School well-being and academic performance of children with juvenile idiopathic arthritis - a national register-based study.

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 the 9th grade (approx. 16 years old) final school marks in Danish and mathematics. The results were analysed using adjusted ordinal logistic regression (SWB) and linear regression (tests and marks). RESULTS: We included in separate cohorts a total of 505,340 children answering DNWQs, 812,461 with NDST results, and 9th grade final marks of 581,804 children. Of these children, 1,042, 1,541, and 1,410 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?" (OR=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 9th grade final marks in neither Danish nor 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 with no JIA and perform equally well in school as children without JIA.

Point-of-care testing and antibiotics prescribing in out-of-hours general practice: a register-based study in Denmark.

BACKGROUND: Point-of-care testing may reduce diagnostic uncertainty in case of suspicion of bacterial infection, thereby contributing to prudent antibiotic prescribing. We aimed to study variations in the use of point-of-care tests (C-reactive protein test, rapid streptococcal antigen detection test, and urine dipstick) among general practitioners (GPs) and the potential association between point-of-care testing and antibiotic prescribing in out-of-hours general practice. METHODS: We conducted a population-based observational register-based study, based on patient contacts with out-of-hours general practice in the Central Denmark Region in 2014-2017. The tendency of GPs to use point-of-care testing was calculated, and the association between the use of point-of-care testing and antibiotic prescribing was evaluated with the use of binomial regression. RESULTS: Out-of-hours general practice conducted 794,220 clinic consultations from 2014 to 2017, of which 16.1% resulted in an antibiotic prescription. The GP variation in the use of point-of-care testing was largest for C-reactive protein tests, with an observed variation (p90/p10 ratio) of 3.0; this means that the GPs in the 90th percentile used C-reactive protein tests three times as often as the GPs in the 10th percentile. The observed variation was 2.1 for rapid streptococcal antigen detection tests and 1.9 for urine dipsticks. The GPs who tended to use more point-of-care tests prescribed significantly more antibiotics than the GPs who tended to use fewer point-of-care tests. The GPs in the upper quintile of the tendency to use C-reactive protein test prescribed 22% more antibiotics than the GPs in the lowest quintile (21% for rapid streptococcal antigen detection tests and 8% for urine dipsticks). Up through the quintiles, this effect exhibited a positive linear dose-response correlation. CONCLUSION: The GPs varied in use of point-of-care testing. The GPs who tended to perform more point-of-care testing prescribed more antibiotics compared with the GPs who tended to perform fewer of these tests.

Psychiatric Morbidity Is Common Among Children With Juvenile Idiopathic Arthritis: A National Matched Cohort Study.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease that causes joint inflammation and pain. Previous studies have indicated affected mental health and increased risk of psychiatric conditions among patients with JIA. We aimed to explore differences in psychiatric morbidity between children with JIA and their peers. We further studied if parental socioeconomic status (SES) influences the association between JIA and the risk of psychiatric morbidity. METHODS: We used a matched cohort design to estimate the association between JIA and psychiatric disease. Children with JIA, born between 1995 and 2014, were identified in Danish national registers. Based on birth registers, we randomly selected 100 age- and sex-matched children per index child. Index date was the date of the fifth JIA diagnosis code or the date of matching for reference children. End of follow-up was the date of psychiatric diagnosis, death, emigration, or December 31, 2018, whatever came first. Data were analyzed using a Cox proportional hazard model. RESULTS: We identified 2086 children with JIA with a mean age at diagnosis of 8.1 years. Children with JIA had a 17% higher instantaneous risk of a psychiatric diagnosis when compared with the reference group, with an adjusted hazard ratio of 1.17 (95% CI 1.02-1.34). Relevant associations were found only for depression and adjustment disorders. Stratifying our analysis for SES showed no modifying effect of SES. CONCLUSION: Children with JIA had a higher risk of psychiatric diagnoses compared to their peers, especially diagnoses of depression and adjustment disorders. The association between JIA and psychiatric disease did not depend on parental SES.

Parental physical disease severity and severe documented physical child abuse: a prospective cohort study.

Successful prevention of physical child abuse is dependent on improvements in risk assessment. The risk of abuse is assumed to increase when family stressors overcome resources. Severe physical disease can increase stress, and parental physical disease has been studied as a risk factor for physical child abuse, but with heterogeneous definitions. This study evaluated the relation between parental physical disease severity and severe documented physical child abuse. Models were based on data on children aged 0-17 years in Denmark between 1997 and 2018, and their parents. Severe documented physical child abuse was modeled as violence against a child registered by either health authorities in treatment or mortality registries, or police authorities in cases confirmed by the courts. Parental physical disease severity was modeled as the sum of Charlson Comorbidity Index scores for the child's parents. The causal connection was examined in two model types: a survival model comparing exposed with non-exposed children, adjusted for covariates at baseline, and a G-model, taking time-varying covariates, including income and parental psychiatric disease into account. Neither model showed an association between parental physical disease severity and severe documented physical child abuse, with RR 0.99 and 95% CI (0.93-1.05) for the survival model and RR 1.08 for the G-model (CI not calculated).  Conclusion: In the model studied, parental physical disease severity was not a risk factor for severe documented physical child abuse. Individual categories of physical disease remain to be examined.  Trial registration: The study was pre-registered on Open Science Framework, https://osf.io/fh2sr . What is Known: • Parental physical disease severity has been studied previously as a risk indicator of physical child abuse, but based on heterogeneous definitions. • Previous studies have not studied parental physical disease severity preceding physical child abuse. What is New: • Parental severe physical disease was not prospectively associated with severe documented physical child abuse in a survival model, a G-model and a number of sensitivity analyses, respectively. • Results should be replicated in samples from populations without universal health care, and using different categories of disease.

Exploratory assessment of parental physical disease categories as predictors of documented physical child abuse.

Improved prediction of physical child abuse could aid in developing preventive measures. Parental physical disease has been tested previously as a predictor of documented physical child abuse but in broad categories and with differing results. No prior studies have tested clinically recognizable categories of parental disease in a high-powered dataset. Using Danish registries, data on children and their parents from the years 1997-2018 were used to explore several parental physical disease categories' associations with documented physical child abuse. For each disease category, survival analysis using pseudovalues was applied. When a parent of a child was diagnosed or received medication that qualified for a category, this family and five comparison families not in this disease category were included, creating separate cohorts for each category of disease. Multiple analyses used samples drawn from 2,705,770 children. Estimates were produced for 32 categories of physical diseases. Using Bonferroni-corrected confidence intervals (CIc), ischemic heart disease showed a relative risk (RR) of 1.44 (CIc 1.13-1.84); peripheral artery occlusive disease, RR 1.39 (CIc 1.01-1.90); stroke, RR 1.19 (1.01-1.41); chronic pulmonary disease, RR 1.33 (CIc 1.18-1.51); ulcer/chronic gastritis, RR 1.27 (CIc 1.08-1.49); painful condition, 1.17 (CIc 1.00-1.37); epilepsy, RR 1.24 (CIc 1.00-1.52); and unspecific somatic symptoms, RR 1.37 (CIc 1.21-1.55). Unspecific somatic symptoms were present in 71.87% of families at some point during the study period. CONCLUSION: Most parental physical disease categories did not show statistically significant associations, but some showed predictive ability. Further research is needed to explore preventive potential. WHAT IS KNOWN: • Few and broad categories of parental physical disease have been examined as risk factors for severe physical child abuse; no prior study has used several categories as predictors. WHAT IS NEW: • Unspecific symptoms, ischemic heart disease, peripheral artery occlusive disease, stroke, chronic pulmonary disease, stomach ulcer/chronic gastritis, painful condition, and epilepsy all showed to be potential predictors, with unspecific symptoms being the most prevalent.

As-needed opioid dosing for emergency patients with a daily use of opioids.

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.

Utilization of healthcare prior to endometriosis diagnosis: a Danish case-control study.

STUDY QUESTION: Do women with endometriosis have higher utilization of primary and secondary healthcare prior to diagnosis compared to women without endometriosis? SUMMARY ANSWER: Women with a hospital-based diagnosis of endometriosis had an overall higher utilization of both primary and secondary healthcare in all 10 years prior to diagnosis. WHAT IS KNOWN ALREADY: Endometriosis is associated with a diagnostic delay, but only a few studies have investigated the potential consequences of this delay with regard to the utilization of healthcare. To the best of our knowledge, no study has investigated it in a period corresponding to the estimated diagnostic delay. STUDY DESIGN, SIZE, DURATION: This national Danish registry-based case-control study included 129 696 women. Cases were women with a first-time hospital-based diagnosis of endometriosis between 1 January 2000 and 31 December 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: We identified 21 616 cases using density sampling. Each case was matched on age at the date of diagnosis (index date) to five women without diagnosed endometriosis (n = 108 080). The utilization of healthcare was assessed for the 10 years before the index. MAIN RESULTS AND THE ROLE OF CHANCE: Cases had significantly higher use of healthcare in all 10 years preceding the index. The mean number of yearly contacts with the GP was 9.99 for cases and 7.85 for controls, with an adjusted incidence rate ratio of 1.28 (1.27; 1.29). For hospital contacts, the association increased slightly in the first 9 years and was most profound in the last year preceding index when the adjusted incidence rate ratio was 2.26 (95% CI 2.28; 2.31). LIMITATIONS, REASONS FOR CAUTION: We were not able to include women with an endometriosis diagnosis from the general practitioner or private gynaecologist. Therefore, our results are only applicable to hospital-based diagnoses of endometriosis. We do not have information on the specific reasons for contacting the healthcare providers and we can therefore only speculate that the higher utilization of healthcare among cases was related to endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: This study is in agreement with the other known studies on the subject. Future studies should include specific reasons for contacting the healthcare system and thereby identify any specific contact patterns for women with endometriosis. With this knowledge, healthcare professionals could be better at relating certain healthcare seeking behaviour to endometriosis earlier and thereby reduce the time from onset of symptoms to diagnosis. STUDY FUNDING/COMPETING INTEREST(S): This study is supported by grants from the project 'Finding Endometriosis using Machine Learning' (FEMaLe/101017562), which has received funding from The European Union's Horizon 2020 research and innovation program and Helsefonden (21-B-0141). K.Z. report grants from Bayer AG, Roche Inc. and Volition, royalties from Oxford-Bayer scientific collaboration in gynaecological therapies, non-financial collaboration with the World Endometriosis Society and World Endometriosis Research Foundation and is a Wellbeing of Women research advisory committee member. All this is outside the submitted work. The other authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Fractures in Childhood and Young Adulthood According to Maternal Smoking in Late Pregnancy. A Danish Cohort Study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Maternal serum dioxin-like activity and gestational age at birth and indices of foetal growth: The Aarhus birth cohort.

Human exposure to lipophilic persistent organic pollutants (lipPOP) is ubiquitous and life-long, beginning during foetal development. Exposure to lipPOP elicits a number of species and tissue specific responses including dioxin-like activity which involve the activation of aryl hydrocarbon receptor (AhR). This study aims i) to describe the combined dioxin-like activity in serum from Danish pregnant women collected during 2011-2013; ii) to assess the association between maternal serum dioxin-like activity, gestational age at birth and foetal growth indices. The serum lipPOP fraction was extracted using Solid Phase Extraction and cleaned-up on Supelco multi-layer silica and florisil columns. The combined dioxin-like activity of the extract was determined using the AhR reporter gene bioassay, expressed as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxic equivalent (TEQ) [AhR-TEQ (pg/g lipid)]. The associations of AhR-TEQ and foetal growth indices (birth weight, birth length and head circumference) and gestational age were assessed by linear regression models. We detected AhR-TEQ in 93.9 % of maternal first trimester serum samples, with a median level of 185 pg/g lipid. Each ln-unit increase in AhR-TEQ was associated with an increase in birth weight of 36 g (95 % CI: 5; 68), birth length of 0.2 cm (95 % CI: 0.01; 0.3) and pregnancy duration of 1 day (95 % CI: 0; 1.5). In women who never smoked, higher AhR-TEQ values were associated with higher birth weight and longer duration of gestation, while in smokers the association was the opposite. Mediation analyses suggested that gestational age may mediate the association of AhR-TEQ with foetal growth indices. We conclude that AhR activating substances are present in the bloodstream of almost all pregnant women in Denmark and the AhR-TEQ level was around four times higher than previously reported. The AhR-TEQ was associated with slightly longer gestational duration and thereby higher birth weight and birth length.

Children of parents with different severities of mental health conditions have higher risk of somatic morbidity: a Danish nationwide register-based cohort study.

BACKGROUND: Children with the most severe parental mental health conditions have an elevated risk of numerous adversities including somatic morbidity. However, there is no knowledge concerning physical health in most children affected by parental mental health conditions. Therefore, the aim was to examine the association between different severities of parental mental health conditions and somatic morbidity in children of different age-groups and further explore the combinations of maternal and paternal mental health conditions on child somatic morbidity. METHODS: In this register-based cohort study, we included all children born in Denmark between 2000-2016 and linked parents. Parental mental health conditions were categorised into four severity groups (no, minor, moderate, and severe). Somatic morbidity in offspring was categorised into broad disease categories corresponding to the International Classification of Diseases. We estimated the risk ratio (RR) using Poisson regression, of the first registered diagnosis in different age-groups. RESULTS: Of the around 1 million children in the study > 14.5% were exposed to minor parental mental health conditions and < 2.3% were exposed to severe parental mental health conditions. Overall, the analyses revealed a higher risk of morbidity in exposed children across all disease categories. The strongest association was observed for digestive diseases in children aged < 1 year exposed to severe parental mental health conditions (RR: 1.87 (95% CI: 1.74-2.00). Generally, the risk of somatic morbidity increased the more severe the parental mental health conditions. Both paternal and especially maternal mental health conditions were associated with a higher risk of somatic morbidity. The associations were strongest if both parents had a mental health condition. CONCLUSION: Children with different severities of parental mental health conditions experience a higher risk of somatic morbidity. Although children with severe parental mental health conditions had the highest risk, children with minor parental mental health conditions should not be neglected as more children are exposed. Children with both parents having a mental health condition were the most vulnerable to somatic morbidity and maternal mental health conditions were more strongly associated with somatic morbidity than paternal. More support and awareness of families with parental mental health conditions is highly needed.

Exposure to persistent organic pollutants in Danish pregnant women: Hormone levels and fetal growth indices.

This study examines possible associations of maternal Persistent Organic Pollutants (POP) exposure during pregnancy, maternal hormone levels and fetal growth indices (FGI). During 1st trimester, we measured maternal thyroids, androgens and estrogens, lipophilic POP and perfluorinated-alkyl-acid (PFAA) levels in serum from nulliparous women. Adjusted multivariate-linear regression models assessed associations between exposure and outcomes. Maternal characteristics and POP exposures associated with maternal hormone levels. Lipophilic POP elicited inverse association with androgen and estrogen levels but no strong association with thyroids. Higher level of PFAA was associated with higher thyroid and androgen levels. The PFAA did not associate with estrogens. Higher thyroid-peroxidase-antibody (TPO-Ab) and estradiol level associated with higher birth weight and length in sons. For daughters, the TPO-Ab associations were the opposite being inversely associated with birth weight and length, and higher TPO-Ab and estradiol associated with lower gestational age. Mediation analyses suggested that TPO-Ab mediates the association of PFAA with FGI.

Visual acuity and causes of central visual loss in the adult Danish population 2020-2022. Results from the FORSYN study.

PURPOSE: Knowledge of visual health in the population is necessary for designing and implementing measures to handle visual handicap. The purpose of the FORSYN (Forekomst af synshandicap og synshjaelpemidler i Danmark) project was to study visual health in the Danish population 2020-2022 after implementation of the recent advances in the management of choroidal and retinal vascular disease. The present study reports visual acuity and causes of central visual loss from this study. METHODS: A population-representative sample of 10 350 citizens living within 40 kilometres from Aarhus University Hospital were invited to answer a questionnaire about quality of life related to vision, measurement of visual acuity and a non-mydriatic examination of the eyes. The data were corrected for selection bias on the basis of demographic and socioeconomic factors so that the results could be projected to represent the adult Danish population. RESULTS: Population-adjusted visual acuity in ETDRS letters (mean ± SD) differed significantly (p < 0.0001) among the worse eye (84.1 ± 0.25), the better eye (88.4 ± 0.11) and binocularly (89.2 ± 0.15). Social blindness affected 0.22% (95% CI: 0.14%-0.33%) of the population and was in none of the studied persons due to exudative age-related macular degeneration (AMD) or diabetic retinopathy. The most frequent causes of visual loss were atrophic AMD, neuro-ophthalmic disorders and other chorioretinal diseases. CONCLUSIONS: Recent advances in the therapy of chorioretinal vascular diseases have been paralleled with a reduction in central vision loss secondary to exudative AMD and diabetic retinopathy in Denmark. The demographic development can be expected to increase the demand for treatments of vision-threatening diseases that mainly affect older persons.

Contacts in general practice during the COVID-19 pandemic: a register-based study.

BACKGROUND: The COVID-19 pandemic has altered the provision of health care and expanded telehealth consultations. AIM: To study the effect of the COVID-19 pandemic on contact patterns in general practice, and to identify patient groups at risk of losing care. DESIGN AND SETTING: Register-based study of Danish general practice, including daytime and out-of-hours (OOH) services. METHOD: All individuals residing in Denmark from 1 January 2017 to 31 October 2020 were included. The incidence rate for six contact types in general practice and adjusted incidence rate ratio were calculated by comparing the incidence rate in the pandemic period with the adjusted expected incidence rate based on the incidence rate in the pre-pandemic period. RESULTS: The number of face-to-face in-clinic consultations declined during the lockdown in March 2020. A subsequent increase in the number of clinic consultations was observed, rising to a level above that of the pre-pandemic period; this increase resulted mainly from the introduction of telehealth consultations (that is, video and extended telephone). The number of daytime email consultations increased, whereas the number of daytime home visits decreased. Likewise, the number of OOH telephone consultations increased, whereas the number of OOH home visits and clinic consultations decreased. Consultation rates of patients who are vulnerable, that is, those with low education, old age, and comorbidity, were most adversely affected by the pandemic. The most adverse impact in OOH clinic consultations was seen for children aged 0-9 years. CONCLUSION: New methods are called for to ensure access to general practice for patients who are vulnerable during a pandemic. The potential of telehealth consultations should be further investigated.

The Patent Ductus Arteriosus in Extremely Preterm Neonates Is More than a Hemodynamic Challenge: New Molecular Insights.

Complications to preterm birth are numerous, including the presence of a patent ductus arteriosus (PDA). The biological understanding of the PDA is sparse and treatment remains controversial. Herein, we speculate whether the PDA is more than a cardiovascular imbalance, and may be a marker in response to immature core molecular and physiological processes driven by biological systems, such as inflammation. To achieve a new biological understanding of the PDA, we performed echocardiography and collected plasma samples on day 3 of life in 53 consecutively born neonates with a gestational age at birth below 28 completed weeks. The proteome of these samples was analyzed by mass spectrometry (nanoLC-MS/MS) and immunoassay of 17 cytokines and chemokines. We found differences in 21 proteins and 8 cytokines between neonates with a large PDA (>1.5 mm) compared to neonates without a PDA. Amongst others, we found increased levels of angiotensinogen, periostin, pro-inflammatory associations, including interleukin (IL)-1ß and IL-8, and anti-inflammatory associations, including IL-1RA and IL-10. Levels of complement factors C8 and carboxypeptidases were decreased. Our findings associate the PDA with the renin-angiotensin-aldosterone system and immune- and complement systems, indicating that PDA goes beyond the persistence of a fetal circulatory connection of the great vessels.

Variation of GP antibiotic prescribing tendency for contacts with out-of-hours primary care in Denmark - a cross-sectional register-based study.

OBJECTIVE: To study variation in antibiotic prescribing rates among general practitioners (GP) in out-of-hours (OOH) primary care and to explore GP characteristics associated with these rates. DESIGN: Population-based observational registry study using routine data from the OOH primary care registration system on patient contacts and antibiotic prescriptions combined with national register data. SETTING: OOH primary care of the Central Denmark Region. SUBJECTS: All patient contacts in 2014-2017. MAIN OUTCOME MEASURES: GPs' tendency to prescribe antibiotics. Excess variation (not attributable to chance). RESULTS: We included 794,220 clinic consultations (16.1% with antibiotics prescription), 281,141 home visits (11.6% antibiotics), and 1,583,919 telephone consultations (5.8% antibiotics). The excess variation in the tendency to prescribe antibiotics was 1.56 for clinic consultations, 1.64 for telephone consultations, and 1.58 for home visits. Some GP characteristics were significantly correlated with a higher tendency to prescribe antibiotics, including 'activity level' (i.e. number of patients seen in the past hour) for clinic and telephone consultations, 'familiarity with OOH care' (i.e. number of OOH shifts in the past 180 days), male sex, and younger age for home visits. Overall, GP characteristics explained little of the antibiotic prescribing variation seen among GPs (Pseudo r2: 0.008-0.025). CONCLUSION: Some variation in the GPs' tendency to prescribe antibiotics was found for OOH primary care contacts. Available GP characteristics, such as GPs' activity level and familiarity with OOH care, explained only small parts of this variation. Future research should focus on identifying factors that can explain this variation, as this knowledge could be used for designing interventions.KEY POINTSCurrent awareness:Antibiotic prescribing rates seem to be higher in out-of-hours than in daytime primary care.Most important results:Antibiotic prescribing rates varied significantly among general practitioners after adjustment for contact- and patient-characteristics.This variation remained even after accounting for variation attributable to chance.General practitioners' activity level and familiarity with out-of-hours care were positively associated with their tendency to prescribe antibiotics.

Multiple health complaints in preadolescence and hospital contacts during adolescence: a prospective cohort study.

Multiple health complaints (MHC) is increasing among preadolescents in many countries, but their prognostic effect for individual thriving or societal resource use is scarcely studied. This makes interpreting the significance of this increase challenging. We contribute by examining whether MHC in preadolescence predicts hospital contacts in adolescence by doing a nation-wide population-based cohort-study following preadolescents from the Danish National Birth-Cohort from 2010 to 2018. 96,382 children were invited at age 11. Responses to a modified version of the Health Behaviour in School Children Symptom Checklist (headache, dizziness, stomachache, irritability, feeling nervous, difficulty in getting to sleep and feeling low) was dichotomized into MHC (≥ 2 concurrent symptoms, each with a frequency of at least weekly, yes/no). Hospital contacts were derived from Danish registers from the date of answering the questionnaire to December 31st 2018. Negative binomial regression estimated incidence rate ratios (IRRs) comparing children with MHC to children without. Analyses were further broken down by hospital sector (psychiatric/somatic) and contact type (in-patient/out-patient/emergency room). 47,365 (49.1%) responded. Mean age was 11.2 years, 52% girls. 10.3% of responders reported MHC. For hospital contacts, the unadjusted IRR was 1.74 [95% CI 1.65, 1.83]. Results were robust to adjustment for sociodemographic variables and somatic/psychiatric morbidity diagnosed before baseline, IRR 1.62 [95% CI 1.54-1.71]. In conclusion, MHC in preadolescents are prognostic of hospital contacts. This shows that we cannot ignore MHC, and to prevent potentially unhelpful healthcare use, we must act. Future research should focus on the underlying causes of MHC to understand which changes will be most helpful and thus how to act.

In utero exposure to perfluoroalkyl and polyfluoroalkyl substances and attention and executive function in the offspring: A study in the Danish National Birth Cohort.

BACKGROUND: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are ubiquitous in the environment and accumulate in humans. PFAS are suspected to affect the neuropsychological function of children, but only few studies have evaluated the association with childhood attention and executive function. OBJECTIVES: To investigate the association between intrauterine exposure to PFAS and offspring attention and executive function. METHODS: A total of 1593 children from the Danish National Birth Cohort, born 1996-2003, were included. The levels of 16 PFAS were measured in maternal plasma during pregnancy. At 5 years of age, the Test of Everyday Attention for Children at Five (TEACh-5) and the Behavior Rating Inventory of Executive Function (BRIEF) were performed. TEACh-5 scores were standardized to a mean of 0 and standard deviation (SD) of 1. BRIEF scores were standardized to a mean of 50 and a SD of 10. The associations between levels of seven PFAS and TEACh-5 and BRIEF were examined by multivariable linear regression adjusted for potential confounders. RESULTS: Perfluorooctane sulfonamide (PFOSA) was associated with poorer selective attention [standardized mean difference (95% confidence interval) -0.5 (-0.7, -0.3), highest versus lowest quartile]. Other PFAS were not clearly associated with selective attention, and we found no clear associations between PFAS exposure and sustained attention. For parent rated executive function, perfluorooctanoate (PFOA) was associated with poorer scores, standardized mean difference 3.8 (95% confidence interval 1.6, 6.0), highest versus lowest quartile. Regarding other PFAS, the associations were less clear. We found no clear associations between any PFAS and executive function rated by preschool teachers. CONCLUSION: Intrauterine exposure to PFOSA was associated with poorer selective attention, while PFOA was associated with poorer executive function. Given the widespread nature of PFAS exposure, these findings may have public health implications, warranting further investigation.

Prenatal exposure to benzodiazepines and the development of the offspring - a systematic review.

OBJECTIVE: To summarize the available literature on long-term-development of children exposed to benzodiazepines in utero, through a systematic review. INFORMATION SOURCES: We conducted a systematic literature search of PubMed, PsycINFO and embase (1/9-2020 to 3/9-2020). ELIGIBILITY CRITERIA: We included original studies with children older than one year prenatally exposed to BZ's and Z-hypnotics with outcomes regarding all psychological-, social-, motor- and neurodevelopmental disorders or disturbances of the children. Studies without a BZ-unexposed comparison group were excluded. Studies with only a single-dose exposure, conference abstracts, case reports and case series were excluded. RISK OF BIAS: The intern validity of the included studies was assessed with the Newcastle Ottawa Scale tool (NOS). INCLUDED STUDIES: 13 cohort studies were included in this systematic review. SYNTHESIS OF RESULTS: The outcomes investigated were internalizing and externalizing problems, language, hearing and communication skills, neurological outcomes and motor function, behavioral and emotional problems, social skills, intellect and academic achievements, psychiatric diagnoses and overall development. We found some evidence of higher risk of developing internalizing problems, impaired gross motor skills, lower academic achievements and increased ADHD-traits among children exposed to benzodiazepines in utero. CONCLUSION: Prenatal exposure to benzodiazepines were associated with 4 developmental outcomes indicating an impaired long-term-development of the offspring. However, results were contradicting, and it cannot be ruled out, that findings might be due to bias. Furthermore, it remains uncertain if the results are of clinical relevance and whether developmental problems persist in later childhood. This study revealed a clear need for further research in the subject.

Pre-adolescents with multiple health complaints redeem more prescriptions: A follow-up study in the Danish National Birth Cohort.

Aims: This study aimed to examine the association between multiple health complaints (MHC) in pre-adolescence and prescription redemption in adolescence. Methods: This was a nationwide population-based study based on the Danish National Birth Cohort for an average of 6.9 years (2010-2018). A total of 96,382 children were invited at the age of 11. A modified version of the Health Behaviour in School Children Symptom Checklist was dichotomised into the World Health Organization's definition of MHC (⩾2 complaints, each with a frequency of at least weekly, yes/no). The number of prescriptions was retrieved from Danish registries. Negative binomial regression estimated incidence rate ratios (IRRs) comparing children with MHC to children without. Prescription redemption was further stratified by psychiatric/somatic medication and into subtypes of prescriptions. Results: A total of 47,365 (49.1%) children participated (Mage=11.2 years, 52% girls). MHC were reported by 10.3%. The unadjusted IRR (MHC vs. no MHC) of all types of redemptions was 1.57 (95% confidence interval (CI) 1.49-1.64). Results were robust to adjustment for socio-demographic variables and somatic/psychiatric morbidity at baseline (IRR=1.47; 95% CI 1.40-1.54). Associations were especially strong for psychiatric medication (adjusted IRR=3.88; 95% CI 3.43-4.40) and were modified by neither sex nor maternal education. Conclusions: MHC in pre-adolescents predict prescription redemption. This implies that changes in MHC might be indicative of changes in public health. This requires further study, as the cause of a change in reporting of symptoms might also cause a change in treatment response. The latter determines whether prescriptions are treating ill-being or needlessly medicalising subjective symptoms.

Prenatal antibiotic exposure and birth weight.

BACKGROUND/OBJECTIVES: Current research suggests an association between antibiotic use in early life and later obesity. Less is known about prenatal antibiotic exposure and foetal growth. We investigated the association between prenatal antibiotic exposure and birth weight. METHODS: Data from the Danish National Birth Cohort were linked to the Danish National Medical Birth Registry. Exposure was self-reported antibiotic use in pregnancy. Outcome was registered birth weight. Multivariable linear regression models were adjusted for confounders defined a priori. RESULTS: A total of 63 300 mother-child dyads from 1996 to 2002 were included. Overall, prenatal antibiotic exposure was not associated with birth weight (-8.90 g, 95%CI: -19.5- +1.64 g, p = 0.10). Findings were similar for those born term and preterm. Antibiotic exposure in second to third trimester, compared to no exposure, was associated with lower birth weight (-12.6 g, 95%CI: -24.1 to -1.1 g, p = 0.03). In sex-stratified analyses, there were no observed associations between antibiotics and birth weight. With further stratifications, prenatal antibiotic exposure and birth weight were associated in boys who were preterm (+91.0 g, 95%CI: +6.8 g- +175.2 g, p = 0.03) but not among girls who were preterm (-44.0 g, 95%CI: -128.1 to +40.0 g, p = 0.30). CONCLUSIONS: Prenatal antibiotic exposure is not consistently associated with birth weight.