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.

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.

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.

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.

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.

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.

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.

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.

Infections in temporal proximity to HPV vaccination and adverse effects following vaccination in Denmark: A nationwide register-based cohort study and case-crossover analysis.

BACKGROUND: Public trust in the human papilloma virus (HPV) vaccination programme has been challenged by reports of potential severe adverse effects. The reported adverse symptoms were heterogeneous and overlapping with those characterised as chronic fatigue syndrome (CFS) and have been described as CFS-like symptoms. Evidence suggests that CFS is often precipitated by an infection. The aim of the study was to examine if an infection in temporal proximity to HPV vaccination is a risk factor for suspected adverse effects following HPV vaccination. METHODS AND FINDINGS: The study was a nationwide register-based cohort study and case-crossover analysis. The study population consisted of all HPV vaccinated females living in Denmark, born between 1974 and 2006, and vaccinated between January 1, 2006 and December 31, 2017. The exposure was any infection in the period ± 1 month around time of first HPV vaccination and was defined as (1) hospital-treated infection; (2) redemption of anti-infective medication; or (3) having a rapid streptococcal test done at the general practitioner. The outcome was referral to a specialised hospital setting (5 national HPV centres opened June 1, 2015) due to suspected adverse effects following HPV vaccination. Multivariable logistic regression was used to estimate the association between infection and later HPV centre referral. The participants were 600,400 HPV-vaccinated females aged 11 to 44 years. Of these, 48,361 (9.7%) females had a hospital-treated infection, redeemed anti-infective medication, or had a rapid streptococcal test ± 1 month around time of first HPV vaccination. A total of 1,755 (0.3%) females were referred to an HPV centre. Having a hospital-treated infection in temporal proximity to vaccination was associated with significantly elevated risk of later referral to an HPV centre (odds ratio (OR) 2.75, 95% confidence interval (CI) 1.72 to 4.40; P < 0.001). Increased risk was also observed among females who redeemed anti-infective medication (OR 1.56, 95% CI 1.33 to 1.83; P < 0.001) or had a rapid streptococcal test (OR 1.45, 95% CI 1.10 to 1.93; P = 0.010). Results from a case-crossover analysis, which was performed to adjust for potential unmeasured confounding, supported the findings. A key limitation of the study is that the HPV centres did not open until June 1, 2015, which may have led to an underestimation of the risk of suspected adverse effects, but stratified analyses by year of vaccination yielded similar results. CONCLUSIONS: Treated infection in temporal proximity to HPV vaccination is associated with increased risk for later referral with suspected adverse vaccine effects. Thus, the infection could potentially be a trigger of the CFS-like symptoms in a subset of the referred females. To our knowledge, the study is the first to investigate the role of infection in the development of suspected adverse effects after HPV vaccination and replication of these findings are needed in other studies.

Use of hydrochlorothiazide in Denmark following publication of skin cancer risk findings.

PURPOSE: The antihypertensive agent hydrochlorothiazide has recently been linked to increased risk of skin cancer. We sought to describe the impact of the dissemination of these findings on the use of hydrochlorothiazide and health care utilization among antihypertensive users in Denmark. METHODS: In this nationwide observational study, we performed descriptive analyses of a cohort comprising all Danish antihypertensive treatment users January 2016 through September 2020 (n = 1 316 476) with special focus on hydrochlorothiazide users (n = 309 743). Data were retrieved from the Danish nationwide health registries, including the Danish National Prescription Registry. RESULTS: The use of hydrochlorothiazide dropped by 44% from January 2016 to September 2020, with the proportion of all antihypertensive fills constituted by hydrochlorothiazide dropping from 12.7% to 7.2%. This decline was more pronounced among younger patients and patients with a history of skin cancer. Simultaneously, the monthly rate of new hydrochlorothiazide users in Denmark dropped from ≈2350 throughout 2017 to 652 during 2020. The publication of an increased risk of nonmelanoma skin cancer led to an estimated excess of up to 11 510 physical and 22 870 e-mail/phone consultations to general practitioners. No evidence for increased risk of adverse outcomes was found. CONCLUSIONS: The publication of increased risk of skin cancer with hydrochlorothiazide use has led to a marked decline in the use of hydrochlorothiazide in Denmark. A temporary increase in rate of GP contacts was also observed. This highlights the potential impact from disseminating research findings to patients and clinicians.

Associations between participation in, intensity of, and time spent on leisure time physical activity and risk of inflammatory bowel disease among older adults (PA-IBD): a prospective cohort study.

BACKGROUND: Inflammatory bowel diseases (IBDs) are diseases of the immune system that share some genetic and lifestyle-related predisposing factors. Increasing incidences have been reported in all age groups. Based on experimental studies suggesting a role of physical activity on intestinal inflammation, this study aimed to investigate the association between leisure time physical activity and the risk of IBD in older adults. METHODS: The study is a prospective cohort study using Danish registry data and questionnaire data from the Danish "Diet, Cancer and Health" cohort. The outcome IBD was defined as having at least two main diagnoses of Crohn's disease or ulcerative colitis registered in the National Patient Registry from the period between December 1993 and May 1997 with an average follow-up of 25 years. Cox proportional hazard models were used to estimate hazard-ratios for IBD onset associated with being physically active and with levels of the metabolic equivalent of task (MET) hours/week of physical activity and hours/week spent on six types of physical activity. All analyses were adjusted for potential confounders. Furthermore, the analyses were stratified according to age-group, occupational physical activity, smoking, BMI and work status to test for effect modification. RESULTS: In total, 54,645 men and women aged between 50 and 64 years were included, and of which there were 529 cases. When comparing physically active with inactive participants measured by MET hours/week there was no statistically significant difference in risk of IBD (0.89 [0.13; 6.27]), regardless of how participation was measured. Results did not indicate any dose-response effect when comparing quartile groups of MET hours/week (HR = 0.97 [0.76; 1.22], HR = 0.82 [0.64; 1.05] and HR = 0.83 [0.65; 1.07] or whether five of the six types of activities were compared with the lowest quartile as reference. For do-it-yourself-work, the third quartile of hours/week was associated with a higher risk of IBD compared to the second quartile of hours/week (HR = 1.44 [1.10; 1.90]. No effect modification was found. CONCLUSIONS: There was no association between physical activity and risk of IBD when comparing physically active with inactive participants. Neither did the results indicate any dose-response effect when comparing quartile groups of MET hours/week with the lowest quartile as reference. Do-it-yourself work, however, appeared to be associated with a higher risk of IBD when comparing the third quartile with the second quartile of hours/week. The study has clinical relevance by its contribution to the explanatory field of the causes of IBD. However, the study has some limitations, and further research is needed to clarify associations between physical activity and risk of IBD.

Maternal rheumatoid arthritis and systemic lupus erythematosus and risk of cryptorchidism and hypospadias in boys: a Danish nationwide study.

OBJECTIVES: RA and SLE are the most prevalent autoimmune rheumatic diseases affecting young women. Both diseases are characterized by systemic inflammation that may affect placental function and fetal development during pregnancy, and both diseases are associated with adverse pregnancy and child outcomes. We investigated the associations between maternal RA or SLE and the two genital malformations, cryptorchidism and hypospadias. METHODS: In this nationwide register-based study including all male singleton live births in Denmark from 1995 to 2016, we assessed the occurrence of cryptorchidism and hypospadias according to the prenatal disease-state of the mothers. Using Cox proportional hazards models we calculated adjusted hazard ratios, accounting for varying age at diagnosis. RESULTS: Among 690 240 boys, 1026 had a mother with RA and 352 had a mother with SLE. We found adjusted hazard ratios of 1.72 (95% CI: 1.15; 2.57) for cryptorchidism among boys born to mothers with RA and 1.46 (95% CI: 0.69; 3.06) for boys born to mothers with SLE, compared with the general population. As the number of hypospadias cases was low, multivariate analysis was not feasible. The crude hazard ratios were 0.51 (95% CI: 0.16; 1.58) and 1.00 (95% CI: 0.25; 4.03) for RA and SLE, respectively. CONCLUSION: Boys born to mothers with RA had higher risk of cryptorchidism, compared with unexposed boys. Boys born to mothers with SLE showed a similar tendency, however with less precision of the estimate. No conclusion could be reached on the risk of hypospadias, due to the low number of events.

Self-harm in women with postpartum mental disorders.

BACKGROUND: Women suffering from first onset postpartum mental disorders (PPMD) have a highly elevated risk of suicide. The current study aimed to: (1) describe the risk of self-harm among women with PPMD and (2) investigate the extent to which self-harm is associated with later suicide. METHODS: We conducted a register-based cohort study linking national Danish registers. This identified women with any recorded first inpatient or outpatient contact to a psychiatric facility within 90 days after giving birth to their first child. The main outcome of interest was defined as the first hospital-registered episode of self-harm. Our cohort consisted of 1 202 292 women representing 24 053 543 person-years at risk. RESULTS: Among 1554 women with severe first onset PPMD, 64 had a first-ever hospital record of self-harm. Women with PPMD had a hazard ratio (HR) for self-harm of 6.2 (95% CI 4.9-8.0), compared to mothers without mental disorders; but self-harm risk was lower in PPMD women compared to mothers with non-PPMD [HR: 10.1, (95% CI 9.6-10.5)] and childless women with mental disorders [HR: 9.3 (95% CI 8.9-9.7)]. Women with PPMD and records of self-harm had a significantly greater risk for later suicide compared with all other groups of women in the cohort. CONCLUSIONS: Women with PPMD had a high risk of self-harm, although lower than risks observed in other psychiatric patients. However, PPMD women who had self-harmed constituted a vulnerable group at significantly increased risk of later suicide.

Urine collection in cervical cancer screening - analytical comparison of two HPV DNA assays.

BACKGROUND: To reach non-participants, reluctant to undergo clinician-based cervical cancer screening and vaginal self-sampling, urine collection for high-risk human papillomavirus detection (hrHPV) may be valuable. Using two hrHPV DNA assays, we evaluated the concordance of hrHPV positivity in urine samples in comparison with vaginal self-samples and cervical cytology samples taken by the general practitioner (GP). We also studied women's acceptance of urine collection and preferences towards the different sampling procedures. METHODS: One hundred fifty paired self-collected urine and vaginal samples and GP-collected cervical cytology samples were obtained from 30 to 59-year-old women diagnosed with ASC-US within the Danish cervical cancer screening program. After undergoing cervical cytology at the GP, the women collected first-void urine and vaginal samples at home and completed a questionnaire. Each sample was hrHPV DNA tested by the GENOMICA CLART® and COBAS® 4800 assays. Concordance in hrHPV detection between sample types was determined using Kappa (k) statistics. Sensitivity and specificity of hrHPV detection in urine was calculated using cervical sampling as reference. RESULTS: With the COBAS assay, urine showed good concordance to the vaginal (k = 0.66) self-samples and cervical samples (k = 0.66) for hrHPV detection. The corresponding concordance was moderate (k = 0.59 and k = 0.47) using CLART. Compared to cervical sampling, urinary hrHPV detection had a sensitivity of 63.9% and a specificity of 96.5% using COBAS; compared with 51.6 and 92.4% for CLART. Invalid hrHPV test rates were 1.8% for COBAS and 26.9% for CLART. Urine collection was well-accepted and 42.3% of the women ranked it as the most preferred future screening procedure. CONCLUSIONS: Urine collection provides a well-accepted screening option. With COBAS, higher concordance between urine and vaginal self-sampling and cervical sampling for hrHPV detection was found compared to CLART. Urinary hrHPV detection with COBAS is feasible, but its accuracy may need to be improved before urine collection at home can be offered to non-participants reluctant to both cervical sampling and vaginal self-sampling.

Acute care pathways for patients calling the out-of-hours services.

BACKGROUND: In Western countries, patients with acute illness or injury out-of-hours (OOH) can call either emergency medical services (EMS) for emergencies or primary care services (OOH-PC) in less urgent situations. Callers initially choose which service to contact; whether this choice reflect the intended differences in urgency and severity is unknown. Hospital diagnoses and admission rates following an OOH service contact could elucidate this. We aimed to investigate and compare the prevalence of patient contacts, subsequent hospital contacts, and the age-related pattern of hospital diagnoses following an out-of-hours contact to EMS or OOH-PC services in Denmark. METHODS: Population-based observational cohort study including patients from two Danish regions with contact to EMS or OOH-PC in 2016. Hospital contacts were defined as short (< 24 h) or admissions (≥24 h) on the date of OOH service contact. Both regions have EMS, whereas the North Denmark Region has a general practitioner cooperative (GPC) as OOH-PC service and the Capital Region of Copenhagen the Medical Helpline 1813 (MH-1813), together representing all Danish OOH service types. Calling an OOH service is mandatory prior to a hospital contact outside office hours. RESULTS: OOH-PC handled 91% (1,107,297) of all contacts (1,219,963). Subsequent hospital contacts were most frequent for EMS contacts (46-54%) followed by MH-1813 (41%) and GPC contacts (9%). EMS had more admissions (52-56%) than OOH-PC. For both EMS and OOH-PC, short hospital contacts often concerned injuries (32-63%) and non-specific diagnoses (20-45%). The proportion of circulatory disease was almost twice as large following EMS (13-17%) compared to OOH-PC (7-9%) in admitted patients, whereas respiratory diseases (11-14%), injuries (15-22%) and non-specific symptoms (22-29%) were more equally distributed. Generally, admitted patients were older. CONCLUSIONS: EMS contacts were fewer, but with a higher percentage of hospital contacts, admissions and prevalence of circulatory diseases compared to OOH-PC, perhaps indicating that patients more often contact EMS in case of severe disease. However, hospital diagnoses only elucidate severity of diseases to some extent, and other measures of severity could be considered in future studies. Moreover, the socio-demographic pattern of patients calling OOH needs exploration as this may play an important role in choice of entrance.

Coffee and tea consumption and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition.

The epidemiological evidence regarding the association of coffee and tea consumption with prostate cancer risk is inconclusive, and few cohort studies have assessed these associations by disease stage and grade. We examined the associations of coffee (total, caffeinated and decaffeinated) and tea intake with prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 142,196 men, 7,036 incident prostate cancer cases were diagnosed over 14 years of follow-up. Data on coffee and tea consumption were collected through validated country-specific food questionnaires at baseline. We used Cox proportional hazards regression models to compute hazard ratios (HRs) and 95% confidence intervals (CI). Models were stratified by center and age, and adjusted for anthropometric, lifestyle and dietary factors. Median coffee and tea intake were 375 and 106 mL/day, respectively, but large variations existed by country. Comparing the highest (median of 855 mL/day) versus lowest (median of 103 mL/day) consumers of coffee and tea (450 vs. 12 mL/day) the HRs were 1.02 (95% CI, 0.94-1.09) and 0.98 (95% CI, 0.90-1.07) for risk of total prostate cancer and 0.97 (95% CI, 0.79-1.21) and 0.89 (95% CI, 0.70-1.13) for risk of fatal disease, respectively. No evidence of association was seen for consumption of total, caffeinated or decaffeinated coffee or tea and risk of total prostate cancer or cancer by stage, grade or fatality in this large cohort. Further investigations are needed to clarify whether an association exists by different preparations or by concentrations and constituents of these beverages.

Maternal smoking during pregnancy and offspring utilisation of health care services: A population-based cohort study.

BACKGROUND: Maternal smoking during pregnancy (MSDP) has been associated with a wide range of adverse effects on offspring health, such as low birthweight, behavioural disorders, and asthma. The number of women that smoke during pregnancy in Denmark is still high, making it relevant to study the long-term health outcomes in offspring exposed to maternal smoking in utero. OBJECTIVE: We investigated whether exposure to MSDP is associated with more frequent use of health care services during the first 10 years of life. METHODS: This population-based cohort study included participants enrolled in the Danish National Birth Cohort between 1996 and 2003. Data on MSDP were obtained from two telephone interviews during pregnancy and one interview after pregnancy. The primary outcome was contacts to the health care system. From Danish national registries, we obtained information on number and type of contacts to the general practitioner (GP), and information on the specific types of services provided. Further, we obtained information on hospital admissions, and redemption of prescribed medicine. We fitted negative binomial regression models and Cox proportional hazards regression models to estimate associations. All analyses were adjusted for socio-economic status, birth year, and various maternal factors. RESULTS: We studied 83,905 liveborn singletons and found that offspring exposed to maternal smoking in utero had more contacts to the GP in the first 10 years of life with an incidence rate ratio of 1.05, 95% confidence interval [CI] 1.04, 1.06. A higher rate of admission to hospital in 9 out of 20 categories was found, as was a higher rate of being prescribed psychoanaleptics (hazard ratio [HR] 1.41, 95% CI 1.25, 1.60), drugs for obstructive pulmonary disease (HR 1.14, 95% CI 1.14, 1.20), and antibiotics (HR 1.03, 95% CI 1.01, 1.05). CONCLUSIONS: We found that offspring exposed to MSDP had a higher use of health care services than unexposed offspring.

The effect on participation rates of including focused spirometry information in a health check invitation: a cluster-randomised trial in Denmark.

BACKGROUND: Early detection of lung disease may help reduce disease development. Detection through preventive health checks may be beneficial. Nevertheless, the knowledge is sparse on how to enhance the participation rate in health checks among citizens at risk of developing lung disease. This study investigates if focused information on spirometry can increase the participation rate in a general health check. METHODS: We conducted an open-label, household cluster-randomised trial with a two-group parallel design including 4407 citizens aged 30-49 years in Denmark and an average cluster size of 1.55 citizens per household. The control group (n = 2213) received a standard invitation describing the content of the general health check and containing practical information. The intervention group (n = 2194) received an extended invitation highlighting the benefits of early detection and prevention of lung disease. The primary outcome was difference in participation rate between the two groups. The secondary outcome was the proportion of participants at risk of lung disease in both groups. Risk profile was defined as current smoking or self-reported lung symptoms. The inclusion period was 25 November 2015-3 February 2017. RESULTS: No major difference in participation rate was seen between the intervention group (53.4%) and the control group (52.0%). Participants had statistically significantly higher education level compared to non-participants. A total of 24.2% of the participants were at risk of developing lung disease, but no difference was found between the intervention group and the control group. CONCLUSION: This study revealed no effect on participation rate of including focused spirometry information in the health check invitation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02615769 . Registered on 25 November 2015. The trial protocol has been published.

Contacting out-of-hours primary care or emergency medical services for time-critical conditions - impact on patient outcomes.

BACKGROUND: Out-of-hours (OOH) healthcare services in Western countries are often differentiated into out-of-hours primary healthcare services (OOH-PC) and emergency medical services (EMS). Call waiting time, triage model and intended aims differ between these services. Consequently, the care pathway and outcome could vary based on the choice of entrance to the healthcare system. We aimed to investigate patient pathways and 1- and 1-30-day mortality, intensive care unit (ICU) stay and length of hospital stay for patients with acute myocardial infarction (AMI), stroke and sepsis in relation to the OOH service that was contacted prior to the hospital contact. METHODS: Population-based observational cohort study during 2016 including adult patients from two Danish regions with an OOH service contact on the date of hospital contact. Patients <18 years were excluded. Data was retrieved from OOH service databases and national registries, linked by a unique personal identification number. Crude and adjusted logistic regression analyses were performed to assess mortality in relation to contacted OOH service with OOH-PC as the reference and cox regression analysis to assess risk of ICU stay. RESULTS: We included 6826 patients. AMI and stroke patients more often contacted EMS (52.1 and 54.1%), whereas sepsis patients predominately called OOH-PC (66.9%). Less than 10% (all diagnoses) of patients contacted both OOH-PC & EMS. Stroke patients with EMS or OOH-PC & EMS contacts had higher likelihood of 1- and 1-30-day mortality, in particular 1-day (EMS: OR = 5.33, 95% CI: 2.82-10.08; OOH-PC & EMS: OR = 3.09, 95% CI: 1.06-9.01). Sepsis patients with EMS or OOH-PC & EMS contacts also had higher likelihood of 1-day mortality (EMS: OR = 2.22, 95% CI: 1.40-3.51; OOH-PC & EMS: OR = 2.86, 95% CI: 1.56-5.23) and 1-30-day mortality. Risk of ICU stay was only significantly higher for stroke patients contacting EMS (EMS: HR = 2.38, 95% CI: 1.51-3.75). Stroke and sepsis patients with EMS contact had longer hospital stays. CONCLUSIONS: More patients contacted OOH-PC than EMS. Sepsis and stroke patients contacting EMS solely or OOH-PC & EMS had higher likelihood of 1- and 1-30-day mortality during the subsequent hospital contact. Our results suggest that patients contacting EMS are more severely ill, however OOH-PC is still often used for time-critical conditions.