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Tina Hovgaard Lützen,1 Charlotte Ulrikka Rask,2,3 Oleguer Plana-Ripoll,4 Bodil Hammer Bech,1 Lene Wulff Krogsgaard,1 Nanna Rolving,5,6 Dorte Rytter1 1Research Unit for Epidemiology, Department of Public Health, Aarhus University, Aarhus C 8000, Denmark; 2Research Unit, Department of Child and Adolescent Psychiatry, Aarhus University Hospital, Aarhus N 8200, Denmark; 3Department of Clinical Medicine, Aarhus University, Aarhus N 8200, Denmark; 4National Centre for Register-Based Research, Department of Economics and Business Economics, Aarhus University, Aarhus V 8210, Denmark; 5University Clinic of Innovative Patient Pathways, Diagnostic Centre, Silkeborg Regional Hospital, Silkeborg 8600, Denmark; 6DEFACTUM, Corporate Quality, Central Denmark Region, Aarhus N 8200, DenmarkCorrespondence: Tina Hovgaard Lützen Research Unit for Epidemiology, Department of Public HealthAarhus University, Bartholins Allé 2, Aarhus C 8000, DenmarkTel +45 22410722Email tina.lutzen@ph.au.dkAim: This study aimed to describe and compare general practitioner (GP) attendance patterns in the years surrounding HPV-vaccination among cases suspected to experience adverse events and their matched controls in order to determine if a potential larger change in GP attendance among cases was observed in temporal relation to vaccination.Methods: Register-based, matched case–control study. Cases were defined as women referred to specialized hospital settings (HPV-centers) for suspected adverse event between June 1st 2015 and December 31st 2015 (n=1458). Information on referral was obtained from the HPV-centers directly. Each case was matched with five controls on age at vaccination, region, time of first vaccine registration and total number of doses, resulting in a total study population of 8670 girls and women. Negative binomial regression analyses were used (i) to estimate mean yearly GP contacts among cases and controls, and (ii) to further investigate the relative difference in change in GP attendance following vaccination between cases and controls.Results: Overall, cases displayed higher GP attendance than controls from five years before vaccination up until five years after. Compared to controls, cases increased their GP attendance more in the years following HPV vaccination, corresponding to a 40% increase in the incidence rate ratios (IRR) from before to after vaccination (ratio-IRR = 1.40 [1.36; 1.44]). The change occurred in close proximity to vaccination, and the pattern was the same independently of the year of vaccination. However, for the later vaccination years cases displayed an additional increase in their GP attendance around time of extensive media attention.Conclusion: Girls and women being referred for suspected adverse events after HPV-vaccination changed their GP attendance pattern in close proximity to their first HPV-vaccination and not solely in temporal linkage to the onset of public debate.Keywords: HPV vaccination, general practice attendance, adverse effects, case–control

Morten Breinholt Søvsø,1,2 Bodil Hammer Bech,3 Helle Collatz Christensen,4 Linda Huibers,2 Erika Frischknecht Christensen,1 Morten Bondo Christensen2 1Centre for Prehospital and Emergency Research, Aalborg University and Aalborg University Hospital, Aalborg, Denmark; 2Research Unit for General Practice, Aarhus, Denmark; 3Department of Public Health, Research Unit for Epidemiology, Aarhus University, Aarhus, Denmark; 4Emergency Medical Services, Copenhagen, University of Copenhagen, Copenhagen, DenmarkCorrespondence: Morten Breinholt SøvsøCentre for Prehospital and Emergency Research, Aalborg University and Aalborg University Hospital, Søndre Skovvej 15, Aalborg 9000, DenmarkTel +45 9764 4446Email morten.soevsoe@rn.dkBackground: Out-of-hours (OOH) health care services are often divided into emergency medical services (EMS) and OOH primary care (OOH-PC). EMS and many OOH-PC use telephone triage, yet the patient still makes the initial choice of contacting a service and which service. Sociodemographic characteristics are associated with help-seeking. Yet, differences in characteristics for EMS and OOH-PC patients have not been investigated in any large-scale cohort studies. Such knowledge may contribute to organizing OOH services to match patient needs. Thus, in this study we aimed to explore which sociodemographic patient characteristics were associated with utilizing OOH health care and to explore which sociodemographic characteristics were associated with EMS or OOH-PC contact.Methods: A population-based observational cohort study of inhabitants in two regions (North Denmark Region and Capital Region of Copenhagen) with or without contact to OOH services during 2016 was conducted. Associations between sociodemographic characteristics and OOH contacts (and EMS versus OOH-PC contact) were evaluated by regression analyses.Results: We identified 619,857 patients with OOH contact. Female sex (IRR=1.16 (95% CI: 1.16– 1.17)), non-western ethnicity (IRR=1.02 (95% CI: 1.01– 1.02)), living alone (IRR=1.08 (95% CI: 1.08– 1.09)), age groups ≥ 81 years (IRR=2.00 (95% CI: 1.98– 2.02)) and 0– 18 years (IRR=1.66 (95% CI: 1.66– 1.67)) and low income (IRR=1.41 (95% CI: 1.40– 1.42)) were more likely to contact OOH health care compared to males, Danish ethnicity, citizens cohabitating, age 31– 65 years and high income. Disability pensioners more often contacted OOH care (IRR=1.79 (95% CI: 1.77– 1.81) compared to employees. Old age (≥ 81 years) (OR=3.21 (95% CI: 3.13– 3.30)), receiving cash benefits (OR=2.45 (95% CI: 2.36– 2.54)), low income (OR=1.76 (95% CI: 1.72– 1.81)) and living alone (OR=1.40 (95% CI: 1.37– 1.42)) were all associated with EMS contacts rather than OOH-PC contacts.Conclusion: Several sociodemographic factors were associated with contacting a health care service outside office hours and with contacting EMS rather than OOH-PC. Old age, low income, low education and low socioeconomic status were of greatest importance.Keywords: out-of-hours health care, delivery of health care, Denmark, telephone hotline, telephone triage

Mette Tranberg,1,2 Bodil Hammer Bech,3 Jan Blaakær,4,5 Jørgen Skov Jensen,6 Hans Svanholm,1,7 Berit Andersen1,2 1Department of Public Health Programmes, Randers Regional Hospital, Randers, Denmark; 2Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 3Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark; 4Department of Obstetrics and Gynecology, Odense University Hospital, Odense, Denmark; 5Department of Clinical Medicine, University of Southern Denmark, Odense, Denmark; 6Research Unit for Reproductive Microbiology, Statens Serum Institut, Copenhagen, Denmark; 7Department of Pathology, Randers Regional Hospital, Randers, Denmark Background: Participation in cervical cancer screening varies by socioeconomic status. The aims were to assess if offering human papilloma virus (HPV) self-sampling kits has an effect on screening participation among various socioeconomic groups and to determine if two invitation strategies for offering self-sampling influence the participation rate equally.Methods: The study was based on registry data that were applied to data from a randomized controlled trial (n=9,791) measuring how offering HPV self-sampling affected screening participation. The women received either 1) a self-sampling kit mailed directly to their homes (directly mailed group); 2) an invitation to order the kit (opt-in group); or 3) a standard second reminder to attend regular cytology screening (control group). The participation data were linked to registries containing socioeconomic information.Results: Women in the directly mailed group participated significantly more than women in the control group, regardless of their socioeconomic status, but the largest effects were observed in Western immigrants (participation difference [PD]=18.1%, 95% CI=10.2%–26.0%) and social welfare recipients (PD=15.2%, 95% CI=9.7%–20.6%). Compared with the control group, opt-in self-sampling only had an insignificant effect on participation among women who were immigrants, retired, or less educated. Western immigrants had a significantly higher increase in participation than native Danish women when kits were mailed directly compared with the opt-in strategy (PD=18.1%, 95% CI=10.2%–26.2% and PD=5.5%, 95% CI=2.9%–8.1%, respectively, P=0.01).Conclusion: All socioeconomic groups benefited from the directly mailed strategy in terms of higher screening participation, but Western immigrants and lower socioeconomic groups seemed to benefit the most. Immigrants and some lower socioeconomic groups only had insignificant benefits of opt-in self-sampling. The directly mailed strategy might be preferable to opt-in self-sampling because it ensures that ethnic minority groups obtain benefits of introducing HPV self-sampling in an organized cervical cancer screening program.Trial registration: Current Controlled Trials NCT02680262. Registered February 10, 2016. Keywords: self-sampling, human papillomavirus testing, cervical cancer screening, screening participation, socioeconomic status, social class, mass screening

Anne Mette Lund Würtz,1,2 Claus Høstrup Vestergaard,1 Dorte Rytter,2 Merete Juul Sørensen,3 Jakob Christensen,4 Mogens Vestergaard,1,5 Bodil Hammer Bech1,2 1Research Unit for General Practice, 2Section for Epidemiology, Department of Public Health, Aarhus University, 3Regional Centre for Child and Adolescent Psychiatry, 4Department of Neurology, Aarhus University Hospital, 5Section for General Practice, Department of Public Health, Aarhus University, Aarhus, Denmark Background: Antipsychotic (AP) medication is increasingly used for many health conditions. Prenatal exposure to AP medication has been associated with several adverse outcomes, but the findings remain inconsistent.Purpose: We aimed to investigate prenatal exposure to AP medication and the use of primary health care system in childhood.Subjects and methods: All live-born singletons in Denmark during 1997–2012 were identified in the nationwide Danish National Patient Register and followed until December 31, 2013 (n = 963,010). Information on prenatal exposure to AP medication was obtained from the Danish Register of Medicinal Product Statistics. Contacts to the general practitioner (GP) were used as a proxy for the overall health of the children. Negative binomial regression was used to calculate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the association between prenatal exposure to AP medication and number and type of GP contacts, excluding routine well-child visits and vaccinations. The models were adjusted for sex and birth date of the child, maternal age, parity, cohabitation status, income, education, smoking status, diagnosis of substance abuse, severe psychiatric disorder, depression and epilepsy as well as the use of antiepileptic drugs, antidepressants, benzodiazepines and insulin.Results: The prenatally AP-exposed children had 7% more GP contacts than unexposed children, IRR: 1.07 (95% CI: 1.03, 1.11). The association was slightly stronger among children of mothers with no diagnosis of severe psychiatric disorder (IRR: 1.08, 95% CI: 1.04–1.13) than among children of mothers with severe psychiatric disorder (IRR: 1.03, 95% CI: 0.96–1.11), but the difference was not statistically significant. We found no difference between prenatally AP-exposed children and their unexposed siblings, IRR: 1.00 (95% CI: 0.97–1.04) for total contacts.Conclusion: Children of women using AP medication in pregnancy had more GP contacts in childhood than children of mothers not using AP medication. However, this might be explained by confounding from maternal behavior and mental illness. Keywords: antipsychotic medication, prenatal drug exposure, primary health care, general practitioner

Tina Hovgaard Lützen,1 Bodil Hammer Bech,2 Jesper Mehlsen,3 Claus Høstrup Vestergaard,1 Lene Wulff Krogsgaard,1 Jørn Olsen,4 Mogens Vestergaard,1 Oleguer Plana-Ripoll,5 Dorte Rytter2 1Research Unit for General Practice, Department of Public Health, Aarhus University, Aarhus C, Denmark; 2Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus C, Denmark; 3Coordinating Research Centre, Frederiksberg Hospital, Frederiksberg, Denmark, 4Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark; 5National Center for Register-based Research, Aarhus University, Aarhus V, Denmark Aim: No association between human papilloma virus (HPV) vaccination and numerous diseases has been found. Still, a large number of Danish women are reporting suspected adverse events. Other factors may play a role, and the aim of this study is to examine the association between psychiatric conditions, general practitioner (GP) attendance and indicators of psychological symptoms prior to HPV vaccination and the risk of referral to an HPV center following vaccination. Study design and setting: Register-based, matched case–control study. Cases were identified from five Danish, regional HPV centers, and health data for cases and controls were obtained from national registries. Participants: Cases were defined as women referred to an HPV center between January 1, 2015 and December 31, 2015 (n=1,496). Each case was matched with five controls on age, region and time of first vaccine registration. The total study population consisted of 8,976 women. Results: Overall, women above 18 years who had been referred to an HPV center were more likely to have used psychiatric medication (odds ratio [OR]: 1.88 [95% CI 1.48–2.40]) or to have been hospitalized because of a psychiatric disorder within 5 years prior to the first vaccine registration (OR: 2.13 [95% CI 1.59–2.86]). Specifically, referred women were more likely to have used antipsychotics, antidepressants, attention deficit hyperactivity disorder (ADHD) medication or anxiolytics, and to have been hospitalized for affective disorders or anxiety, but not to have been hospitalized for schizoid, ADHD or eating disorders. In addition, they were more likely to have had talk therapy or psychometric test performed prior to vaccination (OR: 1.72 [95% CI 0.1.35–2.18] and OR: 1.67 [95% CI 1.30–2.13], respectively). Referred women of all ages had higher use of GP before vaccination. Population attributable fraction analyses indicated that psychiatric medication, hospitalization due to a psychiatric disorder and use of talk therapy, or psychometric test “explained” 13%, 10%, 12% and 11% of the referrals, respectively. Results did not change substantially when adjusted for potential confounders. Conclusion: Women referred to HPV centers because of suspected adverse events after vaccination more often had preexisting psychiatric conditions, psychological symptoms or frequent GP attendance prior to HPV vaccination. Keywords: papillomavirus vaccines, adverse drug events, psychoactive drugs, general practice

Maiken Ina Siegismund Kjaersgaard,1 Peter Vedsted,2 Erik Thorlund Parner,1 Bodil Hammer Bech,3 Mogens Vestergaard,2,4 Kaare Rud Flarup,2 Morten Fenger-Grøn,2 1Section for Biostatistics, 2Research Unit for General Practice, 3Section for Epidemiology, 4Section for General Medical Practice, Department of Public Health, Aarhus University, Aarhus, Denmark Background: The patient list system in Denmark assigns virtually all residents to a general practice. Nevertheless, historical information on this link between patient and general practice is not readily available for research purposes. Objectives: To develop, implement, and evaluate the performance of an algorithm linking individual patients to their general practice by using information from the Danish National Health Service Register and the Danish Civil Registration System. Materials and methods: The National Health Service Register contains information on all services provided by general practitioners from 1990 and onward. On the basis of these data and information on migration history and death obtained from the Civil Registration System, we developed an algorithm that allocated patients to a general practice on a monthly basis. We evaluated the performance of the algorithm between 2002 and 2007. During this time period, we had access to information on the link between patients and general practices. Agreement was assessed by the proportion of months for which the algorithm allocated patients to the correct general practice. We also assessed the proportion of all patients in the patient list system for which the algorithm was able to suggest an allocation. Results: The overall agreement between algorithm and patient lists was 98.6%. We found slightly higher agreement for women (98.8%) than for men (98.4%) and lower agreement in the age group 18–34 years (97.1%) compared to all other age groups (≥98.6%). The algorithm had assigned 83% of all patients in the patient list system after 1 year of follow-up, 91% after 2 years of follow-up, and peaked at 94% during the fourth year. Conclusion: We developed an algorithm that enables valid and nearly complete linkage between patients and general practices. The algorithm performs better in subgroups of patients with high health care needs. The algorithm constitutes a valuable tool for primary health care research. Keywords: general practice, medical record linkage, patient list, primary care, registers

Søren Pauli Bro,1 Maiken Ina Siegismund Kjaersgaard,2 Erik Thorlund Parner,2 Merete Juul Sørensen,3 Jørn Olsen,4 Bodil Hammer Bech,4 Lars Henning Pedersen,4,5 Jakob Christensen,6,7 Mogens Vestergaard11Research Unit and Section for General Practice, Department of Public Health, 2Section for Biostatistics, Department of Public Health, Aarhus University, 3Regional Center for Child and Adolescent Psychiatry, Aarhus University Hospital, 4Section for Epidemiology, Department of Public Health, 5Department of Clinical Medicine – Obstetrics and Gynecology, Aarhus University, 6Department of Clinical Pharmacology, 7Department of Neurology, Aarhus University Hospital, Aarhus, DenmarkObjective: To determine if prenatal exposure to methylphenidate (MPH) or atomoxetine (ATX) increases the risk of adverse pregnancy outcomes in women with attention deficit/hyperactivity disorder (ADHD).Materials and methods: This was a population-based cohort study of all pregnancies in Denmark from 1997 to 2008. Information on use of ADHD medication, ADHD diagnosis, and pregnancy outcomes was obtained from nationwide registers.Results: We identified 989,932 pregnancies, in which 186 (0.02%) women used MPH/ATX and 275 (0.03%) women had been diagnosed with ADHD but who did not take MPH/ATX. Our reference pregnancies had no exposure to MPH/ATX and no ADHD diagnosis. Exposure to MPH/ATX was associated with an increased risk of spontaneous abortion (SA; ie, death of an embryo or fetus in the first 22 weeks of gestation) (adjusted relative risk [aRR] 1.55, 95% confidence interval [CI] 1.03–2.36). The risk of SA was also increased in pregnancies where the mother had ADHD but did not use MPH/ATX (aRR 1.56, 95% CI 1.11–2.20). The aRR of Apgar scores

Objective: To investigate the impact of prenatal antidepressant exposure on behavioural problems in children at 7 years of age.Design: Nationwide population-based study.Setting: Danish National Birth Cohort.Population: A cohort of 49 178 pregnant women recruited between 1996 and 2002.Methods: Data obtained from computer-assisted telephone interviews twice during pregnancy were used to identify children born to: (i) depressed women who took antidepressants during pregnancy (n = 210); (ii) depressed women who did not take any antidepressants during pregnancy (n = 231); and (iii) healthy women who were not depressed (n = 48 737). Childhood behavioural problems at 7 years of age were examined using the validated Danish parent-report version of the Strengths and Difficulties Questionnaire (SDQ).Main Outcome Measures: SDQ scores.Results: No associations were observed between prenatal antidepressant exposure and abnormal SDQ scores for overall problem behaviour (adjusted relative risk, aRR 1.00; 95% confidence interval, 95% CI 0.49-2.05), hyperactivity/inattention (aRR 0.99; 95% CI 0.56-1.75), or peer problems (aRR 1.04; 95% CI 0.57-1.91). Although prenatal antidepressant exposure appeared to be associated with abnormal SDQ scores on the subscales of emotional symptoms (aRR 1.68; 95% CI 1.18-2.38) and conduct problems (aRR 1.58; 95% CI 1.03-2.42), these associations were significantly attenuated following adjustment for antenatal mood status (aRR 1.20; 95% CI 0.85-1.70 and aRR 1.19; 95% CI 0.77 1.83, respectively). Untreated prenatal depression was associated with an increased risk of all behavioural outcomes evaluated, compared with unexposed children, with significant attenuation following adjustment for antenatal mood status.Conclusions: The results of this study suggest that independent of maternal illness, prenatal antidepressant exposure is not associated with an increased risk of behavioural problems in children at 7 years of age.Tweetable Abstract: Prenatal antidepressant exposure is not associated with an increased risk of child behavioural problems. [ABSTRACT FROM AUTHOR]

Objective Coffee and tea consumption is associated with a decreased type 2 diabetes risk in non-pregnant adults. We examined the relation between first trimester coffee and tea consumption and gestational diabetes mellitus ( GDM) risk. Design Population-based cohort study. Setting Denmark 1996-2002. Population Non-diabetic women with singleton pregnancies in the Danish National Birth Cohort ( n = 71 239). Methods Estimated adjusted relative risks ( RR) and 95% confidence intervals (95% CI) for the association between first trimester coffee and tea or estimated total caffeine and GDM. Main outcome measures GDM ascertained from the National Hospital Discharge Register or maternal interview. Results Coffee or tea intake was reported in 81.2% ( n = 57 882) and 1.3% ( n = 912) of pregnancies were complicated by GDM. Among non-consumers, 1.5% of pregnancies were complicated by GDM. Among coffee drinkers, GDM was highest among women who drank ≥8 cups/day (1.8%) with no significant difference across intake levels ( P = 0.10). Among tea drinkers, there was no difference in GDM across intake levels (1.2%; P = 0.98). After adjustment for age, socio-occupational status, parity, pre-pregnancy body mass index, smoking, and cola, there was suggestion of a protective, but non-significant association with increasing coffee ( RR ≥8 versus 0 cups/day = 0.89 [95% CI 0.64-1.25]) and tea ( RR ≥8 versus 0 cups/day = 0.77 [95% CI 0.55-1.08]). Results were similar by smoking status, except a non-significant 1.45-fold increased risk with ≥8 coffee cups/day for non-smokers. There was a non-significant reduced GDM risk with increasing total caffeine. Conclusions Our results suggest that moderate first trimester coffee and tea intake were not associated with GDM increased risk and possibly may have a protective effect. [ABSTRACT FROM AUTHOR]

Objective: To prospectively evaluate the performance of first-trimester combined screening for trisomy 21 using the biochemical markers pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (free β-hCG) obtained before and at the time of the nuchal translucency (NT) scan.Methods: Three fetal medicine departments in Denmark participated in the study. Screening for trisomy 21 was set up as a two-step approach with blood sampling performed before the NT scan (early sample) and again at the time of the NT scan (late sample). PAPP-A and free β-hCG were measured on both the early and late samples. Age-standardized detection and false-positive rates for different screening protocols were calculated.Results: We collected two blood samples in 27 pregnancies affected by trisomy 21 and in 3891 control pregnancies. The early samples were taken between gestational ages 8 + 0 and 13 + 6 weeks, and the late samples between 11 + 3 and 14 + 6 weeks. The median interval between the samples was 17 (range, 1-40) days. We found a significantly better estimated screening performance when using early sampling vs late sampling (P < 0.05). With a risk cut-off of 1 in 100, at the time of the risk assessment the estimated detection and false-positive rates when using the early sample were 91% (95% CI, 81-98%) and 1.6% (95% CI, 1.3-2.0%), respectively. For fixed false-positive rates the highest detection rates were achieved using both blood samples. When comparing early sampling vs double sampling there was no significant difference in screening performance.Conclusion: In combined first-trimester screening for trisomy 21, use of early sampling with measurement of PAPP-A and free β-hCG before the time of the NT scan can optimize screening performance. Using maternal serum markers obtained both before and at the time of the NT scan has the potential to further improve performance, but larger studies are needed to confirm this potential. [ABSTRACT FROM AUTHOR]

We previously reported associations between preeclampsia and the occurrence of metabolic and respiratory diseases in the offspring. In this article we examine whether the associations were due to preeclampsia or factors leading to preeclampsia. [ABSTRACT FROM AUTHOR]

Background: Ophthalmic quality of life (OQoL) has been investigated in selected parts of general populations and in patients with ocular disease, but OQoL in unselected general populations has not been studied in detail. The present study reports OQoL obtained from a representative sample of the adult Danish population 2020-2022., Methods: The FORSYN study invited 10 350 citizen representatives for the adult Danish population for a non-mydriatic eye examination and answer the National Eye Institute Visual Function Questionnaire with 39 items in the validated Danish translation. The results from the 3384 (32.7%) persons who participated in the study were weighted on the basis of relevant socio-economic factors, and data were projected to represent the total population. Binocular visual acuity was below 0.1 corresponding to legal blindness in 0.22% of this population., Results: OQoL was positively correlated with binocular visual acuity up to better than 93 ETDRS letters, negatively correlated with age for persons younger than 60 years of age and again positively correlated with age for persons older than 60 years. OQoL was negatively correlated with increasing ametropia and refractive error above 1 dioptre and encompassed more OQoL parameters for hyperopic than for myopic persons., Conclusions: The study underlines the benefits of improving visual acuity even within the normal range and of adjusting uncorrected refraction errors in the general population. OQoL is positively correlated with age in older persons independently of visual acuity, sex, refractive power and previous cataract surgery., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Study Design: Nationwide epidemiological open cohort study., Objectives: To evaluate whether individuals with traumatic spinal cord injury (TSCI) are more prone to develop autoimmune diseases compared to a general non-TSCI population., Setting: Danish public national registries., Methods: An open nationwide cohort, including individuals born in Denmark from or alive during 1945-2018 was collected and the study period was 1980-2018. Poissons Log-linear regression estimated the incidence rate ratio (IRR) for developing eight groups of autoimmune diseases. A dose-response relationship based on the cervical/thoracic level of injury was assessed by stratification., Results: The cohort included 3,272 individuals with TSCI and 4.8 million background individuals, accounting for 50,865 and 140 million person-years respectively. The TSCI population had an overall IRR of 1.81 (95% CI, 1.59 to 2.05) of getting any autoimmune disease. Subgroup analysis found positive associations for; a) Other neurologic IRR 5.19 (95% CI, 2.79 to 9.65), b) multiple sclerosis IRR 3.70 (95% CI, 2.54 to 5.40), c) Dermatologic IRR 2.57 (95% CI, 1.86 to 3.55), d) Type 1 diabetes mellitus IRR 2.01 (95% CI, 1.54 to 2.61), e) Systemic 1.92 (95% CI, 1.44 to 2.55), and f) Gastroenterologic IRR 1.42 (95% CI, 1.05 to 1.92). Cervical levels of TSCI showed an IRR of 1.70 (95% CI, 1.43 to 2.02), while thoracic levels had an IRR 1.98 (95% CI, 1.63 to 2.39)., Conclusions: TSCI may be an individual risk factor of developing an autoimmune disease. There does not appear to exist a dose-response relationship from the level of injury., Sponsorship: None., (© 2024. The Author(s).)

Background: We quantified relative and absolute risks of postpartum psychiatric episodes (PPE) following risk factors: Young age, past personal or family history of psychiatric disorders, and genetic liability., Methods: We conducted a register-based study using the iPSYCH2012 case-cohort sample. Exposures were personal history of psychiatric episodes prior to childbirth, being a young mother (giving birth before the age of 21.5 years), having a family history of psychiatric disorders, and a high (highest quartile) polygenic score (PGS) for major depression. PPE was defined within 12 months postpartum by prescription of psychotropic medication or in- and outpatient contact to a psychiatric facility. We included primiparous women born 1981-1999, giving birth before January 1st, 2016. We conducted Cox regression to calculate hazard ratios (HRs) of PPE, absolute risks were calculated using cumulative incidence functions., Results: We included 8174 primiparous women, and the estimated baseline PPE risk was 6.9% (95% CI 6.0%-7.8%, number of PPE cases: 2169). For young mothers with a personal and family history of psychiatric disorders, the absolute risk of PPE was 21.6% (95% CI 15.9%-27.8%). Adding information on high genetic liability to depression, the risk increased to 29.2% (95% CI 21.3%-38.4%) for PPE., Conclusions: Information on prior personal and family psychiatric episodes as well as age may assist in estimating a personalized risk of PPE. Furthermore, additional information on genetic liability could add even further to this risk assessment., (© 2023 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Objectives: The nocebo effect refers to an expectation of sickness that leads to sickness in the expectant. Studies have found COVID-19 vaccines to be associated with the nocebo effect. However, the literature in this field is sparse yet important with the continuation of booster vaccines., Study Design: National cohort study., Methods: This study used data from the Danish national cohort "BiCoVac", which contains self-reported information on both health anxiety and specific COVID-19 vaccine concern, as well as 19 systemic AEs following COVID-19 vaccination. Simple and multiple logistic regression was used to estimate the association between health anxiety and specific COVID-19 vaccine concern with having one or more systemic AEs following COVID-19 vaccination. Inverse probability weights were used to compensate for the initial dropout and loss to follow-up., Results: Of the 85,080 participants in the study, 4 % reported health anxiety, 30 % reported specific COVID-19 vaccine concern, and 26 % one or more systemic AEs following vaccination. After adjusting for covariates, participants with health anxiety had higher odds of reporting one or more systemic AEs following vaccination compared to those without (OR, 1·21 CI 95 % [1·10; 1·33]). For specific COVID-19 vaccine concern, the OR was 1·51 CI 95 % [1·45; 1·58]., Conclusions: Participants with specific COVID-19 vaccine concern had higher odds of reporting one or more systemic AEs following vaccination compared with those who had no specific COVID-19 vaccine concern. There might be a potential to reduce AEs, with positive framing of AEs and information about nocebo. Reporting of AEs was also associated with health anxiety, but to a lesser degree., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To assess whether children with febrile seizures and/or epilepsy were at increased risk of experiencing internalizing symptoms or psychotic-like experiences at age 11 years., Methods: This cohort study includes 44 819 children from the 11-year follow up of the Danish National Birth Cohort. Information on childhood seizures was retrieved from the Danish National Patient Registry, whereas child psychiatric symptoms were assessed in a web-based questionnaire using the Adolescent Psychotic-like Symptom Screener and the Strength and Difficulties Questionnaire. Adjusted odds ratios (aORs) with corresponding 95% confidence intervals (CIs) for the association between childhood seizures and internalizing symptoms (symptom score ≥8) and psychotic-like experiences (≥2 definite experiences) were obtained using logistic regression models., Results: A total of 1620 children with febrile seizures (3.6%), and 311 children with epilepsy (0.7%) were identified. When adjusted for potential confounders, no association between febrile seizures and psychiatric symptoms was observed, and no association was observed between epilepsy and psychotic-like experiences. However, the OR for internalizing symptoms was 1.76 (95% CI: 1.20-2.58) in children with epilepsy compared to children without. This higher risk was evident mainly in boys (OR 2.30, 95% CI 1.37-3.85), children with ≥2 epilepsy-related hospital admissions (OR 2.79, 95% CI 1.81-4.32), and children whose age at first epilepsy-related hospital admission was 0-3 years (OR 2.47, 95% CI 1.45-4.19)., Significance: No association was found between febrile seizures and psychiatric symptoms or epilepsy and psychotic-like experiences at age 11. However, boys with epilepsy were at higher risk of experiencing internalizing symptoms., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: Pain is a common complaint among patients presenting to the emergency department (ED), yet pain treatment is frequently suboptimal. The aim of this study was to determine the effectiveness of low-dose ketamine (LDK) as an adjunct to morphine versus morphine alone for treatment of acute pain among ED patients with and without current opioid use., Methods: Adult patients presenting with acute pain of ≥5 on a numeric rating scale (0-10) who were deemed by their treating ED physician to require intravenous opioids were randomized to receive either 0.1 mg/kg ketamine (treatment group) or isotonic saline (placebo) as an adjunct to morphine. Patients with and without current opioid use were randomized separately. Pain was measured at baseline (T0) and 10, 20, 30, 45, 60, and 120 min after randomization. The primary outcome was pain reduction from T0 to T10. Secondary outcomes included pain intensity over 120 min, need of rescue opioids, side effects, and patient and provider satisfaction., Results: A total of 116 patients were included from May 2022 to August 2023. Median (IQR) age was 51 (36.5-67) years; 58% were male and 36% had current opioid use. Pain reduction from T0 to T10 was greater in the LDK group (4 [IQR 3-6]) compared to the placebo group (1 [IQR 0-2]; p = 0.001). Pain intensity was lower in the LDK group at T10, T20, and T30, compared to the placebo group. There was a higher risk of nausea, vomiting, and dissociation in the LDK group during the first 10 min., Conclusions: LDK may be effective as an adjunct analgesic to morphine for short-term pain relief in treatment of acute pain in the ED for both patients with and without current opioid use., (© 2024 The Author(s). Academic Emergency Medicine published by Wiley Periodicals LLC on behalf of Society for Academic Emergency Medicine.)

It has been proposed that poor semen quality may have its origins from fetal programming due to environmental factors. We investigated whether maternal coffee consumption during early pregnancy was associated with biomarkers of reproductive health in adult sons in the Fetal Programming of Semen Quality (FEPOS) cohort. In 2017-2019, 1058 young men provided a semen and blood sample and self-measured their testis volume. Daily maternal coffee consumption was reported by the mothers around gestational week 17. We estimated relative percentage differences with 95 % confidence intervals (CI) for semen quality measures, testis volume, and reproductive hormone levels according to maternal coffee consumption during pregnancy. Maternal coffee consumption (yes/no (reference)) was associated with lower semen volume (-7.0 % (95 % CI:-12.9;-0.7)), lower proportion of morphologically normal spermatozoa (-8.3 % (95 % CI:-16.5;0.8)), higher proportion of non-progressive and immotile spermatozoa (4.3 % (95 % CI:-1.5;10.3)), and lower testis volume (-4.8 % (95 % CI:-9.0;-0.4)). No indication of a dose-response association or threshold effects was observed in the categorized and continuous analyses. No associations with reproductive hormone levels were observed in any of the analyses. Overall, the study does not provide obvious indications that maternal coffee consumption in early pregnancy deteriorates male offspring fecundity. While some minor changes were observed, most estimates were small with confidence intervals overlapping the null. Future studies, preferably with greater exposure contrast, are warranted before a conclusion can be drawn as to whether maternal coffee consumption during pregnancy constitutes a risk for reproductive health in adult sons., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Cecilia Ramlau-Hansen reports financial support was provided by European Research Council. If there are other authors, they 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 Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Despite high COVID-19 vaccination rates in many populations, concerns persist about potential adverse events, including concerns about involuntary movements. While case studies have shown occurrences of involuntary movements following COVID-19 vaccination, no systematic studies have explored this association. Our study aims to investigate the relationship between COVID-19 vaccination and involuntary movements., Methods: This study employs a longitudinal panel design. The study population consists of 165,834 responses from a total of 97,537 unique individuals sourced from the BiCoVac cohort, which is a randomly sampled cohort of Danish individuals aged 16 to 65. Data were collected through a combination of questionnaires and national registers, and analyses were conducted using mixed effects logistic regression., Results: Vaccinated individuals had lower odds of reporting involuntary movements compared to non-vaccinated individuals. Although adjustments attenuated the results, a consistent pattern of lower odds was observed among the vaccinated individuals. The strongest association for the first dose was observed in individuals who received the vaccine within the last 4 weeks before reporting symptoms (OR = 0.72 (0.60; 0.85)). For the second dose, the strongest association was found in individuals who received the second vaccine dose more than 4 weeks before reporting symptoms (OR = 0.77 (0.65; 0.91))., Conclusion: The results of the study do not indicate involuntary movements as an adverse reaction to the COVID-19 vaccine. These findings support the safety profile of the COVID-19 vaccine concerning involuntary movements and contribute to enhancing public trust in vaccination programs., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: We aimed to investigate how school well-being (SWB) and academic performance of children with juvenile idiopathic arthritis (JIA) compare to their peers on a national level using the Danish national registers. Further, we investigated the potential influence of socioeconomic status (SES)., Methods: A population-wide, register-based, cross-sectional study was performed. We compared the results of children with and without JIA in the Danish National Well-Being Questionnaire (DNWQ), the National Danish School Testing (NDST), and their ninth grade (aged approximately 16 yrs) final school marks in Danish and mathematics. The results were analyzed using adjusted ordinal logistic regression (SWB) and linear regression (tests and marks)., Results: In separate cohorts, we included a total of 505,340 children answering the DNWQ, 812,461 children with NDST results, and the ninth-grade final marks of 581,804 children. Of these children, 1042, 1541, and 1410, respectively, fulfilled the criteria of JIA. Children with JIA reported SWB comparable to their peers, except for the question "Do you perform well in school?" (odds ratio 0.89, 95% CI 0.81-0.99). In the NDST, the children with JIA in general did just as well as their peers. We found no differences in the ninth-grade final marks in either Danish or mathematics. Stratifying the analyses on SES showed no significant differences in the associations., Conclusion: Overall, children with JIA report SWB comparable to that of children without JIA and perform equally well in school as children without JIA., (Copyright © 2024 by the Journal of Rheumatology.)

Fractures account for the most frequent cause of hospitalization during childhood and numbers have increased over time. Of all fractures in childhood and young adulthood, 66% are recurrent fractures, suggesting that some people are predestined for fractures. The aim of this study was to investigate the association between maternal smoking during late pregnancy and the risk of fractures in the children.The study included 11,082 mothers and their children from the cohort "Healthy Habits for Two" born between 1984 and 1987. Information about maternal smoking during pregnancy came from questionnaires filled out in pregnancy, while information about fractures was derived from the Danish National Patient Registry. Over a follow-up of 24 years (1994-2018), Cox regression with multiple failures was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for fractures in childhood and young adulthood according to maternal smoking in late pregnancy. Information about body mass index (BMI) and smoking status in young adulthood was included as time variant covariates.During an age span of 8-32 years, 6,420 fractures were observed. Of the mothers, 39.1% smoked during late pregnancy. Compared to children of mothers who did not smoke, children of mothers who smoked 1-9 cigarettes per day and 10+ cigarettes per day had an increased risk of fractures (HR 1.14 [CI: 1.06; 1.21] and HR 1.14 [CI: 1.07; 1.22], respectively). After adjusting for BMI and smoking status in young adulthood, the findings were slightly strengthened, showing an increased risk of fractures of 23 and 25% in children of mothers smoking 1-9 cigarettes per day and 10+ cigarettes per day, respectively.Maternal smoking during late pregnancy was associated with a higher risk of fractures in the child. This result indicates that exposure to cigarette smoke in utero may play a role in lifelong bone health., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Aim: Adolescents' well-being and school absence are important factors for public health. The aim of this study was to examine the association between social well-being and problematic school absence among Danish adolescents in the ninth grade, as well as to examine potential sex differences, using a large cohort of adolescents., Methods: In this cross-sectional study, information on social well-being was obtained from the yearly Danish National Well-being Questionnaire mandatory in compulsory school. Data on school absence was obtained from the Ministry of Children and Education. The study population comprised 203,570 adolescents in the school years 2014/2015 to 2019/2020. The association between social well-being and problematic school-absence was analysed using logistic regression. A stratified analysis was made to investigate potential sex differences., Results: A total of 17,555 (9.16%) adolescents had problematic school absence, defined as >10% illegal absence and/or sickness absence in the ninth grade. Adolescents with low social well-being had higher odds for having problematic school absence compared with adolescents with high social well-being, adjusted odds ratio=2.22 (95% confidence interval 2.10-2.34). When stratifying for sex, the association was strongest for girls. The results remained after adjustment for parents' educational level and family structure., Conclusions: Associations between adolescents' social well-being and problematic school absence were found, where girls had the strongest association. These findings might provide knowledge about social well-being as an important factor for problematic school absence, while underlining the importance of early focus and prevention, which is of importance for both the adolescents and society., Competing Interests: Declaration of conflicting interestsThe authors have no conflicts of interest to declare.

Background: Patients with a daily use of opioids have a higher risk of insufficient pain treatment during hospitalization than other patients. This study aimed to examine whether as-needed opioid doses (PRN) were adequately adjusted when patients were admitted to the emergency department (ED) with pain., Methods: Patients, with a daily use of opioids, who received PRN opioid within the first 3 h after admission at the ED at Aarhus University Hospital, Denmark, were prospectively included from February 2021 to June 2021. The primary outcome was the proportion of patients receiving an inadequate initial dose of PRN opioid, here defined as <15% of daily dose of opioids (DDO) based on sparse evidence, but aligning with the prevailing clinical practice. Secondary outcomes included risk of an inadequate PRN dose in relation to DDO (patients were dichotomized into two groups (DDO <60 or ≥60 mg/day)., Results: Among 252 patients admitted to the ED with a daily use of opioids, 149 were admitted with pain and 82 received a PRN opioid dose within 3 h. Twenty-seven out of 82 (33%) patients received a PRN dose of <15% of DDO (95% CI: 23.7-43). When dichotomised; 10 out of 50 (20%) patients with a DDO <60 mg/day (95% CI: 10.0-33.7) versus 17 out of 32 (53.1%) patients with a DDO ≥60 mg/day (95% CI: 34.7-70.9) received an inadequate PRN dose (relative risk, RR: 2.65 [95% CI: 1.4-5.1])., Conclusions: Patients with daily use of opioids presenting in the ED with acute pain had a high risk of inadequate PRN opioid dose, especially if the DDO was high. Awareness about and education focusing on sufficient PRN doses for patients with a daily use of opioids is (still) called for., (© 2023 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)