Randomized evaluation of 5-month Ticagrelor monotherapy after 1-month dual-antiplatelet therapy in patients with acute coronary syndrome treated with drug-coated balloons: REC-CAGEFREE II trial rationale and design

Background: Patients treated with drug-coated balloons (DCB) have the theoretical advantage of adopting a low-intensity antiplatelet regimen due to the absence of struts and polymers. Nevertheless, the optimal antiplatelet strategy for patients undergoing DCB-only treatment remains a topic of debate and has not been investigated in randomized trials. Methods: The REC-CAGEFREE II is an investigator-initiated, prospective, open-label, multi-center, randomized, non-inferiority trial aimed to enroll 1908 patients from ≥ 40 interventional cardiology centers in China to evaluate the non-inferiority of an antiplatelet regimen consisting of Aspirin plus Ticagrelor for one month, followed by five months Ticagrelor monotherapy, and then Aspirin monotherapy for six months (Experimental group) compared to the conventional treatment of Aspirin plus Ticagrelor for 12 months (Reference group) in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) using paclitaxel-coated balloons (DCB) exclusively. Participants will be randomly assigned to the Experimental or Reference group in a 1:1 ratio. The randomization will be stratified based on the center and the type of lesion being treated (De novo or in-stent restenosis). The primary endpoint is net adverse clinical events (NACE) within 12 months of PCI, which includes the composite of all-cause death, any stroke, any myocardial infarction, any revascularization and Bleeding Academic Research Consortium (BARC) defined type 3 or 5 bleeding. The secondary endpoint, any ischemic and bleeding event, which includes all-cause death, any stroke, MI, BARC-defined type 3 bleeding, any revascularization, and BARC-defined type 2 bleeding events, will be treated as having hierarchical clinical importance in the above order and analyzed using the win ratio method. Discussion: The ongoing REC-CAGEFREE II trial aims to assess the efficacy and safety of a low-intensity antiplatelet approach among ACS patients with DCB. If non-inferiority is shown, the novel antiplatelet approach could provide an alternative treatment for ACS patients with DCB

Implementing health worker training on sepsis in South Eastern Nigeria using innovative digital strategies: an interventional study

Background: Sepsis is a leading cause of morbidity and mortality especially in low- and middle-income countries such as Nigeria. Training of health workers using digital platforms may improve knowledge and lead to better patient outcomes. Objectives: To assess the effectiveness of a digital health educational module on sepsis in improving the knowledge of medical doctors in Cross River State Nigeria on the diagnosis and management of patients presenting with sepsis. Design: Quasi-experimental analytical study. Methods:: We developed and deployed a sepsis module through an innovative application (Sepsis tutorial app) to doctors in Calabar, Nigeria. We assessed quantitative pre- and post-intervention knowledge scores for those completing the tutorial on sepsis between both assessments. A user satisfaction survey evaluated the content of the tutorial and the usability of the app. Results:: One hundred and two doctors completed the course. There were more males than females (58.8% versus 41.2%). Over half (52%) were junior doctors, a minority were general practitioners and house officers (3% and 5%, respectively), and 72.6% had practiced for periods ranging from 1 to 15 years post-qualification. Gender and age appeared to have no significant association with pre- and post-test scores. The oldest age group (61–70) had the lowest mean pre- and post-test scores, while general practitioners had higher mean pre- and post-test scores than other cadres. The majority (95%) of participants recorded higher post-test than pre-test scores with a significant overall increase in mean scores (25.5 ± 14.7%, p < 0.0001). Participants were satisfied with the content and multimodal delivery of the material and found the app usable. Conclusion:: Digital training using context-responsive platforms is feasible and may be used to close the critical knowledge gap required to respond effectively to medical emergencies such as sepsis in low- to middle-income settings

The process of developing a joint theory of change across three global entities: can this help to make their efforts to strengthen capacity for implementation research more effective?

Introduction A Theory of Change is a visual representation of the pathway by which a programme anticipates it will achieve its goal. It usually starts with discussions around the goal and works backwards through outcomes and outputs to activities. Methods We used a Theory of Change to improve coherence across three research entities at the World Health Organisation. Part of the remit of all three entities is to strengthen capacity in low- and middle-income countries for implementation research. Results Representatives from the three entities were able to formulate a joint goal for strengthening capacity in implementation research. They identified three pathways by which this could be achieved: a) conducting implementation research, b) strengthening implementation research systems and c) utilising implementation research for public health priorities. Conclusion The process of developing the Theory of Change and the logic framework it created, provided a means to track progress towards the goal and to guide improvements in programmes within their lifetime. The process we used to develop the Theory of Change and the pathways to achieve the joint goal, are adaptable and could be used by other organisations that also aim to strengthen research capacity. This would lead to more coherence, better translation of research findings into decision-making and ultimately improvements in public health

Three-Dimensional Rotary Culture to Model Mycobacterial Biofilms in Low-Shear Detergent-Free Liquid Suspension.

In vitro biofilm models have allowed researchers to investigate the role biofilms play in the pathogenesis, virulence, and antimicrobial drug susceptibility of a wide range of bacterial pathogens. Rotary cell culture systems create three-dimensional cellular structures, primarily applied to eukaryotic organoids, that better capture characteristics of the cells in vivo. Here, we describe how to apply a low-shear, detergent-free rotary cell culture system to generate biofilms of Mycobacterium bovis BCG. The three-dimensional biofilm model forms mycobacterial cell aggregates in suspension as surface-detached biomass, without severe nutrient starvation or environmental stress, that can be harvested for downstream experiments. Mycobacterium bovis BCG derived from cell clusters display antimicrobial drug tolerance, presence of an extracellular matrix, and evidence of cell wall remodeling, all features of biofilm-associated bacteria that may be relevant to the treatment of tuberculosis

Accuracy of and preferences for blood-based versus oral-fluid-based HIV self-testing in Malawi: a cross-sectional study

Background: HIV self-testing (HIVST) can use either oral-fluid or blood-based tests. Studies have shown strong preferences for self-testing compared to facility-based services. Despite availability of low-cost blood-based HIVST options, to date, HIVST implementation in sub-Saharan Africa has largely been oral-fluid-based. We investigated whether users preferred blood-based (i.e. using blood sample derived from a finger prick) or oral fluid-based HIVST in rural and urban Malawi. Methods: At clinics providing HIV testing services (n = 2 urban; n = 2 rural), participants completed a semi-structured questionnaire capturing sociodemographic data before choosing to test using oral-fluid-based HVST, blood-based HIVST or provider-delivered testing. They also completed a self-administered questionnaire afterwards, followed by a confirmatory test using the national algorithm then appropriate referral. We used simple and multivariable logistic regression to identify factors associated with preference for oral-fluid or blood-based HIVST. Results: July to October 2018, N = 691 participants enrolled in this study. Given the choice, 98.4% (680/691) selected HIVST over provider-delivered testing. Of 680 opting for HIVST, 416 (61.2%) chose oral-fluid-based HIVST, 264 (38.8%) chose blood-based HIVST and 99.1% (674/680) reported their results appropriately. Self-testers who opted for blood-based HIVST were more likely to be male (50.3% men vs. 29.6% women, p < 0.001), attending an urban facility (43% urban vs. 34.6% rural, p = 0.025) and regular salary-earners (49.5% regular vs. 36.8% non-regular, p = 0.012). After adjustment, only sex was found to be associated with choice of self-test (adjusted OR 0.43 (95%CI: 0.3–0.61); p-value < 0.001). Among 264 reporting blood-based HIVST results, 11 (4.2%) were HIV-positive. Blood-based HIVST had sensitivity of 100% (95% CI: 71.5–100%) and specificity of 99.6% (95% CI: 97.6–100%), with 20 (7.6%) invalid results. Among 416 reporting oral-fluid-based HIVST results 18 (4.3%) were HIV-positive. Oral-fluid-based HIVST had sensitivity of 88.9% (95% CI: 65.3–98.6%) and specificity of 98.7% (95% CI: 97.1–99.6%), with no invalid results. Conclusions: Offering both blood-based and oral-fluid-based HIVST resulted in high uptake when compared directly with provider-delivered testing. Both types of self-testing achieved high accuracy among users provided with a pre-test demonstration beforehand. Policymakers and donors need to adequately plan and budget for the sensitisation and support needed to optimise the introduction of new quality-assured blood-based HIVST products

The Enterics for Global Health (EFGH) Shigella Surveillance Study in Malawi

Background: Malawi is among 7 countries participating in the Enterics for Global Health (EFGH) Shigella surveillance study, which aims to determine the incidence of medically attended diarrhea attributed to Shigella, a leading bacterial cause of diarrhea in children in low-resource settings. Methods: We describe the EFGH study site in the densely populated informal settlement of Ndirande Township, Blantyre, Malawi. We explore the site’s geographical location, demographic characteristics, and the healthcare-seeking behavior of its population, particularly for childhood diarrhea. We also describe the management of childhood diarrhea at the health facility, and the associated challenges to attaining optimum adherence to local and national guidelines at the site. Conclusions: Our overarching aim is to improve global health through understanding and mitigating the impact of diarrhea attributed to Shigella

Standardized mean differences in meta‐analysis: A tutorial

This tutorial focuses on standardized mean differences (SMD) as effect measures in meta‐analyses. We will explain what they are, when they should be used, how to correctly compute and interpret them, and some of the most common error made within evidence synthesis

Intention‐to‐treat analyses and missing outcome data: A tutorial

This tutorial focuses on “intention-to-treat” analyses and missing outcome data in systematic reviews. There is a lack of consensus on the definition of the ITT approach. We will explain the principles of an intention-to-treat analysis, and outline the key issues you need to consider when planning, conducting and writing up your systematic review

Bisoprolol in Patients With COPD at High Risk of Exacerbation

Importance: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Observational studies report that β-blocker use may be associated with reduced risk of COPD exacerbations. However, a recent trial reported that metoprolol did not reduce COPD exacerbations and increased COPD exacerbations requiring hospital admission. Objective: To test whether bisoprolol decreased COPD exacerbations in people with COPD at high risk of exacerbations. Design, Setting and Participants: The Bisoprolol in COPD Study (BICS) was a double-blind placebo-controlled randomized clinical trial conducted in 76 UK sites (45 primary care clinics and 31 secondary clinics). Patients with COPD who had at least moderate airflow obstruction on spirometry (FEV1/FVC <0.7, FEV1 <80% predicted) and ≥2 COPD exacerbations treated with oral corticosteroids and/or antibiotics in the prior 12 months were enrolled from October 17, 2018, to May 31, 2022. Follow-up concluded on April 18, 2023. Interventions: Patients were randomly assigned to bisoprolol (n=261) or placebo (n=258). Bisoprolol was started at 1.25 mg orally daily and was titrated as tolerated over 4 sessions to a maximum dose of 5 mg/d using a standardized protocol. Main outcomes and Measures: The primary clinical outcome was the number of patient reported COPD exacerbations treated with oral corticosteroids and/or antibiotics over the 1- year treatment period. Safety outcomes included serious adverse events and adverse reactions. Results: Although the trial planned to enroll 1574 patients, recruitment was suspended from March, 16, 2020, to July 31, 2021, due to the COVID-19 pandemic. Two patients in each group were excluded post randomization. Among the 515 patients (mean age, 68 years; men, 274 [53%]; mean FEV1, 50.1%, primary outcome data were available for 514 (99.8%) and 371 (72%) remained on study drug. The primary outcome of patient-reported COPD exacerbations treated with oral corticosteroids and/or antibiotics was 526 in bisoprolol group, with a mean exacerbation rate of 2.03/year vs 513 exacerbations in the placebo group with a mean exacerbation rate of 2.01/year, adjusted incidence rate ratio (IRR) [95% CI, 0.97 (0.84, 1.13), p=0.72]. Serious adverse events occurred in 37 (14.5%) of the bisoprolol group vs 36 (14.3%) in the placebo group, [relative risk 1.01 95% CI, 0.62, 1.66), p=0.96]. Conclusions and Relevance: Among people with COPD at high risk of exacerbation, treatment with bisoprolol did not reduce the number of self-reported COPD exacerbations requiring treatment with oral corticosteroids and/or antibiotics

Exploring acceptability, opportunities, and challenges of community-based home pregnancy testing for early antenatal care initiation in rural Kenya

Background: Many women in low- and middle-income countries, including Kenya, access antenatal care (ANC) late in pregnancy. Home pregnancy testing can enable women to detect pregnancy early, but it is not widely available. Our study explored the acceptability and potential of home pregnancy testing delivered by community health volunteers (CHV) on antenatal care initiation in rural Kenya. Methods: This study was part of a public health intervention to improve uptake and quality of ANC. Between November and December 2020, we conducted 37 in-depth interviews involving women who tested positive or negative for a urine pregnancy test provided by CHVs; CHVs and their supervisors involved in the delivery of the pregnancy tests; facility healthcare workers; and key informants. Using Sekhon et al.‘s framework of acceptability, the interviews explored participants’ perceptions and experiences of home pregnancy testing, including acceptability, challenges, and perceived effects on early ANC uptake. Data were analysed thematically in NVivo12 software. Results: Home pregnancy testing was well-received by women who trusted test results and appreciated the convenience and autonomy it offered. Adolescents cherished the privacy, preferring home testing to facility testing which could be a stigmatising experience. Testing enabled earlier pregnancy recognition and linkage to ANC as well as reproductive decision-making for those with undesired pregnancies. Community delivery of the test enhanced the reputation and visibility of the CHVs as credible primary care providers. CHVs in turn were motivated and confident to deliver home pregnancy testing and did not find it as an unnecessary burden; instead, they perceived it as a complement to their work in providing ANC in the community. Challenges identified included test shortages, confidentiality and safeguarding risks, and difficulties accessing facility-based care post-referral. Newly identified pregnant adolescents hesitated to seek ANC due to stigma, fear of reprimand, unwanted parental notification, and perceived pressure from healthcare workers to keep the pregnancy. Conclusion: Home pregnancy testing by CHVs can improve early ANC initiation in resource-poor settings. Mitigating privacy, confidentiality, and safeguarding concerns is imperative. Additional support for women transitioning from pregnancy identification to ANC is essential to ensure appropriate care. Future research should focus on integrating home pregnancy testing into routine community health services