Polysubstance use (PSU), particularly opioid-involved and stimulant-involved PSU, is a growing issue in the USA. PSU increases the risk of negative health consequences, including infectious diseases, worsening physical and mental health conditions, and overdose-related deaths. These consequences occur in the context of varying health risk behaviours, substance-related preferences, and treatment engagements among people with PSU. To inform improvements in prevention, harm reduction, and substance use disorder (SUD) treatment, additional research is needed to comprehensively understand the current context and drivers of PSU preferences, motivations, and behaviours.

Herein, we describe the protocol for a prospective cohort study designed to capture detailed patterns, profiles, and trajectories of PSU, with the aim of comprehensively examining the drivers of PSU behaviours and SUD treatment utilisation. Adults (ages 18–75; n=400) who engage in PSU will be recruited from healthcare institutions, an established participant database maintained by an adjacent SUD research team, and online advertisements. Study assessments will capture dynamic patterns, choice preferences, and motivators of PSU via behavioural economic (BE) measures, detailed Timeline Follow-Back (TLFB) interviews, and self-administered surveys. The assessment timeline will include a baseline survey and TLFB interview, weekly TLFB interviews for 4 weeks post-baseline, and follow-up surveys and TLFB interviews at 4-, 8-, and 12-months post-baseline.

The study is funded through the National Institutes of Health Helping to End Addiction Long-term (HEAL) initiative and was approved by the University of Michigan Medical Institutional Review Board. Findings will be disseminated to academic, clinical, and community partners through the Michigan Innovations in Addiction Care through Research and Education programme. Results from this study will inform actionable and practical insights relevant to the delivery of personalised care in the context of PSU.

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).

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).

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).

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.

Patients who survive admission to intensive care unit (ICU) for critical illness are at high risk of developing muscle atrophy and weakness, commonly diagnosed as ICU-acquired weakness (ICUAW). The development of ICUAW is closely linked to long-term symptoms and impairments known as post-intensive care syndrome (PICS). Despite heightened recognition of impairments, there is limited research supporting effective interventions to improve muscle and physical outcomes after hospital discharge. Prior to developing and testing interventions for ICU survivors, it is imperative to understand the trajectory of muscle and physical function recovery following an ICU stay. The purpose of this study is to longitudinally investigate skeletal muscle health and physical function outcomes after ICU admission.

This protocol describes a single site, prospective, observational study in adult patients who have survived a critical illness (ie, sepsis or acute respiratory failure). Patients will participate in a battery of testing including primary outcomes: muscle power and physical function; and secondary outcomes: muscle strength, muscle size, endurance and physical activity (by accelerometry) at hospital discharge and 3, 6, and 12 months post-discharge. A subset of patients will participate in muscle biopsy and venipuncture. To examine if the trajectory of recovery predicts primary outcomes, we will perform multivariate linear regression models in 150 evaluable patients. To examine differences in molecular and cellular outcomes in plasma and muscle tissue, a control group of community-dwelling adults without history of an ICU stay will be enrolled as a comparator group. Enrolment started on 18 October 2022 with an estimated completion date of 1 August 2027.

This protocol was approved by the University of Kentucky Office of Research Integrity Medical Internal Review Board (# 77407), with patients providing informed written consent. We anticipate our findings to establish recovery trajectories, improving the classification of patients who experience sustained physical disability. Improved identification of recovery trajectories of muscle and physical function enables future studies to employ an individually targeted rehabilitation approach, that is, precision medicine, with the goal of improving patient outcomes. The cellular findings will support the development of novel interventions specifically designed for detecting underlying mechanisms. We intend to disseminate findings to patients, healthcare professionals, the public and other relevant groups via conference presentations and manuscripts without publication restrictions.

NCT05537298.

Patient safety culture plays a crucial role in reducing clinical errors. By improving healthcare professionals’ and patients’ understanding of human fallibility and error attribution, patient care can be enhanced, fostering greater engagement from both groups. A Just Culture approach, which balances accountability and learning from errors, is a key factor in fostering this safety culture. The DECIDE Project aims to: (1) examine the conceptualisation of human fallibility within and beyond healthcare, (2) identify barriers and facilitators to Just Culture adoption, (3) assess the impact of psychoeducational interventions on professionals’ and social leaders’ attitudes toward clinical errors and (4) develop a roadmap for Just Culture implementation in healthcare.

A 36-month mixed-methods study including qualitative research, a survey of 1255 healthcare professionals, an experimental study with 180 participants (60 per arm) testing interventions based on cognitive dissonance and reasoned action theories and a consensus conference to develop a Just Culture roadmap. Participants include professionals from hospitals, primary care, long-term care, nursing homes and social leaders in Spain. The qualitative data collected during stages 1 and 4 will be analysed using MAXQDA software. In identifying factors related to the implementation of Just Culture during stage 2, ANOVA, t-tests and multiple linear regression will be conducted. To examine the effects of the interventions in phase 3, a linear mixed-effects model for repeated measures will be employed.

This study has received ethical approval from three institutional review boards. Findings will be disseminated through peer-reviewed publications, conference presentations and policy recommendations aimed at integrating Just Culture into national and international patient safety strategies. By promoting a constructive approach to errors, the project could enhance incident reporting, strengthen professional engagement in safety policies and foster a culture of learning and accountability. Its findings will guide policy recommendations for integrating Just Culture into national and international patient safety strategies, with potential applications beyond Spain.

NCT06835517.

Exposure to prescription opioids following traumatic injury can increase the risk of developing tolerance, persistent opioid use and opioid use disorder. The mechanisms underlying opioid tolerance or dependence are not well understood, and no biomarkers predict risk. Opioid exposure causes epigenetic modifications, including alterations in microRNA (miRNA) expression. Several miRNAs, which regulate synaptic plasticity, are hypothesised to underlie substance use disorders and influence µ-opioid receptor levels, modulating opioid tolerance. This project aims to develop a bio-behavioural signature to predict persistent opioid use and chronic pain up to 6 months post-discharge.

The study will use a prospective cohort design, enrolling 180 adult patients at a Level I Trauma Center who are prescribed opioids at discharge. Prospective data will be collected in the hospital and at 7 days and 1, 3 and 6 months post-discharge. Biological data (genotyping and miRNA levels) and clinical measures of opioid use, pain, pain sensitivity (EEG) and psychosocial functioning will be collected at each time point. Bayesian regression methods will be used to identify baseline clinical, genetic, epigenetic and psychosocial predictors of opioid use and pain outcomes at 6 months post-discharge. Growth mixture modelling will identify distinct subgroups with varying trajectories, followed by Bayesian hierarchical modelling to predict trajectory classification based on predictor variables.

Ethics approval for this study was obtained from the University of Texas Health Science Center at Houston Committee for the Protection of Human Subjects (HSC-MS-24–0314). Findings will be disseminated in peer-reviewed scientific journals and at national and international conferences.