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Disabling Neuropsychiatric Disease in Farmers Exposed to Organophosphates Phase 1

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Disabling Neuropsychiatric Disease in Farmers Exposed to Organophosphates Phase 1 DISABLING NEUROPSYCHIATRIC DISEASE IN FARMERS EXPOSED TO ORGANOPHOSPHATES: PHASE 1: THE STUDY OF HEALTH IN AGRICULTURAL WORK COHORT Project number VM02115 Project investigators Dr AC Povey, Professor RM Agius, Occupational and Environmental Health Research Group, Faculty of Medical and Human Sciences, University of Manchester, Dr R McNamee, Biostatistics, Informatics and Health Economics Research Group, Faculty of Medical and Human Sciences, University of Manchester Professor A Burns, Professor F Creed, Psychiatry Research Group, Faculty of Medical and Human Sciences, University of Manchester Professor D Neary, Clinical Neurosciences Research Group, Faculty of Medical and Human Sciences, University of Manchester IN CONFIDENCE TO SPONSORS DATE: 23/11/07 1 Foreword This report has been prepared to provide information on the SHAW study which has examined the health effects of low dose chronic exposure to organophosphates in sheep farmers with the UK. It includes a detailed description of the study design and methodology used together with the results of the phase 1 of the study. The results from the second phase of the study will be appended as they and those questions subsequent to this report are completed. 2 Contents Foreword 2 Contents 3 List of Tables 5 List of Figures 7 List of Appendices 8 Executive Summary 10 1.0 Introduction 12 1.1 Aims and objectives of the present study 13 2.0 Materials and Methods 14 2.1 Study design 14 2.2 Study population 14 2.2.1 Database entry, merging and cleaning 14 2.2.2 Addition of postcodes and telephone numbers 15 2.3 Study recruitment 15 2.3.1 Office of National Statistics 16 2.4 Screening questionnaire 16 2.5 Case Identification 17 2.5.1 Screen identified depression 17 2.5.2 Screen identified dementia 18 2.5.3 Screen identified neuropathy 18 2.5.4 Screen identified Parkinsonism 18 2.6 Ethical approval 18 2.7 Statistical analysis 19 3.0 Description of study cohort 19 3.1 Study population 19 3.2 Response rates 21 3.2.1 Adjusted response rates 23 3.3 ONS tracing 23 3.3.1 Death certificate tracing 24 4.0 Analysis of screening questionnaire 24 4.1 Demographics of population 24 3 4.2 Farming background and activities 24 4.3 Health status 25 4.4 Screen identified depression 26 4.5 Screen identified dementia 26 4.6 Screen identified neuropathy and Parkinsonism 27 4.7 Associations between screen identified depression and farming 27 4.8 Associations between screen identified dementia and farming 28 4.9 Associations between screen identified neuropathy and farming 29 4.10 Associations between screen identified Parkinsonism and farming 30 4.11 Associations between screen identified ill-health and sheep farming 30 4.12 Associations between screen identified ill-health and cattle farming 31 4.13 Associations between seeking medical advice for pesticide poisoning 31 and farming 4.14 Associations between seeking medical advice for pesticide poisoning 32 and screen identified ill-health 4.15 Risk of screen identified ill-health and farming factors in a population 33 restricted to those who had not sought medical advice for pesticide poisoning 5.0 Discussion 34 5.1 Strengths and weaknesses of the phase 1 study 36 5.1.1 Screen identified ill-health 39 5.1.2 Exposure assessment 40 5.2 SHAW study phases and SHAW study objectives 41 5.3 Summary 43 6.0 Acknowledgements 43 7.0 References 45 Tables 49 Figures 80 Appendices 87 4 List of Tables 1. Response rates in study population by source of information 49 2. Response rates in study population by geographical region 50 3. Demographics and farming variables of study population 51 4. Farming sector worked by study population 52 5. Farming activities carried out by study population 53 6. Handling of different types of concentrate by study population 54 7. Current medical problems in study population 55 8. Seeking medical advice in the study population 56 9. Current medical treatment in study population 57 10. Differences in farmers and farming variables by case status of screen 58 identified depression 11. Risk of screen identified depression by farming sector 59 12. Risk of screen identified depression by farming activity 60 13. Risk of screen identified depression by handling of pesticide 61 concentrate 14. Differences in farmers and farming variables by case status of screen 62 identified dementia 15. Risk of screen identified dementia by farming sector 63 16. Risk of screen identified dementia by farming activity 64 17. Risk of screen identified dementia by handling of pesticide 65 concentrate 18. Differences in farmers and farming variables by case status of screen 66 identified neuropathy 19. Risk of screen identified neuropathy by farming sector 67 20. Risk of screen identified neuropathy by farming activity 68 21. Risk of screen identified neuropathy by handling of pesticide 69 concentrate 22. Differences in farmers and farming variables by case status of screen 70 identified Parkinsonism 23. Risk of screen identified Parkinsonism by farming sector 71 24. Risk of screen identified Parkinsonism by farming activity 72 25. Risk of screen identified Parkinsonism by handling of pesticide 73 5 concentrate 26. Differences in farmers and farming variables by case status of ever 74 seeking medical advice for pesticide poisoning 27. Associations between ever seeking medical advice for pesticide 75 poisoning and farming sectors 28. Associations between ever seeking medical advice for pesticide 76 poisoning and farming activities 29. Associations between ever seeking medical advice for pesticide 77 poisoning and handling of pesticide concentrate 30. Associations between ever seeking medical advice for pesticide 78 poisoning and screen identified ill-health 31. Associations between screen identified ill-health and farming 79 variables in the whole population and a population restricted to those who had never sought medical advice for pesticide poisoning 6 List of Figures 1. Creation of SHAW database for mailing 80 2. Initial and final responses to SHAW mailing and telephone contact 81 3. Regional distribution of the SHAW sampling frame 82 4. Adjusted response rates by (A) Information Source and (B) 83 Geographical Region. 5. Associations between screen identified (A) depression, (B) dementia, 84 (C) neuropathy and (D) Parkinsonism and working with sheep, sheep farming activities and handling sheep dip concentrate 6. Associations between screen identified (A) depression, (B) dementia, 85 (C) neuropathy and (D) Parkinsonism and worki ng with cattle, cattle farming activities and handling cattle concentrate 7. Associations between ever seeking medical advice for pesticide 86 poisoning and (A) working with sheep, sheep farming activities, and handling sheep dip concentrate and (B) wor king with cattle, cattle farming activities and handling cattle concentrate 7 List of Appendices 1 Source of cohort members - NFU Ledger books 87 2 Source of cohort members - Cattle Association Records 88 3 Source of cohort members - Sheep Association Records 89 4 Source of cohort members - Shepherd’s guides 90 5 Introductory letter to cohort members 91 6 Information leaflet 92 7 Consent form 94 8 Health and Work Questionnaire 95 9 Addressee update (Blue form) 103 10 Follow-up letter (England) 104 11 Follow-up letter (Scotland) 105 12 Follow up letter (Wales) 106 13 SHAW non-responders telephone call 107 14 Telephone questionnaire 108 15 Dear occupier letter (general version) 110 16 Dear occupier letter (moved away version) 111 17 Dear occupier letter (deceased version) 112 18 Follow-up letter – retired farmer 113 19 Letter to Health Authority 114 20 Letter to doctor 115 21 Letter to subject 116 22 Number of farm workers and agricultural holdings in 1970 117 23 Geographical distribution of (A) Farmers (1970-71), (B) Regular farm 118 workers (1970-1971), (C) Agricultural holdings (1970-71) and (D) the SHAW cohort 24 Geographical distribution of cohort members identified through (A) 119 NFU ledger books, (B) Sheep associations, (C) Cattle associations and (D) Shepherd’s Guides 25 Geographical distribution of the SHAW sampling frame 120 26 Responses to further contact with initial non-responders 122 27 Responses to telephone contact of initial non-responders 123 28 Responses to “Dear Occupier” letters 124 8 29 Causes of death 125 30 Responses (%) to screening questionnaire (A3 questions) 126 31 Responses (%) to screening questionnaire (A4 questions) 127 32 Responses (%) to screening questionnaire (A2 questions) 128 33 Response rates of various studies in farming communities 129 9 Executive summary Long term low dose exposure to organophosphates (OPs) has been associated with chronic ill-health particularly in sheep farmers. However in the absence of overt acute toxicity the epidemiological evidence linking chronic ill- health to such exposures is weak. To address this specific question, a large historically prospective cohort study of farmers from the 1970s has been carried out. One of the a priori hypotheses was that if OP exposure were a cause of neuropsychiatric disease, then any adverse ill-health would be associated with handling the sheep dip concentrate as this activity is the main determinant of OP exposure. A cohort containing 18958 people who were farmers in the 1970s was identified through contemporaneous records held by the National Farmers’ Union, Sheep and Cattle Associations and through Shepherd’s Guides. Information on the study, a consent form and a brief screening questionnaire were sent to the identified person at the (1970s) address that had been obtained. Responses were obtained from (or about) 7691 people of whom 1380 completed the screening questionnaire (17.9%), 4635 had died (60.3%) and 1102 refused (14.3%). No response was obtained from 11,267 people of whom 5870 (51.4%) were known to have moved away from the address that had been obtained. Using as a denominator only those cohort subjects known to be still alive and to have the received the original letter, 48% of that population completed the screening questionnaire.
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