Browsing by Author "Eddleston, M."

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Acute human self-poisoning with imidacloprid compound: a neonicotinoid insecticide
(Public Library of Science, 2009) Mohamed, F.; Gawarammana, I.; Robertson, T.A.; Roberts, M.S.; Palangasinghe, C.; Zawahir, S.; Jayamanne, S.; Kandasamy, J.; Eddleston, M.; Buckley, N.A.; Dawson, A.H.; Roberts, D.M.
BACKGROUND: Deliberate self-poisoning with older pesticides such as organophosphorus compounds are commonly fatal and a serious public health problem in the developing world. The clinical consequences of self-poisoning with newer pesticides are not well described. Such information may help to improve clinical management and inform pesticide regulators of their relative toxicity. This study reports the clinical outcomes and toxicokinetics of the neonicotinoid insecticide imidacloprid following acute self-poisoning in humans. METHODOLOGY/PRINCIPAL FINDINGS: Demographic and clinical data were prospectively recorded in patients with imidacloprid exposure in three hospitals in Sri Lanka. Blood samples were collected when possible for quantification of imidacloprid concentration. There were 68 patients (61 self-ingestions and 7 dermal exposures) with exposure to imidacloprid. Of the self-poisoning patients, the median time to presentation was 4 hours (IQR 2.3-6.0) and median amount ingested was 15 mL (IQR 10-50 mL). Most patients only developed mild symptoms such as nausea, vomiting, headache and diarrhoea. One patient developed respiratory failure needing mechanical ventilation while another was admitted to intensive care due to prolonged sedation. There were no deaths. Median admission imidacloprid concentration was 10.58 ng/L; IQR: 3.84-15.58 ng/L, Range: 0.02-51.25 ng/L. Changes in the concentration of imidacloprid in serial blood samples were consistent with prolonged absorption and/or saturable elimination. CONCLUSIONS: Imidacloprid generally demonstrates low human lethality even in large ingestions. Respiratory failure and reduced level of consciousness were the most serious complications, but these were uncommon. Substitution of imidacloprid for organophosphorus compounds in areas where the incidence of self-poisoning is high may help reduce deaths from self-poisoning.
Cost-effectiveness analyses of self-harm strategies aimed at reducing the mortality of pesticide self-poisonings in Sri Lanka: a study protocol
(British Medical Association, 2015) Madsen, L. B.; Eddleston, M.; Hansen, K. S.; Pearson, M.; Agampodi, S.; Jayamanne, S.; Konradsen, F.
INTRODUCTION: An estimated 803,900 people worldwide died as a result of self-harm in 2012. The deliberate ingestion of pesticides has been identified as the method most frequently used to commit fatal self-harm globally. In Sri Lanka, it is estimated that up to 60% of all suicides are committed using this method. The aim of the present study is to assess the cost-effectiveness of an ongoing safe storage intervention currently taking place in a rural Sri Lankan district and to model the cost-effectiveness of implementing the safe storage intervention as well as four potential interventions (legislative, medical management, follow-up contact and mobile phone contact) on a national level. METHODS AND ANALYSIS: Study design for all the strategies is a cost-effectiveness analysis. A governmental perspective is adopted. The time horizon for tracking the associated costs and health outcomes of the safe storage intervention on district level runs over 3 years. The time horizon is extended to 5 years when modelling a full national roll-out of the respective interventions. The discounting of costs and health outcomes are undertaken at the recommended real rate of 3%. Threshold analyses of the modelled strategies are employed to assess the strategies potential for cost-effectiveness, running scenarios with health outcome improvements ranging from 1% to 100%. Sensitivity analyses are also performed. The main outcome measures of the safe storage intervention are incremental cost-effectiveness ratios. ETHICS AND DISSEMINATION: Ethical approval was granted for the safe storage project from the University of Peradeniya, Sri Lanka, in March of 2008. An amendment for the present study was granted from Rajarata University of Sri Lanka in November of 2013. Findings will be disseminated to public and private stakeholders in local and national government in Sri Lanka as well as the wider academic audience through peer-reviewed publications and international conferences. TRIAL REGISTRATION NUMBER: The safe storage cluster trial is registered with the Clinical Trials, ref: NCT1146496 (http://clinicaltrialsfeeds.org/clinical-trials/show/NCT1146496).Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Differences in the characteristics of people who purchase pesticides from shops for self-harm versus those who use pesticides available in the domestic environment in Sri Lanka
(Blackwell Publishing, 2023) Weerasinghe, M.; Jobe, L.; Konradsen, F.; Eddleston, M.; Pearson, M.; Jayamanne, S.; Hawton, K.; Gunnell, D.; Agampodi, S.
OBJECTIVE: Data from South Asia indicate that for 15%-20% of suicide attempts, pesticides are purchased from shops; otherwise, pesticides are obtained from an individual's house or nearby environment. We aimed to investigate the difference between individuals who directly purchase pesticides from shops for suicide attempts and suicide deaths versus those related to accessing the pesticides from an individual's house or nearby environment. METHODS: We conducted two comparative studies in rural Sri Lanka: (1) non-fatal shop cases (n = 50) were survivors of self-poisoning with pesticides who ingested the pesticides after purchasing them from a shop; non-fatal domestic cases (n = 192) were survivors who accessed pesticides from their house or nearby environment. (2) fatal shop cases (n = 50) were individuals who died after ingesting pesticides they purchased for the act; fatal domestic cases (n = 102) were patients who died after ingesting pesticides they accessed at house or nearby environment. Logistic regression analysis was used to assess the characteristics which distinguished between the shop and domestic cases. RESULTS: Data indicate that 20.7% and 32.9% of individuals who used pesticides for suicide attempts and suicide deaths had purchased them from shops, respectively. Being a non-farmer was the main distinguishing characteristic of shop cases: adjusted odds ratios (AOR) 8.9, 95% confidence intervals (CI) 3.2-24.4 for non-fatal shop cases, and AOR 4.0, 95% CI 1.5-10.6 for fatal shop cases. Non-fatal shop cases also had higher suicide intent (AOR 3.0, CI 1.0-8.9), and ingesting an insecticide (AOR 4.8, CI 1.8-1.0-8.9) than non-fatal domestic cases. CONCLUSION: A high suicide intent of individuals who purchase pesticides for the event explains the high proportion of such fatal cases. Such high suicide intent makes the prevention implications difficult to spell out for those individuals who purchase pesticides for self-poisoning. However, our findings are valuable for clinicians to assess pesticide poisoning cases in hospitals.
Effectiveness of household lockable pesticide storage to reduce pesticide self-poisoning in rural Asia: a community-based, cluster-randomised controlled trial
(London : J. Onwhyn, 2017) Pearson, M.; Metcalfe, C.; Jayamanne, S.; Gunnell, D.; Weerasinghe, M.; Pieris, R.; Priyadarshana, C.; Knipe, D.W.; Hawton, K.; Dawson, A.H.; Bandara, P.; de Silva, D.; Gawarammana, I.; Eddleston, M.; Konradsen, F.
BACKGROUND: Agricultural pesticide self-poisoning is a major public health problem in rural Asia. The use of safer household pesticidestorage has been promoted to prevent deaths, but there is no evidence of effectiveness. We aimed to test the effectiveness of lockablehousehold containers for prevention of pesticide self-poisoning. METHODS: We did a community-based, cluster-randomised controlled trial in a rural area of North Central Province, Sri Lanka. Clusters of households were randomly assigned (1:1), with a sequence computer-generated by a minimisation process, to intervention or usual practice (control) groups. Intervention households that had farmed or had used or stored pesticide in the preceding agricultural season were given a lockable storage container. Further promotion of use of the containers was restricted to community posters and 6-monthly reminders during routine community meetings. The primary outcome was incidence of pesticide self-poisoning in people aged 14 years or older during 3 years of follow-up. Identification of outcome events was done by staff who were unaware of group allocation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT1146496. FINDINGS: Between Dec 31, 2010, and Feb 2, 2013, we randomly assigned 90 rural villages to the intervention group and 90 to the control group. 27 091 households (114 168 individuals) in the intervention group and 26 291 households (109 693 individuals) in the control group consented to participate. 20 457 household pesticide storage containers were distributed. In individuals aged 14 years or older, 611 cases of pesticide self-poisoning had occurred by 3 years in the intervention group compared with 641 cases in the control group; incidence of pesticide self-poisoning did not differ between groups (293·3 per 100 000 person-years of follow-up in the intervention group vs 318·0 per 100 000 in the control group; rate ratio [RR] 0·93, 95% CI 0·80-1·08; p=0·33). We found no evidence of switching from pesticide self-poisoning to other forms of self-harm, with no significant difference in the number of fatal (82 in the intervention group vs 67 in the control group; RR 1·22, 0·88-1·68]) or non-fatal (1135 vs 1153; RR 0·97, 0·86-1·08) self-harm events involving all methods. INTERPRETATION: We found no evidence that means reduction through improved household pesticide storage reduces pesticide self-poisoning. Other approaches, particularly removal of highly hazardous pesticides from agricultural practice, are likely to be more effective for suicide prevention in rural Asia. FUNDING: Wellcome Trust, with additional support from the American Foundation for Suicide Prevention, Lister Institute of Preventive Medicine, Chief Scientist Office of Scotland, University of Copenhagen, and NHMRC Australia.
Effects of provincial ban of two toxic organophosphorus insecticides on pesticide poisoning hospitaladmissions
(Informa Healthcare, 2012) Eddleston, M.; Adhikari, S.; Egodage, S.; Ranganath, H.; Mohamed, F.; Manuweera, G.; Azher, S.; Jayamanne, S.; Juzczak, E.; Sheriff, M.R.; Dawson, A.H.; Buckley, N.A.
BACKGROUND: Pesticide self-poisoning causes one third of global suicides. Sri Lanka halved its suicide rate by banning WHO Class Iorganophosphorus (OP) insecticides and then endosulfan. However, poisoning with Class II toxicity OPs, particularly dimethoate and fenthion, remains a problem. We aimed to determine the effect and feasibility of a ban of the two insecticides in one Sri Lankan district. METHODS: Sale was banned in June 2003 in most of Polonnaruwa District, but not Anuradhapura District. Admissions with pesticide poisoning to the district general hospitals was prospectively recorded from 2002. RESULTS: Hospital admissions for dimethoate and fenthion poisoning fell by 43% after the ban in Polonnaruwa, while increasing by 23% in Anuradhapura. The pesticide case fatality fell from 14.4% to 9.0% in Polonnaruwa (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.41-0.84) and 11.3% to 10.6% in Anuradhapura (OR 0.93, 95%CI 0.70-1.25; p = 0.051). This reduction was not sustained, with case fatality in Polonnaruwa rising to 12.1% in 2006-2007. Further data analysis indicated that the fall in case fatality had actually been due to a coincidental reduction in case fatality for pesticide poisoning overall, in particular for paraquat poisoning. CONCLUSIONS: We found that the insecticides could be effectively banned from agricultural practice, as shown by the fall in hospital admissions, with few negative consequences. However, the ban had only a minor effect on pesticide poisoning deaths because it was too narrow. A study assessing the agricultural and health effects of a more comprehensive ban of highly toxic pesticides is necessary to determine the balance between increased costs of agriculture and reduced health care costs and fewer deaths.
Emerging pesticides responsible for suicide in rural Sri Lanka following the 2008-2014 pesticide bans.
(BioMed Central, 2020) Weerasinghe, M.; Pearson, M.; Konradsen, F.; Agampodi, S.; Sumith, J. A.; Jayamanne, S.; Senanayake, S. M. H. M. K.; Rajapaksha, S.; Eddleston, M.
BACKGROUND: Sri Lanka has reduced its overall suicide rate by 70% over the last two decades through means restriction, through a series of government regulations and bans removing highly hazardous pesticides from agriculture. We aimed to identify the key pesticide(s) now responsible for suicides in rural Sri Lanka to provide data for further pesticide regulation. METHODS: We performed a secondary analysis of data collected prospectively during a cluster randomized controlled trial in the Anuradhapura district of Sri Lanka from 2011 to 16. The identity of pesticides responsible for suicides were sought from medical or judicial medical notes, coroners' records, and the person's family. Trend analysis was done using a regression analysis with curve estimation to identify relative importance of key pesticides. RESULTS: We identified 337 suicidal deaths. Among them, the majority 193 (57.3%) were due to ingestion of pesticides while 82 (24.3%) were due to hanging. A specific pesticide was identified in 105 (54.4%) of the pesticide suicides. Ingestion of carbosulfan or profenofos was responsible for 59 (56.2%) of the suicides with a known pesticide and 17.5% of all suicides. The increasing trend of suicides due to carbosulfan and profenofos over time was statistically significant (R square 0.846, F 16.541, p 0.027). CONCLUSIONS: Ingestion of pesticides remains the most important means of suicides in rural Sri Lanka. The pesticides that were once responsible for most pesticide suicides have now been replaced by carbosulfan and profenofos. Their regulation and replacement in agriculture with less hazardous pesticides will further reduce the incidence of both pesticide and overall suicides in rural Sri Lanka. KEYWORDS: Pesticide; Pesticide regulation; Self-poisoning; Sri Lanka; Suicide.
Estimating the government health-care costs of treating pesticide poisoned and pesticide self-poisoned patients in Sri Lanka.
(PA : Taylor & Francis, Philadelphia, 2019) Ahrensberg, H.; Madsen, L.B.; Pearson, M.; Weerasinghe, M.; Eddleston, M.; Jayamanne, S.; Hansen, K.S.; Ariyarathna, V.; Rajapaksha, S.; Konradsen, F.
BACKGROUND: Pesticide self-poisoning as a method of suicide is a major global health problem. OBJECTIVES: To estimate the cost and per patient cost of treating pesticide self-poisoning at different hospital levels in a Sri Lankan district, and to examine the distribution of cost components. Another objective was to investigate changes in total cost of treatment of pesticide poisoning for all causes at different administrative levels in Sri Lanka in 2005 and 2015.METHODS: The economic framework was a costing analysis, adopting a government perspective. Cost data were collected prospectively over a 4-month period in 2016 for patients admitted for pesticide self-poisoning to six hospitals in the Anuradhapura District. Assumption-based scenario analyses were run to determine changes in total pesticide poisoning treatment costs. RESULTS: We included 67 self-poisoned patients in the study. The total cost of treatment was US$ 5,714 at an average treatment cost of US$ 85.3 (9.7-286.6) per patient (across all hospital levels). Hospital costs constituted 67% of the total cost for treating self-poisoning cases and patient-specific costs accounted for 29%. Direct cost of patient hospital transfer constituted the smallest share of costs (4%) but accounted for almost half of the total costs at primary level. The estimated total cost of treating all causes of pesticide poisoning in Sri Lanka was US$ 2.5 million or 0.19% of the total government health expenditure (GHE) in 2015. CONCLUSION: Our findings indicate that the average per patient cost of pesticide self-poisoning treatment has increased while the total cost of pesticide poisoning treatment as a percentage of the total GHE in Sri Lanka has declined over the past decade. A continuous focus on banning the most hazardous pesticides available would likely further drive down the cost of pesticide self-poisoning and pesticide poisoning to the government.
Factors associated with purchasing pesticide from shops for intentional self-poisoning in Sri Lanka
(Blackwell Publishing Ltd, 2020) Weerasinghe, M.; Konradsen, F.; Eddleston, M.; Pearson, M.; Jayamanne, S.; Knipe, D.; Hawton, K.; Gunnell, D.; Agampodi, S.
ABSTRACT: Objective: In South Asia, up to one in five individuals who ingest pesticides for self-poisoning and survive purchased them from a shop immediately prior to the event. Thus far, no research has taken place to determine whether interventions implemented through the pesticide sellers might be acceptable or effective, despite the hundreds of thousands of such risk purchases each year. We aimed to investigate factors associated with purchasing pesticides for self-poisoning in Sri Lanka. METHODS: We used a case–control study. Cases (n = 50) were individuals who ingested pesticides after purchasing them for the act, and controls (n = 200) were customers who bought pesticides but did not use them for self-harm. Logistic regression analysis was used to assess socio-demographic and purchase-specific risk factors. RESULTS: Alcohol intoxication (adjusted odds ratios [AOR] 36.5, 95% confidence intervals [CI] 1.7–783.4) and being a non-farmer AOR 13.3, 95% CI 1.8–99.6 were the main distinguishing factors when purchasing pesticides for self-poisoning. The positive predictive values were 93.3% (95% CI 68.0–99.8%) and 88.2% (95% CI 72.5–96.7%), respectively. One and/or other of these factors characterised 72.0% of cases but only 2.5% controls. CONCLUSION: While results need to be interpreted cautiously, sales restrictions to prevent alcohol-intoxicated persons and non-farmers purchasing pesticides for self-poisoning may be effective. © 2020 John Wiley & Sons Ltd AUTHOR KEYWORDS: pesticide shops; pesticides; self-poisoning; Sri Lanka; suicide. INDEX KEYWORDS: pesticide, environmental factor; pesticide; poisoning; regression analysis; risk factor, adult; alcohol consumption; alcohol intoxication; Article; automutilation; case control study; controlled study; female; human; major clinical study; male; predictive value; purchasing; self poisoning; sex difference; social status; Sri Lanka, Sri Lanka
Gatekeeper training for vendors to reduce pesticide self-poisoning in rural South Asia: a study protocol for a stepped-wedge cluster randomised controlled trial
(BMJ Publishing Group Ltd, 2022) Weerasinghe, M.; Pearson, M.; Turner, N.; Metcalfe, C.; Gunnell, D.J.; Agampodi, S.; Hawton, K.; Agampodi, T.; Miller, M.; Jayamanne, S.; Parker, S.; Sumith, J.A.; Karunarathne, A.; Dissanayaka, K.; Rajapaksha, S.; Rodrigo, D.; Abeysinghe, D.; Piyasena, C.; Kanapathy, R.; Thedchanamoorthy, S.; Madsen, L.B.; Konradsen, F.; Eddleston, M.
Introduction: Pesticide self-poisoning kills an estimated 110 000-168 000 people worldwide annually. Data from South Asia indicate that in 15%-20% of attempted suicides and 30%-50% of completed suicides involving pesticides these are purchased shortly beforehand for this purpose. Individuals who are intoxicated with alcohol and/or non-farmers represent 72% of such customers. We have developed a 'gatekeeper' training programme for vendors to enable them to identify individuals at high risk of self-poisoning (gatekeeper function) and prevent such individuals from accessing pesticides (means restriction). The primary aim of the study is to evaluate the effectiveness of the gatekeeper intervention in preventing pesticide self-poisoning in Sri Lanka. Other aims are to identify method substitution and to assess the cost and cost-effectiveness of the intervention. Methods and analysis: A stepped-wedge cluster randomised trial of a gatekeeper intervention is being conducted in rural Sri Lanka with a population of approximately 2.7 million. The gatekeeper intervention is being introduced into 70 administrative divisions in random order at each of 30 steps over a 40-month period. The primary outcome is the number of pesticide self-poisoning cases identified from surveillance of hospitals and police stations. Secondary outcomes include: number of self-poisoning cases using pesticides purchased within the previous 24 hours, total number of all forms of self-harm and suicides. Intervention effectiveness will be estimated by comparing outcome measures between the pretraining and post-training periods across the divisions in the study area. The original study protocol has been adapted as necessary in light of the impact of the COVID-19. Ethics and dissemination: The Ethical Review Committee of the Faculty of Medicine and Allied Sciences, Rajarata University, Sri Lanka (ERC/2018/30), and the ACCORD Medical Research Ethics Committee, Edinburgh University (18-HV-053) approved the study. Results will be disseminated in scientific peer-reviewed journals.
High lethality and minimal variation after acute self-poisoning with carbamate insecticides in Sri Lanka - implications for global suicide prevention
(Informa Healthcare, 2016) Lamb, T.; Selvarajah, L.R.; Mohamed, F.; Jayamanne, S.; Gawarammana, I.; Mostafa, A.; Buckley, N.A.; Roberts, M.S.; Eddleston, M.
BACKGROUND: Highly hazardous organophosphorus (OP) insecticides are responsible for most pesticide poisoning deaths. As they are removed from agricultural practice, they are often replaced by carbamate insecticides of perceived lower toxicity. However, relatively little is known about poisoning with these insecticides. METHODS: We prospectively studied 1288 patients self-poisoned with carbamate insecticides admitted to six Sri Lankan hospitals. Clinical outcomes were recorded for each patient and plasma carbamate concentration measured in a sample to confirm the carbamate ingested. FINDINGS: Patients had ingested 3% carbofuran powder (719), carbosulfan EC25 liquid (25% w/v, 389), or fenobucarb EC50 liquid (50% w/v, 127) formulations, carbamate insecticides of WHO Toxicity Classes Ib, II, and II, respectively. Intubation and ventilation was required for 183 (14.2%) patients while 71 (5.5%) died. Compared with carbofuran, poisoning with carbosulfan or fenobucarb was associated with significantly higher risk of death [carbofuran 2.2%; carbosulfan 11.1%, OR 5.5 (95% CI 3.0-9.8); fenobucarb 6.3%, OR 3.0 (1.2-7.1)] and intubation [carbofuran 6.1%; carbosulfan 27.0%, OR 5.7 (3.9-8.3); fenobucarb 18.9%, OR 3.6 (2.1-6.1)]. The clinical presentation and cause of death did not differ markedly between carbamates. Median time to death was similar: carbofuran 42.3 h (IQR 5.5-67.3), carbosulfan 21.3 h (11.5-71.3), and fenobucarb 25.3 h (17.3-72.1) (p = 0.99); no patients showed delayed onset of toxicity akin to the intermediate syndrome seen after OP insecticide poisoning. For survivors, median duration of intubation was 67.8 h (IQR 27.5-118.8) with no difference in duration between carbamates. Reduced GCS at presentation was associated with worse outcome although some patients with carbosulfan died after presentation with normal GCS. CONCLUSIONS: We did not find carbamate insecticide self-poisoning to vary markedly according to the carbamate ingested although the case fatality varied according to the concentration and formulation of the insecticide. Carbamate poisoning did not appear to be much less toxic than poisoning with some liquid OP insecticide formulations, e.g., chlorpyrifos EC40, that we have previously noted in these same hospitals (Lancet 2005, 366:1452-1459; QJM 2006, 99:513-522). Replacement of WHO Class II Toxicity OP insecticides in agriculture with high-strength liquid carbamate formulations may not substantially reduce case fatality after pesticide poisoning and, therefore, global suicide rates.
Improvement in survival after paraquat ingestion following introduction of a new formulation in Sri Lanka
(Public Library of Science, 2008) Wilks, M.F.; Fernando, R.; Ariyananda, P.L.; Eddleston, M.; Berry, D.J.; Tomenson, J.A.; Buckley, N.A.; Jayamanne, S.; Gunnell, D.; Dawson, A.
BACKGROUND: Pesticide ingestion is a common method of self-harm in the rural developing world. In an attempt to reduce the high case fatality seen with the herbicide paraquat, a novel formulation (INTEON) has been developed containing an increased emetic concentration, a purgative, and an alginate that forms a gel under the acid conditions of the stomach, potentially slowing the absorption of paraquat and giving the emetic more time to be effective. We compared the outcome of paraquat self-poisoning with the standard formulation against the new INTEON formulation following itsintroduction into Sri Lanka. METHODS AND FINDINGS: Clinical data were prospectively collected on 586 patients with paraquat ingestion presenting to nine large hospitals across Sri Lanka with survival to 3 mo as the primary outcome. The identity of the formulation ingested after October 2004 was confirmed by assay of blood or urine samples for a marker compound present in INTEON. The proportion of known survivors increased from 76/297 with the standardformulation to 103/289 with INTEON ingestion, and estimated 3-mo survival improved from 27.1% to 36.7% (difference 9.5%; 95% confidence interval [CI] 2.0%-17.1%; p = 0.002, log rank test). Cox proportional hazards regression analyses showed an approximately 2-fold reduction in toxicity for INTEON compared to standard formulation. A higher proportion of patients ingesting INTEON vomited within 15 min (38% with the originalformulation to 55% with INTEON, p < 0.001). Median survival time increased from 2.3 d (95% CI 1.2-3.4 d) with the standard formulation to 6.9 d (95% CI 3.3-10.7 d) with INTEON ingestion (p = 0.002, log rank test); however, in patients who did not survive there was a comparatively smaller increase in median time to death from 0.9 d (interquartile range [IQR] 0.5-3.4) to 1.5 d (IQR 0.5-5.5); p = 0.02. CONCLUSIONS: The survey has shown that INTEON technology significantly reduces the mortality of patients following paraquat ingestion and increases survival time, most likely by reducing absorption. Comment in : New formulation of paraquat: a step forward but in the wrong direction. [PLoS Med. 2008]
Multiple-dose activated charcoal in acute self-poisoning: a randomised controlled trial
(Lancet Publishing Group, 2008) Eddleston, M.; Juszczak, E.; Buckley, N.A.; Senarathna, L.; Mohamed, F.; Dissanayake, W.; Hittarage, A.; Azher, S.; Jeganathan, K.; Jayamanne, S.; Sheriff, M.R.; Warrell, D.A.; Ox-Col Poisoning Study collaborators
BACKGROUND: The case-fatality for intentional self-poisoning in the rural developing world is 10-50-fold higher than that in industrialised countries, mostly because of the use of highly toxic pesticides and plants. We therefore aimed to assess whether routine treatment with multiple-dose activated charcoal, to interrupt enterovascular or enterohepatic circulations, offers benefit compared with no charcoal in such an environment. METHODS: We did an open-label, parallel group, randomised, controlled trial of six 50 g doses of activated charcoal at 4-h intervals versus no charcoal versus one 50 g dose of activated charcoal in three Sri Lankan hospitals. 4632 patients were randomised to receive no charcoal (n=1554), one dose of charcoal (n=1545), or six doses of charcoal (n=1533); outcomes were available for 4629 patients. 2338 (51%) individuals had ingested pesticides, whereas 1647 (36%) had ingested yellow oleander (Thevetia peruviana) seeds. Mortality was the primary outcome measure. Analysis was by intention to treat. The trial is registered with controlled-trials.com as ISRCTN02920054. FINDINGS: Mortality did not differ between the groups. 97 (6.3%) of 1531 participants in the multiple-dosegroup died, compared with 105 (6.8%) of 1554 in the no charcoal group (adjusted odds ratio 0.96, 95% CI 0.70-1.33). No differences were noted for patients who took particular poisons, were severely ill on admission, or who presented early. INTERPRETATION: We cannot recommend the routine use of multiple-dose activated charcoal in rural Asia Pacific; although further studies of early charcoal administration might be useful, effective affordable treatments are urgently needed. Comment in : Is this the epitaph for multiple-dose activated charcoal? [Lancet. 2008]
Potential interventions for preventing pesticide self-poisoning by restricting access through vendors in Sri Lanka
(Hogrefe Publishing, 2018) Weerasinghe, M.; Konradsen, F.; Eddleston, M.; Pearson, M.; Jayamanne, S.; Gunnell, D.; Hawton, K.; Agampodi, S.
BACKGROUND: In South Asia, up to one in five individuals who use pesticides for self-harm purchase them immediately prior to the event. AIMS: From reviewing the literature we proposed four interventions: (a) farmer identification cards (ID); (b) prescriptions; (c) cooling-off periods; and (d) training pesticide vendors. We aimed to identify the most promising intervention. Method: The study was conducted in Sri Lanka. We mapped stakeholders' interest and power in relation to each intervention, and followed this by a ranking exercise. Seven focus group discussions (FGDs) were conducted to assess facilitators and barriers to implementation. RESULTS:Vendor training was the most supported intervention, being ranked first by the stakeholders. The participants in the FGDs strongly supported training of vendors as it was seen to be easy to implement and was considered more convenient. Farmer IDs, prescriptions, and cooling-off periods were thought to have more barriers than facilitators and they were strongly opposed by end users (farmers and vendors), who would potentially block their implementation. LIMITATIONS: Cost considerations for implementing the proposed intervention were not considered. CONCLUSION: Training vendors might be the most appropriate intervention to restrict sales of pesticides to people at risk of suicidal behavior. This requires field testing
Pralidoxime in acute organophosphorus insecticide poisoning--a randomised controlled trial
(Public Library of Science, 2009) Eddleston, M.; Eyer, P.; Worek, F.; Juszczak, E.; Alder, N.; Mohamed, F.; Senarathna, L.; Hittarage, A.; Azher, S.; Jeganathan, K.; Jayamanne, S.; von Meyer, L.; Dawson, A.H.; Sheriff, M.H.; Buckley, N.A.
BACKGROUND: Poisoning with organophosphorus (OP) insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of pralidoxime, this antidote's effectiveness remains unclear. We aimed to determine whether the addition of pralidoxime chloride to atropine and supportive care offers benefit. METHODS AND FINDINGS: We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receivepralidoxime (121) or saline placebo (114). Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving pralidoxime: 30/121 (24.8%) receiving pralidoxime died, compared with 18/114 (15.8%) receiving placebo (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 0.88-3.26, p = 0.12). Incorporating the baseline amount of acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving pralidoxime compared to placebo, further decreasing the likelihood that pralidoxime is beneficial. The need for intubation was similar in both groups (pralidoxime 26/121 [21.5%], placebo 24/114 [21.1%], adjusted HR 1.27 [95% CI 0.71-2.29]). To reduce confounding due to ingestion of different insecticides, we further analysed patients with confirmed chlorpyrifos or dimethoate poisoning alone, finding no evidence of benefit. CONCLUSIONS: Despite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required.
The Prevalence of previous self-harm amongst self-poisoning patients in Sri Lanka
(Springer International, 2011) Mohamed, F.; Perera, A.; Wijayaweera, K.; Kularatne, K.; Jayamanne, S.; Eddleston, M.; Dawson, A.; Konradsen, F.; Gunnell, D.
BACKGROUND: One of the most important components of suicide prevention strategies is to target people who repeat self-harm as they are a high risk group. However, there is some evidence that the incidence of repeat self-harm is lower in Asia than in the West. The objective of this study was to investigate the prevalence of previous self-harm among a consecutive series of self-harm patients presenting to hospitals in rural Sri Lanka. METHOD: Six hundred and ninety-eight self-poisoning patients presenting to medical wards at two hospitals in Sri Lanka were interviewed about their previous episodes of self-harm. RESULTS: Sixty-one (8.7%, 95% CI 6.7-11%) patients reported at least one previous episode of self-harm [37 (10.7%) male, 24 (6.8%) female]; only 19 (2.7%, 95% CI 1.6-4.2%) patients had made more than one previous attempt. CONCLUSION: The low prevalence of previous self-harm is consistent with previous Asian research and is considerably lower than that seen in the West. Explanations for these low levels of repeat self-harm require investigation. Our data indicate that a focus on the aftercare of those who attempt suicide in Sri Lanka may have a smaller impact on suicide incidence than may be possible in the West.
Reactivation of plasma butyrylcholinesterase by pralidoxime chloride in patients poisoned by WHO class II toxicity organophosphorus insecticides
(Orlando, FL : Academic Press, 2013) Konickx, L.A.; Worek, F.; Jayamanne, S.; Thiermann, H.; Buckley, N.A.; Eddleston, M.
Some clinicians assess the efficacy of pralidoxime in organophosphorus (OP) poisoned patients by measuring reactivation of butyrylcholinesterase (BuChE). However, the degree of BuChE inhibition varies by OP insecticide, and it is unclear how well oximes reactivate BuChE in vivo. We aimed to assess the usefulness of BuChE activity to monitor pralidoxime treatment by studying its reactivation after pralidoxime administration to patients with laboratory-proven World Health Organization (WHO) class II OP insecticide poisoning. Patient data were derived from 2 studies, a cohort study (using a bolus treatment of 1g pralidoxime chloride) and a randomized controlled trial (RCT) (comparing 2g pralidoxime over 20 min, followed by an infusion of 0.5 g/h, with placebo). Two grams of pralidoxime variably reactivated BuChE in patients poisoned by 2 diethyl OP insecticides, chlorpyrifos and quinalphos; however, unlike acetylcholinesterase reactivation, this reactivation was not sustained. It did not reactivate BuChE inhibited by the dimethyl OPs dimethoate or fenthion. The 1-g dose produced no reactivation. Pralidoxime produced variable reactivation of BuChE in WHO class II OP-poisoned patients according to the pralidoxime dose administered, OP ingested, and individual patient. The use of BuChE assays for monitoring the effect of pralidoxime treatment is unlikely to be clinically useful. Comment in : Plasma butyrylcholinesterase as a marker of clinical outcome in diethyl organophosphorus insecticide poisoned patients treated with pralidoxime.[Toxicol Sci. 2014] Reactivation of plasma butyrylcholinesterase by pralidoxime chloride in patients poisoned by WHO class II toxicity organophosphorus insecticides.[Toxicol Sci. 2014]
Risk factors associated with purchasing pesticide from shops for self-poisoning: a protocol for a population-based case-control study
(British Medical Association, 2015) Weerasinghe, M.; Konradsen, F.; Eddleston, M.; Pearson, M.; Gunnell, D.; Hawton, K.; Jayamanne, S.; Pabasara, C.; Jayathilaka, T.; Dissanayaka, K; Rajapaksha, S.; Thilakarathna, P.; Agampodi, S.
INTRODUCTION: Pesticide self-poisoning is one of the most frequently used methods of suicide worldwide, killing over 300,000 people annually. Around 15-20% of pesticide self-poisonings occur soon after the person has bought the pesticide from a shop. We aim to determine the characteristics of individuals who purchase pesticides directly from shops and how they differ from individuals who access pesticides from other sources such as home, home garden or farmland. This information will help inform possible vendor/shop-based intervention strategies aimed at reducing access to pesticides used for self-harm. METHODS AND ANALYSIS: This study will investigate risk factors associated with purchasing pesticides for acts of self-poisoning from pesticide shops, including cases identified over a 9-month period using a population-based case-control group approach. Four interviewer-administered data collection tools will be used for this study: a semistructured questionnaire, Beck Suicidal Intent Scale (SIS), Clinical Interview Schedule-Sinhalese version (CIS-Sn) and Alcohol Use Disorders Identification Test (AUDIT). Each case (expected n=33) will be compared with two groups of individuals: (1) those who have self-poisoned using pesticides from the home, home garden or farmland and (2) those who bought pesticides from the same shops as the above cases, but not did not self-poison. Logistic regression models will be used to identify risk factors of purchasing pesticides for self-poisoning from shops. ETHICS AND DISSEMINATION: The study has received ethical approval from the Ethical Review Committee of the Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka. A sensitive data collection technique will be used and ethical issues will be considered throughout the study. Results will be disseminated in scientific peer-reviewed articles. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Risk factors for deliberate self-harm in young people in rural Sri Lanka: a prospective cohort study of 22,000 individuals
(Sri Lanka Medical Association, 2021) Fernando, K.; Jayamanna, S.; Weerasinghe, M.; Priyadarshana, C.; Ratnayake, R.; Pearson, M.; Gunnell, D.; Dawson, A.; Hawton, K.; Konradsen, F.; Eddleston, M.; Metcalfe, C.; Knipe, D.
Background: Over 90% of youth suicide deaths occur in low- and middle-income countries. Despite this relatively little is known about risk factors in this context. Aims: Investigate risk factors for deliberate self-harm (non-fatal) in young people in rural Sri Lanka. Methods: A prospective cohort study of 22,401 individuals aged 12-18 years with complete data on sex, student status, household asset score, household access to pesticides and household problematic alcohol use. Deliberate self-harm was measured prospectively by reviewing hospital records. Poisson regression estimated incidence rate ratios (IRRs) for the association of risk factors with deliberate self-harm. Results: Females were at higher risk of deliberate self-harm compared to males (IRR 2.05; 95%CI 1.75 – 2.40). Lower asset scores (low compared to high: IRR 1.46, 95%CI 1.12 - 2.00) and having left education (IRR 1.61 95%CI 1.31 – 1.98) were associated with higher risks of deliberate self-harm, with evidence that the effect of not being in school was more pronounced in males (IRR 1.94; 95%CI 1.40 – 2.70) than females. There was no evidence of an association between household pesticide access and deliberate self-harm risk, but problematic household alcohol use was associated with increased risk (IRR 1.23; 95%CI 1.04 – 1.45), with evidence that this was more pronounced in females than males (IRR for females 1.42; 95%CI 1.17 – 1.72). There was no evidence of deliberate self-harm risk being higher at times of school exam stress. Conclusion: Indicators of lower socioeconomic status, not being in school, and problematic alcohol use in households, were associated with increased deliberate self-harm risk in young people.
Risk of suicide and repeat self-harm after hospital attendance for non-fatal self-harm in Sri Lanka: a cohort study.
(Elsevier,, 2019) Knipe, D.; Metcalfe, C.; Hawton, K.; Pearson, M.; Dawson, A.; Jayamanne, S.; Konradsen, F.; Eddleston, M.; Gunnell, D.
BACKGROUND: Evidence from high income countries (HICs) suggests that individuals who present to hospital after self-harm are an important target for suicide prevention, but evidence from low and middle-income countries (LMICs) is lacking. We aimed to investigate the risk of repeat self-harm and suicide, and factors associated with these outcomes, in a large cohort of patients presenting to hospital with self-harm in rural Sri Lanka. METHODS: In this cohort study, hospital presentations for self-harm at 13 hospitals in a rural area of North Central Province (population 224 000), Sri Lanka, were followed up with a self-harm surveillance system, established as part of a community randomised trial, and based on data from all hospitals, coroners, and police stations in the study area. We estimated the risk of repeat non-fatal and fatal self-harm and risk factors for repetition with Kaplan-Meier methods and Cox proportional hazard models. Sociodemographic (age, sex, and socioeconomic position) and clinical (past self-harm and method of self-harm) characteristics investigated were drawn from a household survey in the study area and data recorded at the time of index hospital presentation. We included all individuals who had complete data for all variables in the study in our primary analysis. OUTCOMES: Between July 29, 2011, and May 12, 2016, we detected 3073 episodes of self-harm (fatal and non-fatal) in our surveillance system, of which 2532 (82·3%) were linked back to an individual in the baseline survey. After exclusion of 145 ineligible episodes, we analysed 2259 index episodes of self-harm. By use of survival models, the estimated risk of repeat self-harm (12 months: 3· 1%, 95% CI 2·4-3·9; 24 months: 5·2%, 4·3-6·4) and suicide (12 months: 0·6%, 0·4-1·1; 24 months: 0·8%, 0·5-1·3) in our study was considerably lower than that in HICs. A higher risk of repeat self-harm was observed in men than in women (fatal and non-fatal; hazard ratio 2·0, 95% CI 1·3-3·2; p=0·0021), in individuals aged 56 years and older compared with those aged 10-25 years (fatal; 16·1, 4·3-59·9; p=0·0027), and those who used methods other than poisoning in their index presentation (fatal and non-fatal; 3·9, 2·0-7·6; p=0·00027). We found no evidence of increased risk of repeat self-harm or suicide in those with a history of self-harm before the index episode. INTERPRETATION: Although people who self-harm are an important high-risk group, focusing suicide prevention efforts on those who self-harm might be somewhat less important in LMICs compared with HICs given the low risk of repeat self-harm and subsequent suicide death. Strategies that focus on other risk factors for suicide might be more effective in reducing suicide deaths in LMICs in south Asia. A better understanding of the low incidence of repeat self-harm is also needed, as this could contribute to prevention strategies in nations with a higher incidence of repetition and subsequent suicide death.
The Role of private pesticide vendors in preventing access to pesticides for self-poisoning in rural Sri Lanka
(London : BMJ Pub. Group, 2014) Weerasinghe, M.; Pearson, M.; Peiris, R.; Dawson, A.H.; Eddleston, M.; Jayamanne, S.; Agampodi, S.; Konradsen, F.
In 15% to 20% of self-poisoning cases, the pesticides used are purchased from shops just prior to ingestion. We explored how pesticide vendorsinteracted with customers at risk of self-poisoning to identify interventions to prevent such poisonings. Two strategies were specifically discussed: selling pesticides only to farmers bearing identity cards or customers bearing pesticide 'prescriptions'. Vendors reported refusing to sell pesticides to people thought to be at risk of self-poisoning, but acknowledged the difficulty of distinguishing them from legitimate customers; vendors also stated they did want to help to improve identification of such customers. The community did not blame vendors when pesticides used for self-poison were purchased from their shops. Vendors have already taken steps to restrict access, including selling low toxic products, counselling and asking customer to return the next day. However, there was little support for the proposed interventions of 'identity cards' and 'prescriptions'. Novel public health approaches are required to complement this approach.