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Journal articleChakravorty S, Williams TN, 2015,
Sickle cell disease: A neglected chronic disease of increasing global health importance
, Archives of Disease in Childhood, Vol: 100, Pages: 48-53 -
Journal articleKiguli J, 2015,
Anaemia and blood transfusion in African children presenting to hospital with severe febrile illness
, BMC Medicine, Vol: 13 -
Journal articleRockett KA, Clarke GM, Fitzpatrick K, et al., 2014,
Reappraisal of known malaria resistance loci in a large multicenter study
, Nature Genetics, Vol: 46, Pages: 1197-1204, ISSN: 1061-4036Many human genetic associations with resistance to malaria have been reported, but few have been reliably replicated. We collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 controls from 12 locations in Africa, Asia and Oceania. We tested 55 SNPs in 27 loci previously reported to associate with severe malaria. There was evidence of association at P < 1 × 10−4 with the HBB, ABO, ATP2B4, G6PD and CD40LG loci, but previously reported associations at 22 other loci did not replicate in the multicenter analysis. The large sample size made it possible to identify authentic genetic effects that are heterogeneous across populations or phenotypes, with a striking example being the main African form of G6PD deficiency, which reduced the risk of cerebral malaria but increased the risk of severe malarial anemia. The finding that G6PD deficiency has opposing effects on different fatal complications of P. falciparum infection indicates that the evolutionary origins of this common human genetic disorder are more complex than previously supposed.
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Journal articleStreatfield PK, Alam N, Compaoré Y, et al., 2014,
Pregnancy-related mortality in Africa and Asia: evidence from INDEPTH Health and Demographic Surveillance System sites
, Global Health Action, Vol: 7, ISSN: 1654-9880BACKGROUND: Women continue to die in unacceptably large numbers around the world as a result of pregnancy, particularly in sub-Saharan Africa and Asia. Part of the problem is a lack of accurate, population-based information characterising the issues and informing solutions. Population surveillance sites, such as those operated within the INDEPTH Network, have the potential to contribute to bridging the information gaps. OBJECTIVE: To describe patterns of pregnancy-related mortality at INDEPTH Network Health and Demographic Surveillance System sites in sub-Saharan Africa and southeast Asia in terms of maternal mortality ratio (MMR) and cause-specific mortality rates. DESIGN: Data on individual deaths among women of reproductive age (WRA) (15-49) resident in INDEPTH sites were collated into a standardised database using the INDEPTH 2013 population standard, the WHO 2012 verbal autopsy (VA) standard, and the InterVA model for assigning cause of death. RESULTS: These analyses are based on reports from 14 INDEPTH sites, covering 14,198 deaths among WRA over 2,595,605 person-years observed. MMRs varied between 128 and 461 per 100,000 live births, while maternal mortality rates ranged from 0.11 to 0.74 per 1,000 person-years. Detailed rates per cause are tabulated, including analyses of direct maternal, indirect maternal, and incidental pregnancy-related deaths across the 14 sites. CONCLUSIONS: As expected, these findings confirmed unacceptably high continuing levels of maternal mortality. However, they also demonstrate the effectiveness of INDEPTH sites and of the VA methods applied to arrive at measurements of maternal mortality that are essential for planning effective solutions and monitoring programmatic impacts.
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Journal articleStreatfield PK, Khan WA, Bhuiya A, et al., 2014,
HIV/AIDS-related mortality in Africa and Asia: evidence from INDEPTH health and demographic surveillance system sites
, Global Health Action, Vol: 7, ISSN: 1654-9880BACKGROUND: As the HIV/AIDS pandemic has evolved over recent decades, Africa has been the most affected region, even though a large proportion of HIV/AIDS deaths have not been documented at the individual level. Systematic application of verbal autopsy (VA) methods in defined populations provides an opportunity to assess the mortality burden of the pandemic from individual data. OBJECTIVE: To present standardised comparisons of HIV/AIDS-related mortality at sites across Africa and Asia, including closely related causes of death such as pulmonary tuberculosis (PTB) and pneumonia. DESIGN: Deaths related to HIV/AIDS were extracted from individual demographic and VA data from 22 INDEPTH sites across Africa and Asia. VA data were standardised to WHO 2012 standard causes of death assigned using the InterVA-4 model. Between-site comparisons of mortality rates were standardised using the INDEPTH 2013 standard population. RESULTS: The dataset covered a total of 10,773 deaths attributed to HIV/AIDS, observed over 12,204,043 person-years. HIV/AIDS-related mortality fractions and mortality rates varied widely across Africa and Asia, with highest burdens in eastern and southern Africa, and lowest burdens in Asia. There was evidence of rapidly declining rates at the sites with the heaviest burdens. HIV/AIDS mortality was also strongly related to PTB mortality. On a country basis, there were strong similarities between HIV/AIDS mortality rates at INDEPTH sites and those derived from modelled estimates. CONCLUSIONS: Measuring HIV/AIDS-related mortality continues to be a challenging issue, all the more so as anti-retroviral treatment programmes alleviate mortality risks. The congruence between these results and other estimates adds plausibility to both approaches. These data, covering some of the highest mortality observed during the pandemic, will be an important baseline for understanding the future decline of HIV/AIDS.
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Journal articleMurray CJL, Ortblad KF, Guinovart C, et al., 2014,
Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
, Lancet, Vol: 384, Pages: 1005-1070, ISSN: 1474-547XBackgroundThe Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration.MethodsTo estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010–13) of incidence, drug resistance, and coverage of insecticide-treated bednets.FindingsGlobally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the
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Journal articleHoste AD, 2014,
Four phases of intravenous fluid therapy: A conceptual model
, British Journal of Anaesthesia, Vol: 113, Pages: 740-747, ISSN: 1471-6771I.V. fluid therapy plays a fundamental role in the management of hospitalized patients. While the correct use of i.v. fluids can be lifesaving, recent literature demonstrates that fluid therapy is not without risks. Indeed, the use of certain types and volumes of fluid can increase the risk of harm, and even death, in some patient groups. Data from a recent audit show us that the inappropriate use of fluids may occur in up to 20% of patients receiving fluid therapy. The delegates of the 12th Acute Dialysis Quality Initiative (ADQI) Conference sought to obtain consensus on the use of i.v. fluids with the aim of producing guidance for their use. In this article, we review a recently proposed model for fluid therapy in severe sepsis and propose a framework by which it could be adopted for use in most situations where fluid management is required. Considering the dose–effect relationship and side-effects of fluids, fluid therapy should be regarded similar to other drug therapy with specific indications and tailored recommendations for the type and dose of fluid. By emphasizing the necessity to individualize fluid therapy, we hope to reduce the risk to our patients and improve their outcome.
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Journal articleObonyo N, Maitland K, 2014,
Fluid management of shock in severe malnutrition: what is the evidence for current guidelines and what lessons have been learned from clinical studies and trials in other pediatric populations?
, Food and Nutrition Bulletin, Vol: 35, Pages: S71-78, ISSN: 0379-5721Management of shock in children with severe malnutrition remains controversial. To date, the evidence supporting either benefit or harm of fluid resuscitation or rehydration is weak. This issue, however, is not unique to children with severe malnutrition; pediatric guidelines worldwide have a weak level of evidence and remain unsupported by appropriate clinical studies. In this review we give an overview of the current recommendations in other pediatric populations and appraise the strength of evidence supporting these. We summarize results from the only controlled trial ever undertaken, FEAST (Fluid Expansion As Supportive Therapy), which was conducted in resource-poor hospitals involving 3,141 African children with severe febrile illnesses and shock, including large subgroups with sepsis and malaria but excluding children with severe malnutrition. This high-quality trial provided robust evidence that fluid resuscitation increased the risk of death, leading to an excess mortality of 3 in every 100 children receiving fluid boluses, compared with controls receiving no boluses. These findings may have particular relevance to management of septic shock in children with severe malnutrition. However, they cannot be extrapolated to children with gastroenteritis, since this condition was not included in the trial. Current observational studies under way in East Africa may provide insights into myocardial and hemodynamic function in severe malnutrition, including responses to fluid challenge in those complicated by gastroenteritis. Such studies are an essential step for setting the research agenda regarding fluid management of shock in severe malnutrition.
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Journal articleKotlyar S, Nteziyaremye J, Olupot-Olupot P, et al., 2014,
Spleen volume and clinical disease manifestations of severe <i>Plasmodium falciparum</i> malaria in African children
, TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, Vol: 108, Pages: 283-289, ISSN: 0035-9203- Author Web Link
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Journal articleOlupot-Olupot K, Engoru C, Thompson J, et al., 2014,
Phase II trial of standard versus increased transfusion volume in Ugandan children with acute severe anemia
, BMC Medicine, Vol: 12, ISSN: 1741-7015Background: Severe anemia (SA, hemoglobin <6 g/dl) is a leading cause of pediatric hospital admission in Africa,with significant in-hospital mortality. The underlying etiology is often infectious, but specific pathogens are rarelyidentified. Guidelines developed to encourage rational blood use recommend a standard volume of whole blood(20 ml/kg) for transfusion, but this is commonly associated with a frequent need for repeat transfusion and pooroutcome. Evidence is lacking on what hemoglobin threshold criteria for intervention and volume are associatedwith the optimal survival outcomes.Methods: We evaluated the safety and efficacy of a higher volume of whole blood (30 ml/kg; Tx30: n = 78) againstthe standard volume (20 ml/kg; Tx20: n = 82) in Ugandan children (median age 36 months (interquartile range(IQR) 13 to 53)) for 24-hour anemia correction (hemoglobin >6 g/dl: primary outcome) and 28-day survival.Results: Median admission hemoglobin was 4.2 g/dl (IQR 3.1 to 4.9). Initial volume received followed therandomization strategy in 155 (97%) patients. By 24-hours, 70 (90%) children in the Tx30 arm had corrected SAcompared to 61 (74%) in the Tx20 arm; cause-specific hazard ratio = 1.54 (95% confidence interval 1.09 to 2.18, P = 0.01).From admission to day 28 there was a greater hemoglobin increase from enrollment in Tx30 (global P <0.0001).Serious adverse events included one non-fatal allergic reaction and one death in the Tx30 arm. There were sixdeaths in the Tx20 arm (P = 0.12); three deaths were adjudicated as possibly related to transfusion, but nonesecondary to volume overload.Conclusion: A higher initial transfusion volume prescribed at hospital admission was safe and resulted in anaccelerated hematological recovery in Ugandan children with SA. Future testing in a large, pragmatic clinicaltrial to establish the effect on short and longer-term survival is warranted.
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