Identifying lifelong factors that impact brain health and functional outcomes in adults with childhood-onset type 1 diabetes: the cognition and longitudinal assessments of risk factors over 30 years (CLARiFY) – diabetes complications study protocol

Introduction
Type 1 diabetes (T1D) is associated with changes in brain structure, cognition, mental health, and functional outcomes. While these changes have been linked to dysregulated glycaemic control, findings are inconsistent, and their long-term impact remains unclear. Most evidence comes from cross-sectional or short-term longitudinal studies, limiting insights into causal associations. To address this, we aim to study individuals with T1D approximately 30 years after onset to assess how early dysglycaemic insults during neurodevelopment influence cognitive and functional outcomes in mid-adulthood.

Methods and analysis
This protocol paper outlines an observational, case/control, cross-sectional/longitudinal and descriptive study that follows up the original Royal Children’s Hospital (RCH) Diabetes Cohort Study. The initial study recruited children in Australia diagnosed with T1D between 1990 and 1992, conducting five waves of data collection. We now introduce the Cognition and Longitudinal Assessments of Risk Factors over 30 Years (CLARiFY) Diabetes Complications Study to assess brain, cognition and functional outcomes in mid-adulthood, approximately 30 years post-T1D onset. Both T1D participants from the original cohort and healthy controls will participate in semistructured interviews, neuroimaging and cognitive testing. T1D participants will also undergo complications screening. Data from this study and previous waves will be used to (Aim 1) explore cross-sectional and longitudinal impacts of T1D on brain health over 30 years. Linear regression will analyse cross-sectional outcomes, and multivariate analysis will assess cognitive variables jointly. Longitudinal outcomes will be examined using linear mixed-effects regression for IQ patterns, with secondary outcomes analysed via generalised linear models. Additionally, linear mixed-effects regression (Aim 2) will identify T1D-related metabolic factors affecting brain outcomes, with covariate selection informed by the construction of directed acyclic graphs (DAGs).

Ethics and dissemination
The study was approved by the Royal Children’s Hospital Human Research Ethics Committee (HREC 35 240F and 2019.065). The research findings will be disseminated through peer-reviewed publications, conference presentations, and print and social media. Participants will receive a summary of the study findings on its completion.

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Randomised waitlist-controlled trial of a 10-week community programme using a plant-based diet in a predominantly Maori population in Tairawhiti (Gisborne)

Objectives
Investigate the impact of a 10-week whole-food plant-based (WFPB) community programme on weight and type 2 diabetes up to 36 months postintervention.

Design
Randomised waitlist-controlled trial.

Setting
Community-based General Practice clinic classified as ‘Very Low-Cost Access’ in Gisborne, the main city of the Tairāwhiti region of New Zealand.

Participants
Adults (n=56) aged 30–72 years, with obesity (Body Mass Index (BMI) ≥30) and glycated haemoglobin (HbA1c≥40 mmol/mol) in the last 6 months. Of the participants, 59% identified as Māori and 5% as Pasifika.

Intervention
A 10-week programme consisting of 2 hours, two times per week sessions (40 hours total), involving skills-based learning and health education.

Primary and secondary outcome measures
Primary measures were changes in weight, BMI and HbA1c. Secondary measures included changes in cholesterol, waist circumference, exercise levels, plant-based and non-plant-based dietary scores and association with Big Five Inventory personality traits. The primary endpoint was assessed at post-treatment (10 weeks), with follow-up at 6 and 36 months postintervention.

Results
Differences between the intervention and waitlist control groups at 10 weeks were compared with independent samples t-tests. In intention-to-treat analyses, the intervention group demonstrated significantly greater weight loss of 3.3 kg (95% CI (0.8 to 5.7), p

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What drives clinic follow-up after traumatic spinal injury? An observational cohort study from Tanzania

Objectives
To evaluate factors associated with clinic follow-up after traumatic spinal injury (TSI) in Tanzania, focusing on demographic, injury-related and hospital variables. We hypothesised that socioeconomic and injury-specific factors would predict follow-up adherence.

Design
Retrospective observational cohort study.

Setting
Tertiary government referral centre for neurosurgery and orthopaedics in Dar es Salaam, Tanzania.

Participants
443 adults with TSI admitted between September 2016 and October 2021. Inclusion criteria included survival to discharge and availability of the discharge date. Patients with missing data were excluded.

Primary and secondary outcome measures
Primary outcomes were any clinic follow-up and 1-year follow-up post-discharge. Secondary outcome was time to loss of follow-up. Logistic regression was used to identify factors associated with follow-up, and Kaplan-Meier survival analysis assessed follow-up duration.

Results
Of 443 patients (85.8% male, median age 34 years), 52.4% returned for follow-up. Independent factors associated with return included private insurance (adjusted OR (aOR) 2.69, 95% CI 1.38 to 5.45, p=0.005), involvement in a road traffic accident (aOR 2.15, 95% CI 1.22 to 3.83, p=0.009), lumbar injuries (aOR 2.26, 95% CI 1.30 to 4.00, p=0.004), neurological improvement at discharge (aOR 3.52, 95% CI 1.72 to 7.64, p=0.001) and hospital stays shorter than 24 days (aOR 1.63, 95% CI 1.07 to 2.47, p=0.022). Among those who returned, only 25.4% completed 1 year of follow-up. Predictors of 1-year follow-up included being female (aOR 4.87, 95% CI 2.31 to 10.56, p

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Translational Insights Into Pericyte-Mediated Regulation of Cerebral Blood Flow: Implications for Ischemic Stroke

Stroke, Ahead of Print. Microvascular reperfusion stands as a critical therapeutic objective in ischemic stroke management. Pericytes, specialized contractile mural cells enveloping cerebral capillaries, serve as master regulators of capillary tone and regional hemodynamics, exerting a profound influence on post-ischemic stroke blood flow dynamics. Despite their pivotal role in microcirculatory control, there are limited therapeutic targets specifically aimed at regulating their activity. Here, we summarize the multifaceted roles of pericytes in ischemic stroke and discuss various pericyte-related strategies for ischemic stroke. While these interventions offer some benefits, they also present notable limitations, including adverse reactions, structural instability, suboptimal efficacy, and challenges in clinical translation. Future efforts directed toward deciphering the spatiotemporal responses of pericytes across different ischemic phases and achieving their selective and effective regulation are expected to yield novel strategies for precision microcirculatory rehabilitation.

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Preventing the transition from acute to chronic low back pain using home-based neuromodulation: protocol for a randomised, controlled study

Introduction
Chronic low back pain (LBP) is among the world’s leading causes of disability and declines in quality of life. Despite considerable financial and research investment, current interventions demonstrate only modest success or are associated with deleterious side effects. Furthermore, most treatment efforts are directed towards LBP that has already become chronic, rather than interventions capable of preventing pain chronicity in the first instance. Transcranial direct current stimulation (tDCS), a portable and cost-effective form of non-invasive brain stimulation, presents a potential means of targeting acute pain and preventing the transition to chronic pain. However, this approach has been limited primarily to experimental settings that require intensive appointments and specialist expertise. Thus, this assessor-blinded, participant-blinded, and therapist-blinded, randomised controlled trial aims to explore the effectiveness of home-based tDCS for improving pain and disability in people with acute LBP. This may provide insight into the potential for tDCS to expedite recovery from acute LBP and prevent pain chronicity.

Methods and analysis
40 individuals with acute LBP (onset

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Using qualitative research and the person-based approach to coproduce an inclusive intervention for postpartum blood pressure self-management

Objective
To coproduce an inclusive intervention for blood pressure (BP) self-management post partum.

Design
Using the person-based approach, an intervention was coproduced in three phases. Phase 1 entailed intervention coproduction with a diverse patient and public involvement panel and stakeholders (clinical, academic, government and third sector-based). Phase 2 involved intervention optimisation through think-aloud interviews with former patients and clinicians. Phase 3 was user-testing followed by semistructured interviews with current patients and their clinicians.

Setting
Patients and clinicians from primary and secondary care drawn from Southern and Northern England.

Participants
Seven former patients and 11 clinicians participated in think-aloud interviews to provide their views of intervention prototypes (phase 2). Additionally, 23 patients and 9 of their clinicians participated in semistructured interviews after using the intervention for 2 weeks (phase 3).

Intervention
An interactive patient app—My BP Care—and accompanying leaflet to support BP self-monitoring. These were linked to a clinician dashboard with alerts and an emailing system to facilitate appropriate titration of patient medication.

Results
The intervention was codeveloped following these guiding principles to ensure it was accessible and inclusive: easily comprehensible, motivating, simple and quick to use. Interview findings indicated that patient adherence to the intervention was promoted by the initial patient training conducted by the midwives, the enhanced clinical oversight they felt they received as a result of the intervention, the free BP monitor they received, reassurance they received of the medication safety for them and their baby, the intervention’s simplicity and the motivating reminders they received.

Conclusions
Through coproduction with a diverse group of patients and stakeholders, and optimisation through testing among further diverse patients and clinicians, we developed a multicomponent intervention that is accessible and engaging for diverse patients, compatible with prevailing clinical practice and adaptable to different clinical contexts.

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Annual cases of colon cancer by age group after Medicaid expansion in the USA in 2014: a difference-in-differences study

Background
Studies examining the association between Medicaid expansion (ME) under the Affordable Care Act (ACA) and colon cancer incidence have produced mixed results.

Objective
To re-visit the association between the ACA-ME and annual cases of colon cancer.

Design
Difference-in-differences (DiD).

Setting
The primary analyses used data from the National Cancer Database from 2010 to 2018, a hospital-based cancer registry in the USA. We also conducted exploratory analyses using data from the Surveillance, Epidemiology and End Results (SEER) registry.

Patients
Patients aged 40 and older with newly diagnosed colon cancer.

Measurements
The primary outcome was the percent change in colon cancer of all stages. Secondary outcomes were percent changes in stage I and stage IV cases.

Results
Among those aged 40–49, we observed a statistically significant greater increase in stage I colon cancer in expansion states relative to non-expansion states (DiD (percent change) 9.7% (95% CI, 2.5% to 17.4%)). In those aged 50–64, we did not observe statistically significant differences between the two state groups in any of the outcomes. Among those aged 65+, we observed a statistically significant relative decrease for all stages in ACA-ME states (–1.0% (95% CI, –1.0% to –3.0%)) and for stage IV (–3.0% (95% CI, –2.0% to –5.0%)). We explored our findings among younger individuals (

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Impact of 2014 Japanese practice guidelines on treatment patterns in patients with myasthenia gravis: an insurance claims database study

Objectives
To evaluate changes in oral corticosteroid (OCS) use after the publication of the 2014 Japanese clinical practice guidelines for myasthenia gravis (MG).

Design
Retrospective cohort study performed in three Japanese health insurance databases: the JMDC database between 2005 and 2021; the DeSC database covering the National Health Insurance (NHI) and the DeSC database covering the Late-Stage Elderly Healthcare Service (LSEHS) between 2014 and 2021. Achievement of OCS ≤5 mg/day was defined as ≥90 days of consecutive OCS ≤5 mg/day during follow-up, without any gap longer than 60 days between two consecutive claims. The time to achieve OCS ≤5 mg/day was estimated using Kaplan-Meier survival analysis.

Setting
Real-world treatment setting in Japan.

Participants
Patients aged ≥16 years with a record of MG (International Classification of Diseases 10th edition code: G70.0) with a serological test, who had baseline period ≥180 days before inclusion with no MG claim and who started immunotherapy (including OCS) within 90 days of MG diagnosis.

Outcome measures
Prescription of OCS and other therapies for MG.

Results
Overall, 811 patients were included. The mean age was 49 years in the JMDC, 61 years in the NHI and 80 years in the LSEHS. In the JMDC, the median time to achieve OCS ≤5 mg/day was significantly shorter (p=0.042; log-rank test) in patients included in 2015 or later (11.0 months) than in patients included before 2015 (17.9 months). The median time to achieve OCS ≤5 mg/day was shorter in the LSEHS (6.5 months) than in the JMDC (11.0 months) and the NHI (11.7 months).

Conclusions
Faster tapering of the OCS dose was observed in patients starting treatment after the publication of the 2014 guidelines, although use of higher-dose OCS remained widespread after this date. This highlights the need to improve awareness of guidelines by healthcare providers in order to decrease the burden of higher-dose OCS.

Trial registration number
Clinical Trials Registry (UMIN-CTR): UMIN000051155; Post-results.

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Economic evaluation of a lifestyle intervention for individuals with overweight or obesity suffering from chronic low back pain (the BO2WL trial): a protocol for a health economic analysis

Introduction
Low back pain (LBP) is highly prevalent across the Western world, including Switzerland (CH) and Belgium (BE), with women experiencing higher disability rates than men. Chronic LBP (CLBP), persisting beyond 3 months, leads to diminished health-related quality of life and increased healthcare and societal costs. Evidence indicates a direct relationship between body mass index (BMI) and CLBP severity, with high BMI significantly driving LBP-related healthcare expenses. Current evidence supports combining pain neuroscience education (PNE) with cognition-targeted exercise therapy (CTET) to effectively manage CLBP.
An economic evaluation alongside a randomised controlled trial, entitled ‘Lifestyle Intervention in Overweight/Obese CLBP Patients: an International Multi-centre RCT’ (BO2WL), will be conducted in CH and BE. It aims to evaluate the addition of a lifestyle intervention to PNE and CTET compared with PNE and CTET alone for treating individuals with CLBP and overweight or obesity. This protocol outlines the details of the economic evaluation of this trial.

Methods and analysis
The trial consists of a 14-week intervention followed by a 52-week post-intervention follow-up. Primary outcomes include direct and indirect costs, as well as quality-adjusted life years and pain intensity. Cost data will be converted into 2026 Belgium (BE) and 2026 Swiss Francs (CHF) for CH, with a discount rate of 3.5%. Incremental cost-utility and cost-effectiveness ratios will be calculated from a societal perspective for each country.

Ethics and dissemination
Ethics approval was obtained by the local ethics committees (Bern, CH: project ID 2022–02210; Brussels and Geel, BE: BUN 1432022000296). Results of the main trial and economic evaluation will be submitted for publication in a peer-reviewed journal.

Trial registration number
NCT05811624.

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Cuff leak test and airway obstruction in mechanically ventilated ICU patients (COSMIC): a pilot feasibility randomized controlled trial protocol

Introduction
The cuff leak test (CLT) is hypothesised to help optimise extubation by assessing for laryngeal oedema which, if unrecognised and untreated, could lead to post-extubation stridor, post-extubation airway obstruction, and reintubation. However, the diagnostic accuracy of the CLT to detect post-extubation stridor (and hence potentially airway obstruction) remains uncertain. Given the equipoise that exists surrounding the CLT, we are conducting a pilot randomised clinical trial (RCT) examining the CLT as part of the pathway to extubation. Herein, we report the protocol for the Cuff Leak Test and Airway Obstruction in Mechanically Ventilated ICU Patients (COSMIC): a Pilot Feasibility Randomized Clinical trial (RCT).

Methods and analysis
This is a multicentre, international, parallel-group, pragmatic, pilot RCT. We will enrol 100 mechanically ventilated patients in the intensive care unit (ICU) who are deemed ready for extubation and have at least one risk factor for laryngeal oedema. In the intervention arm, respiratory therapists will perform a qualitative CLT before extubation. If a patient passes the CLT (suggesting no laryngeal oedema), extubation will be performed in keeping with standard care. If the patient fails the CLT (suggesting laryngeal oedema), extubation will be delayed allowing for administration of dexamethasone, consideration of diuresis, and the CLT will be repeated in 12–24 hours. In the control arm, patients will be extubated without completing a CLT, without steroid administration, and without delay. Randomization will be by a 1:1 allocation, stratified by centre. The primary feasibility outcomes will include recruitment and protocol adherence. Secondary outcomes will include post-extubation stridor, reintubation within 72 hours, emergency surgical airway within 72 hours, and ICU and hospital mortality within 30 days.

Ethics and dissemination
This trial has been approved by Clinical Trials Ontario, Hamilton Integrated Research Ethics Board, State of Kuwait Ministry of Health, University of Texas Health Committee for the Protection of Human Subjects and Brant Community Health Systems Research Ethics Committee. The trial has received a No Objection Letter from Health Canada. Trial results will be disseminated via publication in peer-reviewed journals.

Trial registration number
NCT05456542.

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Promoting smoking cessation and preventing relapse to tobacco use following a smoke-free mental health inpatient stay (SCEPTRE feasibility study): a multicentre randomised controlled feasibility study protocol

Introduction
Thousands of patients with mental illness are admitted to acute adult mental health wards every year in England, where local guidance recommends that all mental health settings be entirely smokefree. Mental health Trusts presently invest substantial effort and resources to implement smoke-free policies and to deliver tobacco dependence treatment to patients. Providing adequate support can help those who smoke remain abstinent or quit smoking during their smoke-free inpatient stay and beyond. At present, little is known about how best to support patients to prevent their return to pre-admission smoking behaviours after discharge from a smoke-free mental health inpatient stay. We have developed an intervention which includes targeted resources to support smoking-related behaviour change in patients following discharge from a smoke-free mental health setting. The aim of this trial is to determine the feasibility of a large-scale clinical trial to test the effectiveness and cost-effectiveness of the SCEPTRE intervention, compared with usual care.

Methods and analysis
This feasibility study will be an individually randomised, controlled trial in eight National Health Service mental health Trusts recruiting adults (≥18 years) admitted to an acute adult mental health inpatient setting who smoke tobacco on admission, or at any point during their inpatient stay. Consenting participants will be randomised to receive a 12-week intervention consisting of components aimed at promoting or maintaining positive smoking-related behaviour change following discharge from a smoke-free mental health inpatient setting or usual care. Data will be collected at baseline, 3 months and a second timepoint between 4 and 6 months post-randomisation. With 64 participants (32 in each group), the trial will allow a participation rate of 15% and completion rate of 80% to be estimated within a 95% CI of ±3% and ±10%, respectively. The analysis will be descriptive and follow a prespecified plan.

Ethics and dissemination
Ethics approval was obtained from the North West—Greater Manchester West Research Ethics Committee. We will share results widely through local, national and international academic, clinical and patient and public involvement networks. The results will be disseminated through conference presentations, peer-reviewed journals and will be published on the trial website: https://sceptreresearch.com/.

Trial registration number
ISRCTN77855199.

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Leishmaniases in Ethiopia: a scoping review

Objectives
With recent efforts to eliminate visceral leishmaniasis in East Africa, we aimed to map the breadth of research on leishmaniases in Ethiopia, one of the high-endemic countries in the region, to help understand the current literature landscape and highlight priority areas for future research.

Design
The scoping review was conducted in accordance with the JBI Scoping Review Methodology Group’s guidance and reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses—Extension for Scoping Reviews guidelines.

Data sources
We searched the following databases and sources: PubMed, Embase, Web of Science, Cochrane Library, Global Medicus Index, PROSPERO, ClinicalTrials.gov and the Pan African Clinical Trials Registry and known local journals.

Eligibility criteria
We included studies addressing the issue of leishmaniasis in Ethiopia that were published in English language.

Data extraction and synthesis
Two reviewers independently extracted data from each study, with conflicts resolved by a third reviewer. The identified studies were analysed using an extensive codebook, which was previously developed by this team and adapted to the Ethiopian context to classify the research into different categories.

Results
A total of 8698 articles were identified. A stepwise review was conducted, and 639 papers were selected for inclusion. The research spans different themes and designs and has steadily increased over the past 14 years. Research on prevention and control, health systems/policies and post-kala-azar dermal leishmaniasis, as well as randomised controlled trials, was lacking. Studies on coinfections with other diseases accounted for 14% of research.

Conclusions
The findings underscore the growing amount of research on leishmaniasis in Ethiopia, addressing several themes and emphasising the need for more research in prevention, control, health systems/policy and high-quality studies for evidence-based treatment.

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