Objectively measured physical activity among people with and without HIV in Uganda: associations with cardiovascular risk and coronary artery disease.

Background: Africa has a disproportionate burden of HIV-related cardiovascular disease. We aimed to describe physical activity in people living with HIV (PLHIV) and people without HIV (PWOH) in Uganda and characterize its relationship with the presence of computed tomography angiography-detected (CCTA) coronary artery disease (CAD). Methods: We performed a cross-sectional analysis of the Ugandan Study of HIV Effects on the Myocardium and Atherosclerosis using Computed Tomography (mUTIMA-CT) cohort. From 2017-2019, physical activity in PLHIV and PWOH was assessed by accelerometry over seven days. Participants additionally underwent CCTA. Univariable and multivariable modified Poisson regression was used to analyze the relationship between physical activity and CAD presence. Results: 168 participants were analyzed. The median (IQR) age was 57 (53-58) years old and 64% were female. Males had more moderate-to-vigorous physical activity per week [68 minutes (12-144) vs 15 minutes (0-50), P<0.001] and less light physical activity [788 minutes (497-1,202) vs [1,059 (730-1490), P=0.001] compared to females, but there was no difference by HIV status. After adjusting for age, which accounted for 10% of the variation in steps taken, and sex, no significant associations were found between physical activity and coronary plaque. Conclusion: Objectively measured physical activity was low compared to guideline recommendations, with males being somewhat more active than females and without significant differences by HIV status. Physical activity was not associated with the presence of CAD independently of age and sex.

Outcomes and care quality metrics for people living with rheumatic heart disease and atrial fibrillation in Uganda.

Background: Atrial fibrillation (AF) is a common complication of rheumatic heart disease (RHD) and is challenging to treat in lower-resourced settings in which RHD remains endemic. Objective: We characterized demographics, treatment outcomes, and factors leading to care retention for participants with RHD and AF in Uganda. Methods: We conducted a retrospective analysis of the Uganda national RHD registry between June 2009 and May 2018. Participants with AF or atrial flutter were included. Demographics, survival, and care metrics were compared with participants without AF. Multivariable logistic regression was used to identify factors associated with retention in care among participants with AF. Results: A total of 1530 participants with RHD were analyzed and 293 (19%) had AF. The median age was 24 (interquartile range 14-38) years. Mortality was similar in both groups (adjusted hazard ratio 1.183, P = .77) over a median follow-up of 203 (interquartile range 98-275) days. A total of 79% of AF participants were prescribed anticoagulation, and 43% were aware of their target international normalized ratio. Retention in care was higher in participants with AF (18% vs 12%, P < .01). Factors associated with decreased retention in care include New York Heart Association functional class III/IV (adjusted odds ratio [OR] 0.48, 95% confidence interval [CI] 0.30-0.76) and distance to nearest health center (adjusted OR 0.94, 95% CI 0.90-0.99). Anticoagulation prescription was associated with enhanced care retention (adjusted OR 1.86, 95% CI 1.24-2.79). Conclusion: Participants with RHD and AF in Uganda do not experience higher mortality than those without AF. Anticoagulation prescription rates are high. Although retention in care is poor among RHD participants, those with concurrent AF are more likely to be retained.

Household Economic Consequences of Rheumatic Heart Disease in Uganda.

Background: Rheumatic heart disease (RHD) has declined dramatically in wealthier countries in the past three decades, but it remains endemic in many lower-resourced regions and can have significant costs to households. The objective of this study was to quantify the economic burden of RHD among Ugandans affected by RHD. Methods: This was a cross-sectional cost-of-illness study that randomly sampled 87 participants and their households from the Uganda National RHD registry between December 2018 and February 2020. Using a standardized survey instrument, we asked participants and household members about outpatient and inpatient RHD costs and financial coping mechanisms incurred over the past 12 months. We used descriptive statistics to analyze levels and distributions of costs and the frequency of coping strategies. Multivariate Poisson regression models were used to assess relationships between socioeconomic characteristics and utilization of financial coping mechanisms. Results: Most participants were young or women, demonstrating a wide variation in socioeconomic status. Outpatient and inpatient costs were primarily driven by transportation, medications, and laboratory tests, with overall RHD direct and indirect costs of $78 per person-year. Between 20 and 35 percent of households experienced catastrophic healthcare expenditure, with participants in the Northern and Western Regions 5-10 times more likely to experience such hardship and utilize financial coping mechanisms than counterparts in the Central Region, a wealthier area. Increases in total RHD costs were positively correlated with increasing use of coping behaviors. Conclusion: Ugandan households affected by RHD, particularly in lower-income areas, incur out-of-pocket costs that are very high relative to income, exacerbating the poverty trap. Universal health coverage policy reforms in Uganda should include mechanisms to reduce or eliminate out-of-pocket expenditures for RHD and other chronic diseases.

Economic consequences of rheumatic heart disease: A scoping review.

BACKGROUND: Rheumatic heart disease (RHD) remains endemic in less-resourced regions and countries and results in high medical and non-medical costs to households, health systems, and society. This scoping review maps out the available evidence on the economic impact of RHD and its antecedents and suggests future research priorities. METHOD: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. We identified articles through systematic electronic database search supplemented by expert knowledge of unpublished literature. Studies were included if they collected empirical RHD-related costing data as a primary or secondary objective and if the data were collected from 2000 onward. Main quantitative findings by intervention, costing perspective, and location were charted, and a standardized quality assessment tool was used to appraise included studies. RESULTS: The index search identified 2519 electronic records and two grey-literature graduate theses. Six full texts were included in the review. Primary prevention costs were modest, while secondary and especially tertiary prevention were more costly. Most estimates were of health sector costs and for tertiary interventions. Only two studies described RHD-related costs in non-high-income countries. Most studies were of adequate methodological quality. CONCLUSION: Research into the costs of RHD has mostly been done in wealthy countries. Costs from the household perspective, which are particularly important in countries with limited public healthcare finance, are lacking. To inform advocacy and guide implementation of the 2018 World Health Assembly resolution on RHD, high-quality, local cost estimates will be needed from a range of representative, RHD-endemic countries.

Potential impact of cardiology phone-consultation for patients risk-stratified by the HEART pathway.

Objective: Bedside consultation by cardiologists may facilitate safe discharge of selected patients from the emergency department (ED) even when admission is recommended by the History, Electrocardiogram, Age, Risk factors, Troponin (HEART) pathway. If bedside evaluation is unavailable, phone consultation between emergency physicians and cardiologists would be most impactful if the resultant disposition is discordant with the HEART pathway. We therefore evaluate discordance between actual disposition and that suggested by the HEART pathway in patients presenting to the ED with chest pain for whom cardiology consultation occurred exclusively by phone and to assess the impact of phone-consultation on disposition. Methods: We performed a single-center, retrospective study of adults presenting to the ED with chest pain whose emergency physician had a phone consultation with a cardiologist. Actual disposition was abstracted from the medical record. HEART pathway category (low-risk, discharge; high-risk, admit) was derived from ED documentation. For discharged patients, major adverse cardiac events were assessed at 30 days by chart review and phone follow-up. Results: For the 170 patients that had cardiologist phone consultation, discordance between actual disposition and the HEART pathway was 17%. The HEART pathway recommended admission for nearly 80% of discharged patients. Following cardiologist phone-consultation, 10% of high-risk patients were discharged, with the majority having undergone a functional study recommended by the cardiologist. At 30 days, discharged patients had experienced no episodes of major adverse cardiac events or rehospitalization for cardiac reasons. Conclusion: For patients presenting to the ED with chest pain, cardiology phone-consultation has the potential to safely impact disposition, primarily by facilitating functional testing in high-risk individuals.

pH-Responsive nanoparticle vaccines for dual-delivery of antigens and immunostimulatory oligonucleotides.

Protein subunit vaccines offer important potential advantages over live vaccine vectors but generally elicit weaker and shorter-lived cellular immune responses. Here we investigate the use of pH-responsive, endosomolytic polymer nanoparticles that were originally developed for RNA delivery as vaccine delivery vehicles for enhancing cellular and humoral immune responses. Micellar nanoparticles were assembled from amphiphilic diblock copolymers composed of an ampholytic core-forming block and a redesigned polycationic corona block doped with thiol-reactive pyridyl disulfide groups to enable dual-delivery of antigens and immunostimulatory CpG oligodeoxynucleotide (CpG ODN) adjuvants. Polymers assembled into 23 nm particles with simultaneous packaging of CpG ODN and a thiolated protein antigen, ovalbumin (ova). Conjugation of ova to nanoparticles significantly enhanced antigen cross-presentation in vitro relative to free ova or an unconjugated, physical mixture of the parent compounds. Subcutaneous vaccination of mice with ova-nanoparticle conjugates elicited a significantly higher CD8(+) T cell response (0.5% IFN-γ(+) of CD8(+)) compared to mice vaccinated with free ova or a physical mixture of the two components. Significantly, immunization with ova-nanoparticle conjugates electrostatically complexed with CpG ODN (dual-delivery) enhanced CD8(+) T cell responses (3.4% IFN-γ(+) of CD8(+)) 7-, 18-, and 8-fold relative to immunization with conjugates, ova administered with free CpG, or a formulation containing free ova and CpG complexed to micelles, respectively. Similarly, dual-delivery carriers significantly increased CD4(+)IFN-γ(+) (Th1) responses and elicited a balanced IgG1/IgG2c antibody response. Intradermal administration further augmented cellular immune responses, with dual-delivery carriers inducing ∼7% antigen-specific CD8(+) T cells. This work demonstrates the ability of pH-responsive, endosomolytic nanoparticles to actively promote antigen cross-presentation and augment cellular and humoral immune responses via dual-delivery of protein antigens and CpG ODN. Hence, pH-responsive polymeric nanoparticles offer promise as a delivery platform for protein subunit vaccines.