Risk of haematologic cancers among individuals tested for Borrelia burgdorferi antibodies, and Borrelia burgdorferi seropositive individuals: a nationwide population-based matched cohort study.

OBJECTIVES: In a nationwide, matched cohort study, we aimed to investigate risks of haematologic cancers among individuals tested for Borrelia burgdorferi (Bb) antibodies, and among serum Bb seropositive individuals. METHODS: We identified all Bb seropositive individuals in Denmark (1993-2020) (n = 52 200) and constructed two age- and sex-matched comparison cohorts: (a) Bb seronegative controls (n = 104 400) and (b) background population controls (n = 261 000). We calculated short-term OR (aOR) (<1 month of study inclusion), and long-term hazard ratios (aHR) (>1 month after study inclusion) adjusted for age and sex. We stratified seropositive individuals on only Bb-IgM seropositive (n = 26 103), only Bb-IgG seropositive (n = 18 698), and Bb-IgM-and-IgG seropositive (n = 7399). RESULTS: Compared with the background population, individuals tested for Bb antibodies had increased short-term (aOR: 12.6, 95% CI: 10.1-15.6) and long-term (aHR: 1.3, 95% CI: 1.2-1.4) risk of haematologic cancers. The Bb seropositive individuals had no increased risk of haematologic cancers compared with those who tested negative for Bb, except that Bb-IgM-and-IgG seropositive individuals had increased long-term risk of chronic lymphatic leukaemia (aHR: 2.0, 95% CI: 1.2-3.4). DISCUSSION: Our results suggest that Bb antibody testing is included in the work-up of unspecific symptoms preceding diagnosis of haematologic cancers. Bb-IgM-and-IgG seropositivity was associated with a two-fold increased long-term risk of chronic lymphatic leukaemia, which warrants further investigation.

Experience with sotrovimab treatment of SARS-CoV-2-infected patients in Denmark.

AIMS: To evaluate the experience with use of sotrovimab following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in high-risk groups. METHODS: In a nationwide, population-based cohort study, we identified all individuals treated with sotrovimab (N = 2933) and stratified them by 4 high-risk groups: (A) malignant haematological disease, (B) solid organ transplantation, (C) anti-CD20 therapy ≤1 year and (D) other risks. Cox regression analysis was used to calculate hazard ratios for hospitalization, death and associated prognostic factors. RESULTS: Of 2933 sotrovimab-treated individuals, 83% belonged to high-risk groups (37.6% haematological malignancy, 27.4% solid organ transplantation and 17.5% treatment with anti-CD20 ≤1 year). Only 17.8% had other risks (11.8% were pregnant, 10.7% primary immunodeficiency, 21.2% other malignancy, 4.3% received anti-CD20 >1 year and 52.0% other/unknown causes). Within 90 days of infusion, 30.2% were hospitalized and 5.3% died. The main prognostic factors were the predefined high-risk groups, mainly malignant haematological disease and age ≥65 years. Number of COVID-19 vaccines (≥3) was associated with a decreased risk of hospitalization. The Delta but not the Omicron BA.2 variant was associated with a higher risk of death compared to the BA.1 variant. CONCLUSION: More than 90% of the patients treated with sotrovimab belonged to the very high-risk groups as described in the Danish guidelines. Sotrovimab-treated individuals remained at a high risk of hospitalization and death which was strongly associated with the underlying immunocompromised state and age. Having received >3 COVID-19 vaccines was association with decreased risk of death and hospitalization.

Brain Abscess and Risk of Cancer: A Nationwide Population-Based Cohort Study.

BACKGROUND AND OBJECTIVES: Underlying occult cancer could potentially explain some of the observed increased long-term mortality among patients with brain abscess. METHODS: Nationwide, population-based health care registries were used to examine long-term risks of cancer in patients with brain abscess from 1982 to 2016 compared with a population comparison cohort individually matched (10:1) on age, sex, and residence. Cumulative incidences and adjusted cause-specific hazard rate ratios (HRRs) with 95% CIs for cancer were computed. Potential confounding by family-related factors was explored by comparing cumulative incidences of cancer among siblings of both groups. RESULTS: Among 1,384 patients with brain abscess (37% female, median age 50 years, interquartile ranges [IQR] 33-63), cancer was observed in 218 (16%) compared with 1,657 of 13,838 (12%) in the comparison cohort yielding an adj. HRR of 2.09 (95% CI 1.79-2.45). The median time to diagnosis of cancer was 1.8 years (IQR 0.02-9.1) in patients with brain abscess and 8.6 years (IQR 3.9-15.9) in comparison cohort. Among patients with brain abscess, CNS and eye cancer was diagnosed in 59 (4.3%), of which 47 of 59 (80%) occurred within 90 days of the admission date, metastasizing cancer in 54 (3.9%), respiratory tract cancer in 48 (3.5%), and gastrointestinal cancer in 36 (2.6%). Results remained consistent in almost all subgroups and in sensitivity analyses. Accounting for competing risk of death, the 1-, 5-, 10-, and 35-year cumulative incidence of cancer was 7% (95% CI 6-8), 11% (95% CI 9-12), 13% (95% CI 11-15), and 24% (95% CI 20-27) in patients with brain abscess compared with 0.7% (95% CI 0.6-0.9), 4% (95% CI 4-5), 8% (95% CI 8-9), and 25% (95% CI 23-27) in the comparison cohort, respectively. The cumulative incidences of cancer among siblings of patients with brain abscess were 10% and 12% among siblings of the comparison cohort. DISCUSSION: Brain abscess was associated with substantially increased risk of cancer during the first 10 years after diagnosis.

Improved Survival Among Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) Treated With Remdesivir and Dexamethasone. A Nationwide Population-Based Cohort Study.

BACKGROUND: There are limited data on outcomes of moderate to severe coronavirus disease 2019 (COVID-19) among patients treated with remdesivir and dexamethasone in a real-world setting. We sought to compare the effectiveness of standard of care (SOC) alone versus SOC plus remdesivir and dexamethasone. METHODS: Two population-based nationwide cohorts of individuals hospitalized with COVID-19 during February through December 2020 were studied. Death within 30 days and need of mechanical ventilation (MV) were compared by inverse probability of treatment weighted (ITPW) logistic regression analysis and shown as odds ratio (OR) with 95% confidence interval (CI). RESULTS: The 30-days mortality rate of 1694 individuals treated with remdesivir and dexamethasone in addition to SOC was 12.6% compared to 19.7% for 1053 individuals receiving SOC alone. This corresponded to a weighted OR of 30-day mortality of 0.47 (95% CI: .38-.57) for patients treated with remdesivir and dexamethasone compared to patients receiving SOC alone. Similarly, progression to MV was reduced (OR 0.36; 95% CI: .29-.46). CONCLUSIONS: Treatment of moderate to severe COVID-19 during June through December that included remdesivir and dexamethasone was associated with reduced 30-day mortality and need of MV compared to treatment in February through May.

Risk of skin cancer in patients with HIV: A Danish nationwide cohort study.

BACKGROUND: The risk of skin cancer in patients with HIV has not been extensively studied. OBJECTIVE: We sought to determine the risk of skin cancer in patients with HIV and compare it with the risk in the background population. METHODS: In a matched, nationwide, population-based cohort study, we compared the risk of skin cancer in 4280 patients with HIV from the Danish HIV cohort study with a background population cohort, according to the level of immunosuppression and route of transmission. Primary outcomes were time to first basal cell carcinoma (BCC), squamous cell carcinoma (SCC), or malignant melanoma. RESULTS: Patients with HIV had an increased risk of BCC and SCC with incident rate ratios of 1.79 (95% confidence interval 1.43-2.22) and 5.40 (95% confidence interval 3.07-9.52), respectively, compared with the background population. We observed no increased risk of malignant melanoma. Low nadir CD4 cell count was associated with an increased risk of SCC. The increased risk of BCC among patients with HIV was restricted to men who had sex with men. LIMITATIONS: This study was observational and included a small number of patients with melanoma. CONCLUSION: Patients with HIV have an increased risk of BCC and SCC. Low nadir, but not current, CD4 cell count as a marker of immunosuppression was associated with an increased risk of SCC.

Skin Cancer Risk in Hematopoietic Stem-Cell Transplant Recipients Compared With Background Population and Renal Transplant Recipients: A Population-Based Cohort Study.

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.

Cohort profile update: the Danish HIV Cohort Study (DHCS).

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).

Liver cancer and non-Hodgkin lymphoma in hepatitis C virus-infected patients: results from the DANVIR cohort study.

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.

Long-term mortality in patients diagnosed with Listeria monocytogenes meningitis: a Danish nationwide cohort study.

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.

Long-term mortality in children diagnosed with Haemophilus influenzae meningitis: a Danish nationwide cohort study.

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 <5 years with H. influenzae meningitis from 1977 through 1996 and who were alive 1 year after diagnosis. Data were retrieved from medical databases in Denmark. For each H. influenzae meningitis patient, 6 age- and gender-matched population controls were indentified. We constructed Kaplan-Meier survival curves and used Cox regression analysis to estimate mortality rate ratios (MRR) and analyze causes of death. The risk of inpatient admission and of requiring hospital outpatient services during follow-up was calculated. RESULTS: We identified 1242 H. influenzae meningitis patients and 7452 population controls, with a median follow-up time of 21.3 years. The MRR for patients with H. influenzae meningitis was 1.08 (95% confidence interval, 0.57-2.05), adjusted MRR was 0.97 (95% confidence interval, 0.50-1.89). No increased mortality due to infections, respiratory diseases, or cancer was observed. The overall risk of inpatient admission and of requiring hospital outpatient services for the H. influenzae meningitis patients was increased the first 15 years of follow-up, mainly due to the nervous system diseases and ear diseases, thereafter the risk decreased to that of the population controls. CONCLUSIONS: In a developed country, children younger than 5 years surviving the acute phase of H. influenzae meningitis have no increased long-term mortality and only moderately increased morbidity.

Hepatitis C virus infection and risk of cancer: a population-based cohort study.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with an increased risk of primary liver cancer; however, 5- and 10-year risk estimates are needed. The association of HCV with non-Hodgkin lymphoma (NHL) is uncertain and the association with other cancers is unknown. METHOD: We conducted a nationwide, population-based cohort study of 4,349 HCV-infected patients in Denmark, computing standardized incidence ratios (SIR) of cancer incidence in HCV infected patients compared with cancer incidence of the general population. We calculated 5- and 10-year risks of developing cancer, stratifying our analyses based on the presence of HIV coinfection and cirrhosis. RESULTS: WE RECORDED AN INCREASED RISK OF PRIMARY LIVER CANCER (SIR: 76.63 [95% CI: 51.69-109.40]), NHL (SIR: 1.89 [95% CI: 0.39-5.52]), and several smoking- and alcohol-related cancers in HCV infected patients without HIV coinfection. HCV-infected patients without HIV coinfection had a 6.3% (95% CI: 4.6%-8.7%) risk of developing cancer and 2.0% (95% CI: 1.1%-3.8%) risk of developing primary liver cancer within 10 years. CONCLUSION: We confirmed the association of HCV infection with primary liver cancer and NHL. We also observed an association between HCV infection and alcohol- and smoking-related cancers.

Long-term mortality in patients diagnosed with pneumococcal meningitis: a Danish nationwide cohort study.

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-<20 years to a 1.5-fold increased mortality in those aged 60-<80 years. The increased risk of death stemmed from neoplasms, liver diseases, and nervous system diseases. The excess mortality due to neoplasms stemmed mainly from a 5-fold increased risk of death due to hematologic neoplasms. To improve survival in patients surviving the acute phase of pneumococcal meningitis, physicians should meticulously screen this patient population for neurologic sequelae and comorbidity predisposing to the disease.

Mortality in patients with chronic and cleared hepatitis C viral infection: a nationwide cohort study.

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.

Long-term mortality in patients diagnosed with meningococcal disease: a Danish nationwide cohort study.

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.

Incidence, clinical presentation, and outcome of progressive multifocal leukoencephalopathy in HIV-infected patients during the highly active antiretroviral therapy era: a nationwide cohort study.

BACKGROUND: Human immunodeficiency virus (HIV) infection predisposes to progressive multifocal leukoencephalopathy (PML). Here, we describe the incidence, presentation, and prognosis of PML in HIV-1-infected patients during the period before highly active antiretroviral therapy (HAART) (1995-1996) and during the early HAART (1997-1999) and late HAART (2000-2006) periods. METHODS: Patients from a nationwide population-based cohort of adult HIV-1-infected individuals were included. We calculated incidence rates of PML and median survival times after diagnosis. We also described neurological symptoms at presentation and follow-up. RESULTS: Among 4,649 patients, we identified 47 patients with PML. The incidence rates were 3.3, 1.8, and 1.3 cases per 1000 person-years at risk in 1995-1996, 1997-1999, and 2000-2006, respectively. The risk of PML was significantly associated with low CD4(+) cell count, and 47% of cases were diagnosed by means of brain biopsy or polymerase chain reaction analysis for JC virus. The predominant neurological symptoms at presentation were coordination disturbance, cognitive defects, and limb paresis. Thirty-five patients died; the median survival time was 0.4 years (95% confidence interval [CI], 0.0-0.7) in 1995-1996 and 1.8 years (95% CI, 0.6-3.0) in both 1997-1999 and 2000-2006. CD4(+) cell count >50 cells/microL at diagnosis of PML was significantly associated with reduced mortality. CONCLUSIONS: The incidence of PML in HIV-infected patients decreased after the introduction of HAART. Survival after PML remains poor. In the management of PML, the main focus should be on prophylactic measures to avoid immunodeficiency.