Medical complications in patients with stroke: Data validity, processes of care, and clinical outcome PhD thesis Annette Ingeman Faculty of Health Sciences Aarhus University Department of Clinical Epidemiology, Aarhus University Hospital Supervisors Søren Paaske Johnsen, MD, Ph.D. Department of Clinical Epidemiology Aarhus University Hospital, Denmark Grethe Andersen, MD, DMSc. Department of Neurology Aarhus University Hospital, Denmark Evaluation committee Svend Sabroe, MD, Professor Department of Epidemiology School of Public Health Aarhus University, Denmark Helle Klingenberg Iversen, MD, DMSc. Department of Neurology Glostrup Hospital, Denmark Bo Norrving, MD, Professor Department of Neurology Lund University Hospital, Sweden PREFACE This Ph.D. thesis is based on studies carried out during my employment at the Department of Clinical Epidemiology, University of Aarhus, and at the DNIP secretariat in The Danish National Indicator Project, Aarhus, during the period 2007–2010. I would like to express my sincere gratitude to all who made this work possible. First of all, I thank Søren Paaske Johnsen for outstanding mentorship; for patiently teaching me clinical epidemiology, and sharing his creative ideas; for his trust and unfaltering support at all times; and, not to forget, for always providing thoughtful and constructive feed-back. I am grateful to Grethe Andersen for her never-failing engagement and support, and for providing skilful and constructive feedback on neurological issues. My sincere thanks go to the statistician, Heidi Hundborg, for sharing her excellent statistical skills. She was always there with help with data linkage and support with the many challenges associated with biostatistics. I would like to thank the lead clinicians and the staff in all the Danish hospital departments I visited during the record review process, who helped me finding whatever I needed. I am very grateful to all my colleagues and friends at the Department of Clinical Epidemiology and in the DNIP secretariat for creating a pleasant and stimulating environment. Finally, my warmest thanks go to my family: My husband Jens, our children Kasper and Katrine and my parents for their love, patience, and unconditional support at all times. Århus, May 2010 Den signede dag med fryd vi ser af havet til os opkomme, den lyse på himlen mer og mer os alle til lyst og fromme! det kendes på os som lysets børn, at natten hun er nu omme! N. F. S. Grundtvig, 1826 This work was made possible through financial support from the Danish Heart Foundation and the Central Denmark Research Foundation. LIST OF ABBREVIATIONS BMI Body mass index CI Confidence interval CT Computed tomography CCI Charlson comorbidity index score DNIP The Danish National Indicator Project DVT Deep venous thrombosis HR Hazard ratio H:S Hovedstadens Sygehusfællesskab ICD International classification of diseases LOS Length of stay LPR Landspatientregisteret MRI Magnetic resonance imaging MRR Mortality rate ratio NIP Det Nationale Indikatorprojekt NPV Negative predictive value NR Not reported NRP Danish National Registry of Patients OR Odds ratio PPV Positive predictive value PE Pulmonary embolism RCT Randomized controlled trial SSS Scandinavian Stroke Scale TIA Transient ischemic attack UTI Urinary tract infection VTE Venous thromboembolism WHO World Health Organization This Ph.D. thesis is based on the following studies: I. Ingeman A, Andersen G, Hundborg HH, Johnsen SP. Medical complications in patients with stroke: data validity in a stroke registry and a hospital discharge registry. J Clin Epidemiol 2010;2:5-13. II. Ingeman A, Andersen G, Hundborg HH, Svendsen ML, Johnsen SP. Processes of care and medical complications in patients with stroke. Submitted. III. Ingeman A, Andersen G, Hundborg HH, Svendsen ML, Johnsen SP. Medical complications in patients with stroke and clinical outcome: length of stay and mortality. In preparation. CONTENS INTRODUCTION..............................................................................................................................1 Introduction to stroke.......................................................................................................................1 Background and existing literature ..................................................................................................4 Introduction to medical complications.............................................................................................5 AIMS OF THE THESIS..................................................................................................................44 MATERIALS AND METHODS ....................................................................................................45 Setting ............................................................................................................................................45 Study designs .................................................................................................................................45 Data sources ...................................................................................................................................46 Statistical analyses .........................................................................................................................54 RESULTS .........................................................................................................................................58 Study I............................................................................................................................................58 Study II...........................................................................................................................................62 Study III .........................................................................................................................................65 DISCUSSION ...................................................................................................................................68 Methodological considerations ......................................................................................................68 Comparison with the existing literature.........................................................................................74 Study I............................................................................................................................................74 Study II...........................................................................................................................................74 Study III .........................................................................................................................................75 MAIN CONCLUSIONS ..................................................................................................................77 Study I............................................................................................................................................77 Study II...........................................................................................................................................77 Study III .........................................................................................................................................77 PERSPECTIVES .............................................................................................................................78 SUMMARY ......................................................................................................................................80 DANISH SUMMARY......................................................................................................................82 REFERENCES.................................................................................................................................85 APPENDIX.......................................................................................................................................97 INTRODUCTION Introduction to stroke What is stroke? Stroke is a clinical syndrome with several pathologies.1 Hippocrates (460 to 370 BCE), known as the father of medicine, was the first to describe the phenomenon of sudden paralysis that is often associated with ischemia. In his writings, Hippocrates used the word “Apoplexy”, from the Greek word meaning "struck down with violence”. The word “stroke” was used as a synonym for apoplectic seizure as early as 1599 and is a fairly literal translation of the Greek term. In 1658, in his “Apoplexia”, Johann Jacob Wepfer (1620–1695) identified the cause of haemorrhagic stroke when he suggested that people, who had died of apoplexy, had bleeding in their brains. Wepfer also identified the main arteries supplying the brain, the vertebral and carotid arteries, and identified the cause of ischemic stroke when he suggested that apoplexy might be caused by a blockage of those vessels.2-4 The World Health Organization (WHO) has defined stroke as a clinically defined syndrome “characterized by rapidly developing clinical symptoms and/or signs of focal, and at times global, loss of cerebral function, with symptoms lasting more than 24 hours leading to death with no apparent cause other than that of vascular origin”.5 Stroke is, however, a heterogeneous disease entity that includes several pathologically different conditions.6 It can be due to ischemia (lack of glucose and oxygen supply)7caused by thrombosis or embolism or haemorrhage. As a