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

3. Scandinavian Countries Population mil. GNP per capita mil. USD/ 2004 Life expectancy M/F Denmark5.344.875.2/ 79.9 Finland5.235.775.3/ 82.3 Iceland0.341.878.1/ 82.2 Norway4.554.677.5/ 82.3 Sweden8.938.578.4/ 82.7 24.2

4.  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. Background

5. 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?

6. “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

7. Nation-wide longitudinal databases in Scandinavia; registers on people The Population Registry The Cancer Registry The Cause of Death Registry The Hospital Inpatient Registry The Medication Reimbursement Registry The Multi-Generation Registry The Icelandic Genealogy Database Serum banks linkable to each other by the personal identification code Sokka. Rheum Dis Clin N Am 2004

8. The Population Registry Maintains a file on all citizens and foreigners living permanently in the country. The system’s basic unit is a person, whose personal identifiers are a personal identification code, date of birth, and first and last name. Characteristics of each individual that are recorded include gender, native language, citizenship, current and former address, marital status, membership of a religious group, spouse, children, parents. The date of death is recorded. Sokka. Rheum Dis Clin N Am 2004

9. The Cancer register were begun in most Scandinavian countries during the 1950’s, and reporting became obligatory during the 1960’s collects data on all cancer cases in the population The informants who submit data on cancer cases include all hospitals, physicians, pathological, cytological and hematological laboratories and dentists. Sokka. Rheum Dis Clin N Am 2004

10. The Cause of Death Registry The Cause of Death Registry contains information on dates and causes of all deaths according to the ICD. Official statistics on the death rates are available since the early 1900’s in Scandinavian countries. Sokka. Rheum Dis Clin N Am 2004

11. The Hospital Inpatient Registry Contains information on inpatient care according to the personal identification code For every hospital discharge, information on diagnoses and surgical procedures are recorded according to the ICD. The hospital code, and the date of admission and discharge are recorded. Sokka. Rheum Dis Clin N Am 2004

12. Registers concerning benefits and reimbursements in the case of diseases The government is responsible for sickness allowances and national pensions. If a person becomes unable to do his or her regular or similar job for an illness, he or she is entitled to a sickness allowance/disability pension as compensation for lost income. Data are stored on government’s administrative registers. Sokka. Rheum Dis Clin N Am 2004

13. The Medication Reimbursement Registry In Finland, Social Insurance Institution provides reimbursed drugs for certain chronic diseases. Included: patient ID, date of decision of reimbursement, code of disease group The Medication Reimbursement Registry is a source to identify all individuals nation- wide who have been diagnosed with chronic conditions. Sokka. Rheum Dis Clin N Am 2004

14. The Prescription Registry covers all permanent residents in Finland, comprises all purchases of prescribed medications. The registry includes codes of the medications, date of action, prescribing physicians and the personal identification code. Sokka. Rheum Dis Clin N Am 2004

15. The 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.

16. 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. Sokka. Rheum Dis Clin N Am 2004

17. Serum banks NBSBCCC, The Nordic Biological Specimen Banks for Cancer Causes and Control > 1.5 million samples from the Scandinavian countries –Free maternity programs –Public health programs –Population studies

18. Population Registers Coverage and reliability The quality requirements of the registered data include extensive coverage and high reliability. The requirement about coverage is met when each unit that should be registered is entered in the register. Reliability studies are carried out at certain intervals to ensure reliability of the data. Sokka. Rheum Dis Clin N Am 2004

19. Prescribed by law The registers are strictly regulated by law including –development and control of the registration –maintenance and delivery of information Organizations which operate under the supervision of the government are responsible for the national information services concerning processing the data to be developed and tailored to meet the needs of the institutions and authorities that use the data. Sokka. Rheum Dis Clin N Am 2004

20. The Leading Information 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) services NB2: the purpose is that civil authorities obtain necessary information directly from the system, not from the citizens Timo Salovaara, vrk.fi

21. Privacy and the Population Register Individual has a right to forbid his/her information to be delivered for certain purposes such as: –Marketing –Address search –Genealogy catalogs Sokka. Rheum Dis Clin N Am 2004

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

23. Privacy and the registers - PHI? The historical background and the society’s major role of being responsible for its members may have saved Scandinavia from major concerns regarding the privacy of personal health information, unlike in some other countries where laws concerning protection of privacy have made health information registers almost illegal. Overall, protection and improvement of public health appears to overcome the issue of protection of privacy, both in legislation and in public opinion in Scandinavia. Law: emphasis in reliability, coverage, needs of the users of the data vs. privacy issues Sokka. Rheum Dis Clin N Am 2004

24. Examples of studies that have used national databases in rheumatology research

25. RHEUMATOLOGY RESEARCH AND THE NATIONAL DATABASES Mortality in patients with RA Incidence of rheumatic diseases Risk of cancer in patients with rheumatic diseases Health care costs of RA Work disability and musculoskeletal conditions Familial clustering of musculoskeletal conditions Sokka. Rheum Dis Clin N Am 2004

26. Mortality in patients with RA; Finland The Population Registry -search for people who died in 1989 Search results linked to The Medication Reimbursement Registry -to identify people with RA Search results linked to The Cause of Death Registry -provided causes of death

27. A total of 1666 RA patients died in 1989 in Finland High cardiovascular mortality in women who had RA Accumulation of leukemia and lymphoma in long-lasting RA Frequent occurrence of fatal side effects from NSAIDs Overall shortening of life span by 3-4 years Results: Myllykangas-Luosujärvi et al:

28. 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

29. Results: Kaipiainen-Seppänen et al: Incidence of RA 40 in women, 23 in men /100,000 adults, in 1995 The mean age at diagnosis of RA increased from 50 to 58 between 1975 and 1990 Regional differences in the incidence of RA; highest in the East, lowest in the West Incidence of AS 6.9/100,000 Incidence of psoriatic arthritis 6.0/100,000

30. Risk of cancer in patients with rheumatic diseases Isomäki HA, Hakulinen T, Joutsenlahti U. Excess risk of lymphomas, leukemia and myeloma in patients with rheumatoid arthritis. J Chronic Dis 1978; 31:691-696. Baecklund E, Iliadou A, Askling J, Ekbom A, Backlin C, Granath F, Catrina AI, Rosenquist R, Feltelius N, Sundstrom C, Klareskog L.Baecklund E, Iliadou A, Askling J, Ekbom A, Backlin C, Granath F, Catrina AI, Rosenquist R, Feltelius N, Sundstrom C, Klareskog L. Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum. 2006 Mar;54(3):692-701. Baecklund E, Iliadou A, Askling J, Ekbom A, Backlin C, Granath F, Catrina AI, Rosenquist R, Feltelius N, Sundstrom C, Klareskog L. Askling J, Klareskog L, Fored M, Blomqvist P, Feltelius N. Askling J, Klareskog L, Fored M, Blomqvist P, Feltelius N. Risk for malignant lymphoma in ankylosing spondylitis. a nationwide Swedish case-control study. Ann Rheum Dis. 2006 Jan 13 Askling J, Klareskog L, Fored M, Blomqvist P, Feltelius N.

31. Ekstrom K, Hjalgrim H, Brandt L, Baecklund E, Klareskog L, Ekbom A et al. Risk of malignant lymphomas in patients with rheumatoid arthritis and in their first- degree relatives. Arthritis Rheum 2003; 48(4):963-970.

32. Risk of lymphomas; Sweden The Hospital Inpatient Registry -search for patients with RA 1964-99   Search results linked to The Multi-Generation Registry – –search for 1 st 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

33. 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 1 st degree relatives.

34. J Sørensen Health care costs attributable to the treatment of rheumatoid arthritis. Scand J Rheumatol 2004;33:399-404 Health Care Costs; Denmark

35. The Population Registry – –20% of adults in the registry in 1994 were randomly selected Search results linked to The Inpatient Registry – –to identify people with RA defined, as having inpatient care for RA in 1994-1997 The Death Registry –to identify individuals who died in 1997 Health Services Databases – –That include all contacts that patients have with hospitals, general practitioners and specialists

36. Results, Sørensen: Patients with RA used health care services 3.2 times more than people without RA which translates to incremental costs of 30 million EUROs per year. RA causes the loss of 1,549 years of life per year in Denmark

37. 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

38. Results, Holte et al. an impact of education level and socioeconomic status on work disability from back pain an association of manual work and work disability from osteoarthritis early occurrence of permanent work disability in patients with RA

39. Familial clustering of musculoskeletal conditions; Iceland The Genealogy Database in Iceland covers family relationships of most Icelanders 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. 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. Arthritis Rheum. 2001 Oct;44(10):2247-54.

40. An example of a pedigree algorithm linking 36 rheumatoid arthritis patients to a single founder born in 1755. Arthritis Rheum 2001

41.  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.

42. Scandinavian Population-Based Registers; Conclusions Nationwide population-based longitudinal databases provide excellent resources for epidemiology and medical research in Scandinavia.

43. Scandinavian Registers in Arthritis Local Clinical Databases National Biologics Registers DenmarkDANBIO FinlandCentral Finland RA Database ROB-FIN Iceland NorwayOslo RA Database Kristiansand RA db Norway Biologic Register SwedenSwedish RA Register; TIRA, BARFOT ARTIS STURE SSATG

44. Sweden

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

47. 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.