Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial.

BACKGROUND: Early rapid fluid resuscitation (boluses) in African children with severe febrile illnesses increases the 48-hour mortality by 3.3% compared with controls (no bolus). We explored the effect of boluses on 48-hour all-cause mortality by clinical presentation at enrolment, hemodynamic changes over the first hour, and on different modes of death, according to terminal clinical events. We hypothesize that boluses may cause excess deaths from neurological or respiratory events relating to fluid overload. METHODS: Pre-defined presentation syndromes (PS; severe acidosis or severe shock, respiratory, neurological) and predominant terminal clinical events (cardiovascular collapse, respiratory, neurological) were described by randomized arm (bolus versus control) in 3,141 severely ill febrile children with shock enrolled in the Fluid Expansion as Supportive Therapy (FEAST) trial. Landmark analyses were used to compare early mortality in treatment groups, conditional on changes in shock and hypoxia parameters. Competing risks methods were used to estimate cumulative incidence curves and sub-hazard ratios to compare treatment groups in terms of terminal clinical events. RESULTS: Of 2,396 out of 3,141 (76%) classifiable participants, 1,647 (69%) had a severe metabolic acidosis or severe shock PS, 625 (26%) had a respiratory PS and 976 (41%) had a neurological PS, either alone or in combination. Mortality was greatest among children fulfilling criteria for all three PS (28% bolus, 21% control) and lowest for lone respiratory (2% bolus, 5% control) or neurological (3% bolus, 0% control) presentations. Excess mortality in bolus arms versus control was apparent for all three PS, including all their component features. By one hour, shock had resolved (responders) more frequently in bolus versus control groups (43% versus 32%, P <0.001), but excess mortality with boluses was evident in responders (relative risk 1.98, 95% confidence interval 0.94 to 4.17, P = 0.06) and 'non-responders' (relative risk 1.67, 95% confidence interval 1.23 to 2.28, P = 0.001), with no evidence of heterogeneity (P = 0.68). The major difference between bolus and control arms was the higher proportion of cardiogenic or shock terminal clinical events in bolus arms (n = 123; 4.6% versus 2.6%, P = 0.008) rather than respiratory (n = 61; 2.2% versus 1.3%, P = 0.09) or neurological (n = 63, 2.1% versus 1.8%, P = 0.6) terminal clinical events. CONCLUSIONS: Excess mortality from boluses occurred in all subgroups of children. Contrary to expectation, cardiovascular collapse rather than fluid overload appeared to contribute most to excess deaths with rapid fluid resuscitation. These results should prompt a re-evaluation of evidence on fluid resuscitation for shock and a re-appraisal of the rate, composition and volume of resuscitation fluids. TRIAL REGISTRATION: ISRCTN69856593.

Prevalence of overweight and obesity and associated factors among people living with HIV attending a tertiary care clinic in Uganda.

BACKGROUND: Overweight and obesity are significantly increasing among people living with HIV (PLWH), contributing to the risk of major adverse cardio-metabolic events. However, little is known on its prevalence among PLWH in sub-Saharan Africa. In this study, we report the prevalence and factors associated with overweight and obesity among PLWH in a large tertiary HIV clinic in Kampala, Uganda. METHODS: A cross-sectional, retrospective review of electronic database of all PLWH that attended the Adult Infectious Diseases Institute clinic between November 2018 and April 2019 was conducted. Demographic, body mass index (BMI) [kg/m2] and clinical variables were extracted. Based on BMI, nutritional status was classified as undernutrition (< 18.5kg/m2), normal (≥ 18.5 < 25kg/m2), overweight (≥ 25 < 30kg/m2) and obesity (≥ 30kg/m2). Poisson regression analysis was performed to determine factors associated with overweight and obesity. RESULTS: Overall, 7,818 participants were included in the analysis, 64% (n = 4,976) were female, with a median age of 44 years (interquartile range (IQR): 36-51) and a median BMI of 24.2 (IQR: 21.2-28.1). The prevalence of overweight and obesity combined was 46% (55% female versus 30% male), obesity 18.2% (24.6% female versus 7.1% male) and overweight 27.8% (30.4% female versus 22.9% male). Factors associated with overweight and obesity were: Females (adjusted prevalence ratio [aPR]: 1. 8, 95%CI:1.69-1.87), age category 25-59 years (aPR: 1.9, 95%CI: 1.63-2.24) and ≥ 60 years (aPR: 1.8, 95%CI:1.49-2.12); duration on antiretroviral therapy (ART) for 6-10 years (aPR: 1.1, 95%CI:1.08-1.18), CD4 count 200-500 (aPR:0.08, 95%CI:0.01-0.15) and > 500 (aPR:0.46, 95%CI:0.39-0.54) and having at least one noncommunicable disease (NCD) (aPR: 1.1, 95%CI:1.07-1.18). CONCLUSION: There is a high burden of overweight and obesity among PLWH in Uganda. Nutrition and weight management programs particularly targeting high risk groups such as females and persons with underlying NCDs should be integrated into HIV care.

Chronic obstructive pulmonary disease prevalence and associated factors in an urban HIV clinic in a low income country.

INTRODUCTION: In the last decade, survival of people living with HIV (PLHIV) has dramatically increased due wide availability of effective antiretroviral therapy. However, PLHIV remain at a comparatively higher risk of non-communicable comorbidities. We sought to determine the burden of COPD and its associations in an urban tertiary HIV clinic in Uganda. METHODS AND FINDINGS: HIV-infected adults attending the Makerere University Joint AIDS program; aged ≥30 years without acute ailments were screened for COPD using study questionnaires and spirometry (post-bronchodilator FEV1/FVC<0.7). We determined its prevalence and association with demographic characteristics, body mass index (BMI) and known risk factors. Of 288 participants enrolled, 177 (61%) were female; 253 (88%) were from urban residences, median age was 45 years (IQR: 39-51), 71(25%) were 'ever' smokers, 284(99%) reported biomass fuel use and 72(25%) had a history of tuberculosis. All except 1 participant were on antiretroviral therapy, median current CD4 (cells/mm3) was 558 (IQR 402-753) and 275(96%) were virologically suppressed. Nearly half (130/288, 45%) had recurrent respiratory symptoms. The prevalence of COPD was 3.1% (9/288) [95% CI: 1.63-5.92]. COPD was associated with: previous tuberculosis, (adjusted odds ratio (AOR): 6.36, [95% CI 1.64-35.84], P = 0.036), self-reported chronic shortness of breath (AOR: 9.06, [95% CI 1.34-61.10], P = 0.024) and a BMI <21 Kg/m2 (AOR: 10.42 [95% CI: 1.61-100.00], P = 0.013). CONCLUSION: In this HIV population, COPD prevalence was low and was associated with previous tuberculosis, self-reported chronic shortness of breath and BMI <21 Kg/m2.