South Asian Clinical Toxicology Research Collaboration

Edinburgh, United Kingdom

South Asian Clinical Toxicology Research Collaboration

Edinburgh, United Kingdom

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Sorensen J.B.,Copenhagen University | Rheinlander T.,Copenhagen University | Sorensen B.R.,Copenhagen University | Pearson M.,University of Edinburgh | And 4 more authors.
BMJ Open | Year: 2014

Introduction: Sri Lanka has one of the highest suicide and self-harm rates in the world and although alcohol has been found to be a risk factor for self-harm in Sri Lanka, we know little about the connection between the two. This paper comprises a protocol for a qualitative study investigating alcohol's role in selfharm in rural Sri Lanka at three levels: the individual, community and policy level. The analysis will bring new understanding of the link between alcohol and self-harm in Sri Lanka, drawing on structural, cultural and social concepts. It will equip researchers, health systems and policy makers with vital information for developing strategies to address alcohol-related problems as they relate to self-harm.Methods and analysis: To capture the complexity of the link between alcohol and self-harm in the Anuradhapura district in the North Central Province in Sri Lanka, qualitative methods will be utilised. Specifically, the data will consist of serial narrative life-story interviews with up to 20 individuals who have non-fatally self-harmed and where alcohol directly or indirectly was involved in the incidence as well as with their significant others; observations in communities and families; six focus group discussions with community members; and key-informant interviews with 15-25 stakeholders who have a stake in alcohol distribution, marketing, policies, prevention and treatment as they relate to self-harm.Ethics and dissemination: The study has received ethical approval from the Ethical Review Committee of the Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka. A sensitive data collection technique will be used and ethical issues will be considered throughout the study.Results: The results will be disseminated in scientific peer-reviewed articles in collaboration with Sri Lankan and other international research partners.


Senarathna S.M.D.K.G.,University of Colombo | Senarathna S.M.D.K.G.,South Asian Clinical Toxicology Research Collaboration | Senarathna S.M.D.K.G.,University of Sri Jayewardenepura | Ranganathan S.S.,University of Colombo | And 3 more authors.
BMC Clinical Pharmacology | Year: 2012

Background: Acute paracetamol poisoning is a rapidly increasing problem in Sri Lanka. The antidotes are expensive and yet no health economic evaluation has been done on the therapy for acute paracetamol poisoning in the developing world. The aim of this study is to determine the cost effectiveness of using N-acetylcysteine over methionine in the management of acute paracetamol poisoning in Sri Lanka.Methods: Economic analysis was applied using public healthcare system payer perspective.Costs were obtained from a series of patients admitted to the National Hospital of Sri Lanka with a history of acute paracetamol overdose. Evidence on effectiveness was obtained from a systematic review of the literature. Death due to hepatotoxicity was used as the primary outcome of interest. Analysis and development of decision tree models was done using Tree Age Pro 2008.Results: An affordable treatment threshold of Sri Lankan rupees 1,537,120/death prevented was set from the expected years of productive life gained and the average contribution to GDP. A cost-minimisation analysis was appropriate for patients presenting within 10 hours and methionine was the least costly antidote. For patients presenting 10-24 hours after poisoning, n-acetylcysteine was more effective and the incremental cost effectiveness ratio of Sri Lankan rupees 316,182/life saved was well under the threshold. One-way and multi-way sensitivity analysis also supported methionine for patients treated within 10 hours and n-acetylcysteine for patients treated within 10-24 hours as preferred antidotes.Conclusions: Post ingestion time is an important determinant of preferred antidotal therapy for acute paracetamol poisoning patients in Sri Lanka. Using n-acetylcysteine in all patients is not cost effective. On economic grounds, methionine should become the preferred antidote for Sri Lankan patients treated within 10 hours of the acute ingestion and n-acetylcysteine should continue to be given to patients treated within 10-24 hours. © 2012 Senarathna et al; licensee BioMed Central Ltd.


Rajapakse B.N.,South Asian Clinical Toxicology Research Collaboration | Rajapakse B.N.,Australian National University | Rajapakse B.N.,Prince of Wales Hospital | Thiermann H.,University of Federal Defense Munich | And 8 more authors.
Annals of Emergency Medicine | Year: 2011

Study objective: Measurement of acetylcholinesterase (AChE) is recommended in the management of organophosphorus poisoning, which results in 200,000 deaths worldwide annually. The Test-mate ChE 400 is a portable field kit designed for detecting occupational organophosphorus exposure that measures RBC AChE and plasma cholinesterase (PChE) within 4 minutes. We evaluate Test-mate against a reference laboratory test in patients with acute organophosphorus self-poisoning. Methods: This was a cross-sectional comparison study of 14 patients with acute organophosphorus poisoning between May 2007 and June 2008. RBC AChE and PChE were measured in 96 and 91 samples, respectively, with the Test-mate ChE field kit and compared with a reference laboratory, using the limits of agreement method (Bland and Altman), κ statistics, and Spearman's correlation coefficients. Results: There was good agreement between the Test-mate ChE and the reference laboratory for RBC AChE. The mean difference (Test-matereference) was 0.62 U/g hemoglobin, 95% limits of agreement 10.84 to 9.59 U/g hemoglobin. Good agreement was also observed between the categories of mild, moderate, and severe RBC AChE inhibition (weighted κ 0.85; 95% confidence interval [CI] 0.83 to 0.87). Measurement of PChE also showed good agreement, with a mean difference (Test-matereference) of +0.06 U/mL blood, 95% limits of agreement 0.41 to 0.53 U/mL blood. Spearman's correlation coefficients were 0.87 (95% CI 0.81 to 0.91) for RBC AChE and 0.76 (95% CI 0.66 to 0.84) for PChE. Analysis for within-subject correlation of subjects did not change the limits of agreement. Conclusion: The Test-mate ChE field kit reliably provides rapid measurement of RBC AChE in acute organophosphorus poisoning. © 2011 American College of Emergency Physicians.


Maduwage K.,University of Newcastle | Maduwage K.,South Asian Clinical Toxicology Research Collaboration | Maduwage K.,University of Peradeniya | Isbister G.K.,University of Newcastle | Isbister G.K.,South Asian Clinical Toxicology Research Collaboration
PLoS Neglected Tropical Diseases | Year: 2014

Venomous snakebite is considered the single most important cause of human injury from venomous animals worldwide. Coagulopathy is one of the commonest important systemic clinical syndromes and can be complicated by serious and life-threatening haemorrhage. Venom-induced consumption coagulopathy (VICC) is the commonest coagulopathy resulting from snakebite and occurs in envenoming by Viperid snakes, certain elapids, including Australian elapids, and a few Colubrid (rear fang) snakes. Procoagulant toxins activate the clotting pathway, causing a broad range of factor deficiencies depending on the particular procoagulant toxin in the snake venom. Diagnosis and monitoring of coagulopathy is problematic, particularly in resource-poor countries where further research is required to develop more reliable, cheap clotting tests. MEDLINE and EMBASE up to September 2013 were searched to identify clinical studies of snake envenoming with VICC. The UniPort database was searched for coagulant snake toxins. Despite preclinical studies demonstrating antivenom binding toxins (efficacy), there was less evidence to support clinical effectiveness of antivenom for VICC. There were no placebo-controlled trials of antivenom for VICC. There were 25 randomised comparative trials of antivenom for VICC, which compared two different antivenoms (ten studies), three different antivenoms (four), two or three different doses or repeat doses of antivenom (five), heparin treatment and antivenom (five), and intravenous immunoglobulin treatment and antivenom (one). There were 13 studies that compared two groups in which there was no randomisation, including studies with historical controls. There have been numerous observational studies of antivenom in VICC but with no comparison group. Most of the controlled trials were small, did not use the same method for assessing coagulopathy, varied the dose of antivenom, and did not provide complete details of the study design (primary outcomes, randomisation, and allocation concealment). Non-randomised trials including comparison groups without antivenom showed that antivenom was effective for some snakes (e.g., Echis), but not others (e.g., Australasian elapids). Antivenom is the major treatment for VICC, but there is currently little high-quality evidence to support effectiveness. Antivenom is not risk free, and adverse reactions can be quite common and potentially severe. Studies of heparin did not demonstrate it improved outcomes in VICC. Fresh frozen plasma appeared to speed the recovery of coagulopathy and should be considered in bleeding patients. © 2014 Maduwage, Isbister.


Wijesinghe C.A.,University of Kelaniya | Williams S.S.,University of Kelaniya | Kasturiratne A.,University of Kelaniya | Dolawaththa N.,District General Hospital | And 8 more authors.
PLoS Neglected Tropical Diseases | Year: 2015

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: SLCTR/2011/003. © 2015 Wijesinghe et al.


Eddleston M.,University of Edinburgh | Eddleston M.,Royal Infirmary | Eddleston M.,South Asian Clinical Toxicology Research Collaboration | Eddleston M.,Copenhagen University
British Journal of Clinical Pharmacology | Year: 2013

Self-poisoning with pesticides or plants is a major clinical problem in rural Asia, killing several hundred thousand people every year. Over the last 17 years, our clinical toxicology and pharmacology group has carried out clinical studies in the North Central Province of Sri Lanka to improve treatment and reduce deaths. Studies have looked at the effectiveness of anti-digoxin Fab in cardiac glycoside plant poisoning, multiple dose activated charcoal in all poisoning, and pralidoxime in moderate toxicity organophosphorus insecticide poisoning. More recently, using a Haddon matrix as a guide, we have started conducting public health and animal studies to find strategies that may work outside of the hospital. Based on the 2009 GSK Research in Clinical Pharmacology prize lecture, this review shows the evolution of the group's research from a clinical pharmacology approach to one that studies possible interventions at multiple levels, including the patient, the community and government legislation. © 2012 The British Pharmacological Society.


Pearson M.,University of New South Wales | Zwi A.B.,University of New South Wales | Rouse A.K.,South Asian Clinical Toxicology Research Collaboration | Fernando R.,University of Colombo | And 2 more authors.
Crisis | Year: 2014

Background: Suicide is and has been a major public health problem in Sri Lanka and has generated a wide range of literature. Aims: This review aimed to systematically appraise what is known about suicide in Sri Lanka. The patterns and content of articles were examined and recommendations for further research proposed. Method: The paper describes the systematic search, retrieval, and quality assessment of studies. Thematic analysis techniques were applied to the full text of the articles to explore the range and extent of issues covered. Results: Local authors generated a large body of evidence of the problem in early studies. The importance of the method of suicide, suicidal intention, and the high incidence of suicide were identifi ed as key foci for publications. Neglected areas have been policy and health service research, gender analysis, and contextual issues. Conclusion: The literature reviewed has produced a broad understanding of the clinical factors, size of the problem, and social aspects. However, there remains limited evidence of prevention, risk factors, health services, and policy. A wide range of solutions have been proposed, but only regulation of pesticides and improved medical management proved to be effective to date.© 2014 Hogrefe Publishing.


PubMed | University of Colombo, University of New South Wales and South Asian Clinical Toxicology Research Collaboration
Type: Journal Article | Journal: Crisis | Year: 2014

Suicide is and has been a major public health problem in Sri Lanka and has generated a wide range of literature.This review aimed to systematically appraise what is known about suicide in Sri Lanka. The patterns and content of articles were examined and recommendations for further research proposed.The paper describes the systematic search, retrieval, and quality assessment of studies. Thematic analysis techniques were applied to the full text of the articles to explore the range and extent of issues covered.Local authors generated a large body of evidence of the problem in early studies. The importance of the method of suicide, suicidal intention, and the high incidence of suicide were identified as key foci for publications. Neglected areas have been policy and health service research, gender analysis, and contextual issues.The literature reviewed has produced a broad understanding of the clinical factors, size of the problem, and social aspects. However, there remains limited evidence of prevention, risk factors, health services, and policy. A wide range of solutions have been proposed, but only regulation of pesticides and improved medical management proved to be effective to date.


PubMed | South Asian Clinical Toxicology Research Collaboration
Type: Comparative Study | Journal: Annals of emergency medicine | Year: 2011

Measurement of acetylcholinesterase (AChE) is recommended in the management of organophosphorus poisoning, which results in 200,000 deaths worldwide annually. The Test-mate ChE 400 is a portable field kit designed for detecting occupational organophosphorus exposure that measures RBC AChE and plasma cholinesterase (PChE) within 4 minutes. We evaluate Test-mate against a reference laboratory test in patients with acute organophosphorus self-poisoning.This was a cross-sectional comparison study of 14 patients with acute organophosphorus poisoning between May 2007 and June 2008. RBC AChE and PChE were measured in 96 and 91 samples, respectively, with the Test-mate ChE field kit and compared with a reference laboratory, using the limits of agreement method (Bland and Altman), statistics, and Spearmans correlation coefficients.There was good agreement between the Test-mate ChE and the reference laboratory for RBC AChE. The mean difference (Test-mate-reference) was -0.62 U/g hemoglobin, 95% limits of agreement -10.84 to 9.59 U/g hemoglobin. Good agreement was also observed between the categories of mild, moderate, and severe RBC AChE inhibition (weighted 0.85; 95% confidence interval [CI] 0.83 to 0.87). Measurement of PChE also showed good agreement, with a mean difference (Test-mate-reference) of +0.06 U/mL blood, 95% limits of agreement -0.41 to 0.53 U/mL blood. Spearmans correlation coefficients were 0.87 (95% CI 0.81 to 0.91) for RBC AChE and 0.76 (95% CI 0.66 to 0.84) for PChE. Analysis for within-subject correlation of subjects did not change the limits of agreement.The Test-mate ChE field kit reliably provides rapid measurement of RBC AChE in acute organophosphorus poisoning.


PubMed | Princess Alexandra Hospital, University of Queensland, University of Kelaniya, South Asian Clinical Toxicology Research Collaboration and University of Sri Jayewardenepura
Type: Journal Article | Journal: BMC health services research | Year: 2017

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.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 pharmacists 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.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 pharmacists 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.There was high acceptance and implementation of clinical pharmacists 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.Sri Lanka Clinical Trials Registry SLCTR/2013/029 Date: 13 September 2013; retrospectively registered.

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