Prevalence and Factors Associated With Liver Fibrosis Among Adult HIV-Infected Patients Attending Urban and Rural Care Clinics in Uganda.

BACKGROUND: Liver fibrosis is common among HIV-infected patients. Risk factors vary by location. Understanding this variation may inform prevention strategies. We compared the prevalence and correlates of liver fibrosis among HIV-infected patients attending care clinics in Uganda. METHODS: This was a cross-sectional study involving 2030 HIV-infected patients attending care clinics in urban and rural Uganda. Liver fibrosis was defined as liver stiffness measurement (LSM) >7.1 KPa. Proportions and correlates of liver fibrosis were assessed and compared using logistic regression stratified by gender and site. RESULTS: Prevalence of liver fibrosis was higher among participants in the rural clinic (15% vs 11%; P = .017). History of tobacco use (urban P = .022; rural P = .035) and serologic evidence of hepatitis C infection (HCV; urban P = .028; rural P = .03) was associated with liver fibrosis in all men. Elevated liver transaminases (urban P = .002; rural P = .028) and increasing age (urban P = .008; rural P = .052) were risk factors among all women. Tobacco use among women was only a risk factor in those attending the rural clinic (P = .003), and detectable HIV viral load (P = .002) for men in the urban clinic. CONCLUSIONS: Liver fibrosis is prevalent among HIV-infected persons in Uganda. HIV viral suppression and avoiding tobacco may be strategies to prevent liver fibrosis and cancer risk

Atherogenic Risk Assessment among Persons Living in Rural Uganda

Background. Hypertension and dyslipidemia are independent risk factors for coronary heart disease and commonly coexist. Cardiovascular risk can be reliably predicted using lipid ratios such as the atherogenic index, a useful prognostic parameter for guiding timely interventions. Objective. We assessed the cardiovascular risk profile based on the atherogenic index of residents within a rural Ugandan cohort. Methods. In 2011, a population based survey was conducted among 7507 participants. Sociodemographic characteristics, physical measurements (blood pressure, weight, height, and waist and hip circumference), and blood sampling for non fasting lipid profile were collected for each participant. Atherogenic risk profile, defined as logarithm base ten of (triglyceride divided by high density lipoprotein cholesterol), was categorised as low risk (0.24). Results. Fifty-five percent of participants were female and the mean age was 49.9 years (SD± 20.2). Forty-two percent of participants had high and intermediate atherogenic risk. Persons with hypertension, untreated HIV infection, abnormal glycaemia, and obesity and living in less urbanised villages were more at risk. Conclusion. A significant proportion of persons in this rural population are at risk of atherosclerosis. Key identified populations at risk should be considered for future intervention against cardiovascular related morbidity and mortality. The study however used parameters from unfasted samples that may have a bearing on observed results

Predictors of loss to follow up among patients with type 2 diabetes mellitus attending a private not for profit urban diabetes clinic in Uganda : a descriptive retrospective study

BACKGROUND: Although the prevalence of type 2 diabetes mellitus is increasing in Uganda, data on loss to follow up (LTFU) of patients in care is scanty. We aimed to estimate proportions of patients LTFU and document associated factors among patients attending a private not for profit urban diabetes clinic in Uganda. METHODS: We conducted a descriptive retrospective study between March and May 2017. We reviewed 1818 out-patient medical records of adults diagnosed with type 2 diabetes mellitus registered between July 2003 and September 2016 at St. Francis Hospital - Nsambya Diabetes clinic in Uganda. Data was extracted on: patients' registration dates, demographics, socioeconomic status, smoking, glycaemic control, type of treatment, diabetes mellitus complications and last follow-up clinic visit. LTFU was defined as missing collecting medication for six months or more from the date of last clinic visit, excluding situations of death or referral to another clinic. We used Kaplan-Meier technique to estimate time to defaulting medical care after initial registration, log-rank test to test the significance of observed differences between groups. Cox proportional hazards regression model was used to determine predictors of patients' LTFU rates in hazard ratios (HRs). RESULTS: Between July 2003 and September 2016, one thousand eight hundred eighteen patients with type 2 diabetes mellitus were followed for 4847.1 person-years. Majority of patients were female 1066/1818 (59%) and 1317/1818 (72%) had poor glycaemic control. Over the 13 years, 1690/1818 (93%) patients were LTFU, giving a LTFU rate of 34.9 patients per 100 person-years (95%CI: 33.2-36.6). LTFU was significantly higher among males, younger patients (< 45 years), smokers, patients on dual therapy, lower socioeconomic status, and those with diabetes complications like neuropathy and nephropathy. CONCLUSION: We found high proportions of patients LTFU in this diabetes clinic which warrants intervention studies targeting the identified risk factors and strengthening follow up of patients

Highly Diverse Hepatitis C Strains Detected in Sub‐Saharan Africa Have Unknown Susceptibility to Direct‐Acting Antiviral Treatments

The global plan to eradicate hepatitis C virus (HCV) led by the World Health Organization outlines the use of highly effective direct‐acting antiviral drugs (DAAs) to achieve elimination by 2030. Identifying individuals with active disease and investigation of the breadth of diversity of the virus in sub‐Saharan Africa (SSA) is essential as genotypes in this region (where very few clinical trials have been carried out) are distinct from those found in other parts of the world. We undertook a population‐based, nested case‐control study in Uganda and obtained additional samples from the Democratic Republic of Congo (DRC) to estimate the prevalence of HCV, assess strategies for disease detection using serological and molecular techniques, and characterize genetic diversity of the virus. Using next‐generation and Sanger sequencing, we aimed to identify strains circulating in East and Central Africa. A total of 7,751 Ugandan patients were initially screened for HCV, and 20 PCR‐positive samples were obtained for sequencing. Serological assays were found to vary significantly in specificity for HCV. HCV strains detected in Uganda included genotype (g) 4k, g4p, g4q, and g4s and a newly identified unassigned g7 HCV strain. Two additional unassigned g7 strains were identified in patients originating from DRC (one partial and one full open reading frame sequence). These g4 and g7 strains contain nonstructural (ns) protein 3 and 5A polymorphisms associated with resistance to DAAs in other genotypes. Clinical studies are therefore indicated to investigate treatment response in infected patients. Conclusion: Although HCV prevalence and genotypes have been well characterized in patients in well‐resourced countries, clinical trials are urgently required in SSA, where highly diverse g4 and g7 strains circulate.Supported by the Medical Research Council (MRC) (MC_UU_12014/1) and Wellcome Trust (102789/Z/13/A) (to E.T.). M.S. is funded by the Wellcome Trust Sanger Institute (WT098051), the National Institute for Health Research Cambridge Biomedical Research Centre, the African Partnership for Chronic Disease Research (MRC UK partnership grant number MR/K013491/1), and the UK MRC (G0901213‐92157, G0801566). P.K. is funded by the UK MRC and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement. J.S. is funded by the MRC Confidence in Concept award to the University of Glasgow (MC PC 16045). G.M. is a Gates Cambridge Scholar supported by the Gates Cambridge Trust

Co-limitation towards lower latitudes shapes global forest diversity gradients

The latitudinal diversity gradient (LDG) is one of the most recognized global patterns of species richness exhibited across a wide range of taxa. Numerous hypotheses have been proposed in the past two centuries to explain LDG, but rigorous tests of the drivers of LDGs have been limited by a lack of high-quality global species richness data. Here we produce a high-resolution (0.025° × 0.025°) map of local tree species richness using a global forest inventory database with individual tree information and local biophysical characteristics from ~1.3 million sample plots. We then quantify drivers of local tree species richness patterns across latitudes. Generally, annual mean temperature was a dominant predictor of tree species richness, which is most consistent with the metabolic theory of biodiversity (MTB). However, MTB underestimated LDG in the tropics, where high species richness was also moderated by topographic, soil and anthropogenic factors operating at local scales. Given that local landscape variables operate synergistically with bioclimatic factors in shaping the global LDG pattern, we suggest that MTB be extended to account for co-limitation by subordinate drivers

Liver Injury Patterns and Hepatic Toxicity among People Living with and without HIV and Attending Care in Urban Uganda.

IntroductionThe evaluation of the patterns of liver injury, derived from liver chemistry panels, often may narrow on probable causes of the liver insult especially when coupled with clinical history, examination, and other diagnostic tests.MethodsAmong people living with and without HIV and attending care, we used the R ratio to evaluate for liver injury patterns. Liver injury patterns were defined as cholestatic (R R = 2-5), and hepatocellular (R > 5).ResultsOverall, the proportions of participants with cholestatic liver injury, mixed liver injury, and hepatocellular liver injury were 55%, 34%, and 4%, respectively, with similar distribution when stratified by HIV status. Alcohol use among participants without HIV was associated with all patterns of liver injury (cholestatic liver injury (OR = 4.9 CI (1.0-24.2); p = 0.054), mixed liver injury (OR = 5.3 CI (1.1-27.3); p = 0.043), and hepatocellular liver injury (OR = 13.2 CI (1.0-167.3); p = 0.046)). Increasing age was associated with cholestatic liver injury among participants with HIV (OR = 2.3 CI (1.0-5.3); p = 0.038). Despite a high hepatitis B prevalence among participants with HIV, there was no association with liver injury.ConclusionsLiver injury is prevalent among both people living with and without HIV in care, and cholestatic liver injury is the most common pattern. Alcohol is associated with all patterns of liver injury and increasing age associated with cholestatic liver injury among people living without HIV and people living with HIV, respectively

Indirect serum biomarkers perform sub optimally in screening for significant liver fibrosis among HIV-infected and uninfected adults in Uganda.

INTRODUCTION: Indirect serum bio-markers present an acceptable noninvasive and cheap alternative for screening of significant liver fibrosis (SLF). Evaluation of their use in resource limited settings is important to determine their utility. METHODS: We conducted a cross sectional study among 520 HIV infected and HIV uninfected adults attending care clinics in Kampala Uganda. Presence of SLF was determined using Fibroscan® liver stiffness measurement of ≥7.2KPa. The diagostic value of indirect serum bio-markers for diagnosis of SLF was evaluated using the area under the receiver operating characteristics curve (AUROC) using Fibroscan® as gold standard. RESULTS: Overall AUROC values for Age Platelet Index (API), Aspartate to Alanine Ratio (AAR), AST-to-Platelet Ratio Index (APRI), Fibrosis Index based on 4 Factors (FIB-4) and Gamma glutamyl transferase to Platelet Ratio Index (GPR) were 0.52, 0.49, 0.55, 0.55 and 0.54 respectively. Among HIV-infected participants AUROC values were slightly improved at predicting presence of SLF but still under 70%. CONCLUSION: Despite APRI and FIB-4 being more likely to identify participants with SLF, the overall diagnostic value of all serum bio-markers was poor with and without stratification by HIV status. We recommend the use of Fibroscan® technology as more accurate non-invasive diagnostic method for screening of SLF

Comparing adherence to MDR-TB treatment among patients on self-administered therapy and those on directly observed therapy: non-inferiority randomized controlled trial.

BACKGROUND: Adherence is key to the treatment success of multi-drug resistant tuberculosis (MDR-TB) and prevention of community transmission. Directly observed therapy (DOT) is the recommended approach for the management of patients with MDR-TB. Uganda implements a health facility-based DOT approach where all patients diagnosed with MDR-TB report to the nearest private or public health facility for daily observation of ingesting their medicines by a health care provider. Directly observed therapy is very costly for both the patient and health care system. It follows the assumption that MDR TB patients have a history of poor adherence to TB treatment. But only 21% of MDR-TB patients notified globally and 1.4-12% notified in Uganda had been previously treated for TB. The shift to all oral treatment regimen for MDR-TB provides an opportunity for the exploration of self-administered therapy for this group of patients even with use of remotely operated adherence technology. We are conducting a non-inferiority open-label randomized controlled trial to compare adherence to MDR-TB treatment among patients on self-administered therapy (measured by Medication Events Monitoring System (MEMS) technology) with a control group on DOT. METHODS: We plan to enrol 164 newly diagnosed MDR-TB patients aged ≥ 8 years from three regional hospitals based in rural and urban Uganda. Patients with conditions that affect their dexterity and ability to operate the MEMS-operated medicine equipment will not be eligible to participate in the trial. Patients are randomized to either of the two study arms: self-administered therapy with adherence being monitored using MEMS technology (intervention arm) or health facility-based DOT (control arm) and will be followed up monthly. Adherence is measured by the number of days the medicine bottle is open to access medication as recorded by the MEMS software in the intervention arm and treatment complaint days as recorded in the TB treatment card in the control arm. The primary outcome is the comparison of adherence rates between the two study arms. DISCUSSION: The evaluation of self-administered therapy for patients with MDR-TB is important to inform cost-effective management strategies for these patients. The approval of all oral regimens for the treatment of MDR-TB provides an opportunity for innovations such as MEMS technology to support sustainable options for MDR-TB treatment adherence support in low-resource settings. TRIAL REGISTRATION: Pan African Clinical Trials Registry, Cochrane #PACTR202205876377808. Retrospectively registered on 13 May 2022

Nonselective Beta-Blockers Do Not Affect Survival in Cirrhotic Patients with Ascites

The role of nonselective beta-blockers in cirrhotic patients with ascites has been recently questioned; however, definitive evidence in this regard is still lacking. To analyze published data on the influence of nonselective beta-blockers as compared to control group on survival of cirrhotic patients with ascites. Computerized bibliographic search on the main databases was performed. Hazard ratios from Kaplan-Meier curves were extracted in order to perform an unbiased comparison of survival estimates. Secondary outcomes were mortality in patients with refractory ascites, pooled rate of nonselective beta-blockers interruption, spontaneous bacterial peritonitis and hepato-renal syndrome incidence. Three randomized controlled trials and 13 observational studies with 8279 patients were included. Overall survival was comparable between the two groups (hazard ratio = 0.86, 0.71-1.03, p = 0.11). Study design resulted as the main source of heterogeneity in sensitivity analysis and meta-regression. Mortality in refractory ascites patients was similar in the two groups (odds ratio = 0.90, 0.45-1.79; p = 0.76). No difference in spontaneous bacterial peritonitis (odds ratio = 0.78, 0.47-1.29, p = 0.33) and hepato-renal syndrome incidence (odds ratio = 1.22, 0.48-3.09; p = 0.67) was observed. Pooled rate of nonselective beta-blockers interruption was 18.6% (5.2-32.1%). Based on our findings, nonselective beta-blockers should not be routinely withheld in patients with cirrhosis and ascites, even if refractory