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Background: This qualitative study presents an in-depth evaluation of the contributory psycho-socio-cultural and physical-economic factors related to paediatric poisoning in rural Sri Lanka. Method: The study was conducted at paediatric wards of Anuradhapura teaching hospital (THA) over a period of two years (2012 – 2014). Main methods of data collection were participants’ narrative and focus group discussions (FGDs). All parents of children with acute poisoning were recruited to FGDs. The structure of phenomena was developed based on descriptive phenomenological inquiries and key themes were identified at data analysis stage. Results: 383 parents participated in focus group discussions. Data were categorized to four domains; (1) parental awareness of poisoning risks, (2) presence of child, parent and environment related risk factors, (3) issues related to first aid care and provision of care until child was brought to emergency care unit, and (4) possible measures to prevent further poisoning. Interaction of multiple risk factors was observed in children with both intentional and unintentional poisoning. Accidental poisonings were associated with certain cultural practices, unsafe environment and unsafe storage of poisons. Children with intentional poisoning frequently had disrupted family relationships. Harmful first aid measures and delayed presentation at the primary care unit had negative impact on poisoning related outcomes. Parents believed community education, safe storage of poisons, and safe environment would likely bring down poison related morbidity. Conclusion: Person, poison and environment related risk factors can lead to acute poisoning emergencies in children in rural Sri Lanka. Often multiple risk factors interact to bring about the poisoning event. Avoidance of harmful first aid measures and early presentation at the primary care unit would bring down poisoning related morbidity. Effect of community education, safe storage of poisons and safe environment should be evaluated in the view of preventing poisoning. [ABSTRACT FROM AUTHOR]

Objective To assess if a ward-based clinical pharmacy service resolving drug-related problems improved medication appropriateness at discharge and prevented drug-related hospital readmissions. Method Between March and September 2013, we recruited patients with noncommunicable diseases in a Sri Lankan tertiary-care hospital, for a non-randomized controlled clinical trial. The intervention group received usual care and clinical pharmacy service. The intervention pharmacist made prospective medication reviews, identified drug-related problems and discussed recommendations with the health-care team and patients. At discharge, the patients received oral and written medication information. The control group received usual care. We used the medication appropriateness index to assess appropriateness of prescribing at discharge. During a six-month follow-up period, a pharmacist interviewed patients to identify drug-related hospital readmissions. Results Data from 361 patients in the intervention group and 354 patients in the control group were available for analysis. Resolutions of drug-related problems were higher in the intervention group than in the control group (57.6%; 592/1027, versus 13.2%; 161/1217; P < 0.001) and the medication was more appropriate in the intervention group. Mean score of medication appropriateness index per patient was 1.25 versus 4.3 in the control group (P < 0.001). Patients in the intervention group were less likely to be readmitted due to drug-related problems (44 patients of 311 versus 93 of 311 in the control group; P < 0.001). Conclusion A ward-based clinical pharmacy service improved appropriate prescribing, reduced drug-related problems and readmissions for patients with noncommunicable diseases. Implementation of such a service could improve health care in Sri Lanka and similar settings. [ABSTRACT FROM AUTHOR]

Background: Non-accidental poisoning in the paediatric age group is uncommon and international literature on this subject is limited. There are no Sri Lankan paediatric studies on non-accidental poisoning to date. The objective of the current study was to explore the predisposing factors and profile of children less than 12 years in rural Sri Lanka who had non-accidental poisoning. Method: This cross-sectional study was conducted at Anuradhapura teaching hospital for two years (from February 2012 to January 2014) involving all children below 12 years and presented with either a history of acute non-accidental self-poisoning or non-accidental poisoning by another person. Quantitative data were collected using a structured questionnaire and qualitative data to explore the background socio-cultural factors were collected using focused group discussions. Both quantitative and qualitative data were analysed separately in the two groups. Results: Nineteen children with non-accidental poisoning were recruited among 383 acute poisoning admissions over two years. The majority of children were male - 13 (68.4%). All children who had non-accidental self-poisoning were at least eight years of age while the mean age of children poisoned by another person was 4.6 years. Children mostly ingested pesticides (9/14-64.3%) followed by plant poisons and medicinal poisons. No child was reported to have ingested household chemicals including kerosene oil or miscellaneous substances intentionally. Children with non-accidental self-poisoning often had acute psychological distress and an immediate preceding event which resulted in the poisoning event. Verbal abuse by parents, poor family relationships, psychiatric disorders in children and emotional disturbances were often predisposing factors. Four children had morbidity secondary to aspiration pneumonia, respiratory arrest, and cardiac arrhythmias. Case fatality rate was 14.3% among children with non-accidental selfpoisoning. Children with non-accidental poisoning by another person often did not have acute psychological distress prior to the poisoning event. When the perpetrator was one of the parents, those families had major disruptions in family relationships and functioning. Conclusion: Non-accidental poisoning in paediatric age could be either non-accidental self-poisoning or non-accidental poisoning by another person. The risk factors for the two types of non-accidental poisonings are different and multitudinous. These predisposing factors need to be further evaluated through community-based studies. [ABSTRACT FROM AUTHOR]

Introduction. Kerosene oil poisoning is one of common presentations to emergency departments among children in rural territories of developing countries. This study aimed to describe clinical manifestations, reasons for delayed presentations, harmful first aid practices, complications, and risk factors related to kerosene oil poisoning among children in rural Sri Lanka. Methods. This multicenter study was conducted in North-Central province of Sri Lanka involving all in-patient children with acute kerosene oil poisoning. Data were collected over seven years from thirty-six hospitals in the province. Data collection was done by pretested, multistructured questionnaires and a qualitative study. Results. Male children accounted for 189 (60.4%) while 283 (93%) children were below five years. The majority of parents belonged to farming community. Most children ingested kerosene oil in home kitchen. Mortality rate was 0.3%. Lack of transport facilities and financial resources were common reasons for delayed management. Hospital transfer rate was 65.5%. Thirty percent of caregivers practiced harmful first aid measures. Commonest complication was chemical pneumonitis. Strongest risk factors for kerosene oil poisoning were unsafe storage, inadequate supervision, and inadequate house space. Conclusions. Effect of safe storage and community education in reducing the burden of kerosene oil poisoning should be evaluated. Since many risk factors interact to bring about the event of poisoning in a child, holistic approaches to community education in rural settings are recommended. [ABSTRACT FROM AUTHOR]

Background. Acute poisoning in children is a major preventable cause of morbidity and mortality in both developed and developing countries. However, there is a wide variation in patterns of poisoning and related risk factors across different geographic regions globally. This hospital based case-control study identifies the risk factors of acute unintentional poisoning among children aged 1−5 years of the rural community in a developing Asian country. Methods. This hospital based case-control study included 600 children. Each group comprised three hundred children and all children were recruited at Anuradhapura Teaching Hospital, Sri Lanka, over two years (from February 2012 to January 2014). The two groups were compared to identify the effect of 23 proposed risk factors for unintentional poisoning using multivariate analysis in a binary logistic regression model. Results. Multivariate analysis identified eight risk factors which were significantly associated with unintentional poisoning. The strongest risk factors were inadequate supervision (95% CI: 15.4–52.6), employed mother (95% CI: 2.9–17.5), parental concern of lack of family support (95% CI: 3.65–83.3), and unsafe storage of household poisons (95% CI: 1.5–4.9). Conclusions. Since inadequate supervision, unsafe storage, and unsafe environment are the strongest risk factors for childhood unintentional poisoning, the effect of community education to enhance vigilance, safe storage, and assurance of safe environment should be evaluated. [ABSTRACT FROM AUTHOR]

Background: Pesticides are identified as one of the dangerous poisons globally in children and are associated with increased short- and long-term morbidity. Pesticide poisoning is the most common method of self-poisoning among adults in rural Sri Lanka, and the clinical management is associated with significant healthcare costs to the country. There is however little data published on acute pesticide poisoning among children in rural Sri Lanka. The current study aimed to comprehensively evaluate clinical profiles, harmful first aid measures, emergency clinical management, complications and outcomes related to acute pesticide poisoning among children in the rural community of Sri Lanka. Methods: This multicenter study was conducted in the North Central Province of Sri Lanka involving all children with acute pesticide poisoning and who were between 9 months and 12 years of age. Data were collected over 7 years (2007-2014), and children from 36 hospitals were recruited. Data collection was carried out by pretested, multi-structured, interviewer-administered questionnaires to identify clinical profiles of children, harmful first aid measures, emergency clinical management, reasons for delayed management, complications and outcomes of pesticide poisoning events. Results: Among 1621 children with acute poisoning, 9.5% (155) comprised children with acute pesticide poisoning. Male children outnumbered female children, and the majority of children were less than 5 years. Most common pesticides implicated in poisoning of children were organophosphates and carbamates. Gastrointestinal and neurological symptoms were predominant clinical features. Limited transport and lack of concern regarding urgency among caregivers were leading reasons for delayed management. Most common location for poisoning was cultivation lands. Harmful first aid measures were practiced in 32.4%. 7.1% had intentional pesticide poisoning. The case fatality rate of all pesticide poisonings in the study was 1.9%. 58.1% of patients were transferred between regional hospitals and teaching hospital. Cardiac and respiratory arrests, aspiration pneumonia and convulsions were among the reported complications. Conclusions: Acute pesticide poisoning in paediatric age group (<12 years) is a relatively uncommon yet significant cause of child health-related morbidity and mortality in rural Sri Lanka. Patterns of poisoning represent the pattern of pesticide use by the rural community. The practice of harmful first aid measures by caregivers and delay in attending the emergency department may negatively impact patient outcomes. [ABSTRACT FROM AUTHOR]

Plant poisoning is a common presentation in paediatric practice and an important cause of preventable mortality and morbidity in Sri Lanka. The burden of plant poisoning is largely underexplored. The current multicenter study based in rural Sri Lanka assessed clinical profiles, poison related factors, clinical management, complications, outcomes, and risk factors associated with plant poisoning in the paediatric age group. Among 325 children, 57% were male with 64% being below five years of age. 99.4% had ingested the poison. Transfer rate was 66.4%. Most had unintentional poisoning. Commonest poison plant was Jatropha circus and poisoning event happened mostly in home garden. 29% of parents practiced harmful first-aid practices. 32% of children had delayed presentations to which the commonest reason was lack of parental concern regarding urgency of seeking medical care. Presence of poisonous plants in home garden was the strongest risk factor for plant poisoning. Mortality rate was 1.2% and all cases had Oleander poisoning. The study revealed the value of community awareness regarding risk factors and awareness among healthcare workers regarding the mostly benign nature of plant poisoning in children in view of limiting incidence of plant poisoning and reducing expenditure on patient management. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Agricultural pesticide self-poisoning is a major public health problem in rural Asia. The use of safer household pesticide storage has been promoted to prevent deaths, but there is no evidence of effectiveness. We aimed to test the effectiveness of lockable household 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. [ABSTRACT FROM AUTHOR]

Background: Multidisciplinary patient management including a clinical pharmacist shows an improvement in patient quality use of medicine. Implementation of a clinical pharmacy service represents a significant novel change in practice in Sri Lanka. Although attitudes of doctors and nurses are an important determinant of successful implementation, there is no Sri Lankan data about staff attitudes to such changes in clinical practice. This study determines the level of acceptance and attitudes of doctors and nurses towards the introduction of a ward-based clinical pharmacy service in Sri Lanka.Methods: This is a descriptive cross-sectional sub-study which determines the acceptance and attitudes of healthcare staff about the introduction of a clinical pharmacy service to a tertiary care hospital in Sri Lanka. The level of acceptance of pharmacist's recommendations regarding drug-related problems (DRPs) was measured. Data regarding attitudes were collected through a pre-tested self-administered questionnaires distributed to doctors (baseline, N =13, post-intervention period, N = 12) and nurses (12) worked in professorial medical unit at baseline and post-intervention period.Results: A total of 274 (272 to doctors and 2 to nurses) recommendations regarding DRPs were made. Eighty three percent (225/272) and 100% (2/2) of the recommendations were accepted by doctors and nurses, respectively. The rate of implementation of pharmacist's recommendations by doctors was 73.5% (200/272) (95% CI 67.9 - 78.7%; P < 0.001). The response rate of doctors was higher at the post-intervention period (92.3%; 12/13) compared to the baseline (66.7%; 8/12). At the post-intervention survey 91.6% of doctors were happy to work with competent clinical pharmacists and accepted the necessity of this service to improve standards of care. The nurses' rate of response at baseline and post-intervention surveys were 80.0 and 0.0% respectively. Their perceptions on the role of clinical pharmacist were negative at baseline survey.Conclusions: There was high acceptance and implementation of clinical pharmacist's recommendations regarding DRPs by the healthcare team. The doctors' views and attitudes were positive regarding the inclusion of a ward-based pharmacist to the healthcare team. However there is a need to improve liaison between clinical pharmacist and nursing staff.Trial Registration: Sri Lanka Clinical Trials Registry SLCTR/2013/029 Date: 13 September 2013; retrospectively registered. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is common following paraquat ingestion. The diagnostic performance of injury biomarkers was investigated in serial blood and urine samples from patients from 5 Sri Lankan hospitals. Functional AKI was diagnosed using serum creatinine (sCr) or serum cystatin C (sCysC). The 95th centile in healthy subjects defined the urinary biomarker cutoffs for diagnosing structural AKI. 50 poisoned patients provided 2 or more specimens, 76% developed functional AKI [AKIN stage 1 ( n = 12), 2 ( n = 7) or 3 ( n = 19)]; 19/26 patients with AKIN stage 2/3 also had functional AKI by sCysC criteria (≥50% increase). Urinary cystatin C (uCysC), clusterin (uClu) and NGAL (uNGAL) increased within 24 h of ingestion compared with NoAKI patients and healthy controls. Each biomarker demonstrated moderate diagnostic utility [AUC–ROC: uCysC 0.79, uNGAL 0.79, uClu 0.68] for diagnosis of functional AKI at 16 h. Death occurred only in subjects with functional AKI. Structural biomarker-based definitions detected more AKI than did sCr or sCysC, but did not independently predict death. Renal injury biomarkers did not add clinical value to patients who died rapidly due to multi-organ failure. Use of injury biomarkers within 16–24 h may guide early intervention for reno-protection in less severe paraquat poisoning. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is common after severe paraquat poisoning and usually heralds a fatal outcome. The rapid large increases in serum creatinine (Cr) exceed that which can be explained by creatinine kinetics based on loss of glomerular filtration rate (GFR). Methods and Findings: This prospective multi-centre study compared the kinetics of two surrogate markers of GFR, serum creatinine and serum cystatin C (CysC), following paraquat poisoning to understand and assess renal functional loss after paraquat poisoning. Sixty-six acute paraquat poisoning patients admitted to medical units of five hospitals were included. Relative changes in creatinine and CysC were monitored in serial blood and urine samples, and influences of non-renal factors were also studied. Results: Forty-eight of 66 patients developed AKI (AKIN criteria), with 37 (56%) developing moderate to severe AKI (AKIN stage 2 or 3). The 37 patients showed rapid increases in creatinine of >100% within 24 hours, >200% within 48 hours and >300% by 72 hours and 17 of the 37 died. CysC concentration increased by 50% at 24 hours in the same 37 patients and then remained constant. The creatinine/CysC ratio increased 8 fold over 72 hours. There was a modest fall in urinary creatinine and serum/urine creatinine ratios and a moderate increase in urinary paraquat during first three days. Conclusion: Loss of renal function contributes modestly to the large increases in creatinine following paraquat poisoning. The rapid rise in serum creatinine most probably represents increased production of creatine and creatinine to meet the energy demand following severe oxidative stress. Minor contributions include increased cyclisation of creatine to creatinine because of acidosis and competitive or non-competitive inhibition of creatinine secretion. Creatinine is not a good marker of renal functional loss after paraquat poisoning and renal injury should be evaluated using more specific biomarkers of renal injury. [ABSTRACT FROM AUTHOR]

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 20min, followed by an infusion of 0.5g/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. [ABSTRACT FROM PUBLISHER]

Introduction: The psychological impact of snakebite on its victims, especially possible late effects, has not been systematically studied. Objectives: To assess delayed somatic symptoms, depressive disorder, post-traumatic stress disorder (PTSD), and impairment in functioning, among snakebite victims. Methods: The study had qualitative and quantitative arms. In the quantitative arm, 88 persons who had systemic envenoming following snakebite from the North Central Province of Sri Lanka were randomly identified from an established research database and interviewed 12 to 48 months (mean 30) after the incident. Persons with no history of snakebite, matched for age, sex, geograpical location and occupation, acted as controls. A modified version of the Beck Depression Inventory, Post-Traumatic Stress Symptom Scale, Hopkins Somatic Symptoms Checklist, Sheehan Disability Inventory and a structured questionnaire were administered. In the qualitative arm, focus group discussions among snakebite victims explored common somatic symptoms attributed to envenoming. Results: Previous snakebite victims (cases) had more symptoms than controls as measured by the modified Beck Depression Scale (mean 19.1 Vs 14.4; p<0.001) and Hopkins Symptoms Checklist (38.9 vs. 28.2; p<0.001). 48 (54%) cases met criteria for depressive disorder compared to 13 (15%) controls. 19 (21.6%) cases also met criteria for PTSD. 24 (27%) claimed that the snakebite caused a negative change in their employment; nine (10.2%) had stopped working and 15 (17%) claimed residual physical disability. The themes identified in the qualitative arm included blindness, tooth decay, body aches, headaches, tiredness and weakness. Conclusions: Snakebite causes significant ongoing psychological morbidity, a complication not previously documented. The economic and social impacts of this problem need further investigation. Author Summary: Snakebite envenoming is a neglected public health problem, especially in rural areas of tropical and sub-tropical countries. Little is known about the long term effects, and even less about the possible psychological effects, of snakebites and envenoming. We investigated the possible psychological impact of snakebite in 88 persons who had been envenomed 1 to 4 years ago in a rural agricultural area in Sri Lanka by using accepted measurements of psychological disability and group discussions among victims. 88 persons from the same areas who had not been bitten by a snake, but were of similar age, sex and occupation were also assessed in a similar manner. Compared to those who had not been bitten, snakebite victims had significantly more symptoms suggesting psychological disability, depression and post-traumatic stress. More than a fourth of those bitten claimed that the snakebite caused a negative change in their employment, and 10% had stopped working altogether. 17% claimed to have residual physical disability which they attributed to the bite, although no disability could be detected when they were examined. These findings indicate that snakebite results in ongoing psychological disability even 1 to 4 years after the episode, a complication that has not been previously reported. [ABSTRACT FROM AUTHOR]

Introduction: The psychological impact of snakebite on its victims, especially possible late effects, has not been systematically studied. Objectives: To assess delayed somatic symptoms, depressive disorder, post-traumatic stress disorder (PTSD), and impairment in functioning, among snakebite victims. Methods: The study had qualitative and quantitative arms. In the quantitative arm, 88 persons who had systemic envenoming following snakebite from the North Central Province of Sri Lanka were randomly identified from an established research database and interviewed 12 to 48 months (mean 30) after the incident. Persons with no history of snakebite, matched for age, sex, geograpical location and occupation, acted as controls. A modified version of the Beck Depression Inventory, Post-Traumatic Stress Symptom Scale, Hopkins Somatic Symptoms Checklist, Sheehan Disability Inventory and a structured questionnaire were administered. In the qualitative arm, focus group discussions among snakebite victims explored common somatic symptoms attributed to envenoming. Results: Previous snakebite victims (cases) had more symptoms than controls as measured by the modified Beck Depression Scale (mean 19.1 Vs 14.4; p,0.001) and Hopkins Symptoms Checklist (38.9 vs. 28.2; p,0.001). 48 (54%) cases met criteria for depressive disorder compared to 13 (15%) controls. 19 (21.6%) cases also met criteria for PTSD. 24 (27%) claimed that the snakebite caused a negative change in their employment; nine (10.2%) had stopped working and 15 (17%) claimed residual physical disability. The themes identified in the qualitative arm included blindness, tooth decay, body aches, headaches, tiredness and weakness. Conclusions: Snakebite causes significant ongoing psychological morbidity, a complication not previously documented. The economic and social impacts of this problem need further investigation. [ABSTRACT FROM AUTHOR]

Background: Snakebite incidence shows both spatial and temporal variation. However, no study has evaluated spatiotemporal patterns of snakebites across a country or region in detail. We used a nationally representative population sample to evaluate spatiotemporal patterns of snakebite in Sri Lanka. Methodology: We conducted a community-based cross-sectional survey representing all nine provinces of Sri Lanka. We interviewed 165 665 people (0.8% of the national population), and snakebite events reported by the respondents were recorded. Sri Lanka is an agricultural country; its central, southern and western parts receive rain mainly from Southwest monsoon (May to September) and northern and eastern parts receive rain mainly from Northeast monsoon (November to February). We developed spatiotemporal models using multivariate Poisson process modelling to explain monthly snakebite and envenoming incidences in the country. These models were developed at the provincial level to explain local spatiotemporal patterns. Principal findings: Snakebites and envenomings showed clear spatiotemporal patterns. Snakebite hotspots were found in North-Central, North-West, South-West and Eastern Sri Lanka. They exhibited biannual seasonal patterns except in South-Western inlands, which showed triannual seasonality. Envenoming hotspots were confined to North-Central, East and South-West parts of the country. Hotspots in North-Central regions showed triannual seasonal patterns and South-West regions had annual patterns. Hotspots remained persistent throughout the year in Eastern regions. The overall monthly snakebite and envenoming incidences in Sri Lanka were 39 (95%CI: 38–40) and 19 (95%CI: 13–30) per 100 000, respectively, translating into 110 000 (95%CI: 107 500–112 500) snakebites and 45 000 (95%CI: 32 000–73 000) envenomings in a calendar year. Conclusions/significance: This study provides information on community-based monthly incidence of snakebites and envenomings over the whole country. Thus, it provides useful insights into healthcare decision-making, such as, prioritizing locations to establish specialized centres for snakebite management and allocating resources based on risk assessments which take into account both location and season. Author summary: Snakebite envenoming is a neglected tropical disease which mainly affects people living in rural areas of the tropics. Snakebite can result in in mild, moderate or severe envenomation, psychological disturbances, long-term disability, and deaths. Snakebite incidence demonstrates both spatial variation and seasonal patterns in many countries, but there have been no previous in-depth evaluations of spatiotemporal patterns of snakebite risk at a country level. We undertook an island-wide community survey to determine the spatiotemporal patterns of snakebite in the country. Both snakebites and snakebite envenomings showed clear spatiotemporal patterns where certain hotspots persisted throughout the year while others showed dynamic changes within a year. We found that the monthly snakebite incidence was 39 per 100,000 and envenoming incidences was 19 per 100,000 in Sri Lanka. We developed monthly snakebite and snakebite envenoming risk maps to identify snakebite hotspots and cold spots in the country. These maps provide useful insights into healthcare decision-making, such as, prioritizing locations to establish specialized centres for snakebite management and allocating resources based on risk assessments which consider both location and season. Our methodology demonstrates a general approach to model times and places of individual events and address the effects of variable survey effort and recall bias associated with epidemiological surveys. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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).Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: Health outcomes and causality are usually assessed with individual level sociodemographic variables. Studies that consider only individual-level variables can suffer from residual confounding. This can result in individual variables that are unrelated to risk behaving as proxies for uncaptured information. There is a scarcity of literature on risk factors for snakebite. In this study, we evaluate the individual-level risk factors of snakebite in Sri Lanka and highlight the impact of spatial confounding on determining the individual-level risk effects. Methods: Data was obtained from the National Snakebite Survey of Sri Lanka. This was an Island-wide community-based survey. The survey sampled 165,665 individuals from all 25 districts of the country. We used generalized linear models to identify individual-level factors that contribute to an individual’s risk of experiencing a snakebite event. We fitted separate models to assess risk factors with and without considering spatial variation in snakebite incidence in the country. Results: Both spatially adjusted and non-adjusted models revealed that middle-aged people, males, field workers and individuals with low level of education have high risk of snakebites. The model without spatial adjustment showed an interaction between ethnicity and income levels. When the model included a spatial adjustment for the overall snakebite incidence, this interaction disappeared and income level appeared as an independent risk factor. Both models showed similar effect sizes for gender and age. HEmployment and education showed lower effect sizes in the spatially adjusted model. Conclusions: Both individual-level characteristics and local snakebite incidence are important to determine snakebite risk at a given location. Individual level variables could act as proxies for underling residual spatial variation when environmental information is not considered. This can lead to misinterpretation of risk factors and biased estimates of effect sizes. Both individual-level and environmental variables are important in assessing causality in epidemiological studies. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a major complication of snake envenoming, but early diagnosis remains problematic. We aimed to investigate the time course of novel renal biomarkers in AKI following Russell’s viper (Daboia russelii) bites. Methodology/Principal findings: We recruited a cohort of patients with definite Russell’s viper envenoming and collected serial blood and urine samples on admission (<4h post-bite), 4-8h, 8-16h, 16-24h, 1 month and 3 months post-bite. AKI stage (1–3) was defined using the Acute Kidney Injury Network criteria. AKI stages (1–3) were defined by the Acute Kidney Injury Network (AKIN) criteria. There were 65 Russell’s viper envenomings and 49 developed AKI: 24 AKIN stage 1, 13 stage 2 and 12 stage 3. There was a significant correlation between venom concentrations and AKI stage (p = 0.007), and between AKI stage and six peak biomarker concentrations. Although most biomarker concentrations were elevated within 8h, no biomarker performed well in diagnosing AKI <4h post-bite. Three biomarkers were superior to serum creatinine (sCr) in predicting AKI (stage 2/3) 4-8h post-bite: serum cystatin C (sCysC) with an area under the receiver operating curve (AUC-ROC), 0.78 (95%CI:0.64–0.93), urine neutrophil gelatinase-associated lipocalin (uNGAL), 0.74 (95%CI:0.59–0.87) and urine clusterin (uClu), 0.81 (95%CI:0.69–0.93). No biomarker was better than sCr after 8h. Six other urine biomarkers urine albumin, urine beta2-microglobulin, urine kidney injury molecule-1, urine cystatin C, urine trefoil factor-3 and urine osteopontin either had minimal elevation, and/or minimal prediction for AKI stage 2/3 (AUC-ROC<0.7). Conclusions/Significance: AKI was common and sometimes severe following Russell’s viper bites. Three biomarkers uClu, uNGAL and sCysC, appeared to become abnormal in AKI earlier than sCr, and may be useful in early identification of envenoming. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Snakebite is a neglected tropical disease that has been overlooked by healthcare decision makers in many countries. Previous studies have reported seasonal variation in hospital admission rates due to snakebites in endemic countries including Sri Lanka, but seasonal patterns have not been investigated in detail.Methods: A national community-based survey was conducted during the period of August 2012 to June 2013. The survey used a multistage cluster design, sampled 165 665 individuals living in 44 136 households and recorded all recalled snakebite events that had occurred during the preceding year. Log-linear models were fitted to describe the expected number of snakebites occurring in each month, taking into account seasonal trends and weather conditions, and addressing the effects of variation in survey effort during the study and of recall bias amongst survey respondents.Results: Snakebite events showed a clear seasonal variation. Typically, snakebite incidence is highest during November-December followed by March-May and August, but this can vary between years due to variations in relative humidity, which is also a risk factor. Low relative-humidity levels are associated with high snakebite incidence. If current climate-change projections are correct, this could lead to an increase in the annual snakebite burden of 31.3% (95% confidence interval: 10.7-55.7) during the next 25-50 years.Conclusions: Snakebite in Sri Lanka shows seasonal variation. Additionally, more snakebites can be expected during periods of lower-than-expected humidity. Global climate change is likely to increase the incidence of snakebite in Sri Lanka. [ABSTRACT FROM AUTHOR]

Introduction: Sri Lanka has a population of 21 million and about 80,000 snakebites occur annually. However, there are limited data on health seeking behavior following bites. We investigated the effects of snakebite and envenoming on health seeking behavior in Sri Lanka. Methods: In a community-based island-wide survey conducted in Sri Lanka 44,136 households were sampled using a multistage cluster sampling method. An individual who reported experiencing a snakebite within the preceding 12 months was considered a case. An interviewer-administered questionnaire was used to obtain details of the bite and health seeking behavior among cases. Results: Among 165,665 individuals surveyed, there were 695 snakebite victims. 682 (98.1%) had sought health care after the bite; 381 (54.8%) sought allopathic treatment and 301 (43.3%) sought traditional treatment. 323 (46.5%) had evidence of probable envenoming, among them 227 (70.3%) sought allopathic treatment, 94 (29.1%) sought traditional treatment and 2 did not seek treatment. There was wide geographic variation in the proportion of seeking allopathic treatment from <20% in the Western province to > 90% in the Northern province. Multiple logistic regression analysis showed that seeking allopathic treatment was independently associated with being systemically envenomed (Odds Ratio = 1.99, 95% CI: 1.36–2.90, P < 0.001), distance to the healthcare facility (OR = 1.13 per kilometer, 95% CI: 1.09 to 1.17, P < 0.001), time duration from the bite (OR = 0.49 per day, 95% CI: 0.29–0.74, P = 0.002), and the local incidence of envenoming (OR = 1.31 for each 50 per 100,000, 95% CI: 1.19–1.46, P < 0.001) and snakebite (OR = 0.90 for each 50 per 100,000, 95% CI: 0.85–0.94, P < 0.001) in the relevant geographic area. Conclusions: In Sri Lanka, both allopathic and traditional treatments are sought following snakebite. The presence of probable envenoming was a major contribution to seeking allopathic treatment. [ABSTRACT FROM AUTHOR]

Background: Snakebite is a major problem affecting the rural poor in many of the poorest countries in the tropics. However, the scale of the socio-economic burden has rarely been studied. We undertook a comprehensive assessment of the burden in Sri Lanka. Methods: Data from a representative nation-wide community based household survey were used to estimate the number of bites and deaths nationally, and household and out of pocket costs were derived from household questionnaires. Health system costs were obtained from hospital cost accounting systems and estimates of antivenom usage. DALYs lost to snakebite were estimated using standard approaches using disability weights for poisoning. Findings: 79% of victims suffered economic loss following a snakebite with a median out of pocket expenditure of $11.82 (IQR 2–28.57) and a median estimated loss of income of $28.57 and $33.21 for those in employment or self-employment, respectively. Family members also lost income to help care for patients. Estimated health system costs for Sri Lanka were $ 10,260,652 annually. The annual estimated total number of DALYS was 11,101 to 15,076 per year for envenoming following snakebite. Interpretation: Snakebite places a considerable economic burden on the households of victims in Sri Lanka, despite a health system which is accessible and free at the point of care. The disability burden is also considerable, similar to that of meningitis or dengue, although the relatively low case fatality rate and limited physical sequelae following bites by Sri Lankan snakes means that this burden may be less than in countries on the African continent. [ABSTRACT FROM AUTHOR]

Background Quality use of medicines ( QUM) has been identified as a priority in Sri Lanka. Aim To identify opportunities to optimise QUM, and evaluate medication appropriateness and medication information exchanged with patients and carers on discharge in a Sri Lankan tertiary care hospital. Methods An observational, prospective, cohort study of patients systematically sampled from two medical wards. A research pharmacist determined their pre-admission medication regimen via interview at time of discharge. Issues of poor adherence and discrepancies between the pre- and post-admission medication regimens were recorded. Drug-related problems were categorised into opportunities to optimise drug therapy. The appropriateness of discharge medications was evaluated using a validated tool. The patient or carer was interviewed after discharge regarding the quality of medicine information exchanged in hospital. Results The 578 recruited patients were taking 1756 medications prior to admission, and 657 (37.4%) of these medications were not continued during admission. Opportunities to optimise drug therapy were identified on 1496 occasions during admission (median, 2.0 opportunities/patient), 215 opportunities, (14.4%) were resolved spontaneously by the medical team prior to discharge. The median score for appropriateness of medications on discharge was 1.5 per patient (interquartile range, 0.0-3.5). Of 427 patients surveyed after discharge, 52% recalled being asked about their medications on admission to hospital, 75% about previous adverse medication reactions and 39% recalled being informed about changes to their medications on discharge. Conclusion Significant opportunities exist for pharmacists to enhance quality use of medicines for patients in the current hospital-based healthcare system in Sri Lanka. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is common following glyphosate surfactant herbicide (GPSH) self-poisoning. Serum creatinine (sCr) is the most widely used renal biomarker for diagnosis of AKI although a recent study in rats suggested that urinary kidney injury molecule-1 predicted AKI earlier and better after GPSH-induced nephrotoxicity. We explored the utility of a panel of biomarkers to diagnose GPSH-induced nephrotoxicity in humans. In a prospective multi-centre observational study, serial urine and blood samples were collected until discharge and at follow-up. The diagnostic performance of each biomarker at various time points was assessed. AKI was diagnosed using the Acute Kidney Injury Network (AKIN) definitions. The added value of each biomarker to sCr to diagnose AKI was assessed by the integrated discrimination improvement (IDI) metric. Of 90 symptomatic patients, 51% developed AKI and 5 patients who developed AKIN ≥ 2 died. Increased sCr at 8 and 16 h predicted moderate to severe AKI and death. None of the 10 urinary biomarkers tested increased above normal range in patients who did not develop AKI or had mild AKI (AKIN1); most of these patients also had only minor clinical toxicity. Absolute concentrations of serum and urinary cystatin C, urinary interleukin-18 (IL-18), Cytochrome C (CytoC) and NGAL increased many fold within 8 h in patients who developed AKIN ≥ 2. Maximum 8 and 16 h concentrations of these biomarkers showed an excellent diagnostic performance (AUC-ROC ≥0.8) to diagnose AKIN ≥ 2. However, of these biomarkers only uCytoC added value to sCr to diagnose AKI when assessed by IDI metrics. GPSH-induced nephrotoxicity can be diagnosed within 24 h by sCr. Increases in uCytoC and uIL-18 confirm GPSH-induces apoptosis and causes mitochondrial toxicity. Use of these biomarkers may help to identify mechanism specific targeted therapies for GPSH nephrotoxicity in clinical trials. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: There is a paucity of robust epidemiological data on snakebite, and data available from hospitals and localized or time-limited surveys have major limitations. No study has investigated the incidence of snakebite across a whole country. We undertook a community-based national survey and model based geostatistics to determine incidence, envenoming, mortality and geographical pattern of snakebite in Sri Lanka. Methodology/Principal Findings: The survey was designed to sample a population distributed equally among the nine provinces of the country. The number of data collection clusters was divided among districts in proportion to their population. Within districts clusters were randomly selected. Population based incidence of snakebite and significant envenoming were estimated. Model-based geostatistics was used to develop snakebite risk maps for Sri Lanka. 1118 of the total of 14022 GN divisions with a population of 165665 (0.8%of the country’s population) were surveyed. The crude overall community incidence of snakebite, envenoming and mortality were 398 (95% CI: 356–441), 151 (130–173) and 2.3 (0.2–4.4) per 100000 population, respectively. Risk maps showed wide variation in incidence within the country, and snakebite hotspots and cold spots were determined by considering the probability of exceeding the national incidence. Conclusions/Significance: This study provides community based incidence rates of snakebite and envenoming for Sri Lanka. The within-country spatial variation of bites can inform healthcare decision making and highlights the limitations associated with estimates of incidence from hospital data or localized surveys. Our methods are replicable, and these models can be adapted to other geographic regions after re-estimating spatial covariance parameters for the particular region. [ABSTRACT FROM AUTHOR]

Background: Snakebite results in delayed psychological morbidity and negative psycho-social impact. However, psychological support is rarely provided to victims. Aim: To assess the effectiveness of a brief intervention which can be provided by non-specialist doctors aimed at reducing psychological morbidity following snakebite envenoming. Method: In a single blind, randomized controlled trial, snakebite victims with systemic envenoming [n = 225, 168 males, mean age 42.1 (SD 12.4) years] were randomized into three arms. One arm received no intervention (n = 68, Group A), the second received psychological first aid and psychoeducation (dispelling prevalent cultural beliefs related to snakebite which promote development of a sick role) at discharge from hospital (n = 65, Group B), while the third received psychological first aid and psychoeducation at discharge and a second intervention one month later based on cognitive behavioural principles (n = 69, Group C). All patients were assessed six months after hospital discharge for the presence of psychological symptoms and level of functioning using standardized tools. Results: At six months, there was a decreasing trend in the proportion of patients who were positive for psychiatric symptoms of depression and anxiety from Group A through Group B to Group C (Chi square test for trend = 7.901, p = 0.005). This was mainly due to a decreasing trend for symptoms of anxiety (chi-square for trend = 11.256, p = 0.001). There was also decreasing trend in the overall prevalence of disability from Group A through Group B to Group C (chi square for trend = 7.551, p = 0.006), predominantly in relation to disability in family life (p = 0.006) and social life (p = 0.005). However, there was no difference in the proportion of patients diagnosed with depression between the three groups (chi square for trend = 0.391, p = 0.532), and the intervention also had no effect on post-traumatic stress disorder. Conclusions: A brief psychological intervention, which included psychological first aid and psychoeducation plus cognitive behavioural therapy that can be provided by non-specialist doctors appeared to reduce psychiatric symptoms and disability after snakebite envenoming, but not depression or post-traumatic stress disorder. Trial Registration: Sri Lanka Clinical Trials Registry: [ABSTRACT FROM AUTHOR]

Background: There is limited information on antivenom pharmacokinetics. This study aimed to investigate the pharmacokinetics of an Indian snake antivenom in humans with Russell’s viper bites. Methods/Principal Findings: Patient data and serial blood samples were collected from patients with Russell’s viper (Daboia russelii) envenoming in Sri Lanka. All patients received Indian F(ab’)2 snake antivenom manufactured by VINS Bioproducts Ltd. Antivenom concentrations were measured with sandwich enzyme immunoassays. Timed antivenom concentrations were analysed using MONOLIXvs4.2. One, two and three compartment models with zero order input and first order elimination kinetics were assessed. Models were parameterized with clearance(CL), intercompartmental clearance(Q), central compartment volume(V) and peripheral compartment volume(VP). Between-subject-variability (BSV) on relative bioavailability (F) was included to account for dose variations. Covariates effects (age, sex, weight, antivenom batch, pre-antivenom concentrations) were explored by visual inspection and in model building. There were 75 patients, median age 57 years (40-70y) and 64 (85%) were male. 411 antivenom concentration data points were analysed. A two compartment model with zero order input, linear elimination kinetics and a combined error model best described the data. Inclusion of BSV on F and weight as a covariate on V improved the model. Inclusion of pre-antivenom concentrations or different batches on BSV of F did not. Final model parameter estimates were CL,0.078 Lh-1, V,2.2L, Q,0.178Lh-1 and VP,8.33L. The median half-life of distribution was 4.6h (10-90%iles:2.6-7.1h) and half-life of elimination, 140h (10th-90th percentilesx:95-223h). Conclusion: Indian F(ab’)2 snake antivenom displayed biexponential disposition pharmacokinetics, with a rapid distribution half-life and more prolonged elimination half-life. [ABSTRACT FROM AUTHOR]

In 15% to 20% of self-poisoning cases, the pesticides used are purchased from shops just prior to ingestion. We explored how pesticide vendors interacted 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. [ABSTRACT FROM AUTHOR]

Background. Pesticide self-poisoning causes one third of global suicides. Sri Lanka halved its suicide rate by banning WHO Class I organophosphorus (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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Envenoming from snakebites is most effectively treated by antivenom. However, the antivenom available in South Asian countries commonly causes acute allergic reactions, anaphylactic reactions being particularly serious. We investigated whether adrenaline, promethazine, and hydrocortisone prevent such reactions in secondary referral hospitals in Sri Lanka by conducting a randomised, double-blind placebo-controlled trial. Methods and Findings: In total, 1,007 patients were randomized, using a 2×2×2 factorial design, in a double-blind, placebo-controlled trial of adrenaline (0.25 ml of a 1:1,000 solution subcutaneously), promethazine (25 mg intravenously), and hydrocortisone (200 mg intravenously), each alone and in all possible combinations. The interventions, or matching placebo, were given immediately before infusion of antivenom. Patients were monitored for mild, moderate, or severe adverse reactions for at least 96 h. The prespecified primary end point was the effect of the interventions on the incidence of severe reactions up to and including 48 h after antivenom administration. In total, 752 (75%) patients had acute reactions to antivenom: 9% mild, 48% moderate, and 43% severe; 89% of the reactions occurred within 1 h; and 40% of all patients were given rescue medication (adrenaline, promethazine, and hydrocortisone) during the first hour. Compared with placebo, adrenaline significantly reduced severe reactions to antivenom by 43% (95% CI 25-67) at 1 h and by 38% (95% CI 26-49) up to and including 48 h after antivenom administration; hydrocortisone and promethazine did not. Adding hydrocortisone negated the benefit of adrenaline. Conclusions: Pretreatment with low-dose adrenaline was safe and reduced the risk of acute severe reactions to snake antivenom. This may be of particular importance in countries where adverse reactions to antivenom are common, although the need to improve the quality of available antivenom cannot be overemphasized. [ABSTRACT FROM AUTHOR]

Introduction. Deliberate self-harm with pesticides is a significant public health problem in rural Asia. We have previously shown an improved survival of patients with paraquat self-poisoning following the introduction of a new formulation with an increased emetic concentration, an alginate and a purgative in Sri Lanka. Further, formulation changes were introduced in October 2006; this study was designed to assess the impact of these changes on 6-week mortality following paraquat ingestion. Methods. Prospective, cohort study of patients admitted with paraquat poisoning to 10 hospitals across Sri Lanka between September 2006 and September 2008. Results. Overall, there was a significant (p < 0.001) increase in survival in the 533 patients included in this study compared to previous data (44.5 vs. 35.2%% before September 2006 and 27.1%% before October 2004). Patients ingesting the new INTEON®® formulation had a higher survival rate than those ingesting standard formulation (40.2 vs. 31.0%%), but this effect was not statistically significant in Cox's proportional hazards model (hazard ratio 0.81, 95%% CI 0.61--1.08 (unadjusted) and 1.17, 95%% CI 0.82--1.68 (fully adjusted), respectively). Conclusions. This study has confirmed a continued improvement in survival of patients following self-harm with paraquat in Sri Lanka in recent years; however, in contrast to previous investigations, a beneficial effect associated with the INTEON formulation could not be substantiated. This may be partly due to the large number of patients in whom paraquat concentrations were too low for analytical confirmation of the formulation (n == 105) and who had a very high survival rate (86.7%%). [ABSTRACT FROM AUTHOR]

Introduction. Self-poisoning with herbicides is an important reason for hospital admission and death in Asia. Although some herbicides have a well-described toxicity profile in humans, many of the newer compounds rely on extrapolation from animal results as no published literature on clinical outcomes of human self-poisoning has been described. One example of these compounds is bispyribac, a selective herbicide used in rice and wheat cultivation that is marketed in two containers, one containing bispyribac 400 g/L with a solvent and the other the surfactant, polyethylene glycol. We present the first case series of acute human self-poisoning with an herbicide product containing bispyribac. Methods. Clinical data for all patients who presented with acute poisoning from a bispyribac-containing herbicide (Nominee®) to two general hospitals in Sri Lanka from June 2002 to January 2009 were collected prospectively. Admission and serial blood samples were collected from consenting patients to confirm exposure and to study the toxicokinetics of bispyribac, respectively. Results. One hundred ten patients with a history of bispyribac ingestion presented after a median time of 4 h post-ingestion. There were three deaths at 15, 6, and 5 h post-ingestion because of asystolic cardiac arrest. All three patients had reduced Glasgow Coma Score (GCS) (3, 12, and 13, respectively) of whom the former two had co-ingested ethanol and developed tonic-clonic seizures. Admission blood sample was obtained from the former two of these patients but bispyribac was detected in only one of these patients. The other patient presented 2.5 h post-ingestion with a GCS of 12 but bispyribac was not detected. Excluding the patient with undetectable bispyribac, a conservative estimate of the case fatality ratio at 1.81% (95% confidence interval 0.32–5.8) can be made. The majority of the remaining patients had self-limiting upper gastrointestinal symptoms and eight patients had an abnormal GCS on presentation to hospital. The overall median hospital stay was 3 days. Bispyribac was not detectable on admission in 21 patients; in the remaining patients, the median plasma concentration was 50.55 μg/mL (interquartile range 1.28–116.5; n = 32). The peak concentration was noted around 3 h post-ingestion and plasma bispyribac concentration did not predict the severity of poisoning. Conclusion. The majority of patients developed self-resolving symptoms and were successfully managed in rural general hospitals without transfer to larger tertiary hospitals. Patients who died developed significant poisoning within 6 h and plasma bispyribac concentrations did not appear to predict mortality. The lack of correlation between bispyribac outcomes and the available plasma concentrations may be because of exposure to nonbispyribac components or other undefined factors. Clinical outcomes from acute self-poisoning with bispyribac-containing herbicides appear to be relatively more favorable than other commonly used herbicides. [ABSTRACT FROM AUTHOR]

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 receive pralidoxime (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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article presents a clinical trial to determine the efficacy of treating victims of intentional self-poisoning in developing countries with multiple-dose activated charcoal. Intentional self-poisoning has a tenfold higher mortality rate in developing countries due to the greater access to highly toxic pesticides and plants. The trials were conducted with patients at hospitals in Sri Lanka. The mortality rate among patients treated with charcoal did not improve. The authors cite the urgent need for an effective and affordable means of treatment.

Martin Wilks and colleagues compared the outcome of paraquat self-poisoning with the standard formulation against a new formulation following its introduction into Sri Lanka. [ABSTRACT FROM AUTHOR]

Background: 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 charcoal during 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. [ABSTRACT FROM AUTHOR]

Background: There are an estimated 258 million international migrants worldwide. In Asia low-skilled workers often emigrate on a temporary basis (2–3 years) without their families. There is significant concern over the mental health and wellbeing of left-behind families in this region. No previous study has examined whether the risk of suicidal behaviour is elevated in left-behind family members. Methods: Cohort study using baseline data from a large randomised controlled trial in Sri Lanka (n = 178,730 participants; 8% households had a current temporary foreign migrant) and prospective hospital presentations of suicide attempts. Using multilevel Poisson regression models, we compared the risk of attempted suicide in households with left-behind and non-left-behind family members. We also investigated whether the sex of the migrant or the age/sex of the household member left behind altered any associations. Results: The risk of an attempted suicide was elevated in female migrant households (IRR 1.60 95% CI 1.38, 1.85), but not male migrant households (IRR 1.01 95% CI 0.76,1.36)) with strong evidence that risk differed for female vs. male migrant households (p-value = 0.005). We found no evidence that the age or sex of the left-behind household member altered the association observed. Conclusions: This analysis suggests that members of households with a temporary female foreign migrant are at an increased risk of attempted suicide, but these findings must be interpreted with caution. The increased risk of suicidal behaviour in these households may be due to factors that were present before the migration and persist post-migration (e.g. household violence, poverty). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]