Radiation epidemiology and leukemia b ledoshchuk m d ph d
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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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Radiation epidemiology and leukemia b ledoshchuk m d ph d

RADIATIONEPIDEMIOLOGYAND LEUKEMIAB.Ledoshchuk, M.D.,Ph.D.

Institute of Epidemiology

Research Center for Radiation Medicine of Ukraine

Kyiv-2001


Epidemiology of leukaemia

EPIDEMIOLOGY OF LEUKAEMIA

Results of the 10-year study of leukemia among the Chernobyl accident clean-up workers in Ukraine

1986-96


Radiation epidemiology and leukemia b ledoshchuk m d ph d

GENERAL EPIDEMIOLOGY

  • EPIDEMIOLOGY

  • studies the occurrence and prevalence of diseases among population

  • identifies disease cases

  • determines probable relationship between various risk factors


Radiation epidemiology and leukemia b ledoshchuk m d ph d

UNIVERSITIES AND INSTITUTES OF EPIDEMIOLOGY

ENGLAND

14

CANADA

13

WESTERN

EUROPE

26

USA

89

UKRAINE

1

AUSTRALIA

12

AFRICA-ASIA

5


Radiation epidemiology and leukemia b ledoshchuk m d ph d

GENERAL EPIDEMIOLOGY

Types of Epidemiology

  • medical

  • pharmaceutical

  • veterinary

  • environmental

  • insurance


Radiation epidemiology and leukemia b ledoshchuk m d ph d

GENERAL EPIDEMIOLOGY

Classification of medical epidemiology

  • Infection epidemiology

  • Generalepidemiology

  • Environment epidemiology

  • Clinical epidemiology

  • Military epidemiology

  • Epidemiology of insurance


Radiation epidemiology and leukemia b ledoshchuk m d ph d

Main types of epidemiology research


Radiation epidemiology and leukemia b ledoshchuk m d ph d

GENERAL EPIDEMIOLOGY

Methods of analytical epidemiology

  • Cohort

  • Case control

  • Combined


Radiation epidemiology and leukemia b ledoshchuk m d ph d

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)


Radiation epidemiology and leukemia b ledoshchuk m d ph d

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)


Epidemiology of leukaemia1

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


Epidemiology of leukaemia2

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 .


Epidemiology of leukaemia3

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


Epidemiology of leukaemia4

EPIDEMIOLOGYOF LEUKAEMIA

Main sources of information for case search:

  • Results of annual medical examination of ACW

  • Regional hematological clinics data


Epidemiology of leukaemia5

EPIDEMIOLOGYOF LEUKAEMIA

Main methods of obtaining of information :

  • retrospective

  • current

  • passive

  • active


Epidemiology of leukaemia6

EPIDEMIOLOGYOF LEUKAEMIA

Period of observation ACW:

1987-1996

Calculation were performed for 5-year intervals

1987-1991, 1992-1996


Epidemiology of leukaemia7

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


Classification of diseases

Classification of diseases

Choice:

  • Etiology

  • patogeneses

  • Localizations disease

  • ICD-9 orICD-10

  • Clinical (FAB) Classification of Leukaemia


Reliability of the diagnoses

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


Reliability of the diagnoses1

  • 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


Sensitivity and specificity

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


Model of sensitivity and specificity a ahlbom s norel 1990

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


Radiation epidemiology and leukemia b ledoshchuk m d ph d

Information flows between institutions and the center

  • cCITY HOSPITAL

  • DDISPENSARY

  • OBLAST HOSPITAL OBLAST DISPENSARY

  • INSTITUTIONAL HEMATOLOGICAL DEPARTMENTS

CENTER FOR RADIATION MEDICINE


Radiation epidemiology and leukemia b ledoshchuk m d ph d

Information exchange for quality control

EPIDEMIOLOGIST

SUPERVISER

D/B

TECHNICIAN


Epidemiology of leukaemia8

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 %).


Epidemiology of leukaemia9

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 %).


Epidemiology of leukaemia10

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.


Epidemiology of leukaemia11

EPIDEMIOLOGYOF LEUKAEMIA

LEUKEMIA DIAGNOSIS STRUCTURE


General epidemiology

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


General epidemiology1

GENERAL EPIDEMIOLOGY

Generate rate

  • Absolute rate (number)

  • Popularity

  • Morbidity

  • Mortality

  • Expressed as cases from 106 to 103 in investigated cohort (case/control)


General epidemiology2

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


General epidemiology3

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


General epidemiology4

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


General epidemiology5

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)


Radiation epidemiology and leukemia b ledoshchuk m d ph d

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


General epidemiology6

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]


General epidemiology7

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)


General epidemiology8

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


General epidemiology9

GENERAL EPIDEMIOLOGY

Standardization

- is one of the method of comparison validity

  • direct method of standardization

  • indirect method of standardization


General epidemiology10

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


General epidemiology11

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)


Epidemiology of leukaemia12

EPIDEMIOLOGYOF LEUKAEMIA


Epidemiology of leukaemia13

EPIDEMIOLOGYOF LEUKAEMIA


Radiation epidemiology and leukemia b ledoshchuk m d ph d

EPIDEMIOLOGYOF LEUKAEMIA


Radiation epidemiology and leukemia b ledoshchuk m d ph d

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


Radiation epidemiology and leukemia b ledoshchuk m d ph d

EPIDEMIOLOGYOF LEUKAEMIA


Radiation epidemiology and leukemia b ledoshchuk m d ph d

EPIDEMIOLOGYOF LEUKAEMIA


Design formulas of relation between exposure and incidence

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


Design formulas of relation between exposure and incidence1

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


Radiation epidemiology and leukemia b ledoshchuk m d ph d

Sources of Radiation Exposure

From NCRP Report No: 93


Atom principle diagram craig c freudenrich 2001 haw

ATOM PRINCIPLE DIAGRAM (Craig C. Freudenrich,2001, HAW)

Electron

Nucleus

Orbit


Penentrating radiation

PENENTRATING RADIATION

Alpha Particles

Radiation Source

Stopped by a sheet of paper

Beta Particles

Stopped by a layer of clothing or by a few millimeters of a substance

Stopped by several feet of concrete organic tissue or a few inches of lead

Gamma Rays


Radio biological effects

RADIO-BIOLOGICAL EFFECTS

NOT STOCHASTIC EFFECTS

  • as a result of high irradiation acute radiation sickness and furnaces radiation injuries are developed

    STOCHASTIC EFFECTS

  • developed during prolonged irradiation (external, internal, balanced, critical organs etc.) Somatic, genetic, embryo toxic


Radio biological effects1

RADIO-BIOLOGICAL EFFECTS

STOCHASTIC EFFECTS

  • Somatic and genetic, embryo toxic effects are developed in casual, probabilistic nature

  • Only probability of damage appearance depends on dose, but not weight and depth of damage

  • Frequency of appearance radiation-induced diseases increases with dose increase


Radio biological effects2

RADIO-BIOLOGICAL EFFECTS

STOCHASTIC EFFECTS

  • Summary stochastic effects during population irradiation (population group) are defined by collective dose

  • It is impossible to define an individual effect or additional risk and it is impossible to determine which kind of cancer is typical for additional cases


Models of excess of risk s d pierce d preston 1996 1999

MODELS of EXCESSof RISKSD.Pierce, D.Preston, 1996-1999

Time dependent models of redundant relative risk for solid swellings

Limit of models of risk for a cancer = 10 years

Absolute risk for leukaemia

Limit of models leukaemia = 2 years

The limit of models of risk is a concept latent

Period - between the beginning of effect of the radiation factor and diagnostics leukaemia


Models of excess of risk s d pierce d preston 1996 19991

MODELS of EXCESSof RISKSD.Pierce, D.Preston, 1996-1999

Execes absolute risk for leukaemia

Where  and  - constant:  - depends on categories -

Age for want of effect and, for each from these categories, categories of time from time of effect and sex

D – Doze equivalent red marrow, inSiverts(Sv)


Models of excess of risk s d pierce d preston 1996 19992

MODELS of EXCESSof RISKSD.Pierce, D.Preston, 1996-1999

  • Time dependent models of redundant

    relative risk adapt DOSE dependence

    As linear for SOLIDCANCERS

    As linearly – quadratic for LEUKAEMIA


Radiation epidemiology and leukemia b ledoshchuk m d ph d

EPIDEMIOLOGYOF LEUKAEMIA

RESUME:

  • The comparative analysis was done for clean-up workers CWA of 1986 and 1987 by periods of observation of 1987-1991 and 1992-1996.

    • The results of the conducted study indicate the increasing of the leukemia risk among CWA of 1986 most vividly during 1987-1991.

    • Relative risk was defined at the level of 3,32 (1,08; 10,20), and for 20-59 age group it was 3,45 (1,15; 10,36).

  • No significant differences were defined in leukemia incidence at survey groups in 1992-1996.


Radiation epidemiology and leukemia b ledoshchuk m d ph d

About author

Ledoshchuk Boris Alexandrovich born in 1946 in Russia. In 1970 graduated from Blagoveschensk Medical Institute, where also studied in coordinator and at post-graduate course. In 1975 – 1978 worked in the Institute of clinical and experimental medicine of the Academy of Sciences of USSR in Novosibirsk. Took part in scientific epidemiological studies of Far-East and Siberia regions inhabitants. In 1978 – 1985 possessed various positions in medical institutions of Nikolaev region (Ukraine).

In 1986 – 1988 worked in the Ministry for Health Care of Ukraine where was responsible for rehabilitation programmer of the population of Chernobyl contaminated area.

Since 1988 heads scientific leukemia epidemiology laboratory of the Radiation Medicine Scientific Center. In 1995 – 2000 headed the Medical Department of the Ministry of Atomic Energy.

Since 27 April 1986 was involved in clean-up works in the Chernobyl area.

One of the leading specialists in the problems of automatic systems of long-term medical monitoring of people damaged in result of Chernobyl accident (State Registry of Ukraine).

Author of more than 100 scientific articles and works on the problems of epidemiology, automatic systems of registration and radiation medicine. Prominent participant of international epidemiology projects: AIFIKA, Chernobyl, Leukemia.

B. A. Ledoshchuk

M.D.,Ph.D.


Radiation epidemiology and leukemia b ledoshchuk m d ph d

channels of information

Atlas of Cancer Mortality http://www-dceg.ims.nci.nih.gov/atlas/index.htm/

Epidemiologic Research (Books) www.amazon.com/exec/obidos/

Epidemiology index http://home.beseen.com/technology/bcjung/Episites.htm/

Epidemiology statistics – www.geocities.com/vadivale/internet11.htm/

Epidemiology USA http://acepidemiology.org/ATLANTA.htm/

How Atoms, Radon, Nuclear, Work - www.howstuffworks.com

International Agency Atomic Energy http://www.iaea.org/


Radiation epidemiology and leukemia b ledoshchuk m d ph d

channels of information

International Journal of Epidemiology - www.ije.oupjournals.org

Ionizing Radiation, Health Effects www.epa.gov/radiation

Lessons of Hiroshima and Chernobylwww.whyfiles.org/020radiation/index.html

Leukemia Research http://dspase.dial.pipex.com/lif-/diseases/index/htm

Nuclear Energy Agency-Radiation Protection http://www.oecdnea.org/html/rp/

Radiation Research http://www.radres.org/

Radiation and Health Physics http://www.umich.edu/~radinfo/

Radiation effects Research Foundation www.rerf.or.jp/

Radiation effects www.eh.doe.gov/ihp/rerf/


Radiation epidemiology and leukemia b ledoshchuk m d ph d

channels of information

Radiation Protection Program (EPA) www.epa.gov/radiation/ionize.htm

Research Sources (Radiation, Effects) www.umich.edu/~radinfo/reas.html

Risk assessment of radiation www.radrisk.obninsk.com

Statistics on the Web http://www.execpc.com/~helberg/statistics.htm/

Supercourse –Epidemiology www.pitt.edu/~super1/index.htm

Uranium and Healthwww.antenna.nl/~wise/uranium/uhr.html

What is epidemiology? www.bmj.comepidem/epid.1.html

Ministry of Nuclear of Energy Russia www.minatom.ru

Epidemiology, Radiation, Chernobyl, Ukraine (ERCU) www.epidemUA.svitonline.com


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