Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item Early identification of acute kidney injury in Russell's viper (Daboia russelii) envenoming using renal biomarkers(Public Library of Science, 2019) Ratnayake, I.; Mohamed, F.; Buckley, N.A.; Gawarammana, I.B.; Dissanayake, D.M.; Chathuranga, U.; Munasinghe, M.; Maduwage, K.; Jayamanne, S.; Endre, Z.H.; Isbister, G.K.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.Item Evaluating temporal patterns of snakebite in Sri Lanka: the potential for higher snakebite burdens with climate change(Oxford University Press, 2018) Ediriweera, D.S.; Diggle, P.J.; Kasturiratne, A.; Pathmeswaran, A.; Gunawardena, N.K.; Jayamanne, S.K.; Isbister, G.K.; Dawson, A.; Lalloo, D.G.; de Silva, H.J.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.Item Antivenom for snake venom-induced neuromuscular paralysis (Protocol)(John Wiley and Sons, 2017) Silva, A.; Maduwage, K.; Buckley, N.A.; Lalloo, D.G.; de Silva, H.J.; Isbister, G.K.Item Development of a Snakebite risk map for Sri Lanka(Sri Lanka Medical Association, 2016) Ediriweera, D.S.; Kasturiratne, A.; Pathmeswaran, A.; Gunawardena, N.K.; Wijayawickrama, B.A.; Jayamanne, S.F.; Isbister, G.K.; Dawson, A.; Giorgi, E.; Diggle, P.J.; Lalloo, D.G.; de Silva, H.J.INTRODUCTION: Snakebite is a public health problem in Sri Lanka and about 37,000 patients are treated in government hospitals annually. At present, health care resources which are required to manage snakebite are distributed based on the administrative boundaries, rather than based on scientific risk assessment. OBJECTIVES: The aim of the study is to develop a snakebite risk map for Sri Lanka. METHOD: Epidemiological data was obtained from a community-based island-wide survey. The sample was distributed equally among the nine provinces. 165,665 participants (0.8%of the country’s population) living in 1118 Grama Niladhari divisions were surveyed. Generalized linear and generalized additive models were used for exploratory data analysis. Model-based geostatistics was used to determine the geographical distribution of snakebites. Monte Carlo maximum likelihood method was used to obtain parameter estimates and plug-in spatial predictions were obtained. Probability contour maps (PCM) were developed to demonstrate the spatial variation in the probability that local incidence does or does not exceed national snakebite incidence. RESULTS: Individual point estimate snakebite incidence map and PCM were developed to demonstrate the national incidence of snakebite in Sri Lanka. Snakebite hotspots and cold spots were identified in relation to the national snakebite incidence rate. Risk maps showed a within-country spatial variation in snakebites. CONCLUSIONS: The developed risk maps provide useful information for healthcare decision makers to allocate resources to manage snakebite in Sri Lanka.Item The Socio-economic burden of snakebite in Sri Lanka(Public Library of Science, 2017) Kasturiratne, A.; Pathmeswaran, A.; Wickremasinghe, A.R.; Jayamanne, S.F.; Dawson, A.; Isbister, G.K.; de Silva, H.J.; Lalloo, D.G.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.Item A Randomized controlled trial of fresh frozen plasma for coagulopathy in Russell's viper (Daboia russelii) envenoming(Wiley-Blackwell, 2017) Isbister, G.K.; Jayamanne, S.; Mohamed, F.; Dawson, A.H.; Maduwage, K.; Gawarammana, I.; Lalloo, D.G.; de Silva, H.J.; Scorgie, F.E.; Lincz, L.F.; Buckley, N.A.BACKGROUND: Russell's viper (Daboia russelii) envenoming is a major health issue in South Asia and causes venom induced consumption coagulopathy (VICC). OBJECTIVES: We investigated the effect of fresh frozen plasma (FFP) and two antivenom doses in correcting VICC. METHODS: We undertook an open-label randomized controlled trial in patients with VICC at two Sri Lankan hospitals. Patients with suspected Russell's viper bites and coagulopathy were randomly allocated (1:1) high-dose antivenom (20 vials) or low-dose antivenom (10 vials) plus 4U FFP. The primary outcome was the proportion of patients with an international normalized ratio (INR)<2, 6h post-antivenom. Secondary outcomes included anaphylaxis, major haemorrhage, death and clotting factor recovery. RESULTS: From 214 eligible patients, 141 were randomized; 71 to high-dose antivenom, 70 to low-dose antivenom/FFP; five had no post-antivenom bloods. The groups were similar except for a delay of 1h in antivenom administration for FFP patients. 6h post-antivenom 23/69 (33%) patients allocated high-dose antivenom had an INR<2 compared with 28/67 (42%) allocated low-dose antivenom/FFP [absolute difference 8%;95%Confidence Interval:-8% to 25%]. 15 patients allocated FFP did not receive it. Severe anaphylaxis occurred equally frequently in each group. One patient given FFP developed transfusion related acute lung injury. Three deaths occurred in low-dose/FFP patients including one intracranial haemorrhage. There was no difference in recovery rates of INR or fibrinogen, but more rapid initial recovery of factor V and X in FFP patients. CONCLUSION: FFP post-antivenom in Russell's viper bites didn't hasten recovery of coagulopathy. Low-dose antivenom/FFP did not worsen VICC, suggesting low-dose antivenom is sufficient. This article is protected by copyright. All rights reserved.Item Mapping the risk of snakebite in Sri Lanka - A national survey with geospatial analysis(Public Library of Science, 2016) Ediriweera, E.P.D.S.; Kasturiratne, A.; Pathmeswaran, A.; Gunawardena, N.K.; Wijayawickrama, B.A.; Jayamanne, S.F.; Isbister, G.K.; Dawson, A.; Giorgi, E.; Diggle, P.J.; Lalloo, D.G.; de Silva, H.J.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.Item Development and assessment of a psychological intervention for snakebite victims(Sri Lanka Medical Association, 2014) Wiiesinahe, C.A.; Williams, S.S.; Dolawatta, N.; Wimalaratne, A.K.G.P.; Kasturiratne, A.; Wijewickrema, B.; Jayamanne, S.F.; Lalloo, D.G.; Isbister, G.K.; Dawson, A.; de Silva, H.J.INTRODUCTION AND OBJECTIVES: There is significant delayed psychological morbidity and negative psycho-social impact following snakebite. However, no psychological support is provided to victims. We aimed to develop and assess the effectiveness of a brief intervention which can be provided by non-specialist medical officers aimed at reducing psychological morbidity. METHODS: In a single blind clinical trial at Polonnaruwa Hospital, 187 snakebite victims were randomised into three arms. One arm received no psychological intervention (Group A; n=59; control). Group B (n=60) received psychoeducation at discharge from hospital. Group C (n=68) received psychoeducation and a.second intervention one month later based on cognitive behavioural principles. All patients were assessed six months after discharge from hospital using standardised tools for presence of psychological symptoms and level of functioning. RESULTS: Compared with Group A, there was a significant reduction in anxiety symptoms measured by the Hopkins Psychiatric Symptom check list (16.9% vs. 5.9%, p=0.047, Chi-Squared test) and a non-significant trend towards improvement in the level of functioning measured by the Sheehan Disability inventory (6.47 vs. 4.69) in Group C, but not in Group B. There was no difference in rates of depression and post-traumatic stress disorder (PTSD) between the three groups. CONCLUSIONS: Our preliminary findings suggest that brief psychological interventions which include psychoeducation plus cognitive behavioural therapy given by non-specialist doctors, but not psychoeducation alone seem to reduce anxiety and facilitate a trend towards improved function in snakebite victims. However, these interventions had no effect on depression or PTSD.Item A Randomized Controlled Trial of a brief Intervention for delayed psychological effects in snakebite victims(Public Library of Science, 2015) Wijesinghe, C.A.; Williams, S.S.; Kasturiratne, A.; Dolawaththa, N.; Wimalaratne, P.; Wijewickrema, B.; Jayamanne, S.F.; Isbister, G.K.; Dawson, A.H.; Lalloo, D.G.; de Silva, H.J.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.Item Population pharmacokinetics of an Indian F(ab')2 snake antivenom in patients with Russell's Viper (Daboia russelii) bites(Public Library of Science, 2015) Isbister, G.K.; Maduwage, K.; Saiao, A.; Buckley, N.A.; Jayamanne, S.F.; Seyed, S.; Mohamed, F.; Chathuranga, U.; Mendes, A.; Abeysinghe, C.; Karunathilake, H.; Gawarammana, I.; Lalloo, D.G.; de Silva, H.J.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.