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.

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.

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.

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.

Risk Factors for Brain Abscess: A Nationwide, Population-Based, Nested Case-Control Study.

BACKGROUND: Knowledge on risk factors for brain abscess is limited and relies on single-center cohort studies. METHODS: We accessed nationwide medical registries to conduct a population-based, nested case-control study of risk factors for brain abscess. We applied risk-set sampling for the selection of population controls (1:10), who were individually matched by age, sex, and area of residence. Conditional logistic regression was used to compute adjusted odds ratios (aOR) with 95% confidence intervals (CIs). Population-attributable fractions were calculated. RESULTS: We identified 1384 brain abscess patients in Denmark from 1982 through 2016, and 13 839 matched population controls. The median age of patients was 50 years (interquartile range 33-63) and 37% were female. Cases often had Charlson comorbidity scores >2 (16%), compared with controls (3%). Our calculated aORs were 2.15 (95% CI 1.72-2.70) for head trauma; 19.3 (95% CI 14.3-26.0) for neurosurgery; 4.61 (95% CI 3.39-6.26) for dental infections; 2.57 (95% CI 1.71-3.84) for dental surgery; 3.81 (95% CI 3.11-4.67) for ear, nose, and throat infection; 2.85 (95% CI 2.21-3.70) for ear, nose, and throat surgery; 15.6 (95% CI 9.57-25.4) for congenital heart disease; 1.74 (95% CI 1.33-2.29) for diabetes mellitus; 2.22 (95% CI 1.58-3.11) for alcohol abuse; 2.37 (95% CI 1.53-3.68) for liver disease; 2.04 (95% CI 1.30-3.20) for kidney disease and 8.15 (95% CI 3.59-18.5) for lung abscess or bronchiectasis. The aORs were 4.12 (95% CI 3.37-5.04) for solid cancer; 8.77 (95% CI 5.66-13.6) for hematological cancer; 12.0 (95% CI 6.13-23.7) for human immunodeficiency virus; and 5.71 (95% CI 4.22-7.75) for immunomodulating treatments. Population-attributable fractions showed were substantial contributors to the occurrence of brain abscess neurosurgery (12%); solid cancer (11%); ear, nose, and throat infections (7%); and immunomodulating treatments (5%). CONCLUSIONS: Important risk factors included neurosurgery; cancer; ear, nose, and throat infections; and immunomodulating treatments.

Long-term Mortality and Epilepsy in Patients After Brain Abscess: A Nationwide Population-Based Matched Cohort Study.

BACKGROUND: We aimed to determine the long-term risks of mortality and new-onset epilepsy after brain abscess. METHODS: Using nationwide population-based medical registries, we examined all patients with first-time brain abscess in Denmark, 1982-2016. Comparison cohorts individually matched on age, sex, and residence were identified, as were siblings of all study participants. Next, we computed cumulative incidences and hazard rate ratios (HRRs) with 95% confidence intervals of mortality and new-onset epilepsy among study populations. RESULTS: We identified 1384 brain abscess patients (37% females) with a median follow-up time of 5.9 years (interquartile range [IQR] 1.1-14.2). The 1-year, 2-5 year, and 6-30 year mortality of patients after brain abscess was 21%, 16%, and 27% as compared to 1%, 6%, and 20% for population controls. Cox regression analyses adjusted for Charlson comorbidity index score showed 1-year, 2-5 year, and 6-30 year HRRs of 17.5 (13.9-22.0), 2.61 (2.16-3.16), and 1.94 (1.62-2.31). The mortality in brain abscess patients was significantly increased regardless of sex or age group except among subjects 80 years or older, and in both previously healthy individuals and immunocompromised persons.Among the 30-day survivors of brain abscess (median follow-up 7.6 years [IQR 2.2-15.5]), new-onset epilepsy occurred in 32% compared to 2% in matched population controls. Cause-specific Cox regression analysis adjusted for stroke, head trauma, alcohol abuse, and cancer showed 1-year, 2-5 year, and 6-30 year HRRs for new-onset epilepsy of 155 (78.8-304), 37.7 (23.0-59.9), and 8.93 (5.62-14.2). CONCLUSIONS: Brain abscess is associated with an increased long-term risk of mortality and new-onset epilepsy for several years after infection.

Risk of inflammatory bowel disease after Campylobacter jejuni and Campylobacter concisus infection: a population-based cohort study.

Objectives: In this population-based cohort study, we aimed to examine the risk of IBD following a positive stool culture with Campylobacter jejuni or Campylobacter concisus, as well as following culture-negative stool testing. Materials and methods: Patients with a first-time positive stool culture with C. jejuni or C. concisus, as well as negative stool testing, from 2009 through 2013 in North Denmark Region, Denmark, were identified. Patients diagnosed with IBD during follow-up (to 1 March 2018) were identified using national registries. For each case, we selected ten population comparisons matched by age, gender, and calendar-time. Results: We identified 1693 patients with C. jejuni, 910 C. concisus-positive patients, and 11,383 patients with culture-negative stools. During the first year of follow-up C. jejuni-positive patients had higher risk of IBD (HR 2.2, 95% CI 1.3-3.7) compared to population comparisons, but not after exclusion of the first year (HR 1.1, 95% CI 0.5-2.3). Campylobacter concisus-positive patients and culture-negative patients had similar risk of IBD (HR 12.9, 95% CI 7.2-22.9 and HR 8.7, 95% CI 7.5-10.2), during the first year, which decreased to (HR 3.3, 95% CI 1.3-8.5 and HR 3.2, 95% CI 2.6-4.0) after exclusion of the first year. Conclusions: This study does not support exposure of C. jejuni or C. concisus infection as a causal trigger in subsequent development of IBD, since culture-negative patients had similar risk for IBD on long term follow-up. Additional studies including C. concisus exposures for an evaluation of the specific risk of IBD are needed.

Return to the workforce following infective endocarditis-A nationwide cohort study.

BACKGROUND: The ability to return to work after infective endocarditis (IE) holds important socioeconomic consequences for both patients and society, yet data on this issue are sparse. We examined return to the workforce and associated factors in IE patients of working age. METHODS: Using Danish nationwide registries, we identified 1,065 patients aged 18-60 years with a first-time diagnosis of IE (1996-2013) who were part of the workforce prior to admission and alive at discharge. RESULTS: One year after discharge, 765 (71.8%) patients had returned to the workforce, 130 (12.2%) were on paid sick leave, 76 (7.1%) received disability pension, 23 (2.2%) were on early retirement, 65 (6.1%) had died, and 6 (0.6%) had emigrated. Factors associated with return to the workforce were identified using multivariable logistic regression. Younger age (18-40 vs 56-60 years; odds ratio, 2.85; 95% CI, 1.71-4.76) and higher level of education (higher educational level vs basic school; 5.47, 2.05-14.6) and income (highest quartile vs lowest; 3.17, 1.85-5.46) were associated with return to the workforce. Longer length of hospital stay (>90 vs 14-30 days; 0.16, 0.07-0.38); stroke during IE admission (0.38, 0.21-0.71); and a history of chronic kidney disease (0.29, 0.11-0.75), chronic obstructive pulmonary disease (0.31, 0.13-0.71), and malignancy (0.39, 0.22-0.69) were associated with a lower likelihood of returning to the workforce. CONCLUSIONS: Seven of 10 patients who were part of the workforce prior to IE and alive at discharge were part of the workforce 1 year later. Younger age, higher socioeconomic status, and absence of major comorbidities were associated with return to the workforce.

Time to antibiotic therapy and outcome in bacterial meningitis: a Danish population-based cohort study.

BACKGROUND: Community-acquired bacterial meningitis (CABM) is a life-threatening disease and timing of antibiotic therapy remains crucial. We aimed to analyse the impact of antibiotic timing on the outcome of CABM in a contemporary cohort. METHODS: We conducted a population-based cohort study based on chart reviews of all adult cases (>16 years of age) of CABM in North Denmark from 1998 to 2014 excluding patients given pre-hospital parenteral antibiotics. We used modified Poisson regression analyses to compute the adjusted risk ratio (adj. RR) with 95 % confidence intervals (CIs) for in-hospital mortality and unfavourable outcome at discharge by time after arrival to hospital to adequate antibiotic therapy. RESULTS: We identified 195 adults with CABM of whom 173 patients were eligible for further analyses. The median door-to-antibiotic time was 2.0 h (interquartile range (IQR) 1.0-5.5). We observed increased adjusted risk ratios for in-hospital mortality of 1.6 (95 % CI 0.8-3.2) and an unfavourable outcome at discharge of 1.5 (95 % CI 1.0-2.2, p = 0.03) when treatment delays exceeded 6 h versus treatment within 2 h of admission. These findings corresponded to adjusted risk ratios of in-hospital mortality of 1.1 per hour of delay (95 % CI 0.8-1.5) and an unfavourable outcome at discharge of 1.1 per hour of delay (95 % CI 1.0-1.3) within the first 6 h of admission. Some patients (31 %) were diagnosed after admission and had more delays in antibiotic therapy and correspondingly increased in-hospital mortality (30 vs 14 %, p = 0.01) and unfavourable outcome (62 vs 37 %, p = 0.002). CONCLUSIONS: Delay in antibiotic therapy was associated with unfavourable outcome at discharge.

Risk for myocardial infarction and stroke after community-acquired bacteremia: a 20-year population-based cohort study.

BACKGROUND: Infections may trigger acute cardiovascular events, but the risk after community-acquired bacteremia is unknown. We assessed the risk for acute myocardial infarction and ischemic stroke within 1 year of community-acquired bacteremia. METHODS AND RESULTS: This population-based cohort study was conducted in Northern Denmark. We included 4389 hospitalized medical patients with positive blood cultures obtained on the day of admission. Patients hospitalized with bacteremia were matched with up to 10 general population controls and up to 5 acutely admitted nonbacteremic controls, matched on age, sex, and calendar time. All incident events of myocardial infarction and stroke during the following 365 days were ascertained from population-based healthcare databases. Multivariable regression analyses were used to assess relative risks with 95% confidence intervals (CIs) for myocardial infarction and stroke among bacteremia patients and their controls. The risk for myocardial infarction or stroke was greatly increased within 30 days of community-acquired bacteremia: 3.6% versus 0.2% among population controls (adjusted relative risk, 20.86; 95% CI, 15.38-28.29) and 1.7% among hospitalized controls (adjusted relative risk, 2.18; 95% CI, 1.80-2.65). The risks for myocardial infarction or stroke remained modestly increased from 31 to 180 days after bacteremia in comparison with population controls (adjusted hazard ratio, 1.64; 95% CI, 1.18-2.27), but not versus hospitalized controls (adjusted hazard ratio, 0.95; 95% CI, 0.69-1.32). No differences in cardiovascular risk were seen after >6 months. Increased 30-day risks were consistently found for a variety of etiologic agents and infectious foci. CONCLUSIONS: Community-acquired bacteremia is associated with increased short-term risk of myocardial infarction and stroke.

Dexamethasone treatment and prognostic factors in community-acquired bacterial meningitis: a Danish retrospective population-based cohort study.

INTRODUCTION: The morbidity and mortality in community-acquired bacterial meningitis (CABM) remain substantial and treatment outcomes and predictors of a poor prognosis must be assessed regularly. We aimed to describe the outcome of patients with CABM treated with dexamethasone and to assess the performance of the Dutch Meningitis Risk Score (DMRS). METHODS: We retrospectively evaluated all adults with CABM in North Denmark Region, 1998-2012. Outcomes included in-hospital mortality and Glasgow Outcome Scale (GOS) score. A GOS score of 5 was categorized as a favourable outcome and scores of 1-4 as unfavourable. We used logistic analysis to compute relative risks (RRs) with 95% confidence intervals (CIs) for an unfavourable outcome adjusted for age, sex, and comorbidity. RESULTS: We identified a total of 172 cases of CABM. In-hospital mortality was unaffected by the implementation of dexamethasone in 2003 (19% vs 20%). Dexamethasone treatment was associated with a prompt diagnosis of meningitis and a statistically insignificant decrease in the risk of an unfavourable outcome (33% vs 53%; adjusted RR 0.64, 95% CI 0.41-1.01) and in-hospital mortality (15% vs 24%; adjusted RR 0.72, 95% CI 0.35-1.48). Of the risk factors included in the DMRS, we found age and tachycardia to be significantly associated with an unfavourable outcome in the multivariate analyses. CONCLUSIONS: Patients treated with dexamethasone were more likely to have a favourable outcome, although statistical significance was not reached. Several parameters included in the Dutch risk score were also negative predictors in our cohort, although the entire risk score could not be validated due to a lack of data.

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.

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.

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.