1. Chronic central nervous system effects of acute organophosphate pesticide intoxication Rosenstock et al 1991 Presented by Michael Choi, Dalal Sulaihim and Soodtida Tangpraphaphorn

2. 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

3. 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

4. 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

5. 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

6. 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

7. Susceptibility Oral, respira- tory or dermal intake Biologically Effective Dose Inhibition of AchE Poor Ach reuptake, saturation of Ach on receptors Neuro- psych Dysfunc -tion Chronic Neuro Sequelæ Environment Farmers working with pesticides, pesticide residues on food and clothing, education level Organo- phosphate Model: Pathways of Environmental Effects on Health “Source-Receptor Model”

8. 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

9. 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.

10. 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.

11. 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)

12. 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.

13. 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.

14. 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

15. 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

16. 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.