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Flemming Skjøth,1,2 Henrik Nielsen,3,4 Jacob Bodilsen3,4 1Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 2Unit of Clinical Biostatistics, Aalborg University Hospital, Aalborg, Denmark; 3Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark; 4Institute of Clinical Medicine, Aalborg University, Aalborg, DenmarkCorrespondence: Jacob Bodilsen, Department of Infectious Diseases, Aalborg University Hospital, Mølleparkvej 4, Aalborg, 9000, Denmark, Tel +45 97660566, Email Jacob.bodilsen@rn.dkPurpose: Following the implementation of the 3rd version of the Danish National Patient Register (DNPR-3), information on whether hospitalizations were inpatient, outpatient, or emergency room (ER) contacts was no longer readily available. This study examined the positive predictive values (PPV) of a common algorithm to characterize hospitalizations as inpatient, outpatient, or emergency room (ER) contacts in both DNPR-2 and DNPR-3.Patients and Methods: All hospital contacts in North Denmark Region were identified in the DNPR within a 1-year window of the implementation of DNPR-3 in early 2019. An algorithm based upon proportion of overnight (± 50%) and elective (± 50%) contacts for each hospital department was developed. Next, PPVs of these categorizations were computed using manual characterization of all departments and clinics by two experienced clinicians as reference. Second, the reliability of various time intervals to join department contacts and subsequent categorization of overnight hospital stays as proxies for inpatient contacts was explored.Results: The algorithm yielded PPVs of 91% and 89% for hospital units and related contacts categorized as inpatient in DNPR-2 and 100% for both parameters in DNPR-3. In outpatient units, the PPVs were 99% in both DNPR-2 and DNPR-3, whereas the corresponding PPVs were 99.6% and 99% on the contact level. In contrast, the PPV for ERs was 33% in DNPR-2 and 56% in DNPR-3, primarily due to misclassification of outpatient clinics. Still, the proportion of correctly categorized ER contacts was 87% in DNPR-2 and 85% in DNPR-3. Using time intervals from 0 to 12 hours to join department contacts showed that overnight hospitalizations comprised inpatient contacts in 97% in DNPR-2 and 98% in DNPR-3. However, the sensitivity was moderate at 76– 78% for all inpatient hospitalizations in DNPR-2 and DNPR-3.Conclusion: This algorithm accurately categorized hospitalizations as inpatient, outpatient, or ER contacts in both DNPR-2 and DNPR-3.Keywords: epidemiological methods, medical record linkage, registries, research design, validation studies, Danish National Patient Registry, DNPR, LPR-3, Landspatientregisteret

Lærke Storgaard Duerlund,1 Shakil Shakar,2 Henrik Nielsen,1 Jacob Bodilsen1 1Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark; 2The Department of Medicine, Regionshospitalet Nordjylland Hjørring, Hjørring, DenmarkCorrespondence: Jacob BodilsenDepartment of Infectious Diseases, Aalborg University Hospital, Mølleparkvej, 4, Aalborg, 9000, Denmark, Tel +45 97660566, Email Jacob.bodilsen@rn.dkPurpose: To examine the positive predictive value (PPV) of International Classification version 10 (ICD-10) diagnosis codes for long coronavirus disease 2019 (long-COVID) in a Danish Health registry.Patients and Methods: This was a medical record review of all patients with a diagnosis code of long-COVID (DB948A) at all hospitals in the North Denmark Region from February 27, 2020 through June 30, 2021. Confirmed long-COVID was categorized as fulfillment of all three criteria: (1) a positive polymerase chain reaction (PCR) test for SARS-CoV-2 on a respiratory sample or a positive serum antibody test, (2) symptoms suggestive of long-COVID with no other diagnosis considered more likely, and (3) symptom duration > 6 weeks.Results: A total of 306 patients were assigned a hospital diagnosis code for long-COVID corresponding to 1.4% of all SARS-CoV-2 positive individuals during the study period (n=21,727). Next, 40 patients were excluded due to incomplete diagnostic evaluation at time of record review leaving 266 patients for analysis. The patients had a median age of 51 years (interquartile range 43– 60) and 175/266 (66%) were females. Long-COVID was confirmed in 249/266 yielding an overall PPV of 94% (95%CI: 90– 96) and did not differ substantially according to most age groups, sex, previous hospitalization for COVID-19, or by using 12 weeks of symptom duration as cut-off. The PPV was low for children and adolescents (n=5), the very elderly (n=9), and those included by secondary long-COVID diagnoses (n=10).Conclusion: The overall PPV of diagnosis codes for long-COVID in the North Denmark Region was high and was likely suitable for future registry-based studies of long-COVID. Caution is advised at the extremes of age and secondary diagnosis codes.Keywords: post-COVID, coronavirus disease 2019, diagnosis codes, validation, epidemiology

Jacob Bodilsen,1 Lykke Larsen,2 Christian Thomas Brandt,3,4 Lothar Wiese,4 Birgitte Rønde Hansen,5 Christian Østergaard Andersen,6 Hans Rudolf Lüttichau,7 Jannik Helweg-Larsen,8 Merete Storgaard,9 Henrik Nielsen1,10 1Department of Infectious Diseases, Aalborg University Hospital, Aalborg, 9000, Denmark; 2Department of Infectious Diseases, Odense University Hospital, Odense, 5000, Denmark; 3Department of Infectious Diseases, Nordsjællands Hospital, Hillerød, 3400, Denmark; 4Department of Infectious Diseases, Sjælland University Hospital, Roskilde, 4000, Denmark; 5Department of Infectious Diseases, Hvidovre University Hospital, Copenhagen, 2650, Denmark; 6Department of Clinical Microbiology, Hvidovre University Hospital, Copenhagen, 2650, Denmark; 7Department of Infectious Diseases, Herlev Gentofte Hospital, Copenhagen, 2730, Denmark; 8Department of Infectious Diseases, Rigshospitalet, Copenhagen, 2100, Denmark; 9Department of Infectious Diseases, Aarhus University Hospital, Aarhus, 8200, Denmark; 10Department of Clinical Medicine, Aalborg University, Aalborg, 9000, DenmarkCorrespondence: Jacob BodilsenDepartment of Infectious Diseases, Aalborg University Hospital, Mølleparkvej 4, Aalborg, DK9000, DenmarkTel +45 97660566Email Jacob.bodilsen@rn.dkAbstract: Central nervous system (CNS) infections are rare diseases that are associated with considerable morbidity and mortality. Increased knowledge based on contemporary data is a prerequisite for improved management and prevention of these serious conditions. Yet, population-based databases of patients hospitalized with CNS infections remain scarce. The Danish Study Group of Infections of the Brain (DASGIB) has prospectively registered information on all adults ≥ 18 years of age admitted with CNS infections at departments of infectious diseases in Denmark since 2015. The main variables collected are baseline demographics, blood and cerebrospinal fluid tests, imaging results, and outcome using the Glasgow Outcome Scale score. To investigate important aspects for each type of CNS infections, additional variables are included specifically for bacterial meningitis, viral meningitis, encephalitis, brain abscess, neurosyphilis, and Lyme neuroborreliosis. From 2015 to 2020, a total of 3579 cases of CNS infections have been recorded in the DASGIB database. Using the unique civil registration number assigned to all Danish residents, the database can be unambiguously linked with nationwide healthcare registries at the individual level. This enables researchers to conduct detailed population-based and longitudinal observational studies of risk and prognosis of CNS infections and to compare them with matched population cohorts. The database is well-suited for epidemiological research and the DASGIB network forms a solid infrastructure for future national and international collaborations.Keywords: CNS infections, epidemiology, database, cohort studies, bacterial meningitis, viral meningitis, encephalitis, brain abscess, cerebral abscess, neurosyphilis, syphilis, Lyme neuroborreliosis, borreliosis

Jacob Bodilsen,1 Steffen Leth,2,3 Stig Lønberg Nielsen,4,5 Jon Gitz Holler,6 Thomas Benfield,7 Lars Haukali Omland8 1Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark; 2Department of Infectious Diseases, Aarhus University Hospital Skejby, Aarhus, Denmark; 3Department of Medicine, Regional Hospital Unit West Jutland, Herning, Denmark; 4Research Unit for Infectious Diseases, Odense University Hospital, Odense, Denmark; 5University of Southern Denmark, Odense, Denmark; 6Department of Pulmonary and Infectious Diseases, Hillerød Hospital, Hillerød, Denmark; 7Department of Infectious Diseases, Copenhagen University Hospital – Amager and Hvidovre, Hvidovre, Denmark; 8Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, DenmarkCorrespondence: Jacob BodilsenDepartment of Infectious Diseases, Aalborg University Hospital, Mølleparkvej 4, Aalborg, 9000, DenmarkEmail Jacob.bodilsen@rn.dkPurpose: To examine the positive predictive value (PPV) of International Classification version 10 (ICD-10) diagnosis codes for Coronavirus disease 2019 (COVID-19).Patients and Methods: Medical record review of all patients assigned a diagnosis code of COVID-19 (DB342A or DB972A) at six Danish departments of infectious diseases from February 27 through May 4, 2020. Confirmed COVID-19 diagnosis was defined as either: 1) definite, a positive polymerase chain reaction (PCR) for severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) on a respiratory sample combined with symptoms suggestive of COVID-19: 2) probable, clinical presentation of COVID-19 without detection of SARS-CoV-2 and no alternative diagnoses considered more likely; or 3) possible, clinical presentation of COVID-19 without detection of SARS-CoV-2, and the patient was discharged or deceased before further investigations were carried out. We computed the PPV with 95% confidence intervals (CI) as the number of patients with confirmed (i.e., definite, probable, and possible) COVID-19 divided by the number of patients assigned a diagnosis code for COVID-19.Results: The study included 710 patients with a median age of 61 years (interquartile range [IQR] 47– 74) and 285/710 (40%) were female. COVID-19 was confirmed in 706/710 (99%) with 705/710 (99%) categorized as definite, 1/710 (0.1%) as probable, and 0 patients as possible COVID-19. The diagnosis was disproven in 4/710 (0.6%) patients who were hospitalized due to bacterial pneumonia (n = 2), influenza (n = 1), and urinary tract infection (n = 1). The overall PPV for COVID-19 was 99% (95% CI 99– 100) and remained consistently high among all subgroups including sex, age groups, calendar period, and stratified by diagnosis code and department of infectious diseases (range 97– 100%).Conclusion: The overall PPV of diagnosis codes for COVID-19 in Denmark was high and may be suitable for future registry-based prognosis studies of COVID-19.Keywords: Coronavirus disease 2019; COVID-19, SARS-CoV-2, diagnosis codes, ICD-10, positive predictive value; PPV, validation, epidemiology

Ann-Brit E Hansen,1– 3 Hanne T Vestergaard,4 Ram B Dessau,5 Jacob Bodilsen,6 Nanna S Andersen,7 Lars H Omland,1 Claus B Christiansen,8 Svend Ellermann-Eriksen,9 Lene Nielsen,10 Thomas Benfield,2,3 Henrik T Sørensen,11 Christian Ø Andersen,12 Anne-Mette Lebech,1,3 Niels Obel1,3 1Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 2Department of Infectious Diseases, Amager Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark; 3Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 4Department of Virus & Microbiological Special Diagnostics, Statens Serum Institute, Copenhagen, Denmark; 5Department of Clinical Microbiology, Slagelse Hospital, Slagelse, Denmark; 6Departments of Infectious Diseases and Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark; 7Department of Clinical Microbiology, Odense University Hospital, Odense, Denmark; 8Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 9Department of Clinical Microbiology, Aarhus University Hospital, Aarhus, Denmark; 10Department of Clinical Microbiology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark; 11Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 12Department of Clinical Microbiology, Amager Hvidovre University Hospital, University of Copenhagen, Hvidovre, DenmarkCorrespondence: Ann-Brit E HansenDepartment of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen Ø DK-2100, DenmarkTel +45 30299306Email ann-brit.eg.hansen.02@regionh.dkBackground: The long-term prognosis following herpes simplex virus (HSV) central nervous system (CNS) infection is still debated.Patients and Methods: We examined outcomes in all Danish residents who, during 2000– 2016, tested PCR positive for HSV-1 (n=208) or HSV-2 (n=283) in the cerebrospinal fluid, compared to comparison cohorts from the general population (n=2080 and n=2830).Results: One-year mortality was increased among HSV-1 patients (difference 19.3%; 95% CI: 13.6% to 25.0%) and HSV-2 patients (difference 5.3%; 95% CI: 2.5% to 8.1%), but thereafter mortality was not increased. After exclusion of persons diagnosed with cancer prior to study inclusion, one-year mortality difference for HSV-2 patients was 1.7% (− 0.1% to 3.5%). After five years, HSV-1 patients had lower employment (difference − 19.8%; 95% CI: − 34.7% to − 4.8%) and higher disability pension rates (difference 22.2%; 95% CI: 8.4% to 36.0%) than the comparison cohort, but similar number of inpatient days, outpatient visits, and sick leave. HSV-2 patients had employment and disability pension rates comparable to the comparison cohort, but more inpatient days (difference 1.5/year; 95% CI: − 0.2 to 3.2), outpatient visits (difference 1.3/year; 95% CI: 0.3 to 3.2), and sick leave days (difference 9.1/year; 95% CI: 7.9 to 10.4).Conclusion: HSV-1 and HSV-2 CNS infections differ substantially with respect to prognosis. HSV-1 CNS infection is followed by increased short-term mortality and long-term risk of disability. HSV-2 CNS infection has no substantial impact on mortality or working capability but is associated with increased morbidity.Keywords: herpes simplex virus encephalitis, herpes simplex virus meningitis, prognosis, outcome, cohort study

Jacob Bodilsen,1 Michael Dalager-Pedersen,1 Nicolai Kjærgaard,1 Diederik van de Beek,2 Matthijs C Brouwer,2 Henrik Nielsen,1 and the DASGIB study group 1Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark; 2Department of Neurology, Amsterdam Neuroscience, Academic Medical Centre, Amsterdam, The Netherlands Purpose: To evaluate the positive predictive value (PPV) of ICD-10 diagnosis codes for brain abscess in the Danish National Patient Registry (DNPR). Patients and methods: We examined medical records of all patients with a first-time diagnosis code of brain abscess in the DNPR from 2007 to 2016. Patients were categorized with either confirmed or disproved brain abscess using a priori defined criteria. We computed the PPV as the proportion of confirmed diagnoses. Results: We identified 709 patients, of whom the medical records could not be retrieved for 15 patients, leaving 694 for further analyses. Of these, 444 had a confirmed brain abscess and 250 had another proven diagnosis, including 47 cases of intracranial empyema. The overall PPV was 64% (95% CI: 60–68) ranging from 24% to 96% among the different codes evaluated. By including only patients with either 1) both a diagnosis and surgical procedure code for brain abscess or 2) patients admitted to hospital with certain primary diagnosis codes (DG060[C,E,F] or DG079B) without newly diagnosed central nervous system (CNS) cancer, spondylodiscitis/intraspinal abscess, or procedure codes for evacuation of intracranial empyema, the PPV increased to 84% (95% CI 80–87) and 89% (395/444) of all confirmed cases were identified. Conclusion: The overall PPV of diagnosis codes for brain abscess in the DNPR was moderate. However, by exclusion of newly diagnosed CNS tumors, spondylodiscitis/intraspinal abscess, and intracranial empyemas, the PPV was high and therefore suitable for future registry-based studies of brain abscess. Keywords: cerebral abscess, register, PPV, intracranial abscess, epidemiology