Survival among people with HIV and their families in Denmark 1995-2021: a nationwide population-based cohort study.

Background: Survival among people with HIV (PWH) has vastly improved globally over the last few decades but remains lower than among the general population. We aimed to estimate time trends of survival among PWH and their families from 1995 to 2021. Methods: We conducted a registry-based, nationwide, population-based, matched cohort study. We included all Danish-born PWH from 1995 to 2021 who had been on antiretroviral therapy for 90 days, did not report intravenous drug use, and were not co-infected with hepatitis C (n = 4168). We matched population controls from the general population 10:1 to PWH by date of birth and sex (n = 41,680). For family cohorts, we identified siblings, mothers, and fathers of PWH and population controls. From Kaplan-Meier tables with age as time scale, we estimated survival from age 25. We compared PWH with population controls and families of PWH with families of population controls to calculate mortality rate ratios adjusted for sex, age, comorbidities, and education (aMRR). Findings: The median age of death among PWH increased from 27.5 years in 1995-1997 to 73.9 years (2010-2014), but thereafter survival increased only marginally. From 2015 to 2021, mortality was increased among PWH (aMRR 1.87 (95% CI: 1.65-2.11)) and siblings (aMRR: 1.25 (95% CI: 1.07-1.47)), mothers (aMRR: 1.30 (95% CI: 1.17-1.43)), and fathers (aMRR: 1.15 (95% CI: 1.03-1.29)) of PWH compared to their respective control cohorts. Mortality among siblings of PWH who reported heterosexual route of HIV transmission (aMRR: 1.51 (95% CI: 1.16-1.96)) was higher than for siblings of PWH who reported men who have sex with men as route of HIV transmission (aMRR 1.19 (95% CI: 0.98-1.46)). Interpretation: Survival among PWH improved substantially until 2010, after which it increased only marginally. This may partly be due to social and behavioural factors as PWH families also had higher mortality. Funding: Preben and Anna Simonsen's Foundation and Independent Research Fund Denmark.

Rationale and design of NUDGE-FLU-CHRONIC and NUDGE-FLU-2: Two nationwide randomized trials of electronic nudges to increase influenza vaccination among patients with chronic diseases and older adults during the 2023/2024 influenza season.

BACKGROUND: Yearly influenza vaccination is strongly recommended for older adults and patients with chronic diseases including cardiovascular disease (CVD); however, vaccination rates remain suboptimal, particularly among younger patients. Electronic letters incorporating behavioral nudges are highly scalable public health interventions which can potentially increase vaccination, but further research is needed to determine the most effective strategies and to assess effectiveness across different populations. The purpose of NUDGE-FLU-CHRONIC and NUDGE-FLU-2 are to evaluate the effectiveness of electronic nudges delivered via the Danish governmental electronic letter system in increasing influenza vaccination among patients with chronic diseases and older adults, respectively. METHODS: Both trials are designed as pragmatic randomized implementation trials enrolling all Danish citizens in their respective target groups and conducted during the 2023/2024 influenza season. NUDGE-FLU-CHRONIC enrolls patients aged 18-64 years with chronic diseases. NUDGE-FLU-2 builds upon the NUDGE-FLU trial conducted in 2022/2023 and aims to expand the evidence by testing both previously successful and new nudges among adults ≥65 years during a subsequent influenza season. Persons with exemptions from the electronic letter system are excluded from both trials. In both trials, participants are randomized in a 2.45:1:1:1:1:1:1 ratio to either receive no electronic letter (usual care) or to receive one of 6 different behaviorally informed electronic letters. NUDGE-FLU-CHRONIC has randomized 299,881 participants with intervention letters delivered on September 24, 2023, while NUDGE-FLU-2 has randomized 881,373 participants and delivered intervention letters on September 13, 2023. Follow-up is currently ongoing. In both trials, the primary endpoint is receipt of influenza vaccination on or before January 1, 2024, and the secondary endpoint is time to vaccination. Clinical outcomes including respiratory and cardiovascular hospitalizations, all-cause hospitalization, and mortality are included as prespecified exploratory endpoints. Prespecified individual-level pooled analyses will be conducted across NUDGE-FLU, NUDGE-FLU-CHRONIC, and NUDGE-FLU-2. DISCUSSION: NUDGE-FLU-CHRONIC is the first nationwide randomized trial of electronic nudges to increase influenza vaccination conducted among 18-64-year-old high-risk patients with chronic diseases. NUDGE-FLU-2 will provide further evidence on the effectiveness of electronic nudges among older adults ≥65 years. Collectively, the NUDGE-FLU trials will provide an extensive evidence base for future public health communications. TRIAL REGISTRATION: NUDGE-FLU-CHRONIC: Clinicaltrials.gov: NCT06030739, registered September 11, 2023, https://clinicaltrials.gov/study/NCT06030739. NUDGE-FLU-2: Clinicaltrials.gov: NCT06030726, registered September 11, 2023, https://clinicaltrials.gov/study/NCT06030726.

Cancer risk and temporal trends in people with HIV during a quarter of a century - a nationwide population-based matched cohort study.

BACKGROUND: It is important to understand current trends in cancer risk among people living with HIV (PLWH) to improve outcomes and to commission and delivery appropriate services. METHODS: Nationwide, population-based, matched cohort study on all adult PLWH treated at Danish HIV health care centres since 1 January 1995 and a comparison cohort, randomly selected from the background population and matched on sex and date of birth. RESULTS: We included 6327 PLWH and 63,270 individuals in the comparison cohort - 74% were men and median age was 37 (interquartile range: 30-46). For both smoking related cancers, virological cancers and other cancers, incidence was substantially higher in the first year of observation for PLWH than for the remaining observation period. The risk of smoking related cancer remained stably increased throughout the observation period, whereas the relative risk of virological cancers decreased, especially in the first year of follow up. Finally, the risk of other cancers for PLWH decreased to a level below that of the background population during the study period. CONCLUSION: The fact that the risk of other cancers was probably not higher among PLWH than in the comparison cohort is encouraging, as the excess risk of virological and smoking related cancers is potentially preventable by timely treatment of HIV and smoking cessation.

Risk of Depression in People With Human Immunodeficiency Virus: A Nationwide Population-based Matched Cohort Study.

BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with depression. However, previous studies have not addressed familial factors. METHODS: Nationwide, population-based, matched cohort study of people with HIV (PWH) in Denmark between 1995 and 2021 who were matched on sex and date of birth with a comparison cohort randomly selected from the Danish population. Family-related factors were examined by inclusion of siblings of those in the cohorts. We calculated hazard ratios (HRs) for depression, receipt of antidepressants, electroconvulsive therapy (ECT), and suicide, as well as the yearly proportions of study cohorts with psychiatric hospital contact due to depression and receipt of antidepressants from 10 years before to 10 years after study inclusion. RESULTS: We included 5943 PWH and 59 430 comparison cohort members. Median age was 38 years, and 25% were women. We observed an increased risk of depression, receipt of antidepressants, ECT, and suicide among PWH in the 2 first years of observation (HR, 3.3; 95% confidence interval [CI]: 2.5-4.4), HR, 3.0 (95% CI: 2.7-3.4), HR, 2.8 (95% CI: .9-8.6), and HR, 10.7 (95% CI: 5.2-22.2), thereafter the risk subsided but remained increased. The proportions of PWH with psychiatric hospital contact due to depression and receipt of antidepressants were increased prior to and especially after HIV diagnosis. Risk of all outcomes was substantially lower among siblings of PWH than among PWH (HR for receipt of antidepressants, 1.1; 95% CI: 1.0-1.2). CONCLUSIONS: PWH have an increased risk of depression. Family-related factors are unlikely to explain this risk.

Incidence of Childbirth, Pregnancy, Spontaneous Abortion, and Induced Abortion Among Women With Human Immunodeficiency Virus in a Nationwide Matched Cohort Study.

BACKGROUND: Reproductive health in women with human immunodeficiency virus (HIV) (WWH) has improved in recent decades. We aimed to investigate incidences of childbirth, pregnancy, spontaneous abortion, and induced abortion among WWH in a nationwide, population-based, matched cohort study. METHODS: We included all WWH aged 20-40 years treated at an HIV healthcare center in Denmark from 1995 to 2021 and a matched comparison cohort of women from the general population (WGP). We calculated incidence rates per 1000 person-years and used Poisson regression to calculate adjusted incidence rate ratios (aIRRs) of childbirth, pregnancy, spontaneous abortion, and induced abortion stratified according to calendar periods (1995-2001, 2002-2008, and 2009-2021). RESULTS: We included 1288 WWH and 12 880 WGP; 46% of WWH were of African origin, compared with 1% of WGP. Compared with WGP, WWH had a decreased incidence of childbirth (aIRR, 0.6 [95% confidence interval, .6-.7]), no difference in the incidence of pregnancy (0.9 [.8-1.0]) or spontaneous abortion (0.9 [.8-1.0]), but an increased incidence of induced abortion (1.9 [1.6-2.1]) from 1995 to 2021. The aIRRs for childbirth, pregnancy, and spontaneous abortion increased from 1995-2000 to 2009-2021, while the aIRR for induced abortion remained increased across all time periods for WWH. CONCLUSIONS: From 1995 to 2008, the incidences of childbirth, pregnancy, and spontaneous abortion were decreased among WWH compared with WGP. From 2009 to 2021, the incidence of childbirth, pregnancy, and spontaneous abortion no longer differed among WWH compared with WGP. The incidence of induced abortions remains increased compared with WGP.

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.

Outcomes following severe acute respiratory syndrome coronavirus 2 infection among individuals with and without HIV in Denmark.

OBJECTIVE: To compare the risk of a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test and coronavirus disease 2019 (COVID-19) outcomes in people with HIV (PWH) with the general population, and estimate the association with vaccination status. DESIGN: A nationwide, population based, matched cohort study. METHODS: We included all Danish PWH ≥18 years ( n  = 5276) and an age and sex-matched general population cohort ( n  = 42 308). We used Cox regression analyses to calculate (adjusted) incidence rate ratios [(a)IRR] and further stratified and restricted the analyses. RESULTS: We observed no major difference in risk of first positive SARS-CoV-2 test [aIRR: 0.8 (95% confidence interval (CI): 0.8-0.9)], but a higher risk of first hospital contact with COVID-19 and hospitalization with severe COVID-19 for PWH vs. controls [IRR: 2.0; (1.6-2.5), 1.8 (1.4-2.3)]. Risk of first hospitalization decreased substantially in PWH with calendar time [first half of year 2022 vs. 2020 IRR: 0.3; (0.2-0.6)], whereas the risk compared to population controls remained almost twofold increased. We did not observe increased risk of death after SARS-CoV-2 infection [aIRR: 0.7 (95% CI: 0.3-2.0)]. Compared to PWH who had received two vaccines PWH who receiving a third vaccine had reduced risk of first positive SARS-CoV-2 test, death (individuals ≥60years) and hospitalization [aIRR: 0.9 (0.7-1.0); 0.2 (0.1-0.7); 0.6 (0.2-1.2)]. CONCLUSION: PWH have almost the same risk of a positive SARS-CoV-2 test as the general population. Although risk of hospital contacts and severe outcomes following SARS-CoV-2 infection is increased, the risk of death does not seem to be substantially increased. Importantly, a third vaccine is associated with reduced risk of infection, and death.

Case report: Evolution of pulmonary manifestations and virological markers in critical COVID-19 infection in Bruton's agammaglobulinemia.

Despite several reports and small case series on the disease course of SARS-CoV-2 infection in patients with inborn errors of immunity (IEI), including X-linked agammaglobulinemia (XLA), this topic remains incompletely described. Here we present the case of a 38-year-old unvaccinated man with XLA, who acquired SARS-CoV-2 infection and experienced a protracted disease course with 47 days of SARS-CoV-2 positivity, critical COVID-19 with respiratory insufficiency necessitating intensive care and ventilatory support, and prompting repeated intensified treatments with remdesivir, dexamethasone, and monoclonal antibodies to eventually control infection. We describe the disease course and treatment and review the current literature on COVID-19 susceptibility and evidence for vaccine efficacy in patients with XLA.

Thromboembolic Risk in Patients With Pneumonia and New-Onset Atrial Fibrillation Not Receiving Anticoagulation Therapy.

Importance: New-onset atrial fibrillation (AF) is commonly reported in patients with severe infections. However, the absolute risk of thromboembolic events without anticoagulation remains unknown. Objective: To investigate the thromboembolic risks associated with AF in patients with pneumonia, assess the risk of recurrent AF, and examine the association of initiation of anticoagulation therapy with new-onset AF. Design, Setting, and Participants: This population-based cohort study used linked Danish nationwide registries. Participants included patients hospitalized with incident community-acquired pneumonia in Denmark from 1998 to 2018. Statistical analysis was performed from August 15, 2021, to March 12, 2022. Exposures: New-onset AF. Main Outcomes and Measures: Thromboembolic events, recurrent AF, and all-cause death. Estimated risks were calculated for thromboembolism without anticoagulation therapy, new hospital or outpatient clinic contact with AF, initiation of anticoagulation therapy, and all-cause death at 1 and 3 years of follow-up. Death was treated as a competing risk, and inverse probability of censoring weights was used to account for patient censoring if they initiated anticoagulation therapy conditioned on AF. Results: Among 274 196 patients hospitalized for community-acquired pneumonia, 6553 patients (mean age [SD], 79.1 [11.0] years; 3405 women [52.0%]) developed new-onset AF. The 1-year risk of thromboembolism was 0.8% (95% CI, 0.8%-0.8%) in patients without AF vs 2.1% (95% CI, 1.8%-2.5%) in patients with new-onset AF without anticoagulation; this risk was 1.4% (95% CI, 1.0%-2.0%) among patients with AF with intermediate stroke risk and 2.8% (95% CI, 2.3%-3.4%) in patients with AF with high stroke risk. Three-year risks were 3.5% (95% CI, 2.8%-4.3%) among patients with intermediate stroke risk and 5.3% (95% CI, 4.4%-6.5%) among patients with high stroke risk. Among patients with new-onset AF, 32.9% (95% CI, 31.8%-34.1%) had a new hospital contact with AF, and 14.0% (95% CI, 13.2%-14.9%) initiated anticoagulation therapy during the 3 years after incident AF diagnosis. At 3 years, the all-cause mortality rate was 25.7% (95% CI, 25.6%-25.9%) in patients with pneumonia without AF vs 49.8% (95% CI, 48.6%-51.1%) in patients with new-onset AF. Conclusions and Relevance: This cohort study found that new-onset AF after community-acquired pneumonia was associated with an increased risk of thromboembolism, which may warrant anticoagulation therapy. Approximately one-third of patients had a new hospital or outpatient clinic contact for AF during the 3-year follow-up, suggesting that AF triggered by acute infections is not a transient, self-terminating condition that reverses with resolution of the infection.

Risk of subarachnoid haemorrhages and aneurysms in Danish people with HIV.

OBJECTIVE: It remains unclear whether people with HIV (PWH) have increased risk of aneurysms. We aimed to investigate if the risk of subarachnoid haemorrhage, cerebral aneurysm, aortic aneurysm and other arterial aneurysms and dissections is increased in PWH compared with the general population. DESIGN: We performed a nationwide population-based matched cohort study. METHODS: We compared PWH with age-matched and sex-matched comparison cohort members to calculate incidence rate ratios (IRR) of subarachnoid haemorrhage, cerebral aneurysm, aortic aneurysm and other arterial aneurysms and dissections as well as surgery for these conditions. RESULTS: We included all PWH, who were Danish residents and treated at a HIV healthcare centre between January 1995 and February 2018 ( n  = 6935) and an age-matched and sex-matched comparison cohort ( n  = 55 480). PWH had increased risk of subarachnoid haemorrhage (IRR 1.7, 95% CI, 1.1-2.6), but no increased risk of surgery for this condition. PWH had no increased risk of cerebral aneurysm or aortic aneurysm or surgery for these conditions. The risk of other arterial aneurysms and dissections was increased in PWH (IRR 2.0, 95% CI, 1.4-2.9), but this only applied for PWH who reported intravenous substance use as a route of HIV transmission (IRR 18.4, 95% CI, 9.3-36.6), and not for PWH without reported injection drug use (IRR 1.2, 95% CI, 0.73-1.7). CONCLUSION: PWH were not at an increased risk of cerebral, aortic or other arterial aneurysms and dissections. Although PWH were at an increased risk of subarachnoid haemorrhage, subarachnoid haemorrhages were rare among PWH.

Hospital admission and mortality rates for non-covid diseases in Denmark during covid-19 pandemic: nationwide population based cohort study.

OBJECTIVE: To determine the incidence of hospital admissions and associated mortality rates for non-covid medical conditions during the covid-19 pandemic. DESIGN: Nationwide, population based cohort study. SETTING: Denmark from 13 March 2019 to 27 January 2021. PARTICIPANTS: All Danish residents >1 year of age. MAIN OUTCOMES MEASURES: Population based healthcare registries that encompass the entire Danish population were used to compare hospital admission and mortality rates during the covid-19 pandemic (from 11 March 2020 to 27 January 2021) with the prepandemic baseline data (from 13 March 2019 to 10 March 2020). Hospital admissions were categorised as covid-19 when patients were assigned a diagnosis code for covid-19 within five days of admission. All patients were followed until migration, death, or end of follow-up, whichever came first. Rate ratios for hospital admissions were computed using Poisson regression and were directly standardised using the Danish population on 1 January 2019 as reference. 30 day mortality rate ratios were examined by Cox regression, adjusted for age and sex, and covid-19 diagnosis was used as a competing risk. RESULTS: 5 753 179 residents were identified during 567.8 million person weeks of observation, with 1 113 705 hospital admissions among 675 447 people. Compared with the prepandemic baseline period (mean hospital admission rate 204.1 per 100 000/week), the overall hospital admission rate for non-covid-19 conditions decreased to 142.8 per 100 000/week (rate ratio 0.70, 95% confidence interval 0.66 to 0.74) after the first national lockdown, followed by a gradual return to baseline levels until the second national lockdown when it decreased to 158.3 per 100 000/week (0.78, 0.73 to 0.82). This pattern was mirrored for most major diagnosis groups except for non-covid-19 respiratory diseases, nervous system diseases, cancer, heart failure, sepsis, and non-covid-19 respiratory infections, which remained lower throughout the study period. Overall 30 day mortality rates were higher during the first national lockdown (mortality rate ratio 1.28, 95% confidence interval 1.23 to 1.32) and the second national lockdown (1.20, 1.16 to 1.24), and these results were similar across most major diagnosis groups. For non-covid-19 respiratory diseases, cancer, pneumonia, and sepsis, the 30 day mortality rate ratios were also higher between lockdown periods. CONCLUSIONS: Hospital admissions for all major non-covid-19 disease groups decreased during national lockdowns compared with the prepandemic baseline period. Additionally, mortality rates were higher overall and for patients admitted to hospital with conditions such as respiratory diseases, cancer, pneumonia, and sepsis. Increased attention towards management of serious non-covid-19 medical conditions is warranted.

[Diagnostic approach and evaluation of hospitalized patients with COVID-19].

COVID-19 is the infectious disease caused by coronavirus SARS-CoV-2. The most common symptoms of COVID-19 are dry cough, tiredness and fever. Most patients recover from COVID-19 within a few weeks, but some patients have symptoms lasting for weeks or even months after recovery from acute illness, such as fatigue, shortness of breath and cough. This is a review of what we currently know about the clinical disease and its severity as well as which diagnostic strategies are recommended during and after hospital admission.

[Clinical management of hospitalised patients with COVID-19].

COVID-19 is the infectious disease caused by SARS-CoV-2. This is a review of the current treatment strategies available for patients with COVID-19 during hospital admission. Patients requiring hospitalisation frequently suffer from respiratory failure and may require oxygen therapy. Insufficient response to oxygen may be an indication, that other modalities such as high-flow nasal cannula, continuous positive airway pressure or mechanical ventilation are needed. The only medical treatments currently being used are remdesivir and dexamethasone.

Venous Thromboembolism and Major Bleeding in Patients With Coronavirus Disease 2019 (COVID-19): A Nationwide, Population-Based Cohort Study.

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.

Work exposure and associated risk of hospitalisation with pneumonia and influenza: A nationwide study.

BACKGROUND: Pneumonia and influenza are major health concerns and constitute a high economic burden. However, few data are available on the associated risk of pneumonia and influenza and work exposure on a large population scale. AIM: This study aimed to examine the associated risk of pneumonia and influenza by type of work exposure. METHODS: By cross-linking administrative Danish registries, we classified people in 10 different profession types. The main outcome was hospitalisation with pneumonia or influenza. A multivariable Poisson regression analysis was used to assess the associated incidence rate ratio (IRR) of being hospitalised with pneumonia or influenza by type of profession. RESULTS: A total of 1,327,606 people added risk time to the analyses. In a multivariable model, work in day care, public transportation, sewers and nursing home care was associated with an increased risk of hospitalisation with pneumonia compared to work within public administration: IRR=1.20 (95% confidence interval (CI) 1.12-1.28), IRR=1.21 (95% CI 1.09-1.34), IRR=1.61 (95% CI 1.19-2.19) and IRR=1.10 (95% CI 1.03-1.18), respectively. In a multivariable analysis, people working within public transportation were associated with an increased risk of hospitalisation with influenza compared to people working within public administration: IRR=2.54 (95% CI 1.79-3.58). CONCLUSIONS: Working in day care, public transportation, sewers and nursing home care increased the associated risk of hospitalisation with pneumonia, and working within public transportation increased the associated risk of being hospitalised with influenza compared to working within public administration.

First Danish case of infective endocarditis caused by Enterococcus hirae.

Enterococcus hirae, a member of the Enterococcus genus, is known to cause infections, including infective endocarditis (IE), in animal species. In humans, E. hirae is an uncommon pathogen, but has been associated with severe and recurrent disease. Here, we report the first Danish case of E. hirae native aortic valve IE in a 62-year-old woman with no history of heart disease. She presented to the hospital with symptoms of gastroenteritis but no signs of heart disease. Nevertheless, blood culture revealed growth of E. hirae, and a transoesophageal echocardiography demonstrated a mobile mass adherent to the aortic valve, compatible with a vegetation. The patient was successfully treated for E. hirae native aortic valve IE with 4 weeks of intravenous benzylpenicillin in combination with gentamicin for the initial 2 weeks. To the best of our knowledge, this is the first documented case of E. hirae IE in Denmark and the sixth documented case worldwide.

Long-term Mortality and Risk of Epilepsy in Children and Young Adults With Brain Abscess.

BACKGROUND: The long-term prognosis of brain abscess is unclear. METHODS: Using nationwide, population-based medical registries, we included all individuals <20 years of age hospitalized with first-time diagnosis of brain abscess in Denmark from 1982 to 2016. A comparison cohort individually matched for age, sex and residence was identified, as were siblings of all study participants. Next, cumulative incidence curves of mortality and new-onset epilepsy were constructed, and Cox regression was used for analyses of hazard rate ratios (HRRs) with 95% confidence intervals. RESULTS: We identified 155 brain abscess patients and 1,550 population controls with median follow-up times of 15 years (interquartile range, 6-25) and 16 years (interquartile range, 11-26). Ear-nose-throat infections (22%) and congenital heart disease (13%) were the most common predisposing conditions for brain abscess. Overall mortality was 21/155 (14%) in brain abscess patients versus 20/1,550 (1%) in population controls. The corresponding HRRs were 150 (95% confidence interval: 19.8-1,116) after 1 year of observation, 24.6 (4.78-127) after 2-5 years and 0.66 (0.09-4.98) after 6-30 years. New-onset epilepsy occurred in 28% of 30-day brain abscess survivors versus 1% in population controls yielding a HRR of 29.6 (14.4-60.8) adjusted for previous head trauma, stroke and cancer. Analyses of sibling cohorts showed that family-related factors did not explain the observed increased risks of death or epilepsy among brain abscess patients. CONCLUSIONS: Brain abscess is associated with increased risk of mortality for up to 5 years. New-onset epilepsy occurred in 28% of survivors and remained a risk for several years after infection.

High risk of microscopic colitis after Campylobacter concisus infection: population-based cohort study.

OBJECTIVE: Microscopic colitis (MC) encompasses the two histopathological distinct entities of collagenous colitis (CC) and lymphocytic colitis (LC). In this Danish population-based cohort study, we examined the risk of MC following stool culture with Campylobacter concisus, C. jejuni, non-typhoidal Salmonella or a culture-negative stool test. DESIGN: We identified patients with a first-time positive stool culture with C. concisus, C. jejuni, non-typhoidal Salmonella or negative stool test, from 2009 through 2013 in North Denmark Region, Denmark, and matched each with 10 population comparisons. All subjects were followed up until 1 March 2018 using Systematised Nomenclature of Medicine codes from The Danish Pathology Register for incident diagnoses of CC and LC. We computed risk and adjusted HRs with 95% CIs for MC among patients and comparisons. RESULTS: We identified 962 patients with C. concisus, 1725 with C. jejuni, 446 with Salmonella and 11 825 patients with culture-negative stools. The MC risk and HR versus comparisons were high for patients with C. concisus (risk 6.2%, HR 32.4 (95% CI 18.9 to 55.6)), less for C. jejuni (risk 0.6%, HR 3.7 (95% CI 1.8 to 7.7)), low for Salmonella (risk 0.4%, HR 2.2 (95% CI 0.5 to 10.8)) and for patients with negative stool testing (risk 3.3%, HR 19.6 (95% CI 16.4 to 23.4)). After exclusion of the first year of follow-up, the HRs were 9.3 (95% CI 4.1 to 20.1), 2.2 (95% CI 0.9 to 5.4), 1.3 (95% CI 0.2 to 11.1) and 5.6 (95% CI 4.6 to 7.2), respectively. CONCLUSION: A high risk of MC was observed following C. concisus in stools. Further studies are needed to elucidate any underlying biological mechanisms.