Expanding the genetic and phenotypic landscape of replication factor C complex-related disorders: RFC4 deficiency is linked to a multisystemic disorder.

The precise regulation of DNA replication is vital for cellular division and genomic integrity. Central to this process is the replication factor C (RFC) complex, encompassing five subunits, which loads proliferating cell nuclear antigen onto DNA to facilitate the recruitment of replication and repair proteins and enhance DNA polymerase processivity. While RFC1's role in cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is known, the contributions of RFC2-5 subunits on human Mendelian disorders is largely unexplored. Our research links bi-allelic variants in RFC4, encoding a core RFC complex subunit, to an undiagnosed disorder characterized by incoordination and muscle weakness, hearing impairment, and decreased body weight. We discovered across nine affected individuals rare, conserved, predicted pathogenic variants in RFC4, all likely to disrupt the C-terminal domain indispensable for RFC complex formation. Analysis of a previously determined cryo-EM structure of RFC bound to proliferating cell nuclear antigen suggested that the variants disrupt interactions within RFC4 and/or destabilize the RFC complex. Cellular studies using RFC4-deficient HeLa cells and primary fibroblasts demonstrated decreased RFC4 protein, compromised stability of the other RFC complex subunits, and perturbed RFC complex formation. Additionally, functional studies of the RFC4 variants affirmed diminished RFC complex formation, and cell cycle studies suggested perturbation of DNA replication and cell cycle progression. Our integrated approach of combining in silico, structural, cellular, and functional analyses establishes compelling evidence that bi-allelic loss-of-function RFC4 variants contribute to the pathogenesis of this multisystemic disorder. These insights broaden our understanding of the RFC complex and its role in human health and disease.

Characteristics associated with non-initiation and non-completion of human papillomavirus vaccination among Danish girls: a nationwide register-based cohort study.

AIM: The aim was to identify maternal and paternal socioeconomic and demographic characteristics for non-initiation and non-completion of the human papillomavirus (HPV) vaccination among Danish girls including time-trends. METHODS: This nationwide register-based cohort study included all girls residing in Denmark who were offered free-of-charge HPV vaccination as a part of the childhood vaccination program between 2009 and 2018 (birth cohorts 1996-2005). The study samples included 296,461 daughter-mother dyads and 291,025 daughter-father dyads. Data from the Danish Vaccination Register were linked with socioeconomic and demographic data from Statistics Denmark. HPV vaccination status was classified as 'non-initiation' for girls who received no HPV vaccine and as 'non-completion' for girls who initiated the HPV vaccination program but did not receive all the scheduled HPV vaccines. Data were analyzed using logistic regression models. RESULTS: Non-initiation of HPV vaccination was 13.7%, and non-completion was 24.2% among girls who initiated the HPV vaccination program. Girls of parents who were descendants of immigrants (adjusted odds ratio: 1.50; 95% confidence interval: 1.35-1.68), were at least 35-years old at time of birth, had basic or no education, had a low income, were not in the labor market, and were unmarried had the highest non-initiation and non-completion odds. The associations between socioeconomic and demographic characteristics and HPV vaccination uptake were similar for mothers and fathers. CONCLUSIONS: Despite free-of-charge availability to HPV vaccination in Denmark, we found disparities in non-initiation and non-completion of HPV vaccination among Danish girls by both mothers' and fathers' socioeconomic and demographic characteristics.

The De Morton Mobility Index (DEMMI) in hospitalized geriatric patients is associated with risk of readmission, mortality, and discharge to a post-acute care facility: A nationwide register-based cohort study.

OBJECTIVE: To examine the association between the de Morton Mobility Index (DEMMI) score on admission in geriatric patients and readmission and mortality within 30, 180, and 365 days after discharge, and discharge to a post-acute care facility. METHODS: A nationwide register-based cohort study including 23,941 geriatric in-patients aged ≥65 years admitted to a geriatric ward between 2014 and 2017 and included in the Danish National Database for Geriatrics. The DEMMI score was categorized into four subcategories: very low mobility (DEMMI=0-24), low mobility (DEMMI=27-39), moderately reduced mobility (DEMMI=41-57), and independent mobility (DEMMI=62-100). Patients were followed 30, 180 and 365 days after discharge for readmission and mortality. Their risk of being discharged to a post-acute care facility was examined. Adjusted hazard ratios (HRs) and odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated. RESULTS: HRs for readmission within 30-days were 1.36 (1.24-1.48) for very low mobility, 1.30 (1.20-1.42) for low mobility and 1.17 (1.08-1.28) for moderately reduced compared with independent mobility. Similar results were seen for readmission within 180- and 365-days. For mortality, HR for 30-day mortality ranged from1.93 and 5.66, 180-day mortality between 1.62 and 3.19, and 365-day mortality between 1.54 and 2.81 compared with patients with independent mobility. OR for discharge to a post-acute care facility was 8.76 (7.29-10.53) for lowest compared with the highest DEMMI mobility subcategory. CONCLUSION: In geriatric in-patients, lower DEMMI scores on hospital admission are associated with increased rates of discharge to a post-acute care facility, and for readmission, and mortality within one year.

Do school-based smoking preventive interventions have unintended effects? Post hoc analysis of the Focus cluster randomised controlled trial.

OBJECTIVES: Public health interventions are designed to improve specific health-related outcomes; however, they may also produce negative side effects, such as substitution use, psychological or social harms. Knowledge about the unintended effects of school-based smoking preventive interventions is sparse. Hence, this study examined these potential unintended effects of the smoking-reducing intervention, Focus, among students in the vocational education and training setting. DESIGN: Cluster randomised controlled trial stratified by school type with 5 months follow-up. SETTING AND PARTICIPANTS: Across Denmark, eight schools were randomised to the intervention group (n=844 students, response proportion 76%) and six schools to the control group (n=815 students, response proportion 75%). This study focused solely on students who smoked at baseline (N=491). INTERVENTIONS: The intervention was developed systematically based on theory and a thoroughly mixed-methods needs assessment. Intervention components included a comprehensive school tobacco policy (smoke-free school hours) supported by a 3-day course for school staff and launched by an edutainment session for students; class-based lessons and a quit-and-win competition; and individual telephone smoking cessation support. OUTCOMES: Alternative tobacco and nicotine products (regular use of smokeless tobacco, hookah and e-cigarettes), regular cannabis use, boredom and loneliness at school, stress and perceived stigmatisation among smokers. RESULTS: We found no statistically significant unintended effects of the intervention. Nonetheless, insignificant findings indicated that students in the intervention group were less likely to be bored during school hours (OR 0.59, 95% CI 0.32 to 1.10) and experience stress (OR 0.62, 95% CI 0.35 to 1.10), but more likely to report feeling stigmatised compared with the control group (OR 1.55, 95% CI 0.71 to 3.40). CONCLUSIONS: Overall, findings suggested no unintended effects of the Focus trial with respect to substitution use, psychological, nor group or social harms. Future research is encouraged to report potential harmful outcomes of smoking preventive interventions, and interventions should be aware of the possible stigmatisation of smokers. TRIAL REGISTRATION NUMBER: ISRCTN16455577.

Changes in weight status during the COVID-19 pandemic: impact of educational level and mental health.

BACKGROUND: The COVID-19 pandemic has resulted in a disruption of daily routines and changes in health behaviors leading to widespread concerns about unfavorable changes in weight status and a potential increase in the prevalence of obesity. This study examined the long-term impact of the COVID-19 pandemic on changes in weight status and its possible dependency on educational level and mental health. METHODS: The study utilizes the Danish Health and Well-being Survey with repeated self-reported information on weight status collected before the COVID-19 pandemic (autumn of 2019) and twice during the pandemic (autumns of 2020 and 2021). Information on educational level was derived from registers, whereas mental health was measured using validated scales. Generalized estimating equations were performed to investigate changes in mean weight and body mass index (BMI) category (BMI < 30 to BMI ≥ 30) between 2019 and 2021 and to investigate potential differences in changes in weight status by pre-pandemic educational level and mental health. RESULTS: Mean weight significantly increased by 0.34 kg [95% confidence interval (CI): 0.16-0.51] in 2020 and by 0.46 kg (95% CI: 0.26-0.66) in 2021 compared with pre-pandemic weight status. The increase was greater among individuals with lower educational levels and poorer mental health. There were no significant changes in BMI category during the pandemic. CONCLUSION: The results showed a significant increase in mean weight among the Danish population, particularly among individuals with lower educational levels and poorer mental health, but without detectable differences in obesity, supporting a long-term but minor impact of the COVID-19 pandemic on weight status.

Entorhinohippocampal cholecystokinin modulates spatial learning by facilitating neuroplasticity of hippocampal CA3-CA1 synapses.

The hippocampus is broadly impacted by neuromodulations. However, how neuropeptides shape the function of the hippocampus and the related spatial learning and memory remains unclear. Here, we discover the crucial role of cholecystokinin (CCK) in heterosynaptic neuromodulation from the medial entorhinal cortex (MEC) to the hippocampus. Systematic knockout of the CCK gene impairs CA3-CA1 LTP and space-related performance. The MEC provides most of the CCK-positive neurons projecting to the hippocampal region, which potentiates CA3-CA1 long-term plasticity heterosynaptically in a frequency- and NMDA receptor (NMDAR)-dependent manner. Selective inhibition of MEC CCKergic neurons or downregulation of their CCK mRNA levels also impairs CA3-CA1 LTP formation and animals' performance in the water maze. This excitatory extrahippocampal projection releases CCK upon high-frequency excitation and is active during animal exploration. Our results reveal the critical role of entorhinal CCKergic projections in bridging intra- and extrahippocampal circuitry at electrophysiological and behavioral levels.

Cutaneous manifestations, viral load, and prognosis among hospitalised patients with COVID-19: a cohort study.

INTRODUCTION: Various cutaneous manifestations have been reported as symptoms of coronavirus disease 2019 (COVID-19), which may facilitate early clinical diagnosis and management. This study explored the incidence of cutaneous manifestations among hospitalised patients with COVID-19 and investigated its relationships with viral load, co-morbidities, and outcomes. METHODS: This retrospective study included adult patients admitted to a tertiary hospital for COVID-19 from July to September 2020. Clinical information, co-morbidities, viral load (cycle threshold [Ct] value), and outcomes were analysed. RESULTS: In total, 219 patients with confirmed COVID-19 were included. Twenty patients presented with new onset of rash. The incidence of new rash was 9.1% (95% confidence interval=6.25%-14.4%). The most common manifestations were maculopapular exanthem (n=6, 42.9%, median Ct value: 24.8), followed by livedo reticularis (n=4, 28.6%, median Ct value: 21.3), varicella-like lesions (n=2, 14.3%, median Ct value: 19.3), urticaria (n=1, 7.1%, median Ct value: 14.4), and acral chilblain and petechiae (n=1, 7.1%, median Ct value: 33.1). The median Ct values for patients with and without rash were 22.9 and 24.1, respectively (P=0.58). There were no significant differences in mortality or hospital stay between patients with and without rash. Patients with rash were more likely to display fever on admission (P<0.01). Regardless of cutaneous manifestations, patients with older age, hypertension, and chronic kidney disease stage ≥3 had significantly higher viral load and mortality (P<0.05). CONCLUSION: This study revealed no associations between cutaneous manifestation and viral load or clinical outcomes. Older patients with multiple co-morbidities have risks of high viral load and mortality; they should be closely monitored.

Evaluation of the Abel inversion integral in O-mode plasma reflectometry using Chebyshev-Gauss quadrature.

The Abel transform is often used to reconstruct plasma density profiles from O-Mode polarized reflectometry diagnostics. However, standard numerical trapezoidal evaluation of the Abel inversion integral can be computationally expensive for a large number of evaluation points, and an endpoint singularity exists on the upper-bound of the integral, which can result in an increased error. In this work, Chebyshev-Gauss quadrature is introduced as a new method to evaluate the Abel inversion integral for the problem of O-Mode plasma reflectometry. The method does not require numerical evaluation of an integral singularity and is shown to have similar accuracy compared to existing methods while being computationally efficient.

Glycosylated fibronectin improves first-trimester prediction of pre-eclampsia.

OBJECTIVE: To determine whether maternal serum glycosylated fibronectin (GlyFn) level in the first trimester increases the sensitivity of the Fetal Medicine Foundation (FMF) triple test, which incorporates mean arterial pressure, uterine artery pulsatility index and placental growth factor, when screening for pre-eclampsia (PE) in an Asian population. METHODS: This was a nested case-control study of Chinese women with a singleton pregnancy who were screened for PE at 11-13 weeks' gestation as part of a non-intervention study between December 2016 and June 2018. GlyFn levels were measured retrospectively in archived serum from 1685 pregnancies, including 101 with PE, using an enzyme-linked immunosorbent assay (ELISA), and from 448 pregnancies, including 101 with PE, using a point-of-care (POC) device. Concordance between ELISA and POC tests was assessed using Lin's correlation coefficient and Passing-Bablok and Bland-Altman analyses. GlyFn was transformed into multiples of the median (MoM) to adjust for maternal and pregnancy characteristics. GlyFn MoM was compared between PE and non-PE pregnancies, and the association between GlyFn MoM and gestational age at delivery with PE was assessed. Risk for developing PE was estimated using the FMF competing-risks model. Screening performance for preterm and any-onset PE using different biomarker combinations was quantified by area under the receiver-operating-characteristics curve (AUC) and detection rate (DR) at a 10% fixed false-positive rate (FPR). Differences in AUC between biomarker combinations were compared using the DeLong test. RESULTS: The concordance correlation coefficient between ELISA and POC measurements was 0.86 (95% CI, 0.83-0.88). Passing-Bablok analysis indicated proportional bias (slope, 1.08 (95% CI, 1.04-1.14)), with POC GlyFn being significantly higher compared with ELISA GlyFn. ELISA GlyFn in non-PE pregnancies was independent of gestational age at screening (P = 0.11), but significantly dependent on maternal age (P < 0.003), weight (P < 0.0002), height (P = 0.001), parity (P < 0.02) and smoking status (P = 0.002). Compared with non-PE pregnancies, median GlyFn MoM using ELISA and POC testing was elevated significantly in those with preterm PE (1.23 vs 1.00; P < 0.0001 and 1.18 vs 1.00; P < 0.0001, respectively) and those with term PE (1.26 vs 1.00; P < 0.0001 and 1.22 vs 1.00; P < 0.0001, respectively). GlyFn MoM was not correlated with gestational age at delivery with PE (P = 0.989). Adding GlyFn to the FMF triple test for preterm PE increased significantly the AUC from 0.859 to 0.896 (P = 0.012) and increased the DR at 10% FPR from 64.9% (95% CI, 48.7-81.1%) to 82.9% (95% CI, 66.4-93.4%). The corresponding DRs at 10% FPR for any-onset PE were 52.5% (95% CI, 42.3-62.5%) and 65.4% (95% CI, 55.2-74.5%), respectively. CONCLUSIONS: Adding GlyFn to the FMF triple test increased the screening sensitivity for both preterm and any-onset PE in an Asian population. Prospective non-intervention studies are needed to confirm these initial findings. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Trends in smoking-related diseases by socioeconomic position following a national smoking ban in 2007: a nationwide study in the Danish population.

BACKGROUND: National comprehensive smoke-free legislation has been found to decrease the incidence of several smoking-related diseases. In 2007, Denmark introduced a national smoking ban, which banned smoking indoor in workplaces and public places, although only partial restrictions were applied in certain settings. We examined the impact of the smoking ban on smoking-related diseases and whether this differed across socioeconomic groups. METHODS: Interrupted time series analyses of nationwide register data were performed using Poisson regression models to examine the differential impact of the smoking ban on monthly incidence rates of acute myocardial infarction, chronic obstructive pulmonary disease, and smoking-related cancers from 2002 to 2015. Immediate changes in incidence rates after the smoking ban and long-term changes in disease trends were estimated by comparing data from the pre- and post-ban period. Models were stratified by socioeconomic position. RESULTS: Overall, we found neither immediate changes in rates of acute myocardial infarction, chronic obstructive pulmonary disease, and smoking-related cancers following the smoking ban nor long-term post-ban changes in disease trends as compared to before the ban. Results did not differ across socioeconomic groups. A pronounced socioeconomic gradient in incidence rates was observed for all outcomes both before and after the smoking ban. CONCLUSION: The national smoking ban was not associated with a lower incidence of smoking-related diseases in the post-ban period compared to pre-ban levels and no differences between socioeconomic groups were observed. Future tobacco control in Denmark should consider which measures most effectively target the low socioeconomic groups to decrease the current strong socioeconomic inequality in health.

A novel Doppler backscattering (DBS) system to simultaneously measure radio frequency plasma fluctuations and low frequency turbulence.

A novel quadrature Doppler Backscattering (DBS) system has been developed and optimized for the E-band (60-90 GHz) frequency range using either O-mode or X-mode polarization in DIII-D plasmas. In general, DBS measures the amplitude of density fluctuations and their velocity in the lab frame. The system can simultaneously monitor both low-frequency turbulence (f < 10 MHz) and radiofrequency plasma density fluctuations over a selectable frequency range (20-500 MHz). Detection of high-frequency fluctuations has been demonstrated for low harmonics of the ion cyclotron frequency (e.g., 2fci ∼ 23 MHz) and externally driven high-frequency helicon waves (f = 476 MHz) using an adjustable frequency down conversion system. Importantly, this extends the application of DBS to a high-frequency spectral domain while maintaining important turbulence and flow measurement capabilities. This unique system has low phase noise, good temporal resolution (sub-millisecond), and excellent wavenumber coverage (kθ ∼ 1-20 cm-1 and kr ≲ 30 cm-1). As a demonstration, localized internal DIII-D plasma measurements are presented from turbulence (f ≤ 5 MHz), Alfvenic waves (f ∼ 6.5 MHz), ion cyclotron waves (f ≥ 20 MHz), as well as fluctuations around 476 MHz driven by an external high-power 476 MHz helicon wave antenna. In the future, helicon measurements will be used to validate GENRAY and AORSA modeling tools for prediction of helicon wave propagation, absorption, and current drive location for the newly installed helicon current drive system on DIII-D.

The association between education and fear of recurrence among breast cancer patients in follow-up - and the mediating effect of self-efficacy.

BACKGROUND: Major restructuring of surveillance after breast cancer treatment with less follow-up consultations may result in insecurity and fear of recurrence (FCR) among the less resourceful breast cancer patients. We investigate the association between breast cancer patients' education and FCR and if self-efficacy mediates the associations between education and FCR. MATERIAL AND METHODS: A questionnaire survey was conducted from 2017 to 2019, among 1773 breast cancer patients shortly after having their follow-up switched from regular outpatient visits with an oncologist to either nurse-led or patient-initiated follow-up, with a subsequent questionnaire after 12 months. Data on disease and treatment characteristics were extracted from medical records and the Danish Breast Cancer Group Database. Logistic regression analyses were used to examine the association between education and FCR. Separate analyses were conducted for patients ≤ and >5 years since diagnosis and all models were adjusted for age and cohabitation status. To explore potential mediation by self-efficacy, we conducted regression analyses on education and FCR further adjusting for self-efficacy. RESULTS: The participation rate was 57%, and after the exclusion of patients due to missing data, 917 were included in analyses. Patients with long education had significantly less FCR compared to patients with short education (OR (95% CI) 0.71 (0.51;0,99)). When separated by time since diagnosis, there was no association among patients >5 years since diagnosis while the OR was 0.51 (95% CI, 0.30;0.85) for patients ≤5 years since diagnosis. Further adjusting for self-efficacy among patients <5 years since diagnosis resulted in an OR of 0.56 (95% CI, 0.33;0.95) among patients with long compared to short education. CONCLUSION: Up to 5 years after diagnosis, breast cancer patients with long education are less likely to experience FCR than patients with short education. Self-efficacy mediated only a very small part of this association, indicating that other factors play a role in socioeconomic differences in FCR among breast cancer patients.

End-of-Life Experiences Among "Kinless" Older Adults: A Nationwide Register-Based Study.

Background: The population of older adults who are unpartnered and childless (i.e., "kinless") is increasing across the globe, and may be at risk for lower quality end-of-life (EoL) experiences due to lack of family support, assistance, and advocacy. Yet, little research exists on the EoL experiences of "kinless" older adults. Objectives: To document associations between family structure (i.e., presence or absence of partner or child) and intensity of EoL experiences (i.e., visits to medicalized settings before death). Design: The study design is a cross-sectional population-based register study of the population of Denmark. Subjects: Participants include all adults age 60 years and older who died of natural causes in Denmark from 2009 to 2016 (n = 137,599 decedents). Results: "Kinless" older adults (reference = has partner, has child) were the least likely group to visit the hospital (two or more times; odds ratio [OR] = 0.74, confidence interval [CI] = 0.70-0.77), emergency department (one or more times; OR = 0.90, CI = 0.86-0.93), and intensive care unit (one or more times; OR = 0.71, CI = 0.67-0.75) before death. Conclusions: "Kinless" older adults in Denmark were less likely to experience medically intensive care at the EoL. Further research is needed to understand factors associated with this pattern to ensure that all individuals receive high quality EoL care regardless of their family structure and family tie availability.

Effectiveness of the multi-component intervention 'Focus' on reducing smoking among students in the vocational education setting: a cluster randomized controlled trial.

BACKGROUND: Social inequality in smoking remains an important public health issue. Upper secondary schools offering vocational education and training (VET) comprise more students from lower socioeconomic backgrounds and have higher smoking prevalence than general high schools. This study examined the effects of a school-based multi-component intervention on students' smoking. METHODS: A cluster randomized controlled trial. Eligible participants were schools offering VET basic courses or preparatory basic education in Denmark, and their students. Schools were stratified by subject area and eight schools were randomly allocated to intervention (1,160 invited students; 844 analyzed) and six schools to control (1,093 invited students; 815 analyzed). The intervention program comprised smoke-free school hours, class-based activities, and access to smoking cessation support. The control group was encouraged to continue with normal practice. Primary outcomes were daily cigarette consumption and daily smoking status at student level. Secondary outcomes were determinants expected to impact smoking behavior. Outcomes were assessed in students at five-month follow-up. Analyses were by intention-to-treat and per protocol (i.e., whether the intervention was delivered as intended), adjusted for covariates measured at baseline. Moreover, subgroup analyses defined by school type, gender, age, and smoking status at baseline were performed. Multilevel regression models were used to account for the cluster design. Missing data were imputed using multiple imputations. Participants and the research team were not blinded to allocation. RESULTS: Intention-to-treat analyses showed no intervention effect on daily cigarette consumption and daily smoking. Pre-planned subgroup analyses showed statistically significant reduction in daily smoking among girls compared with their counterparts in the control group (OR = 0.39, 95% CI: 0.16, 0.98). Per-protocol analysis suggested that schools with full intervention had higher benefits compared with the control group (daily smoking: OR = 0.44, 95% CI: 0.19, 1.02), while no marked differences were seen among schools with partial intervention. CONCLUSION: This study was among the first to test whether a complex, multicomponent intervention could reduce smoking in schools with high smoking risk. Results showed no overall effects. There is a great need to develop programs for this target group and it is important that they are fully implemented if an effect is to be achieved. TRIAL REGISTRATION: https://www.isrctn.com/ISRCTN16455577 , date of registration 14/06/2018.

Study protocol for a multicenter randomized controlled trial of personalized exercise therapy and self-management support for people with multimorbidity: The MOBILIZE study.

Background: Despite the great individual and societal burden associated with multimorbidity, little is known about how to effectively manage it. Objective: The aim of this multicenter randomized controlled trial (RCT) is to investigate the 12-month effects of a personalized exercise therapy and self-management support program in addition to usual care in people with multimorbidity. Design: This is a protocol for a pragmatic, parallel-group (1:1 ratio), superiority RCT conducted at five intervention sites (two hospitals, a private practice physiotherapy clinic and two municipal rehabilitation centers) in Region Zealand, Denmark. A total of 228 persons with multimorbidity aged 18 years or older, will be randomly allocated to one of two groups. Both groups will receive usual care, defined as routine care for multimorbidity at the discretion of the treating doctor, while the intervention group will also participate in a 12-week exercise therapy and self-management support program tailored to people with multimorbidity at one of the intervention sites. The primary outcome will be the between-group difference in change in EQ-5D-5L from baseline to the follow-up at 12 months. Secondary outcomes include objectively-measured physical function and physical activity, inflammatory markers, disease and treatment burden, anxiety, depression, stress, sleep, pain and other self-reported parameters. In parallel with the RCT, an observational cohort will follow persons aged ≥18 years with multimorbidity not adhering to all eligibility criteria, as well as people fulfilling all eligibility criteria, but unwilling to participate in the RCT. This study was approved by the Regional Committee on Health Research Ethics for Region Zealand (SJ-857) and results will be communicated in scientific papers, at relevant conferences and to a broader audience. Discussion: Exercise therapy and self-management support is safe and effective in people with single conditions. However, it is still unclear whether this holds true for individuals with multimorbidity. This pragmatic, multicenter RCT will provide high-quality evidence on the benefits and harms of exercise therapy and self-management support and, if the results support it, lead to the development of a plan for implementation in clinical practice.

Factors related to COVID-19 vaccine hesitancy in Denmark: A national study in the autumn of 2021.

AIMS: The novelty of the COVID-19 pandemic and fast-developed vaccines may increase concerns about the safety and effectiveness of the COVID-19 vaccine and thereby influence vaccine hesitancy. The aims of this study were to examine (a) the main reasons for COVID-19 vaccine hesitancy and (b) factors associated with COVID-19 vaccine hesitancy. METHODS: A nationwide survey was conducted in the autumn of 2021 when most Danes had received at least one dose of a COVID-19 vaccine. The sample (N=13,570) was based on a random selection of individuals (⩾15 years), and data were collected via self-administered mailed questionnaires (digital and physical). The participants were asked whether they had been vaccinated against COVID-19, and if they had not, they were asked about their reasons for vaccine hesitancy. Logistic regression models were used to determine factors associated with vaccine hesitancy. RESULTS: In all, 5,384 (39.7%) individuals completed the questionnaire. The main reasons for vaccine hesitancy were worries about adverse effects (57.6%) and the belief that natural immunity is better than vaccination (43.8%). Factors associated with vaccine hesitancy included female sex, younger age, being divorced, a country of origin other than Denmark, lower educational level, being unemployed, previously infected with COVID-19 and being worried to a greater extent about oneself and others getting infected. Mental health indicators were not associated with vaccine hesitancy. CONCLUSIONS: COVID-19 vaccine hesitancy is likely to pose a challenge for population immunity. To reduce vaccine hesitancy and increase vaccination uptake, future vaccination programmes should focus on specific socio-demographic subgroups identified in this study.

Risk of body weight changes among Danish children and adolescents during the COVID-19 pandemic.

BACKGROUND: Knowledge of COVID-19 and the pandemic's effects on Danish children's body weight is limited. OBJECTIVE: Objectives were to investigate (I) risk of weight changes among Danish children with and without SARS-CoV-2, (II) associations between weight changes, psychological symptoms, and long COVID symptoms, and (III) weight distribution pre- and post-pandemic. METHODS: A national survey was administered to all Danish children aged 0-18 years, with prior COVID-19 (cases) and matched references including questions on weight, weight changes during the pandemic and long COVID-related symptoms. Descriptive statistics and logistic regression were used. Weight distribution was compared with a pre-pandemic database. RESULTS: In all, 17 627 cases and 54 656 references were included. The 4-18-year-old cases had lower odds of unintended weight gain. The 2-3-year-old cases had higher odds and the 15-18-year-old cases lower odds of weight loss compared to references. Regardless of COVID-19 status, any reported long COVID-related symptom was associated with a change in body weight. No sign of increasing obesity rates was found among Danish children post-pandemic. CONCLUSION: COVID-19 was associated with higher odds of weight loss in 2-3-year-olds and lower odds of unintended weight gain in 4-18-year-olds. Any long COVID-related symptom was associated with higher odds of weight changes regardless of COVID-19 status.