Mortality from adverse drug reaction-related hospitalizations in south-west Ethiopia: A cross-sectional study.

WHAT IS KNOWN AND OBJECTIVE: Adverse drug reactions (ADRs) are an important cause of mortality during medical care. To our knowledge, no Ethiopian studies have reported on mortality due to ADRs in patients presenting to hospital from the community setting. The aim of this study was to determine the mortality rate attributable to ADRs in patients presenting to hospital, identify drugs implicated in the ADR-related deaths and identify factors contributing to ADR-related mortality at Jimma University Specialised Hospital (JUSH), south-west Ethiopia METHODS: This cross-sectional study included 1001 patients aged ≥18 years consecutively admitted to medical wards from May 2015 to August 2016. ADR-related mortality was determined through detailed review of medical records, laboratory tests and patient interviews followed by causality assessment by the Naranjo algorithm and expert consensus. RESULTS: Of 1001 patients, 15, 1.5% (95% confidence interval [CI]: 0.80%-2.30%) died with an ADR. The primary suspected causes of death were drug-induced hepatotoxicity (7, 43.8%) followed by acute kidney injury (4, 25.0%). Isoniazid (6, 33.3%), pyrazinamide (3, 16.7%), efavirenz (2, 11.1%) and tenofovir (2, 11.1%) were commonly implicated drugs. The majority of ADRs (14, 93.8%) were preventable. Unadjusted bivariate comparisons suggested patients who died with ADRs were more likely to have pre-existing liver disease (40.0% vs 7.0%; 95% confidence interval [CI]: 8.1%-57.8%), a history of ADRs (40% vs 1.4%; 95% CI: 13.8%-63.4%), a lower mean (±SD) body mass index (BMI, 17.6 ± 2.1 vs 20.0 ± 2.9 kg/m2 ; 95% CI = 0.9-3.9), exposure to antitubercular (46.7% vs 18.9%; 95% CI: 2.3%-53.1%) and antiretroviral (40.0% vs 7.7%; 95% CI: 7.5%-57.2%) therapies, and a higher mean number of medications (7.1 ± 3.3 vs 3.8 ± 2.1; 95% CI: 2.2-4.4) and Charlson Comorbidity Index (3.9 ± 2.9 vs 1.6 ± 1.8; 95% CI: 1.4-3.2) than surviving patients without ADRs. WHAT IS NEW AND CONCLUSION: Fatal ADRs were common in patients presenting to hospital. The drugs implicated were mostly antitubercular and antiretroviral therapies, reflecting the high burden of HIV and tuberculosis in the study population. ADR-related deaths were significantly associated with poor nutritional status. The majority of ADR-related deaths were preventable, highlighting the need to develop a multidisciplinary approach to closely monitor patients who are prescribed antitubercular and antiretroviral therapies, particularly in patients with hepatic disease, a history of ADRs, who are malnourished and who are exposed to multiple medications.

Lipid-based nutrient supplements do not affect efavirenz but lower plasma nevirapine concentrations in Ethiopian adult HIV patients.

OBJECTIVES: Lipid-based nutrient supplements (LNSs) are increasingly used in HIV programmes in resource-limited settings. However, the possible effects of LNSs on the plasma concentrations of antiretroviral drugs have not been assessed. Here, we aimed to assess the effects of LNSs on plasma efavirenz and nevirapine trough concentrations in Ethiopian adult HIV-infected patients. METHODS: The effects of LNSs were studied in adults initiating antiretroviral therapy (ART) in a randomized trial. Patients with body mass index (BMI) > 17 kg/m(2) (n = 282) received daily supplementation of an LNS containing whey (LNS/w), an LNS containing soy (LNS/s) or no LNS. Trough plasma concentrations of efavirenz and nevirapine were measured at 1 and 2 months. Genotyping for 516 G>T and 983 T>C polymorphisms of the cytochrome P450 (CYP) 2B6 locus was performed. Multilevel linear mixed-effects models were used to assess the associations between LNS and plasma efavirenz and nevirapine concentrations. RESULTS: In patients with BMI > 17 kg/m(2), nevirapine concentrations were lower in the LNS/w and LNS/s groups by a median of -2.3 µg/mL [interquartile range (IQR) -3.9; -0.9 µg/mL; P = 0.002] and -2.1 µg/mL (IQR -3.9; -0.9 µg/mL; P = 0.01), respectively, compared with the group not receiving supplements. There were no differences between groups with respect to efavirenz plasma concentrations. The CYP2B6 516 G>T polymorphism was associated with a 5 µg/mL higher plasma efavirenz concentration compared with the wild type (P < 0.0001), while it was not associated with plasma nevirapine concentrations. CONCLUSIONS: Intake of an LNS was associated with lower plasma nevirapine trough concentrations, indicating possible drug-LNS interactions. The clinical relevance of such reductions in nevirapine exposure is not clear. Plasma efavirenz concentration was not affected by the LNS.

Physical activity and capacity at initiation of antiretroviral treatment in HIV patients in Ethiopia.

SUMMARY We described levels of habitual physical activity and physical capacity in HIV patients initiating antiretroviral treatment in Ethiopia and assessed the role of HIV and nutritional indicators on these outcomes. Physical activity energy expenditure (PAEE) and activity levels were measured with combined heart rate and movement sensors. Physical capacity was assessed by grip strength, sleeping heart rate and heart rate economy. Grip strength data was also available from a sex- and age-matched HIV-negative reference group. Median PAEE was 27.9 (interquartile range 17.4-39.8) kJ/kg per day and mean ± s.d. grip strength was 23.6 ± 6.7 kg. Advanced HIV disease predicted reduced levels of both physical activity and capacity; e.g. each unit viral load [log(1+copies/ml)] was associated with -15% PAEE (P < 0.001) and -1.0 kg grip strength (P < 0.001). Grip strength was 4.2 kg lower in patients compared to HIV-negative individuals (P < 0.001). Low body mass index (BMI) predicted poor physical activity and capacity independently of HIV status, e.g. BMI <16 was associated with -42% PAEE (P < 0.001) and -6.8 kg grip strength (P < 0.001) compared to BMI ≥18.5. The study shows that advanced HIV and malnutrition are associated with considerably lower levels of physical activity and capacity in patients at initiation of antiretroviral treatment.

Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis: a diagnostic evaluation study.

OBJECTIVES: The diagnosis of extrapulmonary tuberculosis (EPTB) is often made on clinical suspicion alone, resulting in both under- and overdiagnosis and relatively poor outcomes. In this study, we evaluated the clinical utility of the Xpert MTB/RIF on routinely collected extrapulmonary specimens in Ethiopia. METHODS: This study was carried out at Jimma University Specialized Hospital, Southwest Ethiopia. Extrapulmonary specimens were collected from 572 patients clinically suspected of suffering from EPTB. All specimens were tested for TB by smear microscopy, culture, and Xpert MTB/RIF. The diagnostic accuracy of Xpert MTB/RIF was calculated and compared to a composite reference standard (CRS), comprising clinical and laboratory results. RESULTS: In total, 572 extrapulmonary specimens (279 lymph node, 159 pleural, 80 peritoneal, 45 cerebrospinal, and nine pericardial fluids) were tested. The pooled sensitivity and specificity of Xpert MTB/RIF were calculated to be 75% (95% CI 70-80) and 98% (95% CI 97-100) respectively when compared to the CRS. The highest sensitivity was documented for lymph node specimens (90%; 95% CI 86-94), moderate sensitivity for cerebrospinal fluid (53%; 95% CI 28-79), while the sensitivity was lowest for pleural (30%; 95% CI 17-44) and peritoneal (32%; 95% CI 12-51) fluids. Xpert MTB/RIF in addition detected rifampicin resistance in 13 patients, in perfect agreement with results from the line probe assay. CONCLUSIONS: Xpert MTB/RIF may be used as initial diagnostic tool for testing of lymph node specimens from patients suspected of having TB lymphadenitis. The added value of Xpert MTB/RIF to diagnose pleural or peritoneal TB is limited by its poor sensitivity.