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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.

BackgroundChildren 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.MethodsWe conducted a prospective study in 257 children presenting with malaria to two hospitals in Kenya and Uganda. We analysed the clinical presentation, endotoxin and cytokine concentration.ResultsEndotoxaemia (endotoxin activity ≥0.4 EAA Units) was observed in 71 (27.6%) children but its presence was independent of both disease severity and outcome. Endotoxaemia was more frequent in children with severe anaemia but not specifically associated with other complications of malaria. Endotoxaemia was associated with a depressed inflammatory and anti-inflammatory cytokine response. Plasma endotoxin levels in severe malaria negatively correlated with IL6, IL10 and TGFβ (Spearman rho: TNFα: r=−0.122, p=0.121; IL6: r=−0.330, p<0.0001; IL10: r=−0.461, p<0.0001; TGFβ: r=−0.173, p<0.027).ConclusionsEndotoxaemia is common in malaria and results in temporary immune paralysis, similar to that observed in patients with sepsis and experimentally-induced endotoxaemia. Intense sequestration of P. falciparum-infected erythrocytes within the endothelial bed of the gut has been observed in pathological studies and may lead to gut-barrier dysfuction. The association of endotoxaemia with the anaemia phenotype implies that it may contribute to the dyserythropoesis accompanying malaria through inflammation. Both of these factors feasibly underpin the susceptibility to EGNO co-infection. Further research is required to investigate this initial finding, with a view to future treatment trials targeting mechanism and appropriate antimicrobial treatment.

BackgroundHypoglycaemia 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.MethodsRetrospective case notes review of all children admitted to hospital with severe falciparum malaria between April 2002 - July 2009, before and after the introduction of the new WHO quinine regimen. Four-hourly bedside glucose levels were measured until intravenous quinine was discontinued. Clinical events immediately preceding or concurrent with each episode of hypoglycaemia (glucose < = 3.0 mmol/l) were recorded.Results954 children received the old quinine regime and 283 received the new regime. We found no evidence of an increased prevalence of hypoglycaemia (< = 3.0 mmol/L) on the new regime compared to former (15% vs. 15%); similar findings were noted for profound hypoglycaemia (< 2.2 mmols/L) 8% v 5%, P = 0.07. Episodes were co-incident with disease severity markers: coma (57%), circulatory failure (38%) and respiratory distress (21%) but less commonly with seizures (10%). Disruption of maintenance fluids and/or blood transfusion concurred with 42% of the hypoglycaemia episodes. Post admission hypoglycaemia increased odds of fatal outcome (24%) compared to euglycaemic counterparts (8%), odds ratio = 3.45 (95% confidence interval = 2.30-5.16) P < 0.01.ConclusionThere was no evidence to indicate a dose relationship between quinine and occurrence of hypoglycaemia. Hypoglycaemia concurred with severity features, disruption of glucose infusion and transfusion. Careful glucose monitoring should be targeted to these complications where resources are limited.

Efficiency gains is a potential strategy to expand Kenyas fiscal space for health. We explored health sector stakeholders understanding of efficiency and their perceptions of the factors that influence the efficiency of county health systems in Kenya. We collected data during a stakeholder engagement workshop. Workshop participants included health sector stakeholders from the national ministry of health and 10 (out 47) county health departments, and non-state actors in Kenya. We divided stakeholders into three groups and carried out facilitated group discussions followed by whole group feedback and discussion session. A total of 25 health sector stakeholders participated. We analysed data using a thematic approach. Health sector stakeholders indicated the need for the outputs and outcomes of a health system to be aligned to community health needs. They felt that both hardware aspects of the system (such as the financial resources, infrastructure, human resources for health) and software aspects of the system (such as health sector policies, public finance management systems, actor relationships) should be considered as inputs in the analysis of county health system efficiency. They also felt that while traditional indicators of health system performance such as intervention coverage or outcomes for infectious diseases, and reproductive, maternal, neonatal and child health (RMNCH) are still relevant, emerging epidemiological trends characterized by an increase in the burden of non-communicable diseases (NCDs) should also be considered. The stakeholders identified public finance management, human resources for health, political interests, corruption, management capacity, and poor coordination as factors that influence the efficiency of county health systems. An in-depth examination of the factors that influence the efficiency of county health systems could illuminate potential policy levers for generating efficiency gains. Mixed methods approaches could facilitate the study of both hardware and software factors that are considered inputs, outputs or factors that influence health system efficiency.

Background Improving health system efficiency is a key strategy to increase health system performance and accelerate progress towards Universal Health Coverage. In 2013, Kenya transitioned into a devolved system of government granting county governments autonomy over budgets and priorities. We assessed the level and determinants of technical efficiency of the 47 county health systems in Kenya. Methods We carried out a two-stage data envelopment analysis (DEA) using Simar and Wilson’s double bootstrap method using data from all the 47 counties in Kenya. In the first stage, we derived the bootstrapped DEA scores using an output orientation. We used three input variables (Public county health expenditure, Private county health expenditure, number of healthcare facilities), and one outcome variable (Disability Adjusted Life Years) using 2018 data. In the second stage, the bias corrected technical inefficiency scores were regressed against 14 exogenous factors using a bootstrapped truncated regression. Results The mean bias-corrected technical efficiency score of the 47 counties was 69.72% (95% CI 66.41–73.01%), indicating that on average, county health systems could increase their outputs by 30.28% at the same level of inputs. County technical efficiency scores ranged from 42.69% (95% CI 38.11–45.26%) to 91.99% (95% CI 83.78–98.95%). Higher HIV prevalence was associated with greater technical inefficiency of county health systems, while higher population density, county absorption of development budgets, and quality of care provided by healthcare facilities were associated with lower county health system inefficiency. Conclusions The findings from this analysis highlight the need for county health departments to consider ways to improve the efficiency of county health systems. Approaches could include prioritizing resources to interventions that will reduce high chronic disease burden, filling structural quality gaps, implementing interventions to improve process quality, identifying the challenges to absorption rates and reforming public finance management systems to enhance their efficiency.

Objective: A previous meta-analysis has shown a consistent survival benefit in children with severe malaria receiving human albumin solution (HAS) compared to other resuscitation fluids.HAS 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.Design: An open-label randomised controlled, phase II safety and efficacy trial. 23/37 (62%) and 25/39 (64%) respectively (p=0.99). Acidosis resolution and respiratory distress was marginally superior in HES group: 3/39 (8%) remained acidotic at 8 hours versus 10/37 (27%) in Dextran arm (p=0.05). There were 4 deaths (5%), two per arm; including 3 deaths in the coma subgroup (3/39, 8%). No other new adverse event was reported. Conclusions:Correction of shock by volume expansion with either Dextran or HES in children with severe malaria acidosis is safe with low mortality, including the highest risk cases admitted in coma. Both solutions present an attractive and practical option for consideration in future volume resuscitation trials in severe malaria.3

Background Efficiency refers the use of resources in ways that optimise desired outcomes. Health system efficiency is a priority concern for policy makers globally as countries aim to achieve universal health coverage, and face the additional challenge of an aging population. Efficiency analysis in the health sector has typically focused on the efficiency of healthcare facilities (hospitals, primary healthcare facilities), with few studies focusing on system level (national or sub-national) efficiency. We carried out a thematic review of literature that assessed the efficiency of health systems at the national and sub-national level. Methods We conducted a systematic search of PubMed and Google scholar between 2000 and 2021 and a manual search of relevant papers selected from their reference lists. A total of 131 papers were included. We analysed and synthesised evidence from the selected papers using a thematic approach (selecting, sorting, coding and charting collected data according to identified key issues and themes). Findings There were more publications from high-and upper middle-income countries (53%) than from low-income and lower middle-income countries. There were also more publications focusing on national level (60%) compared to sub-national health systems' efficiency. Only 6% of studies used either qualitative methods or mixed methods while 94% used quantitative approaches. Data envelopment analysis, a non-parametric method, was the most common methodological approach used, followed by stochastic frontier analysis, a parametric method. A range of regression methods were used to identify the determinants of health system efficiency. While studies used a range of inputs, these generally considered the building blocks of health systems, health risk factors, and social determinants of health. Outputs used in efficiency analysis could be classified as either intermediate health service outputs (e.g., number of health facility visits), single health outcomes (e.g., infant mortality rate) or composite indices of either intermediate outputs of health outcomes (e.g., Health Adjusted Life Expectancy). Factors that were found to affect health system efficiency include demographic and socio-economic characteristics of the population, macro-economic characteristics of the national and sub-national regions, population health and wellbeing, the governance and political characteristics of these regions, and health system characteristics. Conclusion This review highlights the limited evidence on health system efficiency, especially in low-and middle-income countries. It also reveals the dearth of efficiency studies that use mixed methods approaches by incorporating qualitative inquiry. The review offers insights on the drivers of the efficiency of national and sub-national health systems, and highlights potential targets for reforms to improve health system efficiency.