The main aim of this study is to investigate the connection between a high workload and health-related quality of life among in-home care workers in northern Sweden during the COVID-19 pandemic. We also investigate whether social support and control at work can prevent poor health due to high workload.

A cross-sectional survey was conducted during the pandemic, with 629 (response rate 33 per cent) of an estimated 1,900 in-home care workers responding. Results were compared with a nearly identical survey conducted prior to the pandemic in which 1,154 (response rate 58 per cent) of an estimated 2000 in-home care workers responded. Psychosocial factors were measured using QPSNordic and health-related quality of life using EuroQol 5 Dimensions (EQ-5D). EQ-5D responses were translated into quality-adjusted life year (QALY) scores. Propensity scores were used with absolute risk differences.

During the pandemic, staff with high workload had a statistically significantly (6.2%) lower QALY score (confidence interval 2.2%-10.3%) compared to staff with a normal workload. This was also the case for the usual activities and the anxiety/depression dimensions of EQ-5D. These risk differences were greater, but not statistically significant, during the pandemic than before. The combination of a normal workload and a high degree of control over one's work appeared to protect against a low QALY score, while social support at work did not seem to be protective.

High workload is related to poorer health-related quality of life. This is mainly attributable to anxiety/depression. In-home care organisations need to manage workload better to prevent poor health among staff during strained situations such as a pandemic. The results of our study indicate that in-home care organisations should increase their readiness to promote opportunities for staff to maintain a high degree of control over their work, in order to counteract variations in workload that ultimately appear to have a negative impact on HRQoL.

Nirmatrelvir-ritonavir is an oral antiviral recommended for treating high-risk individuals with COVID-19 in the community. However, there remains uncertainty over its cost-effectiveness in largely vaccinated populations and subgroups defined by age and clinical risk.

To compare the cost-effectiveness of nirmatrelvir-ritonavir vs usual care based on the UK Platform Adaptative Trial of Novel Antivirals for Early Treatment of COVID-19 in the Community (PANORAMIC) trial.

This economic evaluation was a within-trial cost-utility analysis conducted using data from the PANORAMIC trial and linked routine health care data from December 8, 2021, to September 30, 2024, adopting a UK National Health Service (NHS) and personal social services perspective over 6 months. Eligible participants were community-dwelling adults aged 50 years and older or ages 18 to 49 years with comorbidities. Data were analyzed from April 20, 2022, to September 30, 2024, for the nirmatrelvir-ritonavir group and December 8, 2021, to September 30, 2026, for usual care.

Oral nirmatrelvir-ritonavir.

Cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) of nirmatrelvir-ritonavir vs usual care.

There were 1736 participants randomized to receive nirmatrelvir-ritonavir plus usual care (mean [SE] age, 54.7 [0.29] years), and 1768 to usual care alone (mean [SE] age, 54.8 [0.28] years); 2405 in the total cohort were female (69.2%]), and 3455 (98.6%) were vaccinated. Nirmatrelvir-ritonavir was cost-effective, on average, with lower total costs (£124; 95% CI, -£1207 to £1455) and higher QALYs (0.0110; 95% CI, 0.0062-0.0170) over 6 months compared with usual care (ICER, £10 897 per QALY). Nirmatrelvir-ritonavir had a 0.65 probability of being cost-effective at a £20 000 per QALY cost-effectiveness threshold, indicating decision uncertainty. The intervention remained cost-effective in most sensitivity analyses and prespecified subgroups, although several subgroup analyses were based on small sample sizes and should be interpreted as exploratory.

In this economic evaluation of nirmatrelvir-ritonavir for COVID-19, cost-effectiveness varied by age, comorbidity, and vaccination status. Subgroup findings should be interpreted with caution, but targeted prescribing for at-risk adults aged 18 to 64 years, those aged 65 to 69 years, and adults aged 75 years and above, particularly those with comorbidities and not recently vaccinated, was likely to provide the greatest health system value; cost-effectiveness was not observed in low-risk adults aged 50 to 64 years, those aged 70 to 74 years, or in unvaccinated or recently vaccinated individuals.

Seasonal influenza vaccination remains the most effective strategy for reducing influenza burden and preventing severe disease. Despite decades of vaccine development, the seasonal influenza vaccine is administered intramuscularly and provides suboptimal and highly variable effectiveness depending on host factors, pre-existing immunity, and antigenic match between vaccine and circulating strains. Recent advances in vaccine development have highlighted the potential of intranasal vaccine delivery as a strategy to increase protection against influenza virus infection by inducing local and systemic immune responses. Across multiple intranasal platforms under development, mucosal immunity, particularly secretory IgA and T- and B-cell immune responses, plays a central role in shaping protection against influenza virus infection. Live-attenuated influenza vaccines (LAIV) elicit protective immune responses, particularly in the pediatric population, and remain the only currently licensed intranasal seasonal influenza vaccine. However, variable performance in adults, strain-dependent viral fitness, and clinical contraindications have limited their broader applicability. These limitations have driven the development of next-generation intranasal influenza vaccine platforms designed to preserve the immunological advantages of mucosal vaccination while improving consistency, safety, and applicability across diverse populations. This review synthesizes current knowledge on licensed and emerging intranasal influenza vaccine platforms, including replicating viral platforms and non-replicating platforms, and discusses key immunological mechanisms, challenges, and translational progress. Together, these advances underscore the growing potential of intranasal vaccination as a next-generation strategy to improve influenza control.

Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide, and Bacillus Calmette-Guérin (BCG) offers inconsistent protection against adult pulmonary TB. We previously showed that homologous mRNA vaccination encoding the mycobacterial antigen PPE15 (mRNA.PPE15) enhanced immunogenicity but did not improve protection over BCG alone. We hypothesised that a heterologous "prime-pull" strategy, systemic mRNA priming followed by mucosal adenoviral boosting, would enrich lung-resident memory T cells (TRM) and improve efficacy.

Female C57BL/6 mice received BCG prime followed by subunit regimens combining intramuscular mRNA.PPE15 and intranasal ChAdOx1.PPE15 in different administration orders, alongside homologous controls. Cellular responses in spleen and lung were quantified by intracellular cytokine staining after PPE15 peptides stimulation. Intravascular staining was used to distinguish parenchymal (IV-) from vascular (IV+) cells and combined with tetramer staining to identify PPE15-specific CD4+ and CD8+ TRM-phenotype in the lung parenchymal following vaccination. PPE15-specific serum antibodies were measured by ELISA. Protective efficacy was assessed four weeks after aerosol Mycobacterium tuberculosis (M.tb) challenge by lung and spleen CFU enumeration.

Heterologous vaccination induced robust spleen CD4+ and CD8+ responses and PPE15-specific IgG. In the lung, mRNA.PPE15-ChAdOx1.PPE15 induced IFN-γ+ CD4+ and CD8+ T cells in the parenchyma and PPE15-specific TRM-like cells. Following M.tb challenge, both heterologous regimens reduced lung CFU compared to naïve controls, but only mRNA.PPE15-ChAdOx1.PPE15 significantly decreased CFU in both lungs and spleen. When used to boost BCG, BCG-mRNA.PPE15-ChAdOx1.PPE15 achieved 0.8 log10 CFU reductions in lungs and spleen compared to BCG control group and induced the greatest numbers of lung TRM-phenotype cells.

A heterologous prime-pull strategy that combines intramuscular mRNA.PPE15 priming with intranasal ChAdOx1.PPE15 boosting effectively directs PPE15-specific T cells to the lung parenchyma, enriches TRM-like populations, and improves protection over homologous regimens. There was a trend for the mRNA.PPE15-ChAdOx1.PPE15 regimen to outperform the reverse order, particularly as a BCG booster. These data support heterologous platform vaccination and prime-pull strategy as a novel strategy for TB vaccines and indicate potential to progress to the next stages of vaccine development.

IntroductionPersistent asystole following restoration of mechanical circulation during extracorporeal cardiopulmonary resuscitation (E-CPR) is typically considered fatal. However, in profound hypothermia, electrical silence may not reflect irreversible myocardial injury.Case ReportA term neonate with severe meconium aspiration syndrome (MAS) was initially supported on veno-arterial ECMO at a regional hospital and transported to a tertiary ECMO facility. Following decannulation, she suffered cardiac arrest. Mechanical circulation was achieved after prolonged E-CPR with central cannulation, but the patient remained asystolic in the context of profound hypothermia (31.2°C). Electrical activity reappeared only after controlled rewarming to 33°C. She was discharged home on day 35 with a good long term neurological outcome.DiscussionNeonates are particularly prone to rapid hypothermia during resuscitation. Controlled rewarming is essential to determine cardiac viability before establishing futility.ConclusionUnder profound hypothermia, asystole after restoration of mechanical circulation does not preclude irreversible myocardial damage. Cautious rewarming is mandatory to assess myocardial prognosis.

Paradoxical coronary embolism (PCE) is an uncommon cause of acute myocardial infarction (AMI), typically occurring when venous thromboemboli cross a right-to-left shunt in the setting of elevated right-sided pressures. We report a case of mixed obstructive and cardiogenic shock caused by simultaneous pulmonary embolism (PE) and PCE. A previously healthy 43-year-old woman developed profound hypoxemia and inferior ST-segment elevation 3 days after knee surgery. Coronary angiography revealed distal right coronary artery occlusion, successfully treated with aspiration thrombectomy and percutaneous coronary intervention. Persistent hypoxemia, right ventricular injury, and hemodynamic collapse prompted initiation of venoarterial extracorporeal membrane oxygenation (VA ECMO). Subsequent imaging identified extensive bilateral PE and a patent foramen ovale with significant right-to-left shunting. Catheter-based pulmonary embolectomy improved cardiopulmonary function, followed by percutaneous PFO closure. She recovered fully and was discharged home neurologically intact. This case highlights the importance of early recognition, appropriate ECMO configuration, and comprehensive management of PCE with concurrent PE.

IntroductionExtracorporeal membrane oxygenation (ECMO) provides lifesaving support for severe respiratory and cardiac failure. Hybrid modes such as venoarteriopulmonary (VAP) may be necessary when conventional modes fail to meet complex physiological demands.Case ReportA 31-year-old woman with dermatomyositis-associated interstitial lung disease developed severe respiratory failure. She was initiated on venovenous (VV) ECMO, later complicated by right ventricular injury (RVI) requiring conversion to venopulmonary (VP) ECMO, and ultimately required hybrid VAP ECMO for progressive RVI and cardiogenic shock while awaiting heart-lung transplantation. The unique cannulation configuration provided additional cardiorespiratory support and hemodynamic stabilization, which later enabled safe transfer for transplantation.DiscussionHybrid VAP ECMO may provide effective rescue support for patients with refractory RVI and respiratory failure despite VP ECMO, preserve a surgically naïve chest, avoid differential oxygenation, and serve as a bridge to combined heart-lung transplant.ConclusionHybrid VAP ECMO represents an effective salvage strategy and bridge-to-transplant in complex cardiopulmonary failure.

While venous thromboembolism (VTE) is increasingly recognized in neonates and prothrombotic risk factors are being identified, no risk assessment model currently exists to enable early identification of neonates at high risk of VTE. A thorough understanding of existing evidence is necessary to inform the development of a risk-assessment model.

To describe maternal, obstetrical, and neonatal risk factors associated with VTE in neonates.

A literature search of Medline, Embase, CINAHL, and clinicaltrials.gov databases was performed on March 16, 2025, for peer-reviewed publications (1990-2025). Reference lists of included articles were screened to identify other potentially relevant publications.

Peer-reviewed studies describing factors associated with venous thrombosis in neonates up to 44 weeks of corrected gestational age were included. A total of 282 reports were retrieved and assessed for eligibility.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology reporting guidelines were used to guide data abstraction. Studies were screened independently by 4 trained investigators. Data were pooled using a random-effects model.

The primary outcome was the factors associated with venous thrombosis. Maternal and obstetrical and patient-related risk factors were considered; catheter-related risk factors are reported separately. Results are expressed using mean differences (MDs) or odds ratio (ORs) with 95% CIs. The degree of heterogeneity (ie, τ2) was estimated using the restricted maximum-likelihood model estimator. Risk of bias in included studies was assessed using the Risk of Bias in Non-randomised Studies of Interventions tool.

A total of 60 studies (3 366 507 neonates) were included; most were retrospective cohort studies (26 studies [43%]) or case-control studies (15 studies [25%]). The following risk factors were significantly associated with venous thrombosis: preeclampsia (OR, 2.66; 95% CI, 1.70-4.16; P < .001; τ2 = 0.00), low birth weight (OR, 2.05; 95% CI, 1.41-3.00; P < .001; τ2 = 0.00), cardiac disease (OR, 5.90; 95% CI, 1.16-30.05; P = .03; τ2 = 1.27), and infection (OR, 2.90; 95% CI, 1.88-4.48; P < .001; τ2 = 0.33). Several other factors were identified in multiple studies, but with inconsistent results, including maternal diabetes, gestational age and prematurity, asphyxia, mechanical ventilation, surgery, and elevated hemoglobin or hematocrit levels.

In this systematic review and meta-analysis, preeclampsia, low birth weight, cardiac disease, and infection were identified as risk factors of neonatal venous thrombosis. Heterogeneity between studies, lack of thrombosis outcome definition, and limited studies addressing common conditions and medications were identified, highlighting the need for further studies and risk stratification.

Conventional coronary computed tomography angiography (CCTA) lumen assessment is hampered by the similar attenuation of iodine and calcium. We assessed the lumen for Gd-enhanced CCTA on high-resolution color Gd K-edge imaging using a clinical spectral photon-counting computed tomography (SPCCT) prototype in an anthropomorphic phantom.

A hollow cylindrical coronary artery phantom (10-mm outer diameter, 5-mm inner diameter) containing five cylindrical calcifications of different densities (75, 100, 200, 400, and 800 mg/cm³ hydroxyapatite, deemed very low, low, medium, high, and very high, respectively) and equal size was scanned on a clinical SPCCT prototype using a clinical CCTA protocol. The artery model was filled with Gd mixed with saline to achieve 400 HU at 70 keV. The luminal area was compared with the physical area (i.e., 19.6 mm²), and spectral results were compared to conventional acquisition.

In the absence of calcification, physical lumen size was overestimated by 7% and 16% on color Gd K-edge and conventional images, respectively. In the presence of calcification, only color Gd K-edge images enabled the measurement of the lumen, i.e., 22.25 ± 0.43 mm², 22.85 ± 1.77 mm², 14.63 ± 1.17 mm², and 15.37 ± 0.78 for very low to very high calcium density, respectively. Largest underestimation (-26%) and overestimation (16%) were shown for the high- and low-density calcification in comparison to physical size, respectively.

Color Gd K-edge imaging with Gd-enhanced CCTA outperformed conventional imaging in assessing the coronary lumen in both noncalcified and calcified vessels, whilst accuracy depends on the presence and density of calcifications.

In a phantom study, high-resolution color Gd K-edge imaging targeting Gd enabled accurate visualization of the coronary lumen in both calcified and noncalcified arteries, outperforming conventional CT angiography. In the presence of calcifications, only color Gd K-edge imaging provided objective lumen assessment, with accuracy influenced by calcium extent and density.

Color Gd K-edge Gd-enhanced CCTA using SPCCT is feasible in a coronary artery phantom. Color Gd K-edge imaging improves lumen assessment in calcified vessels. Color Gd K-edge imaging potentially enhances diagnostic precision and treatment planning for patients with coronary artery disease.

Intravenous immunoglobulin (IVIg) is the standard of care for the treatment of Kawasaki disease (KD) and should be administered within 10 days of the onset of fever. Management guidelines for children with KD who defervesce spontaneously are not clear. In this study, we analysed patients with KD diagnosed between 1994 and 2024 at our centre who had defervesced spontaneously, had normal acute-phase reactants, and underwent echocardiographic examination, and in whom IVIg had not been administered. We reviewed the records of patients with KD from January 1994 - December 2024. The diagnosis of KD was based on standard guidelines. Patients with KD were said to be in spontaneous defervescence when they remained afebrile for ≥ 48 h, had normal acute-phase reactants [C-reactive protein (CRP), Erythrocyte sedimentation rate (ESR)] and no coronary artery abnormalities (CAAs) on echocardiography at presentation, and when IVIg was not administered. Patients with spontaneous defervescence were subdivided into (i) early defervescence (Ed-KD), if the interval between onset of symptoms and defervescence was < 10 days, and (ii) late defervescence (Ld-KD), if the duration between onset of symptoms and defervescence was ≥ 10 days, respectively. Details of the clinical profile, laboratory investigations, and echocardiography findings were obtained from the records. Of the 1499 patients with KD enrolled during the study period, 115 patients (7.7%; 86 boys) defervesced spontaneously. The median age at disease onset was 6 years (mean, 5.6 years; range, 0.8-15 years). The median duration of fever, defined as the total duration of the febrile episode before spontaneous defervescence, was 5 days (range, 1-21 days). The median interval between illness onset (defined as fever onset) and diagnosis of KD was 15 days (range, 4-40 days), indicating that diagnosis was often made after fever had already subsided. The most common clinical feature was periungual desquamation, followed by rash, oral-mucosal changes, cervical lymphadenopathy, and conjunctival injection. Incomplete presentation was noted in 73.9% (n = 85/115) of patients. No patient has developed CAAs or other cardiac sequelae over a median follow-up of 9 months (range 2 months-156 months). The cumulative follow-up for the cohort was 235 patient-years. The 'low-risk' subgroup of patients with KD who defervesce spontaneously, and have normal acute phase reactants with no CAAs at presentation, have good clinical and coronary outcomes.