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

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

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

Prevalence, risk factors, and antimicrobial resistance of endemic healthcare-associated infections in Africa: a systematic review and meta-analysis

Background Healthcare-associated infections (HCAI) place a significant burden on healthcare systems globally. This systematic review and meta-analysis aimed to investigate the prevalence, risk factors, and aetiologic agents of endemic HCAI in Africa. Methods MEDLINE/PubMed, CINAHL, and Global Health databases (EBSCOhost interface) were searched for studies published in English and French describing HCAI in Africa from 2010 to 2022. We extracted data on prevalence of HCAI, risk factors, aetiologic agents, and associated antimicrobial resistance patterns. We used random-effects models to estimate parameter values with 95% confidence intervals for risk factors associated with HCAI. This study was registered in PROSPERO (CRD42022374559) and followed PRISMA 2020 guidelines. Results Of 2541 records screened, 92 were included, comprising data from 81,968 patients. Prevalence of HCAI varied between 1.6 and 90.2% with a median of 15% across studies. Heterogeneity (I2) varied from 93 to 99%. Contaminated wound (OR: 1.75, 95% CI: 1.31–2.19), long hospital stay (OR: 1.39, 95% CI: 0.92–1.80), urinary catheter (OR: 1.57, 95% CI: 0.35–2.78), intubation and ventilation (OR: 1.53, 95% CI: 0.85–2.22), vascular catheters (OR: 1.49, 95% CI: 0.52–2.45) were among risk factors associated with HCAI. Bacteria reported from included studies comprised 6463 isolates, with E. coli (18.3%, n = 1182), S. aureus (17.3%, n = 1118), Klebsiella spp. (17.2%, n = 1115), Pseudomonas spp. (10.3%, n = 671), and Acinetobacter spp. (6.8%, n = 438) being most common. Resistance to multiple antibiotics was common; 70.3% (IQR: 50–100) of Enterobacterales were 3rd -generation cephalosporin resistant, 70.5% (IQR: 58.8–80.3) of S. aureus were methicillin resistant and 55% (IQR: 27.3–81.3) Pseudomonas spp. were resistant to all agents tested. Conclusions HCAI is a greater problem in Africa than other regions, however, there remains a paucity of data to guide local action. There is a clear need to develop and validate sustainable HCAI definitions in Africa to support the implementation of routine HCAI surveillance and inform implementation of context appropriate infection prevention and control strategies

Transcriptional responses of brain endothelium to Plasmodium falciparum patient-derived isolates in vitro

A hallmark of cerebral malaria (CM) is sequestration of Plasmodium falciparum-infected erythrocytes (IE) within the brain microvasculature. Binding of IE to endothelium reduces microvascular flow and, combined with an inflammatory response, perturbs endothelial barrier function, resulting in breakdown of the blood-brain barrier (BBB). Cytoadherence leads to activation of the endothelium and alters a range of cell processes affecting signaling pathways, receptor expression, coagulation, and disruption of BBB integrity. Here, we investigated whether CM-derived parasites elicit differential effects on human brain microvascular endothelial cells (HBMECs), as compared to uncomplicated malaria (UM)-derived parasites. Patient-derived IE from UM and CM clinical cases, as well as non-binding skeleton-binding protein 1 knockout parasites, were overlaid onto tumour necrosis factor (TNF)-activated HBMECs. Gene expression analysis of endothelial responses was performed using probe-based assays of a panel of genes involved in inflammation, apoptosis, endothelial barrier function, and prostacyclin synthesis pathway. We observed a significant effect on endothelial transcriptional responses in the presence of IE, yet there was no significant correlation between HBMEC responses and type of clinical syndrome (UM or CM). Furthermore, there was no correlation between HBMEC gene expression and both binding itself and level of IE binding to HBMECs, as we detected the same change in endothelial responses when employing both binding and non-binding parasites. Our results suggest that interaction of IE with endothelial cells in this co-culture model induces some endothelial responses that are independent of clinical origin and independent of the expression of the major variant antigen Plasmodium falciparum erythrocyte membrane protein 1 on the IE surface

The effect of emergency obstetric and newborn care training interventions on knowledge and skills of midwifery students prior to graduation in Kenya: A quasi-experimental study using a non-randomised controlled study design

Introduction: Improving access to emergency obstetric and newborn care (EmONC) improves maternal and newborn health. However, there is evidence that the pre-service midwifery training curriculum is deficient in developing countries. Purpose: This study measured the effectiveness of pre-service Emergency obstetric care training intervention package on the knowledge and skills of final year midwifery students in Kenya. Methods: The study was a quasi-experimental controlled trial (ISRCTN 74563398) with one control and two intervention arms (full and partial), involving 12 Kenya Medical Training Colleges (KMTCs) and 381 final year midwifery students. Intervention arms’ KMTCs received EmONC skills training equipment, training of lecturers on teaching methods, EmONC and clinical supervision skills, (and 12 months of mentoring for full intervention arm). Control arm KMTCs had no intervention. Students’ knowledge and practical skills scores 12 months after the bundle of interventions were analysed using mixed effects linear models. Results: A statistically significant difference was detected between the study arms for the practical skills test (p <0.001) but not for the knowledge test (p = 0.23). The odds of achieving scores of 80 % or higher in the knowledge test was significantly higher in the full intervention group A compared to the control group OR 3.2 (1.1 – 9.8), p < 0.05. The scores in the skills tests were significantly higher in the intervention groups A and B compared to the control group 14.5 (4.2 – 24.9), p < 0.001 and 24.9 (14.5–35.2) respectively. Conclusion: The pre-service EmONC intervention package was effective in improving the knowledge and skills of final year midwifery students

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