by Liubov Arbeeva, Virginia B. Kraus, Amanda E. Nelson, Maryalice Nocera, Leigh F. Callahan, Richard F. Loeser, Kenneth L. Cameron, Jesse R. Trump, Stephen W. Marshall, Yvonne M. Golightly
PurposeTo investigate the longitudinal relationships between serum biomarkers of joint metabolism, knee injury, and Knee Injury and Osteoarthritis Outcome Score (KOOS) using novel methodologies.
MethodsData were collected from military officers who enrolled as cadets between 2004–2009, with follow-up conducted between 2015–2017. Analyses included 234 officers who had no history of knee ligament/meniscal injury at the time of military academy matriculation, had serum biomarker measurements at matriculation and graduation, demographic data, and KOOS assessment at follow-up. Biomarkers included Collagen Type II (C2C) and Type I and II (C1,2C) collagenase-generated cleavage epitopes, C-terminal propeptide of Type II collagen (CPII), and C- and N-terminal telopeptides of type I collagen (CTX and NTX). Angle-based Joint and Individual Variation Explained (AJIVE) was used to determine demographic determinants of biomarker levels and individual modes of variation specific to biomarker levels at matriculation and graduation, stratified by sex.
ResultsWe confirmed known associations of joint metabolism biomarkers with age in both sexes and with smoking in males. Matriculation biomarker data in males suggested a protective biomarker profile characterized by high cartilage synthesis and low cleavage of type I and II collagen in association with healthy KOOS scores at follow-up. CPII measured at matriculation was negatively associated with incident injuries after adjustment for smoking status (p = 0.03, logistic regression), confirming results from AJIVE.
ConclusionThese exploratory analyses suggest that CPII alone, or in combination with other joint metabolism biomarkers, may help identify individual risk of knee injury.
The aim in this human trial is to compare the efficacy and safety of polygalacturonic–caprylic acid (PG–CAP) ointment to MediHoney in chronic wounds at three international medical centres. In this prospective open-label study, patients with chronic full-thickness wounds were randomised to daily treatment with PG–CAP ointment or MediHoney. Assessments were obtained weekly for 6 weeks. The validated Pressure Ulcer Scale for Healing (PUSH) score was used to track healing. Efficacies were compared using the Wilcoxon rank-sum test for continuous variables and chi-square or Fisher's exact test for categorical variables. Twenty-six patients with chronic wounds were included. Baseline characteristics were comparable between the groups; however, the history of diabetes mellitus was higher in the PG–CAP group (p = 0.011). All 13 PG–CAP patients showed improvement (100%), compared to only 69% of the 13 MediHoney patients (p = 0.023). Half of the failures in the MediHoney arm were associated with death (15%). No failures, adverse events or deaths occurred in the PG–CAP arm. PG–CAP wound ointment is a novel combination of two plant-based compounds that pose minimal risk of promoting antimicrobial resistance, was highly effective for eradicating wound-pathogen biofilms in vitro and promoted chronic wound healing in vivo with minimal inflammatory reactions. Our findings support PG–CAP as safe, noninferior and possibly more effective than MediHoney in healing chronic contaminated wounds.
by Tatiana Petukhova, Maria Spinato, Tanya Rossi, Michele T. Guerin, Cathy A. Bauman, Pauline Nelson-Smikle, Davor Ojkic, Zvonimir Poljak
Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is endemic in many pig-producing countries and poses significant health and economic challenges. Enhanced surveillance strategies are essential for effective disease management. This study aimed to evaluate and compare the performance of different time-series modeling techniques to predict weekly PRRSV-positive laboratory submissions in Ontario, Canada. Ten years of PRRSV diagnostic data were obtained from the Animal Health Laboratory at the University of Guelph and were processed into a weekly time series. The dataset was analyzed with autoregressive integrated moving average (ARIMA), exponential smoothing (ETS), random forest (RF), and recurrent neural network (RNN) models. Two validation strategies were employed: a traditional train-test split and a simulated prospective rolling forecast. Model accuracy was evaluated using common predictive error metrics. Descriptive analysis indicated a gradual increase in PRRSV positive submissions over time, with no consistent seasonal pattern. ARIMA and ETS models generally overpredict case counts, while RF and RNN tended to underpredict them. Among the evaluated models, the RF regression model most accurately captured the underlying time-series dynamics and produced the lowest prediction errors across both validation approaches. Despite outperforming other models, the RF model’s high relative prediction errors limit its suitability for accurate forecasting of PRRSV-positive submissions in Ontario’s routine surveillance system. Further data refinement and algorithm improvements are warranted.Existing psychological and pharmacological interventions for young people at ultra-high risk (UHR) for psychosis have shown benefit in at least delaying the transition to psychosis, but they have limited benefit for comorbid disorders or social dysfunction, which are prominent for those at UHR. We developed a moderated online social therapy platform (named Momentum) including: (1) transdiagnostic therapeutic interventions targeting social functioning, depression, generalised anxiety and social anxiety; (2) a moderated, peer-led online community and (3) specialised human support from clinicians, career consultants and peer workers. The aim of this trial is to determine whether, in addition to treatment as usual (TAU), Momentum, a 12-month digital intervention, informed by the complex intervention framework, is superior to 12 months of TAU in improving social functioning in UHR young people.
The study design is a prospective, parallel group, rater-masked randomised controlled trial. We will recruit young people aged 14–27 years, meeting one or more UHR for psychosis criteria. Participants are randomly assigned to the condition using randomly permutated blocks with a 1:1 allocation ratio. Participants are stratified by age (
Melbourne Health Human Research Ethics Committee (HREC/42964/MH-2018) provided ethics approval for this study. Findings will be made available through scientific journals and forums and to the public via social media and the Orygen website. De-identified individual participant data will be available after publication for 3 years via the Health Data Australia catalogue (https://www.researchdata.edu.au/health). Requests must include a methodologically sound proposal. Specific conditions of use may apply and will be specified in a data sharing agreement (or similar) that the requester must agree to before access is granted. Supplementary material including study protocol, informed consent material and statistical analysis plan will also be available.
Australian New Zealand Clinical Trial Registry (ANZCTR), ACTRN12619001411134.
by Thea Lynne Hedemann, Yun Lu, Sofia Campitelli, Lisa D. Hawke, Nelson Shen, Sarah Saperia, Brett D. M. Jones, Gillian Strudwick, Chelsey R. Wilks, Wei Wang, Marco Solmi, Michael Grossman, Muhammad Ishrat Husain, Nicole Kozloff, George Foussias, Muhammad Omair Husain
BackgroundYouth at clinical high risk (CHR) for psychosis often experience emotional dysregulation, psychiatric symptoms, substance use, suicidality, and functional impairment. Dialectical behaviour therapy (DBT) is an evidence-based intervention that improves emotion regulation, clinical outcomes, and functioning across psychiatric populations. Digital adaptations (d-DBT) may enhance accessibility and engagement for CHR youth, but acceptability and potential benefits in this group are unknown.
ObjectiveTo adapt d-DBT for CHR youth and evaluate the acceptability of delivering it to this population, as well as the feasibility of a larger-scale clinical trial.
MethodsThis mixed-methods clinical trial has two phases. In Phase 1, d-DBT will be adapted for CHR youth in collaboration with a lived-experience youth advisory group. In Phase 2, an assessor-masked randomized controlled trial will compare d-DBT (n = 30) with treatment as usual (n = 30). The intervention consists of eight weekly modules, with primary outcomes assessing acceptability, usability, and trial feasibility. Secondary outcomes include changes in emotional dysregulation, psychiatric symptoms, substance use, suicidality, and functioning.
ConclusionsWe anticipate that d-DBT will be acceptable to CHR youth and that conducting a larger trial will be feasible. Preliminary findings may demonstrate improvements in emotion regulation, psychiatric symptoms, suicidality, and functioning. Results will guide further refinement of the intervention and inform the design of a confirmatory clinical trial.
Trial registrationClinicalTrials.gov #NCT06928935
Essential care partners (ECPs), also known as family caregivers, play a critical role in the Canadian healthcare system across the continuum of care, particularly in managing complex conditions like stroke. With the rising number of stroke incidents occurring in Canada each year, there is an increased need for caregiver assistance to help manage the care needs of stroke survivors as they transition to home and community services. Although existing research has highlighted the practical and psychosocial needs of stroke ECPs, these challenges have been mainly overlooked. The lack of integrated intersectoral care services across stroke care pathways places additional significant burdens on caregivers, leading to increased stress, social isolation and a decreased quality of life. Nelson and colleagues’ novel Discharge Assistance and Supports at Home model uses community-based interventions mobilised through intersectoral partnerships and volunteers as human resources to facilitate grassroots solutions to the discharge and transition challenges often faced by stroke survivors. As an extension of this work, this rapid review will investigate and detail community-involved or community-led interventions that have been proven effective in addressing the unmet needs of stroke ECPs during critical care transitions. The findings of this review will identify what works, for whom and in what context regarding community-involved caregiver-centred transition interventions to inform the creation of an actionable Research Agenda—DASH-Caregiver.
This rapid review will be conducted using the updated guidance on methods used in Cochrane rapid reviews of effectiveness. The search strategy will be refined by the study team with assistance from an information specialist and applied to six databases: Medline, Cochrane, Embase, CINAHL and PubMed. Grey literature will be searched using Google search engines, targeted websites and consultation with knowledge holders. Two research team members will conduct a two-stage screening process to determine study eligibility. Data from eligible studies will be extracted using a piloted charting form and synthesised narratively.
This review protocol does not require ethics approval, as no data have been collected or analysed. The results will be shared with key knowledge holders through publications and presentations and incorporated into the team’s future research.
by Andrea Salinas, Christa Burgos, Aaron Rodríguez-Ramos, Alberto Burgos-Edwards, Nelson Alvarenga, Pablo H. Sotelo, Patricia Langjahr
Inflammation plays a crucial role in homeostasis and defense responses; however, exaggerated and chronic inflammation contribute to the development and worsening of various diseases. Acanthospermum australe (Loefl.) Kuntze (A. australe) is a medicinal plant traditionally used to alleviate inflammation. However, the anti-inflammatory activity of this plant has not yet been explored. This study aimed to evaluate the immunomodulatory activity of this species using network pharmacology, UPLC-ESI-MS/MS analysis, and in vitro assays. Network pharmacology analysis revealed the involvement of immune system processes, and among the main targets of A. australe related to inflammation were innate immune responses, toll-like receptors (TLRs), and T cell receptor signaling pathways. A methanolic extract was prepared and analyzed using UPLC-ESI-MS/MS, and 15 compounds were detected. Additionally, the potential targets of A. australe predicted by network pharmacology analysis were validated in vitro using monocytic THP-1 cells and splenocytes. The RT-qPCR analysis indicated that A. australe significantly inhibited the production of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α, as well as chemokine CCL-2, in lipopolysaccharide (LPS)-stimulated cells. Finally, the extract significantly decreased concanavalin A (ConA)-induced T cell proliferation. Overall, our study provides evidence for the anti-inflammatory effects of this species and highlights its mechanisms of action.People experiencing severe and multiple disadvantage (SMD: homelessness, substance use and criminal offending) have multiple intersecting unmet health and social care needs and high mortality rates, often due to street-drug overdose. Pilot randomised controlled trials (RCTs) suggest an integrated, holistic, collaborative outreach intervention (Pharmacy Homeless Outreach Engagement Non-medical Independent Prescribing Rx (PHOENIx)) involving generalist-trained pharmacists, nurses or General Practitioners accompanied by staff from third sector homeless organisations may improve outcomes, including reducing overdose.
Multicentre, parallel group, prospective RCT with parallel economic and process evaluation. Set in six areas of Scotland, UK, 378 adults with SMD will be recruited and randomised (stratified by setting and previous non-fatal overdoses) to PHOENIx intervention in addition to usual care (UC) or UC. Aiming to meet participants weekly for 9–15 months, PHOENIx teams assess and address health and social care needs while referring onwards as necessary, co-ordinating care with wider health and third sector teams. During a person-centred consultation, in the participants’ choice of venue, and taking account of the participant’s priorities, the NHS clinician may prescribe, de-prescribe and treat, for example, wound care, and refer to other health services as necessary. The third sector worker may help with welfare benefit applications, social prescribing or advocacy, for example, securing stable housing. Pairings of clinicians and third sector workers support the same participants. The primary outcome is time to first fatal/non-fatal street-drug overdose at nine months. Secondary endpoints include health-related quality of life, healthcare use and criminal justice encounters. A health economic evaluation will assess cost per quality adjusted life year of PHOENIx relative to standard care. A parallel qualitative process evaluation will explore the perceptions and experiences of PHOENIx, by participants, stakeholders and PHOENIx staff.
The primary and other time-to-event secondary outcomes will be analysed by Cox proportional hazards regression.
IRAS number 345246, approved 23/10/2024 by North of Scotland Research Ethics Service. Results will be shared with participants, third sector homelessness organisations, health and social care partnerships, then peer-reviewed journals and conferences worldwide, from the first quarter of 2027.
ISRCTN12234059 registered on 20/2/2025 (ISRCTN).
HIV pre-exposure prophylaxis (PrEP) is an effective HIV prevention tool, reducing infection risk by up to 99% when used as prescribed. Despite its proven efficacy, PrEP uptake remains suboptimal, particularly among high-risk populations in Canada. Barriers to access and uptake, including stigma, financial constraints and healthcare accessibility, persist, highlighting the need for targeted interventions. The objective of this scoping review is to identify and map the extent and types of interventions, programmes, practices and policies aimed at increasing the acceptance, access, uptake and sustained use of HIV PrEP in Canada.
This review will use the Joanna Briggs Institute (JBI) Scoping Review methodology. Databases to be searched are MEDLINE, Embase, PsycINFO, Cochrane Library, CINAHL, Scopus and Web of Science from 2016 onwards. Two independent reviewers will screen studies, based on the inclusion criteria. The search results will be presented in a Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. Data will be extracted from relevant studies by two independent reviewers and summarised to inform future research and policy development. This review will include studies focusing on individuals in Canada who are eligible for or using PrEP for HIV prevention. The interventions considered will address the awareness, acceptance, access, uptake and sustained use of PrEP. Studies must be set within the Canadian context, considering geographic, cultural and systemic factors. Exclusions include studies conducted outside Canada or those not addressing HIV prevention interventions.
This research will rely exclusively on previously published data and will not include human participants. Therefore, ethics approval is not required. For further clarification, please contact Stephen Hwang, Director, MAP Centre for Urban Health Solutions, Unity Health Toronto, at
The protocol has been registered with Open Science Framework at https://doi.org/10.17605/OSF.IO/C7S4Z.
The use of invasive life support in patients with a prolonged critical illness clearly saves lives but carries substantial risks, including intensive care unit-acquired weakness (ICUAW) and long-term disability. Early mobilisation might improve outcomes, yet the evidence is conflicting and complicated by the lack of a responsive outcome measurement to detect change in critically ill patients’ physical function and activity. The Chelsea Critical Care Physical Assessment tool (CPAx) is a valid and reliable instrument for patients at risk of ICUAW. However, its ability to measure change over time (responsiveness) and the minimal clinically important difference (MCID) have not yet been rigorously investigated.
The primary objective of this prospective, international, multicentre, longitudinal cohort study is to investigate responsiveness and to establish the MCID of the CPAx during the ‘intensive care unit (ICU) period’, from ICU baseline to ICU discharge, and ‘hospital period’, from ICU to hospital discharge. Adults with any critical illness who are mechanically ventilated for at least 72 hours, expected to remain in ICU (≥48 hours) and being treated by a physiotherapist are eligible for study inclusion. Functional measurements, including the CPAx and a global rating of change (GRC) scale, will be collected during routine physiotherapy. Responsiveness will be evaluated primarily using the GRC as an anchor to distinguish changed from unchanged/deteriorated patients (criterion validity). As such, the magnitude of change will be analysed with receiver operating characteristics. Additionally, construct validity will be explored with correlation coefficients and effect sizes to confirm/reject a priori formulated hypotheses. MCID will be investigated with anchor-based and distribution-based methods. We plan to recruit 120 patients across three sites in Australia and Switzerland.
Ethical approval has been obtained from each local ethics committee (Canton of Bern, Switzerland (2024-00346), Monash Health, Australia (HREC/106143/MonH-2024-438474(v3)), the Alfred, Australia (490/24)). The results will be disseminated through international/national conferences, peer-reviewed journals and social media. The high quality, rigorous testing of the CPAx could benefit researchers, clinicians and patients.
Recent legislation in the UK regarding requirements for new developments to increase biodiversity may have significant implications for the environment and population health. Despite this, relatively little is known regarding the health and social benefits of increasing biodiversity in densely populated urban areas.
This protocol outlines plans for a mixed-method, longitudinal, natural experiment study which will evaluate the planned, biodiversity-focused redevelopment of six small urban parks in Edinburgh, Scotland (UK). Using systematic observation (at baseline, 1 month post-intervention and 1 year post-baseline) and a longitudinal household survey (at baseline and 1 year post-baseline), the primary outcomes of personal well-being, and secondary outcomes of nature connectedness and park usage behaviours, will be assessed, respectively. Consent for data linkage of respondent’s health records will also be sought. Process evaluation will employ semi-structured, qualitative interviews with stakeholders and walk-along interviews with local residents in order to understand implementation processes. Space-related well-being will also be assessed using citizen science approaches.
This study was approved by the University of Edinburgh’s School of Health in Social Sciences ethics committee. This study will provide further evidence for policymakers, the public and researchers of the health and social well-being effects of urban biodiversity interventions. Study findings will be disseminated via public forums such as community workshops and through publication in peer-reviewed journals and presentation at scientific conferences.
We calculate positive predictive values (PPVs) of patients presenting with unexpected weight loss (UWL) being diagnosed with cancer within 6 months, using data from a population of Australian primary care patients to replicate results from a previous UK study.
A diagnostic accuracy study involving calculation of the PPV for any cancer using retrospective data from routinely collected electronic healthcare records. The index date is defined as the first recorded UWL presentation and the reference standard is cancer diagnosis within 6 months of the index date.
This study uses primary care data from the Patron primary care database, linked to hospital admissions data and the Victorian Cancer Registry. We include only patients who presented to their General Practitioners (GPs) at least once between 1 July 2007 and 1 February 2022.
Patients were included if they were at least 18 years of age at the index date, had no previous diagnosis of cancer or previous weight loss intervention, including being prescribed medications for weight loss. 13 306 patients out of a primary care population of 1 791 051 patients were identified that met the eligibility criteria.
When stratified by age, sex and smoking status, we found PPVs lower than those derived in a previous UK primary care study, though still above 3% for male non-smokers over 60, female smokers over 70 and all males over 70. Patients from ages 60–79 with at least one abnormal blood test result had PPVs consistently above 3%, while overall, patients with abnormal blood test results have PPVs of up to 35%.
We confirmed that many PPVs, while consistently below those derived in the UK study, are above clinically significant thresholds and increasing with age and the number of different abnormal blood test results.
Despite extensive efforts in HIV prevention, significant barriers to accessing interventions such as HIV pre-exposure prophylaxis (PrEP) persist in Canada. Although PrEP has demonstrated efficacy in preventing HIV transmission, various structural, social and systemic factors continue to impede its widespread adoption and use. These factors influence the uptake (acceptance and access) and use (adherence and retention) of PrEP. The purpose of this scoping review is to examine the existing body of evidence regarding the barriers and facilitators to uptake and use of PrEP in Canada. By identifying these factors, the review aims to inform future research, policy development and interventions to improve PrEP access and its integration into HIV prevention strategies in Canada.
This scoping review will focus on studies involving HIV-seronegative individuals in Canada who are either eligible for or currently using PrEP as an HIV prevention option. The review will consider barriers and facilitators within services, programmes, policies or practices related to HIV prevention in Canada. Eligible studies will include experimental, quasi-experimental, observational or qualitative designs. Studies that do not address PrEP or HIV prevention, or that involve populations not aligned with the inclusion criteria, will be excluded. The review will involve searching a range of key databases, including MEDLINE, Embase, PsycINFO, Cochrane Library, CINAHL, Scopus, Web of Science and TRIP, with no language restrictions, and focusing on publications from 2016 onward. Two independent reviewers will screen titles and abstracts, followed by full-text assessment and data extraction, using Covidence. Data will be analysed narratively, with a specific focus on subgroup analyses of key populations. The findings will be synthesised to provide an overview of the key themes, trends, and evidence gaps identified within the existing literature.
This piece of research will not involve human participants and will solely use already published data. Consequently, ethics approval is not necessary. The findings will be disseminated through peer-reviewed journal articles and conference presentations and may be of relevance to governmental health agencies and local HIV/AIDS service organisations.
The protocol has been registered on Open Science Framework registries at https://doi.org/10.17605/OSF.IO/69WJA.