Clinical Epidemiology 1

Clinical Epidemiology

Principal Investigator

Prof. Dr. F.R. Rosendaal

Aim and focus

Clinical epidemiology consists of the application of general epidemiologic principles in clinical research. The department has two aims: to apply these principles to particular research questions, and to study the methods themselves. Generally, the research concerns questions which necessitate a numerical approach, and in which the patient is the unit of observation. Specifically, the programme of the department focuses on aetiology and prognosis in several fields, e.g., haemostasis and thrombosis, renal dialysis, fertility, arthrosis, and side-effects of drugs. Since clinical epidemiology is a fundamental science, its application takes place in close collaboration with clinical and laboratory departments, such as the Einthoven Laboratory for Experimental Vascular Medicine, and the departments of Rheumatology, Endocrinology, Cardiology, Nephrology, Pulmonology, Gynaecology, and Public Health and Primary Care.

Position in international context

Much of the research is performed in international collaborations, amongst others in a Translational Network of the Fondation Leducq (with the universities of Seattle, Oklahoma, Vermont, Leuven and Paris). The research into the methodology of observational research has led to initiatives of the major medical journals to establish standards for the publication of observational research (STROBE initiative).

Content/highlights/achievements

Research themes

The research themes, the current studies and their principal investigators, are:

• Venous thrombosis (LETS, MEGA, VTE, WRIGHT, TROL): Prof. Dr. F.R. Rosendaal, Dr. S.C. Cannegieter, Dr. S. Middeldorp
• Arterial thrombosis (SMILE, RATIO): Prof. Dr. F.R. Rosendaal, Prof. Dr. A. Algra
• Methodology (STROBE): Prof. Dr. J.P. Vandenbroucke
• Renal dialysis (NECOSAD): Dr. F.W. Dekker
• Transfusion (TRALI): Dr. J.G. van der Bom, Prof. Dr. E. Briët
• Metabolic syndrome (NEO): Dr. S. Middeldorp
• Hemophilia (HIN-5): Prof. Dr. F.R. Rosendaal, Dr. J.G. van der Bom

 In the area of thrombosis research, the Leiden centre has initiated the introduction of large, properly designed controlled studies, such as the first case-control study into the aetiology of venous thrombosis (Leiden Thrombophilia Study, LETS), in the early 1990s. This single study  has been instrumental in the identification of a series of new risk factors for venous thrombosis (factor V Leiden, prothrombin 20210A, high levels of FVIII, FIX, FXI, TAFI), published in over 60 papers. Currently, there are several studies into the aetiology of first thrombosis and recurrence, with a broad array of foci: genetic risk factors, global coagulation assays, air travel, endocrine factors, the elderly, imaging and the interaction of risk factors. In the field of arterial thrombosis studies focus on genetics, contact activation and aspirin resistance. Since 1997, over 2000 new patients on renal dialysis have been included in a national prospective cohort study (NECOSAD), with frequent data collection, with a database and biobank at the Leiden centre, which has so far led to over 50 papers. In collaboration with Sanquin, complications of blood transfusions are investigated. The department participates in national studies of the impact of bleeding disorders such as haemophilia and Von Willebrand disease.

Publications

During the last five years (2003-2007) we consistently published in the major medical journals (nearly 400 papers), with 30 full papers in the highest impact journals (JAMA (5), Lancet (4), Annals of Internal Medicine (2), PloS Medicine (6), Circulation (1), Blood (13)).  

Future themes

In the coming years, existing research lines will be continued. A major effort will be a large cohort study in which 8000 overweight and obese individuals will be included and followed, and risk profiles will be assessed by modern techniques, including ultrasound and magnetic resonance measurements. This Netherlands Epidemiology of Obesity (NEO) study will be a joint effort of many departments of the LUMC, and will be performed in collaboration with the Vrije Universiteit in Amsterdam.

Cohesion and connections within the LUMC

Clinical research is of major importance to the LUMC, and clinical epidemiology is an integral part of such research. Therefore, there is a strong network of collaboration with other departments, in some instances involving comprehensive research programmes. The latter include Haemostasis and Thrombosis, Rheumatology, Cardiology, Endocrinology, Pulmonology, Nephrology, Radiology, Public Health and Primary Care. 

Key publications

Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, Pocock SJ, Poole C, Schlesselman JJ, Egger M; STROBE Initiative. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. PLoS Med  2007; 4: e297.
IF 13.8

Plug I, Peters M, Mauser-Bunschoten EP, de Goede-Bolder A, Heijnen L, Smit C, Willemse J, Rosendaal FR, van der Bom JG. Social participation of patients with hemophilia in the Netherlands. Blood 2008; 111 (4): 1811-15
IF 10.4

Smith NL, Hindorff LA, Heckbert SR, Lemaitre RN, Marciante KD, Rice K, Lumley T, Bis JC, Wiggins KL, Rosendaal FR, Psaty BM. Association of genetic variations with nonfatal venous thrombosis in postmenopausal women. JAMA 2007; 297: 489-98.
IF 23.2

Cannegieter SC, Doggen CJ, van Houwelingen HC, Rosendaal FR. Travel-related venous thrombosis: results from a large population-based case control study (MEGA study). PLoS Med 2006; 3: e307.
IF 13.8

Schreijer AJ, Cannegieter SC, Meijers JC, Middeldorp S, Büller HR, Rosendaal FR. Activation of coagulation system during air travel: a crossover study. Lancet 2006; 367: 832-8.
IF 25.8

Hallan SI, Dahl K, Oien CM, Grootendorst DC, Aasberg A, Holmen J, Dekker FW. Screening strategies for chronic kidney disease in the general population: cohort study. Br Med J 2006; 333: 1047-1050.
IF 9.3

Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR. Thrombophilia, clinical factors, and recurrent venous thrombotic events. JAMA 2005;293:2352-2361.
IF 23.2

Blom JW, Doggen CJM, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of  venous thrombosis. JAMA 2005; 293: 715-722.
IF 23.2

Cushman M, Kuller LH, Prentice R, Rodabough RJ, Psaty BM, Stafford RS, Sidney S, Rosendaal FR. Estrogen plus progestin and risk of venous thrombosis. JAMA 2004; 292: 1573-1580.
IF 23.2

Šrámek A, Kriek M, Rosendaal FR. Decreased mortality of ischaemic heart disease among carriers of haemophilia. Lancet 2003; 362: 351-354.
IF 25.8