A cost effectiveness analysis of the preferred antidotes for acute paracetamol poisoning patients in Sri Lanka

Background: Acute paracetamol poisoning is a rapidly increasing problem in Sri Lanka. The antidotes are expensive and yet no health economic evaluation has been done on the therapy for acute paracetamol poisoning in the developing world. The aim of this study is to determine the cost effectiveness of using N-acetylcysteine over methionine in the management of acute paracetamol poisoning in Sri Lanka. Methods:Economic analysis was applied using public healthcare system payer perspective. Costs were obtained from a series of patients admitted to the National Hospital of Sri Lanka with a history of acute paracetamol overdose. Evidence on effectiveness was obtained from a systematic review of the literature. Death due to hepatotoxicity was used as the primary outcome of interest. Analysis and development of decision tree models was done using Tree Age Pro 2008. Results: An affordable treatment threshold of Sri Lankan rupees 1,537,120/death prevented was set from the expected years of productive life gained and the average contribution to GDP. A cost-minimisation analysis was appropriate for patients presenting within 10 hours and methionine was the least costly antidote. For patients presenting 10-24 hours after poisoning, n-acetylcysteine was more effective and the incremental cost effectiveness ratio of Sri Lankan rupees 316,182/life saved was well under the threshold. One-way and multi-way sensitivity analysis also supported methionine for patients treated within 10 hours and n-acetylcysteine for patients treated within 10-24 hours as preferred antidotes.Conclusions: Post ingestion time is an important determinant of preferred antidotal therapy for acute paracetamol poisoning patients in Sri Lanka. Using n-acetylcysteine in all patients is not cost effective. On economic grounds, methionine should become the preferred antidote for Sri Lankan patients treated within 10 hours of the acute ingestion and n-acetylcysteine should continue to be given to patients treated within 10-24 hours

Stabilizing and Improving Livelihoods in Fragile and Conflict-Affected Situations (FCAS) – the Search for Frameworks and Evidence

Interventions to support livelihoods in Fragile and Conflict-Affected Situations (FCAS) are seen by many as subsidiary to the primary (relief-based) imperative to save lives. For others, FCAS interventions remain “stuck” for too long in relief mode, and the potential to get back into support for livelihoods is lost. This paper examines how livelihoods models, initially used in development, not relief, contexts, have been adapted to suit FCAS, and asks what evidence we have on how livelihoods have changed under FCAS and why. It also asks how far efforts to support livelihoods in FCAS have been effective. To provide effective livelihoods support is complex, requiring understanding of how people link into distant opportunities outside the FCAS, how they perceive and respond to risk, and how their livelihoods are affected by power relations, by restrictions on the movement of people and goods, and by reduced capacity to enforce the rule of law in relation to e.g. contracts and the ownership of and access to resources

Apparent permeability (P_app) and efflux ratio of antimalarials through Caco-2 cell monolayers.

<p>Apparent permeability (P_app) and efflux ratio of antimalarials through Caco-2 cell monolayers.</p

Apparent permeability (P_app) and efflux ratio for 5 μM rh123 through Caco-2 cell monolayers when co-incubated with selected antimalarial drugs.

<p>Apparent permeability (P_app) and efflux ratio for 5 μM rh123 through Caco-2 cell monolayers when co-incubated with selected antimalarial drugs.</p

Interspecies allometric scaling of antimalarial drugs and potential application to pediatric dosing

Pharmacopeial recommendations for administration of antimalarial drugs are the same weight-based (mg/kg of body weight) doses for children and adults. However, linear calculations are known to underestimate pediatric doses; therefore, interspecies allometric scaling data may have a role in predicting doses in children. We investigated the allometric scaling relationships of antimalarial drugs using data from pharmacokinetic studies in mammalian species. Simple allometry (Y = a × Wb) was utilized and compared to maximum life span potential (MLP) correction. All drugs showed a strong correlation with clearance (CL) in healthy controls. Insufficient data from malaria-infected species other than humans were available for allometric scaling. The allometric exponents (b) for CL of artesunate, dihydroartemisinin (from intravenous artesunate), artemether, artemisinin, clindamycin, piperaquine, mefloquine, and quinine were 0.71, 0.85, 0.66, 0.83, 0.62, 0.96, 0.52, and 0.40, respectively. Clearance was significantly lower in malaria infection than in healthy (adult) humans for quinine (0.07 versus 0.17 liter/h/kg; P = 0.0002) and dihydroartemisinin (0.81 versus 1.11 liters/h/kg; P = 0.04; power = 0.6). Interpolation of simple allometry provided better estimates of CL for children than MLP correction, which generally underestimated CL values. Pediatric dose calculations based on simple allometric exponents were 10 to 70% higher than pharmacopeial (mg/kg) recommendations. Interpolation of interspecies allometric scaling could provide better estimates than linear scaling of adult to pediatric doses of antimalarial drugs; however, the use of a fixed exponent for CL was not supported in the present study. The variability in allometric exponents for antimalarial drugs also has implications for scaling of fixed-dose combinations