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      Management of acute organophosphorus pesticide poisoning

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          Summary

          Organophosphorus pesticide self-poisoning is an important clinical problem in rural regions of the developing world, and kills an estimated 200 000 people every year. Unintentional poisoning kills far fewer people but is a problem in places where highly toxic organophosphorus pesticides are available. Medical management is difficult, with case fatality generally more than 15%. We describe the limited evidence that can guide therapy and the factors that should be considered when designing further clinical studies. 50 years after first use, we still do not know how the core treatments—atropine, oximes, and diazepam—should best be given. Important constraints in the collection of useful data have included the late recognition of great variability in activity and action of the individual pesticides, and the care needed cholinesterase assays for results to be comparable between studies. However, consensus suggests that early resuscitation with atropine, oxygen, respiratory support, and fluids is needed to improve oxygen delivery to tissues. The role of oximes is not completely clear; they might benefit only patients poisoned by specific pesticides or patients with moderate poisoning. Small studies suggest benefit from new treatments such as magnesium sulphate, but much larger trials are needed. Gastric lavage could have a role but should only be undertaken once the patient is stable. Randomised controlled trials are underway in rural Asia to assess the effectiveness of these therapies. However, some organophosphorus pesticides might prove very difficult to treat with current therapies, such that bans on particular pesticides could be the only method to substantially reduce the case fatality after poisoning. Improved medical management of organophosphorus poisoning should result in a reduction in worldwide deaths from suicide.

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          An overview of clinical research: the lay of the land.

          Many clinicians report that they cannot read the medical literature critically. To address this difficulty, we provide a primer of clinical research for clinicians and researchers alike. Clinical research falls into two general categories: experimental and observational, based on whether the investigator assigns the exposures or not. Experimental trials can also be subdivided into two: randomised and non-randomised. Observational studies can be either analytical or descriptive. Analytical studies feature a comparison (control) group, whereas descriptive studies do not. Within analytical studies, cohort studies track people forward in time from exposure to outcome. By contrast, case-control studies work in reverse, tracing back from outcome to exposure. Cross-sectional studies are like a snapshot, which measures both exposure and outcome at one time point. Descriptive studies, such as case-series reports, do not have a comparison group. Thus, in this type of study, investigators cannot examine associations, a fact often forgotten or ignored. Measures of association, such as relative risk or odds ratio, are the preferred way of expressing results of dichotomous outcomes-eg, sick versus healthy. Confidence intervals around these measures indicate the precision of these results. Measures of association with confidence intervals reveal the strength, direction, and a plausible range of an effect as well as the likelihood of chance occurrence. By contrast, p values address only chance. Testing null hypotheses at a p value of 0.05 has no basis in medicine and should be discouraged.
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            Self poisoning with pesticides.

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              Patterns and problems of deliberate self-poisoning in the developing world.

              Deliberate self-harm is a major problem in the developing world, responsible for around 600 000 deaths in 1990. The toxicity of available poisons and paucity of medical services ensure that mortality from self-poisoning is far greater in the tropics than in the industrialized world. Few data are available on the poisons most commonly used for self-harm in different parts of the world. This paper reviews the literature on poisoning, to identify the important poisons used for self-harm in these regions. Pesticides are the most important poison throughout the tropics, being both common and associated with a high mortality rate. In some regions, particular pesticides have become the most popular method of self-harm, gaining a notoriety amongst both health-care workers and public. Self-poisoning with medicines such as benzodiazepines and antidepressants is common in urban areas, but associated with few deaths. The antimalarial chloroquine appears the most significant medicine, self-poisoning being common in both Africa and the Pacific region, and often fatal. Paracetamol (acetaminophen) is used in many countries but in few has it reached the popularity typical of the UK. Domestic and industrial chemicals are responsible for significant numbers of deaths and long-term disabilities world-wide. Self-poisoning with plant parts, although uncommon globally, is locally popular in some regions. Few of these poisons have specific antidotes. This emphasizes the importance of determining whether interventions aimed at reducing poison absorption actually produce a clinical benefit, reducing death and complication rates. Future research to improve medical management and find effective ways of reducing the incidence of self-harm, together with more widespread provision of interventions proven to be effective, could rapidly reduce the number of deaths from self-poisoning in the developing world.
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                Author and article information

                Journal
                Lancet
                Lancet
                Lancet
                Lancet Publishing Group
                0140-6736
                1474-547X
                16 February 2008
                16 February 2008
                : 371
                : 9612
                : 597-607
                Affiliations
                [a ]Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, England
                [b ]South Asian Clinical Toxicology Research Collaboration Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
                [c ]Department of Clinical Medicine, University of Peradeniya, Peradeniya, Sri Lanka
                [d ]Scottish Poisons Information Bureau, New Royal Infirmary, Edinburgh, Scotland
                [e ]Department of Clinical Pharmacology and Toxicology, Canberra Clinical School, ACT, Australia
                [f ]Walther Straub Institute of Pharmacology and Toxicology, Ludwig Maximilians University, Munich, Germany
                Author notes
                [* ]Correspondence to: Michael Eddleston, Scottish Poisons Information Bureau, New Royal Infirmary, Edinburgh EH16 4SA, UK eddlestonm@ 123456yahoo.com
                Article
                LANCET61202
                10.1016/S0140-6736(07)61202-1
                2493390
                17706760
                15280b6c-91c0-4d8a-bd29-0738bd0b7b86
                © 2008 Elsevier Ltd. All rights reserved.

                This document may be redistributed and reused, subject to certain conditions.

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