A Cost-Effectiveness Analysis for Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis Prophylaxis in the United States.

BACKGROUND & AIMS: Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is the most common adverse event after endoscopic retrograde cholangiopancreatography, and is responsible for substantial morbidity and health care expenditures of at least $200 million. Therapies for PEP prevention include pancreatic stent placement (PSP), rectal indomethacin, sublingual nitrates, and aggressive lactated Ringer's hydration. Our objective was to determine which PEP prophylactic strategies are cost effective. METHODS: We developed 2 separate decision trees to evaluate PEP prophylactic strategies. The first, in high-risk patients, compared rectal indomethacin, PSP, PSP with indomethacin, sublingual nitrates, aggressive hydration with lactated Ringer's, and no prophylaxis. The second, in average-risk patients, compared rectal indomethacin, sublingual nitrates, aggressive hydration, and no prophylaxis. We used incidence rates, transition probabilities, and costs from publications and public data sources. Outcome measures were reported as incremental cost-effectiveness ratios, with a willingness-to-pay (WTP) threshold of $100,000/quality-adjusted life years (QALYs). RESULTS: Compared with no prophylaxis, all strategies were cost effective at a WTP of $100,000 in preventing PEP in high-risk patients. When directly compared with each other, rectal indomethacin was the cost-effective strategy in high-risk patients ($31,589/QALYs). In average-risk patients, indomethacin and sublingual nitrates were cost effective at a WTP of $100,000/QALYs compared with no prophylaxis. When directly compared with each other, rectal indomethacin was the cost-effective strategy ($53,016/QALYs). CONCLUSIONS: Rectal indomethacin was the cost-effective strategy for preventing PEP in both average-risk and high-risk patients undergoing endoscopic retrograde cholangiopancreatography. All strategies were cost effective when compared with no prophylaxis in high-risk patients, whereas all strategies except for aggressive hydration with lactated Ringer's were cost effective in average-risk patients. Further studies are needed to improve the utilization of PEP prevention strategies.

Practice patterns of post-ERCP pancreatitis prophylaxis techniques in the United States: a survey of advanced endoscopists.

BACKGROUND AND AIMS: The American Society for Gastrointestinal Endoscopy recommends prophylactic pancreatic duct stent placement (PPS) and rectal nonsteroidal anti-inflammatory drugs (NSAIDs) to reduce the incidence and severity of post-ERCP pancreatitis (PEP) in high-risk individuals and suggests that rectal indomethacin may decrease the risk and severity of PEP in average-risk individuals. The European Society for Gastrointestinal Endoscopy recommends rectal indomethacin for all patients undergoing ERCP. Previous surveys of European endoscopists revealed low adoption of PPS or rectal NSAIDs to prevent PEP. We sought to capture current practice in the prevention of PEP among endoscopists in the United States involved in advanced endoscopy fellowship programs. METHODS: An anonymous online 16-item survey was e-mailed to 233 advanced endoscopists involved in advanced endoscopy fellowship programs. RESULTS: Of the 233 endoscopists who were invited to participate, 62 responded (26.7%). Most respondents reported working in tertiary referral centers (57; 95.0%) and performing ERCP for greater than 5 years (44; 74.6%). All respondents (60; 100.0%) reported working with fellows. Most PPS users (41; 72.0%) reported use of PPS in high-risk patients only and using PPS for PEP in ≤25% of ERCPs (38; 64.4%). Most respondents reported using rectal NSAIDs for high-risk patients only (34; 59.7%) compared with respondents (23; 40.1%) who reported using rectal NSAIDs for prevention of PEP in average-risk patients undergoing ERCP. Most respondents (49; 83.0%) also reported using rapid intravenous fluids to prevent PEP. CONCLUSIONS: Among endoscopists involved in advanced endoscopy fellowships in the United States, rectal NSAIDs are used more frequently than PPS in the prevention of PEP. Despite mounting evidence supporting the use of rectal NSAIDs to prevent PEP in average-risk patients, less than half of the respondents in this survey reported such practice.

Four percent formalin application for the management of radiation proctitis in carcinoma cervix patients: An effective, safe, and economical practice.

CONTEXT: Radiotherapy is a very effective treatment modality for pelvic malignancies such as carcinoma of the cervix. However, it is quite common for chronic radiation proctitis (CRP) to manifest after radical radiotherapy. CRP is a source of significant morbidity, and there is a lack of effective treatment modalities. There also exists a general lack of guidelines on management of CRP. AIMS: To assess the benefit from 4% formalin application for the treatment of Grade >2 CRP among patients previously treated with radical radiotherapy for cervical carcinoma. SETTINGS AND DESIGN: This retrospective descriptive study involved 29 eligible patients who were treated from November 2010 - November 2015 for CRP with 4% formalin application. MATERIALS AND METHODS: Of the 1864 patients of carcinoma cervix treated during the said patients, 29 patients fulfilled the eligibility criteria. Eligible patients were invited telephonically for follow-up and were assessed for response and complications of the procedure. RESULTS: The treatment of hemorrhagic radiation proctitis with local formalin instillation is effective, well tolerated and safe procedure. The procedure is inexpensive, technically simple and can be done on an outpatient basis. 62% patients had complete freedom from rectal bleed, while 34.5% patients had partial benefit. Only one patient required diversion colostomy for persistent bleeding.

Household costs and time to treatment for children with severe febrile illness in rural Burkina Faso: the role of rectal artesunate.

BACKGROUND: Community health workers (CHWs) were trained to identify children with malaria who could not take oral medication, treat them with rectal artesunate (RA) and refer them to the closest healthcare facility to complete management. However, many children with such symptoms did not seek CHWs' care. The hypothesis was that the cost of referral to a health facility was a deterrent. The goal of this study was to compare the out-of-pocket costs and time to seek treatment for children who sought CHW care (and received RA) versus those who did not. METHODS: Children with symptoms of severe malaria receiving RA at CHWs and children with comparable disease symptoms who did not go to a CHW were identified and their parents were interviewed. Household out-of-pocket costs per illness episode and speed of treatment were evaluated and compared between RA-treated children vs. non-RA treated children and by central nervous symptoms (CNS: repeated convulsions, altered consciousness or coma). RESULTS: Among children with CNS symptoms, costs of RA-treated children were similar to those of non-RA treated children ($5.83 vs. $4.65; p = 0.52), despite higher transport costs ($2.74 vs. $0.91; p < 0.0001). However, among children without CNS symptoms, costs of RA-treated children were higher than the costs of non-RA treated children with similar symptoms ($5.62 vs. $2.59; p = 0.0001), and the main driver of the cost difference was transport. After illness onset, CNS children reached CHWs for RA an average of 9.0 h vs. 16.1 h for non-RA treated children reaching first treatment [difference 7.1 h (95% CI - 1.8 to 16.1), p = 0.11]. For non-CNS patients the average time to CHW-delivered RA treatment was 12.2 h vs. 20.1 h for those reaching first treatment [difference 7.9 h (95% CI 0.2-15.6), p = 0.04]. More non-RA treated children developed CNS symptoms before arrival at the health centre but the difference was not statistically significant (6% vs. 4%; p = 0.58). CONCLUSIONS: Community health worker-delivered RA does not affect the total out-of-pocket costs when used in children with CNS symptoms, but is associated with higher total out-of-pocket costs when used in children with less severe symptoms. RA-treated children sought treatment more quickly.

Evaluation of the Macy Catheter®: a rectal catheter for rapid medication and fluid administration.

INTRODUCTION: Health care providers are increasingly challenged to balance cost considerations for devices, drugs, and staffing all while continuing to provide excellent care. Patients in both the post-acute and acute care settings often require fluid and/or medication when their oral route is compromised and vascular access may not be warranted or immediately accessible. The rectum is an underutilized administration point that can be accessed with speed and relative ease. Areas Covered: Literature reviews of pharmaceutical, medical, and nursing references reveal current and historical science that validates the rectal route as a means of alternative administration for fluids and medications. Expert Commentary: Historically the rectum has been used for medication and fluid delivery but in more recent times, use has waned due to many factors. The physiology of the rectum allows for rapid and reliable administration of a variety of medications as well as hydration. This serves as an introduction to a novel, simple, cost effective device that allows for discreet and painless rectal administration of fluids and medications when the oral route is compromised and/or intravenous access is difficult or unnecessary. This device is used in a variety of patients in many care settings.

A Cost and Quality Analysis of Utilizing a Rectal Catheter for Medication Administration in End-of-Life Symptom Management.

Technology that can improve the ability to provide quick symptom control while decreasing the cost and burden of care could help hospice agencies deal with current hospice industry challenges. This paper describes how the use of a new rectal medication delivery technology at a large hospice in western New York has improved patient care and nursing efficiency while at the same time decreasing the cost of care.

Midazolam vs diazepam in prolonged seizures in children: A pharmacoeconomic approach.

OBJECTIVE: A previous European cost-utility study reported that use of buccal midazolam in the community setting for the treatment of prolonged seizures (ie, seizures lasting ≥5 minutes) in children was associated with an overall €12 507 399 reduction in annual costs charged to the Italian national health service compared with rectal diazepam. We re-evaluated these findings by applying a more conservative approach. METHODS: The Italian Delphi panel reconvened to apply a more conservative assessment of available reports. A decision-tree model was used, allowing for different treatment pathways depending on whether or not a caregiver administers treatment, an ambulance is required for transport of the child to hospital, and an inpatient stay is required. Direct medical costs were derived from Italian healthcare system data. Estimates of the annual number of prolonged tonic-clonic seizures expected in the country were based on studies which assessed seizure duration using video-EEG recordings and medical records. RESULTS: Although drug acquisition costs were greater for buccal midazolam than for rectal diazepam, the acquisition cost difference was outweighed by larger cost savings resulting mostly from a reduction in hospital admissions. Assuming that 1.2% of tonic and/or clonic seizures occurring in children and adolescents over a 12-month period are prolonged, the annual nationwide reduction in costs from preferring buccal midazolam to rectal diazepam was estimated at €3 577 587.9. CONCLUSIONS: In this more conservative revised analysis, the high cost of buccal midazolam is still counteracted by greater cost savings compared with rectal diazepam, but cost reduction was less than previously estimated.

Healthcare Utilization Characteristics for Intranasal Midazolam Versus Rectal Diazepam.

To investigate connections between patient demographics, health care utilization, prescription use, and refills for patients using intranasal midazolam, per rectum diazepam, or both. A retrospective cohort contained patients with epilepsy prescribed intranasal midazolam, per rectum diazepam, or both. We analyzed number of emergency department visits, ambulance services, urgent care visits, and unplanned hospitalizations. A total of 5458 patients were identified. Patients on intranasal midazolam had on average 1.53 fewer emergency department visits (95% confidence interval 1.16-1.89, P < .0001), 0.29 fewer uses of ambulance services (95% confidence interval 0.17-0.41, P < .0001), and 0.60 fewer urgent care visits (95% confidence interval 0.36-0.83, P < .0001) compared to patients in the per rectum diazepam group. Patients with commercial insurance were more likely to have intranasal midazolam prescription (odds ratio = 1.73, 95% confidence interval 1.42-2.11, P < .0001). The results substantiate the cost-effective benefits of prescribing intranasal midazolam compared to per rectum diazepam because several aspects of health care utilization were decreased in those using intranasal midazolam.

Rectal indomethacin or intravenous gabexate mesylate as prophylaxis for acute pancreatitis post-endoscopic retrograde cholangiopancreatography.

OBJECTIVE: We aimed to evaluate the results in our case series of AP ERCP over the last three years. The prophylaxis for acute pancreatitis (AP) post-endoscopic retrograde cholangiopancreatography (ERCP) consists of rectal indomethacin, but some studies are not concordant. PATIENTS AND METHODS: We compared 241 ERCP performed from January 2014 to February 2015 with intravenous gabexate mesylate (Group A), with the 387 ERCP performed from March 2015 to December 2016 with rectal indomethacin (Group B) as prophylaxis for AP post-ERCP. RESULTS: There were 8 (3.31%) AP post-ERCP in Group A vs. 4 (1.03%) in Group B. CONCLUSIONS: Rectal indomethacin shows a better statistically significant performance than intravenous gabexate mesylate in the prophylaxis of AP post-ERCP, besides being cheaper.

Prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a cost-effectiveness analysis.

OBJECTIVES: The aim of the present study was to perform a comparative cost-effectiveness analysis of the different strategies used to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis. METHODS: We performed a cost-effectiveness decision analysis of 4 prophylactic strategies (nonsteroidal anti-inflammatory drugs or NSAIDs, pancreatic stent, stent plus rectal indomethacin, and no prophylaxis) in a simulated cohort of 300 patients during 1 year. Treatment effectiveness was defined as the number of patients who did not develop post-ERCP pancreatitis. RESULTS: The baseline costs of each strategy were as follows: rectal NSAID $359,098, pancreatic stent $426,504, stent plus rectal indomethacin $479,153, and no prophylaxis $491,275. The mean number of cases developing post-ERCP pancreatitis was 16, 21, 23, and 37 for the strategies rectal NSAID, pancreatic stent, stent plus rectal indomethacin, and no prophylaxis, respectively. Taking rectal NSAID prophylaxis as the reference strategy, the odds ratio of an episode of post-ERCP acute pancreatitis after pancreatic stent placement was 1.33 (95% confidence interval [CI], 0.68-2.61); after stent plus indomethacin, it was 1.40 (95% CI, 0.72-2.73), and after no prophylaxis, it was 2.49 (95% CI, 1.35-4.59). CONCLUSIONS: Rectal NSAID administration proved to be the most cost-effective prophylactic strategy used to prevent post-ERCP pancreatitis. The strategy of no prophylaxis for this complication should be avoided.

Assessment of pharmacokinetics and tolerability of intranasal diazepam relative to rectal gel in healthy adults.

Diazepam rectal gel (RG) is currently the only approved rescue therapy for outpatient management of seizure clusters in the United States. There is an unmet medical need for an alternative rescue therapy for seizure clusters that is effective, and more convenient to administer with a socially acceptable method of delivery. An intranasal diazepam formulation has been developed, and this study evaluates the tolerability and bioavailability of diazepam nasal spray (NS) relative to an equivalent dose of diazepam-RG in healthy adults. Twenty-four healthy adults were enrolled in a phase 1, open-label, 3-period crossover study. Plasma diazepam and metabolite concentrations were measured by serial sampling. Dose proportionality for 5- and 20-mg intranasal doses and the bioavailability of 20mg diazepam-NS relative to 20mg diazepam-RG were assessed by maximum plasma concentration (Cmax) and systemic exposure parameters (AUC0-∞ and AUC0-24). The mean Cmax values for 20mg diazepam-NS and 20mg diazepam-RG were 378 ± 106 and 328 ± 152 ng/mL, achieved at 1.0 and 1.5h, respectively. Subjects administered intranasal and rectal gel formulations experienced nasal and rectal leakage, respectively. Diazepam absorption following intranasal administration was consistent but 3 subjects with diazepam-RG had low plasma drug levels at the earliest assessment of 5 min, due to poor retention, and were excluded from analysis. Excluding them, the treatment ratios (20mg diazepam-NS:20mg diazepam-RG) and 90% confidence intervals for diazepam Cmax and AUC0-24 were 0.98 (0.85-1.14) and 0.89 (0.80-0.98), respectively, suggesting that the bioavailability was comparable between the two formulations. Dose proportionality was observed between the lowest and highest dose-strengths of intranasal formulation. Both intranasal and rectal treatments were well tolerated with mild to moderate adverse events. Results suggest that a single-dose of 20mg diazepam-NS is tolerable and comparable in bioavailability to that of diazepam-RG. The intranasal formulation may provide caregivers and patients with a more socially acceptable and convenient alternative rescue therapy in the acute treatment of seizure clusters.

[Cost-effectiveness of buccal midazolam in the treatment of prolonged convulsive seizures in the outpatient setting in Spain]. / Coste-efectividad de una solucion bucal de midazolam en el tratamiento de las crisis convulsivas prolongadas en el entorno ambulatorio en España.

INTRODUCTION: To be able to treat prolonged epileptic crises practical, safe and effective rescue medication is needed. Today, the standard treatment in community healthcare is rectal diazepam. The introduction of a buccal solution of midazolam opens up a new perspective in their treatment. AIMS: To evaluate the cost-effectiveness of buccal midazolam with respect to rectal diazepam for children diagnosed with epilepsy who present prolonged convulsive seizures in the community setting in Spain. MATERIALS AND METHODS: The study produces a model of its cost-effectiveness from the perspective of the Spanish National Health System (SNS), with the outcomes presented in terms of cost-quality adjusted life years. Data were collected from different sources, including estimations regarding the clinical effectiveness from a clinical trial, from a Delphi panel in Spain and from a national survey carried out on parents of children with epilepsy in order to determine the current practices. RESULTS: Treatment with buccal midazolam produces a saving in costs in comparison to rectal diazepam. The amount saved by the Spanish SNS comes to 5,484 euros per patient per year. Treatment with buccal midazolam offers an improved health-related quality of life. This, together with the savings in costs, means that there is a dominance of buccal midazolam over rectal diazepam in all the settings that have been examined. CONCLUSIONS: The results obtained with the model show that buccal midazolam is more cost-effective than rectal diazepam due to a reduction in the need to call out ambulances and for stays in hospital, as well as an improved health-related quality of life.

TITLE: Coste-efectividad de una solucion bucal de midazolam en el tratamiento de las crisis convulsivas prolongadas en el entorno ambulatorio en España.Introduccion. El tratamiento de las crisis epilepticas prolongadas requiere disponer de una medicacion de rescate comoda, segura y efectiva. Actualmente, el tratamiento estandar en la comunidad es el diacepam rectal. La introduccion de una solucion bucal de midazolam abre una perspectiva nueva en el tratamiento. Objetivo. Evaluar el coste-efectividad del midazolam bucal respecto al diacepam rectal para los niños con un diagnostico de epilepsia que presentan crisis convulsivas prolongadas en la comunidad en España. Materiales y metodos. Modelo coste-efectividad desde la perspectiva del Sistema Nacional de Salud (SNS) español, con resultados presentados en terminos de costes y años de vida ajustados por calidad. Los datos se obtuvieron de varias fuentes, incluidas las estimaciones de efectividad clinica de un ensayo clinico, de un panel Delphi en España y de una encuesta nacional a padres de niños con epilepsia para determinar las practicas actuales. Resultados. El tratamiento con midazolam bucal produce un ahorro de costes en comparacion con el diacepam rectal. El ahorro para el SNS español es de 5.484 euros por paciente al año. El tratamiento con midazolam bucal ofrece una mejora en la calidad de vida relacionada con la salud. Esto, unido al ahorro de costes, hace que el midazolam bucal sea dominante frente al diacepam rectal en todos los escenarios examinados. Conclusion. Los resultados del modelo muestran que el midazolam bucal es mas coste-efectivo que el diacepam rectal debido a una reduccion en la necesidad de llamadas a la ambulancia y estancias en el hospital, asi como a una mejora en la calidad de vida relacionada con la salud.

The cost effectiveness of licensed oromucosal midazolam (Buccolam(®)) for the treatment of children experiencing acute epileptic seizures: an approach when trial evidence is limited.

BACKGROUND: In the UK, two treatment options are used for acute epileptic seizures in the community-rectal diazepam and unlicensed buccal midazolam. In practice, the former is rarely used, with unlicensed buccal midazolam being widely recommended and prescribed by physicians. In September 2011, Buccolam(®) (licensed midazolam oromucosal solution) became the first medicine to receive a Paediatric-Use Marketing Authorization (PUMA) and it is indicated for the treatment of prolonged, acute, convulsive seizures by caregivers in the community for children (aged 6 months to <18 years) diagnosed with epilepsy. The approval process for a PUMA product differs from other marketing authorization processes and may be based upon small population subsets and may not, in some cases, require new safety or efficacy data to be generated; a similar situation to that seen for orphan drugs. This can lead to challenges when conducting economic evaluations. OBJECTIVE: The aim of this study was to assess the cost effectiveness of Buccolam(®) for children with a diagnosis of epilepsy suffering prolonged, acute, convulsive seizures occurring in the UK community setting. DESIGN AND PERSPECTIVE: A hybrid model was developed according to a UK payer perspective. The model included a time-to-event simulation for the frequency and location of occurrence of seizures, along with a decision-tree model that assessed the treatment pathway when a seizure occured. The model compared treatment with Buccolam(®) with standard care in the community (95 % unlicensed buccal midazolam and 5 % rectal diazepam) or either treatment alone. The model was informed by data from a variety of sources, including clinical effectiveness estimates, and costs based on published UK data, using 2012-13 prices, where possible. To determine current practice and real-world effectiveness, a Delphi panel and a survey of parents of children with epilepsy were conducted. RESULTS: Buccolam(®) showed a reduction in costs of £2,939 compared with standard care, £14,269 compared with rectal diazepam alone and £886 compared with unlicensed buccal midazolam alone. Increases of 0.025, 0.082 and 0.013 quality-adjusted life-years, respectively, were also seen. Buccolam(®) remained dominant across a range of scenario analyses. CONCLUSION: This model demonstrates the possibility of constructing a thorough economic case when trial or real-world data are not available. The results of the model show Buccolam(®) to be cost saving compared with rectal diazepam due to a reduction in the need for ambulance callouts and hospital stays, and compared with unlicensed buccal midazolam, through reduced drug costs and wastage.

Does rectal indomethacin eliminate the need for prophylactic pancreatic stent placement in patients undergoing high-risk ERCP? Post hoc efficacy and cost-benefit analyses using prospective clinical trial data.

OBJECTIVES: A recent large-scale randomized controlled trial (RCT) demonstrated that rectal indomethacin administration is effective in addition to pancreatic stent placement (PSP) for preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk cases. We performed a post hoc analysis of this RCT to explore whether rectal indomethacin can replace PSP in the prevention of PEP and to estimate the potential cost savings of such an approach. METHODS: We retrospectively classified RCT subjects into four prevention groups: (1) no prophylaxis, (2) PSP alone, (3) rectal indomethacin alone, and (4) the combination of PSP and indomethacin. Multivariable logistic regression was used to adjust for imbalances in the prevalence of risk factors for PEP between the groups. Based on these adjusted PEP rates, we conducted an economic analysis comparing the costs associated with PEP prevention strategies employing rectal indomethacin alone, PSP alone, or the combination of both. RESULTS: After adjusting for risk using two different logistic regression models, rectal indomethacin alone appeared to be more effective for preventing PEP than no prophylaxis, PSP alone, and the combination of indomethacin and PSP. Economic analysis revealed that indomethacin alone was a cost-saving strategy in 96% of Monte Carlo trials. A prevention strategy employing rectal indomethacin alone could save approximately $150 million annually in the United States compared with a strategy of PSP alone, and $85 million compared with a strategy of indomethacin and PSP. CONCLUSIONS: This hypothesis-generating study suggests that prophylactic rectal indomethacin could replace PSP in patients undergoing high-risk ERCP, potentially improving clinical outcomes and reducing healthcare costs. A RCT comparing rectal indomethacin alone vs. indomethacin plus PSP is needed.

Using conjoint analysis to measure the acceptability of rectal microbicides among men who have sex with men in four South American cities.

Conjoint Analysis (CJA), a statistical market-based technique that assesses the value consumers place on product characteristics, may be used to predict acceptability of hypothetical products. Rectal Microbicides (RM)-substances that would prevent HIV infection during receptive anal intercourse-will require acceptability data from potential users in multiple settings to inform the development process by providing valuable information on desirable product characteristics and issues surrounding potential barriers to product use. This study applied CJA to explore the acceptability of eight different hypothetical RM among 128 MSM in Lima and Iquitos, Peru; Guayaquil, Ecuador; and Rio de Janeiro, Brazil. Overall RM acceptability was highest in Guayaquil and lowest in Rio. Product effectiveness had the greatest impact on acceptability in all four cities, but the impact of other product characteristics varied by city. This study demonstrates that MSM from the same region but from different cities place different values on RM characteristics that could impact uptake of an actual RM. Understanding specific consumer preferences is crucial during RM product development, clinical trials and eventual product dissemination.

Prereferral rectal artesunate for treatment of severe childhood malaria: a cost-effectiveness analysis.

BACKGROUND: Severely ill patients with malaria with vomiting, prostration, and altered consciousness cannot be treated orally and need injections. In rural areas, access to health facilities that provide parenteral antimalarial treatment is poor. Safe and effective treatment of most severe malaria cases is delayed or not achieved. Rectal artesunate interrupts disease progression by rapidly reducing parasite density, but should be followed by further antimalarial treatment. We estimated the cost-effectiveness of community-based prereferral artesunate treatment of children suspected to have severe malaria in areas with poor access to formal health care. METHODS: We assessed the cost-effectiveness (in international dollars) of the intervention from the provider perspective. We studied a cohort of 1000 newborn babies until 5 years of age. The analysis assessed how the cost-effectiveness results changed with low (25%), moderate (50%), high (75%), and full (100%) referral compliance and intervention uptake. FINDINGS: At low intervention uptake and referral compliance (25%), the intervention was estimated to avert 19 disability-adjusted life-years (DALYs; 95% CI 16-21) and to cost I$1173 (95% CI 1050-1297) per DALY averted. Under the full uptake and compliance scenario (100%), the intervention could avert 967 DALYs (884-1050) at a cost of I$77 (73-81) per DALY averted. INTERPRETATION: Prereferral artesunate treatment is a cost-effective, life-saving intervention, which can substantially improve the management of severe childhood malaria in rural African settings in which programmes for community health workers are in place. FUNDING: The Disease Control Priorities Project; Fogarty International Center; US National Institutes of Health; and the Peter Paul Career Development Professorship, Boston University.