Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item 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.Item 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.Item 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.Item 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.Item 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.Item Vendor-based restrictions on pesticide sales to prevent pesticide self-poisoning - a pilot study(BioMed Central, 2018) Weerasinghe, M.; Konradsen, F.; Eddleston, M.; Pearson, M.; Jayamanne, S.; Gunnell, D.; Hawton, K.; Agampodi, S.BACKGROUND: In South Asia, up to 20% of people ingesting pesticides for self-poisoning purchase the pesticide from a shop with the sole intention of self-harm. Individuals who are intoxicated with alcohol and/or non-farmers represent 72% of such high-risk individuals. We aimed to test the feasibility and acceptability of vendor-based restrictions on pesticide sales for such high-risk individuals. METHODS: We conducted a pilot study in 14 (rural = 7, urban = 7) pesticide shops in Anuradhapura District of Sri Lanka. A two-hour training program was delivered to 28 pesticide vendors; the aim of the training was to help vendors recognize and respond to customers at high risk of pesticide self-poisoning. Knowledge and attitudes of vendors towards preventing access to pesticides for self-poisoning at baseline and in a three month follow-up was evaluated by questionnaire. Vendors were interviewed to explore the practice skills taught in the training and their assessment of the program. RESULTS: The scores of knowledge and attitudes of the vendors significantly increased by 23% (95% CI 15%-32%, p < 0.001) and by 16% (95% CI 9%-23%, p < 0.001) respectively in the follow-up. Fifteen (60%) vendors reported refusing sell pesticides to a high-risk person (non-farmer or intoxicated person) in the follow-up compared to three (12%) at baseline. Vendors reported that they were aware from community feedback that they had prevented at least seven suicide attempts. On four identified occasions, vendors in urban shops had been unable to recognize the self-harming intention of customers who then ingested the pesticide. Only 2 (8%) vendors were dissatisfied with the training and 23 (92%) said they would recommend it to other vendors. CONCLUSIONS: Our study suggests that vendor-based sales restriction in regions with high rates of self-poisoning has the potential to reduce access to pesticides for self-poisoning. A large-scale study of the effectiveness and sustainability of this approach is needed.Item 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.Item 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.Item 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]Item Study protocol: a randomised controlled trial of multiple and single dose activated charcoal for acute self-poisoning(London : BioMed Central, 2007) Eddleston, M.; Juszczak, E.; Buckley, N.A.; Senarathna, L.; Mohammed, F.; Allen, S.; Dissanayake, W.; Hittarage, A.; Azher, S.; Jeganathan, K.; Jayamanne, S.; Sheriff, M.H.; Warrell, D.A.; Ox-Col Poisoning Study collaboratorsBACKGROUND: The case fatality for intentional self-poisoning in rural Asia is 10-30 times higher than in the West, mostly due to the use of highly toxic poisons. Activated charcoal is a widely available intervention that may - if given early - bind to poisons in the stomach and prevent their absorption. Current guidelines recommend giving a single dose of charcoal (SDAC) if patients arrive within an hour of ingestion. Multiple doses (MDAC) may increase poison elimination at a later time by interrupting any enterohepatic or enterovascular circulations. The effectiveness of SDAC or MDAC is unknown. Since most patients present to hospital after one hour, we considered MDAC to have a higher likelihood of clinical benefit and set up a study to compare MDAC with no charcoal. A third arm of SDAC was added to help determine whether any benefit noted from MDAC resulted from the first dose or all doses. METHODS/DESIGN: We set up a randomised controlled trial assessing the effectiveness of superactivated charcoal in unselected adult self-poisoning patients admitted to the adult medical wards of three Sri Lankan secondary hospitals. Patients were randomised to standard treatment or standard treatment plus either a single 50 g dose of superactivated charcoal dissolved in 300 ml of water or six doses every four hours. All patients with a history of poison ingestion were approached concerning the study and written informed consent taken from each patient, or their relative (for unconscious patients or those <16 yrs), recruited to the study. The exclusion criteria were: age under 14 yrs; prior treatment with activated charcoalduring this poisoning episode; pregnancy; ingestion of a corrosive or hydrocarbon; requirement for oral medication; inability of the medical staff to intubate the patient with a Glasgow Coma Score <13; presentation >72 hrs post-ingestion, and previous recruitment. The primary outcome was in-hospital mortality; secondary outcomes included the occurrence of serious complications (need for intubation, time requiring assisted ventilation, fits, cardiac dysrhythmias). Analysis will be on an intention-to-treat basis; the effects of reported time to treatment after poisoning and status on admission will also be assessed. DISCUSSION: This trial will provide important information on the effectiveness of both single and multiple dose activated charcoal in the forms of poisoning commonly seen in rural Asia. If charcoal is found to be effective, it should be possible to make it widely available across rural Asia in an affordable formulation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN02920054.