The ‘time-limited trial’ for patients with critical illness is a collaborative plan made by clinicians, patients and families to use life-sustaining therapies for a defined duration. After this period, the patient’s response to therapy informs decisions about continuing recovery-focused care or transitioning to comfort-focused care. The promise of time-limited trials to help navigate the uncertain limits and benefits of life-sustaining therapies has been extensively discussed in the palliative and critical care literature, leading to their dissemination into clinical practice. However, we have little evidence to guide clinicians in how to conduct time-limited trials, leading to substantial variation in how and why they are currently used. The overall purpose of this study is to characterise the features of an optimal time-limited trial through a rich understanding of how they are currently shaping critical care delivery.

We are conducting an observational, multicentre, focused ethnography of time-limited trials in patients with acute respiratory failure receiving invasive mechanical ventilation in six intensive care units (ICUs) within five hospitals across the US. Study participants include patients, their surrogate decision makers and ICU clinicians. We are pursuing two complementary analyses of this rich data set using the open-ended, inductive approach of constructivist grounded theory and, in parallel, the structured, deductive methods of systems engineering. This cross-disciplinary, tailored approach intentionally preserves the tension between time-limited trials’ conceptual formulation and their heterogeneous, real-world use.

This study has been reviewed and approved by the University of Wisconsin Institutional Review Board (IRB) as the single IRB (ID: 2022-1681; initial approval date 23 January 2023). Our findings will be disseminated through peer-reviewed publication, conference presentations, and summaries for the public.

NCT06042621.

Many patients receive oral anticoagulation for reduced stroke risk in atrial fibrillation or as treatment or prevention of venous thromboembolism. Oral factor Xa inhibitors (oral FXaI, eg, apixaban, edoxaban or rivaroxaban) are commonly prescribed for this indication. Dabigatran, an oral direct thrombin inhibitor, is similarly approved. In vitro and animal model evidence suggests that dabigatran also has direct effects on Staphylococcus aureus virulence and infection. Observational data have shown that dabigatran users are less likely to develop S. aureus bacteremia (SAB), and a small randomised controlled trial showed that dabigatran has anti-S. aureus effects when compared with low molecular weight heparins during bloodstream infection. We seek to answer whether dabigatran is superior to the oral FXaIs in achieving better SAB outcomes among patients who independently require oral anticoagulation. We report the intervention-specific protocol, embedded in an adaptive platform trial.

The S. aureus Network Adaptive Platform (SNAP) trial [NCT05137119] is a pragmatic, randomised, multicentre adaptive platform trial that compares different SAB therapies for 90-day mortality rates. For this intervention (‘Dabi-SNAP’), patients receiving therapy with an oral FXaI will be randomised to continue as usual or to change to dabigatran as of the next scheduled dose. All subjects will receive standard of care antibiotics and/or antibiotics allocated through other active domains in the platform. As the choice of anticoagulant may not demonstrate large differences in mortality, a ranked composite of death and adverse outcomes (Desirability of Outcome Ranking, or DOOR) was chosen as the primary outcome.

The study is conditionally approved by the research ethics board of the McGill University Health Centre: identifier 2025-10900. Trial results will be published open access in a peer-reviewed journal and presented at a global infectious disease conference. The trial is registered at clinicaltrials.gov with the identifier NCT06650501.

NCT0665050.

Gram negative bloodstream infections (GN BSI) are a leading cause of mortality worldwide, and antibiotic treatment approaches remain understudied. BALANCE+ is a perpetual Bayesian adaptive platform trial to test multiple treatment questions for hospitalised patients with GN BSI. The vanguard phase objective was to test the feasibility of the main trial.

Adaptive platform trial with five initial domains of investigation, each with open label 1:1 randomisation.

Ten hospitals across four Canadian provinces.

Individuals admitted to hospital with blood cultures yielding Gram negative bacteria.

The five initial domains of investigation included: antibiotic de-escalation versus no de-escalation; oral transition to beta-lactam versus non-beta-lactam treatment; routine versus no routine follow-up blood cultures (FUBCs); central vascular catheter replacement versus retention; and, ceftriaxone versus carbapenem treatment for low risk AmpC organisms.

Domain-specific recruitment rates and protocol adherence.

During the vanguard phase, 719 patients were screened, of whom 563 (78.3%) were eligible, with 179 (31.8%) enrolled into the platform. The platform recruitment rate was 1.37 patients/site-week. Recruitment varied by domain: routine versus no FUBC domain 1.23 patients/site-week; oral beta-lactam versus non-beta-lactam domain 0.48; de-escalation versus no de-escalation domain 0.28; low risk AmpC domain 0.02; catheter replacement versus retention domain 0.01. Domain specific protocol adherence rates were 145/158 (91.8%) for routine versus no routine FUBC, 53/60 (88.3%) for oral beta-lactam versus non-beta-lactam, 26/33 (78.8%) for de-escalation versus no de-escalation, 3/3 (100%) for low risk AmpC, and 0/1 (0%) for line replacement versus retention. There was complete ascertainment of all study outcomes in hospital 170/170 (100%) and near complete ascertainment at 90 days 162/170 (95.3%).

The vanguard phase demonstrated overall trial feasibility by recruitment rate and protocol adherence, with differences across interventions, leading to a transition to the main BALANCE+ platform trial with minimal protocol modifications.

NCT05893147.

To assess the early risk of diabetic foot ulcer (DFU) among adult patients with diabetes and to identify clinical and behavioural correlates associated with DFU risk using Inlow’s 60-Second Screening Tool.

A cross-sectional analytical study.

Conducted at a tertiary-level referral hospital in Southwest Ethiopia.

The study included 164 adult patients with diabetes (aged ≥18 years) who attended routine follow-up visits at the diabetic clinic between February and March 2025. Patients who were critically ill, unable to communicate during data collection or pregnant were excluded. The median age of participants was 55 years (IQR 46–60), and 54.9% were male.

The primary outcome was early DFU risk, categorised as ‘at risk’ or ‘not at risk’ using Inlow’s 60-Second Screening Tool. Secondary outcomes included factors associated with DFU risk, such as glycaemic control, lipid profile and foot care practices.

Of the 164 participants, 32.3% (n=53) were found to be at risk for DFU. Participants who performed foot self-checks infrequently had more than threefold higher odds of DFU risk compared with those who practiced daily foot care (adjusted OR (AOR)=3.35; 95% CI 1.48 to 7.58; p=0.004). Poor glycaemic control (AOR=2.39; 95% CI 1.03 to 5.55; p=0.042) and dyslipidaemia (AOR=2.63; 95% CI 1.18 to 5.85; p=0.018) were also significantly associated with increased DFU risk.

Nearly one-third of patients with diabetes in this Ethiopian hospital setting were at early risk for DFU. Factors such as inadequate foot care, poor glycaemic control and dyslipidaemia were associated with increased risk. Incorporating rapid foot screening tools like Inlow’s 60-Second assessment into routine diabetes care, together with strengthened patient education and metabolic management, may help reduce the risk of DFU in resource-limited settings.

Hospital patients are at an increased risk of falls, which are a significant safety concern within healthcare settings.¹ Understanding how the COVID-19 pandemic has influenced fall risks is essential for identifying key factors that could inform future fall prevention strategies.² This scoping review aims to explore the barriers and challenges associated with preventing inpatient falls in the context of the post-COVID-19 environment.

The methodology for this scoping review follows the framework established by Arksey and O’Malley. A comprehensive literature search will be conducted using specific keywords to identify relevant published studies. Searches will be performed across selected electronic databases, including PubMed/MEDLINE, CINAHL, Scopus, ProQuest and Web of Science, covering publications from 2014 to 2024. This review will focus on a global perspective. Two authors will independently screen titles and abstracts to identify potential studies for inclusion. Studies meeting the inclusion criteria will be retrieved for full-text review, and their references will be assessed for relevance using the same criteria. The PRISMA flow diagram will guide the review process. Data will be extracted, analysed and charted according to categories from the selected publications.

This scoping review will provide a comprehensive overview of the barriers and challenges in preventing inpatient falls in the post-pandemic context. The findings will be disseminated through submission for publication in a scientific journal.

This scoping review protocol is registered with Open Science Framework (OSF) available at https://osf.io/.

Falls are highly prevalent among individuals with dementia, largely due to the cognitive and physical impairments associated with the condition. Understanding the barriers and challenges to fall prevention in community-dwelling individuals with dementia is essential for developing tailored strategies that address their unique risks. Despite the existing evidence on fall prevention in older adults, few reviews specifically examine the obstacles faced by persons with dementia and their caregivers in community settings. This scoping review, therefore, aims to map the barriers and challenges to preventing falls among community-dwelling individuals with dementia.

This review will follow Arksey and O’Malley’s five-stage framework and be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses—Extension for Scoping Reviews checklist. Six electronic databases (PsycINFO, PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Scopus and Embase) will be searched for relevant studies published between 2014 and 2024. Grey literature sources, including dissertations and conference proceedings, will also be included. Data will be charted and synthesised thematically to provide an overview of barriers and contextual factors influencing fall prevention. The study commenced in August 2025 and is expected to be completed by February 2026.

As this review involves the analysis of existing literature, ethical approval is not required. Findings will be disseminated through peer-reviewed publications, conference presentations and summaries tailored for healthcare providers and caregiver groups.

The protocol is registered with the Open Science Framework: https://osf.io/gnw47/(dataset).

To assess the validity of the International Classification of Diseases, 10th Revision (ICD-10) healthcare database diagnosis codes for lithium toxicity at hospital admission in Ontario, Canada.

Population-based retrospective validation study.

A total of 152 hospitals linked to a provincial laboratory database in Ontario, Canada, from 2007 to 2023.

Patients 50 years of age or older taking lithium with hospital-based serum lithium laboratory measurements during admission to the hospital (n=2804).

Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) comparing an ICD-10 diagnostic coding algorithm for lithium toxicity to a serum lithium concentration of 1.5 mmol/L or more. The codes used in the algorithm were T568, T435, Y495, X41 and X49. Serum lithium values and changes in the concentration of serum lithium from baseline levels in patients with and without a diagnosis code for lithium toxicity (code-positive and code-negative, respectively).

The sensitivity of the ICD-10 coding algorithm for identifying a serum lithium level≥1.5 mmol/L was 84% (95% CI 81% to 87%). The specificity and the NPV were over 88%, and the PPV was 63% (95% CI 60% to 66%). The median (IQR) serum lithium measurement in code-positive patients was 1.7 (1.2 to 2.2) mmol/L, and it was 0.6 (0.4 to 0.9) mmol/L in code-negative patients. The median (IQR) increase in serum lithium concentration compared with the most recent prehospital baseline values was 0.7 (0.2 to 1.3) mmol/L in code-positive patients and 0.0 (–0.2 to 0.2) mmol/L in code-negative patients.

In Ontario, the sensitivity of the ICD-10 coding algorithms was moderate for identifying a serum lithium level≥1.5 mmol/L at hospital admission. The presence or absence of the ICD-10 codes for lithium toxicity at hospital admission successfully differentiated two groups of patients with distinct serum lithium measurements.

Inherited retinal diseases (IRDs) are a broad range of diseases associated with abnormalities/degeneration of retinal cells. We aimed to identify the top 10 Australian research priorities for IRDs to ultimately facilitate more meaningful and potentially cost-effective research.

We conducted a James Lind Alliance priority setting partnership that involved two Australian-wide surveys and online workshops.

Australia-wide.

Individuals aged 16 years or older were eligible to participate if they had an IRD, were caregivers of an individual with an IRD or were health professionals providing care to this community.

In Survey 1, we gathered participants’ unanswered questions about IRDs. We grouped these into summary questions and undertook a literature review to verify if they were truly unanswered (ie, evidence uncertainties). In Survey 2, participants voted for the uncertainties that they considered a priority. Top-ranked uncertainties progressed for discussion and final prioritisation in two workshops.

In Survey 1, we collected 223 questions from 69 participants. We grouped these into 42 summary questions and confirmed 41 as evidence uncertainties. In Survey 2, 151 participants voted, with the 16 uncertainties progressing to final prioritisation. The top 10 priorities, set by the 24 workshop participants, represented (1) treatment/cure; (2) symptoms and disease progression; (3) psychosocial well-being and (4) health service delivery. The #1 priority was for treatment to prevent, slow down or stop vision loss, followed by the #2 priority to address the psychological impact of having an IRD.

The top 10 research priorities highlight the need for IRD research that takes a whole-person, systems approach. Collaborations to progress priorities will accelerate the translation of research into real-world benefits.

Infertility is a significant reproductive health issue that affects couples physically, emotionally and socially. This qualitative study aims to explore the psycho-social experiences and coping strategies of infertile couples attending infertility clinics at Saint Paul’s Hospital, Addis Ababa, Ethiopia.

This study employed a descriptive phenomenological research design. In-depth interviews were conducted with 12 purposively selected couples experiencing infertility. The study used thematic analysis to capture the emotional, social and psychological impacts of infertility on individuals and their relationships.

Key themes identified include emotional distress, social stigma, marital strain and a sense of isolation. Participants reported experiencing feelings of shame, depression and anxiety, often exacerbated by societal expectations and pressure to conceive. Coping strategies varied across individuals and included seeking medical intervention, social support, religious faith and, in some cases, withdrawal from social interactions.

The study highlights the need for comprehensive psychological support and counselling services in infertility care to address the mental health and social challenges faced by infertile couples. Promoting awareness to reduce stigma and enhancing social support systems may improve the overall well-being of affected individuals.

Canadian guidelines recommend HIV testing for individuals being evaluated for syphilis. Our objective was to examine three aspects of HIV testing (ie, if an HIV test occurred, the timing of the HIV test in relation to the syphilis test and the proportion with a positive HIV test result) among syphilis tests between 2017 and 2022 from individuals with no evidence of a previous HIV diagnosis.

This study is a retrospective analysis of comprehensive laboratory testing data from Ontario’s provincial public health laboratory.

Direct fluorescent antibody (DFA) and serological non-prenatal syphilis tests were conducted from 1 January 2017 to 31 December 2022, from individuals aged ≥15 years with no evidence of a previous HIV diagnosis (n=3 001 058 total tests). Positive syphilis tests were categorised using the rapid plasma reagin (RPR) titre as ‘current’ (DFA+/RPR≥1:8) or ‘historical’ (RPR

The number and proportion of syphilis tests with a corresponding HIV test on the same day or within 7, 28, 90 or 180 days, and, among those with an HIV test within 28 days, the number and proportion with an HIV-positive test result.

From 2017 to 2022, 1 516 726 and 1 484 332 syphilis tests among males and females, respectively, were included in the analysis. Individuals with a positive syphilis result were less likely to be tested for HIV within 28 days of their syphilis test compared with those with a negative syphilis test result (74.7% vs 91.1% in males, 97.5% CI (–0.17 to –0.16); 65.2% vs 92.4% in females, 97.5% CI (–0.28 to –0.26)). Males with ‘current’ positive syphilis test results were less likely than males with ‘historical’ positive syphilis results to be tested for HIV within 28 days (69.1% vs 76.6%, 97.5% CI (–0.084 to –0.066)); this was not true in females (67.1% vs 64.4%, 97.5% CI (0.0062 to 0.049)). Males overall and males with ‘current’ syphilis were more likely to be diagnosed as HIV-positive (p

Most individuals who tested for syphilis at Public Health Ontario were also tested for HIV; however, those who tested positive for syphilis were less likely to be tested, representing an opportunity for enhanced HIV testing. Ensuring that individuals with syphilis are tested for HIV may help identify previously undiagnosed individuals living with HIV.

This study validates the previously tested Screening for Poverty And Related social determinants to improve Knowledge of and access to resources (‘SPARK Tool’) against comparison questions from well-established national surveys (Post Survey Questionnaire (PSQ)) to inform the development of a standardised tool to collect patients’ demographic and social needs data in healthcare.

Cross-sectional study.

Pan-Canadian study of participants from four Canadian provinces (SK, MB, ON and NL).

192 participants were interviewed concurrently, completing both the SPARK tool and PSQ survey.

Survey topics included demographics: language, immigration, race, disability, sex, gender identity, sexual orientation; and social needs: education, income, medication access, transportation, housing, social support and employment status. Concurrent validity was performed to assess agreement and correlation between SPARK and comparison questions at an individual level as well as within domain clusters. We report on Cohen’s kappa measure of inter-rater reliability, Pearson correlation coefficient and Cramer’s V to assess overall capture of needs in the SPARK and PSQ as well as within each domain. Agreement between the surveys was described using correct (true positive and true negative) and incorrect (false positive and false negative) classification.

There was a moderate correlation between SPARK and PSQ (0.44, p60), SPARK correctly classified 90.5% (n=176/191).

SPARK provides a brief 15 min screening tool for primary care clinics to capture social and access needs. SPARK was able to correctly classify most participants within each domain. Related ongoing research is needed to further validate SPARK in a large representative sample and explore primary care implementation strategies to support integration.

Frontotemporal lobar degeneration (FTLD) is the second most common early-onset dementia. Several studies demonstrated that neuroinflammation and iron accumulation occur in FTLD. However, the timing and relevance of these processes and whether these two are merely cause or consequence remains unclear. Elucidating the role is crucial to assess the rationale for using anti-inflammatory therapies in FTLD. Additionally, the process of glymphatic brain clearance has gained attention as a potential contributor in the disease pathophysiology.

In this multimodal biomarker study, we use a combination of ultra-high field (7T) MR, blood and cerebrospinal fluid (CSF) biomarkers to investigate the role of neuroinflammation, iron accumulation and brain clearance in FTLD, and to identify biomarkers to differentiate FTLD-TDP from FTLD-tau. We aim to include 25 patients with probable FTLD-tau, 25 with probable FTLD-TDP and 50 healthy individuals with 50% risk to develop FTLD. We will use several MRI techniques, including magnetic resonance spectroscopy, diffusion weighted spectroscopy and quantitative susceptibility mapping. In addition, we will assess the prevalence of perivascular spaces (PVS) and the mobility of CSF to address glymphatic brain clearance. We will compare quantitative MR markers between patients with FTLD-tau and FTLD-TDP, presymptomatic mutation carriers and healthy controls, and correlate these measures with clinical data and biomarkers in blood and CSF.

We obtained ethical approval from the Medical Ethics Committee Leiden Den Haag Delft (NL78272.058.21). The results will be disseminated through presentations at national and international conferences, open-access peer-reviewed publications, ClinicalTrials.gov and to the public through social media posts and annual newsletters.

NCT06870838; Pre-results.

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.

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.

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).

NCT05614349

Predictive scoring systems support clinicians in decision-making by estimating the prognosis of patients in intensive care units (ICUs). However, there is limited evidence on the accuracy of these systems in predicting mortality and organ dysfunction in special populations. The aim of this review is to assess the performance of predictive scoring systems in forecasting mortality in adult ICU patients in relation to baseline kidney function. It is anticipated that the assessment of predictive scoring systems’ performance and patient outcomes in this review may reveal information that will contribute to improve the quality of care and outcomes for special or under-represented ICU patient populations. It might also inform future research and contribute to the development of novel risk prediction models to address identified gaps or unanswered questions.

This review will include only observational studies, as these allow us to assess the real-world performance of predictive scoring systems in ICU settings by examining the original validation studies. By excluding randomised trials, paediatric studies, case reports and machine learning-derived models, this review focuses on the direct practical use of the scoring systems in adult ICU patients. A comprehensive search of MEDLINE, Embase and Scopus was conducted from database inception to 10 October 2024. The data will be extracted on study characteristics, patient outcomes and performance metrics.

This review will analyse data from previously published studies; no ethical approval is required. All data that will be included in the analysis will be publicly available and will be included in the final manuscript. Results will be disseminated through publication in a peer-reviewed journal and will also be presented at seminars and conferences.

CRD42024611547.

COVID-19 in children is generally of short duration, but some may take longer to recover. This study investigated the time to symptom resolution following SARS-CoV-2 infection among children in a community setting on the outskirts of an urban centre in Brazil.

Prospective cohort study.

This is a community-based cohort of children living in Manguinhos, a favela in Rio de Janeiro. The cohort was followed through home visits and telephone monitoring of symptoms. The analysis focused on symptomatic children from this cohort with confirmed SARS-CoV-2 infection. Recovery time was defined as the interval between the first date with symptoms and the first date without symptoms following a positive SARS-CoV-2 test.

A total of 1276 children (boys and girls aged 2–

COVID-19 recovery time, assessed based on change points on the symptom persistence probability curve (Kaplan-Meier).

Among children who tested positive, 148 (60%) were symptomatic. The median recovery time was 11 days (IQR: 7–16). Two inflection points were identified on the Kaplan-Meier curve: days 16 and 34. Children who were ill during the Omicron wave took longer to recover. More boys became asymptomatic within the first 15 days; about 93% of girls recovered by day 33, and boys were more common among those who recovered in ≥34 days. Children aged 6–

Among children from a vulnerable area in Rio de Janeiro, recovery time was longer than that reported in other countries, with 9.5% of children experiencing persistent symptoms for more than 33 days. These findings are crucial for understanding the implications of COVID-19 in specific socioeconomic contexts and the dynamics of paediatric recovery in community settings.