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•RSV and influenza infections are frequent causes of child hospitalization.•Influenza immunization is possible; RSV vaccines are tested in phase III trials.•Identification of high-risk groups facilitate influenza/RSV vaccination policies.•Vaccines should be prioritized for children with asthma/chronic disease or siblings. To pave the way for universal or risk factor-based vaccination strategies, the present study aimed to describe the epidemiology and compare risk factors for hospitalization associated with respiratory syncytial virus (RSV) and influenza virus infections in Danish children. National register-based cohort study among 403,422 Danish children born 2010–2016. Prior asthma hospitalization, number of children in the household, chronic disease and maternal history of asthma hospitalization were the most important risk factors for both RSV and influenza hospitalization. The incidence of influenza increased at school start. Our findings enable targeted vaccination programs for high-risk children with asthma-like disease, chronic disease, siblings in the household, or maternal history of asthma hospitalization.

Background Excessive cartilage degradation is a known characteristic of osteoarthritis (OA). Biochemical markers, such as uCTX-II, have been shown to be associated with disease severity, yet the tissue origin of CTX-II has been disputed. This analysis investigates the association between OA knee joints at different radiographic stages and pain categories with levels of uCTX-II and biomarkers of bone resorption and formation. Methods Baseline data of two randomised clinical trials (NCT00486434 and NCT00704847) in patients with radiographic OA and presence of pain were analysed post hoc. A subgroup with available urine samples and evaluable radiographs for both knees ( N  = 1241) was analysed. Urine CTX-I, urine CTX-II and serum osteocalcin were analysed for associations with combined Kellgren-Lawrence (KL) scores, gender and pain for both knees to assess the contribution of joints at different stages. Results Pain, BMI, age, gender and KL grade were all significantly associated with uCTX-II. The association between pain and CTX-II appeared to be driven by weight-bearing pain. The level of uCTX-II incrementally increased with higher radiographic severity of each knee. Levels of bone markers CTX-I and osteocalcin were both significantly associated with BMI and gender, but neither were associated with radiographic severity. Biomarker levels between male or female groups of identical KL scores were found to be higher in females compared to males in some but not all KL score groups. Conclusions These results indicate that levels of uCTX-II are independently associated with radiographic severity of OA and pain intensity. CTX-II was associated with weight-bearing pain, but not non-weight-bearing pain, independent of co-variates. Bilateral OA knee joints appear to contribute to uCTX-II levels in an incremental manner according to radiographic severity of single joints. The data suggest that biomarker differences between genders should be taken into account when evaluating these markers in the context of structural features of OA.

The heterogeneous nature of osteoarthritis (OA) and the need to subtype patients is widely accepted in the field. The biomarker CRPM, a metabolite of C-reactive protein (CRP), is released to the circulation during inflammation. Blood CRPM levels have shown to be associated with disease activity and response to treatment in rheumatoid arthritis (RA). We investigated the level of blood CRPM in OA compared to RA using data from two phase III knee OA and two RA studies (N = 1591). Moreover, the association between CRPM levels and radiographic progression was investigated. The mean CRPM levels were significantly lower in OA (8.5 [95% CI 8.3–8.8] ng/mL, n = 781) compared to the RA patients (12.8 [9.5–16.0] ng/mL, n = 60); however, a significant subset of OA patients (31%) had CRPM levels (≥ 9 ng/mL) comparable to RA. Furthermore, OA patients (n = 152) with CRPM levels ≥ 9 ng/mL were more likely to develop contra-lateral knee OA assessed by X-ray over a two-year follow-up period with an odds ratio of 2.2 [1.0–4.7]. These data suggest that CRPM is a blood-based biochemical marker for early identification OA patients with an inflammatory phenotype.

We have previously reported suggestive linkage of type 2 diabetes mellitus to chromosome 10q 1 . We genotyped 228 microsatellite markers in Icelandic individuals with type 2 diabetes and controls throughout a 10.5-Mb interval on 10q. A microsatellite, DG10S478, within intron 3 of the transcription factor 7–like 2 gene ( TCF7L2 ; formerly TCF4 ) was associated with type 2 diabetes ( P = 2.1 × 10 −9 ). This was replicated in a Danish cohort ( P = 4.8 × 10 −3 ) and in a US cohort ( P = 3.3 × 10 −9 ). Compared with non-carriers, heterozygous and homozygous carriers of the at-risk alleles (38% and 7% of the population, respectively) have relative risks of 1.45 and 2.41. This corresponds to a population attributable risk of 21%. The TCF7L2 gene product is a high mobility group box–containing transcription factor previously implicated in blood glucose homeostasis. It is thought to act through regulation of proglucagon gene expression in enteroendocrine cells via the Wnt signaling pathway 2 .

This study implicates five genetic loci in bone mineral density. Two of these loci are new; three implicate genes known to be involved in bone remodeling, such as the receptor activator of nuclear factor-κB ligand gene ( RANKL ). Analyses showed that three of the loci are associated with osteoporotic fracture. This study implicates five genetic loci in bone mineral density. Two of these loci are new; three implicate genes known to be involved in bone remodeling. Osteoporosis confers substantive morbidity and mortality and associated costs and predisposes people to fragility fractures at the hip, spine, forearm, or other skeletal sites. 1 It is a common disease affecting both sexes in populations of various ancestries, although elderly women of European descent are at the highest risk. 2 Bone density is the single best predictor of osteoporotic fractures and is a valuable tool in evaluation of the risk of fractures. 3 , 4 There is abundant evidence for a genetic contribution to variation in bone mineral density, with heritability estimates between 0.6 and 0.8. 5 Bone mineral density is also influenced by environmental . . .

AbstractObjectiveTo estimate long term survival, health, and educational/social functioning in patients with Lyme neuroborreliosis compared with the general population.DesignNationwide population based cohort study using national registers.SettingDenmark.ParticipantsAll Danish residents diagnosed during 1986-2016 as having Lyme neuroborreliosis (n=2067), defined as a positive Borrelia burgdorferi intrathecal antibody test and a clinical diagnosis of Lyme borreliosis, and a comparison cohort from the general population matched on sex and date of birth (n=20 670).Main outcome measuresMortality rate ratios, incidence rate ratios of comorbidities, and differences in educational and social outcomes.ResultsMortality among patients with Lyme neuroborreliosis was not higher than in the general population (mortality rate ratio 0.90, 95% confidence interval 0.79 to 1.03). Lyme neuroborreliosis patients had increased risk of haematological (incidence rate ratio 3.07, 2.03 to 4.66) and non-melanoma skin cancers (1.49, 1.18 to 1.88). At diagnosis, Lyme neuroborreliosis patients had slightly higher employment and lower disability pension rates. After five years, patients and comparison cohort members had similar numbers of hospital contacts (difference −0.22, 95% confidence interval −0.45 to 0.02, in-hospital days/year; 0.37, −0.10 to 0.83, outpatient visits/year), employment rates (difference 1.5%, −2.1% to 5.1%), income (difference −1000, −20 000 to 18 000, Danish kroner), days of sick leave (difference −0.3, −3.5 to 3.0, per year), rates of receipt of a disability pension (difference −0.9%, −3.2% to 1.3%), and number of children (difference –0.10, −0.27 to 0.08). More patients were married (difference 4.8%, 2.2% to 7.4%) and had completed high school education (difference 7%, 1% to 12%).ConclusionA verified diagnosis of Lyme neuroborreliosis had no substantial effect on long term survival, health, or educational/social functioning. Nevertheless, the diagnosis decreased labour market involvement marginally and was associated with increased risk of haematological and non-melanoma skin cancers.

In this trial, tibolone, which has estrogenic, progestogenic, and androgenic effects, was compared with placebo in women between 60 and 85 who had osteoporosis or a vertebral fracture. Tibolone was associated with a reduced risk of fracture, breast cancer, and possibly colon cancer. But the drug was associated with an increased risk of stroke and therefore should generally be avoided in elderly women and in women with risk factors for stroke. Tibolone has estrogenic, progestogenic, and androgenic effects. In this trial, tibolone was associated with a reduced risk of fracture, breast cancer, and possibly colon cancer. But the drug was associated with an increased risk of stroke. Tibolone is approved in 90 countries to treat menopausal symptoms and in 45 countries to prevent osteoporosis. Tibolone metabolites have estrogenic, progestogenic, and androgenic activities. 1 – 3 Tibolone preserves bone mineral density, 4 – 6 reduces hot flushes, 7 – 9 and may increase libido and vaginal lubrication. 10 , 11 Tibolone treatment has little effect on levels of low-density-lipoprotein cholesterol but decreases levels of high-density-lipoprotein (HDL) cholesterol and triglycerides. 5 , 12 Our study, called the Long-Term Intervention on Fractures with Tibolone (LIFT), tested the primary hypothesis that treatment with tibolone reduces the risk of vertebral fracture and, secondarily, modifies the risks of nonvertebral fracture, breast cancer, deep-vein . . .

Background To prevent nosocomial transmission of SARS-CoV-2, infection prevention control (IPC) measures are implemented for patients with symptoms compatible with COVID-19 until reliable test results are available. This delays admission to the most appropriate ward based on the medical condition. SARS-CoV-2 rapid antigen detection (RAD) tests and point-of-care (POC) rapid RT-PCR (VitaPCR) were introduced at emergency department (ED) at Skåne University Hospital, Sweden in late 2020, but the consequence on patient flow and targeted admission is unknown. Methods Patients presenting at the emergency department of a referral hospital (N = 2940) between 13-Nov-2020 and 12-Jan-2021 were included. The study period was delimited into three periods by the introduction of RAD tests and the VitaPCR. Participant data was collected from hospital records, and outcome variables were Length-of-Stay (LoS), intrahospital transfers and targeted admission to COVID-19 ward. Results Compared to baseline (RT-PCR only), RAD tests reduced ED Length-of-Stay (LoS) for participants with positive tests. Negative VitaPCR results reduced mean hospital LoS by 1.5 (95% CI 0.3–2.7) days and admissions to COVID-19 wards from 34.5 (95% CI 28.9–40.5) to 14.7 (95% CI 11.1–19.1) per 100 admissions and reduced transfers between hospital wards in the first 5 days from 50.0 (95% CI 45.0–55.0) to 34.0 (95% CI 30.3–37.9) per 100 admissions. Conclusion RAD tests enabled prompt detection of SARS-CoV-2 infection which had pronounced effects on LoS at the ED. Negative VitaPCR enabled cessation of IPC measures and a negative test was associated with increased targeted admissions, reduced intrahospital transfers and shorter LoS at the hospital.

Citrullinated vimentin has been linked to several chronic and autoimmune diseases, but how citrullinated vimentin is associated with disease prevalence and genetic variants in a clinical setting remains unknown. The aim of this study was to obtain a better understanding of the genetic variants and pathologies associated with citrullinated and MMP-degraded vimentin. Patient Registry data, serum samples and genotypes were collected for a total of 4369 Danish post-menopausal women enrolled in the Prospective Epidemiologic and Risk Factor study (PERF). Circulating citrullinated and MMP-degraded vimentin (VICM) was measured. Genome-wide association studies (GWAS) and phenome wide association studies (PheWAS) with levels of VICM were performed. High levels of VICM were significantly associated with the prevalence of chronic pulmonary diseases and death from respiratory and cardiovascular diseases (CVD). GWAS identified 33 single nucleotide polymorphisms (SNPs) with a significant association with VICM. These variants were in the peptidylarginine deiminase 3/4 (PADI3/PADI4) and Complement Factor H (CFH)/KCNT2 gene loci on chromosome 1. Serum levels of VICM, a marker of citrullinated and MMP-degraded vimentin, were associated with chronic pulmonary diseases and genetic variance in PADI3/PADI4 and CFH/ KCNT2. This points to the potential for VICM to be used as an activity marker of both citrullination and inflammation, identifying responders to targeted treatment and patients likely to experience disease progression.

Truncated tau appears to be specifically related to disease pathology and recent studies have shown the presence and elevation of several truncated tau species in Cerebrospinal fluid (CSF) of subjects with Alzheimer's disease (AD); however, the relevance of truncated Tau measurements in blood is still being studied. The aim of the current study was to assess the longitudinal associations between baseline levels of two novel blood biomarker candidates measuring truncated tau, Tau-A and Tau-C, and the risk of incident dementia and AD in elderly women. Using solid phase competitive ELISA, two tau fragments were detected in serum of 5,309 women from the Prospective Epidemiological Risk Factor study. The study was an observational, prospective study of Danish postmenopausal women. Subjects were followed with registry-linkage for up to 15 years (median follow-up time 13.7 years). Cox regression was used to assess the utility of the biomarker candidates in relation to dementia and AD. High levels of Tau-A and Tau-C (above the median) in blood were associated with lower risk of dementia and AD (Tau-A: Dementia HR[95% CI] = 0.85[0.70-1.04]; AD 0.71[0.52-0.98] and Tau-C: Dementia 0.84[0.70-1.00]; AD 0.78[0.60-1.03]). Tau-C gave a very modest increase in the AUC in a 5-year prediction horizon as compared to a reference model with age and education, while a combination of the two did not improve their predictive capacity. Measurement of tau in serum is feasible. The serological tau turnover profile may be related to the diagnosis and development of dementia and AD. The exact processing and profile in serum in relation to cognitive disorders remains to be further assessed to provide simple non-invasive tests to identify subjects with progressive cognitive disorders.