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.

Inguinal hernia repair is one of the most frequently performed operations in the paediatric population and can be performed according to two approaches: open or laparoscopic. At present, decisive evidence about the best treatment strategy is lacking and consequently, there is an ongoing debate about the most (cost-)effective treatment for the paediatric inguinal hernia. The aim of the Hernia Endoscopic oR opeN repair In chIldren Analysis—trial (HERNIIA2-trial) is to estimate the (cost-)effectiveness of the laparoscopic percutaneous internal ring suturing (PIRS) technique compared with open repair in children aged 0–16 years with a primary unilateral inguinal hernia.

A national multicentre randomised controlled trial will be performed including 464 children aged 0–16 years with a primary unilateral inguinal hernia. Patients will be randomised between the open or PIRS technique. The primary outcome is the number of reoperations within 2 years after primary surgery. Secondary outcome measures are: operative and postoperative complications, total duration of surgery, postoperative pain, length of admission, time to normal daily activities, cosmetic appearance of the scar, social and healthcare costs and health-related quality of life. Furthermore, cost-effectiveness will be assessed from a societal and healthcare perspective.

The protocol was approved by the ethics committee of the Amsterdam University Medical Hospital. Informed consent will be obtained by parents and, if possible, according to age, by patient. The study will be conducted according to the principles of the Declaration of Helsinki (2013) and in accordance with the Medical Research Involving Human Subjects Act (WMO) and Good Clinical Practice. Study findings will be disseminated through scientific publications, conferences and patient-friendly materials. The national study network of participating centres will facilitate rapid dissemination and implementation within the Netherlands and potentially abroad.

ClinicalTrials.gov PRS (ID NCT06451432).

On 1 January 2023, Ontario expanded pharmacists’ scope of practice, allowing them to prescribe medications for 13 minor ailments, including antibiotics for uncomplicated urinary tract infections (UTIs) and Lyme disease (LD) prophylaxis. This study evaluates pharmacist billing claims and pharmacist and physician antibiotic-prescribing rates before and after policy implementation.

An interrupted time series analysis measuring changes in prescribing trends post-implementation.

This retrospective study analysed visit claims and antibiotic prescribing for UTIs and LD prophylaxis before policy implementation (2022) and after (2023–2024) in Ontario.

Data from Ontarians

Prescribing rates were standardised per 1000 inhabitants, stratified by provider type, patient age and sex, and antibiotic type.

In 2023 and 2024, pharmacists submitted over 1.47 million minor ailment claims, with UTIs making up 34.2% and LD prophylaxis making up 2.6% of total claims. UTI claims were primarily for women aged 25–64, and LD prophylaxis peaked in spring and fall. Pharmacist prescribing of eligible urinary drugs in females increased by 33.3 per 1000 person-years (95% CI 30.8 to 36.6) while physician prescribing decreased by 23.3 (95% CI –32.2 to –15.3), leading to a modest net increase of 10.1 (95% CI 0.0 to 18.7). Pharmacist prescribing of doxycycline was offset by decreased physician prescribing, resulting in no change (0.0, 95% CI –1.0 to 0.9). Pharmacist prescribing for other antibiotics was low over the study timeframe, while physician prescribing increased, which was driven by increased prescribing of penicillins and macrolides.

There was a clear increase in pharmacist prescribing for eligible drugs in the eligible population post-policy implementation. Pharmacists in Ontario appear to be prescribing within policy limits for uncomplicated UTIs and LD prophylaxis.

Dysregulated immunity may account for an increased risk of infection and other adverse outcomes among frail hospitalised persons. The primary objective of this study is to examine whether baseline frailty is associated with the risk of developing ventilator-associated pneumonia (VAP) or other intensive care unit (ICU)-acquired infections among invasively ventilated adults. Additional objectives are to examine the relationship between frailty and hospital length of stay, discharge to a long-term care facility and vital status. We hypothesise that persons with frailty compared with others would have an increased risk of VAP and other infections, a longer hospital stay, higher probability of discharge to a long-term care facility and higher mortality.

This is a preplanned secondary analysis of the PROSPECT trial (Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial) which enrolled patients across 44 ICUs in three countries. We will use Cox proportional hazards regression analysis to assess the association of frailty with the clinical outcomes of interest, adjusting for other baseline variables. Baseline demographic and descriptive outcome data will be reported using descriptive statistics. Regression results will be presented as adjusted HRs or ORs with 95% CIs for the associations of each independent variable with the primary, secondary and tertiary outcomes.

Participating hospital research ethics board approved the PROSPECT trial and data collection. The protocol for this study was approved by the Hamilton Integrated Research Ethics Board on 20 August 2015 (Project ID:19128). This study will identify whether frailty is associated with risk of VAP and other healthcare-associated infections in invasively ventilated patients, adjusted for other baseline factors. Results may be useful to patients, their caregivers, clinicians and the design of future research. Findings will be disseminated to investigators at a meeting of the Canadian Critical Care Trials Group. We will present study results at an international conference in the fields of critical care and infectious diseases, to coincide with or precede open-access peer-review publication. To aid knowledge dissemination, we will use a variety of formats. For example, for traditional and social media, we will create two different visual abstracts and infographics of our results suitable to share on clinician-facing and public-facing platforms.

NCT02462590.

Mistreatment and obstetric violence constitute significant human rights violations with profound implications for maternal mental health. These detrimental practices persist globally, particularly in contexts where underfunded health systems, workforce shortages and entrenched gender inequalities intersect, depriving women of adequate psychosocial support and culturally sensitive mental healthcare. Although awareness of the immediate harms of mistreatment is increasing, its cumulative effects throughout the maternal care continuum remain insufficiently understood. This review will synthesise evidence on the impact of mistreatment on perinatal mental health, identify critical gaps and advocate for systemic change.

This systematic review and meta-analysis protocol complies with the guidelines set forth by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. A thorough literature search will be executed across multiple electronic databases, including CINAHL—Cumulative Index to Nursing and Allied Health Literature, Embase via Ovid, MEDLINE, PsycInfo, PubMed, Scopus, as well as other significant or specialised databases and grey literature. The review will incorporate only non-randomised study types and observational studies (cohort, cross-sectional, case-control), along with mixed-method and qualitative studies. Abstract and full-text screening will be performed by two reviewers using Covidence. The methodological quality of the included studies will be assessed using the Newcastle-Ottawa Scale for observational studies, the Risk of Bias in Non-Randomised Studies of Interventions, the Critical Appraisal Skills Programme and the Mixed Methods Appraisal Tool. Statistical heterogeneity will be evaluated using the Higgins test. Meta-analysis will be conducted using R statistical software V.4.4.4, employing random effects models to determine the weights. The study results will be reported sequentially, beginning with primary outcomes, followed by secondary outcomes and significant subgroup outcome analyses.

Ethical approval is not required as no original data will be collected. The findings of this review will be disseminated through publication and conference presentations.

CRD420251044379.

In moderate to high-risk surgical procedures, 15–25% of patients develop a postoperative surgical site infection. Intraoperative incisional wound irrigation has the potential to reduce surgical site infections, and additional randomised controlled trials are required to provide evidence of effectiveness.

This protocol describes a pragmatic, adaptive, participant and adjudicator-blinded trial at 13 sites in Canada in up to 2500 participants. Participants planned for surgery with an abdominal or groin incision, who are eligible and provide verbal consent through an integrated consent model, are randomised to receive intraoperative incisional wound irrigation with povidone-iodine, saline or no irrigation. The primary outcome is surgical site infection within 30 days postoperatively. Secondary outcomes include quality of life measured 30 days postoperatively and morbidity, mortality and healthcare utilisation within 90 days postoperatively.

This trial has been approved by the research ethics board at the participating centres and stopped enrolling participants on May 23, 2025. All participants will provide verbal consent. Results will be disseminated via presentation at conferences, publication and posted on clinicaltrials.gov.

The study is registered with http://clinicaltrial.gov (NCT04548661; 14 September 2020).