Danish Register-based Cohort Study Research Articles

Association between alcohol and substance use disorders and psychiatric service use in patients with severe mental illness: a nationwide Danish register-based cohort study.

Substance use disorder is highly prevalent in people with psychiatric disorders, and known to impede the psychiatric treatment. Some studies show increased rates of service use, while others show a decrease. These conflicting results are further hampered by a lack of large-scale studies. The aim of this study was to investigate the association between substance use disorder and psychiatric service use in psychiatric patients. The study was a prospective registry-based cohort study including patients with severe mental illness. The primary outcome was the number of hospitalisations, bed days and the number of psychiatric emergency department contacts. The association was calculated with incidence rate ratio with 95% confidence intervals. The study included all psychiatric patients born since 1955. In total, 21 558 patients with schizophrenia (47.54% with substance use disorder), 80 778 patients with depression (28.78% with substance use disorder), 10 560 patients with bipolar affective disorder (40.08% with substance use disorder) and 69 252 patients with a personality disorder (39.18% with substance use disorder) were included. Patients with comorbid substance use disorder had significantly increased rates of hospitalisations, bed days and psychiatric emergency department contacts (p < 0.001) for the majority of the included substances, compared with patients without such disorders. Substance use disorder was associated with an increased number of hospitalisations, bed days and increased number of psychiatric emergency department contacts for the majority of the included substances.

Infectious gastroenteritis and the need for strict contact precaution procedures in adults presenting to the emergency department: a Danish register-based study

Acute infectious gastroenteritis requires contact precautions to prevent spread. On acute admission, the cause of diarrhoea is unknown, so the decision regarding which patients to isolate has to be made on clinical information with a risk of inexpedient use of contact precautions. To investigate how often gastroenteritis occurs (and therefore how often the need for isolation has to be assessed) in Danish emergency departments, and how often patients have to remain on contact precautions according to the results of faecal samples. This Danish register-based retrospective cohort study on adults in Danish emergency departments used three data sources: discharge diagnoses from the Danish National Patient Register; microbiological results from faecal samples provided in the emergency department; and the causes of hospital admission based on the chief complaint. Among 66,885 acute admissions, 4.3% of patients had at least one feature of gastroenteritis: admission with diarrhoea as the chief complaint (1.6%); microbiological examination of faecal sample (2.8%); and discharged with a diagnosis of gastroenteritis (1.7%). Nineteen percent of those who had a faecal sample tested were found to have norovirus or Clostridium difficile, and needed to remain on strict contact precautions. The initiation of contact precautions has to be assessed for 4.3% of all emergency department patients; 19% of the patients who had a faecal sample tested had highly contagious gastroenteritis and required strict contact precautions. Further studies are needed to develop tools to determine which patients to isolate.

A Danish register-based cohort study on survey data on respondents with symptoms of depression

A Danish register-based cohort study on survey data on respondents with symptoms of depression

Early childhood adversities and risk of eating disorders in women: A Danish register-based cohort study

Early childhood adversities and risk of eating disorders in women: A Danish register-based cohort study

Educational inequality in alcohol-attributable events: A Danish register-based cohort study

Educational inequality in alcohol-attributable events: A Danish register-based cohort study

Maternal smoking during pregnancy and risk of stillbirth: results from a nationwide Danish register-based cohort study.

Maternal smoking during pregnancy has been associated with an increased risk of stillbirth. Only a few studies have been conducted to determine whether smoking affects the risk of antepartum and intrapartum stillbirth differently or whether smoking cessation in early pregnancy reduces the risk. Previous results are inconclusive. We addressed these questions in a large Danish population-based cohort study. From the Danish Medical Birth Register, we identified 841228 singleton births in Denmark between 1997 and 2010 and gathered detailed information on maternal smoking during pregnancy and the vital status of the infant. Associations (odds ratios with 95% confidence intervals) between maternal smoking and risk of stillbirth overall and separately for antepartum and intrapartum stillbirth were analyzed using logistic regression models (generalized estimating equations), adjusting for potential confounders. Any smoking during pregnancy increased the risk of stillbirth, both overall (odds ratio 1.42, 95% confidence interval 1.30-1.55) and for antepartum (odds ratio 1.38, 95% confidence interval 1.25-1.53) and intrapartum (odds ratio 1.52, 95% confidence interval 1.18-1.96) stillbirths. Women who quit smoking at the beginning of the second trimester at the latest had no increased risk of stillbirth overall (odds ratio 1.03, 95% confidence interval 0.80-1.32). Maternal smoking during pregnancy increases the risk of stillbirth, both overall and for antepartum and intrapartum stillbirth separately. Women who quit smoking in the beginning of their pregnancy reduce their risk compared with that of non-smokers.

Cardiovascular disease in patients with osteogenesis imperfecta — a nationwide, register-based cohort study

BackgroundOsteogenesis imperfecta (OI) is a hereditary connective tissue disease often due to mutations in genes coding for type 1 collagen. Collagen type 1 is important in the development of the heart and vasculature. Little is known about the risk of cardiovascular disease (CVD) in OI. ObjectiveTo investigate the risk of symptomatic CVD in OI. DesignA Danish nationwide, population-based and register-based longitudinal open cohort study. ParticipantsAll patients registered with the diagnosis of OI from 1977 to 2013 and a reference population matched 5:1 to the OI cohort. MeasurementsSub-hazard ratios for mitral and aortic valve regurgitation, atrial fibrillation and flutter, heart failure and vascular aneurisms and dissections comparing the OI cohort to the reference population. ResultsWe identified 687 cases with OI (379 women) and included 3435 reference persons (1895 women). The SHR was 6.3 [95% CI: 2.5–15.5] for mitral valve regurgitation, 4.5 [95% CI: 1.4–13.9] for aortic valve regurgitation, 1.7 [95% CI: 1.1–2.8] for atrial fibrillation/flutter, and 2.3 [95% CI: 1.4–3.7] for heart failure. The SHRs were not increased arterial aneurisms or dissections. LimitationOur results were limited by lacking clinical information about phenotype and genotype of the included patients. ConclusionWe confirm that patients with OI have an increased risk of CVD compared to the general population. This held true even when adjusting for factors that are known to contribute to development of these diseases. Our results suggest that the collagenopathy seen in OI may be part of the pathogenesis of CVD in OI.

Dementia and Traffic Accidents: A Danish Register-Based Cohort Study.

BackgroundAs a consequence of a rapid growth of an ageing population, more people with dementia are expected on the roads. Little is known about whether these people are at increased risk of road traffic-related accidents.ObjectiveOur study aims to investigate the risk of road traffic-related accidents for people aged 65 years or older with a diagnosis of dementia in Denmark.MethodsWe will conduct a nationwide population-based cohort study consisting of Danish people aged 65 or older living in Denmark as of January 1, 2008. The cohort is followed for 7 years (2008-2014). Individual’s personal data are available in Danish registers and can be linked using a unique personal identification number. A person is identified with dementia if the person meets at least one of the following criteria: (1) a diagnosis of the disease in the Danish National Patient Register or in the Danish Psychiatric Central Research Register, and/or (2) at least one dementia diagnosis-related drug prescription registration in the Danish National Prescription Registry. Police-, hospital-, and emergency room-reported road traffic-related accidents occurred within the study follow-up are defined as the study outcome. Cox proportional hazard regression models are used for the main analysis.ResultsOur study protocol has 3 phases including data collection, data analysis, and reporting. The first phase of register-based data collection of 853,228 individual’s personal information was completed in August, 2016. The next phase is data analysis, which is expected to be finished before December 2016, and thereafter writing publications based on the findings. The study started in January 2016 and will end in December 2018.DiscussionThis study covers the entire elderly population of Denmark, and thereby will avoid selection bias due to nonparticipation and loss to follow-up. Furthermore, this ensures that the study results are reliable and generalizable. However, underreporting of traffic-related accidents may occur, which will limit estimation of absolute risks.

Mortality and Causes of Death in Patients With Osteogenesis Imperfecta: A Register-Based Nationwide Cohort Study.

Osteogenesis imperfecta (OI) is a hereditary connective tissue disease that causes frequent fractures. Little is known about causes of death and length of survival in OI. The objective of this work was to calculate the risk and cause of death, and the median survival time in patients with OI. This study was a Danish nationwide, population-based and register-based cohort study. We used National Patient Register data from 1977 until 2013 with complete long-term follow-up. Participants comprised all patients registered with the diagnosis of OI from 1977 until 2013, and a reference population matched five to one to the OI cohort. We calculated hazard ratios for all-cause mortality and subhazard ratios for cause-specific mortality in a comparison of the OI cohort and the reference population. We also calculated all-cause mortality hazard ratios for males, females, and age groups (0 to 17.99 years, 18.00 to 34.99 years, 35.00 to 54.99 years, 55.00 to 74.99 years, and >75 years). We identified 687 cases of OI (379 women) and included 3435 reference persons (1895 women). A total of 112 patients with OI and 257 persons in the reference population died during the observation period. The all-cause mortality hazard ratio between the OI cohort and the reference population was 2.90. The median survival time for males with OI was 72.4 years, compared to 81.9 in the reference population. The median survival time for females with OI was 77.4 years, compared to 84.5 years in the reference population. Patients with OI had a higher risk of death from respiratory diseases, gastrointestinal diseases, and trauma. We were limited by the lack of clinical information about phenotype and genotype of the included patients. Patients with OI had a higher mortality rate throughout their life compared to the general population. © 2016 American Society for Bone and Mineral Research.

Seasonal variations in hospital admissions for mania: Examining for associations with weather variables over time

BackgroundBipolar disorder is characterized by a seasonal pattern with emerging evidence that weather conditions may trigger symptoms. Thus, our aims were to investigate if year-to-year variations in admissions with mania correlated with year-to-year variations in key meteorological variables, if there was a secular trend in light of climate change and if gender or admission status influenced the seasonal pattern. MethodsWe undertook a Danish register-based nationwide historical cohort study. We included all adults hospitalized to psychiatric care from 1995 to 2012 with mania using the Danish Psychiatric Central Research Register. The Danish Meteorological Institute provided the meteorological variables. The association between weather and admissions was tested using linear regression. ResultsOur database comprised 24,313 admissions with mania. There was a seasonal pattern with admission rates peaking in summer. Higher admission rates were associated with more sunshine, more ultraviolet radiation, higher temperature and less snow but were unassociated with rainfall. We did not find a secular trend in the seasonal pattern. Finally, neither gender nor admission status impacted on the overall seasonal pattern of admissions with mania. LimitationsOnly patients in psychiatric care were included. We could not subdivide by type of bipolar disorder. ConclusionThis cohort study based on more than 24,000 admissions identified a distinct seasonal pattern in hospital admissions for those with mania. We found no secular trend. This could indicate that the climate change is not impacting on seasonal patterns, that there is no link between the proposed variables or that change is currently not sufficiently distinctive.

Compliance and persistence with treatment with parathyroid hormone for osteoporosis. A Danish national register-based cohort study

Medical intervention is important in the treatment of osteoporosis, and compliance with medical treatment is essential for an optimal outcome. Based on Danish national registers, we found that compliance with parathyroid hormone (PTH) treatment is high and associated with marital status, working status, and type of PTH treatment. Compliance and persistence are essential for an optimal outcome during medical treatment of osteoporosis. We aimed to evaluate compliance and persistence with treatment with PTH in daily clinical practice in Danish patients and to describe factors affecting compliance. Register-based nationwide cohort study on all patients in Denmark initiates PTH or analogue treatment for osteoporosis in 2003-2010 (n = 4281). PTH drugs included were the PTH analogue teriparatide(1-34) and recombinant human PTH (rhPTH(1-84)). Compliance with treatment was calculated by using medication possession ratio (MPR). In the study period, 3702 patients were exclusively treated with teriparatide and 579 were exclusively treated with rhPTH(1-84). We found that for patients persistent with therapy for at least 18 months and with MPR >0.8, 83 % of the patients in the teriparatide group were compliant versus 72 % in the recombinant PTH group (p < 0.01). Being married/cohabiting, still in the labor market, and taking teriparatide were significantly associated with higher compliance, whereas age, gender, level of education, income, alcoholism, and Charlson comorbidity index were not associated with compliance. Compliance with PTH treatment overall is high, with teriparatide compliance higher than rhPTH(1-84), in patients persistent to therapy for 18 months. Compliance is associated with marital status, working status, and type of PTH treatment.

P-403: Antidepressant drugs and the risk of hyponatremia – a Danish register-based cohort study

P-403: Antidepressant drugs and the risk of hyponatremia – a Danish register-based cohort study

Youth, suicide attempts and low level of education: A Danish historical register-based cohort study of the outcome of suicide attempt

In Denmark, it is a political goal that 95% of all young people should complete an upper secondary education. For some young people, this goal can be difficult to achieve. An association has been established between suicidal behaviour and school performance. We hypothesise that young people who have attempted suicide have a lower chance of finishing secondary education. We used Danish historical population registers to perform a longitudinal cohort design and extended Cox regression modelling to estimate crude and adjusted estimates of the effect of suicide attempt on secondary education. We used the birth cohorts 1983-1989, and all subjects were followed from birth until the end of 2011 (n = 355,725). For suicide attempters, the likelihood of completing secondary education was one-third of non-attempters (crude hazard ratio = 0.38). A part of the impact can be explained by confounding factors. Individuals with a suicide attempt at age 16-20 years or with multiple suicide attempts were most likely not to complete secondary education. Compared to mentally ill non-attempters, suicide attempters with mental illness were more likely not to finish secondary education. A suicide attempt is not necessarily causal for not finishing secondary education, but it is a marker, and it predicts an increased likelihood of not finishing secondary education. We need to identify individuals at risk for suicide attempts and subsequently provide the necessary support. Completing secondary education is important, as it provides better chances of employment, higher wages and more opportunities for individuals in the future.

SSRIs and risk of suicide attempts in young people – A Danish observational register-based historical cohort study, using propensity score

Background: SSRIs are widely used in the treatment of mental illness for both children and adults. Studies have found a slightly increased risk of suicidal thoughts and suicide attempts in young people using SSRIs but SSRIs’ impact on risk for suicides in youth is not well-established. Aim: Is there indication that SSRIs might raise risk for suicide attempts in young people? Methods: We used an observational register-based historical cohort design, a large cohort of all Danish individuals born in 1983–1989 (n = 392,458) and a propensity score approach to analyse the impact from SSRIs on risk for suicide attempts. Every suicide attempt and redeemed prescription of SSRIs was analysed by Cox regression. Results: We found a significant overlap between redeeming a prescription on SSRIs and subsequent suicide attempt. The risk for suicide attempt was highest in the first 3 months after redeeming the first prescription. The hazard ratio for suicide attempts after redeeming a prescription was estimated to 5.23, 95% CI 4.82–5.68. Conclusion: We conclude that the risk of suicide attempt is higher for young people in the first months after redeeming their first prescription for SSRIs, compared to non-users. For SSRI users with lower propensity score (fewer risk factors for SSRIs) the risk of suicide attempt is estimated to be highest. Although the design may miss some explicit reason for prescription of SSRIs and SSRIs might be a marker for those in high risk rather than a causal risk factor, we would recommend systematic risk assessment in the period after redeeming the first prescription.

Increased risk of arterial thromboembolic events after Staphylococcus aureus bacteremia: A matched cohort study

An association between infection and arterial thromboembolic events (ATE) has been suggested. Here we examined the risk of myocardial infarction (MI), stroke and other ATE after Staphylococcus aureus bacteremia (SAB). Danish register-based nation-wide observational cohort study between 1995 and 2008 with matched control subjects from the general population. Within a year, 278 of 15,669 SAB patients and 2570 of 156,690 controls developed MI, stroke or another ATE. The incidence rates among SAB patients were highest within the first 30 days and decreased over a year. The adjusted relative risk of MI, stroke and other ATE during the first 30 days after SAB in patients compared to controls were 2.2 (95% CI: 1.6-3.1), 5.5 (95% CI: 3.8-8.3) and 15.5 (95% CI: 6.9-35), respectively. Compared to controls, the increased adjusted relative risk persisted for 30 days for MI, 180 days for stroke and one year for other ATE. Increasing age, hypertension, atrial flutter/fibrillation, prior ATE and endocarditis in SAB patients were associated with an increased risk of ATE. SAB was associated with a short-term increased risk of ATE that persisted longer dependent on type of event. Studies are warranted to investigate treatment strategies to diminish ATE after SAB.

Does a Caesarean section increase the time to a second live birth? A register-based cohort study.

Does a primary Caesarean section influence the rate of, and time to, subsequent live birth compared with vaginal delivery? Caesarean section was associated with a reduction in the rate of subsequent live birth, particularly among elective and maternal-requested Caesareans indicating maternal choice plays a role. Several studies have examined the relationship between Caesarean section and subsequent birth rate with conflicting results primarily due to poor epidemiological methods. This Danish population register-based cohort study covered the period from 1982 to 2010 (N = 832 996). All women with index live births were followed until their subsequent live birth or censored (maternal death, emigration or study end) using Cox regression models. In all 577 830 (69%) women had a subsequent live birth. Women with any type of Caesarean had a reduced rate of subsequent live birth (hazard ratio [HR] 0.86, 95% confidence intervals [CI] 0.85, 0.87) compared with spontaneous vaginal delivery. This effect was consistent when analyses were stratified by type of Caesarean: emergency (HR 0.87, 95% CI 0.86, 0.88), elective (HR 0.83, 95% CI 0.82, 0.84) and maternal-requested (HR 0.61, 95% CI 0.57, 0.66) and in the extensive sub-analyses performed. Lack of biological data to measure a woman's fertility is a major limitation of the current study. Unmeasured confounding and limited availability of data (maternal BMI, smoking, access to fertility services and maternal-requested Caesarean section) as well as changes in maternity care over time may also influence the findings. This is the largest study to date and shows that Caesarean section is most likely not causally related to a reduction in fertility. Maternal choice to delay or avoid childbirth is the most plausible explanation. Our findings are generalizable to other middle- to high-income countries; however, cross country variations in Caesarean section rates and social or cultural differences are acknowledged. Funding was provided by the National Perinatal Epidemiology Centre, Cork, Ireland and conducted as part of the Health Research Board PhD Scholars programme in Health Services Research (Grant No. PHD/2007/16). L.C.K. is a Science Foundation Ireland Principal Investigator (08/IN.1/B2083) and the Director of the SFI funded Centre, INFANT (12/RC/2272). The authors have no competing interests to declare.

Correction: Cesarean Section and Rate of Subsequent Stillbirth, Miscarriage, and Ectopic Pregnancy: A Danish Register-Based Cohort Study

Correction: Cesarean Section and Rate of Subsequent Stillbirth, Miscarriage, and Ectopic Pregnancy: A Danish Register-Based Cohort Study

Cesarean section and rate of subsequent stillbirth, miscarriage, and ectopic pregnancy: a Danish register-based cohort study.

With cesarean section rates increasing worldwide, clarity regarding negative effects is essential. This study aimed to investigate the rate of subsequent stillbirth, miscarriage, and ectopic pregnancy following primary cesarean section, controlling for confounding by indication. We performed a population-based cohort study using Danish national registry data linking various registers. The cohort included primiparous women with a live birth between January 1, 1982, and December 31, 2010 (n = 832,996), with follow-up until the next event (stillbirth, miscarriage, or ectopic pregnancy) or censoring by live birth, death, emigration, or study end. Cox regression models for all types of cesarean sections, sub-group analyses by type of cesarean, and competing risks analyses for the causes of stillbirth were performed. An increased rate of stillbirth (hazard ratio [HR] 1.14, 95% CI 1.01, 1.28) was found in women with primary cesarean section compared to spontaneous vaginal delivery, giving a theoretical absolute risk increase (ARI) of 0.03% for stillbirth, and a number needed to harm (NNH) of 3,333 women. Analyses by type of cesarean section showed similarly increased rates for emergency (HR 1.15, 95% CI 1.01, 1.31) and elective cesarean (HR 1.11, 95% CI 0.91, 1.35), although not statistically significant in the latter case. An increased rate of ectopic pregnancy was found among women with primary cesarean overall (HR 1.09, 95% CI 1.04, 1.15) and by type (emergency cesarean, HR 1.09, 95% CI 1.03, 1.15, and elective cesarean, HR 1.12, 95% CI 1.03, 1.21), yielding an ARI of 0.1% and a NNH of 1,000 women for ectopic pregnancy. No increased rate of miscarriage was found among women with primary cesarean, with maternally requested cesarean section associated with a decreased rate of miscarriage (HR 0.72, 95% CI 0.60, 0.85). Limitations include incomplete data on maternal body mass index, maternal smoking, fertility treatment, causes of stillbirth, and maternally requested cesarean section, as well as lack of data on antepartum/intrapartum stillbirth and gestational age for stillbirth and miscarriage. This study found that cesarean section is associated with a small increased rate of subsequent stillbirth and ectopic pregnancy. Underlying medical conditions, however, and confounding by indication for the primary cesarean delivery account for at least part of this increased rate. These findings will assist women and health-care providers to reach more informed decisions regarding mode of delivery. Please see later in the article for the Editors' Summary.

Maternal smoking in pregnancy and risk for congenital malformations: results of a Danish register-based cohort study.

To examine the association between maternal smoking during pregnancy and risk for congenital malformations. Population-based prospective cohort study. Denmark. A total of 838265 singleton liveborn babies delivered in Denmark between 1997 and 2010 and registered in the Danish Medical Birth Register containing detailed information on smoking during pregnancy and congenital malformations. Associations [odds ratios (OR) with 95% CI] between maternal smoking and risk for various groups of congenital malformations, investigated using the generalized estimating equation for binary outcomes, with adjustment for potential confounders. Groups of congenital malformations. Ever smoking during pregnancy did not increase the overall risk for congenital malformations, but increased risks were observed for multiple malformations (i.e. when two or more malformations are diagnosed in a child) (odds ratio 1.06, 95% confidence interval 1.01-1.10) and various main groups of congenital malformations including the cardiovascular system (odds ratio 1.13, 95% confidence interval 1.07-1.19), the respiratory system (odds ratio 1.25, 95% confidence interval 1.11-1.41), the digestive system (odds ratio 1.15, 95% confidence interval 1.07-1.24) and oral clefts (odds ratio 1.29, 95% confidence interval 1.14-1.46), as well as for some specific congenital malformations including cardiac septal defects, malformations of the pulmonary and tricuspid valves, malformations of the great arteries, pyloric stenosis and clubfoot. Infants of women who quit smoking during the first two trimesters had no increased risk for most groups of congenital malformations. Maternal smoking increases the risk for a number of congenital malformations. Future smoking cessation programs should focus on this adverse health aspect in order to encourage more women to quit smoking before or in early pregnancy.

Increased risk of long-term sickness absence, lower rate of return to work, and higher risk of unemployment and disability pensioning for thyroid patients: a Danish register-based cohort study.

Context:Little is known about how thyroid diseases affect work ability.Objective:The objective of this study was to evaluate the risk of work disability for patients with thyroid disease compared with the general population.Design, Setting, and Participants:In a longitudinal register study, outpatients (n = 862) with nontoxic goiter, hyperthyroidism, Graves' orbitopathy (GO), autoimmune hypothyroidism, or other thyroid diseases and their matched controls (n = 7043) were observed in the years 1994–2011 in Danish national registers of social benefits, health, and work characteristics. Cox regression analyses estimated adjusted hazard ratios (HRs) for the first year after diagnosis and subsequent years.Main Outcome Measures:Transitions between work, long-term sickness absence, unemployment, and disability pension were measured.Results:Patients differed significantly from the general population with regard to sickness absence, disability pension, return from sickness absence, and unemployment. In the first year after diagnosis, higher risks of sickness absence was seen for GO (HR 6.94) and other hyperthyroid patients (HR 2.08), who also had lower probability of returning from sickness absence (HR 0.62) and higher risk of disability pension (HR 4.15). Patients with autoimmune hypothyroidism showed a lower probability of returning from sickness absence (HR 0.62). In subsequent years, GO patients had significantly higher risk of sickness absence (HR 2.08), lower probability of return from sickness absence (HR 0.51), and unemployment (HR 0.52) and a higher risk of disability pension (HR 4.40). Hyperthyroid patients also had difficulties returning from sickness absence (HR 0.71).Conclusions:Thyroid patients' risk of work disability is most pronounced in the first year after diagnosis and attenuates in subsequent years. GO patients have the highest risk of work disability.