Annual Report. Julius Center for Health Sciences and Primary Care

Transcription

1 Annual Report Julius Center for Health Sciences and Primary Care

2 Annual Report 2007 Julius Center for Health Sciences and Primary Care UMC Utrecht

3 The Julius Center for Health Sciences and Primary Care is one of the twelve divisions of the University Medical Center Utrecht (UMC Utrecht). It carries out scientific research, provides education, and offers expertise and facilities in the clinical health sciences field. The Center aims for a leading and acquisitive position in the enlargement and dissemination of knowledge, especially in the field of health sciences. This is done by means of groundbreaking research on four disease-related themes and research methodology, by offering courses for (bio)medical students, researchers and clinicians, and by providing academic primary care. Disciplines represented in the Center are general practice, (clinical) epidemiology, nursing science, medical technology assessment, public health, medical ethics, and nutritional sciences. In this annual report the reader will find information on activities, output and finances in Contact information M. Kluijtmans, PhD Executive Secretary Management Team & Coordinator Master s Programme Epidemiology Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Visitors: Heidelberglaan 100, Utrecht, The Netherlands Correspondence: Str , P.O. Box 85500, 3508 GA Utrecht, The Netherlands URL: M.Kluijtmans@umcutrecht.nl Contents Introduction 7 Organization 17 Brief History 19 Organizational Structure 19 Research 21 Research Organization 23 Research Themes 26 IRAS 43 International Collaboration 45 External Assessment of Past Performance 50 Education 55 Educational Organization 56 General Practice 59 Epidemiology 67 Public Health 78 Medical Humanities 81 Nursing Science 83 Nutritional Science 87 Patient Care 91 Nutritional Sciences and Dietetics 93 Julius Center Health Care Leidsche Rijn 98 Unit Health Care Innovations Annual Report

4 Operational Support 103 Management Support 105 Clinical Trial Services Unit 106 Data Management 108 Personnel and Finances 111 Personnel, Figures 113 Personnel, Listing 114 Financial Report 127 Research Projects Cardiovascular Diseases 135 Infectious Diseases 143 Cancer 148 Mental Health 150 Theoretical Epidemiology and Biostatistics 154 Miscellaneous 157 Clinical Trial Services Unit 161 Vasculair Imaging Center (VIC) 166 Data Management 167 Publications PhD Theses 173 International Refereed Publications 174 Professional Publications 201 Books and Book Chapters 205 Nederlandse Samenvatting 209 Colophon Annual Report

5 Introduction This year s report again lists the many ational scientific publications by staff members and fellows of the Julius Center which underlines the Center s continued success at the forefront of ational research. (Rick Grobbee)

6 The year 2007 started with a new management team. For a number of reasons, not in the least the continuous growth of the Julius Center and its activities, the team was expanded from three to four members. In addition, the responsibilities of the members were rearranged. Professor Diederick E. Grobbee remains the chairman of the division, with Margot van der Starre, MSc, remaining director of business administration. Professor Theo Verheij decided to leave the management team after having served as the director of education for eight years. His position was taken over by Professor Yolanda van der Graaf, while Professor Arno Hoes was appointed as director of research, a position that was previously combined with the position of chairman. The management team is supported by the executive secretary, Dr Manon Kluijtmans. In the past years, several investments were made in the research support and infrastructure. The research management information system was further optimized and a start was made to upgrade the education management information system. In January a highly innovative in-house developed data capture and management system was launched for use in research projects : Research Online: research without borders. Research Online is fully et based, flexible and modular and can be applied for projects of any size without any geographic or linguistic restriction. Also in other domains, the impact of information technology could be felt. The Dietetics section of the Julius Center was the first UMC Utrecht care department to work fully digitally. Since January 2007 all patients have an electronic file, the EPD, which can never go missing and is accessible form any location within the hospital. As UMU pioneers in comprehensive patient and workflow records, of course initial challenges and difficulties were encountered. Many were solved satisfactorily and other departments will likely benefit from these initial experiences. Introduction 9

7 The Julius Center values education very highly and continues to invest in the development of new teaching activities and improvements in existing programmes. One of the major developments in 2007 was the start of the AsiaLink programme. In collaboration with academic departments in the United Kingdom (Oxford), Indonesia (Jakarta) and Malaysia (Kuala Lumpur), and with support from the European Union, the Julius Center aims to strengthen training and application of Evidence Based Medicine in Asia. AsiaLink has resulted from long existing ties between the participating institutions and a history of annual teaching courses in Asia by staff members of the Julius Center. Apart from stimulating evidence based medicine, AsiaLink will promote teaching in clinical epidemiology by incorporating courses developed in Utrecht and Oxford in the medical curricula in Kuala Lumpur and Jakarta. Closely related to these activities, but more orientated towards collaborative research, a local Julius Center KL has opened at the University of Malaya Medical Center in Kuala Lumpur in November We cherish our stimulating and productive ational collaborations. As a reflection, the Julius Center has one of the highest travel budgets in the UMC Utrecht. A more important reflection is, however, an increasing number of high level affiliations of staff members of the Julius Center with prestigious academic institutions abroad. A prime example was the appointment of Dr Petra Peeters as a professor in Chronic Disease Epidemiology at the Faculty of Medicine, Imperial College London in London, UK in October She will combine this position with her activities as director of cancer epidemiology at the Julius Center. Importantly, the appointment will further reinforce the existing collaboration between these two institutes. In addition to her scientific work and commitment to high quality teaching, the Julius Center is also active in patient care. In 2007, the Julius Health Care Centers in Leidsche Rijn (a residential area southwest of Utrecht) opened a fifth health center in t Zand, and the building of a new health care center in Vleuterweide was commissioned. In its health care centers, the Julius Center aims at setting new standards of care. With regard to quality of care it is noteworthy that the managing director of the Julius Health Care Centers, Rob van Damme, received the first ECB certificate in the Netherlands. The ECB is a certification programme in which the clients judge on the provided care. It is an initiative of the Dutch Patients and Consumers Federation. With an average client satisfaction of 8 the Julius Health Care Centers can be very proud of their performance. This year s report again lists the many ational scientific publications by staff members and fellows of the Julius Center which underlines the Center s continued success at the forefront of ational research. In 2007 the Julius Center again showed a good coverage in the major high ranking and established medical journals; the JAMA, the New England Journal of Medicine, and the Lancet. Senior staff members Michiel L. Bots and Diederick E. Grobbee even managed to publish in all three of these journals in one single year, a major achievement. Among others they published two papers on the effects of lipid modifying drugs on the development (progression) of atherosclerosis. Next to a good representation in the aforementioned general journals, the Julius Center had key methodological publications in major epidemiological journals, as well as papers with immediate practice relevance in leading journals in primary care. 10 Annual Report 2007 Introduction 11

8 In addition to the excellent research output, Julius staff members received awards and other expressions of appreciation of their research. Two prizes deserve special attention: Bert Brunekreef, professor of Environmental Epidemiology at the Julius Center and director of the interfaculty Institute for Risk Assessment Sciences in Utrecht, received two ational awards in the month of September. In Mexico City he received the John Goldsmith Award from the International Society of Environmental Epidemiology (ISEE). This award for Outstanding Contributions to Environmental Epidemiology is granted once a year to someone who has made an exceptional effort in the area of environmental care and health. Professor Brunekreef is the first Dutch recipient of this award. Only a few days later, on 15th of September he received the European Lung Foundation Award in Stockholm. The ELF Award is granted once a year to someone who has made an exceptional effort to improve public health. Following intense evaluation of the structure and organization of the Julius Center in 2006, a number of high impact decisions were made about the way the Julius Center is organized and managed that influence both its research and educational profile. After a long process of discussion and consultation the decision was made to terminate the department of Nursing Sciences in it present form. There appeared to be insufficient basis and prospects to continue the research activities in the area of nursing science. The successful teaching programme in Nursing Science will be continued in another format in close collaboration with the Utrecht School of Professional Education. On a more positive note, Utrecht University decided that as of mid 2008 the University Center for Biostatistics will become part of the Julius Center. It will continue its campus wide statistical consultation services, but strategic investments will be made to foster original biostatistical research with a special emphasis on epidemiologic and genetic statistical problems. With regard to public health, a Unit Health Care Innovation was established directed by Professor Guus Schrijvers to concentrate the advisory and evaluative work done on health care innovation. Over the years, the Julius Center has introduced and refined a matrix model to direct and monitor its research and teaching. In this matrix, education is being organized by scientific discipline and research by disease oriented research theme. To monitor the performance of the structure, a planning and control system was initiated in 2007 with increased responsibility for the educational and research coordinators. This system will be further improved and implemented in To support their new role, several of the coordinating staff members involved enrolled in personal and management development programmes. In addition, staff development in general received attention, the acquisition of educational qualifications was stimulated and the board of the UMC Utrecht granted no less than five female staff members of the Julius Center a Steyn Parvé personal development award. The Steyn Parvé programme comprises training and coaching and aims to support talented female researchers in reaching academic top positions was a year of evaluation. In two external research assessments by ational review committee s the scientific performance of the Julius Center s was judged to be excellent. The committees also were very positive about the future prospects, and applauded the societal impact of the Center. Although it is impossible to capture the full range of the Julius center s activities in a short introduction, we can safely conclude that 2007 was a very productive and successful year, in education and research as well as 12 Annual Report 2007 Introduction 13

9 in patient care. The Center received excellent scores in external assessments of past research performance, and made important steps towards securing these results for the future. Medical care in Leidsche Rijn expanded with a high ambition in quality and patient satisfaction. Last, but certainly not least, the educational activities remained of high quality, and attracted students from first year medical and biomedical bachelors to health care professionals. The assessment of 2007 is positive and rewarding. But none of this would have been possible without the people that together make up the Julius Center. They are to be complemented for their creativity, hard work, inspiration and devotion of many. Either being in support, care, education, research or administration: thank you all for your commitment and I sincerely hope that this annual report will make you feel proud and satisfied with the continued success of the Julius Center. Professor Diederick E. Grobbee, MD, PhD Chairman 14 Annual Report 2007 Introduction 15

10 Organization The Julius Center is and remains succesfull thanks to the huge capacity of its researchers to acquire funds, and the flexibility of all who support both acquisition, administration and conduct of the research projects. (Margot van der Starre)

11 Brief History The Julius Center for patient-oriented research was established on 16 December 1996, founded upon the previous departments of epidemiology and public health, and on the hospital unit of clinical epidemiology. Both scope and size have since then markedly increased, as is reflected by the Julius Center s subdivisions; former departments that have been integrated in the current center. In 1999 the department of General Practice merged with the department of patient-oriented research to become the Julius Center for Patient-Oriented Research and General Practice. In 2002 the department of Nursing Science and the Nutritional Sciences group joined the Center to become the current Julius Center for Health Sciences and Primary Care. In 2007 it was decided that Nursing Sciences will be terminated in its present form in the division. As per mid 2008, the Utrecht University Center for Biostatistics will become part of the Julius Center. Organizational Structure The organizational structure can be found on the inside of the cover. Organization 19

12 Research We often gain more by improving timely diagnosis, than by adding therapeutic interventions. (Arno Hoes) Research 21

13 Research Organization The University Medical Center Utrecht has formulated seven main research themes. These fit into a matrix with four disease-related themes on the horizontal and three methodological themes on the vertical axis. The Julius Center s main contribution to the total body of research of the UMC Utrecht is through the research theme Epidemiology. With rare exceptions, all of the Center s research activities can be classified as clinical epidemiological research, i.e. etiologic, diagnostic, prognostic and intervention research with relevance for patient care. Building upon this, the Julius Center contributes to all four disease-related areas of research: cardiovascular disease, infection & immunity, cancer, and mental health. In addition, there are strong links with the other two methodological research themes of the UMC Utrecht: Imaging sciences and Genetics. The Julius Center s research activities focused on 5 research themes, i.e. the same 4 disease-related areas as the UMC Utrecht (Cardiovascular Disease, Infection & Immunity, Cancer, and Mental Health) and one methodological theme (Theoretical Epidemiology & Biostatistics). Within these themes, there is further focus on subfields, as for example research on (etiology and prognosis of) diabetes mellitus as part of the cardiovascular disease theme or on the effects of vaccinations within the infection & immunity theme. All 5 research themes are headed by one (or two for the largest theme, cardiovascular disease) research coordinator. Importantly, the research activities of the (clinical or methodological) disciplines represented in the Julius Center (Clinical Epidemiology, General Practice/Primary Care, Public Health/Medical Technology Assessment/Medical Ethics, Nursing Science, and Nutritional Sciences) are also incorporated in Research 23

14 these 5 research themes and not in separate research organizations. The research methods for all of these disciplines can be broadly categorized as (clinical) epidemiological, which was one of the main reasons for these disciplines to be combined within the Julius Center. The research activities can, thus, be represented by a matrix structure, in which the vertical axis comprises the five research themes and the disciplines are depicted in the horizontal axis. The Center s policy is to concentrate its research as much as possible on the matrix s overlapping areas so that each of its disciplines benefit most from the Center s scientific and clinical expertise and the UMC Utrecht s scientific themes as a whole are strengthened. of Prof. Bert Brunekreef and honorary appointee Prof. Dick Heederik. There is also collaboration with other epidemiological research groups at Utrecht University, in particular with the Pharmaco-epidemiology group (from the Pharmacy Department) and Veterinary Epidemiology groups. In addition to the acquisition and conduct of its own research projects, either independently as an institute or in collaboration with other research groups, a major responsibility of the Center is to provide methodological advice and to support clinical research in virtually all departments of the University Medical Center. Staff members act as consultants for research methods on a range of clinical investigations within as well as outside the UMC Utrecht. The Center also plays a pivotal and formal role in quality assurance of randomized trials performed in the UMC Utrecht. These are important and growing activities for the Julius Center. For many clinical departments the intense and continuous interaction with epidemiology has resulted in joint appointments of staff, including the departments of anesthesiology, neurology, cardiology, cardio-thoracic surgery, al medicine, psychiatry, radiology and pediatrics. The Julius Center has a formalized link with the interfacultary Institute for Risk Assessment Sciences (IRAS), environmental and occupational epidemiology at UU. This has been embodied by the joint appointment 24 Annual Report 2007 Research 25

15 Research Themes Cardiovascular Diseases The disease-based research line Heart and Vascular Disease is the largest research line in the Julius Center. A considerable part of the research carried out within this research line focuses on the causes, diagnosis, prognosis and therapy of cardiovascular diseases. The approaches include the full range of epidemiological research methods, including multi-centered randomized controlled trials to study the effects of preventive and therapeutic interventions. Within the research line focus is on atherosclerosis progression as this underlies the occurrence of ischemic vascular disease. In 2007 results from several large ational multicenter trials conducted by the Julius Center on the effect of lipid modifying drugs were published. In the METEOR study statin treatment slowed progression of atherosclerosis, assesses as carotid intima-media thickness, in a population of healthy men and women, free from previous vascular disease and diabetes and with a low Framingham risk score (JAMA. 2007;297: ). A multicenter ational trial among familial hypercholesterolemia patients (RADIAN I) on the effect of increasing HDL cholesterol levels by cholesteryl ester transfer protein inhibitor on atherosclerosis progression showed no benefit of the intervention (N Engl J Med. 2007;356: ). Similar results were found in RADIAN II among patients mixed dyslipidemia (Lancet 2007;370:153-60). Findings from a large national trial on the effect of folic acid supplementation on carotid atherosclerosis progression in expected in With respect to large population based cohort studies several initiatives were completed in A large, population based cohort study was started in Utrecht in 1993, as part of the European Prospective Investigation into Cancer and nutrition (EPIC). Women participating in the national breast cancer screening programme and living in Utrecht and surroundings were invited to participate between 1993 and 1997, and 17,357 could be enrolled in Prospect-EPIC. Extensive information on lifestyle behavior, such as smoking, alcohol consumption, physical activity, and dietary habits were collected at baseline. Also a brief physical examination was done, for collecting information on anthropometry and blood pressure. Serum, plasma, erythrocyte and DNA samples were collected and stored locally as well as centrally in Lyon, France. Information on cardiovascular, cancer and diabetes morbidity and mortality is collected through linkage with registries, such as the Cause of Death registration at the Central Bureau of Statistics, the cancer registries from the Comprehensive Cancer Centres, and the national hospital discharge diagnosis registry, and through follow-up questionnaires to participants. Information on type 2 diabetes was verified through general practitioners and pharmacies. The National Institute for Public Health and the Environment also contributes a cohort to EPIC, the Morgen- EPIC-cohort. Since there has always been close collaboration between the Dutch investigators, and baseline measurements are identical for both cohorts, it was decided that the cohorts would be combined into the EPIC-NL cohort. This major enterprise started in 2006, and was successfully finalized in The EPIC-NL cohort now consists of 40,000 men and women aged between 20 and 70 years, with 10 years of followup, 2000 cardiovascular disease cases, 2000 cancer cases, and 750 diabetics. In 2008 cardiovascular risk factors will be measured in the cardiovascular and diabetes cases, and a random sample of the cohort, in order to have a set ready for extensive analysis and exciting papers. Information can be found at 26 Annual Report 2007 Research 27

16 A second large population based cohort of within the Julius Center is the Utrecht Health Project. All new inhabitants in the newly developed large residential area Leidsche Rijn, part of the city of Utrecht, are invited by their general practitioner to participate in the Utrecht Health Project (UHP). Informed consent is obtained and an individual health profile (IHP) is recorded by dedicated research nurses. The IHP is the starting point for the UHP research database as well as for the primary care electronic medical records. Follow-up data are collected through continuous linkage with the computerized medical files recorded by the general practitioners. UHP staff in each practice takes care of quality management of registration as well as data handling. Currently, over 50% of invited new residents in the area have given informed consent with participation steadily increasing. At present over 10,000 inhabitants are participating in Utrecht Health Project. Information is available at Using the infrastructure of the Utrecht Health Project, a weight reduction programme was initiated and finished in The aim was to reduce weight and subsequently reduce cardiovascular risk in 180 overweight subjects (BMI 28-35). The project involved efforts and intense collaboration of various health care workers: general practitioners, physiotherapists, dieticians. In addition to weight and risk reduction, the process of the programme was carefully evaluated. A factor that was related to success of weight reduction in particular was the direct contact of the patient by the general practitioners outside his regular appointments. The weight reduction programme was designated as being very innovative by the Dutch Minister of Health. Also making use of the infrastructure of the Utrecht Health Study, a study started into the early roots of cardiovascular disease in the young, in which indicators of vascular damage are being studied in 6 year old children. Using state-of-the-art ultrasound techniques information on the thickness of the arterial wall and on the stiffness of the arterial wall is collected. Furthermore, with in the research line, studies are being conducted on genetic information and the interplay between genes and environment in, for example, studies on genetic and non-genetic factors that determine the occurrence of type 2 diabetes. The studies are conducted in close collaboration with partners within and outside the UMC Utrecht and abroad. In addition, the Center is involved in the setting up and scientific evaluation of both diagnostic and therapeutic heart failure outpatient departments in the broader Utrecht region. The purpose of this is to gain a better understanding of the nature and causes of heart failure and to improve early detection and adequate treatment and follow-up of this syndrome, which constitutes an increasing burden on our ageing society. Other studies include the etiology and prognostic role of coronary collateral formation, and the risk-benefit ratio of anticoagulation in patients at a high risk of stroke. In addition, the Julius Center is increasingly involved in the execution of large-scale diagnostic studies, aimed at improving the early detection of cardiovascular diseases, both in the population at large and in patients requiring the hospital s primary care unit. These include studies on the added value of, e.g., various diagnostic imaging techniques and early (bed-side) biomarkers in recognizing atherosclerotic disease (such as stroke, coronary artery disease, peripheral arterial disease) as well as heart failure, deep venous thrombosis and pulmonary embolism. 28 Annual Report 2007 Research 29

17 Infectious Diseases Infectious diseases research at the Julius Center is centered around five topics: 1 Prevention, diagnosis and prognosis of respiratory tract infections. This research is mainly positioned within the primary care and Ear Nose and Throat area and, as an example, it is investigated to what extent certain patient characteristics predict an abnormal and serious clinical progression of bronchial infections, and what the consequences for treatment and patient advice are. In addition, antibiotic use and indications for prescribing in general practice are being studied. This research has been expanded to the development of asthma and allergy, in relation to exposure to infectious agents and other environmental determinants, both in young children and in occupationally exposed subjects. 2 Efficacy (and cost-efficacy) of vaccination strategies. In collaboration with the department of Pediatric Immunology, the National Vaccine Institute and pharmaceutical industries an increasing number of vaccination studies have been executed and are ongoing. Apart from these studies, the role of confounding in determining vaccination efficacy is investigated. 3 Mathematical modeling of infectious diseases. In collaboration with the Mathematical Institute of the University Utrecht and the National Institute of Health and Environment, the dynamics (and prevention of acquisition) of multi-resistant bacteria and influenza within hospitals and the community at large is being investigated, as well as potential effects of intervention. In 2007 a collaboration between the National Institute of Health and Environment, the Mathematical Institute, the Veterinary Faculty and the Julius Center resulted in the Utrecht Epicenter for the study of Infectious Disease Dynamics. 4 Infections in patients with diabetes mellitus. The project Development and evaluation of an educational programme on the prevention of complicated infections in patients with diabetes is currently being carried out. It focuses on respiratory and urinary tract infections. New research topics include the treatment of urinary tract infections and the relationship between onychomycosis and the diabetic foot. 5 The effects of nosocomial infections and transmission of antibioticresistant bacteria on patient outcome. The attributable mortality of ventilator-associate pneumonia is investigated and the Julius center coordinates a ational clusterrandomized trial in European ICUs to determine the efficacy of several approaches to reduce the transmission of antibiotic-resistant bacteria. Cancer Cancer research at the Julius Center focuses on the etiology, early diagnosis and prognosis of hormone dependant cancer, predominantly in women. With approximately 30,000 new cases a year amongst Dutch women, cancer is a serious health threat. However, the known causes can explain barely 30% of the cases encountered. An explanation for this rather low percentage may be sought in the fact that environmental and hormonal factors are predominantly studied without any consideration to genetic predisposition. Cancer etiological research within the Julius Center strongly focuses on the interaction between genes, hormones and the environment (or lifestyle habits). For the study of genetic determinants or gene-environmental interactions, the Julius Center has access to biological material originating from two large-scale on-going population-based cohorts, DOM and EPIC-NL, which is a merger of the two 30 Annual Report 2007 Research 31

18 Dutch cohorts participating in the European Prospective Investigation into Cancer and Nutrition: Prospect-EPIC and Morgen-EPIC. For studies of the optimal (early) diagnostic and (clinical) follow-up procedures in cancer patients, collaboration has been established with clinicians from other departments of the University Medical Center in Utrecht. Examples are the COBRA and MONET studies, both assessing optimal diagnostic and therapeutic procedures in women with non-palpable breast diseases. Studies to assess quality of life and evaluate nurse practitioners in the daily care of cancer patients also fall in the domain of the oncology research at the Julius Center. In 2007, Petra Peeters, the head of the cancer research group, was appointed Professor of Chronic Disease Epidemiology at the Faculty of Medicine of Imperial College London in London, UK. 1 The presentation of depression in primary care, and its association with somatic disease such as dementia, diabetes, gastro-enterological and vascular disease. 2 Functional disease and somatoform disorders: presentation, determinants and treatment in primary care 3 Psychiatric morbidity in relation to socio-demographic context and consultation patterns The common background hypothesis is that somatic and psychiatric disorders share an overlapping etiology and that this overlap has social and psychological as well as physiological components. Our assessments typically aim to characterize individuals on several levels (psychological, physical and physiological). Mental Health The Julius Center s psychiatric epidemiology section studies psychiatric disease and related co-morbidity in primary care and the general population. Mental illness represents a sizeable proportion of the global burden of disease in the general population, but is only partly presented to health care professionals. Major psychiatric disease represents 5% of the prevalent morbidity in primary care, with an annual prevalence of 125 per 1000 patients. A substantial part of minor psychiatric morbidity is presented in relation to somatic disease or functional syndromes or expressed through excessive consultation frequency of unexplained functional syndromes. Mental illness is - though closely linked to somatic ill-health - traditionally studied in isolation. The psychiatric epidemiology section focuses on the study of somatic - psychiatric comorbidity, with the following themes: These themes are studied on the various levels at which disorders manifest themselves: - The general population, by using existing and developing sampling frames such as LRGP (Leidsche Rijn Gezondheidsproject), NEMESIS (Netherlands Mental Health Survey and Incidence Study), AGIS health database and others. - Primary health care, in primary care networks such as HNU (Huisartsen Netwerk Utrecht), PREDICT, the Julius Gezondheidscentra in Leidsche Rijn and the database of Emergency Primary Care service in the Gelderse Vallei area. - Populations of people with reported mental illness like those registered in our psychiatric case registry (RIPAG). - Populations of people with reported somatic illness, such as samples of cardiovascular compromised patients (SMART), (pre)diabetic patients (UDES), and medication-using people (PHARMO). 32 Annual Report 2007 Research 33

19 This approach of studying the phenomenon of somatic psychiatric comorbidity on various levels of the health care system is unique. From a clinical point of view it will yield information on the etiology and prognosis of somatic-psychiatric co-morbidity, and allow preventive interventions. It will also facilitate evaluation of the patient flow through the mental health care system, and its effectiveness - Investigating innovative methods for meta-analysis and individual patient data-analysis of therapeutic studies. - Development of models to combine data from randomized and observational studies including genetic information, for estimating (long term) prognosis according to specific patient characteristics in addition to treatment effects. Most research projects are carried out in collaboration with partners within primary or secondary care health care: primary care physicians, secondary care centers for psychiatry, neurology and gastro-enterology, often in cooperation with other (ational) academic centers. Theoretical Epidemiology and Biostatistics Besides more applied studies on improving insights in the etiology, diagnosis, prognosis and therapy of specific disorders, the Julius Center also aims to further develop the theory and methodology of the discipline itself. The section Methodology conducts studies aiming to improve existing methods and to develop innovative methods for design and analysis of (clinical) epidemiological studies. The section focuses on the following themes: - Developing innovative designs for diagnostic and prognostic (prediction) research. - Developing innovative methods for quantifying the true value or contribution of (new) diagnostic and prognostic tests in a multivariable clinical context. - Developing innovative methods for the validation and updating of socalled clinical prediction rules. - Testing and improving sophisticated methods for dealing with missing values in epidemiologic research. Notably the improvement of methods for design and analysis of multivariable diagnostic and prognostic research is unique. Most research in this field focuses on single test evaluations rather than evaluations in a clinical context, accounting for other test results. But also the methodology for modeling data from randomized and non-randomized studies combined, is in its infancy. This type of research is situated at the crossroad of clinical epidemiology and medical technology assessment. All above methodological themes are not only studied on a purely theoretical level, but are also applied by using empirical data from various medical disciplines, notably from the four disease-oriented sections of the Julius Center. For example, data are used from the above-mentioned LRGP (Leidsche Rijn Gezondheidsproject), the Predict study and the AMUSE study, and from other large ongoing studies in the UMC Utrecht. It may be obvious that the results of our methodological studies do not only serve the clinical domains studied, but may serve all medical domains in which e.g. diagnosis, prognosis and therapy are at issue. Most methodological projects are carried out in close collaboration with other clinical departments from the UMC Utrecht. Other epidemiological and (bio)statistical departments from national an ational academic centers are also consulted, such as the Utrecht University, Academic Medical Center Amsterdam, Erasmus Medical Center 34 Annual Report 2007 Research 35

20 Rotterdam, Dutch National Institute for Health and the Environment, Vanderbilt University (USA), Harvard University (USA) and Oxford University (UK). Cohorts The Julius Center coordinates and participates in several large research cohorts. These cohorts are an important base for research and provide ample opportunities for obtaining financial research support. Moreover, the projects of the GP-network Utrecht and the Utrecht Health Project have the intention to create an infrastructure in which research questions on efficacy and effectiveness of health care, and effects of (local) health care policy, can be answered. The latter is of major importance for increasing the expertise in the areas of health care improvement, extramural health care, and general practice. The major cohorts are: AGIS Health database The AGIS Health database is a registry of all health care procedures of 1.7 million health insured persons. It contains data on health care procedures by all contracted health care providers such as general practitioners, specialists, physiotherapists, pharmacists, midwives and hospitals. Besides data on health care procedures in primary (consultations, referrals, prescriptions) and secondary care (consultations, prescriptions and procedures), a number of personal characteristics are documented, such as date of birth and gender. The insured persons are representative of the Dutch population. The purpose of the database is to improve knowledge on health care consumption, interaction between primary, secondary care and public health, and to provide data to support health care management and to improve quality of care. 36 Annual Report 2007 Research 37