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BackgroundAlthough the incidence of acute myocardial infarction (AMI) is rising in sub-Saharan Africa, the uptake of evidence-based care for the diagnosis and treatment of AMI is limited throughout the region. In Tanzania, studies have revealed common misdiagnosis of AMI, infrequent administration of aspirin, and high short-term mortality rates following AMI. ObjectiveThis study aims to evaluate the implementation and efficacy outcomes of an intervention, the Multicomponent Intervention to Improve Acute Myocardial Infarction Care (MIMIC), which was developed to improve the delivery of evidence-based AMI care in Tanzania. MethodsThis single-arm pilot trial will be conducted in the emergency department (ED) at a referral hospital in northern Tanzania. The MIMIC intervention will be implemented by the ED staff for 1 year. Approximately 400 adults presenting to the ED with possible AMI symptoms will be enrolled, and research assistants will observe their care. Thirty days later, a follow-up survey will be administered to assess mortality and medication use. The primary outcome will be the acceptability of the MIMIC intervention, which will be measured by the Acceptability of Intervention Measurement (AIM) instrument. Acceptability will further be assessed via in-depth interviews with key stakeholders. Secondary implementation outcomes will include feasibility and fidelity. Secondary efficacy outcomes will include the following: the proportion of participants who receive electrocardiogram and cardiac biomarker testing, the proportion of participants with AMI who receive aspirin, 30-day mortality among participants with AMI, and the proportion of participants with AMI taking aspirin 30 days following enrollment. ResultsImplementation of MIMIC began on September 1, 2023. Enrollment is expected to be completed by September 1, 2024, and the first results are expected to be published by December 31, 2024. ConclusionsThis study will be the first to evaluate an intervention for improving AMI care in sub-Saharan Africa. If MIMIC is found to be acceptable, the findings from this study will inform a future cluster-randomized trial to assess effectiveness and scalability. Trial RegistrationClinicalTrials.gov NCT04563546; https://clinicaltrials.gov/study/NCT04563546 International Registered Report Identifier (IRRID)DERR1-10.2196/59917

Abstract Background Evidence-based care for acute myocardial infarction (AMI) reduces morbidity and mortality. Prior studies in Tanzania identified substantial gaps in the uptake of evidence-based AMI care. Implementation science has been used to improve uptake of evidence-based AMI care in high-income settings, but interventions to improve quality of AMI care have not been studied in sub-Saharan Africa. Methods Purposive sampling was used to recruit participants from key stakeholder groups (patients, providers, and healthcare administrators) in northern Tanzania. Semi-structured in-depth interviews were conducted using a guide informed by the Consolidated Framework for Implementation Research (CFIR). Interview transcripts were coded to identify barriers to AMI care, using the 39 CFIR constructs. Barriers relevant to emergency department (ED) AMI care were retained, and the Expert Recommendations for Implementing Change (ERIC) tool was used to match barriers with Level 1 recommendations for targeted implementation strategies. Results Thirty key stakeholders, including 10 patients, 10 providers, and 10 healthcare administrators were enrolled. Thematic analysis identified 11 barriers to ED-based AMI care: complexity of AMI care, cost of high-quality AMI care, local hospital culture, insufficient diagnostic and therapeutic resources, inadequate provider training, limited patient knowledge of AMI, need for formal implementation leaders, need for dedicated champions, failure to provide high-quality care, poor provider-patient communication, and inefficient ED systems. Seven of these barriers had 5 strong ERIC recommendations: access new funding, identify and prepare champions, conduct educational meetings, develop educational materials, and distribute educational materials. Conclusions Multiple barriers across several domains limit the uptake of evidence-based AMI care in northern Tanzania. The CFIR-ERIC mapping approach identified several targeted implementation strategies for addressing these barriers. A multi-component intervention is planned to improve uptake of evidence-based AMI care in Tanzania.

Abstract Hierarchically porous, high‐surface‐area silica materials are excellent candidates for multiple applications like catalysis and environmental remediation. Shaping these materials with additive manufacturing (AM) techniques, like robocasting, could enable their use with the benefit of on‐demand, customized shaping and maximizing performance. Herein, ordered mesoporous silica COK‐12 slurries were robocasted into monoliths, containing different ratios of uncalcined COK‐12 and sodium bentonite (0–25 wt.%). The rheology of the mixed slurries is characterized by lower flow indexes (0.69 vs. 0.32) and higher yield stresses (96 vs. 259 Pa) compared to pure COK‐12 ones. Monoliths were printed in woodpile structures and calcined at 600°C. Micro‐CT measurements showed a linear shrinkage of 25% after calcination. Mechanical characterization showed increased uniaxial strength (0.20 ± 0.07 to 1.0 ± 0.3 MPa) with increasing binder/solids ratio from 13 to 25%. The amorphous, mesoporous structure of COK‐12 was retained. The structures exhibited open porosities of 52 ± 4% and showed higher specific mesopore volumes, and increased average mesopore size (6 vs. 8 nm) compared to COK‐12. Small‐angle x‐ray scattering analysis revealed an increased lattice parameter (10.3 vs. 11.0 nm) and reduced wall thickness (3.1 nm vs. 4.1 nm) of the COK‐12 in the monoliths. These properties indicate suitability for their application as porous supports and adsorbents.

Background The prevalence of multimorbidity (the presence of two or more chronic health conditions) is rapidly increasing in sub–Saharan Africa. Hospital care pathways that focus on single presenting complaints do not address this pressing problem. This has the potential to precipitate frequent hospital readmissions, increase health system and out-of-pocket expenses, and may lead to premature disability and death. We aim to present a description of inpatient multimorbidity in a multicentre prospective cohort study in Malawi and Tanzania. Primary objectives Determine prevalence of multimorbid disease among adult medical admissions and measure patient outcomes. Health Economic: Measure economic costs incurred and changes in health-related quality of life (HRQoL) at 90 days post-admission. Situation analysis: Qualitatively describe pathways of patients with multimorbidity through the health system. Secondary objectives Determine hospital readmission free survival and markers of disease control 90 days after admission. Health Economic: Present economic costs from patient and health system perspective, sub-analyse costs and HRQoL according to presence of different diseases. Situation analysis: Understand health literacy related to their own diseases and experience of care for patients with multimorbidity and their caregivers. Methods This is a prospective longitudinal cohort study of adult (≥18 years) acute medical hospital admissions with nested health economic and situation analysis in four hospitals: 1) Queen Elizabeth Central Hospital, Blantyre, Malawi; 2) Chiradzulu District Hospital, Malawi; 3) Hai District Hospital, Boma Ng’ombe, Tanzania; 4) Muhimbili National Hospital, Dar-es-Salaam, Tanzania. Follow-up duration will be 90 days from hospital admission. We will use consecutive recruitment within 24 hours of emergency presentation and stratified recruitment across four sites. We will use point-of-care tests to refine estimates of disease pathology. We will conduct qualitative interviews with patients, caregivers, healthcare providers and policymakers; focus group discussions with patients and caregivers, and observations of hospital care pathways.

BackgroundChronic myocardial injury is a condition defined by stably elevated cardiac biomarkers without acute myocardial ischemia. Although studies from high-income countries have reported that chronic myocardial injury predicts adverse prognosis, there are no published data about the condition in sub-Saharan Africa.MethodsBetween November 2020 and January 2023, adult patients with chest pain or shortness of breath were recruited from an emergency department in Moshi, Tanzania. Medical history and point-of-care troponin T (cTnT) assays were obtained from participants; those whose initial and three-hour repeat cTnT values were abnormally elevated but within 11% of each other were defined as having chronic myocardial injury. Mortality was assessed thirty days following enrollment.ResultsOf 568 enrolled participants, 81 (14.3%) had chronic myocardial injury, 73 (12.9%) had acute myocardial injury, and 412 (72.5%) had undetectable cTnT values. Of participants with chronic myocardial injury, the mean (± sd) age was 61.5 (± 17.2) years, and the most common comorbidities were CKD (n = 65, 80%) and hypertension (n = 60, 74%). After adjusting for CKD, thirty-day mortality rates (38% vs. 36%, aOR 1.03, 95% CI: 0.52-2.03, p = 0.931) were similar between participants with chronic myocardial injury and those with acute myocardial injury, but significantly greater (38% vs. 13.6%, aOR 3.63, 95% CI: 1.98-6.65, pConclusionIn Tanzania, chronic myocardial injury is a poor prognostic indicator associated with high risk of short-term mortality. Clinicians practicing in this region should triage patients with stably elevated cTn levels in light of their increased risk.

Background The prevalence of multimorbidity (the presence of two or more chronic health conditions) is rapidly increasing in sub–Saharan Africa. Hospital care pathways that focus on single presenting complaints do not address this pressing problem. This has the potential to precipitate frequent hospital readmissions, increase health system and out-of-pocket expenses, and may lead to premature disability and death. We aim to present a description of inpatient multimorbidity in a multicentre prospective cohort study in Malawi and Tanzania. Primary objectives Clinical: Determine prevalence of multimorbid disease among adult medical admissions and measure patient outcomes. Health Economic: Measure economic costs incurred and changes in health-related quality of life (HRQoL) at 90 days post-admission. Situation analysis: Qualitatively describe pathways of patients with multimorbidity through the health system. Secondary objectives Clinical: Determine hospital readmission free survival and markers of disease control 90 days after admission. Health Economic: Present economic costs from patient and health system perspective, sub-analyse costs and HRQoL according to presence of different diseases. Situation analysis: Understand health literacy related to their own diseases and experience of care for patients with multimorbidity and their caregivers. Methods This is a prospective longitudinal cohort study of adult (≥18 years) acute medical hospital admissions with nested health economic and situation analysis in four hospitals: 1) Queen Elizabeth Central Hospital, Blantyre, Malawi; 2) Chiradzulu District Hospital, Malawi; 3) Hai District Hospital, Boma Ng’ombe, Tanzania; 4) Muhimbili National Hospital, Dar-es-Salaam, Tanzania. Follow-up duration will be 90 days from hospital admission. We will use consecutive recruitment within 24 hours of emergency presentation and stratified recruitment across four sites. We will use point-of-care tests to refine estimates of disease pathology. We will conduct qualitative interviews with patients, caregivers, healthcare providers and policymakers; focus group discussions with patients and caregivers, and observations of hospital care pathways.

IntroductionMyocardial Infarction (MI) is a leading cause of death worldwide. In high income countries, quality improvement strategies have played an important role in increasing uptake of evidence-based MI care and improving MI outcomes. The incidence of MI in sub-Saharan Africa is rising, but uptake of evidence-based care in northern Tanzania is low. There are currently no published quality improvement interventions from the region. The objective of this study was to determine provider attitudes towards a planned quality improvement intervention for MI care in northern Tanzania.MethodsThis study was conducted at a zonal referral hospital in northern Tanzania. A 41-question survey, informed by the Theoretical Framework for Acceptability, was developed by an interdisciplinary team from Tanzania and the United States. The survey, which explored provider attitudes towards MI care improvement, was administered to key provider stakeholders (physicians, nurses, and hospital administrators) using convenience sampling.ResultsA total of 140 providers were enrolled, including 82 (58.6%) nurses, 56 (40.0%) physicians, and 2 (1.4%) hospital administrators. Most participants worked in the Emergency Department or inpatient medical ward. Providers were interested in participating in a quality improvement project to improve MI care at their facility, with 139 (99.3%) strongly agreeing or agreeing with this statement. All participants agreed or strongly agreed that improvements were needed to MI care pathways at their facility. Though their facility has an MI care protocol, only 88 (62.9%) providers were aware of it. When asked which intervention would be the single-most effective strategy to improve MI care, the two most common responses were provider training (n = 66, 47.1%) and patient education (n = 41, 29.3%).ConclusionProviders in northern Tanzania reported strongly positive attitudes towards quality improvement interventions for MI care. Locally-tailored interventions to improve MI should include provider training and patient education strategies.

Background: Uptake of evidence-based care for acute myocardial infarction (AMI) is suboptimal in Tanzania, but there are currently no published interventions to improve AMI care in sub-Saharan Africa. Objectives: Co-design a quality improvement intervention for AMI care tailored to local contextual factors. Methods: An interdisciplinary design team consisting of 20 physicians, nurses, implementation scientists, and administrators met from June 2022 through August 2023. Half of the design team consisted of representatives from the target audience, emergency department physicians and nurses at a referral hospital in northern Tanzania. The design team reviewed multiple published quality improvement interventions focusing on ED-based AMI care. After selecting a multicomponent intervention to improve AMI care in Brazil (BRIDGE-ACS), the design team used the ADAPT-ITT framework to adapt the intervention to the local context. Findings: The design team audited current AMI care processes at the study hospital and reviewed qualitative data regarding barriers to care. Multiple adaptations were made to the original BRIDGE-ACS intervention to suit the local context, including re-designing the physician reminder system and adding patient educational materials. Additional feedback was sought from topical experts, including patients with AMI. Draft intervention materials were iteratively refined in response to feedback from experts and the design team. The finalized intervention, Multicomponent Intervention to Improve Myocardial Infarction Care in Tanzania (MIMIC), consisted of five core components: physician reminders, pocket cards, champions, provider training, and patient education. Conclusion: MIMIC is the first locally tailored intervention to improve AMI care in sub-Saharan Africa. Future studies will evaluate implementation outcomes and efficacy.

Objectives We aimed to prospectively describe incident cardiovascular events among people living with HIV (PLWH) in northern Tanzania. Secondary aims of this study were to understand non-communicable disease care-seeking behaviour and patient preferences for cardiovascular care and education.Design A prospective observational study.Setting This study was conducted at the Majengo HIV Care and Treatment Clinic, an outpatient government-funded clinic in Moshi, TanzaniaParticipants Adult patients presenting to an HIV clinic for routine care in northern Tanzania were enrolled from 1 September 2020 to 1 March 2021.Interventions At enrolment, participants completed a survey and a resting 12-lead ECG was obtained. At 6 month follow-up, a repeat survey regarding interim health events and repeat ECG was obtained.Primary and secondary outcome measures Interim major adverse cardiovascular events (MACE) were defined by: self-reported interim stroke, self-reported hospitalisation for heart failure, self-reported interim myocardial infarction, interim myocardial infarction by ECG criteria (new pathologic Q waves in two contiguous leads) or death due to cardiovascular disease (CVD).Results Of 500 enrolled participants, 477 (95.4%) completed 6 month follow-up and 3 (0.6%) died. Over the 6 month follow-up period, 11 MACE occurred (3 strokes, 6 myocardial infarctions, 1 heart failure hospitalisation and 1 cardiovascular death), resulting in an incidence rate of 4.58 MACE per 100 person-years. Of participants completing 6 month follow-up, 31 (6.5%) reported a new non-communicable disease diagnosis, including 23 (4.8%) with a new hypertension diagnosis.Conclusions The incidence of MACE among PLWH in Tanzania is high. These findings are an important preliminary step in understanding the landscape of CVD among PLWH in Tanzania and highlight the need for interventions to reduce cardiovascular risk in this population.

The cystic fibrosis landscape has changed dramatically over the last few decades, with improvements in patient quality of life, prognosis and predicted survival. In part, this is related to the availability of novel CFTR modulator drugs, although prior advances in symptom-directed therapies and diagnosis had already led to substantial improvements. However, the authors, part of a national CF focused group, recognize that more needs to be done and outline their considerations on research priorities in this perspective.

The prevalence of cardiovascular disease (CVD) is rising among people with HIV (PWH) in sub-Saharan Africa (SSA). Despite the utility of the electrocardiogram (ECG) in screening for CVD, there is limited data regarding longitudinal ECG changes among PWH in SSA. In this study, we aimed to describe ECG changes over a 6-month period in a cohort of PWH in northern Tanzania. Between September 2020 and March 2021, adult PWH were recruited from Majengo HIV Care and Treatment Clinic (MCTC) in Moshi, Tanzania. Trained research assistants surveyed participants and obtained a baseline ECG. Participants then returned to MCTC for a 6-month follow-up, where another ECG was obtained. Two independent physician adjudicators interpreted baseline and follow-up ECGs for rhythm, left ventricular hypertrophy (LVH), bundle branch blocks, ST-segment changes, and T-wave inversion, using standardized criteria. New ECG abnormalities were defined as those that were absent in a patient's baseline ECG but present in their 6-month follow-up ECG. Of 500 enrolled participants, 476 (95.2%) completed follow-up. The mean (± SD) age of participants was 45.7 (± 11.0) years, 351 (73.7%) were female, and 495 (99.8%) were taking antiretroviral therapy. At baseline, 248 (52.1%) participants had one or more ECG abnormalities, the most common of which were LVH (n = 108, 22.7%) and T-wave inversion (n = 89, 18.7%). At six months, 112 (23.5%) participants developed new ECG abnormalities, including 40 (8.0%) cases of new T-wave inversion, 22 (4.6%) cases of new LVH, 12 (2.5%) cases of new ST elevation, and 11 (2.3%) cases of new prolonged QTc. Therefore, new ECG changes were common over a relatively short 6-month period, which suggests that subclinical CVD may develop rapidly in PWH in Tanzania. These data highlight the need for additional studies on CVD in PWH in SSA and the importance of routine CVD screening in this high-risk population.

Data describing the incidence of hypertension and diabetes among people with HIV in sub-Saharan Africa remain sparse. In this study, adults with HIV were enrolled from a public clinic in Moshi, Tanzania (September 2020-March 2021). At enrollment, a survey was administered to collect information on comorbidities and medication use. Each participant's blood pressure and point-of-care glucose were measured. Baseline hypertension was defined by blood pressure ≥140/90 mmHg or self-reported hypertension at enrollment. Baseline diabetes was defined by self-reported diabetes or hyperglycemia (fasting glucose ≥126 mg/dl or random glucose ≥200 mg/dl) at enrollment. At 6-month follow-up, participants' blood pressure and point-of-care glucose were again measured. Incident hypertension was defined by self-report of new hypertension diagnosis or blood pressure ≥140/90 mmHg at follow-up in a participant without baseline hypertension. Incident diabetes was defined as self-report of new diabetes diagnosis or measured hyperglycemia at follow-up in a participant without baseline diabetes. During the study period, 477 participants were enrolled, of whom 310 did not have baseline hypertension and 457 did not have baseline diabetes. At six-month follow-up, 51 participants (95% CI: 38, 67) had new-onset hypertension, corresponding to an incidence of 33 new cases of hypertension per 100 person-years. Participants with incident hypertension at 6-month follow-up were more likely to have a history of alcohol use (90.2% vs. 73.7%, OR = 3.18, 95% CI:1.32-9.62, p = 0.008) and were older (mean age = 46.5 vs. 42.3, p = 0.027). At six-month follow-up, 8 participants (95% CI: 3, 16) had new-onset diabetes, corresponding to an incidence of 3 new cases of diabetes per 100 person-years. In conclusion, the incidence of elevated blood pressure and diabetes among Tanzanians with HIV is higher than what has been reported in high-income settings.

BackgroundPeople with HIV in sub-Saharan Africa are increasingly developing age-related comorbidities. The purpose of this prospective observational study was to describe 6-month outcomes among Tanzanians with HIV and elevated blood pressure or hyperglycemia under current care pathways.MethodsAdults presenting for routine HIV care were enrolled and underwent blood pressure and blood glucose measurements. Participants with abnormal blood pressure or glucose were referred for further care, as per current guidelines. Participants' blood pressure and point-of-care glucose were re-evaluated during their 6-month follow-up visit. Elevated blood pressure was defined as systolic ≥140 mmHg or diastolic ≥90 mmHg. Hyperglycemia was defined as fasting glucose ≥126 mg/dl or random glucose ≥200 mg/dl. An electrocardiogram was obtained at enrollment and at follow-up. Interim myocardial infarction and interim myocardial ischemia were defined as new pathologic Q waves and new T-wave inversions, respectively.ResultsOf 500 participants, 155 had elevated blood pressure and 17 had hyperglycemia at enrolment. At 6-month follow-up, 7 (4.6%) of 155 participants with elevated blood pressure reported current use of an anti-hypertensive medication, 100 (66.2%) had persistent elevated blood pressure, 12 (7.9%) developed interim myocardial infarction, and 13 (8.6%) developed interim myocardial ischemia. Among 17 participants with hyperglycemia, 9 (56%) had persistent hyperglycemia at 6 months and 2 (12.5%) reported current use of an anti-hyperglycemic medication.ConclusionsInterventions are needed to improve non-communicable disease care pathways among Tanzanians with HIV.

BackgroundSub-Saharan Africa has a high prevalence of hypertension with a low rate of awareness, treatment adherence, and control. The emergency department (ED) may represent a unique opportunity to improve hypertension screening, awareness, and linkage to care. We conducted a qualitative study among hypertensive patients presenting to the ED and their healthcare providers to determine barriers to hypertension care and control.MethodsIn northern Tanzania, between November and December 2017, we conducted three focus group discussions among patients with hypertension presenting to the emergency department and three in-depth interviews among emergency department physicians. In our study, hypertension was defined as a single blood pressure of ≥160/100 mm Hg or a two-time average of ≥140/90 mm Hg. Barriers to care were identified by thematic analysis applying an inductive approach within the framework method.ResultsWe enrolled 24 total patients into three focus groups and performed three in-depth interviews with individual providers. Thematic analysis identified two major domains: 1) patient knowledge, attitudes, and practices, and 2) structural barriers to hypertension care. Four major themes emerged within the knowledge, attitudes, and practices domain, including disease chronicity, provider communication, family support, and fear-based attitudes. Within the structural domain, several themes emerged that identified barriers that impeded hypertension follow-up care and self-management, including cost, access to care, and transportation and wait time.ConclusionPatients and physicians identified multiple barriers and facilitators to hypertension care. These perspectives may be helpful to design emergency department-based interventions that target blood pressure control and linkage to outpatient care.

Introduction: Data describing atrial fibrillation (AF) care in emergency centres (ECs) in sub-Saharan Africa is lacking. We sought to describe the prevalence and outcomes of AF in a Tanzanian EC. Methods: In a prospective, observational study, adults presenting with chest pain or shortness of breath to a Tanzanian EC were enrolled from January through October 2019. Participants underwent electrocardiogram testing which were reviewed by two independent physician judges to determine presence of AF. Participants were asked about their medical history and medication use at enrollment, and a follow-up questionnaire was administered via telephone thirty days later to assess mortality, interim stroke, and medication use. Results: Of 681 enrolled patients, 53 (7.8%) had AF. The mean age of participants with AF was 68.1, with a standard deviation (sd) of 21.1 years, and 23 of the 53 (43.4%) being male. On presentation, none of the participants found to have AF reported a previous history of AF. The median CHADS-VASC score among participants was 4 with an interquartile range (IQR) of 2-4. No participants were taking an anticoagulant at baseline. On index presentation, 49 (92.5%) participants with AF were hospitalised with 52 (98.1%) participants completing 30-day follow-up. 18 (34%) participants died, and 5 (9.6%) suffered a stroke. Of the surviving 31 participants with AF and a CHADS-VASC score ≥ 2, none were taking other anti-coagulants at 30 days. Compared to participants without AF, participants with AF were more likely to be hospitalised (OR 5.25, 95% CI 2.10-17.95, p

Growing evidence suggests considerable variation in endemic typhoid fever incidence at some locations over time, yet few settings have multi-year incidence estimates to inform typhoid control measures. We sought to describe a decade of typhoid fever incidence in the Kilimanjaro Region of Tanzania. Cases of blood culture confirmed typhoid were identified among febrile patients at two sentinel hospitals during three study periods: 2007-08, 2011-14, and 2016-18. To account for under-ascertainment at sentinel facilities, we derived adjustment multipliers from healthcare utilization surveys done in the hospital catchment area. Incidence estimates and credible intervals (CrI) were derived using a Bayesian hierarchical incidence model that incorporated uncertainty of our observed typhoid fever prevalence, of healthcare seeking adjustment multipliers, and of blood culture diagnostic sensitivity. Among 3,556 total participants, 50 typhoid fever cases were identified. Of typhoid cases, 26 (52%) were male and the median (range) age was 22 (

Introduction: HIV confers increased risk of myocardial infarction (MI), but there has been little study of ischemic electrocardiogram (ECG) findings among people with HIV in sub-Saharan Africa. Objectives: To compare the prevalence of ischemic ECG findings among Tanzanians with and without HIV and to identify correlates of ischemic ECG changes among Tanzanians with HIV. Methods: Consecutive adults presenting for routine HIV care at a Tanzanian clinic were enrolled. Age- and sex-matched HIV-uninfected controls were enrolled from a nearby general clinic. All participants completed a standardized health questionnaire and underwent 12-lead resting ECG testing, which was adjudicated by independent physicians. Prior MI was defined as pathologic Q-waves in contiguous leads, and myocardial ischemia was defined as ST-segment depression or T-wave inversion in contiguous leads. Pearson’s chi-squared test was used to compare the prevalence of ECG findings among those with and without HIV and multivariate logistic regression was performed to identify correlates of prior MI among all participants. Results: Of 497 participants with HIV and 497 without HIV, 272 (27.8%) were males and mean (sd) age was 45.2(12.0) years. ECG findings suggestive of prior MI (11.1% vs 2.4%, OR 4.97, 95% CI: 2.71–9.89, 'p' < 0.001), and myocardial ischemia (18.7% vs 12.1% OR 1.67, 95% CI: 1.18–2.39, 'p' = 0.004) were significantly more common among participants with HIV. On multivariate analysis, ECG findings suggestive of prior MI among all participants were associated with HIV infection (OR 4.73, 95% CI: 2.51–9.63, 'p' = 0.030) and self-reported family history of MI or stroke (OR 1.96, 95% CI: 1.08–3.46, 'p' = 0.023). Conclusions: There may be a large burden of ischemic heart disease among adults with HIV in Tanzania, and ECG findings suggestive of coronary artery disease are significantly more common among Tanzanians with HIV than those without HIV.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease characterized by progressive and catastrophic heterotopic ossification (HO) of skeletal muscle and associated soft tissues. FOP is caused by dominantly acting mutations in the gene encoding the bone morphogenetic protein (BMP) type I receptor, ACVR1 (ALK2), the most prevalent of which results in an arginine to histidine substitution at position 206 (ACVR1[R206H]). The fundamental pathological consequence of FOP-causing ACVR1 receptor mutations is to enable activin A to initiate canonical BMP signaling in fibro-adipogenic progenitors (FAPs), which drives HO. We developed a monoclonal blocking antibody (JAB0505) against the extracellular domain of ACVR1 and tested its effect on HO in 2 independent FOP mouse models. Although JAB0505 inhibited BMP-dependent gene expression in wild-type and ACVR1(R206H)-overexpressing cell lines, JAB0505 treatment profoundly exacerbated injury-induced HO. JAB0505-treated mice exhibited multiple, distinct foci of heterotopic lesions, suggesting an atypically broad anatomical domain of FAP recruitment to endochondral ossification. This was accompanied by dysregulated FAP population growth and an abnormally sustained immunological reaction following muscle injury. JAB0505 drove injury-induced HO in the absence of activin A, indicating that JAB0505 has receptor agonist activity. These data raise serious safety and efficacy concerns for the use of bivalent anti-ACVR1 antibodies to treat patients with FOP.

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The article discusses the vulnerabilities in the capacity of health systems in sub-Saharan Africa (SSA) to control the spread of infectious diseases, particularly highlighted by the COVID-19 pandemic. It mentions the diagnostic test shortages and data collection issues faced by many countries in SSA, leading to underdiagnosis of COVID-19 cases. The region also has low rates of COVID-19 vaccination due to vaccine hesitancy and profiteering by resource-rich countries. The article emphasizes the need for investment in the health infrastructure of SSA to prevent future pandemics and presents recommendations such as strengthening public health data infrastructure, establishing a domestic pandemic response workforce, advancing vaccines and therapeutics, and improving public health education. [Extracted from the article]

Abstract Background T helper (Th) 17 cells are a highly plastic subset of T cells, which in the context of neuroinflammation, are able to acquire pathogenic features originally attributed to Th1 cells (resulting in so called ex-Th17 cells). Thus, a strict separation between the two T cell subsets in the context of experimental autoimmune encephalomyelitis (EAE) is difficult. High variability in culture and EAE induction protocols contributed to previous conflicting results concerning the differential contribution of Th1 and Th17 cells in EAE. Here, we systematically evaluate the role of different T cell differentiation and transfer protocols for EAE disease development and investigate the functional dynamics of encephalitogenic T cells directly within the inflamed central nervous system (CNS) tissue. Methods We compiled the currently used EAE induction protocols reported in literature and investigated the influence of the different Th1 and Th17 differentiation protocols as well as EAE induction protocols on the EAE disease course. Moreover, we assessed the cytokine profile and functional dynamics of both encephalitogenic Th1 and Th17 cells in the inflamed CNS using flow cytometry and intravital two-photon laser scanning microscopy. Lastly, we used astrocyte culture and adoptive transfer EAE to evaluate the impact of Th1 and Th17 cells on astrocyte adhesion molecule expression in vitro and in vivo. Results We show that EAE courses are highly dependent on in vitro differentiation and transfer protocols. Moreover, using genetically encoded reporter mice (B6.IL17A-EGFP.acRFP x 2d2/2d2.RFP), we show that the motility of interferon (IFN)γ-producing ex-Th17 cells more closely resembles Th1 cells than Th17 cells in transfer EAE. Mechanistically, IFNγ-producing Th1 cells selectively induce the expression of cellular adhesion molecules I-CAM1 while Th1 as well as ex-Th17 induce V-CAM1 on astrocytes. Conclusions The behavior of ex-Th17 cells in EAE lesions in vivo resembles Th1 rather than Th17 cells, underlining that their change in cytokine production is associated with functional phenotype alterations of these cells.