay and delayed discharge rates remain unchanged. Reducing lengths of stay in line with national benchmarks reduces bed utilisation to an estimated 60%, allowing for additional theatre activity such as weekend working. Further, reducing the proportion of patients with a delayed discharge by 75% reduces bed utilisation to below 40%, even with weekend working. A range of other scenarios can also be investigated directly by NHS planners using the interactive web app.

Conclusions

The simulation model is intended to support capacity planning of orthopaedic elective services by identifying a balance of capacity across theatres and beds and predicting the impact of productivity measures on capacity requirements. It is applicable beyond the study site and can be adapted for other specialties.

Haematological dynamics following treatment of visceral leishmaniasis: a protocol for systematic review and individual participant data (IPD) meta-analysis

Por: Munir · A. · Dahal · P. · Kumar · R. · Singh-Phulgenda · S. · Siddiqui · N. A. · Naylor · C. · Wilson · J. · Buck · G. · Rahi · M. · Alves · F. · Malaviya · P. · Sundar · S. · Ritmeijer · K. · Stepniewska · K. · Pandey · K. · Guerin · P. J. · Musa · A.
Introduction

Visceral leishmaniasis (VL) is a parasitic disease with an estimated 30 000 new cases occurring annually. Despite anaemia being a common haematological manifestation of VL, the evolution of different haematological characteristics following treatment remains poorly understood. An individual participant data meta-analysis (IPD-MA) is planned to characterise the haematological dynamics in patients with VL.

Methods and analysis

The Infectious Diseases Data Observatory (IDDO) VL data platform is a global repository of IPD from therapeutic studies identified through a systematic search of published literature (PROSPERO registration: CRD42021284622). The platform currently holds datasets from clinical trials standardised to a common data format. Corresponding authors and principal investigators of the studies indexed in the IDDO VL data platform meeting the eligibility criteria for inclusion were invited to be part of the collaborative IPD-MA. Mixed-effects multivariable regression models will be constructed to identify determinants of haematological parameters by taking clustering within study sites into account.

Ethics and dissemination

This IPD-MA meets the criteria for waiver of ethical review as defined by the Oxford Tropical Research Ethics Committee (OxTREC) granted to IDDO, as the research consists of secondary analysis of existing anonymised data (exempt granted on 29 March 2023, OxTREC REF: IDDO). Ethics approval was granted by the ICMR-Rajendra Memorial Research Institute of Medical Sciences ethics committee (letter no.: RMRI/EC/30/2022) on 4 July 2022. The results of this analysis will be disseminated at conferences, the IDDO website and peer-reviewed publications in open-access journals. The findings of this research will be critically important for control programmes at regional and global levels, policymakers and groups developing new VL treatments.

PROSPERO registration number

CRD42021284622.

Socio-demographic profile of medical students in Aotearoa, New Zealand (2016-2020): a nationwide cross-sectional study

Por: Bagg · W. · Curtis · E. · Eggleton · K. S. · Nixon · G. · Bristowe · Z. · Brunton · P. · Hendry · C. · Kool · B. · Scarf · D. · Shaw · S. · Tukuitonga · C. · Williman · J. · Wilson · D. · Crampton · P.
Objective

To determine the socio-demographic profile of all students enrolled to study medicine in Aotearoa New Zealand (NZ).

Design and setting

Observational, cross-sectional study. Data were sought from the Universities of Auckland and Otago, the two NZ tertiary education institutions providing medical education, for the period 2016–2020 inclusive. These data are a subset of the larger project ‘Mirror on Society’ examining all regulated health professional enrolled students in NZ. Variables of interest: gender, citizenship, ethnicity, rural classification, socioeconomic deprivation, school type and school socioeconomic scores. NZ denominator population data (18–29 years) were sourced from the 2018 census.

Participants

2858 students were enrolled to study medicine between 2016 and 2020 inclusive.

Results

There were more women (59.1%) enrolled to study medicine than men (40.9%) and the majority (96.5%) were in the 18–29 years age range. Māori students (rate ratio 0.92; 95% CI 0.84 to 1.0) and Pacific students (rate ratio 0.85; 95% CI 0.73 to 0.98) had lower overall rates of enrolment. For all ethnic groups, irrespective of rural or urban origin, enrolment rates had a nearly log-linear negative relationship with increasing socioeconomic deprivation. Enrolments were lower for students from rural areas compared with those from urban areas (rate ratio 0.53; 95% CI 0.46–0.61). Overall NZ’s medical students do not reflect the diverse communities they will serve, with under-representation of Māori and Pacific students and students who come from low socioeconomic and rural backgrounds.

Conclusions

To meaningfully address these issues, we suggest the following policy changes: universities commit and act to Indigenise institutional ways of knowing and being; selection policies are reviewed to ensure that communities in greatest need of doctors are prioritised for enrolment into medicine (specifically, the impact of low socioeconomic status should be factored into selection decisions); and the government fund more New Zealanders to study medicine.

Self-reported and parent-reported mental health in children from low-income families in Agder, Norway: results from baseline measurements of New Patterns project participants

Por: Boe · T. · Ostojic · H. A. · Haraldstad · K. · Abildsnes · E. · Wilson · P. · Vigsnes · K. · Molland · E.
Background

Poverty may pose risks to child and adolescent mental health, but few studies have reported on this association among children and adolescents in low-income families in Norway.

Methods

Based on a sample participating in an intervention for low-income families in Norway, we report data from the survey administered at the start of the intervention. Mental health problems were measured using the Strengths and Difficulties Questionnaire (SDQ; self-report (SR) n = 148; parent/proxy-report (PR) n = 153, mean age = 10.8). Demographic and family characteristics were obtained from parent reported data. Results are presented by gender and migration background. Regression analysis was used to investigate the relative contribution of background factors to mental health symptoms. The distribution of scores is compared to UK norms.

Results

Participants reported relatively high scores on the Strengths and Difficulties Questionnaire (SDQ) Total Difficulties Scale (parent/proxy-report, PR mean=10.7; self-report, SR mean=10.1). Participants with non-immigrant backgrounds scored considerably higher on the Total Difficulties Scale (PR mean difference=2.9; SR 5.3) and on most other domains measured with the SDQ compared with their peers with immigration backgrounds. Participants generally scored higher than or equal to UK norms.

Conclusion

Participants in the current study had many symptoms of mental health problems, with large differences between those with and without a migrant background. Interventions for low-income families should be based on detailed knowledge about differences in family risks, resources and needs.

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