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Henrik Schrøder,1 Catherine Rechnitzer,2 Peder Skov Wehner,3 Steen Rosthøj,4 Jens Kjølseth Møller,5 Birgitte Lausen,2 Gitte Petersen,2 Mette Nørgaard6 1Department of Pediatrics, Aarhus University Hospital, Aarhus, 2Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, 3Department of Pediatric Hematology and Oncology, Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, 4Department of Pediatrics, Aalborg University Hospital, Aalborg, 5Department of Clinical Microbiology, Vejle Sygehus, Vejle, 6Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Aim of database: The overall aim is to monitor the quality of childhood cancer care in Denmark; to register late effects of treatment; to analyze complications of permanent central venous catheters (CVCs); to study blood stream infections in children with cancer; and to study acute toxicity of high-dose methotrexate infusions in children with leukemia. Study population: All children below 15 years of age at diagnosis living in Denmark diagnosed after January 1, 1985 according to the International Classification of Diseases 10, including diagnoses DC00–DD48. Main variables: Cancer type, extent of disease, treatment, participation in international studies, recurrence of malignant disease, survival, yearly follow-up status, causes of death, and development of secondary malignancies. Type of CVC, causes for removal of the CVC, type of blood stream infection, pathogens isolated, antimicrobial sensitivity, and outcome of antimicrobial chemotherapy. Descriptive data: Since 1985, 4,944 children below 15 years of age have been registered in the database. There has been no significant change in the incidence of childhood cancer in Denmark since 1985. The 5-year survival has increased significantly since 1985 and is now 86%. The median number of days from diagnosis to initiation of therapy is 7 days and in 80% of the children less than 14 days. Clinical data of 95% of the patients are reported to open international studies. Conclusion: The survival of Danish children with cancer since 2003 compares favorably with other international population-based studies. The annual reports support the collaboration within pediatric oncology in Denmark. Keywords: childhood cancer, epidemiology, survival, complications

BACKGROUND: Urogenital Chlamydia trachomatis infections are widespread, and each year many tests are performed in general practice. AIM: First, to quantify the magnitude of stigmatization, problems related to partner, and anxiety of infertility among men and women tested for C. trachomatis in general practice. Second, to investigate the effect of a C. trachomatis test result on planned future condom use. DESIGN OF STUDY: Comparative cross-sectional study. SETTING: General practices in Aarhus County, Denmark. METHOD: Men and women tested for C. trachomatis in general practice were given a questionnaire about feelings of stigmatization, fear of partner's reaction, fear of future infertility and other psychosocial side effects related to being infected or not infected with C. trachomatis. RESULTS: A total of 277 participated in the study. The response rates were 61% (82/135) and 54% (195/365) among infected and non-infected individuals, respectively. Among the infected individuals 32% (9/28) of the men's partners and 35% (19/54) of the women's partners were upset about the test result, 9% (5/54) of the women and 11% (3/28) of the men split with their partner, 59% (32/54) of the women and 54% (15/28) of the men expressed nervousness about infertility, and 91% (19/21) of the women but only 56% (5/9) of the men said that they would use a condom more often in the future. All these figures were significantly lower for both men and women having C. trachomatis negative test results. CONCLUSION: A chlamydia test affects the individual in terms of sexuality, relation to partner, reproduction, and future contraceptive strategy. The influence is highest among women and individuals with a positive test result. These findings should be taken into account in screening programmes targeting young women and men. [ABSTRACT FROM AUTHOR]

Objective: Gender-affirming care could be associated with higher employment rate. We assessed employment rates in transgender persons compared to controls and demographic, health, and treatment-related factors associated with employment in transgender persons., Methods: National register-based cohort study in Danish persons with diagnosis code of gender dysphoria during year 2000-2021. Five age-matched controls of the same sex at birth and 5 age-matched controls of the other sex at birth were included. The date of study inclusion was the first date of transgender diagnosis. Employment was the primary study outcome., Results: The cohort included 3812 transgender persons and 38 120 cisgender controls. The median age (interquartile range) was 19 (15; 24) years for transgender men, n = 1993 and 23 (19; 33) years for transgender women, n = 1819. In transgender men compared to control cisgender women, the odds ratio (OR) (95% CI) for employment was 0.33 (0.29; 0.38) before study inclusion and 0.24 (0.20; 0.29) in the fifth calendar year after index; in transgender women compared to control cisgender men, corresponding ORs were 0.30 (0.70; 0.34) and 0.21 (0.18; 0.25). Similar findings were observed between transgender persons and cisgender controls of other sex. Use of gender-affirming hormone in transgender men increased probability of employment at all time points after 5 years (OR 1.61 [95% CI: 1.08; 2.42], P = .02). In transgender women, use of hormone treatment was not associated with changed employment rates at 5 years (OR 1.31 [0.94; 1.82], P = .11)., Conclusion: Masculinizing hormone treatment was associated with higher probability of employment., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Objectives: To investigate receipt of antibiotics among patients with neuroborreliosis after initial antibiotic treatment, likely attributable to posttreatment symptoms., Methods: We performed a nationwide, matched, population-based cohort study in Denmark (2009-2021). We included all Danish patients with neuroborreliosis, i.e. a positive Borrelia burgdorferi intrathecal antibody index test and a cerebrospinal fluid leukocyte count ≥10 × 10 6 /l, and initially treated with doxycycline. To form a comparison cohort, we randomly extracted individuals from the general population matched 1:10 to patients with neuroborreliosis on date of birth and sex. The main outcome was receipt of doxycycline, and the secondary outcome was receipt of phenoxymethylpenicillin. We calculated short-term (<1 year) and long-term (≥1 year) hazard ratios (HR) with 95% confidence intervals (95%CI)., Results: We included 463 patients with neuroborreliosis and 2,315 comparison cohort members. Compared with the comparison cohort members, patients with neuroborreliosis initially treated with doxycycline had increased receipt of additional doxycycline within 1 year (HR: 38.6, 95%CI: 17.5-85.0) and ≥1 years (HR: 3.5, 95%CI: 1.9-6.3). Compared with comparison cohort members, patients with neuroborreliosis had no increased receipt of phenoxymethylpenicillin (<1 year HR 1.0, 95%CI: 0.7-1.3; ≥1 years HR 1.2, 95%CI: 0.9-1.5)., Conclusions: After initial antibiotic treatment, patients with neuroborreliosis have increased receipt of doxycycline particularly within one year after initial antibiotic therapy but also subsequently. The lack of increased receipt of phenoxymethylpenicillin suggests that the receipt of doxycycline was not merely due to differences in healthcare-seeking behaviour, increased risk of early Lyme borreliosis due to exposure, or differences in antibacterial usage in general.

Background and Purpose:  Prosthetic joint infection (PJI) following total hip arthroplasty (THA) has a severe impact on patients. We investigated the risk of second revision and mortality following first-time revision due to PJI., Methods:  We identified 1,669 first-time revisions including 416 treated with debridement, antibiotics, and implant retention (DAIR) from the Danish Hip Arthroplasty Register (DHR). First-time revision due to PJI was defined as a revision with ≥ 2 culture-positive biopsies for the same bacteria or re-ported as PJI to the DHR within 1 year after primary THA with non-PJI revisions as controls. We retrieved information on Charlson Comorbidity Index (CCI), death, cohabitation status, and cultures from intraoperative biopsies. The adjusted relative risk (RR) with 95% confidence interval (CI) was calculated by first-time revision (PJI or non-PJI). Patients were followed from first-time revision until end of study., Results:  PJI was found in 140 of 280 patients having a second revision following any first-time revision. Of these 280 patients, 200 were treated with DAIR as second revision. Patients with first-time revision due to PJI had an increased risk of second revision compared with first-time revision for non-PJI with an adjusted RR for second revision due to any cause of 2.7 (CI 1.9-3.8) and second revision due to PJI of 6.3 (CI 4.0-10). The 10-year adjusted RR for mortality for patients with first-time revision due to PJI compared with non-PJI was 1.8 (CI 0.7-4.5)., Conclusion:  The risk of second revision was increased both for second revision due to any reason and due to PJI following first-time revision due to PJI. Mortality risk following first-time revision due to PJI was increased, but not statistically significant.

Background: Few studies have investigated the risk of psychiatric neurodevelopmental disorders (PNDD) after childhood meningitis., Methods: Nationwide population-based cohort study (Denmark, 1995-2021) of children with positive cerebrospinal fluid for bacteria or enterovirus, stratified on age as young infants (0 to <90 days, n  = 637) or older children (≥90 days to <17 years, n  = 1,218). We constructed a comparison cohort from the general population ( n  = 18,550), and cohorts of siblings of participants. As risk estimates of PNDD we calculated age- and sex-adjusted hazard ratios (aHRs) with 95% confidence intervals (95%CI)., Results: Children with bacterial meningitis had increased risks of PNDD, especially learning and intellectual developmental disorders (young infants: aHR 4.2, 95%CI: 2.4-7.1; older children: aHR 1.5, 95%CI: 1.0-2.3), attention deficit disorder (ADHD) (young infants: aHR 2.8, 95%CI: 1.5-5.2; older children: 1.4, 95%CI: 0.9-2.2) and redemption of ADHD medication (young infants: aHR 2.2, 95%CI: 1.0-4.7; older children: 1.5, 95%CI: 1.0-2.3). Young infants with bacterial meningitis additionally had increased risks of autism spectrum disorders (aHR 1.9, 95%CI: 0.9-4.1) and behavioural and emotional disorders (aHR 2.0, 95%CI: 1.0-3.9). In young infants, the excess risk of PNDD was especially observed in premature children. Siblings of older children with bacterial meningitis also had increased risks of PNDD. Children with enteroviral meningitis at any age did not have increased risks of PNDD or redemption of ADHD medication., Conclusions: Bacterial meningitis in childhood is associated with subsequent diagnosis of PNDD, while enteroviral meningitis is not. The association appears to be partly explained by prematurity and familial and socioeconomic factors.

Objectives: To identify diagnostic opportunities, we investigated healthcare-seeking behaviour among patients with Lyme neuroborreliosis (LNB) within 28 weeks before diagnosis., Methods: We conducted a population-based, nationwide matched nested case-control study (Denmark, 2009-2021). As cases, we included all Danish residents with LNB (positive Borrelia burgdorferi intrathecal antibody index test and cerebrospinal fluid pleocytosis). We randomly selected controls from the general population and matched 10:1 on date of birth and sex. Exposures were assignment of diagnostic codes for symptoms, contact to medical specialties, medical wandering, and undergoing diagnostic procedures. We calculated the weekly and 3-month proportions of individuals with exposures and calculated absolute risk differences with corresponding 95% CI., Results: We included 1056 cases with LNB and 10 560 controls. Within 3 months before diagnosis, the most frequent assigned symptoms were pain (difference: 13.0%, 95% CI: 10.9-15.1). Cases with LNB exhibited increased contact with most specialties, particularly general practitioners (difference: 48.7%, 95% CI: 46.0-51.4), neurology (difference: 14.3%, 95% CI: 11.7-16.8), and internal medicine (difference: 11.1%, 95% CI: 8.7-13.5), and medical wandering (difference: 17.1%, 95% CI: 14.3-20.0). Common diagnostic procedures included imaging of the brain (difference: 10.2, 95% CI: 8.3-12.1), the spine (difference: 8.8%, 85% CI: 7.0-10.6), and the abdomen (difference: 7.2%, 95% CI: 5.4-9.1). The increase in healthcare-seeking behaviour was observed ≤12 weeks preceding diagnosis., Discussion: Pain appears to be an ambiguous symptom of LNB, potentially contributing to delays in establishing the correct diagnosis. It would be difficult to identify patients with LNB more effectively as the increased healthcare-seeking behaviour preceding diagnosis is distributed across many medical specialties., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Study Question: What is the prospective risk of Type 2 diabetes (T2D) in Nordic women with polycystic ovary syndrome (PCOS) compared to controls?, Summary Answer: A diagnosis of PCOS and BMI ≥30 kg/m2 is a high-risk phenotype for a prospective risk of T2D diagnosis across Nordic countries., What Is Known Already: The risk of T2D in women with PCOS is increased. The risk of T2D is related to BMI and the magnitude of risk in normal weight women with PCOS has been discussed. However, prospective data regarding risk of T2D in population-based cohorts of women with PCOS are limited., Study Design, Size, Duration: This national register-based study included women with PCOS and age-matched controls. The main study outcome was T2D diagnosis occurring after PCOS diagnosis. T2D was defined according to ICD-10 diagnosis codes and/or filled medicine prescriptions of anti-diabetic medication excluding metformin., Participants/materials, Setting, Methods: The study cohort included women originating from Denmark (PCOS Denmark, N = 27 016; controls, N = 133 994), Finland (PCOS Finland, N = 20 467; controls, N = 58 051), and Sweden (PCOS Sweden, N = 52 409; controls, N = 254 010). The median age at cohort entry was 28 years in PCOS Denmark, Finland, and Sweden with a median follow-up time (interquartile range) in women with PCOS of 8.5 (4.0-14.8), 9.8 (5.1-15.1), and 6.0 (2.0-10.0) years, respectively. Cox regression analyses were adjusted for BMI and length of education., Main Results and the Role of Chance: The crude hazard ratio (HR, 95% CI) for T2D diagnosis in women with PCOS was 4.28 (3.98-4.60) in Denmark, 3.40 (3.11-3.74) in Finland, and 5.68 (5.20-6.21) in Sweden. In adjusted regression analyses, BMI ≥30 vs <25 kg/m2 was associated with a 7.6- to 11.3-fold risk of T2D. In a combined meta-analysis (PCOS, N = 99 892; controls, N = 446 055), the crude HR for T2D in PCOS was 4.64 (3.40-5.87) and, after adjustment for BMI and education level, the HR was 2.92 (2.32-3.51)., Limitations, Reasons for Caution: Inclusion of more severe cases of PCOS in the present study design could have lead to an overestimation of risk estimates in our exposed population. However, some women in the control group would have undiagnosed PCOS, which would lead to an underestimation of T2D risk in women with PCOS. BMI data were not available for all participants. The present study should be repeated in study cohorts with higher background risks of T2D, particularly in populations of other ethnicities., Wider Implications of the Findings: The prospective risk for diagnosis of T2D is increased in women with PCOS, and the risk is aggravated in women with BMI ≥30 kg/m2., Study Funding/competing Interest(s): Funding in Denmark was from the Region of Southern Denmark, Overlægerådet, Odense University Hospital. Funding in Finland was from Novo Nordisk Foundation, Finnish Research Council and Sigrid Juselius Foundation, the National Regional Fund, Sakari Alhopuro Foundation and Finnish Diabetes Research Foundation. E.E. has received a research grant from Ferring Pharmaceuticals (payment to institution) and serves as medical advisor for Tilly AB, not related to this manuscript. The remaining authors declare no conflict of interest., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: We aimed to identify specific anaerobic bacteria causing bacteraemia and a subsequent diagnosis of colorectal cancer., Methods: A nationwide population-based cohort study, which included all episodes of defined specific anaerobic bacteraemia from 2010 (5,534,738 inhabitants) through 2020 (5,822,763 inhabitants) and all cases of colorectal cancer diagnosed from 2010 through 2021 in Denmark. We calculated the incidence and risk of colorectal cancer after bacteraemia with specific anaerobic bacteria using Escherichia coli bacteraemia as reference., Results: Nationwide data on colorectal cancer and specific anaerobic bacteraemia (100% complete, representing 11,124 episodes). The frequencies of colorectal cancer within one year following anaerobic bacteraemia were higher for species, which almost exclusively reside in the colon, such as Phocaeicola vulgatus/dorei (5.5%), Clostridium septicum (24.2%), and Ruminococcus gnavus (4.6%) compared to 0.6% in 50,650 E. coli bacteraemia episodes. Bacteroides spp. had a subhazard ratio for colorectal cancer of 3.9 (95% confidence interval [CI], 3.0 to 5.1) and for Clostridium spp. it was 8.9 (95% CI, 6.7 to 11.8, with C. septicum 50.0 [95% CI, 36.0 to 69.5]) compared to E. coli (reference)., Conclusion: This nationwide study identified specific colorectal cancer-associated anaerobic bacteria, which almost exclusively reside in the colon. Bacteraemia with these bacteria could be an indicator of colorectal cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: The AIRCARD study is designed to investigate the relationship between long-term exposure to air and noise pollution and cardiovascular disease incidence and mortality. We aim to conduct a robust prospective cohort analysis assessing the cumulative and differential impacts of air and noise pollution exposure on cardiovascular disease and mortality. This study will adjust for relevant confounders, including traditional cardiovascular risk factors, socioeconomic indicators, and lipid-lowering agents., Methods: This prospective cohort study will include 27,022 male participants aged 65-74, recruited from the two large Danish DANCAVAS and VIVA trials, both population-based randomized, multicentered, clinically controlled studies. We will assess long-term exposure to air pollutants using the state-of-the-art DEHM/UBM/AirGIS modeling system and noise pollution through the Nord2000 and SoundPLAN models, covering data from 1979 to 2019. This statistical analysis plan is strictly formulated to predefine the analytical approach for all outcomes and key study variables before data access. The primary analysis will utilize Cox proportional hazards models, adjusted for confounders identified in our cohort (age, body mass index, hypertension, diabetes, smoking status, family history of heart disease, socioeconomic factors, and lipid-lowering agents). This statistical analysis plan further includes Spearman rank correlation to explore inter-pollutant associations., Conclusion: The AIRCARD study addresses global concerns about the impact of air and noise pollution on cardiovascular disease. This research is important for understanding how the pollutants contribute to cardiovascular disease. We aim to provide insights into this area, emphasizing the need for public health measures to mitigate pollution exposure. Our goal is to provide policymakers and healthcare professionals with information on the role of environmental factors in cardiovascular health that could influence global strategies to reduce the cardiovascular disease burden associated with pollution. The design of this SAP ensures transparency and verifiability, considering the complexities of evaluating environmental health impacts over an extended period., (© 2024 S. Karger AG, Basel.)

Background: Lyme borreliosis is a tick-borne disease caused by the bacterium Borrelia burgdorferi (Bb) sensu lato complex. Previous studies have suggested an association between Lyme borreliosis and heart failure, which have been suggested to be a possible manifestation of Lyme carditis. We aimed to investigate the risk of heart failure among individuals tested for serum Bb antibodies, and serum Bb seropositive individuals., Methods: We performed a matched nationwide cohort study (Denmark, 1993-2020) and included 52,200 Bb seropositive individuals, and two age- and sex-matched comparison cohorts: 1) 104,400 Bb seronegative comparison cohort members, and 2) 261,000 population controls. We investigated the risk associated with 1) being tested for serum Bb antibodies, and 2) being Bb seropositive. Outcomes were: 1) a composite of heart failure, cardiomyopathy, and/or myocarditis diagnosis, and 2) redemption of cardiovascular medicine used for treatment of heart failure. We calculated short-term odds ratios (aOR) (within 1 month) and long-term hazard rates (aHR) (after 1 month) adjusted for age, sex, diabetes, pre-existing heart failure, and kidney disease., Results: Compared with the population controls, individuals tested for Bb antibodies, regardless of the test result, had increased short-term risk of heart failure, cardiomyopathy, and myocarditis (aOR 8.3, 95 %CI: 6.7-10.2), and both increased short- and long-term risk of redemption of cardiovascular medicine (aOR 4.3, 95 %CI: 3.8-4.8, aHR 1.13, 95 % CI: 1.11-1.15). The Bb seropositive individuals had no increased short- or long-term risk of any outcome compared with Bb seronegative comparison cohort members., Conclusions: In conclusion, Bb antibody tests seemed to be performed in the diagnostic work-up of heart failure, but Bb seropositivity was not associated with heart failure., Competing Interests: Conflict of interest MMT has received travel grants outside this work from GlaxoSmithKline Pharma A/S. RBD has advisory board activity with Pfizer. JHS reports institutional research grant from Medtronic (outside this study), speakers’ honorarium from Medtronic and membership of an advisory board in Medtronic. AML reports speakers’ honorarium/travel grants/advisory board activity and unrestricted grant from Gilead, speakers honorarium /travel grants from GSK, speaker's honorarium/advisory board activity from Pfizer outside this work. None of the authors report any conflict of interests in connection with this article., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Metabolomics data is often complex due to the high number of metabolites, chemical diversity, and dependence on sample preparation. This makes it challenging to detect significant differences between factor levels and to obtain accurate and reliable data. To address these challenges, the use of Design of Experiments (DoE) techniques in the setup of metabolomic experiments is crucial. DoE techniques can be used to optimize the experimental design space, ensuring that the maximum amount of information is obtained from a limited sample space., Aim of Review: This review aims at providing a baseline workflow for applying DoE when generating metabolomics data., Key Scientific Concepts of Review: The review provides insights into the theory of DoE. The review showcases the theory being put into practice by highlighting different examples DoE being applied in metabolomics throughout the literature, considering both targeted and untargeted metabolomic studies in which the data was acquired using both nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry techniques. In addition, the review presents DoE concepts not currently being applied in metabolomics, highlighting these as potential future prospects., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Radicular pain is the most predominant symptom among adults with Lyme neuroborreliosis (LNB) but the duration preceding and following diagnosis remains unknown. We aimed to investigate whether patients with LNB have increased obtainment of analgesics before and after diagnosis and for how long., Methods: We performed a nationwide, population-based, matched cohort study (2009-2021). all Danish residents with LNB (positive Borrelia burgdorferi intrathecal antibody index test and cerebrospinal fluid pleocytosis) were included. To form a comparison cohort, individuals from the general population were randomly extracted and matched 10:1 to patients with LNB on age and sex. Outcomes were obtainment of simple analgesics, antiepileptics, tricyclic antidepressants, serotonin and noradrenaline reuptake inhibitors, tramadol, and other opioids. We calculated monthly and six-monthly proportions of individuals with obtainment of analgesics and absolute risk differences., Results: 1,056 patients with LNB and 10,560 comparison cohort members were included. An increased proportion of patients with LNB obtained analgesics from 3 months before study inclusion, especially simple analgesics, tramadol, and other opioids. Within the 0-1-month period after study inclusion, patients with LNB most frequently obtained simple analgesics (15 %), antiepileptics (11 %), and tramadol (10 %). Thereafter, obtainment of analgesics declined within a few months. A slightly larger proportion of patients with LNB obtained antiepileptics up to 2.5 years after diagnosis., Conclusions: Up to 3 months preceding diagnosis, LNB was preceded by increased obtainment of analgesics, which suggests diagnostic delay. Importantly, most patients with LNB did not obtain analgesics after the immediate disease course, although obtainment remained more frequent up to 2.5 years after., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Aims: (a) To investigate support for caregivers of people diagnosed with stroke, cancer, chronic obstructive pulmonary disease (COPD), dementia, or heart disease provided across healthcare settings in Denmark; (b) to assess differences in caregiver support across diagnoses and settings., Methods: A cross-sectional nationwide survey among professionals representing healthcare settings at municipalities ( n = 479) and hospital wards and outpatient clinics ( n = 425). The survey assessed identification of caregivers and support initiatives., Results: The response rate was 81% for municipalities and 49% for hospitals. Identification of caregivers was frequent in dementia care (81% and 100%) and less frequent in COPD care (58% and 64%) in municipalities and hospitals, respectively. Caregiver support differed significantly across diagnoses within municipalities ( p = 0.009) and hospitals ( p < 0.001). Systematic identification of vulnerable caregivers was <25% for all diagnoses except dementia. The most common support initiatives involving caregivers were primarily aimed at the ill person and included guidance about the disease and consequences for everyday life and lifestyle changes. Caregivers were least involved in support initiatives addressing physical training, work retention, sexuality, or cohabitation., Conclusions: Disparities and significant differences across diagnoses exist in the identification of caregivers and the provision of support initiatives. Support initiatives involving caregivers primarily targeted patients. Future studies should investigate how caregivers' needs can be met across different diagnoses and healthcare settings and investigate potential changes in caregivers' needs during disease trajectories. In clinical practice, identification of vulnerable caregivers should be a major focus, and disease-specific clinical guidelines may be required to ensure sufficient support for caregivers., Competing Interests: Declaration of conflicting interestsThe authors have no conflicts of interest to declare.

Objective: Timing of administration of antibiotics and concentrations in maternal blood and the umbilical cord blood are important prerequisites for optimal intrapartum antibiotic prophylaxis (IAP) of neonatal early-onset group B streptococcus (GBS) disease. This cohort study aimed to explore penicillin concentrations in mothers and infants at birth in relation to time elapsed from administration to delivery and to the minimal inhibitory concentration (MIC) for GBS., Main Outcome Measures: Penicillin G concentrations in maternal and umbilical cord blood in relation to time and dose from administration to time of delivery., Results: In 44 mother-infant dyads, median maternal penicillin G concentration was 0.2 mg/L (IQR 0-0.8 mg/L; range 0-1.6 mg/L). Median infant penicillin G concentration was 1.2 mg/L (IQR 0.5-5.0 mg/L; range 0-12.7 mg/L). In all infants (N=38) born less than 4 hours after the latest IAP administration, penicillin G concentrations far exceeded MIC (0.125 mg/L), even after short time intervals between IAP administration and birth. The highest plasma concentrations were reached in umbilical cord blood within 1 hour from IAP administration to birth.For 44 mother-infant dyads, maternal concentrations were very low compared with their infants'; particularly, very high concentrations were seen in the 20 infants with only one dose of IAP., Conclusion: High concentrations of penicillin G were found in umbilical cord blood of infants born less than 4 hours after IAP administration, well above the MIC for GBS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Previous studies have indicated that glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) may enhance bone formation and have neutral or beneficial effects on fracture risk. We evaluated the effect of the GLP-1RA semaglutide on the bone formation marker Procollagen type I N-terminal propeptide (PINP) in adults with increased fracture risk., Methods: This randomised, placebo-controlled, double-blinded, phase 2 clinical trial was conducted at two public hospitals in Denmark. We enrolled 64 men and women with increased fracture risk based on a T-score < -1.0 at the total hip or lumbar spine and/or low-energy fracture within three years of recruitment. Participants were randomised (1:1) to receive once-weekly subcutaneous semaglutide 1.0 mg or placebo. The primary outcome was changes in plasma (P)-PINP from baseline to week 52. Primary and safety outcomes were assessed and evaluated for all participants. This trial is complete and registered with ClinicalTrials.gov, NCT04702516., Findings: Between March 24 and December 8, 2021, 55 (86%) postmenopausal women and nine men with a mean age of 63 years (SD 5.5) and BMI of 27.5 kg/m 2 (SD 4.5) were enrolled. There was no effect on changes in P-PINP from baseline to week 52 between the two groups (estimated treatment difference (ETD) semaglutide versus placebo 3.8 μg/L [95% CI -5.6 to 13.3]; p = 0.418), and no difference in P-PINP levels between groups at week 52 (semaglutide 64.3 μg/L versus placebo 62.3 μg/L [95% CI -10.8 to 15.0]; p = 0.749). The secondary outcomes showed higher plasma levels of bone resorption marker Collagen type I cross-linked C-terminal telopeptide (P-CTX) in the semaglutide group than in the placebo group (ETD 166.4 ng/L [95% CI 25.5-307.3]; p = 0.021). Compared to placebo, lumbar spine and total hip areal bone mineral densities (aBMD) were lower in the semaglutide group after 52 weeks ((ETD lumbar spine -0.018 g/cm 3 [95% CI -0.031 to -0.005]; p = 0.007); ETD total hip -0.020 g/cm 2 ([95% CI -0.032 to -0.008]; p = 0.001). Treatment differences in femoral neck aBMD were not observed ([95% CI [-0.017 to 0.006]; p = 0.328). Further, body weight was lower in the semaglutide group than in the placebo group after 52 weeks (ETD -6.8 kg [95% CI -8.8 to -4.7]; p < 0.001). Thirty-one [97%] in the semaglutide group and 18 [56%] in the placebo group experienced at least one adverse event, including four serious events (two in each group). No episodes of hypoglycaemia or deaths were reported., Interpretation: In adults with increased fracture risk, semaglutide once weekly did not increase bone formation based on the bone formation marker P-PINP. The observed increase in bone resorption in the semaglutide group may be explained by the accompanying weight loss., Funding: Region of Southern Denmark, Novo Nordisk Foundation, and Gangsted Foundation. Novo Nordisk provided the investigational drug and placebo., Competing Interests: EMW, SJ, SGH, JJM, and CE declare no conflicts of interest. MSH and MF have received funding from the Novo Nordisk Foundation. RE receives consultancy funding from Immunodiagnostic Systems, Sandoz, Samsung, CL Bio, Biocon, Takeda, UCB, meeting presentations for Pharmacosmos, Alexion, UCB and Amgen, and grant funding from Alexion. NRJ has received assays and reagents from IDS and Roche for clinical studies. MF has received consultancy funding from Novo Nordisk and is shareholder at Novo Nordisk and Eli Lily. Novo Nordisk, Denmark, provided the investigational drug and placebo., (© 2024 The Author(s).)

Objectives: To investigate the short- and long-term risks of atrioventricular block and other cardiac conduction disorders associated with being tested for Borrelia burgdorferi (Bb) antibodies or Bb seropositivity as measures of confounding by indication and Bb infection, respectively., Methods: We performed a nationwide population-based matched cohort study (Denmark, 1993-2021). We included 52 200 Bb-seropositive individuals (stratified as only Bb-IgM-seropositive [n = 26 103], only Bb-IgG-seropositive [n = 18 698], and Bb-IgM-and-IgG-seropositive [n = 7399]) and two age- and sex-matched comparison cohorts: 104 400 Bb-seronegative individuals and 261 000 population controls. We investigated the risk associated with being tested for serum Bb antibodies and being Bb seropositive. Outcomes were atrioventricular block and other conduction disorders. We calculated short-term odds ratios (aOR) (within 1 month), and long-term hazard ratios (aHR) (after 1 month) adjusted for age, sex, diabetes, chronic heart failure, and kidney disease with 95% CI., Results: Compared with population controls, individuals tested for Bb antibodies had increased short- and long-term risks of atrioventricular block (aOR 47.9, 95% CI: 30.0-76.7, aHR 1.3, 95% CI:1.2-1.3), and other conduction disorders (aOR 18.2, 95% CI: 10.1-32.8, aHR 1.2, 95% CI: 1.1-1.4). Compared with Bb-seronegative individuals, only Bb-IgM-and-IgG-seropositive individuals had increased short-term risk of atrioventricular block (aOR: 2.1, 95% CI: 1.5-3.1)., Discussion: The results suggest that Bb antibody testing is included in the diagnostic work-up of conduction disorders. Finally, that Bb seropositivity is not associated with other conduction disorders than atrioventricular block or with increased long-term risk of conduction disorders., (Copyright © 2024. Published by Elsevier Ltd.)

Burden of bacteraemia is rising due to increased average life expectancy in developed countries. This study aimed to compare the epidemiology and outcomes of bacteraemia in two similarly ageing populations with different ethnicities in Singapore and Denmark. Historical cohorts from the second largest acute-care hospital in Singapore and in the hospitals of two Danish regions included patients aged 15 and above who were admitted from 1 January 2006 to 31 December 2016 with at least 1 day of hospital stay and a pathogenic organism identified. Among 13 144 and 39 073 bacteraemia patients from Singapore and Denmark, similar 30-day mortality rates (16.5%; 20.3%), length of hospital stay (median 14 (IQR: 9-28) days; 11 (6-21)), and admission rate to ICU (15.5%; 15.6%) were observed, respectively. Escherichia coli , Klebsiella pneumoniae , and Staphylococcus aureus ranked among the top four in both countries. However, Singaporeans had a higher proportion of patients with diabetes (46.8%) and renal disease (29.5%) than the Danes (28.0% and 13.7%, respectively), whilst the Danes had a higher proportion of patients with chronic pulmonary disease (18.0%) and malignancy (35.3%) than Singaporeans (9.7% and 16.2%, respectively). Our study showed that top four causative organisms and clinical outcomes were similar between the two cohorts despite pre-existing comorbidities differed.

Objectives: We compared characteristics and outcomes of individuals who in the cerebrospinal fluid (CSF) were positive for herpes simplex virus (HSV) or varicella-zoster virus (VZV)-intrathecal antibody index test ([AI]-positive) vs. individuals who were PCR-positive for HSV type 1 (HSV1), type 2 (HSV2), and for VZV., Methods: Nationwide cohort study of all Danish residents with positive CSF-AI or -PCR for HSV or VZV (1995-2021). We calculated short- and long-term risks as age-, sex-, and comorbidity-adjusted odds ratios (aOR), adjusted hazard ratios (aHR), and absolute risk differences with 95% CIs., Results: Compared with individuals with positive PCR for HSV1 (n = 321), HSV2 (n = 497), and VZV (n = 1054), individuals with a positive AI for HSV (n = 177) and VZV (n = 219) had CSF pleocytosis less frequently (leucocyte count >10/μL: HSV-AI: 39%, VZV-AI: 52%, HSV1-PCR: 81%, HSV2-PCR: 92%, VZV-PCR: 83%), and were less frequently diagnosed with central nervous system infection ([aOR {95%CI}]: HSV-AI vs. HSV1-PCR: [0.1 {0.1, 0.2}], HSV-AI vs. HSV2-PCR: [0.1 {0.0, 0.1}], VZV-AI vs. VZV-PCR: [0.2 {0.2, 0.3}]). Individuals with a positive HSV-AI or VZV-AI had increased risk of demyelinating disease ([aOR {95%CI}; aHR {95%CI}]: HSV-AI vs. HSV1-PCR: [4.6 {0.9, 24.5}; aHR not applicable], HSV-AI vs. HSV2-PCR: [10.4 {2.3, 45.9}; 12.4 {2.3, 66.0}], VZV-AI vs. VZV-PCR: [aOR not applicable; 10.3 {1.8, 58.8}]). Disability pension was less frequent among HSV-AI than HSV1-PCR cohort members (5-year risk difference: -23.6%, 95%CI: -35.2, -11.8), and more frequent among VZV-AI than VZV-PCR cohort members (5-year risk difference: 16.8%, 95%CI: 5.0, 28.7)., Discussion: AI-positive individuals differ from PCR-positive individuals in several aspects. AI appears unspecific for current central nervous system infections., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: In a nationwide, matched cohort study, we aimed to investigate risks of haematologic cancers among individuals tested for Borrelia burgdorferi (Bb) antibodies, and among serum Bb seropositive individuals., Methods: We identified all Bb seropositive individuals in Denmark (1993-2020) (n = 52 200) and constructed two age- and sex-matched comparison cohorts: (a) Bb seronegative controls (n = 104 400) and (b) background population controls (n = 261 000). We calculated short-term OR (aOR) (<1 month of study inclusion), and long-term hazard ratios (aHR) (>1 month after study inclusion) adjusted for age and sex. We stratified seropositive individuals on only Bb-IgM seropositive (n = 26 103), only Bb-IgG seropositive (n = 18 698), and Bb-IgM-and-IgG seropositive (n = 7399)., Results: Compared with the background population, individuals tested for Bb antibodies had increased short-term (aOR: 12.6, 95% CI: 10.1-15.6) and long-term (aHR: 1.3, 95% CI: 1.2-1.4) risk of haematologic cancers. The Bb seropositive individuals had no increased risk of haematologic cancers compared with those who tested negative for Bb, except that Bb-IgM-and-IgG seropositive individuals had increased long-term risk of chronic lymphatic leukaemia (aHR: 2.0, 95% CI: 1.2-3.4)., Discussion: Our results suggest that Bb antibody testing is included in the work-up of unspecific symptoms preceding diagnosis of haematologic cancers. Bb-IgM-and-IgG seropositivity was associated with a two-fold increased long-term risk of chronic lymphatic leukaemia, which warrants further investigation., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims : Danish surveillance data indicated a higher risk of revision due to prosthetic joint infection (PJI) following total hip arthroplasty (THA) performed during the summer season. We investigated the association between summer and revision risk following primary THA. Methods : This study identified 58 449 patients from the Danish Hip Arthroplasty Register (DHR) with unilateral primary THA due to osteoarthritis from 2010-2018. From Danish Health Registries, we retrieved information on Charlson Comorbidity Index (CCI), immigration, and death and microbiological data on intraoperative biopsies and cohabitation status. Meteorological data were received from the Danish Meteorological Institute. Summer was defined as June-September, and THAs performed during October-May were used as controls. The primary outcome was revision due to PJI: the composite of revision with ≥ 2 culture-positive biopsies or reported PJI to the DHR. The secondary outcome was any revision. The cumulative incidences of revision and the corresponding adjusted relative risk (RR) with 95 % confidence intervals (CI) were calculated by season of the primary THA. Results : A total of 1507 patients were revised, and 536 were due to PJI. The cumulative incidence for THAs performed during summer and the rest of the year was 1.1 % (CI 1.0-1.3) and 1.1 % (CI 1.0-1.2) for PJI revision and 2.7 % (CI 2.5-3.0) and 2.5 % (CI 2.4-2.7) for any revision, respectively. The adjusted RR for THAs performed during summer vs. the rest of the year for PJI revision and any revision was 1.1 (CI 0.9-1.3) and 1.1 (CI 1.0-1.2), respectively. Conclusion : We found no association between summer and the risk of PJI revision or any revision in a northern European climate., Competing Interests: The contact author has declared that none of the authors has any competing interests., (Copyright: © 2024 Rajzan Joanroy et al.)

Ultra-low temperature (ULT) freezers are used to store perishable biological contents and are among the most energy-intensive equipment in laboratory buildings, biobanks, and similar settings. To ensure reliable and efficient operation, it is essential to implement data-driven fault detection and diagnostic algorithms, along with energy optimization techniques. This study presents labelled and long-term ULT-freezer performance dataset, the first of its kind, derived from 53 ULT freezers featuring two different control strategies. The dataset comprises high-resolution historical operation data spanning up to 10 years. More than 10 attributes are recorded from the freezing chamber and critical locations in the refrigeration systems. The dataset is labelled with regular events, such as door openings, as well as fault events obtained from 46 service reports. A scalable data pipeline, consisting of extraction, transformation, and loading processes, is developed to convert the raw data into a format ready for analysis. The dataset can be utilized to support the development of data-driven models and algorithms that advance the intelligent digital operation of ULT freezers., (© 2023. The Author(s).)

Background: In a country with a high-test frequency, societal lockdown, and pregnancy leave granted from 28 gestational weeks, we investigated SARS-CoV-2 infection in women admitted in labor and their newborn in the pre-vaccine period. Material and methods: A total of 1042 women admitted for delivery in two Danish hospitals agreed to a plasma sample and nasopharyngeal, vaginal, and rectal swabs and to sampling of umbilical cord blood and a nasopharyngeal swab from their newborn at delivery. Plasma samples from women were examined for SARS-CoV-2 antibodies. If antibodies were detected, or the woman had a positive nasopharyngeal swab upon admission or had a household contact with symptoms consistent with COVID-19, SARS-CoV-2 PCR was performed on plasma and swab samples from mother and child. Results: Seventeen women (1.6%) were seropositive. Half the newborn ( n = 9 (53%)) of seropositive mothers were also seropositive. None of the seropositive women or newborns had clinical signs of COVID-19 and all had SARS-CoV-2 PCR negative plasma and swab samples. Conclusion: Adherence to specific national guidelines pertaining to testing, self-imposed isolation, and cautious behaviors among pregnant women likely contributed to the exceptionally low prevalence of both prior and current COVID-19 infections detected at the time of childbirth preceding the routine vaccination of pregnant women in Denmark.

Objectives: To identify and investigate different cohorts of cancer patients' use of physical rehabilitation and specialised palliative care (SPC) services, focusing on patients with incurable cancer and the impact of social vulnerability., Methods: The sample originated from patients diagnosed during 2013-2018 and alive 1 January 2015. Use of physical rehabilitation and/or SPC units were identified from contacts registered in population-based administrative databases. Competing-risks regression models were applied to investigate disparities with regard to social vulnerability, disease duration, gender and age., Results: A total of 101 268 patients with cancer were included and 60 125 survived longer than 3 years after their diagnosis. Among the 41 143 patients, who died from cancer, 66%, survived less than 1 year, 23% survived from 1 to 2 years and 11% survived from 2 to 3 years. Contacts regarding physical rehabilitation services appeared in the entire cancer trajectory, whereas contacts regarding SPC showed a steep increase as time drew closer to death. The largest disparity was related to disease duration. Socially vulnerable patients had less contact with SPC, while a larger proportion of the socially vulnerable cancer survivors used rehabilitation, compared with the non-vulnerable patients., Conclusions: This study provides a previously unseen detailed overview of the use of physical rehabilitation and/or SPC among patients with incurable cancer. The services appeared to overlap at a group level in the cancer trajectory, emphasising the importance of awareness with regard to coordination and combination of the services. Disparities between socially vulnerable or non-vulnerable patients were identified., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Sensitive and rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a vital goal in the ongoing COVID-19 pandemic. We present in this comprehensive work, for the first time, detailed fabrication and clinical validation of a point of care (PoC) device for rapid, onsite detection of SARS-CoV-2 using a real-time reverse-transcription loop-mediated isothermal amplification (RT-LAMP) reaction on a polymer cartridge. The PoC system, namely PATHPOD, consisting of a standalone device (weight less than 1.2 kg) and a cartridge, can perform the detection of 10 different samples and two controls in less than 50 min, which is much more rapid than the golden standard real-time reverse-transcription Polymerase Chain Reaction (RT-PCR), typically taking 16-48 h. The novel total internal reflection (TIR) scheme and the reactions inside the cartridge in the PoC device allow monitoring of the diagnostic results in real-time and onsite. The analytical sensitivity and specificity of the PoC test are comparable with the current RT-PCR, with a limit of detection (LOD) down to 30-50 viral genome copies. The robustness of the PATHPOD PoC system has been confirmed by analyzing 398 clinical samples initially examined in two hospitals in Denmark. The clinical sensitivity and specificity of these tests are discussed., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors.)

Objective: To map existing research concerning rehabilitation interventions for young adult cancer survivors (YACS) that address at least one factor from the biopsychosocial health model., Design: Scoping review., Data Sources: Searches were performed in EMBASE, MEDLINE, PsycINFO, CINAHL and Cochrane in January 2022 and updated in March 2023, and grey literature between February and April 2022., Methods: The review followed Joanna Briggs Institute's methodology for scoping reviews. Quantitative, qualitative and mixed methods studies evaluating interventions for YACS of any cancer who had completed primary treatment and were between 18 and 39 years old at diagnosis were included. Two authors independently screened studies for eligibility, and standardised forms were used for data extraction. Descriptive statistics, narrative summaries and thematic analysis were used to analyse the data., Results: The search revealed 5706 records, of which 70 were full-text screened. The 20 included studies represented a heterogeneous group of 444 young adults with different cancer types, mean age above 25, and an overrepresentation of females. Most studies were feasibility and pilot studies. The 20 studies consisted of 14 unique interventions focusing primarily on one dimension of the biopsychosocial health model like biological or psychological factors. In the 14 interventions, the most frequent intervention element was peer-to-peer support ( n  = 12). The interventions were often delivered online ( n  = 9), lasting 3-12 months ( n  = 8). A wide variety of theories, providers and outcome measures were used., Conclusion: The results show that current research on multicomponent, biopsychosocial and age-specific rehabilitation for YACS remains at an early stage.

Importance: Gender affirming treatment aims to improve mental health., Objective: To investigate longitudinal mental health outcomes in Danish transgender persons., Design: National register-based cohort study in Danish transgender persons with diagnosis code of "gender identity disorder" during the period 2000-2021., Participants: Five age-matched controls of the same sex at birth and five age-matched controls of the other sex at birth were included for each transgender person., Main Outcomes: Diagnosis codes of mental and behavioral disorders and/or prescription of psychopharmacological agents until June 2022., Results: The cohort included 3812 transgender persons with median age (interquartile range) 19 (15; 24) years for persons assigned female at birth (AFAB, N = 1993) and 23 (19; 33) years for persons assigned male at birth (AMAB, N = 1819) and 38 120 controls. Follow up duration was up to 10 years with mean (standard deviation) 4.5 (4.3) years. In transgender persons AFAB compared to control women, the odds ratio (OR) (95% confidence interval) for mental and behavioral disorders was 6.7 (5.5; 8.1) before the index date, 9.9 (8.4; 11.7) at 1 year, 5.8 (4.4; 7.7) at 5 years, and 3.4 (2.1; 7.5) at 8 years follow up. In transgender persons AMAB compared to control men, corresponding ORs were 5.0 (4.0; 6.4), 11.3 (9.3; 13.7), 4.8 (3.5; 6.5), and 6.6 (4.2; 10.3) at 8 years follow up (all P < .001)., Conclusion: The OR for mental health disorders was higher in transgender persons compared to controls and remained elevated throughout follow up, especially in transgender persons AMAB., Competing Interests: Conflicts of interest: The authors declare that they have no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We developed four algorithms for the automatic capture of C-reactive protein (CRP) peaks in 296 adult patients with acute myeloid leukemia who had bloodstream infection (BSI) episodes, negative blood cultures (BCs) or possible infections where no BCs were performed. The algorithms detected CRP peaks for 418-446 of the 586 documented BSI episodes (71.3-76.1%) and 2714-3118 of the 4382 negative BCs (61.9-71.2%). The four algorithms captured 382-789 CRP peaks in which there were neither BSI episodes nor negative BCs. We conclude that automatic capture of CRP peaks is a tool for the monitoring of BSI episodes and possibly other infections in patients with acute myeloid leukemia.

Background: Identification of socially vulnerable cancer patients in the health care system is difficult. Only little is known concerning changes in the patients' social circumstances during the trajectory. Such knowledge is valuable regarding the identification of socially vulnerable patients in the health care system. The objective of this study was to use administrative data to identify population-based characteristics of socially vulnerable cancer patients and investigate how social vulnerability changed during the cancer trajectory., Methodology: A registry-based social vulnerability index (rSVI) was applied to each cancer patient prior to their diagnosis, and used to assess changes in social vulnerability after the diagnosis., Results: A total of 32,497 cancer patients were included. Short-term survivors (n = 13,994) died from cancer from one to three years after the diagnosis, and long-term survivors (n = 18,555) survived at least three years after the diagnosis. 2452 (18 %) short-term survivors and 2563 (14 %) long-term survivors were categorized as socially vulnerable at diagnosis, of these 22 % and 33 % changed category to not socially vulnerable during the first two years after the diagnosis, respectively. For patients changing status of social vulnerability, several social and health-related indicators changed, which is in line with the complexity of the multifactorial social vulnerability. Less than 6 % of the patients categorized as not vulnerable at diagnosis, changed to become vulnerable during the following two years., Conclusion: During the cancer trajectory, social vulnerability may change in both directions. Surprisingly, more patients, who were categorized as socially vulnerable when their cancer was diagnosed, changed status to not socially vulnerable during follow-up. Future research should attempt to increase knowledge on identifying cancer patients, who experience deterioration after the diagnosis., Competing Interests: Declaration of Competing Interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023. Published by Elsevier Ltd.)

Molecular methods for diagnosing Lyme neuroborreliosis (LNB) have shown suboptimal diagnostic sensitivities. The objective of this study was to improve the clinical sensitivity of PCR detection of Borrelia burgdorferi sensu lato spirochetes by inoculating cerebrospinal fluid (CSF) from patients suspected of LNB directly into culture medium at the time of lumbar puncture, with this pursuing enrichment of Borrelia spirochetes before PCR analysis. Adult patients with symptoms suggestive of LNB were prospectively enrolled at two hospitals in the Region of Southern Denmark. The CSF-culture samples were incubated for at least eight weeks. During this period, culture sample aliquots were analysed for the presence of Borrelia DNA by separate PCR protocols in two independent clinical laboratories. The included patients were diagnosed with definite (n=12) or possible (n=2) LNB, and non-LNB (n=171) based on clinical and paraclinical findings. Patients in the LNB and the non-LNB group had a median duration from symptom onset to lumbar puncture of 40 days (IQR [23-90] days) and 120 days (IQR [32-365] days), respectively. Pre-enrichment growth of Borrelia spirochetes was accomplished from three patients (21 %) in the LNB group. The positive culture samples were confirmed by both the digital droplet PCR and the real-time PCR methods employed. All CSF samples were PCR negative in the non-LNB group. The results of this study do not support the use of Borrelia-specific PCR as a general routine diagnostic tool in adults. Still, they suggest it may prove of additional value in selected patients with a limited time from symptom onset to sample collection., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Objective: To examine the effect of including maternal age and body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters) as additional risk factors in the traditional risk-based strategy at term pregnancies consisting of previous early-onset group B streptococcus (GBS) disease, GBS bacteriuria during pregnancy, maternal temperature of 38.0°C or more intrapartum, and rupture of membranes of 18 h or longer., Methods: A secondary analysis of a Danish cohort including 902 pregnant women. Exposures were maternal age and pre-pregnancy BMI. Outcome was rectovaginal GBS colonization at the time of labor. The logistic regression analysis adjusted for parity, gestational age, vaginal delivery, and smoking., Results: The GBS prevalence was 17% in the entire population, 35% among participants older than 40 years, and 23% among those with a BMI of 25 or greater. Including maternal "age > 40" as an additional risk factor increased the sensitivity of the risk-based strategy from 21% to 26% and decreased the specificity from 90% to 87%. Inclusion of "BMI ≥ 25" increased the sensitivity from 21% to 57% and decreased the specificity from 90% to 59%., Conclusions: Maternal age and BMI might be included as additional risk factors in risk-based programs for identification of GBS-positive laboring women to receive intrapartum antibiotics prophylaxis., (© 2022 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

The purpose of this study was to examine the transfer rate of SARS-CoV-2 IgG antibodies in pregnancy and newborns. Two Danish labor wards screened all women for SARS-CoV-2 by PCR upon arrival. Women (n = 99) with a SARS-CoV-2 PCR-positive nasopharyngeal (NP) swab or with a household member with a positive swab at labor or any time during pregnancy, or COVID-19 symptoms upon admission (November 2020 through August 2021), were included. Mother and infant were tested by NP swabs at delivery, and maternal and infant (umbilical cord) venous blood samples were collected. We obtained clinical information including previous PCR test results from the medical records. SARS-Cov-2 IgM and quantified IgG antibodies were measured by enzyme-linked immunosorbent assay and transfer ratios of IgG. We detected IgG antibodies in 73 women and 65 cord blood sera and found a strong correlation between SARS-CoV-2 IgG concentrations in maternal and umbilical cord sera (r = 0.9; p < 0.05). Transfer ratio was > 1.0 in 51 out of 73 (69%) infants and > 1.5 in 26 (35%). We found that transfer was proportional to time from a positive SARS-CoV-2 PCR NP swab to delivery (r = 0.5; p < 0.05). Transfer ratios of SARS-CoV-2 antibodies were associated with time from infection to delivery with transfer ratios of more than 1.0 in the majority of seropositive mother-infant dyads., (© 2023. The Author(s).)

Professional development programs for teachers in higher education are often characterized by top-down approaches, which fail to make appreciable differences in teaching practices. This study uses a qualitative approach to explore activity-oriented design (AOD) as an instrument for collaborative learning in higher education teacher professional development. We examine Teknosofikum, an ongoing project developed in Denmark along three iterations, involving a total of 64 course participants (42 in the hybrid format; 22 online). The study applies the methodology of design-based research: data was collected via 15 semi-structured group interviews, online forums, and field notes/recordings from online meetings and onsite workshops. Data analysis follows the methodology of grounded theory and evidence is given significance inductively, based on contextual data. Four activities were selected to assess the potential of AOD methods in enhancing teacher collaboration, with different aims reflection, discussion, theory-practice alignment, and participation. Our analysis revolved around three main categories: trust, deep interaction, and shared beliefs/values. The results show how collaborative group work activities have improved trust and knowledge-sharing among participants and have contributed to creating a safe learning environment. The paper concludes that AOD methods could better assist educational designers in promoting professional development courses that aim at enhancing teacher collaboration in higher education., Competing Interests: Conflict of interestThe authors declare no conflicts of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objective: To explore factors associated with a high vaginal GBS load during labor considering (1) the recto-vaginal GBS load at 35-37 weeks' gestation determined by culture and (2) the vaginal GBS colonization determined by a polymerase chain reaction (PCR) assay during labor., Methods: From an unselected cohort of 902 pregnant women, we obtained (1) recto-vaginal swabs for culture of GBS at 35-37 weeks' gestation (GBS rectovag-36 ), (2) vaginal swabs for GBS PCR detection at labor (PCR vag-labor ), and (3) vaginal swabs for culture of GBS at labor (GBS vag-labor ). The GBS load was classified semi quantitatively according to a culture protocol without prior broth enrichment of the swab samples: none (0), few (+), some (++), or many (+++) GBS colonies., Results: Among 902 unselected pregnant women, 859 (95%) had a vaginal swab culture taken at labor, which was classified semi quantitatively. High load GBS vag-labor (+++) were found in 31 participants. GBS rectovag-36 showed a sensitivity of 90% (28/31) and a PPV of 23% (28/121), whereas PCR vag-labor had a sensitivity of 98% (30/31, non-significant difference) and a PPV of 42% (30/71, p  < .01). PCR at labor had a lower sensitivity (78%) for detection of vaginal colonization with GBS at labor (any load) compared to recto/vaginal colonization with GBS at 36 weeks (92%). Vaginal colonization with GBS at 36 weeks seemed to have a lower sensitivity for detecting GBS in vagina at labor for high load (48%) and for any load (39%)., Conclusion: PCR at labor has higher detection rate (non-significant) and PPV in identification of laboring women with a high load of vaginal GBS compared with recto-vaginal culture at 36 weeks' gestation.

Objectives and study design: In this population-based study of 602 patients, we amended C-reactive protein (CRP) and plasma albumin (PA) levels around the diagnosis of diffuse large B-cell lymphoma (DLBCL) to the International Prognostic Index (IPI) and assessed 0-90, 91-365, and +365-day survival. Results: The CRP did not contribute to the IPI's prognostic or discriminatory ability, regardless of time period, particularly not in models with PA. In contrast, the PA was an important contributor, especially in the 0-90 day period, but also up to one year after the diagnosis. For day 0-90, the model with the IPI only had an Area Under the Receiver Operating Characteristics (AUROC) of 0.742, whereas the IPI with PA as a continuous variable rendered an AUROC of 0.841. Especially the lower PA quartile (18-32 g/L) contributed to the worse prognosis. Conclusions: The amendment of PA to the IPI may significantly improve the short-term prognostic and discriminative ability.Key messagesThe amendment of the plasma albumin (PA) level to the International Prognostic Index significantly improved the prediction of mortality up to one year after the diagnosis of diffuse large B-cell lymphoma.It was especially the lower quartile of the PA level (18-32 g/L) that contributed to the worse prognosis.

Direct detection of Borrelia burgdorferi sensu lato bacteria in patient samples for diagnosis of Lyme neuroborreliosis (LNB) is hampered by low diagnostic sensitivity, due to few bacteria in cerebrospinal fluids (CSF) samples. Evaluation of novel molecular methods, including digital PCR (dPCR), as future tools in diagnostics of LNB is desirable. This study aimed to establish a dPCR assay and validate pre-PCR procedures for detection of Borrelia in CSF. Synthetic DNA fragments and cultured Borrelia reference strains were used during optimisation experiments. In addition, 59 CSF specimens from patients examined for LNB were included for clinical validation. The results showed that the pre-PCR parameters with the highest impact on Borrelia-specific dPCR method performance were incubation of the PCR-plate at 4 °C for stabilization of droplets, centrifugation for target concentration, quick-spin for dPCR rain reduction, and PCR inhibition by matrix components. Borrelia DNA in CSF was detected in one out of nine patients with LNB. Diagnostic sensitivity was determined to be 11.1% and specificity 100%. In conclusion, this study reports an optimized Borrelia-specific dPCR method for direct detection of Borrelia in CSF samples. The present study does not support the use of Borrelia-specific dPCR as a routine method for diagnosing LNB., (© 2022. The Author(s).)

Background: There is a well-described association between bacteremia with bovis group streptococci or Clostridium septicum and an increased probability of a colorectal cancer (CRC) diagnosis. We wanted to investigate the existence of a similar association between CRC and bacteremia with other bacteria belonging to the gut microbiota.., Methods: A population based cohort study in a population about 2 million people including 45 774 bacteremia episodes and 231 387 blood culture negative cases was performed in the Region of Southern Denmark and Region Zealand from 2007-2016. Episodes of bacteremia were combined with the Danish central register for CRC. We performed Cox's regression analysis with hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: The study results confirmed previous findings of an increased risk of a CRC diagnosis after bacteremia with the bovis group streptococci (risk within a year: 4.3%; HR [95% CI]: 8.46 [3.51-20.4]) or C. septicum (20.8%; 76.2 [42.0-138]). Furthermore, Bacteroides ovatus (6.7%; 20.3 [5.04-81.8]), Bacteroides uniformis (5.4%; 16.2 [4.02-65.7]), Clostridium tertium (3.6 %; 13.9 [1.96-99.4]), Fusobacterium spp. (excluding F. necrophorum) (3.0 %; 8.51 [2.73-26.5]), and Gram-positive anaerobic cocci (3.6 %; 10.9 [4.50-26.3]) were also associated with an increased risk of a CRC diagnosis compared to patients with negative blood cultures (0.4%)., Conclusions: Bacteremia with specific gut microbiota anaerobic bacteria is associated with a high risk of a diagnosis of CRC, indicating the need for colorectal workup. Importantly, this strategy also holds the possible additional benefit of detecting adenomas or other premalignant conditions, which were not included in the present study., Competing Interests: Potential conflicts of interests. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: Clinical guidelines disagree on the diagnostic usefulness of Borrelia burgdorferi (Bb) serum antibodies (serum-Bb) in investigation of Lyme neuroborreliosis (LNB). We investigated the association between serum-Bb and Bb intrathecal antibody index (Bb-AI) and rates of seroconversion and seroreversion after LNB., Methods: Danish residents who had a Bb-AI and corresponding serum-Bb measured between 1994 and 2020 were identified at all Danish departments of clinical microbiology. We used descriptive statistics to examine the proportions of positive Bb-AI combined with positive or negative serum-Bb antibody tests. Next, the rate of seroconversion and seroreversion among those with positive Bb-AI and either an initial negative or positive serum-Bb was estimated., Results: We included 34 609 individuals with a Bb-AI and corresponding serum-Bb. The proportion of individuals with positive Bb-AI who had negative serum-Bb was 16.8% (95% CI, 15.1-18.6). The proportion of individuals with positive serum-Bb IgM, serum-Bb IgG, or serum-Bb IgM and IgG antibodies who had positive Bb-AI was 10.6% (95% CI, 9.5-11.8), 24.7% (95% CI, 23.0-26.4), and 45.0% (95% CI, 42.4-48.0), respectively. The proportion of children (<18 years) with positive serum-Bb IgM and IgG antibodies who had a positive Bb-AI was 59.7% (95% CI, 53.4-65.8). The proportion of individuals with positive Bb-AI with initial negative or positive serum-Bb antibodies who seroconverted or seroreverted within 2 years was 17.3% (95% CI, 6.9-27.8) and 23.2% (95% CI, 19.1-27.7), respectively., Conclusions: Serum-Bb antibodies could not predict results of Bb-AI. A fifth of both seronegative and seropositive individuals with positive Bb-AI seroconverted or seroreverted within 2 years., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

CXCL13 in cerebrospinal fluid has gradually become an established biomarker for Lyme neuroborreliosis (LNB), however the diagnostic performance of CXCL13 may be improved by the addition of IL-6, a non-specific infection biomarker. The aim of this study was to measure the concentrations of CXCL13 and IL-6 in cerebrospinal fluid, in the attempt to evaluate the diagnostic performance of these two biomarkers, in the differentiation between definite and possible LNB, as well as between LNB and other neuroinfections. This study used a cross-sectional design to quantify the levels of CXCL13 and IL-6 in cerebrospinal fluid (CSF) specimens from consecutive patients examined for central nervous system (CNS) infections at Lillebaelt Hospital in the Region of Southern Denmark. CXCL13 and IL-6 were measured simultaneously using the Bio-Plex 200 multiplex Cytokine Immunoassay System (Bio-Rad). Based on clinical and paraclinical findings, we grouped patients into six separate groups: definite LNB, possible LNB, Viral CNS infection, non-Borrelia Bacterial CNS infection, Other CNS disease (with pleocytosis) and Negative (without pleocytosis). A combined interpretation of four variables (leukocyte cell counts, protein concentration, CXCL13 and IL-6 concentrations in CSF) is presented using principal component cluster analysis. We included by chart review 390 patients discharged with definite LNB (n = 31), possible LNB (n = 10), confirmed Viral or non-Borrelia Bacterial CNS infection (n = 34), Other CNS disease (n = 58), and Negative (n = 257) for CXCL13 and IL-6 analysis. Principal component analysis (PCA) revealed three distinct clusters based on leukocyte cell counts, protein concentration, CXCL13 and IL-6 concentrations in CSF from 380 included patients (10 possible LNB patients excluded). The clusters clearly differentiate the groups: definite LNB, non-Borrelia Bacterial CNS infection and Negative (without pleocytosis). A receiver operating characteristic (ROC) curve comparing LNB patients (n = 31) and all non-LNB conditions with CSF pleocytosis (n = 99) indicated an optimal CXCL13 cut-off value of 50.7 pg/mL, resulting in a sensitivity and a specificity of 93.6 and 91.1%, respectively. The ROC analysis comparing patients with confirmed non-LNB CNS infection (n = 34) and all others with CSF pleocytosis (n = 97) resulted in an optimal IL-6 cut-off value of 111.5 pg/mL, yielding a sensitivity and a specificity of 78.8% and 82.5% respectively. Of the ten possible LNB patients, three cases (with CXCL13 levels above cut-off) fall within the LNB cluster, and one case is just outside, providing some laboratory support for the diagnosis of LNB. The remaining six possible LNB patients (with CXCL13 levels below the 50.7 cut-off) had little support for the diagnosis of LNB in the PCA-plot. The results of this study confirm that CXCL13 is a valuable supplement for diagnosis of LNB, and that the combination of CXCL13 and IL-6 may be used to differentiate cases of LNB from other CNS infections. Furthermore, IL-6 can be of differential diagnostic value when evaluating patients with possible LNB., (Copyright © 2022. Published by Elsevier GmbH.)

Background: Social vulnerability is a complex construct which is beyond relying on single measures. If socially vulnerable patients should be identified, we need a composite measure capturing the patient's overall circumstances. This study presents the development of a social vulnerability index (rSVI) for cancer patients based on administrative data from population-based registers., Methods: All patients, who died from cancer within 5 years after the cancer diagnosis during 2013-2018 (n = 44,187), were identified and divided in four subcohorts according to survival; index cohort surviving 3-5 years (n = 3044 surviving 3-5 years), cohort 1 (n = 27,170 surviving < 1 year), cohort 2 (n = 9450 surviving 1-2 years), and cohort 3 (n = 4523 surviving 2-3 years). Variables from ten registries on health and social issues were linked to each individual patient. Variables of interest were weighted to construct the rSVI using the index-cohort. rSVI was subsequently tested on the three other cohorts for validation., Results: The rSVI included weighted values for marital status, ethnicity, education, income, unemployment, psychiatric comorbidity, and somatic comorbidity. The validity of the rSVI was supported by the expected trend in proportions of vulnerable patients when applied on the other cohorts. Single social measures appeared insufficient in identification of vulnerable patients when compared with the rSVI., Conclusion: The rSVI provides a tool for identification of socially vulnerable cancer patients using administrative data. The index requires further validation in other patient groups and is tested against other measures of vulnerability. Future perspectives are to use the rSVI as predictor of advanced cancer patients' use of healthcare services., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To investigate the impact of administering Intrapartum Antibiotic Prophylaxis (IAP) to laboring women with one or more risk factors for Early Onset Group B Streptococcal neonatal infection (EOGBS) based on the result of a rapid bedside test for Group B Streptococci (GBS)., Study Design: Quality assessment study., Methods: Three-hundred-sixty-six laboring women admitted to our maternity ward, with one or more risk factors for EOGBS, were prospectively included. Rectovaginal swab-samples were examined bedside by the GenomEra® GBS Polymerase Chain Reaction (PCR) assay upon admission. Time from administration of IAP to delivery was registered. According to national guidelines, one-hundred-two women mandatorily received IAP independent of the PCR test result fulfilling one of the following three risk factors: prior infant with EOGBS, preterm labor before 35 gestational week, temperature ≥ 38 °C during labor. Women with GBS bacteriuria during current pregnancy, rupture of membranes ≥ 18 h IAP, and preterm labor between 35 and 37 gestational week, received IAP solely if the PCR test was positive. Predictive values were calculated for each risk factor., Results: Previous GBS bacteriuria was strongly associated (PPV = 71%) with a positive GBS PCR test, whilst the corresponding positive percent of ROM > 18 h and of GA 35-37 was only PPV = 16% and 22%, respectively. Seventy-four women, 74/251 (31%), received IAP because they were GBS PCR positive. IAP was thus reduced by about two-thirds compared to the risk-based strategy of offering IAP to all women with one or more risk factors for EOGBS. Two women, 2/254 (0.8%), received inferior care, as they did not receive IAP within the recommended 4 h prior to delivery due to the extra time spend on the test procedure., Conclusion: Bedside intrapartum PCR testing of women with risk factors for EOGBS effectively diminishes use of IAP during labor compared to the present risk factor-based strategy alone. In this project, the extra time spend on the PCR test procedure did not lead to noticeable delay in IAP., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: We describe the serotype distribution of Streptococcus agalactiae (GBS) carriage isolates from women in labor and among GBS isolates causing invasive infections during the same period to see if the distribution of carriage serotypes reflects the GBS serotypes causing invasive diseases including early-onset disease (EOGBS)., Methods: Data on invasive isolates from 2019 including serotype, erythromycin and clindamycin susceptibility was retrieved from the Danish national reference laboratory, Statens Serum Institut. Carriage isolates were collected from women with risk factors for EOGBS enrolled at delivery at the maternity ward at a Danish University Hospital, first half of 2019., Results: Among carriage isolates, the dominant serotype was IX (21 %) followed by serotype III (19 %). The resistance to erythromycin and clindamycin was 21 and 26 %, respectively. Among invasive GBS isolates, no case of EOGBS with serotype IX was detected but the distribution of serotypes were otherwise similar to the GBS carrier strains. The corresponding resistance to erythromycin and clindamycin was 23  and 15 %, respectively. Penicillin resistance was not detected among carriage nor invasive isolates., Conclusions: The distribution of serotypes among carriage and invasive GBS reflects the assumption that EOGBS occur following transmission of GBS from mother to newborn, with the exception of serotype IX., (© 2021. The Author(s).)

This study aimed to develop a highly sensitive SARS-CoV-2 nucleocapsid antigen assay using the single molecule array (Simoa) technology and compare it with real time RT-PCR as used in routine clinical practice with the ambition to achieve a comparative technical and clinical sensitivity. Samples were available from 148 SARS-CoV-2 real time RT-PCR positive and 73 SARS-CoV-2 real time RT-PCR negative oropharyngeal swabs. For determination of technical sensitivity SARS-CoV-2 virus culture material was used. The samples were treated with lysis buffer and analyzed using both an in-house and a pre-commercial SARS-CoV-2 nucleocapsid antigen assay on Simoa. Both nucleocapsid antigen assays have a technical sensitivity corresponding to around 100 SARS-CoV-2 RNA molecules/mL. Using a cut-off at 0.1 pg/mL the pre-commercial SARS-CoV-2 nucleocapsid antigen assay had a sensitivity of 96% (95% CI 91.4-98.5%) and specificity of 100% (95% CI 95.1-100%). In comparison the in-house nucleocapsid antigen assay had sensitivity of 95% (95% CI 89.3-98.1%) and a specificity of 100% (95% CI 95.1-100%) using a cut-off at 0.01 pg/mL. The two SARS-CoV-2 nucleocapsid antigen assays correlated with r = 0.91 (P < 0.0001). The in-house and the pre-commercial SARS-CoV-2 nucleocapsid antigen assay demonstrated technical and clinical sensitivity comparable to real-time RT-PCR methods for identifying SARS-CoV-2 infected patients and thus can be used clinically as well as serve as a reference method for antigen Point of Care Testing., (© 2021. The Author(s).)