Scandinavian Registers in Arthritis and Normal Populations Tuulikki Sokka, MD, PhD Jyväskylä Central Hospital, Jyväskylä, Finland

Scandinavian Registers in Scandinavian Registers in Arthritis and Normal PopulationsArthritis and Normal Populations

Tuulikki Sokka, MD, PhDTuulikki Sokka, MD, PhDJyvJyväskylä Central Hospital, äskylä Central Hospital,

JyvJyväskylä, Finlandäskylä, Finland

Scandinavian CountriesScandinavian Countries

Population mil.

GNP per capita mil. USD/ 2004

Life expectancyM/F

Denmark 5.3 44.8 75.2/ 79.9

Finland 5.2 35.7 75.3/ 82.3

Iceland 0.3 41.8 78.1/ 82.2

Norway 4.5 54.6 77.5/ 82.3

Sweden 8.9 38.5 78.4/ 82.7

24.2

Population registers in Scandinavia date back to the 16th century in the former Sweden-Finland.

In the 17th century a law was passed that all births, marriages, and deaths must be recorded.

Genealogic information has been collected by Icelanders through the nations’ history of 11 centuries.

BackgroundBackground

The initial reason for population registers in Scandinavia was to collect taxes more effectively – as was the case in the most well-known census:

“In those days Caesar Augustus issued a decree that a census should be taken of the entire Roman world. This was the first census that took place while Quirinius was governor of Syria. And everyone went to his own town to register” Luke 2:1-3

Why population registers?Why population registers?

“The base registers are the corner stones of INFORMATION SOCIETY. To build society where services are available in digital or electronic form means that information concerning people, buildings and apartments, real estates and companies must be available and must be reliable. On the other hand, the citizens must rely on data security, data protection and privacy.”

Mr. Hannu Luntiala, Director General, Population Register Centre, Finland at Conference REGNO 2006

Nation-wide longitudinal databases in Nation-wide longitudinal databases in Scandinavia; registers on peopleScandinavia; registers on people

The Population RegistryThe Population RegistryThe Cancer RegistryThe Cancer RegistryThe Cause of Death RegistryThe Cause of Death RegistryThe Hospital Inpatient RegistryThe Hospital Inpatient RegistryThe Medication Reimbursement RegistryThe Medication Reimbursement RegistryThe Multi-Generation RegistryThe Multi-Generation RegistryThe Icelandic Genealogy DatabaseThe Icelandic Genealogy DatabaseSerum banks Serum banks

linkable to each other by the personal linkable to each other by the personal identification code identification code

Sokka. Rheum Dis Clin N Am 2004

The Population RegistryThe Population Registry

Maintains a file on Maintains a file on all citizens and foreigners all citizens and foreigners living permanently in the countryliving permanently in the country. . The system’s basic unit is a person, whose The system’s basic unit is a person, whose personal identifiers are a personal identifiers are a personal identification personal identification code, date of birth, and first and last namecode, date of birth, and first and last name..Characteristics of each individual that are Characteristics of each individual that are recorded include recorded include gender, native language, gender, native language, citizenship, current and former address, marital citizenship, current and former address, marital status, membership of a religious group, spouse, status, membership of a religious group, spouse, children, parents.children, parents. The The date of deathdate of death is recorded. is recorded.


The Cancer registerThe Cancer register

were begun in most Scandinavian were begun in most Scandinavian countries during the countries during the 1950’s1950’s, and reporting , and reporting became obligatory during the 1960’s became obligatory during the 1960’s collects data on collects data on all cancerall cancer cases in the cases in the populationpopulationThe informants who submit data on cancer The informants who submit data on cancer cases include all cases include all hospitals, physicians, hospitals, physicians, pathological, cytological and hematological pathological, cytological and hematological laboratories and dentistslaboratories and dentists. .


The Cause of Death RegistryThe Cause of Death Registry

The Cause of Death Registry contains The Cause of Death Registry contains information on information on dates and causes of all dates and causes of all deaths according to the ICD.deaths according to the ICD.

Official statistics on the death rates are Official statistics on the death rates are available since the early 1900’s in available since the early 1900’s in Scandinavian countries. Scandinavian countries.


The Hospital Inpatient RegistryThe Hospital Inpatient Registry

Contains information on Contains information on inpatient careinpatient care according to the personal identification according to the personal identification codecodeFor every hospital discharge, information For every hospital discharge, information on on diagnoses and surgical proceduresdiagnoses and surgical procedures are are recorded according to the ICD. recorded according to the ICD. The The hospital code, and the date of hospital code, and the date of admission and dischargeadmission and discharge are recorded. are recorded.


Registers concerning benefits and Registers concerning benefits and reimbursements in the case of diseasesreimbursements in the case of diseases

TheThe government is responsible for sickness government is responsible for sickness allowances and national pensions.allowances and national pensions.

If a person becomes unable to do his or her If a person becomes unable to do his or her regular or similar job for an illness, he or she is regular or similar job for an illness, he or she is entitled to a sickness allowance/disabilityentitled to a sickness allowance/disability pensionpension as compensation for lost income. as compensation for lost income.

Data are stored on government’s administrative Data are stored on government’s administrative registers.registers.


The Medication Reimbursement The Medication Reimbursement RegistryRegistry

In Finland, Social Insurance Institution In Finland, Social Insurance Institution provides reimbursed drugs for certain provides reimbursed drugs for certain chronic diseases.chronic diseases.Included: patient ID, date of decision of Included: patient ID, date of decision of reimbursement, code of disease groupreimbursement, code of disease groupThe Medication Reimbursement Registry The Medication Reimbursement Registry is ais a source to identify all individuals nation- source to identify all individuals nation-wide who have been diagnosed with wide who have been diagnosed with chronic conditionschronic conditions. .


The Prescription RegistryThe Prescription Registry

covers all permanent residents in Finland, covers all permanent residents in Finland, comprises all purchases of prescribed comprises all purchases of prescribed medications.medications.

The registry includes The registry includes codes of the codes of the medications, date of action, prescribing medications, date of action, prescribing physiciansphysicians and the personal identification and the personal identification code. code.


The Multi-Generation RegistryThe Multi-Generation Registry

The Multi-Generation Registry consists of persons who have been residents in Sweden after 1960, born 1932 or later.

This registry provides information on all these persons and their biological parents.

Through this information it is possible to trace all first- and second-degree relatives.

The Iceland Genealogy Database The Iceland Genealogy Database

Includes a personal identification code, identifier of parents, gender, date of birth and death

all presently living Icelanders (c. 270 000), and almost all of their ancestors since 1100 years ago

Furthermore, genotypes of >25,000 Islanders have been studied.


Serum banksSerum banks

NBSBCCC,NBSBCCC, The Nordic Biological The Nordic Biological Specimen Banks for Cancer Causes and Specimen Banks for Cancer Causes and Control Control

> 1.5 million samples from the > 1.5 million samples from the Scandinavian countriesScandinavian countries– Free maternity programsFree maternity programs– Public health programsPublic health programs– Population studiesPopulation studies

Population Registers Population Registers Coverage and reliabilityCoverage and reliability

The quality requirements of the registered The quality requirements of the registered data include extensive coverage and high data include extensive coverage and high reliability.reliability.The requirement about coverage is met The requirement about coverage is met when when each unit that should be registered each unit that should be registered is entered in the register.is entered in the register.Reliability studies are carried out at certain Reliability studies are carried out at certain intervals to ensure reliability of the data. intervals to ensure reliability of the data.


Prescribed by lawPrescribed by law

The registers are strictly regulated by law The registers are strictly regulated by law including including – development and control of the registrationdevelopment and control of the registration– maintenance and delivery of informationmaintenance and delivery of information

Organizations which operate under the Organizations which operate under the supervision of the government are responsible supervision of the government are responsible for the national information services concerning for the national information services concerning processing the processing the data to be developed and data to be developed and tailored to meet the needs of the institutions and tailored to meet the needs of the institutions and authorities that use the dataauthorities that use the data..


The Leading Information Centre

Population Register Centre

PURPOSED USES OF POPULATION INFORMATION

(According to the Population Information Act of 1993)

• judical proceedings• administrative decision-making• scientific research• national statistics• updating of customer registers• polls, opinion surveys and market research• direct marketing

NB1: population information is collected and maintained for the purposes of both public (government) services and private (business) servicesNB2: the purpose is that civil authorities obtain necessary information directly from the system, not from the citizens Timo Salovaara, vrk.fi

Privacy and the Population RegisterPrivacy and the Population Register

Individual has a right to forbid his/her Individual has a right to forbid his/her information to be delivered for certain information to be delivered for certain purposes such as:purposes such as:– MarketingMarketing– Address searchAddress search– Genealogy catalogsGenealogy catalogs


Privacy and the registers - PHI?Privacy and the registers - PHI?

Registers are regarded as part of the Registers are regarded as part of the infrastructure of the society. infrastructure of the society. Registers that contain information on individuals’ Registers that contain information on individuals’ health were established to recognize public health were established to recognize public health problems, in order to develop preventive health problems, in order to develop preventive strategies. strategies. The society assumes responsibility for an The society assumes responsibility for an individual who develops an illness, providing individual who develops an illness, providing access to medical care almost without cost, as access to medical care almost without cost, as well as benefits including sick leave, well as benefits including sick leave, rehabilitation and a disability pension. rehabilitation and a disability pension.

Privacy and the registers - PHI?Privacy and the registers - PHI?

The The historical backgroundhistorical background and the and the society’s major role of society’s major role of being responsible for its membersbeing responsible for its members may have saved may have saved Scandinavia from major concerns regarding the privacy Scandinavia from major concerns regarding the privacy of personal health information, unlike in some other of personal health information, unlike in some other countries where laws concerning protection of privacy countries where laws concerning protection of privacy have made health information registers almost illegal. have made health information registers almost illegal.

Overall, Overall, protection and improvement of public protection and improvement of public health appears to overcome the issue of health appears to overcome the issue of protection of privacy, both in legislation and in protection of privacy, both in legislation and in public opinion in Scandinaviapublic opinion in Scandinavia.. Law: emphasis in reliability, coverage, needs of Law: emphasis in reliability, coverage, needs of the users of the data vs. privacy issuesthe users of the data vs. privacy issues


Examples of studies that have Examples of studies that have used national databases in used national databases in

rheumatology researchrheumatology research

RHEUMATOLOGY RESEARCH AND THE NATIONAL DATABASES

Mortality in patients with RAIncidence of rheumatic diseasesRisk of cancer in patients with rheumatic diseasesHealth care costs of RAWork disability and musculoskeletal conditionsFamilial clustering of musculoskeletal conditions


Mortality in patients with RA;Finland

The Population Registry-search for people who died in 1989

•Search results linked toThe Medication Reimbursement Registry

-to identify people with RA•Search results linked to

The Cause of Death Registry-provided causes of death

A total of 1666 RA patients died in 1989 in A total of 1666 RA patients died in 1989 in FinlandFinland

High cardiovascular mortality in women who had High cardiovascular mortality in women who had RARA

Accumulation of leukemia and lymphoma in Accumulation of leukemia and lymphoma in long-lasting RAlong-lasting RA

Frequent occurrence of fatal side effects from Frequent occurrence of fatal side effects from NSAIDsNSAIDs

Overall shortening of life span by 3-4 yearsOverall shortening of life span by 3-4 years

Results: Myllykangas-Luosujärvi et al:

Incidence of rheumatic diseases; Finland

The Medication Reimbursement Registry

-search for subjects who were entitled to reimbursed medication for rheumatic diseases in Finland in 1975, 1980, 1985, 1990

• Data were confirmed from reimbursement certificates and medical records

Results: Kaipiainen-Seppänen et al:

Incidence of RA 40 in women, 23 in men Incidence of RA 40 in women, 23 in men /100,000 adults, in 1995/100,000 adults, in 1995

The mean age at diagnosis of RA increased The mean age at diagnosis of RA increased from 50 to 58 between 1975 and 1990from 50 to 58 between 1975 and 1990

Regional differences in the incidence of RA; Regional differences in the incidence of RA; highest in the East, lowest in the Westhighest in the East, lowest in the West

Incidence of AS 6.9/100,000Incidence of AS 6.9/100,000

Incidence of psoriatic arthritis 6.0/100,000Incidence of psoriatic arthritis 6.0/100,000

Risk of cancer in patients with rheumatic diseases

Isomäki HA, Hakulinen T, Joutsenlahti U.Isomäki HA, Hakulinen T, Joutsenlahti U. Excess risk of Excess risk of lymphomas, leukemia and myeloma in patients with lymphomas, leukemia and myeloma in patients with rheumatoid arthritis. J Chronic Dis 1978; 31:691-696. rheumatoid arthritis. J Chronic Dis 1978; 31:691-696. BaecklundBaecklund E, E, IliadouIliadou A, A, AsklingAskling J, Ekbom A, J, Ekbom A, BacklinBacklin C, C, GranathGranath F, F, CatrinaCatrina AI, AI, RosenquistRosenquist R, R, FelteliusFeltelius N, N, SundstromSundstrom C, C, KlareskogKlareskog L. L. Association of chronic Association of chronic inflammation, not its treatment, with increased lymphoma inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum. 2006 risk in rheumatoid arthritis. Arthritis Rheum. 2006 Mar;54(3):692-701.Mar;54(3):692-701.AsklingAskling J, J, KlareskogKlareskog L, L, ForedFored M, M, BlomqvistBlomqvist P, P, FelteliusFeltelius N. N. Risk for malignant lymphoma in ankylosing spondylitis. a Risk for malignant lymphoma in ankylosing spondylitis. a nationwide Swedish case-control study.nationwide Swedish case-control study.Ann Rheum Dis. 2006 Jan 13Ann Rheum Dis. 2006 Jan 13

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16508929&query_hl=17&itool=pubmed_docsum






























http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16414970&itool=iconabstr&query_hl=21&itool=pubmed_docsum

Ekstrom K, Hjalgrim H, Brandt L, Ekstrom K, Hjalgrim H, Brandt L, Baecklund E, Klareskog L, Ekbom A et al.Baecklund E, Klareskog L, Ekbom A et al.

Risk of malignant lymphomas in patients Risk of malignant lymphomas in patients with rheumatoid arthritis and in their first-with rheumatoid arthritis and in their first-

degree relatives.degree relatives. Arthritis Rheum 2003; 48(4):963-970.Arthritis Rheum 2003; 48(4):963-970.

Risk of lymphomas; SwedenRisk of lymphomas; Sweden

The Hospital Inpatient Registry-search for patients with RA 1964-99

Search results linked toThe Multi-Generation Registry– search for 1st degree relatives

The obtained database linked to 5 population-based nation-wide registers

– The Cancer Registry– The Cause of Death Registry– The Hospital Inpatient Registry– The Population Registry– The Registry of Population Changes

Results, Ekstrom et al:Results, Ekstrom et al:

The obtained database included all incident cancers, deaths, emigrations, inpatient care for RA and other rheumatic diseases and included 731,206 person years in patients and 1,081,094 person years in relatives.

Patients with RA had an increased risk of lymphoma, while the risk of lymphoma was not increased in their 1st degree relatives.

J SJ SørensenørensenHealth care costs attributable to Health care costs attributable to

the treatment of rheumatoid the treatment of rheumatoid arthritis.arthritis.

Scand J Rheumatol Scand J Rheumatol 2004;33:399-4042004;33:399-404

Health Care CostsHealth Care Costs; Denmark; Denmark

The Population RegistryThe Population Registry– 20% of adults in the registry in 1994 were randomly

selected

Search results linked to

The Inpatient RegistryThe Inpatient Registry– to identify people with RA defined, as having

inpatient care for RA in 1994-1997

The Death RegistryThe Death Registry– to identify individuals who died in 1997to identify individuals who died in 1997

Health Services Databases – That include all contacts that patients have with

hospitals, general practitioners and specialists

Results, Results, SSørensen:ørensen:

Patients with RA used health care services Patients with RA used health care services 3.2 times more than people without RA 3.2 times more than people without RA which translates to incremental costs of 30 which translates to incremental costs of 30 million EUROs per year.million EUROs per year.

RA causes the loss of 1,549 years of life RA causes the loss of 1,549 years of life per year in Denmarkper year in Denmark

Work disability and musculoskeletal diseases; Norway

The Population Registry– Search for employed individuals in Norway

in 1980, ages of 20 to 53 years Search results linked to

The National Insurance Admin Database– to identify people who had new disability

pension during 1983-1993

Results, Holte et al.Results, Holte et al.

an impact of education level and an impact of education level and socioeconomic status on work disability socioeconomic status on work disability from back painfrom back pain

an association of manual work and work an association of manual work and work disability from osteoarthritisdisability from osteoarthritis

early occurrence of permanent work early occurrence of permanent work disability in patients with RAdisability in patients with RA

Familial clustering of musculoskeletal conditions; Iceland

The Genealogy Database in Iceland The Genealogy Database in Iceland covers family relationships of most covers family relationships of most Icelanders over the past centuriesIcelanders over the past centuries

Grant SF, Thorleifsson G, Frigge ML, Thorsteinsson J, Gunnlaugsdottir B, Geirsson AJ, Gudmundsson M, Vikingsson A, Erlendsson K, Valsson J, Jonsson H,

Gudbjartsson DF, Stefansson K, Gulcher JR, Steinsson K.

The inheritance of rheumatoid arthritis in Iceland.The inheritance of rheumatoid arthritis in Iceland.Arthritis Rheum. 2001 Oct;44(10):2247-54. Arthritis Rheum. 2001 Oct;44(10):2247-54.






























An example of a pedigree algorithm linking 36 rheumatoid arthritis patients to a single founder born in 1755.

Arthritis Rheum 2001

This epidemiologic study was conducted to investigate familial clustering of Icelandic RA patients.

Findings were similar to the findings with human longevity that the minimum number of founders for the patients was significantly lower compared with the minimum number of founders for the control sets.

Therefore, the RA patients were more related to each other than were the matched Icelandic controls. The results encourage the search for the genes responsible for RA in the population.

Scandinavian Population-Based Scandinavian Population-Based Registers; ConclusionsRegisters; Conclusions

Nationwide population-based longitudinal Nationwide population-based longitudinal databases databases provide excellent resources for provide excellent resources for epidemiology and medical research in epidemiology and medical research in ScandinaviaScandinavia. .

Scandinavian Registers in ArthritisScandinavian Registers in Arthritis

Local Clinical Databases

National Biologics Registers

Denmark DANBIO DANBIO

Finland Central Finland RA Database

ROB-FIN

Iceland

Norway Oslo RA DatabaseKristiansand RA db

Norway Biologic Register

Sweden Swedish RA Register; TIRA,

BARFOT

ARTISSTURESSATG

Sweden

A yellow house model:A yellow house model:

A dream of a development of a uniform A dream of a development of a uniform database for international use, to collect database for international use, to collect longitudinal datalongitudinal data of Rheumatoid Arthritis, of Rheumatoid Arthritis, according to standard measures in many according to standard measures in many countries.countries.

Acknowledgments: Mirja Rekola, librarian, at Rheumatism Foundation Hospital in Heinola, Finland, for her help with historical publications.Drs. Markku Heliövaara, Kimmo Aho, Eva Baecklund, Lena Bjornadal, Pekka Hannonen, Marjatta Leirisalo-Repo, Eero Pukkala, Hans Rasker, Timo Salovaara, Yusuf Yazici, and Theodore Pincus for their constructive comments for the article.

Documents

Scandinavian Registers in Arthritis and Normal Populations Tuulikki Sokka, MD, PhD Jyväskylä Central Hospital, Jyväskylä, Finland