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Introduction The prevalence of sleep disorders and use of sleep medication, particularly melatonin, are rising among adolescents and young adults (13–24 years). In Denmark, melatonin is approved for use in children with autism and ADHD up to 18 years of age, with other prescriptions being off-label in these age groups. The perspectives of medical practitioners on prescribing sleep medications to this age group remain largely unexplored.Aim This study aims to investigate the considerations of general practitioners (GPs) and child and adolescent psychiatrists (psychiatrists) when prescribing and deprescribing sleep medications for 13–24-year-olds.Methods We conducted qualitative semi-structured interviews with 10 GPs and six psychiatrists. Data were analyzed using an inductive approach.Results Psychiatrists typically prescribed melatonin with the expectation that deprescription would occur in general practice. Despite the universal goal of deprescription, it was hindered by various challenges. GPs identified patient motivation and a clear focus on deprescription as facilitative factors and expressed a need for enhanced emphasis on these aspects in general practice.Discussion and implications The findings align with existing prescription trends and literature on factors that promote and inhibit deprescription. The study underscores the complexities of deprescribing sleep medications for adolescents and young adults, suggesting the need for expanded guidelines and enhanced continuing education for GPs.Conclusions The research highlights significant discrepancies among medical practitioners regarding the deprescription process of sleep medications for young individuals, complicated by multiple factors. This underscores the need for better guidelines and further studies.

Introduction Patients with complex multimorbidity face a high treatment burden and frequently have low quality of life. General practice is the key organisational setting in terms of offering people with complex multimorbidity integrated, longitudinal, patient-centred care. This protocol describes a pragmatic cluster randomised controlled trial to evaluate the effectiveness of an adaptive, multifaceted intervention in general practice for patients with complex multimorbidity.Methods and analysis In this study, 250 recruited general practices will be randomly assigned 1:1 to either the intervention or control group. The eligible population are adult patients with two or more chronic conditions, at least one contact with secondary care within the last year, taking at least five repeat prescription drugs, living independently, who experience significant problems with their life and health due to their multimorbidity. During 2023 and 2024, intervention practices are financially incentivised to provide an extended consultation based on a patient-centred framework to eligible patients. Control practices continue care as usual. The primary outcome is need-based quality of life. Outcomes will be evaluated using linear and logistic regression models, with clustering considered. The analysis will be performed as intention to treat. In addition, a process evaluation will be carried out and reported elsewhere.Ethics and dissemination The trial will be conducted in compliance with the protocol, the Helsinki Declaration in its most recent form and good clinical practice recommendations, as well as the regulation for informed consent. The study was submitted to the Danish Capital Region Ethical Committee (ref: H-22041229). As defined by Section 2 of the Danish Act on Research Ethics in Research Projects, this project does not constitute a health research project but is considered a quality improvement project that does not require formal ethical approval. All results from the study (whether positive, negative or inconclusive) will be published in peer-reviewed journals.Trial registration number NCT05676541.

This paper investigates the competition between two charge point operators at the same site for future battery electric long-haul trucks. The charge point operators are located along one of the busiest highways in Sweden. The investigation is carried out using an agent-based model where trucks select charge point operators based on charging prices and the length of any queues, while charge point operators adjust their prices and number of chargers to improve their profitability. The study aims to predict conditions for trucks and charge point operators in a future public fast-charging market. Our findings indicate the potential for a well-functioning future public fast-charging market with small queuing problems, high utilisation, and reasonable prices for public fast charging. Assuming a price for electricity of EUR 0.08/kWh and a minimum profit margin of EUR 0.001/kWh for charge point operators, the findings indicate that the price level outside rush hours will be low, approximately EUR 0.1/kWh. The prices during rush hours will likely be much higher, but it is harder to predict the value due to uncertainties of how charge point operators will act in the future market. Still, from the model result, the price during rush hours is suggested to be just above EUR 0.5/kWh, with an average charging price of around EUR 0.15/kWh. It also seems likely that it is profitable for charge point operators to build enough chargers so that charging queues are short.

Background and aimsCirrhosis entails high risk of serious infections and abated efficiency of vaccination, but the underlying mechanisms are only partially understood. This study aimed at characterizing innate and adaptive immune functions, including antigen-specific T cell responses to COVID-19 vaccination, in patients with compensated and decompensated cirrhosis.MethodsImmune phenotype and function in peripheral blood from 42 cirrhotic patients and 44 age-matched healthy controls were analysed after two doses of the mRNA-based COVID-19 vaccines [BNT162b2 (Pfizer BioNTech) or mRNA-1273 (Moderna)].ResultsCirrhotic patients showed significantly reduced blood counts of antigen-presenting dendritic cells (DC) and high counts of monocytic myeloid-derived suppressor cells (M-MDSC) as compared to healthy controls. In addition, monocytic cells recovered from cirrhotic patients showed impaired expression of the antigen-presenting molecule HLA-DR and the co-stimulatory molecule CD86 upon Toll-like receptor (TLR) stimulation. These features were more prominent in patients with decompensated cirrhosis (Child-Pugh classes B & C). Interestingly, while patients with compensated cirrhosis (Child-Pugh class A) showed an inflammatory profile with myeloid cells producing the proinflammatory cytokines IL-6 and TNF, decompensated patients produced reduced levels of these cytokines. Cirrhotic patients, in particular those with more advanced end-stage liver disease, mounted reduced antigen-specific T cell reactivity to COVID-19 vaccination. Vaccine efficiency inversely correlated with levels of M-MDSC.ConclusionThese results implicate MDSC as mediators of immunosuppression, with ensuing deficiency of vaccine-specific T cell responses, in cirrhosis.

Adolescent idiopathic scoliosis (AIS) is the most common musculoskeletal disorder of childhood development. The genetic architecture of AIS is complex, and the great majority of risk factors are undiscovered. To identify new AIS susceptibility loci, we conducted the first genome-wide meta-analysis of AIS genome-wide association studies, including 7956 cases and 88 459 controls from 3 ancestral groups. Three novel loci that surpassed genome-wide significance were uncovered in intragenic regions of the CDH13 (P-value_rs4513093 = 1.7E-15), ABO (P-value_ rs687621 = 7.3E-10) and SOX6 (P-value_rs1455114 = 2.98E-08) genes. Restricting the analysis to females improved the associations at multiple loci, most notably with variants within CDH13 despite the reduction in sample size. Genome-wide gene-functional enrichment analysis identified significant perturbation of pathways involving cartilage and connective tissue development. Expression of both SOX6 and CDH13 was detected in cartilage chondrocytes and chromatin immunoprecipitation sequencing experiments in that tissue revealed multiple HeK27ac-positive peaks overlapping associated loci. Our results further define the genetic architecture of AIS and highlight the importance of vertebral cartilage development in its pathogenesis.

Type 1 conventional dendritic cells (cDC1) efficiently cross-present antigens that prime cytotoxic CD8+ T cells. cDC1 therefore constitute conceivable targets in cancer vaccine development. We generated recombinant fusion cancer vaccines that aimed to concomitantly deliver tumor antigen and adjuvant to CD103+ migratory cDC1, following intranasal administration. The fusion vaccine constructs comprised a cDC1-targeting anti-CD103 single chain antibody (aCD103) and a cholera toxin A1 (CTA1) subunit adjuvant, fused with MHC class I and II- or class II-restricted tumor cell antigens to generate a CTA1-I/II-aCD103 vaccine and a CTA1-II-aCD103 vaccine. The immunostimulatory and anti-tumor efficacy of these vaccines was evaluated in murine B16F1-ovalbumin (OVA) melanoma models in C57BL/6 J mice. The CTA1-I/II-aCD103 vaccine was most efficacious and triggered robust tumor antigen-specific CD8+ T cell responses along with a Th17-polarized CD4+ T cell response. This vaccine construct reduced the local growth of implanted B16F1-OVA melanomas and efficiently prevented hematogenous lung metastasis after prophylactic and therapeutic vaccination. Anti-tumor effects of the CTA1-I/II-aCD103 vaccine were antigen-specific and long-lasting. These results imply that adjuvant-containing recombinant fusion vaccines that target and activate cDC1 trigger effective anti-tumor immunity to control tumor growth and metastasis.

This paper investigates the charging needs and charger utilisation of a system of battery electric trucks and their public fast chargers, along the highway between the Swedish cities of Helsingborg and Stockholm, in a possible future scenario in which all trucks are battery electric. The system is investigated via an agent-based model which simulates a typical day with current levels of truck traffic on the road. The traffic flow is based on hourly truck flow data during a day and the annual flow of trucks. The findings indicate major potential for a well-functioning system of public chargers for trucks, with high utilisation, few queuing problems at charging stations, cheap public fast charging and a robust response to queues caused by peaks or increases in the traffic flow. The number of 900 kW chargers along the road needed to achieve this has been estimated at 140, and the utilisation factor for the chargers is predicted to be 30%.

Background & Aims: Cirrhosis entails elevated risk of COVID-19-associated mortality. This study determined T cell-mediated and antibody reactivity against the spike 1 (S1) protein of SARS-CoV-2 among 48 patients with cirrhosis and 39 healthy controls after mRNA COVID-19 vaccination. Methods: SARS-CoV-2-specific T-cell reactivity was measured by induced level of T cell-derived interferon-γ (IFN-γ) in blood cells stimulated ex vivo with multimeric peptides spanning the N-terminal portion of S1. S1-induced IFN-γ was quantified before and after the 1st and 2nd vaccination (BNT162b2, Pfizer-BioNTech or mRNA-1273, Moderna) alongside serum IgG against the receptor-binding domain (RBD) within S1 (anti-RBD-S1 IgG). Results: T-cell reactivity against S1 was reduced in patients with cirrhosis after the 1st (p

This paper investigates the economic consequences of a haulage company replacing its line-haul diesel trucks with battery-electric ones. It also examines how large truck batteries should be, whether the haulage companies should use public fast chargers to complement their own, and whether public fast chargers have the potential to be profitable. The potential extra cost of losing payload capacity is estimated and there is an investigation of whether a charge-point operator should meet the peak demand for charging. The case under analysis is designed to represent a typical line-haul service between terminals in a major logistics system, with the finding that, in this case, a transition to battery-electric trucks seems cost effective for the company. Moreover, it is advisable for the company to use public fast chargers and these will likely become profitable given that the utilisation factor of the investigated public fast chargers may realistically exceed 20%.

This paper investigates the competition between two charge point operators at the same site for future battery electric long-haul trucks. The charge point operators are located along one of the busiest highways in Sweden. The investigation is carried out using an agent-based model where trucks select charge point operators based on charging prices and the length of any queues, while charge point operators adjust their prices and number of chargers to improve their profitability. The study aims to predict conditions for trucks and charge point operators in a future public fast-charging market. Our findings indicate the potential for a well-functioning future public fast-charging market with small queuing problems, high utilisation, and reasonable prices for public fast charging. Assuming a price for electricity of EUR 0.08/kWh and a minimum profit margin of EUR 0.001/kWh for charge point operators, the findings indicate that the price level outside rush hours will be low, approximately EUR 0.1/kWh. The prices during rush hours will likely be much higher, but it is harder to predict the value due to uncertainties of how charge point operators will act in the future market. Still, from the model result, the price during rush hours is suggested to be just above EUR 0.5/kWh, with an average charging price of around EUR 0.15/kWh. It also seems likely that it is profitable for charge point operators to build enough chargers so that charging queues are short. [ABSTRACT FROM AUTHOR]

One possible step for reducing humans’ use of fossil fuel due to transport tasks is to replace diesel trucks with battery electric ones. This paper introduces the energy distribution diagram, which makes it easy to visualise the trucks’ daily energy consumption over their full service life. The energy distribution is used to investigate which driving patterns are suitable for cost-effective battery electric trucks when compared to commercial diesel trucks. It is shown that the battery capacity that results in the lowest cost per kilowatt-hour propulsion energy depends on the driving pattern, and an algorithm for selecting the most cost-effective capacity is presented. In many instances, it was found that battery electric trucks competed favourably with diesel trucks, especially when the trucks had low variations in daily energy consumption. It is beneficial to determine the circumstances under which they may be cheaper, as this will facilitate the transition to battery electric trucks in segments with a reduced overall cost of ownership.

Transport of ore and overburden in open-pit mines is often performed with large haul trucks. Battery-electric operation of haul trucks can significantly reduce the CO2 emissions and the fossil fuel dependence of open-pit mining. This simulation study investigates the feasibility and economy of operating large haul trucks battery-electrically, charging from an electric road system in the form of overhead trolley lines. The used simulation model is verified against measurements on diesel-electric haul trucks in normal operation. The simulation model is then tested with five drive cycles representing typical operations in the Aitik copper mine in northern Sweden. This simulation study shows that battery-electric operation with an electric road is feasible. It is shown that battery-electric operation is much cheaper than diesel-electric operation under reasonable assumptions. It is also much cheaper than diesel-electric operation assisted by an electric road.

Interleukin-1 beta (IL-1β), a pro-inflammatory cytokine, has been ascribed a role in the expansion of myeloid progenitors in acute myeloid leukemia (AML) and in promoting myeloid cell-induced suppression of lymphocyte-mediated immunity against malignant cells. This study aimed at defining the potential impact of IL-1β in the post-remission phase of AML patients receiving immunotherapy for relapse prevention in an international phase IV trial of 84 patients (ClinicalTrials.gov; NCT01347996). Consecutive serum samples were collected from AML patients in first complete remission (CR) who received cycles of relapse-preventive immunotherapy with histamine dihydrochloride (HDC) and low-dose interleukin-2 (IL-2). Low IL-1β serum levels before and after the first HDC/IL-2 treatment cycle favorably prognosticated leukemia-free survival and overall survival. Serum levels of IL-1β were significantly reduced in patients receiving HDC/IL-2. HDC also reduced the formation of IL-1β from activated human PBMCs in vitro. Additionally, high serum levels of the IL-1 receptor antagonist IL-1RA were associated with favorable outcome, and AML patients with low IL-1β along with high IL-1RA levels were strikingly protected against leukemic relapse. Our results suggest that strategies to target IL-1β might impact on relapse risk and survival in AML.

Aim: To investigate the association between clusters of conditions and psychological well-being across age groups. Method: This cross-sectional study used data collected in the Danish population-based Lolland-Falster Health Study. We included adults over the age of 18 years. Self-reported chronic conditions were divided into 10 groups of conditions. The primary outcome was psychological well-being (the WHO-5 Well-Being Index). Factor analysis constructed the clusters of conditions, and regression analysis investigated the association between clusters and psychological well-being. Results: Of 10,781 participants, 31.4% were between 18 and 49 years, 35.7% were between 50 and 64 years and 32.9% were above ≥65 years. 35.2% had conditions represented in 1 and 32.9% in at least 2 of 10 condition groups. Across age groups, living with one or more chronic conditions was associated with poorer psychological well-being. Two chronic condition patterns were identified; one comprised cardiovascular, endocrine, kidney, musculoskeletal and cancer conditions, the second mental, lung, neurological, gastrointestinal and sensory conditions. Both patterns were associated with poorer psychological well-being (Pattern 1: −4.5 (95% CI: −5.3 to −3.7), Pattern 2: −9.1 (95% CI −13.8 to −8.2). For pattern 2, participants ≥65 years had poorer psychological well-being compared to younger (−12.6 (95% CI −14.2 to −11.0) vs −6.6 (95% CI: −7.8 to −5.4) for 18–49 years and −8.7 (95% CI: −10.1 to −7.3) for 50–64 years, interaction: p ≤ 0.001) Conclusion: Living with one or more chronic conditions is associated with poorer psychological well-being. Findings point toward a greater focus on supporting psychological well-being in older adults with both mental and somatic conditions.

Abstract Background Many register studies make use of information about permanent nursing home residents. Statistics Denmark (StatD) identifies nursing home residents by two different indirect methods, one based on reports from the municipalities regarding home care in taken place in a nursing home, and the other based on an algorithm created by StatD. The aim of the present study was to validate StatD’s nursing home register using dedicated administrative municipality records on individual nursing home residents as gold standard. Methods In total, ten Danish municipalities were selected. Within each Danish Region, we randomly selected one municipality reporting to Stat D (Method 1) and one not reporting where instead an algorithm created by StatD was used to discover nursing home residents (Method 2). Method 1 means that municipalities reported to Stat D whether home care has taken place in a nursing home or in a private home. Method 2 is based on an algorithm created by Stat D for the municipalities where Method 1 is not applicable. Our gold standard was the information from the local administrative system in all ten selected municipalities. Each municipality provided a list with all individuals > 65 years living in a nursing home on January 1st, 2013 as well as the central personal number. This was compared to the list of individuals >65 living in nursing home facilities in the same ten municipalities on January 1st, 2013 retrieved from StatD. Results According to the data received directly from the municipalities, which was used as our gold Standard 3821 individuals were identified as nursing home residents. The StatD register identified 6,141 individuals as residents. Additionally, 556 of the individuals identified by the municipalities were not identified in the StatD register. Overall sensitivity for the ten municipalities in the StatD nursing home register was 0.85 (95% CI 0.84-0.87) and the PPV was 0.53 (95% CI 0.52-0.54). The municipalities for which nursing home status was based on the StatD algorithm (method 2) had a sensitivity of 0.84 (95% CI 0.82-0.86) and PPV of 0.48 (95% CI 0.46-0.50). Both slightly lower than the reporting municipalities (method 1) where the sensitivity was 0.87(95% CI 0.85-0.88) and the PPV was 0.57 (95% CI 0.56-0.59). Additionally, the sensitivity and PPV of the Stat D register varied heavily among the ten municipalities from 0.51 (95% CI 0.43-0.59) to 0.96 (95% CI 0.95-0.98) and PPV correspondingly, from 0.14 (95% CI: 0.11-0.17) to 0.73 (95% CI 0.69-0.77). Conclusions The overall PPV of StatD nursing home register was low and differences between municipalities existed. Even in countries with extensive nation-wide registers, validating studies should be conducted for outcomes based on these registers.