http://nova.newcastle.edu.au/vital/access/services/Feed ${session.getAttribute("locale")} 5 http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12274 Background: Acute organophosphorus pesticide poisoning causes tens of thousands of deaths each year across the developing world. Standard treatment involves administration of intravenous atropine and oxime to reactivate inhibited acetylcholinesterase. The clinical usefulness of oximes, such as pralidoxime and obidoxime, has been challenged over the past 20 years by physicians in many parts of the world. Objectives: To quantify the effectiveness and safety of the administration of oximes in acute organophosphorus pesticide-poisoned patients. Search Strategy: We searched both English and Chinese databases: Cochrane Injuries Group Specialised Register, Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE (Ovid SP), EMBASE (Ovid SP), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), ISI Web of Science: Conference Proceedings Citation Index-Science (CPCI-S) and the Chinese language databases CNKI and WANGFANG. All searches were run in September 2009. Selection Criteria: Articles that could possibly be RCTs were retrieved to determine if they were randomised. Data Collection and Analysis: The published methodology of three RCTs was not clear. We contacted the principal authors of these, but did not obtain further information. Main Results: Seven pralidoxime RCTs were found. Three RCTs including 366 patients studied pralidoxime vs placebo and four RCTs including 479 patients compared two or more different doses. These trials found quite disparate results with treatment effects ranging from benefit to harm. However, many studies did not take into account several issues important for outcomes. In particular, baseline characteristics were not balanced, oxime doses varied widely, there were substantial delays to treatment, and the type of organophosphate was not taken into account. Only one RCT compared the World Health Organization (WHO) recommended doses with placebo. This trial showed no clinical benefits and a trend towards harm in all sub-groups, despite clear evidence that these doses reactivated acetylcholinesterase in the blood. Authors's Conclusions: Current evidence is insufficient to indicate whether oximes are harmful or beneficial. The WHO recommended regimen (30 mg/kg pralidoxime chloride bolus followed by 8 mg/kg/hr infusion) is not supported. Further RCTs are required to examine other strategies and regimens. There are many theoretical and practical reasons why oximes may not be useful, particularly for late presentations of dimethyl OP and those with a large excess of OP that simply re-inhibits reactivated enzymes. Future studies should screen for patient sub-groups that may benefit and may need flexible dosing strategies as clinical effectiveness and doses may depend on the type of OP. 2013-01-30T03:28:21.329Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10617 Context: The case fatality from acute poisoning with glyphosate-containing herbicides is approximately 7.7% from the available studies but these have major limitations. Large prospective studies of patients with self-poisoning from known formulations who present to primary or secondary hospitals are needed to better describe the outcome from acute poisoning with glyphosate containing herbicides. Furthermore, the clinical utility of the glyphosate plasma concentration for predicting clinical outcomes and guiding treatment has not been determined. Objective: To describe the clinical outcomes, dose–response, and glyphosate kinetics following self-poisoning with glyphosate-containing herbicides. Methods: This prospective observational case series was conducted in two hospitals in Sri Lanka between 2002 and 2007. We included patients with a history of acute poisoning. Clinical observations were recorded until discharge or death. During a specified time period, we collected admission (n = 216, including five deaths) and serial (n = 26) blood samples in patients. Severity of poisoning was graded using simple clinical criteria. Results: Six hundred one patients were identified; the majority ingested a concentrated formulation (36%, w/v glyphosate). Twenty-seven percent were asymptomatic, 63.7% had minor poisoning, and 5.5% of patients had moderate to severe poisoning. There were 19 deaths (case fatality 3.2%) with a median time to death of 20 h. Gastrointestinal symptoms, respiratory distress, hypotension, altered level of consciousness, and oliguria were observed in fatal cases. Death was strongly associated with greater age, larger ingestions, and high plasma glyphosate concentrations on admission (>734 μg/mL). The apparent elimination half-life of glyphosate was 3.1 h (95% CI = 2.7–3.6 h). Conclusions: Despite treatment in rural hospitals with limited resources, the mortality was 3.2%, which is lower than that reported in previous case series. More research is required to define the mechanism of toxicity, better predict the small group at risk of death, and find effective treatments. 2012-04-12T01:58:01.241Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7937 Background: Poisoning with organophosphorus (OP) insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of pralidoxime, this antidote's effectiveness remains unclear. We aimed to determine whether the addition of pralidoxime chloride to atropine and supportive care offers benefit. Methods and Findings: We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receive pralidoxime (121) or saline placebo (114). Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving pralidoxime: 30/121 (24.8%) receiving pralidoxime died, compared with 18/114 (15.8%) receiving placebo (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 0.88–3.26, p = 0.12). Incorporating the baseline amount of acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving pralidoxime compared to placebo, further decreasing the likelihood that pralidoxime is beneficial. The need for intubation was similar in both groups (pralidoxime 26/121 [21.5%], placebo 24/114 [21.1%], adjusted HR 1.27 [95% CI 0.71–2.29]). To reduce confounding due to ingestion of different insecticides, we further analysed patients with confirmed chlorpyrifos or dimethoate poisoning alone, finding no evidence of benefit. Conclusions: Despite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required. 2012-01-30T05:23:36.995Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:9577 Background: Agricultural pesticide poisoning is a major public health problem in the developing world, killing at least 250,000-370,000 people each year. Targeted pesticide restrictions in Sri Lanka over the last 20 years have reduced pesticide deaths by 50% without decreasing agricultural output. However, regulatory decisions have thus far not been based on the human toxicity of formulated agricultural pesticides but on the surrogate of rat toxicity using pure unformulated pesticides. We aimed to determine the relative human toxicity of formulated agricultural pesticides to improve the effectiveness of regulatory policy. Methods and Findings: We examined the case fatality of different agricultural pesticides in a prospective cohort of patients presenting with pesticide self-poisoning to two clinical trial centers from April 2002 to November 2008. Identification of the pesticide ingested was based on history or positive identification of the container. A single pesticide was ingested by 9,302 patients. A specific pesticide was identified in 7,461 patients; 1,841 ingested an unknown pesticide. In a subset of 808 patients, the history of ingestion was confirmed by laboratory analysis in 95% of patients. There was a large variation in case fatality between pesticides-from 0% to 42%. This marked variation in lethality was observed for compounds within the same chemical and/or WHO toxicity classification of pesticides and for those used for similar agricultural indications. Conclusion: The human data provided toxicity rankings for some pesticides that contrasted strongly with the WHO toxicity classification based on rat toxicity. Basing regulation on human toxicity will make pesticide poisoning less hazardous, preventing hundreds of thousands of deaths globally without compromising agricultural needs. Ongoing monitoring of patterns of use and clinical toxicity for new pesticides is needed to identify highly toxic pesticides in a timely manner. 2012-01-30T05:01:44.706Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7395 Background: Deliberate self-poisoning with older pesticides such as organophosphorus compounds are commonly fatal and a serious public health problem in the developing world. The clinical consequences of self-poisoning with newer pesticides are not well described. Such information may help to improve clinical management and inform pesticide regulators of their relative toxicity. This study reports the clinical outcomes and toxicokinetics of the neonicotinoid insecticide imidacloprid following acute self-poisoning in humans. Methodology/Principal Findings: Demographic and clinical data were prospectively recorded in patients with imidacloprid exposure in three hospitals in Sri Lanka. Blood samples were collected when possible for quantification of imidacloprid concentration. There were 68 patients (61 self-ingestions and 7 dermal exposures) with exposure to imidacloprid. Of the self-poisoning patients, the median time to presentation was 4 hours (IQR 2.3–6.0) and median amount ingested was 15 mL (IQR 10–50 mL). Most patients only developed mild symptoms such as nausea, vomiting, headache and diarrhoea. One patient developed respiratory failure needing mechanical ventilation while another was admitted to intensive care due to prolonged sedation. There were no deaths. Median admission imidacloprid concentration was 10.58 ng/L; IQR: 3.84–15.58 ng/L, Range: 0.02–51.25 ng/L. Changes in the concentration of imidacloprid in serial blood samples were consistent with prolonged absorption and/or saturable elimination. Conclusions: Imidacloprid generally demonstrates low human lethality even in large ingestions. Respiratory failure and reduced level of consciousness were the most serious complications, but these were uncommon. Substitution of imidacloprid for organophosphorus compounds in areas where the incidence of self-poisoning is high may help reduce deaths from self-poisoning. 2012-01-30T04:59:46.026Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7237 Herbicides are commonly ingested for self-harm, but relatively little has been published on poisoning with herbicides other than paraquat and glyphosate. We report here a case series of patients with acute exposure to a combination herbicide (brand name Tiller Gold or Whip Super) containing the selective phenoxy herbicide compounds fenoxaprop-P-ethyl and ethoxysulfuron and a safener isoxadifen ethyl. Clinical data on all patients presenting with Tiller Gold or Whip Super poisoning to two General Hospitals in Sri Lanka from 2002–2008 were collected prospectively until discharge. Eighty-six patients with a history of Tiller Gold or Whip Super ingestion were included. The main clinical features were an epigastric burning sensation and vomiting; however, most of those who vomited had received gastric lavage or forced emesis. Eight patients had a reduced level of consciousness on admission (Glasgow coma scale 9–14) that resolved without intervention over several hours. Only symptomatic and supportive care was required. The median hospital stay was 1 day (IQR: 1–2) and the case fatality was zero (95% confidence interval: 0–4.2%). This low case fatality compared favorably with the case fatality of other common herbicides in our cohort: paraquat >40%, propanil >10%, 4-chloro-2-methylphenoxyacetic acid > 5%, and glyphosate >2%. This combination herbicide product appears to be safe in patients with acute self-poisoning, particularly in comparison with other herbicides, and causing few clinical features. 2011-02-21T04:00:09.724Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:4376 Background: Self-poisoning with pesticides is the cause of an estimated 300,000 deaths annually in rural Asia. The great majority of these deaths are from impulsive acts of self-harm using pesticides that are readily available in the home. The secure storage of pesticides under lock has been emphasized as a possible answer to the problem. This aspect, however, has been poorly researched. In this paper, we report on the design and use, in rural Sri Lanka, of a variety of different lockable storage devices. Methods: Following a baseline survey of pesticide storage practices, randomly selected households received a pesticide safe storage device. The study was conducted in two phases. In the first phase a total of 200 households in two villages were provided with in-house safe storage devices and two follow-up surveys were conducted seven and 24 months after distribution. The results of the seven month post-distribution survey have already been published. In the second phase, a further 168 households were selected in two additional villages and given a choice between an in-house and an in-field storage device and a follow-up survey conducted seven months after distribution. Both follow-up surveys aimed to assess the use of the device, obtain detailed user feedback on the different storage designs, and to identify problems faced with safeguarding the key. Twelve focus group discussions were held with representatives of households that received a storage device to derive from the community qualitative feedback on the design requirements for such devices. Results: One hundred and sixty one of the 200 households selected during the first phase were using pesticides at the time of the follow-up survey, 24 months after distribution. Of these 161 households 89 (55%) had the pesticides stored and locked in the provided device. Among the 168 households that were given a choice between an in-house and an in-field storage device 156 used pesticides at the time of survey and of these 103 (66%) selected in-field storage devices and 34% chose in-house storage devices. Of the 156 households, 106 (68%) stored all pesticides in a locked storage device at the time of the follow-up survey seven months after distribution. The majority of households that received an in-field storage device chose to install the device within their compound rather than in the field as they were concerned about the possibility of theft. The preferred design of the storage device was influenced by a number of occupational factors such as land size, crop patterns, types and the quantity of pesticides used. The presence of termites, perceived safety, material used to manufacture the device and ease of location influenced their choice. The study revealed that it was difficult to keep the key to the device hidden from children; and that the person in charge of the key would have easy access to the stored poison. Conclusion: This study confirms the high acceptance of lockable storage devices by the community although the use of the device reduced over time. A large proportion of pesticides stored within the compound after the introduction of the device may have implications for accessibility to pesticides in the domestic environment. The ability of other household members, including children, to easily find the key is also worrying. 2010-04-27T05:01:41.070Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:4457 Background: Pesticide ingestion is a common method of self-harm in the rural developing world. In an attempt to reduce the high case fatality seen with the herbicide paraquat, a novel formulation (INTEON) has been developed containing an increased emetic concentration, a purgative, and an alginate that forms a gel under the acid conditions of the stomach, potentially slowing the absorption of paraquat and giving the emetic more time to be effective. We compared the outcome of paraquat self-poisoning with the standard formulation against the new INTEON formulation following its introduction into Sri Lanka. Methods and Findings: Clinical data were prospectively collected on 586 patients with paraquat ingestion presenting to nine large hospitals across Sri Lanka with survival to 3 mo as the primary outcome. The identity of the formulation ingested after October 2004 was confirmed by assay of blood or urine samples for a marker compound present in INTEON. The proportion of known survivors increased from 76/297 with the standard formulation to 103/289 with INTEON ingestion, and estimated 3-mo survival improved from 27.1% to 36.7% (difference 9.5%; 95% confidence interval [CI] 2.0%–17.1%; p = 0.002, log rank test). Cox proportional hazards regression analyses showed an approximately 2-fold reduction in toxicity for INTEON compared to standard formulation. A higher proportion of patients ingesting INTEON vomited within 15 min (38% with the original formulation to 55% with INTEON, p ≺ 0.001). Median survival time increased from 2.3 d (95% CI 1.2–3.4 d) with the standard formulation to 6.9 d (95% CI 3.3–10.7 d) with INTEON ingestion (p = 0.002, log rank test); however, in patients who did not survive there was a comparatively smaller increase in median time to death from 0.9 d (interquartile range [IQR] 0.5–3.4) to 1.5 d (IQR 0.5–5.5); p = 0.02. Conclusions: The survey has shown that INTEON technology significantly reduces the mortality of patients following paraquat ingestion and increases survival time, most likely by reducing absorption. 2010-04-27T04:59:01.233Z ]]>