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Chronic central nervous system effects of acute organophosphate pesticide intoxication. Rosenstock et al 1991 Presented by Michael Choi, Dalal Sulaihim and Soodtida Tangpraphaphorn. Introduction.
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Chronic central nervous system effects of acute organophosphate pesticide intoxication Rosenstock et al 1991 Presented by Michael Choi, Dalal Sulaihim and Soodtida Tangpraphaphorn
Introduction • Research question: Do single episodes of acute organophosphate intoxication lead to chronic neuropsychological dysfunction? • Exposure: hospitalization for acute organophosphate pesticide poisoning • Outcome: chronic neuropsychological dysfunction • Retrospective cohort study of farm workers in Nicaragua hospitalized for occupationally-related acute organophosphate poisoning testing for impaired neurological functions
Toxicology • Organophosphates are used as pesticides and chemical weapons • Organophosphates inhibit acetylcholinesterase enzyme • Symptoms include sweating, salivation, diarrhea, (SLUDGE) • Treatable in early stages via oxime therapy and atropine
Subjects • 36 matched pairs of men (n=72) ages 15-44 at time of hospitalization • no history of serious illness or neurological disorders • recruited from hospital discharge records in Leon, Nicaragua • matched by age to close male friend or sibling in same community
Methods • 6 (out of 7) WHO subtests modified • WAIS-R digit span and symbol • Spanish-translated standardized tests (including WAIS-R vocabulary) • Brief symptom inventory (self-reported) • Investigator-devised literacy test
Results • Cases had lower performance scores on 6 WHO subtests, 5 were stat. sig. • Reaction time, vocabulary and motor speed scores not stat. sig. different between groups • Cases tended towards greater number somatic complaints
Model: Pathways of Environmental Effects on Health “Source-Receptor Model” Susceptibility Oral, respira-tory or dermal intake Poor Ach reuptake, saturation of Ach on receptors Biologically Effective Dose Inhibition of AchE Neuro-psych Dysfunc-tion Organo-phosphate Chronic Neuro Sequelæ Environment Farmers working with pesticides, pesticide residues on food and clothing, education level
Strengths • Innovative study • Cases and control matched on age and alcohol consumption in the last month. • Neuropsychological deficit cannot be explained by any other factor • Found statistical differences in neuropsychological tests for acute exposure even with occupational exposure among the control group. • Neurological testing not conducted via computer keyboard
Weaknesses • Problems with sample selection (cases & controls) • 14 of the 36 claimed to have sought medical treatment for at least one pesticide poisoning. • 5 reported previous poisoning related admission to hospital. • Not enough information about how and where data were collected.
Weaknesses (continued) • The cases have higher percentage of working with solvents. • The control group has higher education level (17% of cases and 12% of the control have no formal education). • They reported that SES is not a confounder but they did not give any information about the SES of either group.
Measurement Bias • “Acutely poisoned” may have more background exposure compared to controls; may be partially responsible for observed associations • Experimenter bias unlikely since investigators were blinded • Recall bias unlikely as hospital records were used, but possible for other measured variables (e.g. drinking habits)
Selection Bias • Selection bias unlikely, criteria for exclusion does not suggest those excluded may have influenced the results. • Most of the people invited to take part in the study (95%) agreed to participate.
Confounding • Pre-morbid intelligence of study participants unknown • Traumatic effects of being hospitalized for acute organophosphate poisoning • Resulting psychiatric effects such as depression may have resulted in poorer performance on tests • Not all psychiatric problems would be reported because of a possible stigma. Also, access to care in Nicaragua is presumably poor.
Non-differential Misclassification • Not all those “acutely poisoned” sought treatment. Conversely, some less acutely poisoned may have sought treatment • Likely to some extent in general, as measurement techniques and instruments (e.g. WHO test battery) are imperfect
Discussion • Study not replicable, lacks info about stat. analyses, methodology • It is consistent with similar literature; study was unprecedented • Multicenter study would vastly improve generalizability of results • Future research should include prospective cohort studies
References • McConnell, R.; Keifer, M.; Rosenstock, L. (1994). Elevated Quantitative Vibrotactile Threshold Among Workers Previously Poisoned with Methamidophos and other Organophosphate Pesticides. American Journal of Industrial Medicine. 25:325-334. • Savage, E.; Keefe, T.J.; Mounce, L.; Heaton, R.K.; Lewis, J. A.; Burcar, P.J. (Chronic Neurological Sequelae of Acute Organophosphate Pesticide Poisoning. Archives of Environmental Health. 38-44. • Stallone, L.; Beselert, C. (2002. Pesticide illness, Farm Practice, and Neurological Symptoms among Farmers in Colorado. Environmental Research Section A/89-97. • Stephens, R. Spurgeon, A.; Calvert, I.; Jermey, B.; Levy, L.; Helen, B.; Harrington, J.M. (1995). Neuropsychological effects of long-term exposure to organophosphates in sheep dip. The Lancet. 345(8958):1135-1139. • Tai, C.K. (2002). Organophosphate Pesticides: Biochemistry and clinical toxicology. Therapeutic Drug Monitoring. 24(1):144-149.