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.

China has continued to improve tuberculosis (TB) control in the past decade; however, the sudden outbreak of COVID-19 hindered this progress. As a province with a large population and frequent international exchanges, Guangdong has been seriously affected by COVID-19. This study aimed to understand the effect of COVID-19 on TB detection in Guangdong based on the autoregressive integrated moving average (ARIMA) model.

Time-series study.

Guangdong, China.

We used the ARIMA model to quantify the effect of COVID-19 by comparing reported cases during the COVID-19 pandemic with predicted cases under a counterfactual scenario of no COVID-19 pandemic. After model evaluation, we chose ARIMA (0,1,2)(0,1,1)₁₂ as the prediction model. We also highlighted that there were three emergency response periods in which the responses and public responses to COVID-19 varied.

During the pandemic period, the average annual TB notification rate was 57.95/100 000, which decreased by 27.97% compared with the pre-pandemic period. Although it decreased by 6.17% on average annually in the pre-pandemic period, it decreased by 14.92% in 2020 as compared with 2019, but only decreased by 0.34% in 2021 as compared with 2020. The results of the ARIMA model showed that the number of reported cases in 2020 decreased by 6.62% compared with that of the predicted cases, but this decreased by 0.42% only in 2021. The most seriously affected period was the second-level emergency response period in 2020, when the relative difference between reported and predicted cases reached the peak (–16.43%). The least affected period was the third-level emergency response period of 2021, the reported cases recovered and exceeded the predicted cases, with a gap of 0.77%.

TB detection in Guangdong had generally declined during the COVID-19 pandemic, which might be related to the movement restrictions, diverted resources and patients’ concerns. This decline would lead to the delay or even interruption of diagnosis and treatment, which would cause the regression of TB control. To improve TB detection, it is important for stakeholders to take consorted effort during public health emergencies.

Research for pandemic response needs to be timely to inform evidence-based decision making. The lack of epidemiological data at the start of the COVID-19 pandemic led experts to call for cohorts that could rapidly supply data about newly emerging infectious diseases. The ‘Bern, get ready’ (BEready) study aims to establish a prospective ‘pandemic preparedness cohort’ in the canton of Bern, Switzerland. This cohort can be pivoted to the needs of a new pandemic pathogen. The aim of this pilot study was to investigate the potential response and to test the feasibility of procedures for BEready.

Closed population-based cohort study.

Random sample of private households in the canton of Bern, Switzerland, that had previously responded to an online survey.

Adults, children and pets.

Enrolment as a percentage, associations between the agreement to participate and the demographic and socioeconomic variables of the invited household member, number of social contacts, proportion of samples collected, proportion of complete questionnaires and proportion of participants responding after 12 months.

After the initial in-person visit with venous blood sampling, participants were followed up for 1 year. We tested remote data collection methods, with online questionnaires and self-collected capillary blood and nasopharyngeal samples, and established a biobank.

The pilot study enrolled 106/1138 (9%) of invited households plus two additional households that had proactively contacted us. In total, we enrolled 193 people in 108 households (1.8 per household) and 44 pets between April and September 2023. We obtained and stored at least one venous and/or capillary baseline blood sample from 184/193 (95%) people and 40/44 (91%) pets. After 1 year, 172/193 (89%) people in 101/108 (94%) of households completed a follow-up survey, as did 22 owners of 34/44 (77%) pets. 151/172 (88%) respondents returned a follow-up capillary blood sample.

The response rate to the pilot study shows that obtaining high levels of participant enrolment in a pandemic preparedness cohort study is challenging. Data collection without face-to-face contact with a study team is feasible for household members and will be needed in BEready if control measures during a pandemic prevent in-person studies.

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.

Since 2018, WHO has endorsed the use of whole-genome sequencing (WGS) of Mycobacterium tuberculosis complex isolates to detect drug-resistant tuberculosis (DR-TB). This endorsement was based on the assumption that a faster and more detailed description of the resistance profile would improve treatment prescription for DR-TB by healthcare providers, and hence the treatment outcomes of patients. Nonetheless, this assumption has not been tested in routine clinical practice and different scenarios. In Brazil, WGS is not routinely used for the diagnosis of DR-TB, having been carried out in only a few centres for research purposes. With this trial, we will evaluate whether a WGS-based drug-resistance report improves treatment adequacy in patients with pulmonary DR-TB, compared with the current standard-of-care diagnostic methods used in the state of São Paulo, Brazil.

We will conduct a non-randomised controlled clinical trial with two arms to compare the intervention group (ie, individuals receiving a WGS-based report) with a historical control group (i.e., individuals who received resistance diagnostics based on the standard of care of conventional genotyping and phenotyping techniques). The primary outcome will be the proportion of patients whose treatment scheme was adequate based on complete resistance profile determined by WGS and/or phenotypic drug-susceptibility testing (pDST). Other secondary outcomes will also be considered. The target sample size is 88 eligible patients per group. The intervention group will be prospectively recruited over 18 months and the control group will be composed of patients diagnosed with pulmonary DR-TB up to 2 years before the start of the trial. To ensure comparability, isolates from the control group will undergo WGS retrospectively, and pDST will be performed retrospectively in both groups. This clinical trial will take place in six medical centres for the treatment of DR-TB in the state of São Paulo. This study is intended to support the implementation of the WGS in the routine diagnosis of DR-TB in the state of São Paulo.

Ethical approval was obtained from the Human Research Committee of the Institute of Biomedical Sciences, University of São Paulo, Brazil (CAAE: 79497924.1.1001.5467). Study results will be published in peer-reviewed journals and disseminated to policymakers and stakeholders.

U1111-1308-4669.

Predicting the progression to severe dengue remains a critical yet challenging aspect of patient management. This umbrella review aims to identify biomarkers associated with the development of severe dengue. The primary objective is to determine which biomarkers can predict progression to severe disease in dengue-infected patients. Secondary objectives include identifying (a) early biomarkers (detected on days 1–3 of illness), (b) late biomarkers (detected after day 3), (c) biomarkers requiring further investigation and (d) differences in predictive biomarkers between patients aged

The review questions were formulated based on the Population, Concept and Context (PCC) framework. This review will follow the Joanna Briggs Institute methodology for umbrella reviews and be reported in accordance with the Preferred Reporting Items for Overviews of Systematic Reviews guidelines. The protocol has been registered in PROSPERO (CRD420251058284). MEDLINE, Embase, CINAHL, Cochrane Database of Systematic Reviews, JBI Evidence Synthesis and DARE databases will be searched from 1/1/1990 to 1/6/2025. The findings are expected to support early risk stratification and guide future biomarker research in dengue infection. The systematic reviews included in this umbrella review may define severe dengue according to either the WHO 1997 or 2009 guidelines.

Ethical approval is not required since the work involves published documents. The review findings will be communicated to relevant stakeholders through conference presentations and publication in an open-access journal.

PROSPERO 2025 CRD420251058284. Available from: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251058284.

To examine how cultural health brokers, as trusted intermediaries between formal systems and diverse ethnocultural communities, help navigate decisional conflict and misinformation regarding COVID-19 vaccination and to identify how their work contributes to system resilience in crisis contexts.

A community-based participatory action sensemaking research project to capture the real-time work of cultural health brokers in helping people navigate decisional conflict for vaccination.

Multicultural Health Broker Cooperative in Edmonton, Alberta where brokers speak 54 languages and serve more than 10 000 people from diverse ethnolinguistic communities. 28 cultural health brokers (9 male; experience 4–25 years) contributed to data collection and analysis between 16 September 2021 and 16 December 2021.

The brokers captured real-time reflections and self-interpretations in the SenseMaker platform through a theoretically informed, codesigned, mixed-method data collection tool. The team engaged in 13 weekly, 90 minute, audio-recorded and transcribed sessions: seven focused on understanding and action planning and five reflecting on the SenseMaker data, the focus of the thematic analysis. Data were managed in NVivo (QSR International, Version 12, 2018).

Brokers collected 277 narratives and conducted 13 sensemaking sessions. Understanding and purpose were identified in 68% of narratives as key to achieving coherence; 81% of narratives highlighted trust as crucial to what was needed for action; 62% of narratives reflected on a potential risk, with loss of trust a concern in 70% of them. A rich understanding of the sources of decisional conflict and misinformation was achieved and managed through outreach. There were four entwined components to navigation of the evolving complexity of COVID-19 vaccination: (1) building and sustaining trust; (2) strengthening relationships; (3) creating safe spaces for collective sensemaking and solution finding; and (4) leveraging cultural and social capital to address barriers. Through these mechanisms, brokers reduced decisional conflict and misinformation, supporting informed, values-congruent decisions.

Cultural health brokers, embedded within communities and linked to formal systems, play a critical role in crisis response by fostering trust, mobilising resources and enabling collective sensemaking. This study demonstrates how these intermediaries’ contextually and culturally attuned work provides a model for building system resilience for future crisis response.

Military personnel are a unique population with heightened vulnerability to sexually transmitted infections (STIs), often exhibiting higher prevalence rates than civilians due to demographic, environmental and occupational factors. These vulnerabilities underscore the need for global prevalence estimates to guide effective, evidence-based interventions. This study aims to quantify the global burden of STIs among military personnel, providing a comprehensive and up-to-date assessment.

This systematic review will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Guidelines (2020). Using the CoCoPop (Condition, Context, and Population) framework, a comprehensive search strategy will be conducted in MEDLINE, Embase, Global Health and Scopus to retrieve peer-reviewed records published between January 2010 and June 2025. Eligible studies will report numerical STI prevalence data among military personnel. Studies with insufficient information to calculate prevalence or those relying on self-reported STI data will be excluded. Data extraction will include study details, military descriptors, STI prevalence and diagnostic methods. Risk of bias will be assessed using the Joanna Briggs Institute critical assessment tool for prevalence and incidence studies. Prevalence estimates with 95% CIs will be reported for each STI and, where appropriate, pooled for curable STIs. Subgroup analyses will stratify prevalence by geographic region, service status, deployment status and socioeconomic factors. Heterogeneity will be evaluated within predefined subgroups using the I² statistic. Data will be presented in comprehensive tables and visualised with graphical tools, including forest plots for subgroup analyses and pooled estimates.

Ethical approval is not required for this review. The results will be disseminated through a peer-reviewed publication and conference presentations.

CRD42023472113.

Streptococcus pneumoniae serotype 3 (SPN3) remains a significant contributor to invasive pneumococcal disease globally, despite its inclusion in widely administered vaccines. The next generation of pneumococcal vaccines may confer better protection against this serotype, reducing disease burden. We describe an ethically approved protocol for a double-blind randomised controlled trial assessing the impact of VAXNEUVANCE (15-valent pneumococcal conjugated vaccine (PCV15)) and 0.9% saline (placebo) on the acquisition, density and duration of SPN3 carriage using a controlled human infection model.

Healthy adults aged 18–50 years will be randomised 1:1 to receive PCV15 or placebo. Participants will be considered enrolled on the trial at vaccination. One month following vaccination, all participants will be intranasally inoculated with SPN3. Following inoculation, participants will be followed up on days 2, 7, 14 and 28 to monitor safety, SPN3 colonisation status, density and duration, as well as immune responses. The primary endpoint of the study is to assess the rate of SPN3 acquisition between vaccinated and unvaccinated participants defined by classical microbiological methods. Secondary endpoints will determine the density and duration of SPN3 colonisation and compare the immune responses between study groups. An exploratory cohort of 5 participants will be asked to consent to a nasal biopsy procedure during a screening visit and a second nasal biopsy 28 days after PCV15 vaccination. This cohort will only receive PCV15 and will not be challenged. Through this exploratory cohort, we will explore gene expression changes induced by PCV15 vaccination and their visualisation (spatial location) within the nasal tissue.

This protocol has been reviewed by the sponsor, funder and external peer reviewers. The study is approved by the NHS Research and Ethics Committee (Reference: 24/SC/0388) and by the Medicines and Healthcare Products Regulatory Agency (Reference: CTA 21584/0485/001-0001).

NCT06731374 – ISRCTN91656864.

The UK Health Security Agency and the National Health Service England (NHSE) led a hepatitis C virus (HCV) patient re-engagement exercise beginning in 2018, which entailed sharing public health surveillance data with NHSE Operational Delivery Networks (ODNs) in England. The ODNs used the data to contact and offer testing and treatment to people historically diagnosed with HCV, but who did not have evidence of successfully clearing the virus. A quantitative evaluation found that of 55 329 individuals whose details were shared with ODNs, around 13% had treatment after the exercise commenced. This qualitative evaluation aims to identify the barriers and facilitators to the re-engagement exercise as reported by ODN staff.

Semistructured interviews. The topic guide and analysis were guided by the Theoretical Domains Framework, using a combined deductive framework and inductive thematic analysis approach.

21 staff from 13 ODNs. The sampling frame was designed to capture participants from all regions of England and with varied outcomes from the re-engagement exercise.

Interviewees reported the most barriers in environmental context and resources (including staffing limitations, interruptions during COVID-19, restricted laboratory access), and social influences (with limited responses from general practitioners and patients). Interviewees discussed whether it was appropriate for ODNs and individual staff to be assigned the data validation work and reported some stress and memory/attention barriers due to the volume of the exercise. They had varied beliefs about the consequences of the exercise, with most believing it was worthwhile due to treatment yield, lessons learnt and confirmation that some people had cleared the virus. Further facilitators included the ODN goals fitting with the exercise, and regional resources such as patient databases. Interviewees also reported adaptations to the exercise that facilitated patient contact, and their ongoing work to re-engage patients emphasised outreach partnerships and peer support.

The evaluation revealed insights into methods for re-engaging patients and of sharing and using public health data to support clinical practice. Government support and funding provision for regionally tailored holistic re-engagement approaches, alongside enhancements to health surveillance data, could enable barriers to re-engagement to be overcome.

To assess the pooled prevalence of self-reported sexually transmitted infections (STIs) and their associated factors among adults in South and Southeast Asia, using the Demographic and Health Survey data collected between 2015 and 2023.

A community-based cross-sectional study design was conducted using a multistage cluster sampling approach. Multilevel multivariable logistic regression analysis was employed to identify predictors of self-reported sexually transmitted infections (STIs). Model selection was guided by Akaike’s information criterion, and adjusted odds ratios (AORs) with 95% CIs were estimated to determine statistically significant associations.

South and Southeast Asia.

This analysis included a weighted sample of 791 019 adults aged 15–49 who reported ever having had sexual intercourse. The majority of the participants were female (n=6 87 880; 87%), and most were from Southeast Asia (n=7 00 539; 89%).

The pooled prevalence of self-reported STIs among adults in South and Southeast Asia was 12.94% (95% CI 7.73% to 18.14%). At the individual level, higher odds of reporting STIs were associated with being female (AOR 1.84; 95% CI1.68 to 2.02), having middle (AOR 1.11; 95% CI 1.04 to 1.19) or high wealth status (AOR 1.15; 95% CI 1.07 to 1.24]), being employed (AOR 1.14; 95% CI 1.07 to 1.22), having multiple sexual partners (AOR 2.79; 95% CI 2.22 to 3.52) and having undergone HIV testing (AOR 1.10; 95% CI: 1.02 to 1.20). Conversely, lower odds of self-reported STIs were observed among individuals aged 35–39 years (AOR 0.78; 95% CI 0.66 to 0.92), 40–44 years (AOR 0.68; 95% CI 0.58 to 0.82) and 45–49 years (AOR 0.61; 95% CI 0.52 to 0.73); those who had ever been in a union (AOR 0.71; 95% CI 0.62 to 0.83); individuals with higher education (AOR 0.84; 95% CI 0.76 to 0.93); and those with comprehensive HIV knowledge (AOR 0.82; 95% CI 0.77 to 0.87). At the community level, high illiteracy rates (AOR 1.25; 95% CI 1.15 to 1.35) and high media non-exposure (AOR 1.11; 95% CI 1.02 to 1.20) were positively associated with STIs, while rural residence (AOR 0.81; 95% CI 0.74 to 0.89) and living in Southeast Asia (AOR: 0.47; 95% CI 0.42 to 0.53) were linked to lower odds of self-reported STIs.

A substantial prevalence of self-reported STIs was observed among adults in South and Southeast Asia. Both individual- and community-level factors influence STI risk. The individual-level determinants include socio-demographic characteristics, sexual behaviours, HIV-related knowledge and testing history, while community-level factors reflect disparities in geographic location, educational attainment and media exposure.

To determine the prevalence and factors associated with the uptake of HIV self-testing (HIVST) among adolescent girls and young women (AGYW) attending middle learning institutions in Dodoma City, Tanzania, in 2024.

Design: A cross-sectional study design was employed.

The study was conducted in five randomly selected colleges in Dodoma City, Tanzania.

A total of 771 female students aged 15–24 years who provided informed consent were enrolled. Students who declined participation or were reported by the college matron as medically unfit were excluded. In this study, ‘sick’ referred to participants with a clinically diagnosed illness rendering them unable to participate.

The primary outcome was the uptake of HIVST among participants.

The mean age of participants was 20.78 years (SD=1.85). Overall, 360 participants (46.7% (95% CI 43.2% to 50.2%) reported having used HIVST. Among those who had not tested, the most commonly reported barriers included cultural resistance 392 (95.4%), fear of judgement from healthcare providers, 372 (90.5%); legal restrictions on kit provision, 360 (87.6%); fear of testing procedures, 291 (70.8%); concerns about test reliability, 286 (69.6%); fear of test results, 283 (68.9%); limited accessibility to HIVST kits, 280 (68.1%); fear of others discovering they had tested, 273 (66.4%); low awareness of HIVST, 193 (47.0%); and a perceived low risk of HIV infection, 73 (17.8%).

Factors significantly associated with HIVST uptake included having multiple sexual partners adjusted prevalence ratio (aPR 1.23, 95% CI 1.05 to 1.45), studying health-related courses (aPR 1.14, 95% CI 1.04 to 1.27), availability of kits (aPR 2.83, 95% CI 2.21 to 3.62), previous HIV testing experience (aPR 2.65, 95% CI 2.05 to 3.43) and perceiving oneself at risk of HIV infection (aPR 1.29, 95% CI 1.11 to 1.50).

The uptake of HIVST among AGYW in Dodoma City remains below the national target of 95% HIV awareness among people living with HIV. Uptake was influenced by factors such as multiple sexual partnerships, study discipline, kit availability, prior testing experience and perceived risk of infection. Addressing the identified barriers and improving awareness and accessibility of HIVST could enhance testing rates among AGYW.

Cardiovascular events (CVEs), in particular acute coronary syndrome (ACS), complicate the course of a significant number of patients hospitalised for community-acquired pneumonia (CAP) or influenza. Emerging evidence suggests that this increased risk of CVEs could be mitigated by the use of acetylsalicylic acid (aspirin). The ASCAP study investigates whether the addition of aspirin to standard therapy in hospitalised patients with moderate-to-severe CAP or influenza can reduce the incidence of CVEs.

The ASCAP study is a multicentre, double-blind, placebo-controlled randomised trial in 16 university and general hospitals in the Netherlands, in which patients are randomised to acetylsalicylic acid or matching placebo for 90 days. Eligible patients are adults hospitalised for moderate-to-severe CAP or influenza. Patients with antithrombotic or anticoagulant drugs, or those with contraindications for aspirin, are excluded. The primary outcome is the incidence of ACS up to day 180. Secondary outcomes include the incidence of 4-point major adverse cardiovascular events up to day 180, as well as the incidence of major bleeding and clinically relevant non-major bleeding events up to day 90, all-cause mortality up to day 180 and quality of life and societal costs up to day 180. Survival time will be analysed by the log-rank test, stratified for CAP and influenza, with a two-sided alpha of 0.05. Assuming an average baseline ACS risk of 7.5% over 180 days with up to 30% variation across strata, and a 60% hazard reduction due to aspirin, the required sample size to achieve 80% power is 760 patients. Currently, 114 patients are enrolled in the study.

This study is approved by the Medical Ethics Committee Amsterdam UMC (Amsterdam, The Netherlands) under reference number 2023.0741 and registered under EU trial number 2023-504553-12-01 in the EU portal CTIS (Clinical Trials Information System). Results of the study will be published in a peer-reviewed journal.

EU CTIS: 2023-504553-12-01.

Several antibiotic stewardship interventions have been proven effective and safe for reducing the high number of antibiotic prescriptions in late preterm and term neonates at risk of early-onset sepsis (EOS). For successful translation of EOS interventions to clinical practice, implementation strategies should be employed targeting stakeholders. The primary aim of this study is to assess the impact of implementing an antibiotic stewardship bundle, including the EOS calculator, procalcitonin-guided therapy and intravenous-to-oral switch therapy on antibiotic exposure for EOS in Dutch secondary hospitals. Secondary aims are to examine additional clinical outcomes and implementation outcomes.

We will conduct a multicentre, prospective implementation study with interrupted time series and before-after analyses at the paediatric or specialised neonatal departments of 11 Dutch secondary hospitals and their surrounding neonatal care networks. A multimodal implementation strategy, designed using Implementation Mapping, is employed to facilitate implementation. The study population is twofold: (1) neonates born at 34 weeks of gestation or later with suspected EOS that will receive intervention-related care and (2) paediatricians, paediatric residents, neonatal nurses, maternity nurses and parents who are the focus of the implementation strategies. The primary outcome is days of antibiotic therapy per 1000 live-born neonates, which will be evaluated using interrupted time series analysis as well as before-after comparison. Secondary clinical outcomes will be assessed by comparing clinical data from the 12 months pre-implementation and post implementation. Implementation outcomes are adoption, fidelity, feasibility and acceptability of the interventions and fidelity and appropriateness of the implementation strategies. Implementation outcomes will be assessed using both qualitative and quantitative methods, including surveys, individual interviews and focus group interviews. A mixed-methods approach will be used to integrate clinical and implementation outcomes.

The Medical Ethics Committee United (MEC-U) declared (reference: W24.132) that this study does not fall under the Dutch Medical Research Involving Human Subjects Act (WMO). Subsequently, ethical approval was granted by the Scientific Committee of the Franciscus Hospital (T110). The scientific committees of all participating sites adopted this decision and granted permission for local conduct of the study. As electronic health record data are sampled retrospectively and anonymously, a waiver of consent was given to collect these data. Informed consent will be obtained from participants completing surveys or taking part in interviews and focus group discussions. The findings will be disseminated through journal publications and conference presentations. Furthermore, practice and policy recommendations will be collaboratively developed with partner organisations.

NCT06845332.

Infections caused by carbapenemase-producing organisms have become a major problem during the treatment of secondary bloodstream infection in patients with severe intra-abdominal infection (sIAI). Early detection and identification of potential carbapenemases by colloidal gold immunochromatography assay kit can provide information about the susceptibility of pathogenic bacteria before conventional microbial testing results are obtained. This study aims to evaluate the effects of rapid carbapenemase detection-guided antibiotic therapy on patients with sIAI.

The RAPID study is a multicentre, single-blinded, randomised controlled trial. All patients with intra-abdominal infection will be screened for eligibility on any given day that the first gram-negative bacilli-positive blood culture is detected. In total, 640 eligible study participants assigned informed consent will be randomised to either carbapenemase detection-directed antimicrobial treatment or the conventional group, receiving antimicrobial agents based on different bacterial identification and susceptibility tests. Patients will be followed until discharge or death within a follow-up 28 days after randomisation. The primary outcome is all-cause 28-day mortality. Secondary outcomes include antibiotic duration, length of stay in the hospital and intensive care unit and bacterial clearance. The desirability of outcome ranking and response adjusted for duration of antibiotic risk will also be used to comprehensively assess treatment effectiveness at 28 days.

The study has been approved by the Ethics Committee of Jinling Hospital (2023DZKY-069–01) and all participating centres. Written informed consent will be obtained from all participants or their legal representatives. The results of this trial will be disseminated through peer-reviewed publications and presented at national and international scientific conferences.

ChiCTR2300076159.

Tuberculosis (TB) is a major global cause of morbidity and mortality. Emerging evidence in high-burden settings suggests significant long-term sequelae among people surviving TB; however, evidence from high-income, low-TB burden settings like Canada is lacking. In a person with TB infection, provision of TB preventive treatment (TPT) can prevent TB disease and its sequelae, but remains underused. We propose the Functional Outcomes, Lung health and Livelihood Outcomes among people With Tuberculosis study, a multicentre, prospective cohort study in Canada to help improve our understanding of the impacts of TPT and TB disease on individuals.

This is a prospective cohort study taking place in Montreal and Vancouver, Canada. We aim to recruit and retain at least 120 people with microbiologically confirmed TB disease, 340 people treated for TB infection and 120 without TB disease or infection who will be considered our unexposed group. All participants must be ≥6 years of age. Participants with TB disease or infection will be recruited within 2 weeks of treatment initiation. We will follow-up unexposed participants and participants with TB disease for 24 months, and participants with TB infection for 12 months. Throughout follow-up, participants will complete assessments measuring lung health and function, quality of life, disability, dyspnoea, psychological distress, as well as changes in employment and direct and indirect costs incurred because of treatment. Among participants with TB disease, our primary outcome is the difference in quality-adjusted life years between participants with TB disease and those unexposed at 24 months. For participants with TB infection, our primary outcome is the identification of non-patient characteristics (eg, patient cost, quality of life) associated with participant decision to discontinue treatment. Patient partners have contributed to the design of the study and will be involved with the study through to its dissemination.

This study has been approved by institutional ethics review boards at The Research Institute of the McGill University Health Centre (2025–10344) and The University of British Columbia (H24-02071). All participants will provide informed consent (and assent, if required) prior to participating in the study. We will disseminate study results to participants, national and international organisations, and through open-access peer-reviewed academic journals and conferences.

To provide population-level insights into COVID-19 testing behaviour and test results among all pregnant women in the Netherlands and to assess the effects of SARS-CoV-2 infection during pregnancy on maternal and neonatal health outcomes.

Retrospective population-based cohort study.

Dutch registry data on maternal and neonatal health outcomes linked with COVID-19 testing and sociodemographic data for the study period 2020 and 2021.

To study testing behaviour, all pregnant women who gave birth in the Netherlands during 2020 and 2021 were included (N=322 720). To study the effects of maternal infection, women who gave birth between June 2020 and September 2021 and who were tested for COVID-19 were included (N=68 059).

For testing behaviour: number of COVID-19 tests performed and COVID-19 test results. For neonatal health outcomes: preterm birth, low birth weight for gestational age (small for gestational age (SGA)), BIG2 (preterm birth and/or SGA), Apgar score at 5 min below seven (low Apgar), Apgar score at 5 min below four (very low Apgar), neonatal intensive care unit admission, congenital anomalies and mortality. For maternal health outcomes: major postpartum haemorrhage (>1000 mL), severe ruptures (third or fourth degree), type of delivery and episiotomy.

Compared with the reference group (women aged 30–34), women under 20 had the lowest probability of being tested (16.5% vs 31.3%; OR 0.43, 95% CI 0.38 to 0.49), but when tested, they had significantly higher odds of testing positive (19.3% vs 12.9%; OR 1.62, 95% CI 1.21 to 2.14). Women originating from ‘other African’ countries were least likely to be tested (15.1%; OR 0.37, 95% CI 0.35 to 0.39), while women whose country of origin was ‘Morocco’ were most likely to test positive when tested (33.4%; OR 3.63, 95% CI 3.35 to 3.93). While over all trimesters a SARS-CoV-2 infection during pregnancy did not show significant effects, an infection during the first trimester was associated with an increased risk of preterm birth (5.2% vs 6.4%; OR 1.25, 95% CI 1.03 to 1.52) and a low 5-min Apgar score (1.9% vs 2.9%; OR 1.50, 95% CI 1.12 to 2.02). No significant adverse maternal health effects were observed.

There were significant differences in testing behaviour and the probability of testing positive for COVID-19 among pregnant women from different age groups, countries of origin and socioeconomic backgrounds. SARS-CoV-2 infection during pregnancy was not associated with significant effects on maternal health outcomes, and only limited effects on neonatal health were observed. Only infections occurring in the first trimester were linked to an increased risk of preterm births and low 5-min Apgar scores.

Coronavirus disease 2019 (COVID-19) caused a global public emergency between 2020 and 2022 with various morbidity and mortality across the regions. While the impact in sub-Saharan Africa appeared relatively limited, data from regional referral hospitals remain scarce.

To determine the in-hospital mortality rate, risk factors and clinical characteristics of COVID-19 patients admitted to the COVID-19 treatment unit (CTU) at Lira Regional Referral Hospital (LRRH) in northern Uganda

Cross-sectional study with the use of secondary data

This study was conducted at LRRH between January 2023 and December 2023. The data used were for patients admitted from May 2020 to March 2022.

Records of 490 patients admitted with laboratory confirmed COVID-19 were collected and analysed. Selection was by simple census sampling technique. Inclusion criteria were moderately to critically ill patients and those with mild/asymptomatic infection but with comorbidities.

Of the 490 participants, 52% were females and 41% were aged ≥60 years. The most common symptoms were cough (89.6%), difficulty in breathing (78.8%) and chest pain (69.3%). Hypertension (30%), diabetes mellitus (19.5%) and human immunodeficiency virus (10%) were the leading comorbidities. Severe and critical illness was observed in 40% and 7% of cases, respectively. The overall in-hospital mortality rate was 29%. Factors significantly associated with reduced mortality included normal oxygen saturation (SPO₂) (adjusted odds ratios (aOR) 0.11, 95% CI 0.03 to 0.44), normal body temperature (aOR 0.22, 95% CI 0.05 to 0.99), absence of chronic liver disease (aOR 0.01, 95% CI 0.001 to 0.46) and younger age (31–45 years; aOR 0.14, 95% CI 0.03 to 0.74).

The study revealed a high in-hospital mortality rate of 29% among COVID-19 patients admitted to the CTU at LRRH, primarily driven by severe disease presentation and limited access to critical interventions such as oxygen therapy. Independent predictors of survival included younger age, normal oxygen saturation, absence of chronic liver disease and normal body temperature at admission. These findings underscore the urgent need for early identification of high-risk patients and improved access to supportive care, particularly oxygen delivery systems, to reduce mortality in future outbreaks. Strengthening diagnostic capacity, clinical monitoring and preparedness for respiratory pandemics—alongside prospective studies capturing broader patient data—will be essential to refine response strategies and improve outcomes.

The Omicron variant of SARS-CoV-2 has emerged as the predominant strain of COVID-19 since 2022. Its association with prior vaccines remained under investigation.

Retrospective cohort study.

Clinical data for patients, from 1 May 2022 to 31 January 2023, were extracted from the Chi-Mei Medical Center, Chiali electronic medical record databases.

Hospitalised COVID-19 patients in dedicated wards were enrolled in the study. Cases of COVID-19 reinfection and relapse were also included. Patients who did not have COVID-19, those with PCR repositivity, or those with incomplete laboratory data were excluded.

Various doses of vaccines included primary series, additional dose and booster. The types of vaccines included ChAdOx1-S, mRNA-based vaccines and recombinant protein vaccine. The interval between the last vaccination date and the diagnosis date of COVID-19 was assessed.

The primary outcome was all-cause mortality by day 30. The secondary outcomes were severe disease of COVID-19 and 90-day survival.

Among 469 cases, the adjusted HR for 30-day mortality in vaccinated compared with unvaccinated patients was 0.831 (95% CI 0.541 to 1.277; p=0.398), indicating no statistically significant association. Age, Charlson Comorbidity Index (CCI), quick Sequential Organ Failure Assessment score and administration of dexamethasone were recognised as powerful predictors for survival in multivariable analysis. In subgroup analysis, a statistically significant association with better 30-day survival was observed among patients aged

Vaccination was associated with lower mortality in younger or low-CCI patients, but not in older or highly comorbid patients.

To evaluate medication adherence, available social support and types of accessible support among patients with drug-sensitive tuberculosis (DS-TB). Coping mechanism(s) in TB management and associations between accessible support(s) and medication adherence were also explored.

Prospective questionnaire-guided cross-sectional study.

The WHO-certified TB directly observed therapy (DOT) clinic of two tertiary hospitals in Ibadan, southwest Nigeria.

Adult patients with DS-TB attending the TB-DOT clinic of the hospitals.

Primary outcomes were level of adherence to TB regimens, available social support and type(s) of accessible support. Secondary outcomes were coping mechanisms in TB management, as well as associations between accessible support(s) and medication adherence.

Overall, 152 (89.4%) had optimal adherence. Available social supports were ranked as family (168; 98.8%) >healthcare providers (166; 97.6%) >government (119; 70.0%) >non-governmental organisation (NGO) (118; 69.4%) >religious affiliations (81; 47.6%) >friends (65; 38.2%) >patient association (3; 1.8%). Emotional (168; 98.8%) and financial (137; 80.6%) supports were mostly accessible from family, while drug support (118; 69.4%) was largely received from NGO. Seeking emotional support from family or friends (159; 93.5%) was the most effective coping mechanism. Medication adherence was higher among patients who received health information (p=0.02) and drug support (p=0.03) from the NGO. There was no difference in medication adherence of patients with or without emotional (p=0.20) and financial support (p=0.53) from family, as well as from friends (p=0.31 and p>0.99, respectively).

Nearly ninety per cent of DS-TB patients had optimal adherence. Family was the most available source of social support for TB management, with one hundred and approximately eighty-two per cent respectively citing emotional and financial support as most accessible from the family. Emotional support from family or friends was the most effective coping mechanism in TB management. There is generally a need for initiation and implementation of an expanded social support system for DS-TB patients as a critical step towards achieving the WHO End-TB strategy milestone target.