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RADIATION EPIDEMIOLOGY AND LEUKEMIA B.Ledoshchuk, M . D.,Ph . D.

RADIATION EPIDEMIOLOGY AND LEUKEMIA B.Ledoshchuk, M . D.,Ph . D. Institute of Epidemiology Research Center for Radiation Medicine of Ukraine Kyiv-2001. EPIDEMIOLOGY OF LEUKAEMIA. Results of the 10-year study of leukemia among the Chernobyl accident clean-up workers in Ukraine 1986-96 .

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RADIATION EPIDEMIOLOGY AND LEUKEMIA B.Ledoshchuk, M . D.,Ph . D.

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  1. RADIATIONEPIDEMIOLOGYAND LEUKEMIAB.Ledoshchuk, M.D.,Ph.D. Institute of Epidemiology Research Center for Radiation Medicine of Ukraine Kyiv-2001

  2. EPIDEMIOLOGY OF LEUKAEMIA Results of the 10-year study of leukemia among the Chernobyl accident clean-up workers in Ukraine 1986-96

  3. GENERAL EPIDEMIOLOGY • EPIDEMIOLOGY • studies the occurrence and prevalence of diseases among population • identifies disease cases • determines probable relationship between various risk factors

  4. UNIVERSITIES AND INSTITUTES OF EPIDEMIOLOGY ENGLAND 14 CANADA 13 WESTERN EUROPE 26 USA 89 UKRAINE 1 AUSTRALIA 12 AFRICA-ASIA 5

  5. GENERAL EPIDEMIOLOGY Types of Epidemiology • medical • pharmaceutical • veterinary • environmental • insurance

  6. GENERAL EPIDEMIOLOGY Classification of medical epidemiology • Infection epidemiology • Generalepidemiology • Environment epidemiology • Clinical epidemiology • Military epidemiology • Epidemiology of insurance

  7. Main types of epidemiology research

  8. GENERAL EPIDEMIOLOGY Methods of analytical epidemiology • Cohort • Case control • Combined

  9. GENERAL EPIDEMIOLOGY Methods of analytical epidemiology Cohort study, Follow-up study Investigation for a certain period of time of a group of people defined prior to onset of disease • Registration of new disease cases • Exposed group (clean-up workers-86 ) • Unexposed group(clean-up workers-87, 88-90 ) There is a risk of healthy worker effect in comparison with population (underestimation IR in exposed group)

  10. GENERAL EPIDEMIOLOGY Methods of analytical epidemiology Case/control studies • Investigation of groups of people defined by presence or absence of disease • Case - ( patient) exposed and unexposed • Control - (healthy) exposed and unexposed • Only estimation of relative risk is possible RR (relative risk) or OR (odds ratio)

  11. EPIDEMIOLOGYOF LEUKAEMIA • Goal of research: Define the dependenceof incidence of leukemia among Chernobyl accident clean-up workers (ACW) on the year of participation in emergency works and period of time that passed since exposure to radiation

  12. EPIDEMIOLOGYOF LEUKAEMIA Results and discussion • Subject of observation: Chernobyl accident clean-up workers (ACW), males, included in State Chernobyl Registry of Ukraine. • The number of persons under study at the end of the observation period is 179 026 .

  13. EPIDEMIOLOGYOF LEUKAEMIA Sources of information • State Registry of victims of Chernobyl accident (CA) • specialized registries and subregistries • primary data from medical clinics • data of official disease registration and death cases registration • special selective registration of cases • data of expert commission for victims of CA

  14. EPIDEMIOLOGYOF LEUKAEMIA Main sources of information for case search: • Results of annual medical examination of ACW • Regional hematological clinics data

  15. EPIDEMIOLOGYOF LEUKAEMIA Main methods of obtaining of information : • retrospective • current • passive • active

  16. EPIDEMIOLOGYOF LEUKAEMIA Period of observation ACW: 1987-1996 Calculation were performed for 5-year intervals 1987-1991, 1992-1996

  17. EPIDEMIOLOGYOF LEUKAEMIA Diagnostic criteria • - under-record of cases due to strong diagnostic criteria • - over-record of cases (including irrelevant to the diagnosis cases) due to insufficient demands to diagnosis

  18. Classification of diseases Choice: • Etiology • patogeneses • Localizations disease • ICD-9 orICD-10 • Clinical (FAB) Classification of Leukaemia

  19. Reliability of the Diagnoses the Factors influencing the quality of the diagnoses • subjective, objective symptoms; outcomes of laboratory and tool researches • Diagnostic criterions (the majority of diseases has no precise criterions) • Classification of diseases (in case of indeterminacies; vague, not updated cases) • Reliability of the diagnosis - autopsy (types of researches) • interpretation errors of classification

  20. Strict selection of cases • Loss of true diseases • Soft selection of cases • Deriving cases not have significance Gipo diagnostics Giper diagnostics Reliability of the Diagnoses

  21. Sensitivity and specificity Under the sensitivity one understand probability that, the patient canl be classified as the patient  Numberof the patients classified as the patients Se = Total number of the patients Under the specificity one understand to probability that healthy can be classified as healthy  Number of Healthy, classified as healthy Sp = Total number of healthy

  22. MODEL of SENSITIVITY And SPECIFICITYA. Ahlbom, S.Norel 1990 Classified cs the patients The patients The population Healthy classified as the patients The patients classified as healthy (Is false Negative) (Is false Positive) The patients classified as the patients

  23. Information flows between institutions and the center • cCITY HOSPITAL • DDISPENSARY • OBLAST HOSPITAL OBLAST DISPENSARY • INSTITUTIONAL HEMATOLOGICAL DEPARTMENTS CENTER FOR RADIATION MEDICINE

  24. Information exchange for quality control EPIDEMIOLOGIST SUPERVISER D/B TECHNICIAN

  25. EPIDEMIOLOGYOF LEUKAEMIA LEUKEMIA DIAGNOSIS STRUCTURE There are 48 cases of leukemia among clean-up workers of 1986 • 13 – acute leukemia - AL (27 %), • 20 – CLL (42 %), • 14 – CML (29 %), • 1 – other forms of leukemia (2 %).

  26. EPIDEMIOLOGYOF LEUKAEMIA LEUKEMIA DIAGNOSIS STRUCTURE There are 15 cases of leukemia among clean-up workers of 1987 • 8 cases of AL (53 %), • 2 cases of CLL (13 %), • 4 cases of CML (27 %), • 1 case of unspecified leukemia (7 %).

  27. EPIDEMIOLOGYOF LEUKAEMIA LEUKEMIA DIAGNOSIS STRUCTURE There are 8 cases of leukemia among clean-up workers of 1988-90 • 1 case of AL , • 4 cases of CLL, • 3 cases of CML.

  28. EPIDEMIOLOGYOF LEUKAEMIA LEUKEMIA DIAGNOSIS STRUCTURE

  29. GENERAL EPIDEMIOLOGY • Crude measure – calculated for population as a whole • Specific measure – calculated for specific groups of population • Standardized measure – for completion of summary comparison between two or more groups diversified according to age or other criteria

  30. GENERAL EPIDEMIOLOGY Generate rate • Absolute rate (number) • Popularity • Morbidity • Mortality • Expressed as cases from 106 to 103 in investigated cohort (case/control)

  31. GENERAL EPIDEMIOLOGY Popularity prevalence rate, ratio - PR • It is a quota of morbidity among population in certain moment of time PR =number of existing cases of disease population during the same of time period

  32. GENERAL EPIDEMIOLOGY Morbidity incidence rate - IR Represents rate at which new cases are occurring. • IR =number of new cases of disease over a specified time period person-years, person-time, time at risk

  33. GENERAL EPIDEMIOLOGY CUMULATIVE INCIDENCE • cumulative incidence rate - CI • It is a quota of healthy persons that can fall ill during a certain period of time • CI =number of new cases over a specified time period population at the beginning of a specified time period • , where IR – incidence rate – duration of observation period

  34. GENERAL EPIDEMIOLOGY confidence interval Calculation of 95% confidence intervals for • prevalence rate (PR) • cumulative incidence rate (CI) • incidence rate (IR) IR1.96 (R- person-years)

  35. GENERAL EPIDEMIOLOGY confidence interval Calculation of 95% confidence intervals for • relative risk where e - logarithmic base = 2,718 ln - logarithmic function with e base (natural logarithm) ln(RR) - survey number = square root of dispersion var calculated number

  36. GENERAL EPIDEMIOLOGY Calculation of Relative Risk For cumulative incidence RR=(A1/N1)/(A0/N0) where А=number of cases N=number of person year 95% confidence interval for relative risk ln(RR)-dispersion var[ln(RR)] =[(N1-A1)/(N1*A1)]+[(N0-A0)/(N0*A0]

  37. GENERAL EPIDEMIOLOGY Calculation of Relative Risk For incidence rate RR=(A1/R1)/(A0/R0) where А=number of cases R=number of person-years 95% confidence interval for relative risk ln(RR)-dispersion var[ln(RR)] =(1/A1)+(1/A0)

  38. GENERAL EPIDEMIOLOGY Stratification • Division of the population into subgroups (strata) if there is the base to assume that the incidence is unequal in different groups • strata distribute according to: • age • sex • occupation • radiation dose • other effects

  39. GENERAL EPIDEMIOLOGY Standardization - is one of the method of comparison validity • direct method of standardization • indirect method of standardization

  40. GENERAL EPIDEMIOLOGY Direct Method of Standardization • within group, intergroup and international standard age is used for comparison of incidence rates in two groups • ratio of standardized incidence rates is presented by formula (R1.1/R1.n)*RR1.1+(R1.2/R1.n)*RR1.2=ASR1 (R2.1/R2.n)*RR2.1+(R2.2/R2.n)*RR2.2=ASR2

  41. GENERAL EPIDEMIOLOGY indirect method of standardization SIR(O/E)*100(standardized incidence ratio SIR) • ratio of O-observed number of cases at exposed group and E - expected number of cases at control group • standard age of exposed group is used for comparison incidence rates in two groups E= (N1*IR1)+(N2*IR2)

  42. EPIDEMIOLOGYOF LEUKAEMIA

  43. EPIDEMIOLOGYOF LEUKAEMIA

  44. EPIDEMIOLOGYOF LEUKAEMIA

  45. EPIDEMIOLOGYOF LEUKAEMIA Age Standardized Rate (per 100.000) -Number of cases from 20 to 29 years/1000,000 clean-up workers of 1986 - А1 1987г. – B1 -Number of males from 20 to 29 years/100,000 clean-up workers of 1986 - A2 1987г. – B2 Calculation For clean-up workers of 1986 A1*(12,000/A2)=ASR1 For clean-up workers of 1987 B1*(12,000/B2)=ASR2 where 12,000 – world standard in this interval

  46. EPIDEMIOLOGYOF LEUKAEMIA

  47. EPIDEMIOLOGYOF LEUKAEMIA

  48. GENERAL EPIDEMIOLOGY Design formulasof relation between exposure and incidence - COHORT data are presented as relation risk estimation RR=IR1 / IR0 where IR1 and IR0 are incidence coefficients A1 and A0 - number of cases R1 и R0 - person-years at risk

  49. GENERAL EPIDEMIOLOGY Design formulasof relation between exposure and incidence - CASE-CONTROL relative risk estimation - odds ratio (OR) where A1=a, A0=b R1=c, R0=d A1 andA0 - number of cases R1 andR0 - person-years at risk

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