High-Dose Influenza Vaccine Effectiveness against Hospitalization in Older Adults.

Background: High-dose inactivated influenza vaccine has been shown to provide protection against influenza that is superior to that with the standard dose. However, data from individually randomized trials on the effectiveness of the high-dose vaccine against severe outcomes are limited.

Methods: In this pragmatic, open-label, randomized, controlled trial conducted in Denmark during the 2022-2023, 2023-2024, and 2024-2025 influenza seasons, we assigned older adults (≥65 years of age) to receive the high dose of the inactivated influenza vaccine or the standard dose.

RSV Prefusion F Vaccine for Prevention of Hospitalization in Older Adults.

Background: Respiratory syncytial virus (RSV) can cause serious illness in older adults. The bivalent RSV prefusion F protein-based vaccine (RSVpreF) has been shown to prevent RSV-associated respiratory illness, but data from randomized trials with regard to its effect on outcomes involving hospitalization are limited.

Methods: In this pragmatic, open-label trial with individual randomization, participants who were 60 years of age or older were assigned in a 1:1 ratio to receive the RSVpreF vaccine (the RSVpreF group) or no vaccine (the control group) during the 2024-2025 winter season.

Bivalent RSV Prefusion F Protein-Based Vaccine for Preventing Cardiovascular Hospitalizations in Older Adults: A Prespecified Analysis of the DAN-RSV Trial.

Importance: Respiratory syncytial virus (RSV) infection is linked to elevated cardiovascular risk, particularly in individuals with preexisting cardiovascular disease (CVD). A bivalent RSV prefusion F protein (RSVpreF) vaccine was recently approved for preventing RSV-related lower respiratory tract illness, but its effectiveness against cardiovascular outcomes has not been evaluated in a randomized trial.

Objective: To investigate the vaccine effectiveness of RSVpreF compared with no vaccine against cardiovascular outcomes among adults aged 60 years or older.

High-Dose vs Standard-Dose Influenza Vaccine and Cardiovascular Outcomes in Older Adults: A Prespecified Secondary Analysis of the DANFLU-2 Randomized Clinical Trial.

Importance: The high-dose inactivated influenza vaccine (HD-IIV) has demonstrated superior protection against laboratory-confirmed influenza infection vs standard-dose IIV (SD-IIV); however, data regarding its effectiveness against cardiovascular (CV) outcomes are mainly from observational studies or specific high-risk groups.

Objective: To investigate the relative vaccine effectiveness (rVE) of HD-IIV vs SD-IIV against CV outcomes in the general older adult population in Denmark.

Design, Setting, And Participants: This was a prespecified secondary analysis of DANFLU-2, a pragmatic, open-label, individually randomized clinical trial (RCT) using nationwide administrative health registries in Denmark during the 2022/2023 to 2024/2025 influenza seasons.

Effectiveness of bivalent respiratory syncytial virus prefusion F protein-based vaccine in individuals with or without atherosclerotic cardiovascular disease: the DAN-RSV trial.

Background And Aims: It is not known whether the bivalent respiratory syncytial virus prefusion F protein-based (RSVpreF) vaccine reduces outcomes in individuals with atherosclerotic cardiovascular disease (ASCVD). The aim was to evaluate the vaccine effectiveness (VE) of an RSVpreF vaccine vs no vaccine on respiratory and cardiovascular outcomes in persons with or without pre-existing ASCVD.

Methods: We conducted a prespecified secondary analysis of the DAN-RSV trial.

High-dose vs. standard-dose inactivated influenza vaccine and cardiovascular outcomes in persons with or without pre-existing atherosclerotic cardiovascular disease: the DANFLU-2 trial.

Background And Aims: The aim was to evaluate and compare the relative vaccine effectiveness (rVE) of high-dose (HD-IIV) vs. standard-dose inactivated influenza vaccination (SD-IIV) on respiratory and cardiovascular outcomes in persons with or without pre-existing atherosclerotic cardiovascular disease (ASCVD).

Methods: A prespecified exploratory analysis of a pragmatic, open-label, individually randomized trial conducted in Denmark during three influenza seasons.

High-Dose vs. Standard-Dose Influenza Vaccine in Heart Failure: A Prespecified Analysis of the DANFLU-2 Trial.

Influenza contributes substantially to disease burden in individuals with heart failure (HF) and is an established trigger of cardiovascular (CV) and HF events. Standard-dose inactivated influenza vaccine (SD-IIV) is recommended for HF, though immune responses may be attenuated. High-dose IIV (HD-IIV) was developed to enhance immunogenicity, but its effectiveness compared with SD-IIV against hospitalization for influenza and CV disease by HF status remains uncertain.

Patient-reported outcomes and home-based self-swabs for influenza-like illness events - lessons learned from the 2023/2024 DANFLU-2 Homeswab PRO substudy.

Background: Self-swabs and digital patient-reported outcomes (PROs) offer innovative tools for decentralized monitoring of infectious diseases. The DANFLU-2 HomeSwab PRO substudy evaluated the feasibility of using these methods for tracking influenza-like illness (ILI) within a large-scale, pragmatic, randomized trial.

Methods: During the 2023/2024 influenza season, adults aged ≥ 65 years were recruited from the DANFLU-2 trial, which evaluates the relative effectiveness of high-dose influenza vaccine compared to standard-dose.

A pragmatic individually randomized trial to evaluate the effectiveness of high-dose vs standard-dose influenza vaccine in older adults: Rationale and design of the DANFLU-2 trial.

Background: The high-dose inactivated influenza vaccine (HD-IIV) has been shown to reduce the incidence of influenza infection compared with standard-dose inactivated influenza vaccine (SD-IIV); however, its effectiveness in preventing severe respiratory and cardiovascular outcomes in the older general population has not yet been assessed in a fully powered individually randomized trial.

Methods: DANFLU-2 is an ongoing pragmatic, registry-based, open-label, active-controlled, individually randomized trial conducted in Denmark during the 2022/2023, 2023/2024, and 2024/2025 influenza seasons. Utilizing innovative electronic recruitment strategies and an online informed consent process, the trial has enrolled 332,438 older adults ≥65 years; enrollment was completed in October 2024.

A pragmatic individually randomized trial to evaluate bivalent RSV prefusion F protein-based vaccine effectiveness for preventing RSV hospitalizations in adults aged 60 years or above (DAN-RSV): Rationale and trial design.

Background: Respiratory syncytial virus (RSV) can cause serious illness in older adults and those with chronic conditions. While the bivalent RSVpreF vaccine has been shown to protect against RSV-related respiratory tract disease, its impact on severe RSV-related and broader cardiorespiratory hospitalizations remains untested in a fully powered randomized trial. This pragmatic, individually randomized, open-label, parallel-group trial aims to evaluate RSVpreF vaccine effectiveness (VE) in reducing the risk of RSV-related and all-cause cardiorespiratory hospitalizations in adults aged 60 and older.

Hyperglycemia and insulin use in patients with COVID-19 and severe hypoxemia allocated to 12 mg vs. 6 mg of dexamethasone: a secondary analysis of the COVID STEROID 2 randomized trial.

Background: While dexamethasone has been shown to improve survival in COVID-19, its dose-response relationship with plasma glucose (PG) levels and insulin requirements is poorly understood. This study investigated the impact of 12 mg (higher dose) versus 6 mg (standard dose) of dexamethasone on hyper- or hypoglycemic events and the use of insulin.

Methods: A secondary analysis of a subpopulation of the COVID STEROID 2 trial.

Patients' experience of self-testing measuring total white cell count and C reactive protein during treatment at home with antibiotics: a qualitative study.

Objective: To explore patients' experiences and preferences of self-testing using white cell count point-of-care test (POCT) and C reactive protein POCT during antibiotic treatment at home.

Setting: A University Hospital in the Region of Zealand (DK).

Participants: 10 inpatients treated with antibiotics who were discharged from hospital to continue antibiotic treatment at home.

Non-Operative versus Neurosurgical Treatment of Brain Abscess: An Emulated Trial Nested within a Nationwide, Population-Based Cohort.

Background: Uncertainty about the role of neurosurgery in brain abscess treatment is reflected in surveys and observational studies.

Methods: Nationwide population-based cohort study of all adults (≥18 years) diagnosed with brain abscess in Denmark from 2007 until 2023. Inverse probability weighting was applied to balance covariates according to neurosurgical treatment strategy.

Lung Surfactant Deficiency in Severe Respiratory Failure: A Potential Biomarker for Clinical Assessment.

Critical lung infection affects alveolar cells and probably also their ability to perform surfactant procedures, but bedside tools for monitoring lung surfactants are lacking. In this descriptive exploratory study, we aimed to evaluate lung surfactant levels in bronchial aspirate (BA) from patients admitted to the intensive care unit due to severe respiratory failure. Bronchial aspirates were collected from nine patients (median age: 72 years, range: 52-85) who required orotracheal intubation.

Tick-borne encephalitis in adults in Denmark: a nationwide prospective cohort study from 2015 to 2023.

Background: Our aim was to characterize the clinical presentation and outcome in adults with tick-borne encephalitis (TBE) and to determine the incidence and test activity of TBE in Denmark.

Methods: A nationwide prospective cohort study of all adults hospitalized with TBE at departments of infectious diseases in Denmark from 2015 to 2023. An age- and sex-matched cohort of herpes simplex virus type 1 (HSV-1) encephalitis patients was included to compare outcome.

Electronic Nudge Letters to Increase Influenza Vaccination Uptake in Younger and Middle-Aged Individuals With Diabetes.

Background: Despite evidence demonstrating that influenza vaccination is associated with reduced risk of cardiovascular events and all-cause mortality in individuals with diabetes mellitus (DM), vaccine uptake remains suboptimal.

Objectives: The purpose of this study was to assess the effectiveness of electronically delivered nudges on influenza vaccine uptake according to the presence of DM status versus other chronic diseases.

Methods: NUDGE-FLU-CHRONIC was a nationwide, randomized, pragmatic implementation trial among younger and middle-aged (18-64 years) Danish citizens with chronic disease during the 2023/2024 influenza season.

Use of nonbarrier contraceptives among women with HIV.

Objective: The aim of this study was to investigate the use of nonbarrier contraceptives among women with HIV (WWH) compared to women from the general population (WGP) in Denmark.

Design: A nationwide, population-based, matched cohort study.

Methods: We included WWH aged 16-50 years, treated at an HIV specialized clinic, and included in The Danish HIV Cohort Study between 1995 and 2021 and an age-matched comparison cohort of WGP.

Emergence and fixation of SARS-CoV-2 minority variants in a chronically infected patient receiving therapy in Denmark.

SARS-CoV-2 variants of concern (VOC), such as Delta and Omicron have harbored mutations, which increased viral infectivity or ability to evade neutralizing antibodies. Immunocompromised patients might be a source of some of these emerging variants. In this study, we sequenced 17 consecutive samples from an immunocompromised patient with a long-term SARS-CoV-2 infection with the pre-VOC era lineage B.

Development of antibody levels and subsequent decline in individuals with vaccine induced and hybrid immunity to SARS-CoV-2.

Objectives: This study aimed to compare antibody trajectories among individuals with SARS-CoV-2 hybrid and vaccine-induced immunity.

Methods: Danish adults receiving three doses of BTN162b2 or mRNA-1237 were included prior to first vaccination (Day 0). SARS-CoV-2 anti-spike IgG levels were assessed before each vaccine dose, at Day 90, Day 180, 28 days after 3rd vaccination (Day 251), Day 365, and prior to 4th vaccination (Day 535).