The effect of an early resuscitation protocol on sepsis outcomes in developing countries remains unknown.OBJECTIVE To determine whether an early resuscitation protocol with administration of intravenous fluids, vasopressors, and blood transfusion decreases mortality among Zambian adults with sepsis and hypotension compared with usual care. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of 212 adults with sepsis (suspected infection plus Ն2 systemic inflammatory response syndrome criteria) and hypotension (systolic blood pressure Յ90 mm Hg or mean arterial pressure Յ65 mm Hg) presenting to the emergency department at a 1500-bed referral hospital in Zambia between
The rising prevalence of noncommunicable diseases globally, with a strikingly disproportionate increase in prevalence and related mortality in low- and middle-income countries (LMICs), is a major threat to sustainable development. The epidemiologic trend of cancers in LMICs is of particular concern. Despite a lower incidence of cancer in LMICs compared with high-income countries, total cancer-related mortality is significantly higher in LMICs, especially in people younger than 65 years of age. The enormous economic impact of premature mortality and lost productive life years highlights the critical importance of galvanizing cancer prevention and management to achieve sustainable development. The rising burden of cancer in LMICs stresses an already weak health care and economic infrastructure and poses unique challenges. Although the WHO acknowledges that the effective management of cancer relies on early detection, accurate diagnosis, and access to appropriate multimodal therapy, the placement of priority on early detection cannot be assumed to be effective in LMICs, where limited downstream resources may be overwhelmed by the inevitable increases in number of diagnoses. This review discusses several factors and considerations that may compromise the success of cancer control programs in LMICs, particularly if the focus is only on early detection through screening and surveillance. It is intended to guide optimal implementation of cancer control programs by accentuating challenges common in LMICs and by emphasizing the importance of cancer prevention where relevant so that communities and stakeholders can work together to devise optimal means of combatting the growing burden of cancer.
of inflammatory response in relation to malnutrition syndromes is described. This discussion serves to highlight a research agenda to address deficiencies in diagnostics, biomarkers, and therapeutics of inflammation in relation to malnutrition. (JPEN J Parenter Enteral Nutr. 2009;33:710-716)
BackgroundThere exist significant challenges to the receipt of comprehensive oncologic treatment for children diagnosed with cancer in sub-Saharan Africa. To better define those challenges, we investigated treatment outcomes and risk factors for treatment abandonment in a cohort of children diagnosed with cancer at the University Teaching Hospital (UTH), the site of the only pediatric oncology ward in Zambia.MethodsUsing an established database, a retrospective cohort study was conducted of children aged 0–15 years admitted to the pediatric oncology ward between July 2008 and June 2010 with suspected cancer. Diagnosis, mode of diagnosis, treatment outcome, and risk factors for abandonment of treatment were abstracted from this database and clinical medical records.ResultsAmong 162 children treated at the UTH during the study time period that met inclusion criteria, only 8.0% completed a treatment regimen with most of the patients dying during treatment or abandoning care. In multivariable analysis, shorter distance from home to the UTH was associated with a lower risk of treatment abandonment (Adjusted Odds Ratio [aOR] = 0.48 (95% confidence interval [CI] 0.23–0.97). Conversely maternal education less than secondary school was associated with increased risk for abandonment (aOR = 1.65; 95% CI 1.05–2.58).ConclusionsDespite availability of dedicated pediatric oncology treatment, treatment completion rates are poor, due in part to the logistical challenges faced by families, low educational status, and significant distance from the hospital. Alternative treatment delivery strategies are required to bring effective pediatric oncology care to the patients in need, as their ability to come to and remain at a central tertiary care facility for treatment is limited. We suggest that the extensive system now in place in most of sub-Saharan Africa that sustains life-long antiretroviral therapy for children with human immunodeficiency virus (HIV) infection be adapted for pediatric cancer treatment to improve outcome.
To assess the efficacy of a simple, goal-directed sepsis treatment protocol for reducing mortality in patients with severe sepsis in Zambia.
Single center non-blinded randomized controlled trial
Emergency room, ICU, and medical wards of the national referral hospital in Lusaka, Zambia
112 patients enrolled within 24 hours of admission with severe sepsis, defined as systemic inflammatory response syndrome with suspected infection and organ dysfunction
Simplified Severe Sepsis Protocol (SSSP) consisting of up to 4 liters of intravenous fluids within 6 hours, guided by jugular venous pressure assessment, and dopamine and/or blood transfusion in selected patients. Control group was managed as usual care. Blood cultures were collected and early antibiotics administered for both arms.
Measurements and Main Results
Primary outcome was in-hospital all-cause mortality. 109 patients were included in the final analysis. 88 (80.7%) were HIV positive. Pulmonary infections were the most common source of sepsis. In-hospital mortality rate was 64.2% in the intervention group and 60.7% in the control group (RR 1.05, 95%CI:0.79-1.41). Mycobacterium tuberculosis complex was isolated from 31 of 82 (37.8%) HIV positive patients with available mycobacterial blood culture results. SSSP patients received significantly more IV fluids in the first 6 hours (2.7 liters vs. 1.7 liters, p=0.002). The study was stopped early because of high mortality rate among patients with hypoxemic respiratory failure in the intervention arm (8/8, 100%) compared with the control arm [7/10, 70%, RR 1.43 (95%CI:0.95-2.14)].
Factors other than tissue hypoperfusion probably account for much of the end organ dysfunction in African patients with severe sepsis. Studies of fluid-based interventions should utilize inclusion criteria to accurately capture patients with hypovolemia and tissue hypoperfusion who are most likely to benefit from fluids. Exclusion of patients with severe respiratory distress should be considered when ventilator support is not readily available.
Access to antiretroviral therapy (ART) for HIV infection has expanded rapidly throughout sub-Saharan Africa, but malnutrition and food insecurity have emerged as major barriers to program success. Protein-calorie malnutrition (a common form in the region) hastens HIV disease progression, and food insecurity is a barrier to medication adherence. Analyses of patient outcomes have identified a low body mass index (BMI) at ART initiation as an independent predictor of early mortality, but the causes of low BMI are multi-factorial may represent normal anthropometric variation, chronic inadequate food intake, or wasting associated with HIV and other infections. While there is much experience population-level humanitarian food assistance, few data exist to measure the effectiveness of macronutrient supplementation or to identify individuals most likely to benefit. In this report, we review the current evidence supporting macronutrient supplementation for HIV-infected adults; clinical trials in resource-adequate and resource-constrained settings; and highlight priority areas for future research.
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