Annual Report 2006. Julius Center for Health Sciences and Primary Care

Annual Report 2006 Julius Center for Health Sciences and Primary Care

Annual Report 2006 Julius Center for Health Sciences and Primary Care UMC Utrecht

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 into four disease-related themes and into research methodology, and by providing courses for (bio)medical students, researchers and clinicians. Disciplines represented in the Center are general practice, (clinical) epidemiology, nursing science, medical technology assessment, public health, and nutritional sciences. In this annual report the reader will find information on activities, output and finances in 2006. Contact information: M. Kluijtmans, PhD Executive Secretary Management Team & Coordinator Master Program Epidemiology Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Visitors: Universiteitsweg 100, 3584 CG Utrecht, The Netherlands Correspondence: Str.6.131, P.O. Box 85500, 3508 GA Utrecht, The Netherlands URL: www.juliuscenter.nl E-mail: M.Kluijtmans@umcutrecht.nl Annual Report 2006

Contents Introduction 5 Organization 13 Brief history 15 Research 17 Research organization 19 Research themes 22 IRAS 31 International collaboration 33 Research, al assessment of past performance 37 Education 39 Overview 41 Medical school 44 Bachelor Biomedical sciences 48 MSc Biomedical sciences, masters program Epidemiology 50 MA Applied ethics 54 MSc Nursing science 55 General practice vocational training 58 Graduate schools 61 (UGS Life Sciences, Nihes, ImagO, Eijkman and P&H) Advanced training in public health 66 Advanced training in general practice 68 Advanced training in clinical epidemiology 71

Patient care 75 Nutritional Sciences and Dietetics 77 Julius Center Health Care Leidsche Rijn 81 Operational support 83 Management support 85 Research Services, Vascular Imaging Center, Data management 86 Personnel and finances 89 Personnel, figures 91 Personnel, listing 92 Financial report 108 Research projects 2006 111 Cardiovascular diseases 113 Infectious diseases 121 Cancer 126 Mental health 128 Research methodology and biostatistics 133 Miscellaneous 136 Research services 140 Vascular imaging center 145 Data management 147 Publications 2006 151 PhD theses 153 Books and book chapters 156 Professional publications 158 International refereed publications 162 Annual Report 2006

Introduction The Julius Center has expanded its scientific reach and strengthened its position at the University Medical Center Utrecht as well as at Utrecht University.

Looking back at 2006, the first event that comes to mind is the 10 th anniversary of the Julius Center. A moment to celebrate and to reflect but also an excellent opportunity to look to the future. There is so much activity at the Julius Center that it is impossible to mention all that is going on. Therefore, we will recall some highlights of the past year, and refer you to the full annual report for a complete overview. In September several festivities took place to celebrate our anniversary. In an afternoon symposium the close ties that connect the Center to the other UMC Utrecht departments were addressed. The extensive collaboration that exists both in research and in education with clinical departments is of critical importance for a department where patient-oriented research is a primary activity. Also in our teaching, a multidisciplinary approach has shown to be a key factor to successful courses and educational programs. The afternoon session closed with a hilarious performance by the Professors Cabaret of the UMC Utrecht. The evening was devoted to the people who make up the Julius Center: a closed party for all personnel and their partners. It was a memorable evening for all Julians with lots of good food, drinks and conversation, but most of all of dancing into the late hours to the sounds of the Julius staff band and. Let us here also reflect upon the Center s most recent history. Since the Julius Center was established in 1996, it has built up a solid reputation in research and education. After taking over the Julius Health Care Centers Leidsche Rijn, the Center more recently broadened its objective to obtain a similar reputation in patient care. The University Medical Center s designation of epidemiology as a main research theme underlines the prominent role the center has played in applied research in Utrecht. In 2006 two events put Utrecht as a major epidemiological Center into the spotlight. Utrecht University defined Epidemiology as Introduction

one of its sixteen university focus themes; also, the four collaborating epidemiological research groups at Utrecht University organized a European Epidemiology congress. These events ensured that Utrecht University is now perceived as a leading academic institution for epidemiological research in the Netherlands. It is also enjoying greater renown in the ational health science community. In order to maintain the Center s successes and strong profile within the UMC Utrecht, it is important to look forward and define future goals. A document proposing the Center s mission and strategy for the next 10 years was distributed for discussion among all the Center s staff and personnel. The plans were actively discussed in several meetings and a oneday conference for the middle management, and a final version was decided upon. The next challenge will be to translate the overall strategy into explicit management guidelines and work plans. This year s report lists the many articles the Julius Center contributed to ational scientific publications, showing its repeated success in research activities. In an analysis ordered by the UMC Utrecht as part of their al review process, the Center s scientific output for the period between 1998 and 2005 was analyzed and judged to be of exceptionally high quality with an average citation impact score of 1.86; significantly higher-than-world average and the UMC Utrecht average. One scientific achievement merits extra mentioning. In December 2006, Marc Bonten, MD, PhD, professor of molecular epidemiology at both the Julius Center and the department of Internal Medicine, received a prestigious VICI grant to conduct research into the spread of antibiotics resistance, notably with regard to MRSA and Pseudomonas aeruginosa. By integrating molecular biology and mathematic modeling, he aims to promote insight to the determinants of spread of these bacteria, both in Annual Report 2006

and outside the hospital. His findings should lead to more effective preventive measures. In 2006 we also celebrated the retirement of Wija van Staveren, PhD, professor in nutritional sciences. The occasion was celebrated with ambivalent feelings as an excellent scientist and dear colleague is lost from our ranks. In March 2006, the fourth Julius Health Care Center (www.lrjg.nl) was opened in the Vleuterweide district. We also paid specific attention last year to patient safety in our health care centers. Using a prospective error analysis (HFMEA) the process of repeated medication was scrutinized in health care center Veldhuizen. To our knowledge this was the first HFMEA conducted in primary care in the Netherlands. Furthermore the health care centers obtained widespread exposure by the Dutch television series De Stadsdokter (freely translated: City GP ), with one of our GP s, Tjarda Scheltens, MD, in the lead role. Because of the series success (between 600,000 and 700,000 watchers per broadcast), the number of episodes was increased from seven to nineteen. Our GP vocational training program remains an important educational activity which strongly supports the Julius Center s role as a major player in primary care, both nationally and regionally. The education is of high quality and constant attention is given to primary care s current needs and demands. In 2006 a renewed competency-oriented curriculum was launched, with possibilities for differentiation in the third and final year of training. Seven competencies have been formulated that will form the basis of trainee education. Extra staff was appointed to fulfill the required increase in teaching capacity. The distinctive profile of the GP training program compared to similar programs in the Netherlands Introduction

remains its emphasis on evidence-based primary care. The untimely death of Monneke Smulders overshadowed satisfaction with this year s achievements. She was a very dear and valued colleague who devoted almost fifteen years to the training of young doctors specializing in general practice. Her efforts contributed significantly the recent improvements of the curriculum and the Teach The Trainer program. More progress in other areas of evidence-based medicine was also made. EBM is an important subject of study in the sixth year of the medical curriculum. An innovative and highly stimulating form of education was developed which aims at an optimal synergy between care, research and education: Evidence-Based Case Reports. In brief, residents and clinical staff from the UMC Utrecht clinical departments propose practice cases for which they seek evidence with regard to diagnosis and treatment. Next, medical students search and select best available evidence and formulate a recommendation: the evidence-based case report. Students, clinical staff and teachers have found these recommendations to be well appreciated and applicable. Four hundred and fifty recommendations are written annually and the best are offered for publication. With a grant from the UMC Utrecht s Smarter better program, a database with over 800 evidence-based case reports is currently being made available (with index) for use in clinical practice. A state-of-the-art administrative and financial system is of critical importance for the Julius Center s success. In 2006 several infrastructural improvements were made. The management structure and business organization was strengthened and further professionalized. The capacity was expanded to support the increased volume and complexity of research projects and the educational and care activities. A new policy was started in which the middle management will become more actively 10 Annual Report 2006

involved in budget monitoring and decisions, output measurement, and strategies to further reduce absence due to illness. An extensive budgetary analysis of the Center was conducted which has resulted in a decision by the UMC Utrecht s board to increase the Center s central budget. Moreover, the Julius foundation was fully integrated in the Center by the end of 2006. To maintain and expand the competitive advantage of the Julius Center in obtaining outside grants, a dedicated marketing and communication plan was begun in accordance with the UMC Utrecht s overall marketing strategy. All in all, 2006 was another productive and successful year in which the Center, like a tree, showed a modest increase in size and developed her tenth year ring. It has expanded its scientific reach and strengthened its position in the University Medical Center Utrecht as well as at Utrecht University. Moreover, it has solidified its base by giving necessary attention to its management and business structure and investing in consolidation. The center has grown several new branches of research, care and educational activities. All of this is due to just one factor: its people. None of this would have been possible without the commitment, hard work, inspiration and devotion of many. A heartfelt word of thanks to all involved in contributing to the continued success of the Julius Center. Prof. Diederick E. Grobbee, MD, PhD Chair Introduction 11

Organization In 2006 the Center celebrated its tenth anniversary. Introduction 13

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 2006 the Center celebrated its tenth anniversary. Organizational structure The organizational structure can be found at the inside of the cover. Organization 15

Research The Center s policy is to concentrate its research in such a way that the disciplines within the Center maximally support the scientific themes of the UMC Utrecht as a whole and cross-fertilize each other where possible. Research 17

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 can be classified as epidemiological. Building upon this, the Julius Center contributes to all four disease-related areas of research: heart and vascular diseases, infections and immunity, cancer, and mental health. In addition, there is also collaboration with the other two methodological research themes, Image sciences and Genomics. The Julius Center s research is similarly organized in a matrix structure. The vertical columns are formed by the scientific disciplines of the Center: Clinical Epidemiology, General Practice, MTA/Public Health/ Medical Ethics, Nursing Science, and Nutritional Sciences. The research methods for all of these disciplines can be broadly categorized as epidemiological, which was the incentive for all these disciplines to fall under the Center. The horizontal rows comprise five research lines: the four UMC-defined disease-based fields of interest (heart and vascular disease, infectious diseases, cancer, and mental health) as well a fifth methodological research line. Within some of these fields, there is a further focus on subfields, as for example research on (etiology and complications of) diabetes mellitus as part of the vascular disease line. Research 19

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 and the UMC Utrecht s scientific themes as a whole are strengthened. 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 of Prof. Bert Brunekreef and honorary appointee Prof. Dick Heederick. There is also collaboration with other epidemiological research groups at Utrecht University, in particular with the Pharmacoepidemiology 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 depart- 20 Annual Report 2006

ments 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. This is an important and growing activity for the Julius Center. For several 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. Research 21

Research themes Cardiovascular diseases A considerable part of the research carried out at the Julius Center 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. One example is research on the influence of natural or synthetic sex hormones on the condition of the heart and blood vessels in postmenopausal women and elderly men. ADVAN is an example of one of the larger ational multi-centered cardiovascular trials the Julius Center is involved in. The Center coordinates a large number of other multi-center ational cardiovascular prevention and treatment trials (see also: Research services and Vascular imaging center ). Increasingly, research includes genetic information and the interplay between genes and environment in, for example, studies on genetic and non-genetic factors that determine the prognosis of patients with vascular diseases. The studies are conducted in close collaboration with partners within and outside the UMC Utrecht and abroad. A unique cohort study of patients at high risk of cardiovascular disease (CVD) was started in Utrecht in 1996, called the Second Manifestations of ARTerial disease (SMART) Study. All patients referred to the UMC Utrecht who either have a high risk of CVD (hypertension, hyperlipidemia, diabetes) or clinically manifest vascular disease (ischemic cerebral disease, asymptomatic stenosis of the al carotid artery, myocardial infarction, angina pectoris, abdominal aortic aneurysm, intermittent claudication) are eligible for inclusion in the study. Patients undergo an extensive screening program to detect asymptomatic atherosclerotic 22 Annual Report 2006

lesions and to identify risk factors. Then, a multidisciplinary team formulates a treatment plan, consistent with evidence-based medicine, to reduce the patient s risk of future cardiovascular events. This treatment advice is sent to the patient s general practitioner and to the treating hospital specialist. In addition, patients are carefully monitored to identify future occurrences of cardiovascular disease. Currently, approximately 7,000 patients have been enrolled in the study, and the scientific output includes more than 45 papers in peer-reviewed journals. Furthermore, 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. Various cardiovascular studies are also being carried out on diabetes mellitus patients and on the metabolic syndrome. The Research Group on Diabetology conducts several trials in large networks of general practices, notably in the adherence region of the Stichting Huisartsen Laboratorium Etten Leur and the Apeldoorn Region. In collaboration with Cambridge University (UK) and Aarhus University (Denmark) the ADDITION-trial has been set up, a five-year follow-up RCT to study the effects on cardiovascular morbidity and mortality of intensive multifactorial treatment in 3,000 screen-detected diabetes patients. Other studies include the early roots of cardiovascular disease in the young, 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 Research 23

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. Infectious diseases Infectious diseases research at the Julius Center is centered around four topics: 1 Prevention, diagnosis and prognosis of respiratory tract infections. For example, research is being carried out to establish whether or not certain patient characteristics are predictive with regard to 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 them in general practice are being studied. In this area, research has also been expanding into 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. Large vaccination trials are being done in collaboration with the department of Pediatric Immunology, the National Vaccine Institute and pharmaceutical industries,. 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 prevention of multi-resistant bacteria and influenza transmission 24 Annual Report 2006

within hospitals and the community at large is being investigated, as well as potential effects of intervention. 4 Infections in patients with diabetes mellitus. The project Development and evaluation of an educational program 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. 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, Prospect-EPIC (European Prospective Investigation into Cancer and Nutrition) and DOM. In 2006 the Julius Center strengthened the co-operation with the RIVM to join efforts in merging data of two large-scale population based epidemiological projects, the Prospect-EPIC and the Morgen-EPIC studies. Research 25

The result will be a cohort of 40,000 healthy Dutch inhabitants being tracked for the occurrence of chronic diseases, including cancer. 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. 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: 1 The presentation of depression in primary care, and its association with somatic disease such as dementia, diabetes and vascular disease. 2 Functional disease and somatoform disorders: presentation, determinants and treatment in primary care 26 Annual Report 2006

3 Psychiatric morbidity in relation to socio-demographic context and consultation patterns 4 Nurse delegated interventions in mental health care 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). These themes are studied on the various levels at which disorders manifest themselves: a The general population, by using existing and developing sampling frames such as Utrecht Health Project (Leidsche Rijn Gezondheidsproject), NEMESIS (Netherlands Mental Health Survey and Incidence Study), AGIS health database and others. b Primary health care, in primary care networks such as HNU (Huisartsen Netwerk Utrecht), PREDICT and Julius Gezondheidscentra. c Populations of people with reported mental illness like those registered in our psychiatric case registry (RIPAG). d Populations of people with reported somatic illness, such as samples of cardiovascular compromised patients (SMART), (pre)diabetic patients (UDES), and medication-using people (PHARMO). e Populations of primary care emergency attenders like the Huisartsenpost Gelderse Vallei and the emergency department of the UMC Utrecht This approach of studying the phenomenon of somatic psychiatric comorbidity on various levels of the health care system is unique. It will Research 27

yield information not only on the etiology of somatic-psychiatric comorbidity but also on its implications for the health care system. 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 and gastro-enterology, departments of nursing sciences, often in cooperation with other (ational) academic centers. Research Methodology 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: 1 Developing innovative designs for diagnostic and prognostic (prediction) research. 2 Developing innovative methods for quantifying the true value or contribution of (new) diagnostic and prognostic tests in a multivariable clinical context. 3 Developing innovative methods for the validation and updating of socalled clinical prediction rules. 4 Testing and improving sophisticated methods for dealing with missing values in epidemiologic research. 5 Investigating innovative methods for meta-analysis and individual patient data-analysis of therapeutic studies. 28 Annual Report 2006

6 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. 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 Utrecht Health Project (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 Rotterdam, Dutch National Institute for Health and the Environment, Research 29