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Background: Comparative data on clinical presentation, laboratory characteristics, treatment, and outcome of neurosyphilis (NS) in people living with HIV (PLWH) and NS patients without HIV are scarce.Methods: Nationwide, population-based, prospective cohort study on all adults with NS diagnosed between 2015 and 2021 at departments of infectious diseases in Denmark.Results: We identified 108 patients with NS, which equals a yearly incidence of 0.3/100,000 adults. The median age was 49 years, 85 (79%) were male, 43 (40%) were men having sex with men and 20 (22%) were PLWH. Ninety-five (88%) had early NS, 37 (34%) had ocular or ocular and otogenic NS, and 27 (25%) had symptomatic meningitis. Most common symptoms were visual disturbance (44%), skin rash (40%), fatigue (26%) and chancre (17%). Median CSF leukocyte count was 27 × 106 cells/L. PLWH less often had neurological deficits (p = 0.02). Unfavorable outcome was observed in 23 (21%) at discharge of whom 0 were PLWH (p = 0.01). Among the 88 NS patients without HIV a CSF leukocyte count of ≥ 30 × 106 cells/L was associated with unfavorable outcome (OR = 3.3 (95% confidence interval: 1.1-10.4)).Conclusions: PLWH with NS have better outcomes than NS patients without HIV infection. Background: Comparative data on clinical presentation, laboratory characteristics, treatment, and outcome of neurosyphilis (NS) in people living with HIV (PLWH) and NS patients without HIV are scarce.Methods: Nationwide, population-based, prospective cohort study on all adults with NS diagnosed between 2015 and 2021 at departments of infectious diseases in Denmark.Results: We identified 108 patients with NS, which equals a yearly incidence of 0.3/100,000 adults. The median age was 49 years, 85 (79%) were male, 43 (40%) were men having sex with men and 20 (22%) were PLWH. Ninety-five (88%) had early NS, 37 (34%) had ocular or ocular and otogenic NS, and 27 (25%) had symptomatic meningitis. Most common symptoms were visual disturbance (44%), skin rash (40%), fatigue (26%) and chancre (17%). Median CSF leukocyte count was 27 × 106 cells/L. PLWH less often had neurological deficits (p = 0.02). Unfavorable outcome was observed in 23 (21%) at discharge of whom 0 were PLWH (p = 0.01). Among the 88 NS patients without HIV a CSF leukocyte count of ≥ 30 × 106 cells/L was associated with unfavorable outcome (OR = 3.3 (95% confidence interval: 1.1-10.4)).Conclusions: PLWH with NS have better outcomes than NS patients without HIV infection.

Background It is unknown whether patients diagnosed with brain abscess have an increased risk of psychiatric disorders. Methods In this nationwide, population-based matched cohort study from Denmark, we compared the incidence of psychiatric disorders, use of psychiatric hospitals, and receipt of psychiatric medications between patients diagnosed with brain abscess and individuals from the general population, matched on date of birth, sex, and residential area. Results We included 435 patients diagnosed with brain abscess and 3909 individuals in the comparison cohort: 61% were male and median age was 54 years. Patients diagnosed with brain abscess were more likely to suffer from comorbidity. The risk of a hospital diagnosis of psychiatric disorders was increased the first 5 years of observation. In the subpopulation, who had never been in contact with psychiatric hospitals or received psychiatric medication before study inclusion, the risk of developing psychiatric disorders was close to that of the background population, especially when we excluded dementia from this outcome. There was a substantial increase in the receipt of anxiolytics and antidepressants. The difference in the proportion of individuals who received anxiolytics and antidepressants increased from 4% (95% confidence interval [CI], 0%–7%) and 2% (95% CI, −1% to 5%) 2 years before study inclusion to 17% (95% CI, 12%–21%) and 11% (95% CI, 7%–16%) in the year after study inclusion. Conclusions Patients with brain abscess without prior psychiatric disorders or receipt of psychiatric medicine are not at increased risk psychiatric disorders diagnosed in psychiatric hospitals, but they have an increased receipt of psychiatric medication.

OBJECTIVES: Long-term functional outcomes of brain abscess remains sparsely elucidated.METHODS: Nationwide, population-based cohort study of all Danish patients with a culture verified brain abscess and a comparison cohort from the general population individually matched on date of birth and sex.RESULTS: Among 435 patients and 1740 members of the comparison cohort, 61% were men and median age was 54 years. In the year of study inclusion, patients with brain abscess had more hospital admission days, more outpatient visits and more sick leave days, compared with the comparison cohort. With time, these differences subsided. Brain abscess was associated with permanent lower employment rates and a higher risk of disability pension (difference of proportion employed of -26% (95% CI: -36% to -17%) and of proportion on disability pension of 29% (95% CI: 20% to 38%) 5 years after study inclusion). Two years after study inclusion, 1.4% of patients with brain abscess lived in residential care homes (difference of 1.1% (-0.2% to 2.5%)).CONCLUSIONS: In this nationwide, population-based cohort study, brain abscess was associated with permanently decreased employment rates. Only a minority were dependent on residential care residency following a diagnosis of brain abscess suggesting that severe disability is probably rare.

Background Migrants face an increased risk of HIV infection and late presentation for HIV care. Aim To examine delays in HIV diagnosis, linkage to care (LTC), and risk of late presentation for migrants living with HIV in Denmark. Methods We conducted a population-based, nationwide study of adult migrants (n = 2,166) presenting for HIV care between 1 January 1995 and 31 December 2020 in Denmark. Time from immigration to HIV diagnosis and from diagnosis to LTC, and late presentation were assessed, stratified by migrants’ geographical regions of origin, using descriptive statistics. Results The demographics of the migrant population changed over time. Overall, migrants diagnosed with HIV after immigration to Denmark resided a median of 3.7 (IQR: 0.8–10.2) years in Denmark before diagnosis. Median time from HIV diagnosis to LTC was 6 (IQR: 0–24) days. Migrants diagnosed with HIV infection before immigration had a median of 38 (IQR: 0–105) days from arrival in Denmark to LTC. The corresponding median times for 2015–20 alone were 4.1 (IQR: 0.9–13.1) years, 0 (IQR: 0–8) days, and 62 (IQR: 25–152) days, respectively. The overall proportion of late presentation among migrants diagnosed with HIV after immigration was 60%, and highest among migrants from sub-Saharan Africa and East and South Asia. Conclusion HIV diagnosis is still substantially delayed in Danish migrants, while LTC is timely. The proportions with late presentation are high. These results call for targeted interventions to reduce the number of migrants with undiagnosed HIV infections and of late presenters.

Background Venous thromboembolism (VTE) is a potentially fatal complication of SARS-CoV-2 infection and thromboprophylaxis should be balanced against risk of bleeding. This study aimed to examine risks of VTE and major bleeding in hospitalized and community-managed SARS-CoV-2 patients compared with control populations. Methods Using nationwide population-based registries, 30-day risks of VTE and major bleeding in SARS-CoV-2 positive patients were compared with those of SARS-CoV-2 test-negative patients and with an external cohort of influenza patients. Medical records of all COVID-19 patients at six departments of infectious diseases in Denmark were reviewed in detail. Results The overall 30-day risk of VTE was 0.4% (40/9,460) among SARS-CoV-2 patients (16% hospitalized), 0.3% (649/226,510) among SARS-CoV-2 negative subjects (12% hospitalized), and 1.0% (158/16,281) among influenza patients (59% hospitalized). VTE risks were higher and comparable in hospitalized SARS-CoV-2 positive (1.5%), SARS-CoV-2 negative (1.8%), and influenza patients (1.5%). Diagnosis of major bleeding was registered in 0.5% (47/9,460) of all SARS-CoV-2 positive individuals and in 2.3% of those hospitalized. Medical record review of 582 hospitalized SARS-CoV-2 patients observed VTE in 4% (19/450) and major bleeding in 0.4% (2/450) of ward patients, of whom 31% received thromboprophylaxis. Among intensive care patients (100% received thromboprophylaxis), risks were 7% (9/132) for VTE and 11% (15/132) for major bleeding. Conclusions Among people with SARS-CoV-2 infection in a population-based setting, VTE risks were low to moderate and were not substantially increased compared with SARS-CoV-2 test-negative and influenza patients. Risk of severe bleeding was low for ward patients, but mirrored VTE risk in the intensive care setting. BACKGROUND: Venous thromboembolism (VTE) is a potentially fatal complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and thromboprophylaxis should be balanced against risk of bleeding. This study examined risks of VTE and major bleeding in hospitalized and community-managed SARS-CoV-2 patients compared with control populations. METHODS: Using nationwide population-based registries, 30-day risks of VTE and major bleeding in SARS-CoV-2 positive patients were compared with those of SARS-CoV-2 test-negative patients and with an external cohort of influenza patients. Medical records of all COVID-19 patients at 6 departments of infectious diseases in Denmark were reviewed in detail. RESULTS: The overall 30-day risk of VTE was 0.4% (40/9460) among SARS-CoV-2 patients (16% hospitalized), 0.3% (649/226 510) among SARS-CoV-2 negative subjects (12% hospitalized), and 1.0% (158/16 281) among influenza patients (59% hospitalized). VTE risks were higher and comparable in hospitalized SARS-CoV-2 positive (1.5%), SARS-CoV-2 negative (1.8%), and influenza patients (1.5%). Diagnosis of major bleeding was registered in 0.5% (47/9460) of all SARS-CoV-2 positive individuals and in 2.3% of those hospitalized. Medical record review of 582 hospitalized SARS-CoV-2 patients observed VTE in 4% (19/450) and major bleeding in 0.4% (2/450) of ward patients, of whom 31% received thromboprophylaxis. Among intensive care patients (100% received thromboprophylaxis), risks were 7% (9/132) for VTE and 11% (15/132) for major bleeding. CONCLUSIONS: Among people with SARS-CoV-2 infection in a population-based setting, VTE risks were low to moderate and were not substantially increased compared with SARS-CoV-2 test-negative and influenza patients. Risk of severe bleeding was low for ward patients, but mirrored VTE risk in the intensive care setting.

ObjectiveTo assess the long-term risk of hematologic cancers, invasive solid tumors, and nonmelanoma skin cancer (NMSC) among sarcoidosis patients with biopsy-verified nonnecrotizing granulomatous inflammation.MethodsWe used Danish administrative registers with nationwide coverage to construct a cohort of 3892 patients with sarcoidosis and an age- and sex-matched comparison cohort of 38,920 population controls. For all patients, a biopsy demonstrating nonnecrotizing granulomatous inflammation had been obtained from the lower respiratory tract at the time of diagnosis. Study outcome was time to diagnosis of cancer. Follow-up began at time of sarcoidosis diagnosis and continued for up to 10 years. We calculated hazard ratios (HRs) as estimates of the cancer risk among the patients with sarcoidosis relative to that among the population controls and used cumulative incidence functions to calculate absolute 10-year risk estimates.ResultsWe observed an increased long-term risk of hematologic cancers (HR during the first 2 years of follow-up: 2.71 [95% CI 1.18–6.25]; HR after > 2 years of follow-up: 2.12 [95% CI 1.29–3.47]) and NMSC (HR after > 2 years of follow-up: 1.82 [95% CI 1.43–2.32]) among the patients with sarcoidosis. An increased risk of invasive solid tumors was only observed during the first 2 years (HR 1.55, 95% CI 1.18–2.04). Compared with the population controls, the patients with sarcoidosis had an increased absolute 10-year risk of hematologic cancers (risk difference 0.56%, 95% CI 0.11–1.01%) and NMSC (risk difference 1.58%, 95% CI 0.70–2.47%).ConclusionSarcoidosis patients with biopsy-verified nonnecrotizing granulomatous inflammation have an increased long-term risk of hematologic cancers and NMSC compared with the general population.

BackgroundPeople with human immunodeficiency virus (PWH) may be at increased risk of several respiratory syndromes including chronic obstructive pulmonary disease (COPD). In matched cohort studies, we examined risk factors for COPD in PWH and their parents and siblings compared with population controls.MethodsUsing data from national registries, competing risk regression models were constructed and used to calculate adjusted hazard ratios (aHRs) for COPD. We evaluated the effect of human immunodeficiency virus characteristics, smoking, and educational attainment on COPD incidence in PWH.ResultsA total of 226 PWH and 1029 population controls were diagnosed with COPD during 63 661 and 562 171 person-years of follow-up. PWH had increased risk of being diagnosed with COPD compared to controls (aHR, 2.02 [95% confidence interval, 1.75–2.33]). Parents and siblings of PWH were also more likely to be diagnosed with COPD compared to controls. CD4+ T-cell counts were not associated with COPD, but unsuppressed viral replication, smoking status, and educational attainment were associated with COPD in PWH. No COPD diagnoses were registered in PWH with high educational attainment and absence of smokingConclusionsPWH have an increased risk of being diagnosed with COPD, as have their parents and siblings. This seems to be driven primarily by smoking and low socioeconomic status.

Background: Late HIV diagnosis is detrimental both to the individual and to society. Strategies to improve early diagnosis of HIV must be a key health care priority. We examined whether nation-wide electronic registry data could be used to predict HIV status using machine learning algorithms. Methods: We extracted individual level data from Danish registries and used algorithms to predict HIV status. We used various algorithms to train prediction models and validated these models. We calibrated the models to mimic different clinical scenarios and created confusion matrices based on the calibrated models. Findings: A total 4,384,178 individuals, including 4,350 with incident HIV, were included in the analyses. The full model that included all variables that included demographic variables and information on past medical history had the highest area under the receiver operating characteristics curves of 88·4% (95%CI: 87·5% – 89·4%) in the validation dataset. Performance measures did not differ substantially with regards to which machine learning algorithm was used. When we calibrated the models to a specificity of 99·9% (pre-exposure prophylaxis (PrEP) scenario), we found a positive predictive value (PPV) of 8·3% in the full model. When we calibrated the models to a sensitivity of 90% (screening scenario), 384 individuals would have to be tested to find one undiagnosed person with HIV. Interpretation: Machine learning algorithms can learn from electronic registry data and help to predict HIV status with a fairly high level of accuracy. Integration of prediction models into clinical software systems may complement existing strategies such as indicator condition-guided HIV testing and prove useful for identifying individuals suitable for PrEP. Funding: The study was supported by funds from the Preben and Anne Simonsens Foundation, the Novo Nordisk Foundation, Rigshospitalet, Copenhagen University, the Danish AIDS Foundation, the Augustinus Foundation and the Danish Health Foundation. Keywords: HIV prevention, HIV diagnosis, Machine learning, Registry data, Big data

Background & Aims: The association between Hepatitis C virus (HCV)-infection and fracture risk is not well characterized. We compared fracture risk between HCV-seropositive (HCV-exposed) patients and the general population and between patients with cleared and chronic HCV-infection. Methods: Outcome measures were time to first fracture at any site, time to first low-energy and first non-low-energy (other) fracture in 12,013 HCV-exposed patients from the DANVIR cohort compared with a general population control cohort (n = 60,065) matched by sex and age. Within DANVIR, 4500 patients with chronic HCV-infection and 2656 patients with cleared HCV-infection were studied. Results: Compared with population controls, HCV-exposed patients had increased overall risk of fracture [adjusted incidence rate ratio (aIRR) 2.15, 95% Confidence Interval (CI) 2.03–2.28], increased risk of low-energy fracture (aIRR 2.13, 95% CI: 1.93– 2.35) and of other fracture (aIRR 2.18, 95% CI: 2.02–2.34). Compared with cleared HCV-infection, chronic HCV-infection was not associated with increased risk of fracture at any site (aIRR 1.08, 95% CI: 0.97–1.20), or other fracture (aIRR 1.04, 95% CI: 0.91–1.19). The aIRR for low-energy fracture was 1.20 (95% CI: 0.99–1.44). Conclusions: HCV-exposed patients had increased risk of all fracture types. In contrast, overall risk of fracture did not differ between patients with chronic vs. cleared HCV-infection, although chronic HCV-infection might be associated with a small excess risk of low-energy fractures. Our study suggests that fracture risk in HCV-infected patients is multi-factorial and mainly determined by lifestyle-related factors associated with HCVexposure. 2014 European Association for the Study of the Liver. Published

Objective To estimate annual employment rates and disability retirement rates (DRRs) among HIV-infected individuals and population controls during the period 1996-2011. Design A population-based cohort study including all HIV-infected individuals born in Denmark and not reporting intravenous (i.v.) drug abuse as a route of HIV infection or diagnosed with hepatitis C infection (n = 2799) and 22,369 individually matched persons from the background population. Study inclusion was 1 January 1996 or HIV diagnosis, which ever came last. Methods Data on employment status and disability pension were extracted from Danish national registries. Employment rate and DRR were estimated in each calendar year after study inclusion for the cohorts included before 1996 (pre-1996), 1996-1999 and 2000-2011. Results Employment rate in the year of study inclusion increased from 54.8% [95% confidence interval (CI) 50.5-59.6] in the pre-1996 cohort to 74.6% (66.9-83.2) and 77.4% (72.8-82.2) in the 1996-1999 and 2000-2011 cohorts, respectively, compared with 85.9-87.2% in the comparison cohorts. Five years from study inclusion, employment rates were 56.1 (51.4-61.1), 66.2 (58.7-74.6) and 70.9% (65.0-77.3) in the pre-1996, 1996-1999 and 2000-2011 cohorts, respectively, compared with 82.5-85.6% in the comparison cohorts. Five years from study inclusion, DRRs were 32.3 (28.9-36.3) in the pre-1996 cohort and decreased to 17.8 (14.1-22.4) and 11.6% (9.4-14.4) in the 1996-1999 and 2000-2011 cohorts, respectively, compared with 5.1-7.2% in the comparison cohorts. Conclusion After the introduction of HAART, employment rates have increased profoundly among HIV-infected individuals, but have remained lower than in the background population. During the same period, DRRs decreased among HIV-infected individuals, but still remained higher than in the background population.

The protozoan parasite Toxoplasma gondii causes severe opportunistic infections. Here, we report an unexpected diagnosis of cerebral toxoplasmosis. T. gondii was diagnosed by 16S and D2 large-subunit (LSU) ribosomal DNA (rDNA) sequencing of a cerebral biopsy specimen and confirmed by T. gondii -specific PCR and immunohistochemistry. The patient was later diagnosed with HIV/AIDS.

Summary Objectives To determine the long-term mortality, the causes of death and the incidence of cancer in listeria meningitis patients. Methods Nationwide, population-based cohort study including all adult patients diagnosed with listeria meningitis from 1977 to 2006 and alive 1 year after diagnosis, and an age-and gender-matched, population control cohort. Kaplan–Meier tables, Cox regression analysis and cumulative incidence function were used as outcome analyses. Results We identified 114 listeria meningitis patients and 1026 population controls. The adjusted mortality rate ratio (MRR) for listeria meningitis patients the first 5 years of follow-up was 2.35(95% confidence interval (CI) 1.60–3.45) thereafter the MRR was 0.93(95% CI: 0.56–1.55). Listeria meningitis patients had an increased risk of death due to cancer the first 5 years of follow-up, and in the same period patients above 50 years of age had a 2-fold increased risk of being diagnosed with cancer, thereafter the risks declined to that of the background population. Conclusions The long-term mortality in adult patients diagnosed with listeria meningitis was increased the first 5 years of follow-up, mainly due to death from cancer, thereafter the mortality did not differ from the background population. To improve survival this patient population should be meticulously screened for predisposing conditions, mainly underlying malignant diseases.

BACKGROUND: The long-term mortality in children diagnosed with Haemophilus influenzae meningitis is poorly documented. METHODS: We performed a nationwide, population-based cohort study including all Danish children diagnosed at the age between 0 and

We determined the incidence of hepatitis C virus among Danish human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) and described their characteristics. We included 871 HIV-positive MSM seen from 1 January 2006 to 31 December 2009 at Rigshospitalet in Copenhagen; drug users were excluded. We found 13 incident infections, i.e. a yearly incidence of 0.4%.

Udgivelsesdato: 2010-Dec Abstract The objective of this study was to determine the effect of highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV)-infected patients infected through injecting drug use (injecting drug users, IDUs) compared to patients infected via other routes (non-IDUs). We conducted a nationwide population-based cohort study of all HIV-infected patients who initiated HAART during the study period of 1 January 1995 to 31 December 2007. We compared changes in CD4(+) cell counts, percentage of full viral suppression (

The objective of the study was to determine the long-term mortality and the causes of death in patients diagnosed with pneumococcal meningitis. The authors performed a nationwide, population-based cohort study including all Danish patients diagnosed with pneumococcal meningitis from 1977 through 2006 and alive 1 year after diagnosis. Data were retrieved from medical databases in Denmark. The absolute and relative risks of all-cause and cause-specific death were analyzed by using Kaplan-Meier survival curves, Poisson regression analysis, Cox regression analysis, and cumulative incidence functions. The authors identified 2,131 pneumococcal meningitis patients and an age- and gender-matched, population-based cohort of 8,524 individuals. Compared with the background population, the pneumococcal meningitis patients had an increased long-term mortality varying from an 8-fold increased mortality in the age category 0

To estimate annual employment rates and disability retirement rates (DRRs) among HIV-infected individuals and population controls during the period 1996-2011.A population-based cohort study including all HIV-infected individuals born in Denmark and not reporting intravenous (i.v.) drug abuse as a route of HIV infection or diagnosed with hepatitis C infection (n = 2799) and 22,369 individually matched persons from the background population. Study inclusion was 1 January 1996 or HIV diagnosis, which ever came last.Data on employment status and disability pension were extracted from Danish national registries. Employment rate and DRR were estimated in each calendar year after study inclusion for the cohorts included before 1996 (pre-1996), 1996-1999 and 2000-2011.Employment rate in the year of study inclusion increased from 54.8% [95% confidence interval (CI) 50.5-59.6] in the pre-1996 cohort to 74.6% (66.9-83.2) and 77.4% (72.8-82.2) in the 1996-1999 and 2000-2011 cohorts, respectively, compared with 85.9-87.2% in the comparison cohorts. Five years from study inclusion, employment rates were 56.1 (51.4-61.1), 66.2 (58.7-74.6) and 70.9% (65.0-77.3) in the pre-1996, 1996-1999 and 2000-2011 cohorts, respectively, compared with 82.5-85.6% in the comparison cohorts. Five years from study inclusion, DRRs were 32.3 (28.9-36.3) in the pre-1996 cohort and decreased to 17.8 (14.1-22.4) and 11.6% (9.4-14.4) in the 1996-1999 and 2000-2011 cohorts, respectively, compared with 5.1-7.2% in the comparison cohorts.After the introduction of HAART, employment rates have increased profoundly among HIV-infected individuals, but have remained lower than in the background population. During the same period, DRRs decreased among HIV-infected individuals, but still remained higher than in the background population.

Importance While a high risk of nonmelanoma skin cancer is well recognized in solid-organ transplant recipients, the risk of skin cancer in hematopoietic stem-cell transplant (HSCT) recipients has not been extensively studied. Objective To determine the risk of cutaneous cancer in HSCT recipients and compare it with the risk in renal transplant recipients (RTRs) and individuals who have not received any transplant. Design, Setting, and Participants A nationwide population-based cohort study from the Danish National Hospital Register including 3302 patients who underwent HSCT (1007 allogeneic, 2295 autologous) from 1999 through 2014, 4789 RTRs from 1976 through 2014, and 10 age- and sex-matched nontransplanted individuals for each of the groups from the background population. Person-years at risk were calculated from the time of study inclusion until first cutaneous cancer. To compare the risk of skin cancer between transplant recipients and background population, we used a stratified proportional hazard regression model for hazard ratio (HR) estimations. By use of the cumulative incidence, we estimated 5- and 10-year risks of skin cancers. All RTR and HSCT recipients were treated and followed up in specialized hospital departments in Denmark (total population 5.7 million). Main Outcomes and Measures Primary outcomes were time to first appearance of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), or malignant melanoma (MM) and comparative risk estimates of cutaneous cancers in HSCT recipients and RTRs. The hypothesis was tested during data collection. Results Allogeneic HSCT recipients had an increased risk of BCC, SCC, and MM, with respective HRs of 3.1 (95% CI, 1.9-5.2), 18.3 (95% CI, 4.1-81.8), and 5.5 (95% CI, 1.7-17.7) compared with the background population. Compared with RTRs, allogeneic HSCT recipients had a 3-fold higher risk of MM. The risk of BCC after allogeneic HSCT was seen only in patients conditioned with total-body irradiation (HR, 3.9 [95% CI, 2.6-6.8]). The risk of BCC was similar for allogeneic HSCT recipients and RTRs, while the risk of SCC was highest for RTRs. Autologous HSCT recipients had no increased risk of skin cancer. Conclusions and Relevance Allogeneic HSCT recipients have an increased risk of BCC, SCC, and MM. Total-body irradiation was a major determinant for BCC. Our findings indicate the relevance of dermatologic follow-up in HSCT recipients.

Background A national survey for chronic hepatitis C has not been performed in Denmark and the prevalence is unknown. Our aim was to estimate the prevalence of chronic hepatitis C from public registers and the proportion of these patients who received specialized healthcare. Methods Patients with a diagnosis of chronic hepatitis C were identified from four national registers: a laboratory register, the Hospital Discharge Register, a clinical database of chronic viral hepatitis and the Register of Communicable Diseases. The total population diagnosed with hepatitis C was estimated by capture-recapture analysis. The population with undiagnosed hepatitis C was derived from the national register of drug users by comparing diagnosed and tested persons. Results A total of 6,935 patients diagnosed with chronic hepatitis C were identified in the four registers and the estimated population diagnosed with the disease was 9,166 persons (95% C.I. interval 8,973 – 9,877), corresponding to 0.21% (95% CI 0.21%-0.23%) of the Danish population over 15years of age. The prevalence was highest among persons 40–49years old (0.39%) and males (0.28%). It was estimated that 40% of the diagnosed patients lived in the capital region, and 33.5% had attended specialised healthcare. It was estimated that 46% of hepatitis C patients had not been diagnosed and the total population with chronic hepatitis C in Denmark was 16,888 (95% C.I. 16,474-18,287), corresponding to 0.38% (95% CI 0.37-0.42) of the population over 15years of age. Conclusions The estimated prevalence of chronic hepatitis C in Denmark was 0.38%. Less than half of the patients with chronic hepatitis C in Denmark have been identified and among these patients, one in three has attended specialised care.

Objective The risk of neurocognitive disorders in human immunodeficiency virus (HIV)-infected patients in the era of highly active antiretroviral therapy (HAART) is controversial. We aimed to compare the incidence and impact on mortality of severe neurocognitive disorders (SNCDs) in HIV-infected patients with that of the background population. Methods The method used was a nationwide, population-based cohort study using Danish registries. We calculated incidence rates, incidence rate ratios, mortality rate ratios, and Kaplan-Meier tables to estimate the incidence of and survival after SNCD in HIV-infected patients, compared with a general population control cohort matched by age and sex. Results We observed 32 cases of SNCDs among 4452 HIV-infected patients and 120 cases of SNCDs among 62 328 population control subjects. The overall risk of SNCD among HIV-infected patients was 1.0 case per 1000 person-years (PYR), compared with 0.23 cases per 1000 PYR for population control subjects but became 0.35 cases/1000 PYR after 2004, compared with 0.27 cases/1000 PYR in population control subjects. The absence of HAART and a low CD4 lymphocyte count increased the risk of SNCD. The mortality among HIV-infected patients with SNCD was higher than that among population controls with SNCD (median survival, 4.3 years vs 9.7 years [P = .02]). Conclusion HIV-infected patients have an increased risk of SNCD, but the risk is low and has, in recent years, become comparable to that seen in the background population. In contrast, the mortality remains high among HIV-infected patients diagnosed with SNCD.

Hepatitis C virus (HCV)-infection can cause hepatocellular carcinoma (HCC) and most likely non-Hodgkin lymphoma (NHL). No studies have compared the risk of these cancers between patients with chronic and cleared HCV-infection. The aim of this study was to estimate the 10-year risk of HCC and NHL in HCV-infected patients and to compare the risk of these cancers between HCV-infected patients and the general population in Denmark and between patients with chronic and cleared HCV-infection. Nationwide cohorts were used: 11,975 HCV-infected patients in the DANVIR cohort and 71,850 individuals from an age- and gender-matched general population cohort. Within DANVIR, 4,158 patients with chronic HCV-infection and 2,427 patients with cleared HCV-infection were studied. The 10-year risks of HCC and NHL in HCV-infected patients were 1.0% (95% confidence interval (CI): 0.8 - 1.3%) and 0.1% (95% CI: 0.1 - 0.2%), respectively. Compared to the general population, HCV-infected patients had a 62.91 -fold increased risk of HCC (95% CI: 28.99 - 136.52), a 29.97 -fold increased risk of NHL during the first year of follow-up (95% CI: 6.08 - 147.84), and a 1.26-fold increased risk of NHL after the first year (95% CI: 0.36 - 4.41). Chronic HCV-infection was associated with a 4.71-fold increased risk of HCC (95% CI: 1.67 - 13.32) compared to cleared HCV-infection; 5 and 0 events of NHL occurred in patients with chronic and cleared HCV-infection, respectively. HCC-risk is increased substantially in HCV-infected patients compared to the general population. Chronic as opposed to cleared HCV-infection increases the risk of HCC and perhaps NHL.

Background Previous studies have indicated an increased risk of myocardial infarction (MI) in HIV infected individuals especially after start of highly active antiretroviral therapy (HAART). It is however controversial whether the increased risk of atherosclerotic disease is exclusively associated with the HIV disease and HAART or whether life-style related or genetic factors also increase the risk in this population. To establish whether the increased risk of myocardial infarction in HIV patients partly reflects an increased risk of MI in their families, we estimated the relative risk of MI in parents of HIV-infected individuals. Methods From the Danish HIV Cohort Study and the Danish Civil Registration System we identified the parents of all HIV-infected patients born in Denmark after 1952 in whom a Danish born mother was identifiable. For each HIV patient, 4 matched population controls and their parents were identified. Cumulative incidence functions were constructed to illustrate time to first MI of the parents as registered in the Danish National Hospital Registry. Incidence rate ratios (IRR) were estimated by Cox's regression analyses. Due to the confidential type of the analysed data the study was approved by the Danish Data Protection Agency. Results 2,269 mothers and 2,022 fathers of HIV patients as well as 9,076 mothers and 8,460 fathers of control subjects were identified. We observed an increased risk of MI in mothers of HIV patients (adjusted IRR, 1.31; 95% CI: 1.08-1.60). The strongest association was seen in case the offspring was infected heterosexually (adjusted IRR, 1.59; 95% CI: 1.07-2.35) or by IV drug abuse (IVD) (adjusted IRR, 1.63; 95% CI: 1.02-2.60). In fathers of HIV patients the risk of MI was only increased if the offspring was infected by IVD (adjusted IRR, 1.42; 95% CI: 1.01-2.00). Conclusion Mothers of HIV-infected patients have an increased risk of MI. We presume that this stems from family related life style risk factors, some of which may also influence the risk of MI in HIV-infected patients.

BACKGROUND & AIMS:: The long-term mortality of patients infected with hepatitis C virus (HCV) is not known; few studies have controlled for potential confounders, investigated how mortality changes with age at diagnosis and length of follow-up evaluation, provided absolute risk estimates of death, or analyzed specific causes of death. METHODS:: By using a Danish population, we compared mortality of a cohort of 10,991 HCV-infected patients with that of an age- and sex-matched cohort. By using regression analysis, we adjusted for municipality of residence, history of psychiatric illness, comorbidities, alcohol and drug abuse, and income. We analyzed causes of death and effects of HCV with age and length of follow-up evaluation. RESULTS:: HCV-infected patients had lower income levels and more comorbidities, psychiatric illnesses, and substance and alcohol abuse than the comparison cohort. The 10-year survival rate decreased from 84.1% among HCV-infected patients aged 20 to 29 years to 21.1% among those age 70 years or older. The increased risk of death among HCV-infected patients was more pronounced in the first year of follow-up evaluation than in subsequent years and in the unadjusted than in the adjusted analysis. Starting in the second year of follow-up evaluation, HCV-infected patients aged 20 to 29 years had an 18.2-fold increased risk of death, whereas those that were 70 years or older had a 1.6-fold increased risk. Most deaths among younger patients were from unnatural causes and most deaths among patients 70 years or older were from non-liver-related natural causes. CONCLUSIONS:: HCV infection is associated with increased mortality; younger patients (age, 20-29 y) have an increased risk of unnatural death.

Objectives To estimate the impact of injecting drug use (IDU) on mortality in HIV-infected patients in the highly active antiretroviral therapy (HAART) era. Design Population-based, nation-wide prospective cohort study in Denmark (the Danish HIV Cohort Study). Methods A total of 4578 HIV-infected patients were followed from 1 January 1997 or date of HIV diagnosis. We calculated mortality rates stratified on IDU. One-, 5- and 10-year survival probabilities were estimated by Kaplan–Meier methods, and Cox regression analyses were used to estimate mortality rate ratios (MRR). Results Of the patients, 484 (10.6%) were categorized as IDUs and 4094 (89.4%) as non-IDUs. IDUs were more likely to be women, Caucasian, hepatitis C virus (HCV) co-infected and younger at baseline; 753 patients died during observation (206 IDUs and 547 non-IDUs). The estimated 10-year survival probabilities were 53.2% [95% confidence interval (CI): 48.1–58.3] in the IDU group and 82.1% (95% CI: 80.7–83.6) in the non-IDU group. IDU as route of HIV infection more than tripled the mortality in HIV-infected patients (MRR: 3.2; 95% CI: 2.7–3.8). Adjusting for potential confounders did not change this estimate substantially. The risk of HIV-related death was not increased in IDUs compared to non-IDUs (MRR 1.1; 95% CI 0.7–1.7). Conclusions Although Denmark's health care system is tax paid and antiretroviral therapy is provided free of charge, HIV-infected IDUs still suffer from substantially increased mortality in the HAART era. The increased risk of death seems to be non-HIV-related and is due probably to the well-known risk factors associated with intravenous drug abuse.

Udgivelsesdato: 2010-Mar-29 BACKGROUND & AIMS: It is unknown whether mortality differs between patients with chronic hepatitis C virus (HCV) replication and those who cleared the virus after infection. We examined the impact of chronic HCV replication on mortality among Danish patients testing positive for HCV antibodies. METHODS: This nationwide cohort study focused on Danish patients with at least one HCV RNA measurement available after testing positive for HCV antibodies between 1996 and 2005. To capture long-term prognosis, eligible patients needed to be alive 1year after HCV RNA assessment. We estimated mortality rate ratios (MRRs) using Cox regression (for overall mortality) and subdistribution hazard ratios (SDHRs) for cause-specific mortality, controlling for gender, age, comorbidity, calendar period, alcohol abuse, injection drug use and income. RESULTS: Of the 6292 patients under study, 63% had chronic HCV-infection and 37% had cleared the virus. Five-year survival was 86% (95% confidence interval (CI): 84-87%) in the chronic HCV group and 92% (95% CI: 91-94%) in the cleared HCV group. Chronic HCV-infection was associated with higher overall mortality (MRR: 1.55, 95% CI: 1.28-1.86) and liver-related death (SDHR: 2.42, 95% CI: 1.51-3.88). Chronic HCV-infection greatly increased the risk of death from primary liver cancer (SDHR: 16.47, 95% CI: 2.24-121.00). CONCLUSIONS: Patients with chronic HCV-infection are at higher risk of death than patients who cleared the infection. The substantial association found between chronic HCV-infection and death from primary liver cancer supports early initiation of antiviral treatment in chronically HCV-infected patients.

Background Hospital-based discharge registries are used increasingly for longitudinal epidemiological studies of HIV. We examined completeness of registration of HIV infections and of chronic hepatitis B (HBV) and hepatitis C (HCV) coinfections in the Danish National Hospital Registry (DNHR) covering all Danish hospitals. Methods The Danish HIV Cohort Study (DHCS) encompasses all HIV-infected patients treated in Danish HIV clinics since 1 January 1995. All 2,033 Danish patients in DHCS diagnosed with HIV-1 during the 10-year period from 1 January 1995 to 31 December 2004 were included in the current analysis. We used the DHCS as a reference to examine the completeness of HIV and of HBV and HCV coinfections recorded in DNHR. Cox regression analysis was used to estimate hazard ratios of time to diagnosis of HIV in DNHR compared to DHCS. Results Of the 2,033 HIV patients in DHCS, a total of 2,006 (99%) were registered with HIV in DNHR. Of these, 1,888 (93%) were registered in DNHR within one year of their first positive HIV test. A CD4 < 200 cells/μl, a viral load >= 100,000 copies/ml and being diagnosed after 1 January 2000, were associated with earlier registration in DNHR, both in crude and adjusted analyses. Thirty (23%) HIV patients registered with chronic HBV (n = 129) in DHCS and 126 (48%) of HIV patients with HCV (n = 264) in DHCS were registered with these diagnoses in the DNHR. Further 17 and 8 patients were registered with HBV and HCV respectively in DNHR, but not in DHCS. The positive predictive values of being registered with HBV and HCV in DHCS were thereby estimated to 0.88 and 0.97 and in DNHR to 0.32 and 0.54. Conclusion The study demonstrates that secondary data from national hospital databases may be reliable for identification of patients diagnosed with HIV infection. However, the predictive value of co-morbidity data may be low.

Background The impact of chronic hepatitis B virus (HBV) infection on viral suppression, immune recovery and mortality in HIV-1 infected patients on highly active antiretroviral treatment (HAART) is a matter of debate. The impact of HBeAg status is unknown. Methods This prospective cohort study included all adult Danish HIV-1 infected patients who started HAART between 1 January 1995 and 1 December 2006 (3180 patients). Patients were classified as chronic HBV-infected (6%), HBV-negative (87%) or HBV-unknown (7%). HBV-positive patients were divided into HBeAg-positive or -negative (3.0 vs. 2.6%). Study endpoints were viral load, CD4 cell count and mortality. Results HBV co-infection had no impact on response to HAART regarding viral suppression or immune recovery. HBV co-infection was associated with several outcomes: overall mortality [mortality rate ratio (MRR) 1.5; 95% confidence interval (CI) 1.1–2.1], liver-related mortality (MRR 4.0; 95% CI 1.6–9.9) and AIDS-related deaths (MRR 1.7; 95% CI 1.0–3.0). The presence of HBeAg did not influence patients' response to HAART. Conclusions In HIV patients, chronic HBV infection has no impact on response to HAART concerning viral load and increase in CD4 cell count. However, co-infected patients have an increased mortality compared to HIV-monoinfected patients.

Herpes simplex virus type 2 (HSV-2) infections of the central nervous system (CNS) are rare with meningitis as the most common clinical presentation. We have investigated the clinical spectrum of CNS infections in 49 adult consecutive patients with HSV-2 genome in the cerebrospinal fluid (CSF). HSV-2 in the CSF was determined by polymerase chain reaction (PCR), and patients were diagnosed as encephalitis or meningitis according to predefined clinical criteria by retrospective data information from consecutive clinical journals. The annual crude incidence rate of HSV-2 CNS disease was 0.26 per 100,000. 43 (88%) had meningitis of whom 8 (19%) had recurring lymphocytic meningitis. Six patients (12%) had encephalitis. 11 of 49 patients (22%) had sequelae recorded during follow-up. None died as a result of HSV-2 CNS disease. Thus, the clinical presentation of HSV-2 infection of the CNS is mainly meningitis but encephalitis does occur and neurological sequelae are common. Recurring lymphocytic meningitis is associated with reactivation of HSV-2 and the condition might be underdiagnosed. Udgivelsesdato: 2008-null

The DHCS is a cohort of all HIV-infected individuals seen in one of the eight Danish HIV centres after 31 December 1994. Here we update the 2009 cohort profile emphasizing the development of the cohort. Every 12-24 months, DHCS is linked with the Danish Civil Registration System (CRS) in order to extract an age- and sex-matched comparison cohort from the general population, as well as cohorts of family members of the HIV-infected patients and of the comparison cohort. The combined cohort is linked with CRS, the Danish Cancer Registry, the Danish National Hospital Registry, the Danish Registry of Causes of Death, the Danish National Prescription Registry, the Attainment Register and the Integrated Database for Labour Market Research to get information on vital status, migration, cancer, hospital contacts, causes of death, dispensed prescriptions, education and employment. Using this design, rates of a range of outcomes have been compared between HIV-infected patients and the comparison cohort, as well as between families of these two cohorts in order to disaggregate the effects of HIV infection and familial/environmental factors. Data can be shared with foreign institutions following approval from the Danish Data Protection Agency. Potential collaborators can contact the study director, Niels Obel (e-mail: niels.obel@regionh.dk).

Importance To our knowledge, no previous study has examined functioning in adult life among persons who had bacterial meningitis in childhood. Objective To study educational achievement and economic self-sufficiency in adults diagnosed as having bacterial meningitis in childhood. Design, Setting, and Participants Nationwide population-based cohort study using national registries of Danish-born children diagnosed as having meningococcal, pneumococcal, or Haemophilus influenzae meningitis in the period 1977-2007 (n=2784 patients). Comparison cohorts from the same population individually matched on age and sex were identified, as were siblings of all study participants. End of study period was 2010. Main Outcomes and Measures Cumulative incidences of completed vocational education, high school education, higher education, time to first full year of economic self-sufficiency, and receipt of disability pension and differences in these outcomes at age 35 years among meningitis patients, comparison cohorts, and siblings. Results By age 35 years, among persons who had a history of childhood meningococcal (n=1338), pneumococcal (n=455), and H influenzae (n=991) meningitis, an estimated 11.0% (41.5% vs 52.5%; 95% CI, 7.3%-14.7%), 10.2% (42.6% vs 52.8%; 95% CI, 3.8%-16.6%), and 5.5% (47.7% vs 53.2%; 95% CI, 1.9%-9.1%) fewer persons, respectively, had completed high school and 7.9% (29.3% vs 37.2%; 95% CI, 1.6%-14.2%), 8.9% (28.1% vs 37.0%; 95% CI, 0.6%-17.2%), and 6.5% (33.5% vs 40.0%; 95% CI, 1.4%-11.6%) fewer had attained a higher education compared with individuals from the comparison cohort. Siblings of meningococcal meningitis patients also had lower educational achievements, while educational achievements of siblings of pneumococcal and H influenzae meningitis patients did not differ substantially from those in the general population. At end of follow-up, 3.8% (90.3% vs 94.1%; 95% CI, 1.1%-6.5%), 10.6% (84.0% vs 94.6%; 95% CI, 5.1%-16.1%), and 4.3% (90.6% vs 94.9%; 95% CI, 2.0%-6.6%) fewer meningococcal, pneumococcal, and H influenzae meningitis patients were economically self-sufficient and 1.5% (3.7% vs 2.3%; 95% CI, −0.2% to 3.2%), 8.7% (10.0% vs 1.3%; 95% CI, 5.0%-12.4%), and 3.7% (6.2% vs 2.5%; 95% CI, 1.6%-5.8%) more received disability pension compared with individuals from the comparison cohort. Conclusions and Relevance In a Danish population, bacterial meningitis in childhood was associated with lower educational achievement and economic self-sufficiency in adult life. This association may apply particularly to pneumococcal and H influenzae meningitis, whereas for meningococcal meningitis the lower educational achievement may be family-related.

BACKGROUND: With high short-term mortality and substantial excess morbidity among survivors, tuberculous meningitis (TBM) is the most severe manifestation of extra-pulmonary tuberculosis (TB). The objective of this study was to assess the long-term mortality and causes of death in a TBM patient population compared to the background population. METHODS: A nationwide cohort study was conducted enrolling patients notified with TBM in Denmark from 1972-2008 and alive one year after TBM diagnosis. Data was extracted from national registries. From the background population we identified a control cohort of individuals matched on gender and date of birth. Kaplan-Meier survival curves and Cox regression analysis were used to estimate mortality rate ratios (MRR) and analyse causes of death. FINDINGS: A total of 55 TBM patients and 550 individuals from the background population were included in the study. Eighteen patients (32.7%) and 107 population controls (19.5%) died during the observation period. The overall MRR was 1.79 (95%CI: 1.09-2.95) for TBM patients compared to the population control cohort. TBM patients in the age group 31-60 years at time of diagnosis had the highest relative risk of death (MRR 2.68; 95%CI 1.34-5.34). The TBM patients had a higher risk of death due to infectious disease, but not from other causes of death. CONCLUSION: Adult TBM patients have an almost two-fold increased long-term mortality and the excess mortality stems from infectious disease related causes of death.

Background In contrast to the case fatality rate of patients diagnosed with meningococcal disease (MD) the long-term mortality in these patients is poorly documented. Methodology/Principal Findings We performed a nationwide, population-based cohort study including all Danish patients diagnosed with MD from 1977 through 2006 and alive one year after diagnosis. Data was retrieved from the Danish National Hospital Register, the Danish Civil Registration System and the Danish Register of Causes of Death. For each patient four age- and gender-matched individuals were identified from the population cohort. The siblings of the MD patients and of the individuals from the population cohort were identified. We constructed Kaplan-Meier survival curves and used Cox regression analysis, cumulative incidence function and subdistribution hazard regression to estimate mortality rate ratios (MRR) and analyze causes of death. We identified 4,909 MD patients, 19,636 individuals from the population cohort, 8,126 siblings of MD patients and 31,140 siblings of the individuals from the population cohort. The overall MRR for MD patients was 1.27 (95% confidence interval (CI), 1.12–1.45), adjusted MRR, 1.21 (95% CI, 1.06–1.37). MD was associated with increased risk of death due to nervous system diseases (MRR 3.57 (95% CI, 1.82–7.00). No increased mortality due to infections, neoplasms or cardiovascular diseases was observed. The MRR for siblings of MD patients compared with siblings of the individuals from the population cohort was 1.17 (95% CI, 0.92–1.48). Conclusions Patients surviving the acute phase of MD have increased long-term mortality, but the excess risk of death is small and stems mainly from nervous system diseases.