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Opium Use and Mortality: A Prospective Cohort of 50,000 Adults in Iran

Opium Use and Mortality: A Prospective Cohort of 50,000 Adults in Iran. Farin Kamangar. Outline. Significance of the Study Objectives Golestan Cohort Study Statistical methods Results Discussion Lessons learned and suggestions for further research. Outline. Significance of the Study

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Opium Use and Mortality: A Prospective Cohort of 50,000 Adults in Iran

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  1. Opium Use and Mortality: A Prospective Cohort of 50,000 Adults in Iran Farin Kamangar

  2. Outline Significance of the Study Objectives Golestan Cohort Study Statistical methods Results Discussion Lessons learned and suggestions for further research

  3. Outline Significance of the Study Objectives Golestan Cohort Study Statistical methods Results Discussion Lessons learned and suggestions for further research

  4. Opium and Opioid Use Recreational and medicinal use Long history 13 – 22 million used opium or its derivatives in 2008 Many areas of the world

  5. Opium: Recreational Use (19th Century)

  6. Opium: Medicinal Use

  7. Opium: Distributed and Used Worldwide

  8. Long History: Goddess of Opium

  9. Tintin and Opium Use

  10. Epidemiologic Studies of Opium and Health Very few epidemiologic studies of chronic opium use, despite such widespread use and long history Only a few case-control studies

  11. Studies of Opium and Health Increases the risk of esophageal cancer (Ghadirian 1985, Nasrollahzadeh2008) Increases the risk of bladder cancer (Behmard 1981, Aliasgari 2004, Shakhssalim 2010, Hosseini 2010) Increases the risk of laryngeal cancer (Mousavi, 2003) Increases the risk of two other cancers (unpublished)

  12. Studies of Opium and Health Increases the risk of cardiovascular disease (Sadeghian 2007, Sadeghian 2010, Masoomi 2010, Masoumi 2010) Increases the risk of deep vein thrombosis (Safaii 2010) Increases the risk of lung disease with chronic obstruction (Da Costa 1971)

  13. Research Gap • No large-scale or long-term prospective cohort studies of opium and health

  14. Outline Significance of the Study Objectives Golestan Cohort Study Statistical methods Results Discussion Lessons learned and suggestions for further research

  15. Objectives Use data from Golestan Cohort Study • To determine the effect of opium use on overall and cause-specific mortality • To determine this effect by type of opium use • Teriak • Shireh • Sukhteh • Heroin

  16. Outline Significance of the Study Objectives Golestan Cohort Study Statistical methods Results Discussion Lessons learned and suggestions for further research

  17. Golestan Cohort • In Golestan Province, northeast of Iran • 50,045 adults, 40 to 75 years of age • Detailed questionnaire data • General Questionnaire • Food Frequency Questionnaire • Biologic samples • Blood • Urine • Hair • Nail

  18. Very High Rates of Esophageal Cancer • Anecdotal reports • Reports from central institutions (Habibi 1965, Haghighi 1971) • Exploratory observations (Kmet 1966) • Cancer registry (1968 to 1971, Iran-IARC collaborations)

  19. Registry Results • The highest rates ever reported in the world • Rates also very high in women • Large differences in rates in 500 kilometers

  20. Ecologic Studies in the 1970s • Differences in fauna and flora • Differences in foods consumed (sheep’s milk, fruit and vegetables, sesame oil, etc) • Hot tea consumption in high quantities • Chewing of nass (a mixture of ash, lime, and tobacco) • Opium use (up to 50% of both sexes over 35 years)

  21. Case-Control Study(350 cases and 700 controls) • Not associated: sheep’s milk, sesame oil, chewing of nass, use of pregnancy diets, salting and sun-drying • Moderately associated: cigarette smoking, drinking hot tea, low intake of fresh fruits and vegetables, low socio-economic status • Not assessed: opium use Cook-Mozaffari, BJC 1979

  22. Opium: Further Studies • Types: • Crude opium • Sukhteh (opium pipe residues): mutagen in Ames test • Shireh (refined opium extract) • Hewer , Lancet 1978 • Case-control study of families • A half-completed case-control study showed a non-significant two-fold risk associated with EC risk Ghadirian, IJC 1985

  23. Summary Results from the 1970s • Northeastern Iran: a very high-risk area for EC • Risk similar in men and women • Smoking a weak risk factor, and alcohol consumption very uncommon • Some risk factors suggested (low SES, low intake of fresh fruit and vegetables, hot tea intake, but none striking) • Opium: some suggestions, but studies incomplete

  24. Case-Control Study:Basic idea • To re-evaluate the previous hypotheses for the very high incidence of esophageal cancer (e.g., opium use, hot tea intake, low socioeconomic status, low intake of fresh fruits and vegetables) • To test new hypotheses (e.g., animal contact, oral hygiene, genetic studies) • Use new technology (e.g., new genotyping capabilities, proteomics)

  25. Cases and controls • 300 esophageal cancer cases (all squamous cell) • 600 neighborhood controls, matched for age, sex, and neighborhood of residence

  26. Data and samples • General questionnaire • Food Frequency Questionnaire (validated against 24-hour recalls) • Blood • Hair and Nail • Biopsy samples

  27. General Questionnaire • Demographic characteristics • Residential history • Occupational history • Family and SES • Personal history of disease • Upper GI signs and symptoms • Personal and family history of cancer • Tobacco and opium use • Alcohol consumption • Medication history • Oral health • Anthropometric indices • Animal contact • Tea consumption • Physical activity • Methods of cooking and food preservation and water source

  28. Esophageal Cancer Lecture for Turkmen Doctors

  29. Case-Control Study • Recruitment started in 2003 and was completed in 2007. • A total of 300 cases and 571 matched controls were recruited. • Several papers have been published.

  30. Opium and Tobacco Use in Relation to Esophageal Cancer • Tobacco and/or opium • Neither 1.00 • Tobacco only 1.70 (1.05 – 2.73) • Opium only 2.12 (1.21 – 3.74) • Both 2.35 (1.50 – 3.67) • Some 30% of all cases can be attributed to these two factors. Nasrollahzadeh et al. BJC

  31. Cohort Study

  32. Cohort Study • This cohort study was designed to enroll 50,000 subjects from the eastern part of Golestan Province, with objectives similar to the case-control study. • Design was very similar to the case-control study. • General questionnaire • Dietary questionnaire • Blood • Hair and nail • Urine

  33. Cohort Study • Plasma (x8), RBC (x2), and buffy coat (x4) are stored in bar-coded straws and kept in – 80 freezers or nitrogen tanks. • Urine samples (used for PAH and opium assays) are also stored in -20 freezers or nitrogen tanks. • Half the samples in Iran and half in IARC.

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