Compliance with national snakebite treatment guidelines in rural Sri Lankan hospitals: a cluster randomized controlled trial of a brief educational intervention.

BACKGROUND: Snakebite is a global health problem that predominantly occurs in rural areas. In Sri Lanka, the majority of snakebite patients first present to smaller rural primary hospitals. Improving care delivered at rural hospitals has the potential to reduce morbidity and mortality from snakebites. OBJECTIVE: In this study, we evaluated whether an educational intervention would increase compliance with national snakebite treatment guidelines in primary hospitals. METHODS: The hospitals were randomized into educational intervention (n = 24) and control groups (n = 20). The intervention hospitals received a brief educational intervention based on Sri Lankan Medical Association (SLMA) guidelines on the management of snakebites. Control hospitals had free access to the guidelines but no additional promotion. Four outcomes were assessed: pre- and post-test knowledge at the completion of a one-day workshop of educational intervention (intervention group only); improvement in the quality of the patient's medical records; appropriateness of transfers to higher hospitals; and quality of overall management graded by a blinded expert. The data was collected over a period of 12 months. RESULTS: All case notes of snakebite hospital admissions were reviewed. There were 1021 cases in the intervention group hospitals and 1165 cases in the control hospitals. Four hospitals in the intervention group and three hospitals in the control group did not have snakebite admissions and were excluded from the cluster analysis. The absolute quality of care was high in both groups. Post-test knowledge was improved (p < 0.0001) following the intervention group's educational workshop. There was no statistical difference between the two groups in terms of clinical data documentation in hospital notes (scores, p = 0.58) or transfer appropriateness (p = 0.68)-both of which were significantly different from the guidelines. CONCLUSION: Education of primary hospital staff improved the immediate knowledge gained but did not improve record-keeping or the appropriateness of inter-hospital patient transfer. TRIAL REGISTRATION: The study was registered with Sri Lanka Medical Associations' clinical trial registry. Reg. No SLCTR -2013-023. Registered: 30/07/2013.

Epidemiology and renal injury following 2-methyl-4-chlorophenoxyacetic acid (MCPA) poisoning.

2-Methyl-4-chlorophenoxyacetic acid (MCPA) is a widely used chlorophenoxy herbicide. MCPA poisoning causes mitochondrial dysfunction, which can lead to kidney injury and death. The objective of this study is to describe the epidemiology, case fatality and extent of renal injury in a large cohort of MCPA self-poisonings. The study consists of two parts: (1) A report of epidemiological data and clinical outcomes in MCPA poisoned patients in Sri Lanka between 2002 and 2019; (2) Evaluation of acute kidney injury (AKI) using renal biomarkers in a subset from this cohort. Serum creatinine (sCr) and biomarkers were measured soon after hospitalization (2 [IQR 1-3] h) and at different time intervals. We measured serum biomarkers: sCr, cystatin C (sCysC), creatine kinase (CK), and urinary biomarkers: creatinine, kidney injury molecule-1 (KIM-1), clusterin, albumin, beta-2-microglobulin (ß2M), cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), trefoil factor 3 (TFF3) and cytochrome C (CytoC). Kidney Disease Improving Global Outcomes (KDIGO) criteria was used to define acute kidney injury (AKI). There were 1653 patients; 65% were male. The median time from ingestion to examination was 3:54 (IQR 2:19-6:57) h. The overall case-fatality rate was 5.3%. Patients who died were older (42 [IQR 33.5-54] vs 27 [IQR 20-37] for survivors). The median estimated amount of MCPA ingested by patients who died was also greater (88 [IQR 34-200] vs. 30 [IQR 15-63] ml in survivors). Moderate to severe AKI (AKI2/3) was uncommon (6/59 patients in the biomarker study had KDIGO stage 2 or 3). Most patients in AKI2/3 group with increased sCr were older (median age 35 years [IQR 27-41]) compared to No AKI (23 years (19-29) years) or AKI1 (26 years (21-40) years) group who had no or mild increase in sCr. These patients had no pre-existing kidney diseases. In these patients, serum creatinine (maximum medium concentration; 1.12 [IQR 0.93-1.67] mg/dl) and CK (maximum medium concentration; 284 [IQR 94-428] U/l) were increased but sCysC (maximum medium concentration; 0.79 [IQR 0.68-0.81] mg/l) remained in the normal range within 72 h. All urinary biomarkers performed poorly in diagnosing AKI (area under the receiver operating characteristic curve < 0.68). The higher numbers of men with MCPA poisoning likely reflects greater occupational access to pesticides. Fatal outcome and higher ingested dose were more common in the elderly. Significant AKI with tubular injury biomarkers was uncommon. Most people with raised sCr were older and appeared to have no pre-existing kidney disease.

Circulating intestinal fatty acid binding protein and intestinal toxicity in Russell's viper envenomation.

OBJECTIVE: Abdominal pain is known to be an early clinical predictor of severe systemic Russell's viper (RV) envenomation and is often associated with the later development of coagulopathy and neurotoxicity. The mechanism of abdominal pain is unknown, but we postulated it might be due to intestinal microvascular endothelial gut damage. Gut-toxicity can be detected using the novel biomarker Intestinal Fatty Acid Binding Protein (IFABP). We also wanted to explore the mechanisms and consequences of this toxicity by measuring procalcitonin as a specific marker of sepsis triggered by bacterial endotoxin, and serum cystatin-C (CysC) as a measure of acute kidney injury. We hypothesised that severe gut-injury might lead to gut-barrier failure, translocation of gastrointestinal microorganisms, associated sepsis and systemic inflammatory response syndrome (SIRS), with a possible exacerbation of snake-bite severity, including acute kidney injury that was previously attributed to direct venom effects. METHODS: Serial plasma samples previously collected from 16 RV envenomations with abdominal pain, 15 RV envenomations without abdominal pain and 25 healthy controls were assayed for IFABP. A subgroup of these RV envenomations were assayed for procalcitonin (n = 24) and serum CysC (n = 11). RESULTS: The median peak IFABP for RV envenomations was much higher than healthy controls [3703.0 pg/mL (IQR 2250.1-13702.0 pg/mL) vs. 270.1 pg/mL (IQR 153.5-558.0 pg/mL) (p < 0.001)]. There was no difference in those with and without abdominal pain [3801.4 pg/mL (IQR 2080.5-22446.3 pg/mL) vs. 3696.6 pg/mL (IQR 2280.3-4664.7 pg/mL) (p = 1.0)]. Peak procalcitonin levels were elevated in envenomed patients 30.1 ng/ml (IQR: 13.1-59.7 ng/ml) with a level >2ng/mL indicative of severe sepsis] and also correlated with peak IFABP (r = 0.55, p = 0.006, n = 24). Peak serum CysC was also elevated and also correlated with IFABP (r = 0.71, p = 0.037, n = 9). CONCLUSION: IFABP is significantly elevated indicating enterocyte damage occurs in RV envenomation. IFABP correlated with markers of sepsis (procalcitonin) and acute kidney injury (serum CysC) suggesting that enterocyte damage resulting in translocation of microbial associated molecular patterns (MAMPs) contributes to RV envenomation associated SIRS and sepsis.

Changes of attention-related brain activity over 6 months after acute organophosphate pesticide poisoning: a prospective follow-up study.

CONTEXT: Ingestion of organophosphate (OP) pesticides is a common method of self-harm in developing countries. Apart from acute cholinergic effects, limited evidence implicates OP poisoning in long-term neurocognitive deficits. However, prospective neurophysiological evidence of long-term deficits is scarce in humans. We aimed to determine long-term cognitive changes of acute OP pesticide self-poisoning in a prospective follow-up study, using event-related potentials (ERPs), an electroencephalographic index of cognitive functioning. METHODS: We recruited 203 patients (147 men) hospitalised with OP pesticide ingestion (OP group; all had significant erythrocyte cholinesterase inhibition) and 50 patients (23 men) with paracetamol overdose (control group) as a means of self-harm. We recorded their ERPs and behavioural performance in a selective attention task at three post-exposure time points: on discharge from hospital (around 14 days post-ingestion), 6 weeks and 6 months post-ingestion. We compared the reaction time and ERP components of the two groups at each time point, adjusting for sex, age, education and comorbid depression in multiple regression models. RESULTS: OP group had significantly slower reaction times than the control group on discharge and at 6 weeks, but not at 6 months. On discharge, the OP group also showed significantly prolonged latency of the parietal P3b component, signifying delayed attentional processing. P3b amplitudes were also significantly smaller in the OP group on discharge and at 6 months. Within the OP group, greater clinical severity of poisoning was associated with smaller P3b amplitudes. Early pre-attentive cortical processing (as indexed by N1 ERP component) showed no significant intergroup differences. CONCLUSIONS: Acute OP pesticide poisoning was associated with impaired behavioural and neurophysiological indices of selective attention. These deficits outlast the cholinergic phase of intoxication. The neurobehavioral impairment disappears over months, but neurophysiological deficits seem to last even after 6 months. This impairment could potentially compromise the performance and safety of patients for months following clinical recovery.

Serum and urinary biomarkers for early detection of acute kidney injury following Hypnale spp. envenoming.

BACKGROUND: Hump-nosed pit viper (HNV; Hypnale spp.) bites account for most venomous snakebites in Sri Lanka. Acute kidney injury (AKI) is the most serious systemic manifestation (1-10%) following HNV envenoming. We aimed to identify the value of functional and injury biomarkers in predicting the development of AKI early following HNV bites. METHODS: We conducted a prospective cohort study of patients with confirmed HNV envenoming presenting to two large tertiary care hospitals in Sri Lanka. Demographics, bite details, clinical effects, complications and treatment data were collected prospectively. Blood and urine samples were collected from patients for coagulation and renal biomarker assays on admission, at 0-4h, 4-8h, 8-16h and 16-24h post-bite and daily until discharge. Follow-up samples were obtained 1 and 3 months post-discharge. Creatinine (sCr) and Cystatin C (sCysC) were measured in serum and kidney injury molecule-1 (uKIM-1), clusterin (uClu), albumin (uAlb), ß2-microglobulin (uß2M), cystatin C (uCysC), neutrophil gelatinase associated lipocalin (uNGAL), osteopontin (uOPN) and trefoil factor-3 (uTFF-3) were measured in urine. Definite HNV bites were based on serum venom specific enzyme immunoassay. Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to stage AKI. Two patients had chronic kidney disease at 3 month follow-up, both with pre-existing abnormal sCr, and one developed AKI following HNV envenoming. RESULTS: There were 52 patients with confirmed HNV envenoming; median age 48y (Interquartile range [IQR]:40-59y) and 29 (56%) were male. Median time to admission was 1.87h (IQR:1-2.75h). Twelve patients (23%) developed AKI (AKI stage 1 = 7, AKI stage 2 = 1, AKI stage 3 = 4). Levels of five novel biomarkers, the functional marker serum Cystatin C and the damage markers urinary NGAL, cystatin C, ß2-microglobulin and clusterin, were elevated in patients who developed moderate/severe acute kidney injury. sCysC performed the best at 0-4 h post-bite in predicting moderate to severe AKI (AUC-ROC 0.95;95%CI:0.85-1.0) and no biomarker performed better than sCr at later time points. CONCLUSIONS: sCysC appears to be a better marker than sCr for early prediction of moderate to severe AKI following HNV envenoming.

Case fatality of agricultural pesticides after self-poisoning in Sri Lanka: a prospective cohort study.

BACKGROUND: Pesticide poisoning is among the most common means of suicide globally, but can be prevented with regulation of the most hazardous agents. We aimed to compare the lethality of pesticides ingested by our cohort, seek evidence on variation between human and regulatory animal toxicity, and establish change over time in the case fatality of individual pesticides in Sri Lanka. METHODS: We examined the case fatality of agricultural pesticides in a prospective cohort in nine hospitals serving rural populations in Sri Lanka. We included all patients (>11 years) who had presented to a South Asian Clinical Toxicology Research Collaboration study hospital during the study period. Patients were enrolled by clinical research assistants and were regularly reviewed. Identification of the ingested pesticide was generally on the basis of history or positive identification of the container, supported by nested blood analysis. FINDINGS: From March 31, 2002, to Dec 31, 2019, 34 902 patients (median age 29 years [IQR 21-40]; 23 060 [66·1%] male) presented with a possible or known pesticide self-poisoning. We identified 23 139 specific pesticides that were ingested. Poisoning was fatal in 2299 (6·6%) patients. Case fatality varied greatly from 0·0% (several substances) to 41·8% (paraquat). The three most toxic agents (ie, paraquat, dimethoate, and fenthion) were banned between 2008 and 2011. Since 2013, the five agents causing the most deaths (ie, profenofos, propanil, fenobucarb, carbosulfan, and quinalphos) had a case fatality of 7·2-8·6%. A steady decline was seen in overall case fatality of pesticide poisoning (10·5% for 2002-06 to 3·7% for 2013-19), largely attributable to pesticide bans. A modest fall in case fatality for non-banned pesticides was also seen. INTERPRETATION: Declines seen in case fatalities of poisonings with non-banned pesticides suggest that medical management improved over time. The human data for acute toxicity of pesticides should drive hazard classifications and regulation. We believe that a global benchmark for registration of pesticides should include a less than 5% case fatality after self-poisoning, which could prevent many deaths and have a substantial effect on global suicide rates. FUNDING: The Wellcome Trust and the National Health and Medical Research Council of Australia. TRANSLATIONS: For the Sinhala and Tamil translations of the abstract see Supplementary Materials section.

Urinary microRNAs as non-invasive biomarkers for toxic acute kidney injury in humans.

MicroRNAs in biofluids are potential biomarkers for detecting kidney and other organ injuries. We profiled microRNAs in urine samples from patients with Russell's viper envenoming or acute self-poisoning following paraquat, glyphosate, or oxalic acid [with and without acute kidney injury (AKI)] and on healthy controls. Discovery analysis profiled for 754 microRNAs using TaqMan OpenArray qPCR with three patients per group (12 samples in each toxic agent). From these, 53 microRNAs were selected and validated in a larger cohort of patients (Russell's viper envenoming = 53, paraquat = 51, glyphosate = 51, oxalic acid = 40) and 27 healthy controls. Urinary microRNAs had significantly higher expression in patients poisoned/envenomed by different nephrotoxic agents in both discovery and validation cohorts. Seven microRNAs discriminated severe AKI patients from no AKI for all four nephrotoxic agents. Four microRNAs (miR-30a-3p, miR-30a-5p, miR-92a, and miR-204) had > 17 fold change (p < 0.0001) and receiver operator characteristics area-under-curve (ROC-AUC) > 0.72. Pathway analysis of target mRNAs of these differentially expressed microRNAs showed association with the regulation of different nephrotoxic signaling pathways. In conclusion, human urinary microRNAs could identify toxic AKI early after acute injury. These urinary microRNAs have potential clinical application as early non-invasive diagnostic AKI biomarkers.

Dysfunction in macula, retinal pigment epithelium and post retinal pathway in acute organophosphorus poisoning.

CONTEXT: Organophosphorus (OP) insecticide poisoning is a significant health problem in South Asian countries. Although cholinergic receptors are present at the junction between photoreceptors and the retinal pigment epithelium (RPE), human studies of the effects of OP poisoning on the visual pathways are very few. This study aims to demonstrate the pattern of changes in retina and post retinal pathways in patients with acute OP poisoning using visual electrophysiological tests. METHODS: This is an observational, cross-sectional study conducted at the Neurophysiology Unit, Teaching Hospital, Peradeniya, Sri Lanka. We tested 16 patients recovered from cholinergic phase, at least 24 h after deatropinization and within 8 weeks of OP ingestion. We assessed the functional integrity of the photoreceptors and ganglion cells of the macula by pattern electroretinography (PERG); RPE by electro-oculography (EOG); and post retinal pathways by pattern reversal visual evoked potentials (PR-VEP). Latencies and amplitudes of PR-VEP and PERG, light peak (LP), dark trough (DT) and Arden ratio of EOG were determined in patients and compared with 16 controls using the Mann-Whitney U test. RESULTS: Of the 16 OP-poisoned patients (median age of 37 ± IQR 20 years), six (37.5%) had reduced Arden ratio with reference to the International Society of Clinical Electrophysiology of Vision cut-off value of 1.7. The median Arden ratio in patients (1.69 ± IQR 0.36) was significantly lower compared to controls (1.90 ± IQR 0.4). The median latencies and amplitudes of PR-VEP or PERG were not significantly different between patients and controls. However, three patients had prolonged P100 latencies in PR-VEP and one had prolonged P50 latency in PERG. CONCLUSIONS: Acute OP poisoning seems to affect the functions of the RPE and the visual electrophysiological changes outlast the cholinergic phase. Limited evidence suggests that photoreceptors of the macula region and post retinal pathway might be affected in some patients.

Effectiveness of Low-dose Ethinylestradiol/Cyproterone Acetate and Ethinylestradiol/Desogestrel with and without Metformin on Hirsutism in Polycystic Ovary Syndrome: A Randomized, Double-blind, Triple-dummy Study.

BACKGROUND: The effectiveness of different combined oral contraceptive pills and metformin in reducing hirsutism in patients with polycystic ovary syndrome (PCOS) remains unclear. OBJECTIVE: We sought to determine the effects of ethinylestradiol (35µg)/cyproterone acetate (2mg) (EE/CPA) and ethinylestradiol (20µg)/desogestrel (0.15mg) (EE/DES), alone or with metformin, on hirsutism in PCOS. METHODS: A randomized, double-blind, triple-dummy study was conducted on women with PCOS and hirsutism (N=107) who received one of four drug combinations (Arm A: EE/CPA; Arm B: EE/DES; Arm C: EE/CPA plus metformin; or Arm D: EE/DES plus metformin). Hirsutism was assessed at baseline, six months, and 12 months by using five outcomes variables. RESULTS: No outcomes variable showed a significant difference between the four arms at 12 months. There was a significant reduction in both hair density and modified Ferriman-Gallwey score (mFGS) in Arm A, mFGS in Arm B, hair density in Arm C, and diameter of sideburn hair in Arm D, respectively. Separately, there was a significant increase noted in the hair growth rate of chin and an improvement in patients' perceptions of hirsutism in all four study arms. CONCLUSION: EE/CPA and EE/DES were equally effective in improving hirsutism in PCOS, with no added benefit from low-dose metformin. Sri Lanka Clinical Trials Registry (http://www.slctr.lk) registration no. SLCTR/2015/007.

Coronary Artery Spasms Mimicking Acute ST-Elevation Myocardial Infarction in Dengue Haemorrhagic Fever.

Dengue is an arboviral febrile illness endemic in many tropical and subtropical regions with frequent epidemics. Although most cases are self-limiting, progression into dengue haemorrhagic fever can have dire outcomes. The course can also be complicated by infrequent occurrence of unusual clinical manifestations which are increasingly recognized. We describe the case of a 16-year-old previously healthy girl diagnosed with dengue, who went on to develop severe ischaemic-type central chest pain towards the end of the critical phase of dengue haemorrhagic fever. Urgent investigation revealed acute ST-segment elevations in the high lateral leads of a surface electrocardiogram which completely reverted to normal within 2 hours, associated with elevated cardiac biomarkers but normal findings on transthoracic 2D echocardiography. She was managed with high-dose statins, nitrates, and pain relievers and made an uneventful recovery without any further episodes. The possible explanation for the presentation was focal myocarditis leading to coronary artery spasms.

Differences between organophosphates in respiratory failure and lethality with poisoning post the 2011 bans in Sri Lanka.

Introduction: Self-poisoning with organophosphorus pesticides (OPs) has high morbidity and mortality. The most toxic OP formulations have been progressively banned in Sri Lanka over the past three decades. However, respiratory failure (RF) requiring ventilation remains a major contributor to fatalities. Therefore, this study was conducted to examine the frequency of RF and death after poisoning with the currently available OPs to determine if further bans might be warranted to reduce the burden of OP poisoning in Sri Lanka.Methods: Five hundred and forty patients with confirmed OP self-poisoning were prospectively observed throughout their hospital stay following admission to Peradeniya hospital in the Central Province of Sri Lanka. Clinical data including the time and duration of intubation were documented prospectively in structured datasheets.Results: One hundred and forty-nine patients required ventilation (27%), and 34 (23%) of those died. Males with alcohol co-ingestion were more likely to develop RF. Compared to other OPs, profenofos (Odds Ratio [OR] = 2.5, 95% CI: 1.5-3.9), and quinalphos (OR = 4.5, 95% CI: 1.6-12.6) were more likely to, and chlorpyrifos (OR = 0.2, 95% CI: 0.1-0.4) less likely to lead to RF than other OPs. Profenofos was also associated with higher mortality (OR = 2.3, 95% CI: 1.1-4.6) than other OPs. The median time to intubation was longer for profenofos, but the duration of intubation was similar for all OP formulations.Conclusion: RF and deaths following OP ingestion continue to be a major problem in Sri Lanka, with profenofos being the major current agent of concern. Strategies to replace profenofos and quinalphos use with less toxic insecticides should be explored. Doctors should be alert to the high probability of delayed and prolonged RF after profenofos poisoning.

Clinico-epidemiology and management of Russell's viper (Daboia russelii) envenoming in dogs in Sri Lanka.

INTRODUCTION: Russell's viper envenoming in dogs is a significant problem in Sri Lanka. The current study focused on investigating clinical profile, laboratory findings of three selected tests and to develop a treatment strategy with Indian polyvalent Anti-Venom Serum (AVS). It was also intended to report adverse effects and complications caused by both Russell's viper venom (RVV) and AVS in Russell's Viper (RV) envenomed dogs. OBJECTIVE: To evaluate and report the clinical manifestations, to find out the minimum effective vials of AVS and to record AVS induced adverse reactions of RV envenoming in dogs. MATERIALS AND METHODS: A prospective study was conducted on Russell's viper bitten dogs (n = 65) admitted to the Veterinary Teaching Hospital (VTH) in Sri Lanka. Indian polyvalent AVS was used to treat all the envenomed dogs. The number of vials of AVS that was administered to a patient was decided upon by a second degree polynomial model with a number of vials of AVS in the X axis verses Prothrombine Time (PT), Activated Partial Thromboplastine Time (aPTT) and Clotting Time (CT) in the Y axis respectively. RESULTS: Varying degrees of pain were exhibited by all the victim dogs. Mild swelling and necrosis at the site of bite was seen in 54% (n = 35) and 37% (n = 24) of dogs respectively. Prolonged values of, PT, aPTT and CT were seen from all the RV envenomed dogs. The mean leukocyte count in these dogs was 39.79 × 103/µL (normal range; 4-20 × 103/µL) (IQR:29.05 × 103/µL-45.92 × 103/µL). Statistical analysis showed that the initial vials of 7 AVS would be the minimum required vials. Therefore, a range of 6-15 AVS vials in total were administered to these dogs and in 7.6% (n = 5) of dogs, the results of PT, aPTT and CT became normal with 6 AVS vials at 32-97 minutes. Acute Renal Failure (ARF) was detected from 29% (n = 19) of dogs as a complication. CONCLUSIONS: Systemic clinical signs of haemorrhagic lesions, cardio respiratory toxicities were common in Russell's viper envenomed dogs. Initially 6 vials of AVS must be administered. AVS induced reactions were reported commonly. Russell's viper envenoming was found to be lethal in dogs.

Early identification of acute kidney injury in Russell's viper (Daboia russelii) envenoming using renal biomarkers.

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.

Association between visceral adiposity index, hirsutism and cardiometabolic risk factors in women with polycystic ovarian syndrome: A cross-sectional study

Introduction: Visceral adiposity index (VAI) is a mathematical index derived from the body mass index (BMI), waist circumference (WC), serum fasting triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C). It reflects visceral adipocyte dysfunction (VAD) and is associated with cardiometabolic risk. Women with polycystic ovarian syndrome (PCOS) have adipocyte dysfunction, which is associated with metabolic disorders. Hirsutism in PCOS is considered to be due to high insulin levels which enhances androgen activity at the pilosebaceous unit. Objectives: To determine the association between VAI, hirsutism and cardiometabolic risk factors in patients with PCOS. Methods: A total of 99 patients aged 18-40 years with PCOS diagnosed by the Rotterdam consensus criteria-2003 and a hirsutism score of 8 or more according to the Ferriman-Gallway Score (FGS) were studied. BMI, WC, fasting lipid profile, serum leptin, insulin, sex hormone binding globulin (SHBG), free-androgen index (FAI), fasting blood glucose (FBG) and oral glucose tolerance test (OGTT) were determined. Homeostasis model assessment (HOMA)-beta, HOMA-insulin resistance (IR) and VAI were calculated. Diameter and rate of hair growth at sideburns and chin; density of hair at sideburns were measured. Data were analyzed by SPSS-22.0. Results: There was no significant association between parameters of hirsutism and VAI. There was a significant association between VAI and OGTT, FAI, systolic and diastolic blood pressure: but not between VAI and other metabolic parameters. Conclusion: Visceral adipocyte dysfunction is closely linked to glucose intolerance and blood pressure in women with PCOS. However, hirsutism is unlikely to be due to adipocyte dysfunction.

Prediction of organophosphorus insecticide-induced intermediate syndrome with stimulated concentric needle single fibre electromyography.

BACKGROUND: Deliberate self-poisoning (DSP) using organophosphorus (OP) insecticides are a common clinical problem in Asia. OPs inhibit acetylcholine esterase (AChE), leading to over-activity of muscarinic and nicotinic cholinergic circuits. Intermediate syndrome (IMS) is mediated via prolonged nicotinic receptor stimulation at the neuromuscular junction and its onset is between 24-96 hours post ingestion. The aims of the present study were 1) to investigate whether neuromuscular junction dysfunction within the first 24 hours following exposure, quantified by jitter in single fibre electromyography (SfEMG), can predict IMS, and 2) to compare the changes in SfEMG jitter over the course of the illness among patients who developed IMS (IMS+) and those who did not (IMS-). METHODS AND FINDINGS: We conducted a prospective cohort study in a tertiary care hospital in Sri Lanka on 120 patients admitted between September 2014 and August 2016 following DSP by OP insecticides viz., profenofos 53, phenthoate 17, diazinon 13, chlorpyrifos 5, others 12, unknown 20. SfEMG was performed every second day during hospitalization. Exposure was confirmed based on the history and red blood cell AChE assays. IMS was diagnosed in patients who demonstrated at least three out of four of the standard IMS criteria: proximal muscle weakness, bulbar muscle weakness, neck muscle weakness, respiratory paralysis between 24-96 hours post ingestion. Respiratory failure requiring intubation occurred in 73 out of 120 patients; 64 of these were clinically diagnosed with IMS. Of the 120 patients, 96 had repeated SfEMG testing, 67 of them being tested within the first 24 hours. Prolonged jitter (>33.4µs) within the first 24 hours was associated with greatly increased risk of IMS (odds ratio = 8.9, 95% confidence intervals = 2.4-29.6, p = 0.0003; sensitivity 86%, specificity 58%). The differences in jitter between IMS+ and IMS- patients remained significant for 72 hours and increased jitter was observed in some patients for up to 216 hours. For intubated patients, the median time for jitter to normalize and median time to extubate were similar, and the two variables had a moderate positive correlation (r = 0.49, P = 0.001). CONCLUSIONS: Prolonged jitter recorded with SfEMG <24 hours of ingestion of an OP strongly correlates with subsequent occurrence of IMS. The time course of electrophysiological recovery of the NMJ was similar to the time course of respiratory recovery in IMS patients.

Study protocol: a pilot randomized controlled trial to evaluate the acceptability and feasibility of a counseling intervention, delivered by nurses, for those who have attempted self-poisoning in Sri Lanka.

BACKGROUND: Deliberate self-harm in the form of non-fatal self-poisoning is a major public health problem in Sri Lanka. Previous work suggests that many nurses in Sri Lanka-particularly those who work in primary care in the medical treatment of persons who attempt self-poisoning-already approach their role in a holistic fashion and consider "advising" or "counseling" patients after self-poisoning to be a part of their nursing role. But there is no formal training given to such nurses at present nor has the efficacy or feasibility of such an intervention been assessed in Sri Lanka. The aims of this pilot study are to explore the potential efficacy, acceptability, and feasibility of carrying out a counseling intervention that could be delivered by nurses for persons who present to hospital for medical management of non-fatal self-poisoning. METHODS/DESIGN: The study will be carried out at the Toxicology Unit of Teaching Hospital Peradeniya, Sri Lanka. A pilot randomized controlled trial will be carried out among participants admitted to Teaching Hospital Peradeniya for medical management of non-fatal self-poisoning. The primary objective of this study is to explore the acceptability and feasibility of a counseling intervention being delivered by nurses. The secondary objectives are to explore the efficacy of the intervention for the improvement of skills to cope with situations of acute emotional distress, and to reduce rates of anxiety, depression, and future repetition and suicidal ideation. A nurse's experiences and attitudes regarding the acceptability and feasibility of implementing this intervention and participant experiences of the intervention and its effects will be explored via qualitative interviews and focus group discussions. DISCUSSION: It is anticipated that the findings of this pilot study will help determine and assess the acceptability and feasibility of this counseling intervention, as well as indicate the more useful aspects of this intervention in order to develop it for further exploration in a larger trial. TRIAL REGISTRATION: SLCTR/2017/008 Registered on 21st March 2017.

Relationship between alcohol co-ingestion and outcome in profenofos self-poisoning - A prospective case series.

INTRODUCTION: The importance of alcohol co-ingestion for outcome in organophosphorus (OP) insecticide self-poisoning has only been studied for the relatively hydrophilic dimethyl insecticide, dimethoate. We aimed to assess the effect of alcohol in acute poisoning with the lipophilic S-alkyl OP insecticide, profenofos. METHODOLOGY: Demographic and clinical data, including an alcohol history, were prospectively collected from all cases of acute poisoning with agricultural profenofos EC50 presenting to two Sri Lankan hospitals over seven years. RESULTS: Of 1859 patients with acute OP insecticide self-poisoning, 243 (13.1%) reported ingestion of profenofos (male 182/243, 74.9%). Alcohol co-ingestion was reported by 64/243 (26.3%). All patients reporting alcohol co-ingestion were male (64/64 [100%] vs 118/179 [65.9%] not reporting alcohol ingestion, p<0.001). More patients reporting alcohol co-ingestion died (10/64 [15.6%] vs 10/179 [5.6%]; p = 0.013) and required intubation (13/64 [20.3%] vs 16/179 [8.9%], p = 0.016) compared to those who did not co-ingest alcohol. Using multi-logistic regression, controlling for the estimated dose ingested, age (OR 11.1 [2.5 to 48.9] for age > 35 years vs ≤35 years) and alcohol co-ingestion (OR 3.1 [1.2 to 7.9]) were independently associated with increased risk of death. Increased risk of intubation was independently associated with age (OR 3.2 [1.6 to 6.6] for age > 35 years vs ≤35 years) and alcohol co-ingestion (OR 3.2 [1.6 to 6.4]). CONCLUSION: A history of alcohol co-ingestion, as well as older age, is independently associated with worse outcome in patients' self-poisoned with profenofos.

Effect of a brief outreach educational intervention on the translation of acute poisoning treatment guidelines to practice in rural Sri Lankan hospitals: a cluster randomized controlled trial.

BACKGROUND: In developing countries, including Sri Lanka, a high proportion of acute poisoning and other medical emergencies are initially treated in rural peripheral hospitals. Patients are then usually transferred to referral hospitals for further treatment. Guidelines are often used to promote better patient care in these emergencies. We conducted a cluster randomized controlled trial (ISRCTN73983810) which aimed to assess the effect of a brief educational outreach ('academic detailing') intervention to promote the utilization of treatment guidelines for acute poisoning. METHODS AND FINDINGS: This cluster RCT was conducted in the North Central Province of Sri Lanka. All peripheral hospitals in the province were randomized to either intervention or control. All hospitals received a copy of the guidelines. The intervention hospitals received a brief out-reach academic detailing workshop which explained poisoning treatment guidelines and guideline promotional items designed to be used in daily care. Data were collected on all patients admitted due to poisoning for 12 months post-intervention in all study hospitals. Information collected included type of poison exposure, initial investigations, treatments and hospital outcome. Patients transferred from peripheral hospitals to referral hospitals had their clinical outcomes recorded. There were 23 intervention and 23 control hospitals. There were no significant differences in the patient characteristics, such as age, gender and the poisons ingested. The intervention hospitals showed a significant improvement in administration of activated charcoal [OR 2.95 (95% CI 1.28-6.80)]. There was no difference between hospitals in use of other decontamination methods. CONCLUSION: This study shows that an educational intervention consisting of brief out-reach academic detailing was effective in changing treatment behavior in rural Sri Lankan hospitals. The intervention was only effective for treatments with direct clinician involvement, such as administering activated charcoal. It was not successful for treatments usually administered by non-professional staff such as forced emesis for poisoning. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN73983810 ISRCTN73983810.

Medical management of paraquat ingestion.

Poisoning by paraquat herbicide is a major medical problem in parts of Asia while sporadic cases occur elsewhere. The very high case fatality of paraquat is due to inherent toxicity and lack of effective treatments. We conducted a systematic search for human studies that report toxicokinetics, mechanisms, clinical features, prognosis and treatment. Paraquat is rapidly but incompletely absorbed and then largely eliminated unchanged in urine within 12-24 h. Clinical features are largely due to intracellular effects. Paraquat generates reactive oxygen species which cause cellular damage via lipid peroxidation, activation of NF-κB, mitochondrial damage and apoptosis in many organs. Kinetics of distribution into these target tissues can be described by a two-compartment model. Paraquat is actively taken up against a concentration gradient into lung tissue leading to pneumonitis and lung fibrosis. Paraquat also causes renal and liver injury. Plasma paraquat concentrations, urine and plasma dithionite tests and clinical features provide a good guide to prognosis. Activated charcoal and Fuller's earth are routinely given to minimize further absorption. Gastric lavage should not be performed. Elimination methods such as haemodialysis and haemoperfusion are unlikely to change the clinical course. Immunosuppression with dexamethasone, cyclophosphamide and methylprednisolone is widely practised, but evidence for efficacy is very weak. Antioxidants such as acetylcysteine and salicylate might be beneficial through free radical scavenging, anti-inflammatory and NF-κB inhibitory actions. However, there are no published human trials. The case fatality is very high in all centres despite large variations in treatment.