Browsing by Author "Ssinabulya, Isaac"

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    Atorvastatin reduces T-cell activation and exhaustion among HIV-infected cART-treated suboptimal immune responders in Uganda: a randomised crossover placebo-controlled trial
    (Tropical medicine & international health, 2015) Nakanjako, Damalie; Ssinabulya, Isaac; Nabatanzi, Rose; Bayigga, Lois; Kiragga, Agnes; Joloba, Moses; Kaleebu, Pontiano; Kambugu, Andrew D.; Kamya, Moses R.; Sekaly, Rafick; Elliott, Alison; Mayanja-Kizza, Harriet
    T-cell activation independently predicts mortality, poor immune recovery and non-AIDS illnesses during combination antiretroviral therapy (cART). Atorvastatin showed anti-immune activation effects among HIV-infected cART-naĆÆve individuals. We investigated whether adjunct atorvastatin therapy reduces T-cell activation among cART-treated adults with suboptimal immune recovery.A randomised double-blind placebo-controlled crossover trial, of atorvastatin 80 mg daily vs. placebo for 12 weeks, was conducted among individuals with CD4 increase <295 cells/Ī¼l after seven years of suppressive cART. Change in T-cell activation (CD3 + CD4 + /CD8 + CD38 + HLADR+) and in T-cell exhaustion (CD3 + CD4 + /CD8 + PD1 + ) was measured using flow cytometry.Thirty patients were randomised, 15 to each arm. Atorvastatin resulted in a 28% greater reduction in CD4 T-cell activation (60% reduction) than placebo (32% reduction); P = 0.001. Atorvastatin also resulted in a 35% greater reduction in CD8-T-cell activation than placebo (49% vs. 14%, P = 0.0009), CD4 T-cell exhaustion (27% vs. 17% in placebo), P = 0.001 and CD8 T-cell exhaustion (27% vs. 16%), P = 0.004. There was no carry-over/period effect. Expected adverse events were comparable in both groups, and no serious adverse events were reported.Atorvastatin reduced T-cell immune activation and exhaustion among cART-treated adults in a Ugandan cohort. Atorvastatin adjunct therapy should be explored as a strategy to improve HIV treatment outcomes among people living with HIV in sub-Saharan Africa.
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    Coronary artery calcium, HIV and inflammation in Uganda compared with the USA
    (Open Heart, 2019) Alencherry, Ben; Erem, Geoffrey; Mirembe, Grace; Ssinabulya, Isaac; Yun, Chun-Ho; Hung, Chung-Lieh; Siedner, Mark J.; Bittencourt, Marcio; Kityo, Cissy; McComsey, Grace A.; Longenecker, Chris T.
    To compare the prevalence of detectable coronary artery calcium (CAC) among higher risk, older people living with HIV (PLWH) and uninfected persons in Uganda versus the USA, and second to explore associations of CAC with HIV-specific variables and biomarkers of inflammation. This cross-sectional study of 430 total subjects compared 100 PLWH on antiretroviral therapy and 100 age-matched and sex-matched HIV-uninfected controls in Uganda with 167 PLWH on antiretroviral therapy and 63 uninfected controls in the USA. Multivariable logistic regression was used to examine associations with detectable CAC (CAC >0). Compared with US subjects, Ugandans were older (mean age 56 vs 52 years) and were more likely to have diabetes (36% vs 3%) and hypertension (85% vs 36%), but were less likely to be male (38% vs 74%) or smokers (4% vs 56%). After adjustment for HIV serostatus, age, sex and traditional risk factors, Ugandans had substantially lower odds of CAC >0 (adjusted OR 0.07 (95%ā€‰CI 0.03 to 0.17), p<0.001). HIV was not associated with CAC >0 in either country (p>0.1). Among all PLWH, nadir CD4 count was associated with the presence of CAC, and among Ugandans soluble intercellular adhesion molecule (p=0.044), soluble CD163 (p=0.004) and oxidised low-density lipoprotein (p=0.043) were all associated with the presence of CAC. Ugandans had a dramatically lower prevalence of any coronary calcification compared with US subjects. The role of HIV infection and inflammation as risk factors for subclinical coronary disease in sub-Saharan Africa merits further investigation.
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    HIV and Pericardial Fat are Associated with Abnormal Cardiac Structure and Function among Ugandans
    (Heart, 2020) Buggey, Jonathan; Yun, Chun-Ho; Hung, Chung-Lieh; Kityo, Cissy; Mirembe, Grace; Erem, Geoffrey; Ssinabulya, Isaac; McComseya, Grace A.; Longenecker, Chris T.
    To examine the relationship between pericardial fat (PCF) and cardiac structure and function among HIV-infected patients in the sub-Saharan African country of Uganda. People living with HIV (PLHIV) have altered fat distribution and an elevated risk for heart failure. Whether altered quantity and radiodensity of fat surrounding the heart relates to cardiac dysfunction in this population is unknown. One hundred HIV-positive Ugandans on antiretroviral therapy were compared with 100 age and sex-matched HIV-negative Ugandans; all were >45 years old with >1 cardiovascular disease risk factor. Subjects underwent ECG-gated non-contrast cardiac CT and transthoracic echocardiography with speckle tracking strain imaging. Multivariable linear and logistic regression models were used to explore the association of PCF with echocardiographic outcomes. Median age was 55% and 62% were female. Compared with uninfected controls, PLHIV had lower body mass index (27 vs 30, p=0.02) and less diabetes (26% vs 45%, p=0.005). Median left ventricular (LV) ejection fraction was 67%. In models adjusted for traditional risk factors, HIV was associated with 10.3ā€‰g/m2 higher LV mass index (LVMI) (95%ā€‰CI 3.22 to 17.4; p=0.005), 0.87% worse LV global longitudinal strain (GLS) (95%ā€‰CI āˆ’1.66 to āˆ’0.07; p=0.03) and higher odds of diastolic dysfunction (OR 1.96; 95%ā€‰CI 0.95 to 4.06; p=0.07). In adjusted models, PCF volume was significantly associated with increased LVMI and worse LV GLS, while PCF radiodensity was associated with worse LV GLS (all p<0.05). In Uganda, HIV infection, PCF volume and density are associated with abnormal cardiac structure and function.
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    An implementation science study to enhance cardiovascular disease prevention in Mukono and Buikwe districts in Uganda: a stepped-wedge design
    (BMC health services research, 2019) Musinguzi, Geofrey; Wanyenze, Rhoda K.; Ndejjo, Rawlance; Ssinabulya, Isaac; Van Marwijk, Harm; Ddumba, Isaac; Bastiaens, Hilde; Nuwaha, Fred
    Uganda is experiencing a shift in major causes of death with cases of stroke, heart attack, and heart failure reportedly on the rise. In a study in Mukono and Buikwe in Uganda, more than one in four adults were reportedly hypertensive. Moreover, very few (36.5%) reported to have ever had a blood pressure measurement. The rising burden of CVD is compounded by a lack of integrated primary health care for early detection and treatment of people with increased risk. Many people have less access to effective and equitable health care services which respond to their needs. Capacity gaps in human resources, equipment, and drug supply, and laboratory capabilities are evident. Prevention of risk factors for CVD and provision of effective and affordable treatment to those who require it prevent disability and death and improve quality of life. The aim of this study is to improve health profiles for people with intermediate and high risk factors for CVD at the community and health facility levels. The implementation process and effectiveness of interventions will be evaluated. The overall study is a type 2-hybrid stepped-wedge (SW) design. The design employs mixed methods evaluations with incremental execution and adaptation. Sequential crossover take place from control to intervention until all are exposed. The study will take place in Mukono and Buikwe districts in Uganda, home to more than 1,000,000 people at the community and primary healthcare facility levels. The study evaluation will be guided by; 1) RE-AIM an evaluation framework and 2) the CFIR a determinant framework. The primary outcomes are implementation ā€“ acceptability, adoption, appropriateness, feasibility, fidelity, implementation cost, coverage, and sustainability. Discussion: The study is envisioned to provide important insight into barriers and facilitators of scaling up CVD prevention in a low income context. This project is registered at the ISRCTN Registry with number ISRCTN15848572. The trial was first registered on 03/01/2019.
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    Internal Medicine Clerkship Amidst COVID-19 Pandemic: A Cross-Sectional Study of the Clinical Learning Experience of Undergraduate Medical Students at Makerere University, Uganda
    (Advances in Medical Education and Practice, 2021) Bongomin, Felix; Olum, Ronald; Nakiyingi, Lydia; Lalitha, Rejani; Ssinabulya, Isaac; Sekaggya- Wiltshire, Christine; Ocama, Ponsiano; Byakika-Kibwika, Pauline
    The coronavirus-2019 (COVID-19) pandemic continues to impose a significant impact on medical education. We aimed to describe the clinical learning experience of undergraduate medical students undertaking internal medicine clerkship during the COVID-19 pandemic at Makerere University, Uganda. Methods: A descriptive, cross-sectional study among medical students in clinical years of study pursuing the Bachelor of Medicine and Bachelor of Surgery undergraduate degree program was conducted in November 2020. Only 3rd (junior clerks) and 5th (senior clerks) year medical students whose internal medicine clerkships were interrupted by the COVID-19 pandemic were studied. Results: Data of 188 (95%) eligible clinical year students; junior (101, 54.0%) and senior (86, 46.0%) were analysed. Median age was 24 (range: 22ā€“42) years. Majority (70.1%) were male and Ugandan nationals (94.1%). Sixty-four (30.3%) students reported inadequate personal protective equipment, 152 (81.7%) felt at risk of contracting COVID-19, and 127 (67.9%) said it was difficult to observe COVID-19 standard operating procedures. Twentytwo students (11.9%) were discouraged from pursuing a career in internal medicine. Overall, most students reported good or excellent clinical experience pre-COVID-19 era compared to during the COVID-19 era (4.0 vs 3.5, p<0.0001). Senior clerks significantly believed that the time allocated for the rotation was adequate (p<0.0001) and they were able to complete their study objectives (p<0.001), compared to the junior clerks. Senior clerks believed that learning was difficult when combined with junior clerks (p=0.013). About half of the students (51.4%, n=95) reported clinical teaching should remain as it was in the pre- COVID-19 era. Conclusion: The COVID-19 pandemic has had a significantly negative effect on the clinical learning experience of the students. There is need to review the current teaching and learning methods to suit teaching and learning during pandemics of highly infectious diseases to ensure safe and effective learning experience.
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    Modified EarlyWarning Score (MEWS) Identifies Critical Illness among Ward Patients in a Resource Restricted Setting in Kampala, Uganda: A Prospective Observational Study
    (PloS one, 2016) Kruisselbrink, Rebecca; Kwizera, Arthur; Crowther, Mark; Fox-Robichaud, Alison; O'Shea, Timothy; Nakibuuka, Jane; Ssinabulya, Isaac; Nalyazi, Joan; Bonner, Ashley
    Providing optimal critical care in developing countries is limited by lack of recognition of critical illness and lack of essential resources. The Modified Early Warning Score (MEWS), based on physiological parameters, is validated in adult medical and surgical patients as a predictor of mortality. The objective of this study performed in Uganda was to determine the prevalence of critical illness on the wards as defined by the MEWS, to evaluate the MEWS as a predictor of death, and to describe additional risk factors for mortality