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Find video protocols related to scientific articles indexed in Pubmed.
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 Nutr Bull
PUBLISHED: 07-30-2014
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Management 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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Phase II trial of standard versus increased transfusion volume in Ugandan children with acute severe anemia.
BMC Med
PUBLISHED: 03-17-2014
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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 rarely identified. 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 poor outcome. Evidence is lacking on what hemoglobin threshold criteria for intervention and volume are associated with the optimal survival outcomes.
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Spleen volume and clinical disease manifestations of severe Plasmodium falciparum malaria in African children.
Trans. R. Soc. Trop. Med. Hyg.
PUBLISHED: 03-16-2014
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Plasmodium falciparum malaria is common in African children. Severe disease manifestations include severe malarial anemia (SMA) and cerebral malaria (CM). In vitro studies suggest that splenic sequestration is associated with SMA and protective against CM. We sought to characterize the relationship between ultrasonographically derived spleen volume (SV), clinical manifestations and outcome.
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Invasive bacterial co-infection in African children with Plasmodium falciparum malaria: a systematic review.
BMC Med
PUBLISHED: 01-21-2014
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Severe malaria remains a major cause of pediatric hospital admission across Africa. Invasive bacterial infection (IBI) is a recognized complication of Plasmodium falciparum malaria, resulting in a substantially worse outcome. Whether a biological relationship exists between malaria infection and IBI susceptibility remains unclear. We, therefore, examined the extent, nature and evidence of this association.
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Strategies for efficient computation of the expected value of partial perfect information.
Med Decis Making
PUBLISHED: 01-21-2014
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Expected value of information methods evaluate the potential health benefits that can be obtained from conducting new research to reduce uncertainty in the parameters of a cost-effectiveness analysis model, hence reducing decision uncertainty. Expected value of partial perfect information (EVPPI) provides an upper limit to the health gains that can be obtained from conducting a new study on a subset of parameters in the cost-effectiveness analysis and can therefore be used as a sensitivity analysis to identify parameters that most contribute to decision uncertainty and to help guide decisions around which types of study are of most value to prioritize for funding. A common general approach is to use nested Monte Carlo simulation to obtain an estimate of EVPPI. This approach is computationally intensive, can lead to significant sampling bias if an inadequate number of inner samples are obtained, and incorrect results can be obtained if correlations between parameters are not dealt with appropriately. In this article, we set out a range of methods for estimating EVPPI that avoid the need for nested simulation: reparameterization of the net benefit function, Taylor series approximations, and restricted cubic spline estimation of conditional expectations. For each method, we set out the generalized functional form that net benefit must take for the method to be valid. By specifying this functional form, our methods are able to focus on components of the model in which approximation is required, avoiding the complexities involved in developing statistical approximations for the model as a whole. Our methods also allow for any correlations that might exist between model parameters. We illustrate the methods using an example of fluid resuscitation in African children with severe malaria.
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Management of severe malaria: results from recent trials.
Adv. Exp. Med. Biol.
PUBLISHED: 05-10-2013
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Globally, malaria remains a substantial public health burden with an estimated 349-552 million clinical cases of P. falciparum malaria each year--leading to 780,000 deaths directly attributable to the disease. Whilst the outcome from severe malaria in Africa children remains poor, recent developments in the management of malaria have come from two key sources--the introduction of new, safe and rapidly-effective anti-malarials and high quality evidence from two of the largest clinical trials ever conducted in African children with severe malaria. As a result, the time-honoured anti-malarial treatment for severe malaria, quinine, will now be replaced by artesunate, a water-soluble artemisinin derivative. Supportive care, specifically the management of shock, has been informed by a large late phase clinical trial which concluded that bolus resuscitation is harmful and therefore should be avoided in children with severe malaria, including the high risk group with severe metabolic acidosis and advanced shock.
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Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial.
BMC Med
PUBLISHED: 03-14-2013
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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.
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Endotoxaemia is common in children with Plasmodium falciparum malaria.
BMC Infect. Dis.
PUBLISHED: 02-27-2013
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Children presenting to hospital with recent or current Plasmodium falciparum malaria are at increased the risk of invasive bacterial disease, largely enteric gram-negative organisms (ENGO), which is associated with increased mortality and recurrent morbidity. Although incompletely understood, the most likely source of EGNO is the bowel. We hypothesised that as a result of impaired gut-barrier function endotoxin (lipopolysaccharide), present in the cell-wall of EGNO and in substantial quantities in the gut, is translocated into the bloodstream, and contributes to the pathophysiology of children with severe malaria.
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The words will pass with the blowing wind: staff and parent views of the deferred consent process, with prior assent, used in an emergency fluids trial in two African hospitals.
PLoS ONE
PUBLISHED: 02-11-2013
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To document and explore the views and experiences of key stakeholders regarding the consent procedures of an emergency research clinical trial examining immediate fluid resuscitation strategies, and to discuss the implications for similar trials in future.
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The microbiologic safety of umbilical cord blood transfusion for children with severe anemia in Mombasa, Kenya.
Transfusion
PUBLISHED: 12-21-2011
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Severe anemia requiring blood transfusion is common in hospitalized young children in sub-Saharan Africa but blood is often in short supply. Umbilical cord blood may be a useful source of blood if microbiologic safety concerns can be addressed.
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Dosing regimens of oral ciprofloxacin for children with severe malnutrition: a population pharmacokinetic study with Monte Carlo simulation.
J. Antimicrob. Chemother.
PUBLISHED: 08-10-2011
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Severe malnutrition is frequently complicated by sepsis, leading to high case fatality. Oral ciprofloxacin is a potential alternative to the standard parenteral ampicillin/gentamicin combination, but its pharmacokinetics in malnourished children is unknown.
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Diagnostic performance of visible severe wasting for identifying severe acute malnutrition in children admitted to hospital in Kenya.
Bull. World Health Organ.
PUBLISHED: 05-29-2011
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To determine the diagnostic value of visible severe wasting in identifying severe acute malnutrition at two public hospitals in Kenya.
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Mortality after fluid bolus in African children with severe infection.
N. Engl. J. Med.
PUBLISHED: 05-26-2011
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The role of fluid resuscitation in the treatment of children with shock and life-threatening infections who live in resource-limited settings is not established.
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Excess child mortality after discharge from hospital in Kilifi, Kenya: a retrospective cohort analysis.
Bull. World Health Organ.
PUBLISHED: 04-12-2011
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To explore excess paediatric mortality after discharge from Kilifi District Hospital, Kenya, and its duration and risk factors.
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Use of deferred consent for severely ill children in a multi-centre phase III trial.
Trials
PUBLISHED: 03-31-2011
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Voluntary participation of a subject in research respects a subjects rights, strengthens its ethical conduct, and is formalized by the informed consent process. Clinical trials of life-saving interventions for medical emergencies often necessitate enrollment of patients where prior written individual informed consent is impossible. Although there are regulations and guidelines on protecting subjects in emergency research, these have been criticised for being limited and unnecessarily restrictive. Across Europe and the United States stringent regulations have resulted in a substantial decline of clinical trials involving emergency interventions.
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Likely health outcomes for untreated acute febrile illness in the tropics in decision and economic models; a Delphi survey.
PLoS ONE
PUBLISHED: 02-03-2011
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Modelling is widely used to inform decisions about management of malaria and acute febrile illnesses. Most models depend on estimates of the probability that untreated patients with malaria or bacterial illnesses will progress to severe disease or death. However, data on these key parameters are lacking and assumptions are frequently made based on expert opinion. Widely diverse opinions can lead to conflicting outcomes in models they inform.
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Choice of fluids for resuscitation in children with severe infection and shock: systematic review.
BMJ
PUBLISHED: 09-04-2010
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To systemically review the evidence from clinical trials comparing the use of crystalloids and colloids for fluid resuscitation in children with severe infection.
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Changing trends in blood transfusion in children and neonates admitted in Kilifi District Hospital, Kenya.
Malar. J.
PUBLISHED: 08-06-2010
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Severe anaemia is a common cause for hospitalization in children in sub-Saharan Africa. Malaria plays an important aetiological role, resulting in a substantial burden of paediatric transfusion in hospitals. A decline in malaria and paediatric admissions to the Kilifi District Hospital has been reported recently. This study aimed to investigate whether this trend affected clinical burden, clinical severity of anaemia and requirements for paediatric transfusion.
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Hypoglycaemia in severe malaria, clinical associations and relationship to quinine dosage.
BMC Infect. Dis.
PUBLISHED: 07-30-2010
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Hypoglycaemia is an independent risk factor for death in severe malaria and a recognized adverse treatment effect of parenteral quinine. In 2006 our hospital changed quinine treatment policy from 15 mg/kg loading (plus 10 mg/kg 12-hourly) to 20 mg/kg loading (plus 10 mg/kg 8-hourly) to comply with new WHO guidelines. This presented us with the opportunity to examine whether there was any dose relationship of quinine and hypoglycaemia occurrence.
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Determination of ciprofloxacin in human plasma using high-performance liquid chromatography coupled with fluorescence detection: application to a population pharmacokinetics study in children with severe malnutrition.
J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.
PUBLISHED: 07-09-2010
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Clinical pharmacokinetic studies of ciprofloxacin require accurate and precise measurement of plasma drug concentrations. We describe a rapid, selective and sensitive HPLC method coupled with fluorescence detection for determination of ciprofloxacin in human plasma. Internal standard (IS; sarafloxacin) was added to plasma aliquots (200 ?L) prior to protein precipitation with acetonitrile. Ciprofloxacin and IS were eluted on a Synergi Max-RP analytical column (150 mm×4.6 mm i.d., 5 ?m particle size) maintained at 40°C. The mobile phase comprised a mixture of aqueous orthophosphoric acid (0.025 M)/methanol/acetonitrile (75/13/12%, v/v/v); the pH was adjusted to 3.0 with triethylamine. A fluorescence detector (excitation/emission wavelength of 278/450 nm) was used. Retention times for ciprofloxacin and IS were approximately 3.6 and 7.0 min, respectively. Calibration curves of ciprofloxacin were linear over the concentration range of 0.02-4 ?g/mL, with correlation coefficients (r(2))?0.998. Intra- and inter-assay relative standard deviations (SD) were <8.0% and accuracy values ranged from 93% to 105% for quality control samples (0.2, 1.8 and 3.6 ?g/mL). The mean (SD) extraction recoveries for ciprofloxacin from spiked plasma at 0.08, 1.8 and 3.6 ?g/mL were 72.8±12.5% (n=5), 83.5±5.2% and 77.7±2.0%, respectively (n=8 in both cases). The recovery for IS was 94.5±7.9% (n=15). The limits of detection and quantification were 10 ng/mL and 20 ng/mL, respectively. Ciprofloxacin was stable in plasma for at least one month when stored at -15°C to -25°C and -70°C to -90°C. This method was successfully applied to measure plasma ciprofloxacin concentrations in a population pharmacokinetics study of ciprofloxacin in malnourished children.
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Phase II trial of isotonic fluid resuscitation in Kenyan children with severe malnutrition and hypovolaemia.
BMC Pediatr
PUBLISHED: 06-17-2010
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Children with severe malnutrition who develop shock have a high mortality. Contrary to contemporaneous paediatric practice, current guidelines recommend use of low dose hypotonic fluid resuscitation (half-strength Darrows/5% dextrose (HSD/5D). We evaluated the safety and efficacy of this guideline compared to resuscitation with a standard isotonic solution.
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Phase II trial on the use of Dextran 70 or starch for supportive therapy in Kenyan children with severe malaria.
Crit. Care Med.
PUBLISHED: 06-08-2010
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A previous meta-analysis has shown a consistent survival benefit in children with severe malaria receiving human albumin solution compared to other resuscitation fluids. Human albumin solution is expensive and not readily available in Africa. We examined the safety and efficacy of the fluid resuscitation with two synthetic colloids, Dextran 70 and hydroxyethyl starch, to inform future trial design.
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Iron deficiency and acute seizures: results from children living in rural Kenya and a meta-analysis.
PLoS ONE
PUBLISHED: 04-09-2010
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There are conflicting reports on whether iron deficiency changes susceptibility to seizures. We examined the hypothesis that iron deficiency is associated with an increased risk of acute seizures in children in a malaria endemic area.
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The prognostic value of dipstick urinalysis in children admitted to hospital with severe malnutrition.
Arch. Dis. Child.
PUBLISHED: 04-06-2010
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Children with severe malnutrition (SAM) present to hospital with an array of complications, resulting in high mortality despite adherence to WHO guidelines. Diagnostic resources in developing countries are limited and bedside tests could help identify high-risk children. Dipstick urinalysis is a bedside screening test for urinary tract infections (UTIs). UTIs are common in SAM and can lead to secondary invasive bacterial sepsis. Very few studies have examined the usefulness of dipstick screening of urine specimens in SAM and none has explored its prognostic value.
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Cardiac function and hemodynamics in Kenyan children with severe malaria.
Crit. Care Med.
PUBLISHED: 01-14-2010
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Mortality from severe malaria remains unacceptably high in sub-Saharan Africa. Several markers of cardiovascular compromise and metabolic acidosis correlate with mortality. The role of cardiac dysfunction in the pathogenesis of severe childhood malaria remains unknown.
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The quality of stored umbilical cord and adult-donated whole blood in Mombasa, Kenya.
Transfusion
PUBLISHED: 11-13-2009
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In sub-Saharan Africa umbilical cord blood may be a useful source of blood for transfusion. Before clinical trials, evidence is needed that cord blood donations, which vary greatly in volume, can be collected and stored into a fixed volume of anticoagulant-preservative solution obviating the need for prestorage processing.
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Bacterial contamination of pediatric whole blood transfusions in a Kenyan hospital.
Transfusion
PUBLISHED: 08-04-2009
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Hospitalized children in sub-Saharan Africa frequently receive whole blood transfusions for severe anemia. The risk from bacterial contamination of blood for transfusion in sub-Saharan Africa is not known. This study assessed the frequency of bacterial contamination of pediatric whole blood transfusions at a referral hospital in Kenya.
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Emergency triage assessment for hypoxaemia in neonates and young children in a Kenyan hospital: an observational study.
Bull. World Health Organ.
PUBLISHED: 06-25-2009
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To describe the prevalence of hypoxaemia in children admitted to a hospital in Kenya for the purpose of identifying clinical signs of hypoxaemia for emergency triage assessment, and to test the hypothesis that such signs lead to correct identification of hypoxaemia in children, irrespective of their diagnosis.
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HIV infection, malnutrition, and invasive bacterial infection among children with severe malaria.
Clin. Infect. Dis.
PUBLISHED: 06-25-2009
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Human immunodeficiency virus (HIV) infection, malnutrition, and invasive bacterial infection (IBI) are reported among children with severe malaria. However, it is unclear whether their cooccurrence with falciparum parasitization and severe disease happens by chance or by association among children in areas where malaria is endemic.
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Joint BAPEN and Nutrition Society Symposium on Feeding size 0: the science of starvation. Severe malnutrition: therapeutic challenges and treatment of hypovolaemic shock.
Proc Nutr Soc
PUBLISHED: 06-03-2009
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The systematic failure to recognise and appropriately treat children with severe malnutrition has been attributed to the elevated case-fatality rates, often as high as 50%, that still prevail in many hospitals in Africa. Children admitted to Kilifi District Hospital, on the coast of Kenya, with severe malnutrition frequently have life-threatening features and complications, many of which are not adequately identified or treated by WHO guidelines. Four main areas have been identified for research: early identification and better supportive care of sepsis; evidence-based fluid management strategies; improved antimicrobial treatment; rational use of nutritional strategies. The present paper focuses on the identification of children with sepsis and on fluid management strategies.
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Hypothermia in children with severe malnutrition: low prevalence on the tropical coast of Kenya.
J. Trop. Pediatr.
PUBLISHED: 06-02-2009
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Hypothermia is stated as a common complication of severe malnutrition although there are little primary data to support this. We performed a prospective study of children with severe acute malnutrition (SAM) admitted to a district hospital in Kenya. We documented the prevalence of hypothermia and examined its association with outcome and ambient temperature. During a 2-year period 667 children were recruited. Hypothermia was recorded in only 12 out of 15 191 (0.08%) temperature observations and as a single event in 12 children (2% of cases). There was no correlation with ambient temperature. Although mortality rates were higher in children with hypothermia (4/12, 33%) than those without (121/655, 18%), the timing of hypothermia did not coincide with clinical deterioration. Hypothermia was a rare marker of severity in our setting. We recommend that other observations be highlighted to identify high risk groups and that routine temperature observations be reduced wherever staff are few.
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External financial aid to blood transfusion services in sub-Saharan Africa: a need for reflection.
PLoS Med.
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Jean-Pierre Allain and colleagues argue that, while unintended, the foreign aid provided for blood transfusion services in sub-Saharan Africa has resulted in serious negative outcomes, which requires reflection and rethinking.
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Diagnosing severe falciparum malaria in parasitaemic African children: a prospective evaluation of plasma PfHRP2 measurement.
PLoS Med.
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In African children, distinguishing severe falciparum malaria from other severe febrile illnesses with coincidental Plasmodium falciparum parasitaemia is a major challenge. P. falciparum histidine-rich protein 2 (PfHRP2) is released by mature sequestered parasites and can be used to estimate the total parasite burden. We investigated the prognostic significance of plasma PfHRP2 and used it to estimate the malaria-attributable fraction in African children diagnosed with severe malaria.
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Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria.
Malar. J.
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Plasmodium falciparum histidine-rich protein PFHRP2 measurement is used widely for diagnosis, and more recently for severity assessment in falciparum malaria. The Pfhrp2 gene is highly polymorphic, with deletion of the entire gene reported in both laboratory and field isolates. These issues potentially confound the interpretation of PFHRP2 measurements.
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Diarrhoea complicating severe acute malnutrition in Kenyan children: a prospective descriptive study of risk factors and outcome.
PLoS ONE
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Severe acute malnutrition (SAM) accounts for two million deaths worldwide annually. In those hospitalised with SAM, concomitant infections and diarrhoea are frequent complications resulting in adverse outcome. We examined the clinical and laboratory features on admission and outcome of children with SAM and diarrhoea at a Kenyan district hospital.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.