Lessons from the field: compound-specific management in acute pesticide poisoning.

Pesticide poisoning is a common medical emergency in the rural tropics, with significant associated mortality. Pesticide poisoning is an umbrella term that encompasses a wide variety of substances with differing clinical toxidromes and outcomes. Despite this, confirmation of the specific compound ingested is rarely performed. In this Lessons from the Field, we argue that pesticide-specific management is integral to optimise management. Using data from a quality improvement project in Chittagong, Bangladesh, we demonstrate that identifying the specific compound is possible in most patients through careful history taking and examination of the pesticide bottle. Identification of the specific compound is essential for anticipating and reducing complications, administering appropriate and timely management and reducing the length of hospital stay and cost of unnecessary medical intervention.

The role of alcohol use in pesticide suicide and self-harm: a scoping review.

PURPOSE: Suicide and self-harm by pesticide self-poisoning is common in low- and middle-income countries (LMICs). Alcohol is an important risk factor for self-harm; however, little is known about its role in pesticide self-poisoning. This scoping review explores the role that alcohol plays in pesticide self-harm and suicide. METHODS: The review followed the Joanna Briggs Institute scoping review guidance. Searches were undertaken in 14 databases, Google Scholar, and relevant websites. Articles were included if they focussed on pesticide self-harm and/or suicide and involvement of alcohol. RESULTS: Following screening of 1281 articles, 52 were included. Almost half were case reports (n = 24) and 16 focussed on Sri Lanka. Just over half described the acute impact of alcohol (n = 286), followed by acute and chronic alcohol use (n = 9), chronic use, (n = 4,) and only two articles addressed harm to others. One systematic review/meta-analysis showed increased risk of intubation and death in patients with co-ingested alcohol and pesticides. Most individuals who consumed alcohol before self-harming with pesticides were men, but alcohol use among this group also led to pesticide self-harm among family members. Individual interventions were recognised as reducing or moderating alcohol use, but no study discussed population-level alcohol interventions as a strategy for pesticide suicide and self-harm prevention. CONCLUSION: Research on alcohol's role in pesticide self-harm and suicide is limited. Future studies are needed to: further assess the toxicological effects of combined alcohol and pesticide ingestion, explore harm to others from alcohol including pesticide self-harm, and to integrate efforts to prevent harmful alcohol use and self-harm.

Banning highly hazardous pesticides saves the lives of young people, particularly females, in low- and middle-income countries.

Pesticide self-poisoning is a public health problem mostly affecting low- and middle-income countries. In Sri Lanka, India and China suicide rates have reduced among young people, particularly females, following highly hazardous pesticides (HHP) bans. This success story requires attention to encourage more research on differential effects of HHP bans.

Viper envenomation in Central and Southeastern Europe: a multicentre study.

INTRODUCTION: Snakebite incidence varies across Europe. However, there is limited research from Central and Southeastern Europe. These regions are notable for the presence of the common European adder (Vipera berus) and the more venomous nose-horned viper (Vipera ammodytes). No standard European antivenom protocol exists. The aim was to assess the epidemiology and treatment of viper bites in this region, focusing on a comparison of bites from Vipera berus and Vipera ammodytes. METHODS: We conducted a prospective multicenter study in Central and Southeastern Europe from 2018 to 2020. This study included poison centres and toxicology-associated hospital wards in Poland, the Czech Republic, Slovakia, Hungary, Slovenia, Croatia, Serbia, and Bulgaria. The following data were collected: age, gender, Vipera species, snakebite site, clinical picture, laboratory results, Audebert's clinical severity grading score, and antivenom therapy. RESULTS: The annual incidence of viper bites in Central and Southeast Europe was estimated at 2.55 bites per million population. Within their respective geographical distribution areas, the incidence of Vipera ammodytes bites (1.61 bites per million population) was higher than Vipera berus bites (1.00 bites per million population). Patients bitten by Vipera ammodytes more frequently reported local pain and developed thrombocytopenia. Antivenom treatment was more commonly administered in Vipera ammodytes bites (72%) compared to Vipera berus bites (39%). The incidence of Vipera ammodytes bites treated with antivenom within its geographical distribution area was three times higher than Vipera berus bites treated with antivenom (1.16 bites per million population versus 0.39 bites per million population). No deaths were reported. CONCLUSIONS: The estimated incidence of viper bites in Central and Southeastern Europe is at least 2.55 per million population. Vipera ammodytes bites are more common and severe, characterized by higher frequencies of pain and thrombocytopenia. Antivenom is needed more often for Vipera ammodytes bites. It is vital that enough European Medicines Agency-approved Vipera ammodytes antivenom is produced and offered affordably.

A lethal cocktail - shining a light on the relationship between alcohol use and pesticide self-poisoning.

INTRODUCTION: Alcohol and pesticides are toxic substances that each cause acute and chronic harm to humans. Alcohol plays an important and complex role in pesticide self-poisoning, involving toxicological, public health, and social aspects important for research, prevention, and interventions. ALCOHOL USE DISORDER AND SOCIAL HARMS: While the evidence on alcohol co-ingestion in the context of pesticide self-poisoning is limited, it appears that alcohol use increases complications. Even fewer studies address alcohol use disorder and dependence among pesticide self-poisoning patients. The harmful use of alcohol also impacts social life, families, and communities in several ways, including pesticide self-poisoning among individuals around the alcohol user. This, however, is vastly understudied. OUTSIDE INFLUENCES: Agrochemicals and alcohol are produced by industries with financial interests, and the outcome of individual acts of pesticide self-poisoning depends on the lethality of the pesticide purchased and ingested. The promotion of acutely toxic pesticides by companies must be acknowledged within this issue. CONCLUSION: The relationship between alcohol and pesticide self-poisoning is increasingly clear, but more studies are needed to guide management. We cannot ignore that pesticide self-poisoning and harmful use of alcohol occur within the context of wider, often structural, stressors and are influenced by commercial entities.

Differences in the characteristics of people who purchase pesticides from shops for self-harm versus those who use pesticides available in the domestic environment in Sri Lanka.

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.

Impact of pesticide regulations on mortality from suicide by pesticide in China: an interrupted time series analysis.

Background: Pesticide bans and regulatory restrictions have been shown to be effective strategies for preventing suicide in several countries. Suicide and suicide by pesticides have decreased significantly in China over the past two decades. However, whether the reduction was associated with pesticide regulation is unknown. Methods: The monthly data on suicide and suicide by pesticide from 2006 to 2018 were obtained from China's Disease Surveillance Point (DSP) system. Information on China's pesticide regulations since 1970 was obtained from Pesticide Action Network International (PAN International), Joint Meeting on Pesticide Management Highly Hazardous Pesticides (JMPM HHP) lists, the website of the Ministry of Agriculture of China, Pesticide Information Network of China, and the Wan Fang database. Change point detection and policy analysis were combined to identify the time of any trend change breakpoint of suicide and suicide by pesticide. Interrupted time series analysis was used to investigate the pre- and post-breakpoint trends of monthly standardized rates in suicide and suicide by pesticide. Results: The standardized pesticide suicide rate decreased by 60.5% from 6.50 in 2006 to 2.56 per 100,000 in 2018. Larger declines were evident among people in urban areas (67.3%), female individuals (63.5%), and people aged 15-44 years (68.1%). The effect of policies banning highly hazardous organophosphorus pesticides (HHOP) [rate ratio (RR) = 0.993, 95% CIs (0.991-0.994)] in December 2008 and stopping domestic sales and use of paraquat aqueous solution (RR = 0.992, 95% CIs: 0.990-0.994) in July 2016 were more pronounced than regulating the paraquat-related products (RR = 1.003, 95% CIs: 1.002-1.004) in April 2012. Conclusion: Declines in suicide by pesticide in China occurred contemporaneously with regulatory bans and restrictions implemented on several pesticides, particularly in urban areas, among female individuals, and the relatively low age profile. These findings indicate the potential influence of these bans on trends of suicide by pesticides.

Quantification of Organophosphorus Insecticide Removed by Gastric Lavage in Acutely Poisoned Patients: An Observational Study.

Introduction: The effectiveness of gastric lavage in organophosphorus (OP) poisoning has not been established. We assessed the ability of gastric lavage to remove OP insecticides as a preliminary stage in assessing effectiveness. Patients and methods: Organophosphorus poisoning patients presenting within 6 hours were included, irrespective of prior gastric lavage. A nasogastric tube was placed and gastric contents aspirated, followed by at least three cycles of gastric lavage with 200 mL of water. Samples from the initial aspirate and the first three lavage cycles were sent for identification and quantification of the OP compounds. Patients were monitored for complications of gastric lavage. Results: Around 42 patients underwent gastric lavage. Eight (19.0%) patients were excluded from the study because of a lack of analytical standards for ingested compounds. Insecticides were detectable in the lavage samples of 24 of 34 (70.6%) patients. Lipophilic OP compounds were detected in 23 of 24 patients, while no hydrophilic OP compounds could be detected in six patients with reported ingestion of hydrophilic compounds. For chlorpyrifos poisoning (n = 10), only 0.65 mg (SD 1.2) of the estimated ingested amount (n = 5) of 8,600 mg (SD 3,200) was recovered by gastric lavage. The mean proportion of the compound removed by initial gastric aspirate was 79.4% and subsequent three cycles removed 11.5, 6.6, and 2.7%. Conclusion: Lipophilic OP insecticides could be quantified in the stomach contents of OP poisoning patients with the first aspiration or lavage being most effective. The amount removed was very low; hence, routine use of gastric lavage for OP poisoning patients arriving within 6 hours is unlikely to be beneficial. How to cite this article: Mathansingh AJ, Jose A, Fleming JJ, Abhilash KPP, Chandiraseharan VK, Lenin A, et al. Quantification of Organophosphorus Insecticide Removed by Gastric Lavage in Acutely Poisoned Patients: An Observational Study. Indian J Crit Care Med 2023;27(6):397-402.

Surveillance of pesticide poisoning in an East and a West Malaysian hospital: characteristics of pesticide poisoning and the early impact of a national Paraquat ban.

BACKGROUND: Previous studies have shown that pesticide bans were associated with reduced fatal pesticide self-poisoning cases in high, and low-and-middle-income countries. We aimed to investigate the characteristics of pesticide poisoning patients admitted to two Malaysian hospitals and the early impact of the national paraquat ban implemented on 1st January 2020 in a culturally heterogenous South-East-Asian upper-middle-income setting. METHODS: Data were collected from an East (Bintulu) and a West (Ipoh) Malaysian hospital medical records in 2015-2021 and 2018-2021, respectively. Logistic regression analyses were conducted to investigate the association of aspects such as socio-demographic and clinical characteristics, paraquat ban with the types of pesticides involved (paraquat versus non-paraquat versus unknown) ,and the outcomes (fatal versus non-fatal). RESULTS: From the study sample of 212 pesticide poisoning patients aged 15 years or above, the majority were self-poisoning cases (75.5%) with a disproportionate over-representation of Indian ethnic minority (44.8%). Most pesticide poisoning cases had socio-environmental stressors (62.30%). The commonest stressors were domestic interpersonal conflicts (61.36%). 42.15% of pesticide poisoning survivors had a psychiatric diagnosis. Paraquat poisoning accounted for 31.6% of all patients and 66.7% of fatalities. Case fatality was positively associated with male gender, current suicidal intent, and paraquat poisoning. After the paraquat ban, the proportion of pesticide poisoning cases using paraquat decreased from 35.8 to 24.0%, and the overall case-fatality dropped slightly from 21.2 to 17.3%. CONCLUSIONS: Socio-environmental stressors in specific domestic interpersonal conflicts, seemed more prominent in pesticide poisoning compared to psychiatric diagnosis. Paraquat accounted for the majority of pesticide-associated deaths occurring in hospitals in the study areas. There was preliminary evidence that the 2020 paraquat ban led to a fall in case fatality from pesticide poisoning.

Conceptualising the commercial determinants of suicide: broadening the lens on suicide and self-harm prevention.

Suicide is preventable, yet, in many settings, robust suicide prevention strategies have not been implemented. Although a commercial determinants of health lens is increasingly being applied to industries important to the field of suicide prevention, the interplay between the vested interests of commercial actors and suicide has received little attention. There is a need to shift attention to the causes of the causes, directing more focus to the ways that commercial determinants influence suicide and shape suicide prevention strategies. Such a shift in perspective, with an evidence base and precedents to draw upon, has transformative potential for research and policy agendas dedicated to understanding and addressing upstream modifiable determinants of suicide and self-harm. We propose a framework intended to help guide efforts to conceptualise, research, and address the commercial determinants of suicide and their inequitable distribution. We hope these ideas and lines of inquiry help to catalyse connections between disciplines and open further debate and discussion as to how to take such an agenda forward.

Suicides by pesticide ingestion in Pakistan and the impact of pesticide regulation.

INTRODUCTION: Suicide is a major public health problem in Pakistan, accounting to approximately 19,331 deaths every year. Many are due to consumption of acutely toxic pesticides; however, there is a lack of national suicide data, limiting knowledge and potential for intervention. In this paper, we aimed to review the literature on pesticide self-poisoning in Pakistan to identify the most problematic pesticides in relation to national pesticide regulations. METHODS: Information on the currently registered and banned pesticides was obtained from Ministry of National Food Security and Research while data on pesticide import and use was extracted from FAOSTAT. We searched the following sources for articles and research papers on poisoning in Pakistan: Cumulative Index to Nursing and Allied Health (CINAHL), Google Scholar, Applied Social Sciences Index and Abstracts (ASSIA), Excerpta Medica (EMBASE), National Library of Medicine's MEDLINE (PUBMED), PS102YCHINFO and Pakmedinet.com using the search terms 'self-poisoning', 'deliberate self-harm', 'suicide', 'methods and means of suicide', 'organophosphate', 'wheat pill', 'aluminium phosphide', 'acute poisoning', OR 'pesticides', AND 'Pakistan'. RESULTS: As of May 2021, 382 pesticide active ingredients (substances) were registered in Pakistan, of which five were WHO hazard class Ia (extremely hazardous) and 17 WHO hazard class Ib (highly hazardous). Twenty-six pesticides, four formulations, and seven non-registered pesticides had been banned, of which two were WHO class Ia and five Ib. We identified 106 hospital-level studies of poisoning conducted in Pakistan, of which 23 did not mention self-poisoning cases and one reported no suicidal poisoning cases. We found no community or forensic medicine studies. Of 52,323 poisoning cases identified in these papers, 24,546 [47%] were due to pesticides. The most commonly identified pesticide classes were organophosphorus (OP) insecticides (13,816 cases, 56%) and the fumigant aluminium phosphide (3 g 56% tablets, often termed 'wheat pills'; 686 cases, 2.7%). Few studies identified the particular pesticides involved or the resulting case fatality. CONCLUSION: We found pesticide poisoning to be a major cause of poisoning in Pakistan, with OP insecticides and the fumigant aluminium phosphide the main pesticides identified. Withdrawal of Class I pesticides (as proposed to occur nationally in 2022) and high concentration aluminium phosphide tablets should rapidly reduce suicidal deaths by reducing the case fatality for low-intention poisoning cases. National cause of death data and forensic toxicology laboratory data identifying the pesticides responsible for deaths will be important to assess impacts of the proposed national ban.

Co-Benefits of Largescale Organic farming On huMan health (BLOOM): Protocol for a cluster-randomised controlled evaluation of the Andhra Pradesh Community-managed Natural Farming programme in India.

The BLOOM study (co-Benefits of Largescale Organic farming On huMan health) aims to determine if a government-implemented agroecology programme reduces pesticide exposure and improves dietary diversity in agricultural households. To achieve this aim, a community-based, cluster-randomised controlled evaluation of the Andhra Pradesh Community-managed Natural Farming (APCNF) programme will be conducted in 80 clusters (40 intervention and 40 control) across four districts of Andhra Pradesh state in south India. Approximately 34 households per cluster will be randomly selected for screening and enrolment into the evaluation at baseline. The two primary outcomes, measured 12 months post-baseline assessment, are urinary pesticide metabolites in a 15% random subsample of participants and dietary diversity in all participants. Both primary outcomes will be measured in (1) adult men ≥18 years old, (2) adult women ≥18 years old, and (3) children <38 months old at enrolment. Secondary outcomes measured in the same households include crop yields, household income, adult anthropometry, anaemia, glycaemia, kidney function, musculoskeletal pain, clinical symptoms, depressive symptoms, women's empowerment, and child growth and development. Analysis will be on an intention-to-treat basis with an a priori secondary analysis to estimate the per-protocol effect of APCNF on the outcomes. The BLOOM study will provide robust evidence of the impact of a large-scale, transformational government-implemented agroecology programme on pesticide exposure and dietary diversity in agricultural households. It will also provide the first evidence of the nutritional, developmental, and health co-benefits of adopting agroecology, inclusive of malnourishment as well as common chronic diseases. Trial registration: Study registration: ISRCTN 11819073 (https://doi.org/10.1186/ISRCTN11819073). Clinical Trial Registry of India CTRI/2021/08/035434.

Agriculture without paraquat is feasible without loss of productivity-lessons learned from phasing out a highly hazardous herbicide.

A small proportion of the thousands of pesticides on the market today are associated with a disproportionately high incidence of severe acute pesticide poisoning and suicide. Paraquat stands out as one of the most lethal pesticides in common use, frequently involved in fatal incidents due to suicides or accidental exposure. Even though paraquat has been banned in over 67 countries, it is still widely used in many others, particularly in Asia and Latin America. Based on a literature review and consultations, this paper identifies options for replacing paraquat and distils practical lessons from numerous successes around the world. Our aim is to support regulators, policymakers, agronomists and the supply chain sector with practical information related to phasing out paraquat. Production data consistently failed to show any negative effects of banning paraquat on agricultural productivity. A wide range of alternative approaches to weed management and crop defoliation are available, many of which do not rely on herbicides. Over 1.25 million farmers in low- and middle-income countries (LMICs) successfully produce a range of crops for private voluntary standards (PVS) in food and fiber supply chains which prohibit paraquat use. We conclude from the findings of this study that eliminating paraquat will save lives without reducing agricultural productivity. Less hazardous and more sustainable alternatives exist. To enhance successful adoption and uptake of these methods on a wide scale, farmers require training and support within an enabling policy environment.

Correction: The 20-minute whole blood clotting test (20WBCT) for snakebite coagulopathy-A systematic review and meta-analysis of diagnostic test accuracy.

[This corrects the article DOI: 10.1371/journal.pntd.0009657.].

Accuracy of substance exposure history in patients attending emergency departments after substance misuse; a comparison with biological sample analysis.

CONTEXT: Acute toxicity caused by illicit substance use is a common reason for emergency department (ED) presentation. Knowledge of the substances involved is helpful for predicting and managing potential toxicity, but limited information is available about the accuracy of patient-reported substance exposure. This study assessed the accuracy of the history of exposure in those reporting use of a single substance by comparison with those identified by detailed toxicological analysis, focusing on synthetic cannabinoid receptor agonists (SCRA). METHODS: Adults (≥16 years) presenting between March 2015 and July 2021 to participating UK hospitals with toxicity after reporting use of a single illicit substance were included. Exposure details were documented from medical records and blood and/or urine samples analysed using high-resolution accurate mass liquid chromatography-mass spectrometry (HRAM LCMS). Sensitivity, specificity, and positive and negative predictive values of the exposure history were calculated by comparison with biological sample analysis ("gold standard"). RESULTS: Single substance exposure was reported for 474 (median age 33 years, IQR: 18 range 16-75, 80% males) patients. Analysis commonly identified multiple substances (Median 3, IQR 2-5). A history of exposure was documented for 121 of 151 patients where a SCRA or metabolite was detected on analysis (sensitivity 80.1%, 95% CI 72.9, 86.2%). Corresponding proportions were lower for 3,4-methylenedioxymethamphetamine (MDMA, 44/70, 62.9%., 95% CI 50.5%, 74.1%), heroin 41/108 (38.0% 95% CI 28.8-47.8%) and cocaine (22/56, 31.3%, 95% CI 20.9, 43.6%). CONCLUSIONS: Multiple undeclared substances were detected analytically in most patients reporting single substance use. Clinicians should be alert to the potential presence and toxicity of unreported substances when managing patients presenting after substance misuse.

Dose ingested, vomiting, and outcome in patients ingesting a standard paraquat 20SL formulation.

BACKGROUND: FAO specifications for liquid paraquat dichloride SL formulations require the use of an emetic agent to stimulate vomiting within 30 min of ingestion. To date, there is no high-quality evidence of efficacy, despite use of the PP796 emetic since 1979. We first examined the validity of patients' self-reported dose of paraquat ingested by examining the relationship with blood paraquat concentration and time to death for patients ingesting the standard paraquat SL formulation in a Sri Lankan cohort. As a secondary outcome, we assessed whether ingestion resulted in vomiting within 30 min and whether vomiting was associated with good outcome. METHODS: Patients presenting with paraquat SL self-poisoning were prospectively studied in ten Sri Lankan hospitals in 2003-08. Data on reported dose ingested, incidence and timing of vomiting after ingestion, treatment received, plasma paraquat concentration, and outcome were collected prospectively on presentation to hospital. Time between ingestion and blood sampling was incorporated by covariate adjustment. RESULTS: 441 patients were recruited to the case series, presenting a median (IQR) of 3.0 (1.5-8.1] h post ingestion. Outcome was known for 435 patients of whom 322 (74.0%) died within 42 days, a median of 1.3 (0.6-4.4) days post ingestion. Median reported dose ingested was 15 to <30 mL. There was a highly significant linear trend between log plasma paraquat and reported dose ingested (p < .001); adjustment for the log of the time from ingestion to sampling further improved the model fit. Case fatality and median time to death also showed good agreement with estimated ingestion amount. 347/438 patients (79.2%) were stated to have vomited before reaching the study hospital with 300 (68.5%) vomiting within 30 min of ingestion; time to vomiting was unknown for a further 12 (2.7%). The proportion vomiting was strongly associated with reported dose ingested (p < .001); of note the proportion vomiting within 30 min only increased to 83.3% for the highest ingestion group. Patients vomiting within 30 min had higher plasma paraquat concentrations (p = .008), and higher hazard ratio in the adjusted Cox regression model of 2.01 (95% CI 1.45-2.77) compared to those who did not. Vomiting within 30 min was associated with a higher case fatality (241/295 [81.7%] vs 68/125 [54.4%], p < .001). Forty-three (47.3%) of the 91 patients who did not vomit before reaching hospital died (one had unknown outcome). CONCLUSION: Importantly, we found good agreement between reported dose ingested and plasma paraquat concentration, case fatality, and time to death, suggesting that the reported dose is a valid marker for the dose ingested. Vomiting occurred within 30 min for 68.5% of patients, exceeding the characteristics for a purported effective emetic in the FAO specifications. However, vomiting within 30 min was associated with approximately double the risk of death compared to those who did not vomit, larger paraquat ingestions, and higher blood paraquat concentrations. In addition, death occurred in many patients who did not vomit, and the proportion vomiting within 30 min only reached 82.1% for the highest ingested dose group. Overall, we found no evidence of benefit resulting from incorporation of the emetic, suggesting that the current FAO specification is not effective at preventing deaths after ingestion of the paraquat SL formulation.

Relationship Between Alcohol Co-Ingestion and Clinical Outcome in Pesticide Self-Poisoning: A Systematic Review and Meta-Analysis.

AIM: Alcohol is a commonly co-ingested compound during self-poisoning with pesticides. Clinical experiences suggest alcohol co-ingestion (or withdrawal) makes patient management more difficult after self-poisoning and may contribute to poor clinical outcomes. We aimed to systematically review the world literature to explore the relationship between alcohol co-ingestion and outcome in pesticide self-poisoning. METHODS: We searched 13 electronic databases and Google scholar, conducted citation searching and a review of reference lists to find studies which investigated the relationship of alcohol with clinical outcome of pesticide self-poisoning in different countries. Thirteen studies, including 11 case series/reports and two cohort studies were considered for inclusion. RESULTS: Meta-analysis showed that alcohol co-ingestion in pesticide self-poisoning was associated with increased risk of death [odds ratio (OR) 4.9, 95% confidence interval (CI) 2.9-8.2 P<0.0001] and that alcohol co-ingested group required intubation eight times more often than non-co-ingested group in organophosphorus insecticide self-poisoning (OR 8.0, 95% CI 4.9-13.0 P<0.0001). Cases who co-ingested alcohol were older than non-alcohol group in two studies. One cohort study demonstrated that alcohol co-ingestion was associated with larger pesticide ingestions but did not itself affect the outcome. CONCLUSIONS: This systematic review indicates that alcohol co-ingestion may worsen clinical outcome in pesticide self-poisoning.

"Calcium bombs" as harbingers of synaptic pathology and their mitigation by magnesium at murine neuromuscular junctions.

Excitotoxicity is thought to be an important factor in the onset and progression of amyotrophic lateral sclerosis (ALS). Evidence from human and animal studies also indicates that early signs of ALS include degeneration of motor nerve terminals at neuromuscular junctions (NMJs), before degeneration of motor neuron cell bodies. Here we used a model of excitotoxicity at NMJs in isolated mouse muscle, utilizing the organophosphorus (OP) compound omethoate, which inhibits acetylcholinesterase activity. Acute exposure to omethoate (100 µM) induced prolonged motor endplate contractures in response to brief tetanic nerve stimulation at 20-50 Hz. In some muscle fibers, Fluo-4 fluorescence showed association of these contractures with explosive increases in Ca2+ ("calcium bombs") localized to motor endplates. Calcium bombs were strongly and selectively mitigated by increasing Mg2+ concentration in the bathing medium from 1 to 5 mM. Overnight culture of nerve-muscle preparations from WldS mice in omethoate or other OP insecticide components and their metabolites (dimethoate, cyclohexanone, and cyclohexanol) induced degeneration of NMJs. This degeneration was also strongly mitigated by increasing [Mg2+] from 1 to 5 mM. Thus, equivalent increases in extracellular [Mg2+] mitigated both post-synaptic calcium bombs and degeneration of NMJs. The data support a link between Ca2+ and excitotoxicity at NMJs and suggest that elevating extracellular [Mg2+] could be an effective intervention in treatment of synaptic pathology induced by excitotoxic triggers.