Pralidoxime in Acute Organophosphorus Insecticide Poisoning-A Randomised Controlled Trial

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

Pattern of pesticide storage before pesticide self-poisoning in rural Sri Lanka

<p>Abstract</p> <p>Background</p> <p>Deliberate self-poisoning with agricultural pesticides is the commonest means of suicide in rural Asia. It is mostly impulsive and facilitated by easy access to pesticides. The aim of this large observational study was to investigate the immediate source of pesticides used for self-harm to help inform suicide prevention strategies such as reducing domestic access to pesticides.</p> <p>Methods</p> <p>The study was conducted in a district hospital serving an agricultural region of Sri Lanka. Patients who had self-poisoned with pesticides and were admitted to the adult medical wards were interviewed by study doctors following initial resuscitation to identify the source of pesticides they have ingested.</p> <p>Results</p> <p>Of the 669 patients included in the analysis, 425 (63.5%) were male; the median age was 26 (IQR 20-36). In 511 (76%) cases, the pesticides had been stored either inside or immediately outside the house; among this group only eight patients obtained pesticides that were kept in a locked container. Ten percent (n = 67) of the patients used pesticides stored in the field while 14% (n = 91) purchased pesticides from shops within a few hours of the episode. The most common reasons for choosing the particular pesticide for self-harm were its easy accessibility (n = 311, 46%) or its popularity as a suicide agent in their village (n = 290, 43%).</p> <p>Conclusion</p> <p>Three quarters of people who ingested pesticides in acts of self-harm used products that were available within the home or in close proximity; relatively few patients purchased the pesticide for the act. The study highlights the importance of reducing the accessibility of toxic pesticides in the domestic environment.</p

Poisoning with the S-Alkyl organophosphorus insecticides profenofos and prothiofos

Background: Many organophosphorus (OP) insecticides have either two O-methyl or two O-ethyl groups attached to the phosphorus atom. This chemical structure affects their responsiveness to oxime-induced acetylcholinesterase (AChE) reactivation after poisoning. However, several OP insecticides are atypical and do not have these structures

Careers in family business: New avenues for careers and family business research in the 21st century

The purpose of our special issue is to demonstrate how a careers perspective can contribute to the study of family businesses and bring to light how the family business context extends and challenges career theories and concepts. Inspired by the studies in our special issue and our review of previous research, we propose a conceptual model that leverages the concept of family embeddedness and intertwines it with career processes and outcomes. Building on the family embeddedness perspective, we propose several avenues for future research for family business and career scholars

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

<div><p>Introduction</p><p>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.</p><p>Methodology</p><p>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.</p><p>Results</p><p>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]).</p><p>Conclusion</p><p>A history of alcohol co-ingestion, as well as older age, is independently associated with worse outcome in patients’ self-poisoned with profenofos.</p></div

Evaluation of acceptability and use of lockable storage devices for pesticides in Sri Lanka that might assist in prevention of self-poisoning

<p>Abstract</p> <p>Background</p> <p>Self-poisoning with pesticides is a major reason for high suicide rates in rural areas of many developing countries. Safer storage of pesticides may be one means of prevention. We have conducted a study to assess the acceptability and use of lockable boxes for storing pesticides in rural Sri Lanka.</p> <p>Methods</p> <p>Four hundred lockable metal storage boxes were given to farming households, 100 in each of four villages. Assessment interviews were conducted by Sumithrayo (NGO) field workers immediately after boxes were supplied (T1), 11 – 14 weeks later (T2), 30 weeks later (T3), and 18 months later (T4). Data on suicide and self-harm were collected from local police and hospitals.</p> <p>Results</p> <p>At T1 only 1.8% (7/396) of households reported locking up pesticides, 72.5% (279/385) easy access to pesticides for adults and 50.4% (195/387) easy access for children. At T3 most informants in households using pesticides reported using the box all (82.3%, 298/362) or most of the time (7.2%, 26/362). Informants usually reported always locking the box (92.8%, 336/362) and most boxes were locked on inspection (93.6%, 339/362). By T4 there was some reduction in reporting that the box was kept locked all of the time (75.2%, 267/355) and the box being locked on inspection (73.8%, 262/355). Easy child access to the key was reported in relatively few households (10.7% at T4), although interviewers judged that this was possible in rather more (20.6%). Most informants regarded the box as useful (100% at T3 and 99.4% at T4), with convenience for storage, security, avoiding wastage, and protection of children being major factors. A message on the box about how to deal with bad feelings and the importance of safer storage was well received. The locks had been broken or the key lost in a few households.</p> <p>Conclusion</p> <p>Introduction of lockable boxes for storing pesticides to farming households in Sri Lanka appeared to be acceptable. Most households used the boxes responsibly, although there was some decline in the proper usage over time. A large-scale trial of lockable storage devices in farming households in rural areas as a means of prevention of suicide and accidental poisoning is now indicated.</p

Fructose-1, 6-diphosphate (FDP) as a novel antidote for yellow oleander-induced cardiac toxicity: A randomized controlled double blind study

BACKGROUND: Cardiac toxicity due to ingestion of oleander plant seeds in Sri Lanka and some other South Asian countries is very common. At present symptomatic oleander seed poisoning carries a mortality of 10% in Sri Lanka and treatment of yellow oleander poisoning is limited to gastric decontamination and atropine administration. The only proven effective antidote is digoxin antibodies but these are not available for routine use because of the high cost. The main objective of this study is to investigate the effectiveness of a new and inexpensive antidote for patients with life threatening arrhythmias due oleander poisoning. METHOD/DESIGN: We set up a randomised double blind clinical trial to assess the effectiveness of Fructose 1, 6 diphosphate (FDP) in acute yellow oleander poisoning patients admitted to the adult medical wards of a tertiary hospital in Sri Lanka. Patients will be initially resuscitated following the national guidelines and eligible patients will be randomised to receive either FDP or an equal amount of normal saline. The primary outcome measure for this study is the sustained reversion to sinus rhythm with a heart rate greater than 50/min within 2 hours of completion of FDP/placebo bolus. Secondary outcomes include death, reversal of hyperkalaemia on the 6, 12, 18 and 24 hour samples and maintenance of sinus rhythm on the holter monitor. Analysis will be on intention-to-treat. DISCUSSION: This trial will provide information on the effectiveness of FDP in yellow oleander poisoning. If FDP is effective in cardiac glycoside toxicity, it would provide substantial benefit to the patients in rural Asia. The drug is inexpensive and thus could be made available at primary care hospitals if proven to be effective. TRIAL REGISTRATION: Current Controlled trial ISRCTN71018309

A community-based cluster randomised trial of safe storage to reduce pesticide self-poisoning in rural Sri Lanka: study protocol

BACKGROUND: The WHO recognises pesticide poisoning to be the single most important means of suicide globally. Pesticide self-poisoning is a major public health and clinical problem in rural Asia, where it has led to case fatality ratios 20-30 times higher than self-poisoning in the developed world. One approach to reducing access to pesticides is for households to store pesticides in lockable "safe-storage" containers. However, before this approach can be promoted, evidence is required on its effectiveness and safety. METHODS/DESIGN: A community-based cluster randomised controlled trial has been set up in 44,000 households in the North Central Province, Sri Lanka. A census is being performed, collecting baseline demographic data, socio-economic status, pesticide usage, self-harm and alcohol. Participating villages are then randomised and eligible households in the intervention arm given a lockable safe storage container for agrochemicals. The primary outcome will be incidence of pesticide self-poisoning over three years amongst individuals aged 14 years and over. 217,944 person years of follow-up are required in each arm to detect a 33% reduction in pesticide self-poisoning with 80% power at the 5% significance level. Secondary outcomes will include the incidence of all pesticide poisoning and total self-harm. DISCUSSION: This paper describes a large effectiveness study of a community intervention to reduce the burden of intentional poisoning in rural Sri Lanka. The study builds on a strong partnership between provincial health services, local and international researchers, and local communities. We discuss issues in relation to randomisation and contamination, engaging control villages, the intervention, and strategies to improve adherence

Correction:The role of alcohol use in pesticide suicide and self-harm: a scoping review (Social Psychiatry and Psychiatric Epidemiology, (2023), 10.1007/s00127-023-02526-9)

The Funding information section was missing from this article and should have read as given below, “The Centre for Pesticide Suicide Prevention is funded by a grant from Open Philanthropy, at the recommendation of GiveWell”. The original article has been corrected.</p

Self-poisoning in rural Sri Lanka: small-area variations in incidence

<p>Abstract</p> <p>Background</p> <p>Self-poisoning is one of the most common methods of suicide worldwide. The intentional ingestion of pesticides is the main contributor to such deaths and in many parts of rural Asia pesticide self-poisoning is a major public health problem. To inform the development of preventive measures in these settings, this study investigates small-area variation in self-poisoning incidence and its association with area-based socioeconomic and agricultural factors.</p> <p>Methods</p> <p>Ecological analysis of intentional self-poisoning in a rural area (population 267,613) of Sri Lanka in 2002. The geographic distribution of cases was mapped to place of residence. Using administrative division (GN), median population size 1416, as unit of analysis, associations with socioeconomic and agricultural indicators were explored using negative binomial regression models.</p> <p>Results</p> <p>The overall incidence of intentional self-poisoning in the study area was 315 per 100,000 (range: 0 – 2168 per 100,000 across GNs). Socioeconomic disadvantage, as indexed by poor housing quality (p = 0.003) and low levels of education (p < 0.001) but not unemployment (p = 0.147), was associated with a low self-poisoning incidence. Areas where a high proportion of the population worked in agriculture had low overall levels of self-poisoning (p = 0.002), but a greater proportion of episodes in these areas involved pesticides (p = 0.01). An association with extent of cultivated land was found only for non-pesticide poisoning (p = 0.01).</p> <p>Conclusion</p> <p>Considerable small-area variation in incidence rates of intentional self-poisoning was found. The noteworthy concentration of cases in certain areas and the inverse association with socioeconomic deprivation merit attention and should be investigated using individual-level exposure data.</p