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Association between glucosamine use and albuminuria in the UK: a cohort and Mendelian randomisation study

Por: Hayward · S. J. · Constantinescu · A. · Hazelwood · E. · Butler · M. J. · Vincent · E. E. · Satchell · S. C.
Background

Glucosamine is a commonly used ‘over the counter’ dietary supplement. Previous research has identified an association between glucosamine use and several positive health outcomes. However, a plausible biological mechanism for these associations has not yet been identified, meaning the causality of these relationships remains unclear. A protective effect of glucosamine on the vascular endothelium has been suggested as one such possible mechanism. Albuminuria is an early marker of endothelial dysfunction within the kidney and is associated with progression of kidney disease and adverse cardiovascular outcomes. In order to provide insights into the potential biological mechanisms underlying a protective association of glucosamine use with health outcomes, we evaluated evidence for an association between glucosamine use and albuminuria in UK Biobank (N=436 200).

Methods

Univariable and multivariable ordinal logistic regression were performed to evaluate evidence for an association between self-reported glucosamine use and albuminuria (measured as urine albumin creatinine ratio (uACR) categories). As a secondary analysis, we performed Mendelian randomisation (MR) to demonstrate the difficulties in inferring causality in this relationship using currently available data, using summary genetic data from UK Biobank and CDKGen (N=67 452).

Results

We found that people who used glucosamine were more likely to be in a lower uACR group (OR 0.81, 95% CI 0.80 to 0.83, px10–16). This association was robust to sensitivity analyses and was maintained after adjustment for age, sex and measures of obesity. In our MR analysis, we found little evidence for an association of genetically proxied glucosamine use on albuminuria (change in log uACR (mg/g) per SD change in genetic liability=1.11, 95% CI –3.01 to 5.23, p=0.60).

Conclusions

We found that detectable albuminuria was common in UK Biobank participants and we are the first to show that use of glucosamine supplements was associated with lower levels. Though this fits with a plausible biological role of the vascular endothelium in a potential protective effect of glucosamine use on many health outcomes, whether this relationship is causal or confounded remains unclear. We further discuss the inherent difficulties in using genetic instruments to proxy supplement use in MR analyses and highlight the need for a genome-wide association study of measured circulating glucosamine levels.

Running with rheumatoid arthritis: a qualitative study of Australian rheumatologists perceptions and recommendations

Por: Shearman · S. · Butler · J. · Hodges · A.
Objective

To explore how Australian rheumatologists perceive and recommend running for individuals with rheumatoid arthritis (RA), including their clinical experiences, observations and personal views.

Design

Qualitative exploratory study using semistructured interviews. Interviews were conducted via Microsoft Teams, transcribed verbatim and analysed thematically using NVivo software.

Setting

Australia; interviews were conducted remotely via Microsoft Teams with participants joining from either clinical or home environments.

Participants

13 practising Australian rheumatologists recruited through purposive and snowball sampling.

Results

Five themes were identified from thematic analysis: (1) perceived benefits of running, (2) risks and clinical cautions, (3) criteria required for discussing running, (4) barriers to running and (5) facilitators to running. Participants acknowledged various benefits of running for individuals with RA, such as improved mental health, lifestyle changes and support for joint health. Concerns included risks of running during active disease phases and overly rapid progression of training loads. Key criteria for recommending running included good disease control, the patient’s running history and personal goals. Barriers included patient concerns around joint harm, lack of guidelines and socioeconomic challenges. Facilitators included stable disease, symptom-guided pacing, gradual load increases, allied health referral and appropriate footwear.

Conclusion

Rheumatologists acknowledged both the potential benefits and risks of running for people with RA. Individualised recommendations based on disease status and patient preferences could enhance the integration of running into care plans. Further research is needed to develop specific guidelines and understand patient outcomes.

Imprisonment and mortality among adults with neurodevelopmental disabilities in New South Wales, Australia, 2001-2015: a data-linkage cohort study

Por: Spike · E. · Srasuebkul · P. · Kariminia · A. · Butler · T. · Trollor · J.
Objectives

(1) Examine the associations between imprisonment history and mortality among adults with neurodevelopmental disabilities and (2) examine the associations between receipt of disability services and post-release mortality among adults with neurodevelopmental disabilities released from prison.

Design

Population-based data-linkage cohort study using historical administrative data.

Setting

New South Wales (NSW), Australia.

Participants

67 217 adults aged ≥18 years (59.1% male) with one or more neurodevelopmental disabilities in NSW, Australia, from July 2001 to June 2015.

Outcome measures

The main outcome measure was all-cause mortality. In the full cohort, we used Cox regression to examine the associations between release from imprisonment and all-cause mortality. In a subcohort of those released from prison, we used Poisson regression to examine the associations between receipt of disability services and post-release all-cause mortality.

Results

3.3% of participants (n=2214) were imprisoned and released at least once during follow-up. In all age groups

Conclusions

Among adults with neurodevelopmental disabilities, mortality was increased among those released from prison compared with their peers who had not been imprisoned, although this was largely explained by health-related factors, including mental illness, substance use and physical comorbidity. Comprehensive policy and service system responses are required to meet the health and safety needs of people with neurodevelopmental disabilities who have complex needs, including criminal legal system involvement, mental illness and substance use.

Development and validation of diagnostic and prognostic prediction tools for dental caries in young children through prospective and cross-sectional observational studies: a protocol

Por: Khazaei · Y. · Kodikara · S. · Butler · C. A. · Messina · N. L. · Le Cao · K.-A. · Dashper · S. G. · Silva · M. J.
Introduction

Dental caries is the most common oral disease worldwide, affecting up to 90% of children globally. It can lead to pain, infection and impaired quality of life. Early prevention is a key strategy for reducing the prevalence of dental caries in young children. Valid and reliable diagnostic or prognostic tools that enable accurate individualised prediction of current or future dental caries are essential for facilitating personalised caries prevention and early intervention. However, no efficacious tools currently exist in early childhood—the optimal period for disease prevention. We aim to develop and validate diagnostic and prognostic prediction tools for dental caries in young children, using a combination of environmental, physical, behavioural and biological early life data.

Methods and analysis

Data sources include two prospective studies, with a total sample size of approximately 600 children. These cohorts have collected detailed demographic, antenatal, perinatal and postnatal data from medical records and parent-completed questionnaires and biological samples including a dental plaque swab. Candidate predictor variables will include sociodemographic characteristics, health history, behavioural and microbiological characteristics. The outcome variable will be the presence, incidence or severity of dental caries diagnosed using the International Caries Detection and Assessment System. Statistical and machine learning approaches will be used for selection of predictor variables and model development. Internal validation will be conducted using resampling methods (i.e., bootstrapping) and nested cross-validation. Model performance will be evaluated using standard performance metrics such as accuracy, discrimination and calibration. Where feasible, external validation will be performed in an independent cohort. Model development and reporting will be guided by the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) statement and the Prediction model Risk Of Bias Assessment Tool (PROBAST) guidelines.

Ethics and dissemination

This study has ethical and governance approval from The Royal Children’s Hospital Melbourne Human Research Ethics Committee (HREC/111803/RCHM-2024). Results of this study will be published in peer-reviewed journals and presented at scientific conferences.

Trial registration number

Infant2Child: ACTRN12622000205730—pre-results; MisBair: NCT01906853—post results.

Psychosis and self-harm in prison: a population-based case-control study

Por: Chowdhury · N. Z. · Hwang · Y. I. · Spike · E. · Kariminia · A. · Dean · K. · Adily · A. · Ellis · A. · Greenberg · D. M. · Grant · L. · Allnutt · S. · Butler · T.
Background

Self-harm and suicide are common among prison inmates, but less is known about these phenomena in those with psychosis.

Objectives

The aim of this study was to examine self-harm behaviour in New South Wales (NSW) prisons in Australia among inmates diagnosed with psychosis. This study also examined self-harm-related alerts applied by Corrective Services to assist staff with the management of the security and well-being of inmates.

Design and setting

A retrospective case-control data-linkage study was conducted using administrative data collections in NSW, Australia.

Participants

The study included all individuals diagnosed with psychosis and incarcerated between 2001 and 2020 in NSW as cases and an age and sex matched control group with no such diagnosis with a record of incarceration in the same time period.

Primary and secondary outcome measures

The primary outcome measure was self-harm among the cases and controls. The secondary outcome measure was the application of alerts by Corrective Services in relation to self-harm incidents.

Results

Multivariate regression analysis was used to examine predictors of self-harm in prison. Prisoners with psychosis (n=14 900) were more likely to self-harm than controls (n=2713), with 15.0% versus 3.6% engaging in self-harm (highest odds of self-harm observed in those with schizophrenia and related psychoses, aOR=4.84, 95% CI: 3.93 to 5.98). Those of Aboriginal heritage had an increased risk of self-harm (aOR=1.58, 95% CI: 1.43 to 1.75). Factors associated with a lower risk of self-harm were male sex and older age (≥25 years) at the time of their first incarceration. 35.6% of those released from prison with a prior psychosis diagnosis had at least one alert applied during incarceration compared with 10.1% of prisoners without a diagnosis of psychosis. Overall, 35 individuals with psychosis and 1 individual from the control group died while in prison between 2001 and 2020. 17 prison suicides were recorded from the study population; all occurred in the psychosis group.

Conclusions

Given the heightened risk of self-harm in those with histories of psychosis, consideration should be given to sharing mental health information between agencies to improve the care and management of this group during incarceration. Prison alerts may be a useful tool to help staff manage inmates’ well-being if used appropriately.

The adaptive physical activity programme in stroke (TAPAS): protocol for a process evaluation in a sequential multiple assignment randomised trial

Por: Rocliffe · P. · Whiston · A. · O Mahony · A. · OReilly · S. M. · OConnor · M. · Cunningham · N. · Glynn · L. · Walsh · J. C. · Walsh · C. · Hennessy · E. · Murphy · E. · Hunter · A. · Butler · M. · Paul · L. · Fitzsimons · C. F. · Richardson · I. · Bradley · J. G. · Salsberg · J. · Hayes
Introduction

Participation in physical activity (PA) is a cornerstone of the secondary prevention of stroke. Given the heterogeneous nature of stroke, PA interventions that are adaptive to individual performance capability and associated co-morbidity levels are recommended. Mobile health (mHealth) has been identified as a potential approach to supporting PA post-stroke. To this end, we used a Sequential Multiple Assignment Randomised Trial design to develop an adaptive, mHealth intervention to improve PA post-stroke – The Adaptive Physical Activity programme in Stroke (TAPAS) (Clinicaltrials.Gov NCT05606770). As the first trial in stroke recovery literature to use this design, there is an opportunity to conduct a process evaluation for this type of adaptive intervention. The aim of this process evaluation is to examine the implementation process, mechanism of change and contextual influences of TAPAS among ambulatory people with stroke in the community.

Methods and analysis

Guided by the Medical Research Council Framework for process evaluations, qualitative and quantitative methods will be used to examine the (1) implementation process and the content of TAPAS (fidelity adaptation, dose and reach); (2) mechanisms of change (participants’ response to the intervention; mediators; unexpected pathways and consequences) and (3) influence of the context of the intervention. Quantitative data will be presented descriptively, for example, adherence to exercise sessions. Qualitative data will be collected among TAPAS participants and the interventionist using semi-structured one-to-one or focus group interviews. Transcribed interviews will be analysed using reflexive thematic analysis. Key themes and sub-themes will be developed.

Ethics and dissemination

Ethical approval has been granted by the Health Service Executive Mid-Western Ethics Committee (REC Ref: 026/2022) (25/03/2024). The findings will be submitted for publication and presented at relevant national and international academic conferences.

Left Write Hook: trial protocol for a community-based type II hybrid effectiveness-implementation cluster randomised controlled trial of a boxing and writing-based intervention for adult survivors of child sexual abuse and gender-based violence in Austral

Por: Butler · M. · Veltman · E. · Lyon · D. · Koye · D. N. · Fitzpatrick · P. · Alisic · E. · Ney · L. · Goode · A. · Healy · G. · Hitchcock · C.
Introduction

Sexual and gender-based violence can have long-term impacts on the physical and mental health of survivors, with demonstrated impairments to immune, endocrine and nervous systems, and increased risk of chronic conditions such as cardiovascular disease, depression and post-traumatic stress. Moreover, survivors commonly experience low self-efficacy and lack of perceived control over their lives. Creating space for survivors to feel empowered through a multidimensional approach to health promotion, considering both physical and psychological influences on health, is necessary to reduce chronic disease.

Methods and analysis

In this type II hybrid effectiveness-implementation cluster randomised controlled trial, we evaluate a novel peer-led intervention that combines expressive writing and trauma-informed boxing, Left Write Hook, against trauma-informed boxing alone—an intervention approach that is currently accessible in the community and has been shown to improve both mental and physical health. 20 clusters of 8–10 adults (n=150) with a self-reported history of child sexual abuse or other gender-based violence will be recruited in Melbourne, Australia, through health services and the community. Clusters will be randomly assigned to complete either 8x weekly group sessions of Left Write Hook (intervention) involving both expressive writing and trauma-informed boxing led by a trained peer facilitator, or 8x weekly group boxing sessions led by a trauma-informed boxing facilitator (control). Implementation will be evaluated against the PRISM Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework. The primary effectiveness outcome is change in self-efficacy from preintervention to postintervention (8 weeks). Secondary effectiveness outcomes are changes in symptoms of complex post-traumatic stress disorder, trauma-related cognition and indicators of physical fitness (strength, flexibility, aerobic fitness and balance). Assessment will be completed online or over the phone with a member of the research team at preintervention (0 weeks), postintervention (8 weeks) and at 1 month following completion of the intervention (12 weeks). The primary implementation outcome is the fidelity of the train-the-champion implementation strategy for intervention training and delivery, and the secondary implementation outcome is adoption of the intervention and training delivery.

Ethics and dissemination

Ethical approval was received from the Human Research Ethics Committee of The University of Melbourne (2024-28998-60131-11) and the Alfred Hospital Ethics Committee (110810). Results will be disseminated via publication in a peer-reviewed journal, and data will be made available via Open Science Framework at the conclusion of the trial.

Trial registration number

ACTRN12624000862549.

Comparative relationships between physical and verbal abuse of children, life course mental well-being and trends in exposure: a multi-study secondary analysis of cross-sectional surveys in England and Wales

Por: Bellis · M. A. · Hughes · K. · Ford · K. · Quigg · Z. · Butler · N. · Wilson · C.
Objectives

To test associations between mental well-being across the life course and exposure to childhood physical and/or verbal abuse.

Design

Secondary analysis of combined data from seven cross-sectional general adult population surveys measuring childhood experience of physical and/or verbal abuse and current mental well-being.

Setting

Households across England and Wales.

Participants

20 687 residents in England and Wales aged 18 years or over.

Measures

Self-reported childhood physical and verbal abuse using questions from an Adverse Childhood Experiences tool. Individual and combined components of adult mental well-being measured using the short Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS).

Results

Exposure to either childhood physical abuse or verbal abuse was associated independently with a similar significant increase in likelihood of low adult mental well-being, with exposure to both abuse types compounding increases (adjusted ORs 1.52, 1.64, 2.15 respectively, reference category: neither abuse type). Individual components of mental well-being showed similar associations, with adjusted prevalence of never or rarely having felt close to people in the last 2 weeks rising from 7.7% (neither abuse type) to 9.9% (physical abuse), 13.6% (verbal abuse) and 18.2% (both types of abuse). Within sample trends showed a significant drop in the prevalence of child physical abuse from around 20% in those born from 1950 to 1979 to 10% in those born in 2000 or after. However, verbal abuse rose from 11.9% in those born before 1950 to nearly 20% in those born in 2000 or after.

Conclusion

Exposure to childhood physical or verbal abuse have similar associations with lower mental well-being during adulthood. Interventions to reduce child abuse, including physical chastisement, should consider both physical and verbal abuse and their individual and combined consequences to life course health. The potential role of childhood verbal abuse in escalating levels of poor mental health among younger age groups needs greater consideration.

Minimum effective dose of a multicomponent behaviour change intervention to increase the physical activity of individuals on primary statin therapy: an adaptive study using the time-to-event continual reassessment method (TiTE-CRM)

Por: Goodwin · A. M. · Friel · C. · Miller · D. · Vicari · F. · Duer-Hefele · J. · Chandereng · T. · Davidson · K. W. · Alfano · C. M. · Cheung · Y. K. · Butler · M. J.
Objectives

To identify the minimum effective dose of a multi-behaviour change technique (BCT) intervention to increase physical activity among individuals on primary statin therapy using the time-to-event continual reassessment method (TiTE-CRM).

Setting

A large New York metropolitan area healthcare system comprising approximately 85 000 employees and 5.5 million patient encounters annually.

Participants

42 participants enrolled in 13 cohorts of 3 participants, 1 cohort of 2 participants and 1 cohort of 1 participant. The sample was composed of 16.7% individuals aged 66 and older (n=7), 64.3% women (n=27), 69.0% white individuals (n=29) and 7.1% Hispanic individuals (n=3).

Interventions

A variable-duration, four-BCT text message intervention and a 2-week follow-up. Dose assignment relied on TiTE-CRM to adjust the duration of the intervention based on adherence of participants in prior cohorts. Five mechanisms of action (MoAs) were assessed: self-efficacy, intrinsic regulation, discrepancy in behaviour, motivation and barriers to activity.

Primary and secondary outcome measures

The primary outcome measure was the proportion of participants who achieved a 2000 step/day increase between baseline and follow-up. The secondary outcomes were within-participant changes in daily steps (examined as a continuous variable at the daily level) and potential MoAs for increased physical activity.

Results

Of the 40 participants who completed follow-up, 7 (17.5%) achieved the goal of 2000 or more steps per day during their follow-up period. Though participants did increase the number of steps they walked during the intervention (B(SE)=373.1 (154.7) steps; p=0.016), there was no association between increased intervention duration and increased daily average steps. The intervention was also associated with increases in self-efficacy (p=0.002), intrinsic regulation (p=0.037), discrepancy in behaviour (p

Conclusions

The results of this trial did not show a traditional dose-response curve to increasing the length of a multicomponent BCT intervention. Results did show that the intervention successfully increased steps during the intervention period and that the benefit of the intervention dwindled during follow-up. Further, potential MoAs for the intervention were confirmed.

Trial registration number

NCT05273723.

Canadian Adaptive Platform Trial of Treatments for COVID in Community Settings (CanTreatCOVID): protocol for a randomised controlled adaptive platform trial of treatments for acute SARS-CoV-2 infection in community settings

Por: Hosseini · B. · Condon · A. · da Costa · B. R. · Daley · P. · Greiver · M. · Jüni · P. · Lee · T. C. · McBrien · K. · McDonald · E. G. · Murthy · S. · Selby · P. · Andrew · M. · Aubrey-Bassler · K. · Barber · D. · Barrett · B. · Butler · C. C. · Crampton · N. · Dahrouge · S. · Damji · A.
Introduction

SARS-CoV-2 is now endemic and expected to remain a health threat, with new variants continuing to emerge and the potential for vaccines to become less effective. While effective vaccines and natural immunity have significantly reduced hospitalisations and the need for critical care, outpatient treatment options remain limited, and real-world evidence on their clinical and cost-effectiveness is lacking. In this paper, we present the design of the Canadian Adaptive Platform Trial of Treatments for COVID in Community Settings (CanTreatCOVID). By evaluating multiple treatment options in a pragmatic adaptive platform trial, this study will generate high-quality, generalisable evidence to inform clinical guidelines and healthcare decision-making.

Methods and analysis

CanTreatCOVID is an open-label, individually randomised, multicentre, national adaptive platform trial designed to evaluate the clinical and cost-effectiveness of therapeutics for non-hospitalised SARS-CoV-2 patients across Canada. Eligible participants must present with symptomatic SARS-CoV-2 infection, confirmed by PCR or rapid antigen testing (RAT), within 5 days of symptom onset. The trial targets two groups that are expected to be at higher risk of more severe disease: (1) individuals aged 50 years and older and (2) those aged 18–49 years with one or more comorbidities. CanTreatCOVID uses numerous approaches to recruit participants to the study, including a multifaceted public communication strategy and outreach through primary care, outpatient clinics and emergency departments. Participants are randomised to receive either usual care, including supportive and symptom-based management, or an investigational therapeutic selected by the Canadian COVID-19 Outpatient Therapeutics Committee. The first therapeutic arm evaluates nirmatrelvir/ritonavir (Paxlovid), administered two times per day for 5 days. The second therapeutic arm investigates a combination antioxidant therapy (selenium 300 µg, zinc 40 mg, lycopene 45 mg and vitamin C 1.5 g), administered for 10 days. The primary outcome is all-cause hospitalisation or death within 28 days of randomisation.

Ethics and dissemination

The CanTreatCOVID master protocol and subprotocols have been approved by Health Canada and local research ethics boards in the participating provinces across Canada. The results of the study will be disseminated to policy-makers, presented at conferences and published in peer-reviewed journals to ensure that findings are accessible to the broader scientific and medical communities. This study was approved by the Unity Health Toronto Research Ethics Board (#22-179) and Clinical Trials Ontario (Project ID 4133).

Trial registration number

NCT05614349

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