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Background: Mood stabilisers are the main treatment for bipolar disorder. However, it is uncertain which drugs have the best outcomes. Aims: To investigate whether rates of suicide, self-harm and psychiatric hospital admission in individuals with bipolar disorder differ between mood stabilisers. Method: A cohort design was applied to people aged ≥15 years who were diagnosed with bipolar disorder and living in Denmark during 1995–2016. Treatment with lithium, valproate, other mood stabilisers and antipsychotics were compared in between- and within-individual analyses, and adjusted for sociodemographic characteristics and previous self-harm. Results: A total of 33 337 individuals with bipolar disorder were included (266 900 person-years). When compared with individuals not receiving treatment, those receiving lithium had a lower rate of suicide (hazard ratio 0.40, 95% CI 0.31–0.51). When comparing treatment and non-treatment periods in the same individuals, lower rates of self-harm were found for lithium (hazard ratio 0.74, 95% CI 0.61–0.91). Lower rates of psychiatric hospital admission were found for all drug categories compared with non-treatment periods in within-individual analyses (P<0.001). The low rates of self-harm and hospital admission for lithium in within-individual analyses were supported by results of between-individual analyses. Conclusions: Lithium was associated with lower rates of suicide, self-harm and psychiatric hospital readmission in all analyses. With respect to suicide, lithium was superior to no treatment. Although confounding by indication cannot be excluded, lithium seems to have better outcomes in the treatment of bipolar disorder than other mood stabilisers. [ABSTRACT FROM AUTHOR]

This study aims to describe the prevalence of spinal pain among Danish children, explore the differential nature of spinal pain, and investigate socio-demographic factors predisposing spinal pain. A descriptive study of 46,726 11-14-year-olds participating in the Danish National Birth Cohort was conducted. Self-reported spinal pain (neck, middle back, and low back pain) was registered and classified according to severity. Socioeconomic data on children and their parents were identified in Statistics Denmark registers. Associations between socio-demographic factors and aspects of spinal pain were estimated using multinomial logistic regression models. To account for sample selection, inverse probability weighting (IPW) was applied. Almost 10% boys and 14% girls reported severe spinal pain, whereas around 30% of all children reported moderate pain. Effect estimates indicated the risk to increase with increasing age. Further, children without biological full siblings, not living with both of their parents, or children living in less-educated or lower-income families were more likely to experience spinal pain. The study conclusions were essentially unaffected by IPW.Conclusion: A considerable number of children suffer from spinal pain, and it is more common among children in more disadvantaged families. Etiology of spinal pain needs to be explored further with the aim of informing efficient and targeted prevention. What is Known: • Childhood spinal pain may cause marked discomfort and impairment in children's everyday life, and is suggested as important predictor of later-in-life spinal pain. • Methodological heterogeneity in previous studies and complexity of measuring pain make inferences at a broader level inadequate. What is New: • Prevalence of severe spinal pain in 11-14-year-olds was estimated to almost 10% for boys and 14% for girls, and children in more disadvantaged families were more likely to experience spinal pain. • The results seemed unaffected by sample selection. [ABSTRACT FROM AUTHOR]

Introduction: The decline in birth rates is a concern in public health. Fertility is partly determined before birth by the intrauterine environment and prenatal exposure to maternal stress could, through hormonal disturbance, play a role. There has been such evidence from animal studies but not from humans. We aimed to examine the association between prenatal stress due to maternal bereavement following the death of a relative and childbirths in the offspring. Materials and Methods: This population-based cohort study included all subjects born in Denmark after 1968 and in Sweden after 1973 and follow-up started at the age of 12 years. Subjects were categorized as exposed if their mothers lost a close relative during pregnancy or the year before and unexposed otherwise. The main outcomes were age at first child and age-specific mean numbers of childbirths. Data was analyzed using Cox Proportional Hazards models stratified by gender and adjusted for several covariates. Subanalyses were performed considering the type of relative deceased and timing of bereavement. Results: A total of 4,121,596 subjects were followed-up until up to 41 years of age. Of these subjects, 93,635 (2.3%) were exposed and 981,989 (23.8%) had at least one child during follow-up time. Compared to unexposed, the hazard ratio (HR) [95% confidence interval] of having at least one child for exposed males and females were 0.98 [0.96–1.01] and 1.01 [0.98–1.03], respectively. We found a slightly reduced probability of having children in females born to mothers who lost a parent with HR = 0.97 [0.94–0.99] and increased probability in females born to mothers who lost another child (HR = 1.09 [1.04–1.14]), the spouse (HR = 1.29 [1.12–1.48]) or a sibling (HR = 1.13 [1.01–1.27]). Conclusions: Our results suggested no overall association between prenatal exposure to maternal stress and having a child in early adulthood but a longer time of follow-up is necessary in order to reach a firmer conclusion. [ABSTRACT FROM AUTHOR]

Background Marriage is associated with lower risk of coronary heart disease, but it is unknown if the association depends on time since break-up with a partner. In this study we included both married and unmarried couples to study if the association between broken partnership (BP) and first time incident myocardial infarction (MI) changes with time since BP.Methods Register study of the entire Danish population: the population was restricted to those aged 30 to 65 years with follow-up for incident MI between 1985 and 2006 with an annual record on each individual; in total 43 million records. The register data were used to identify MI events. Poisson regression was used to study associations between time since BP and MI adjusted for socio-demographic confounders and hospital admissions. Analyses were stratified by sex.Results Compared with unexposed (no BP), the incidence rate ratio (IRR) of MI in men with BP in the same year was 0.97 [95% confidence interval (CI) 0.90–1.05], year before BP was 1.25 (95% CI 1.17–1.34), 2–3 years after BP was 1.12 (95% CI 1.06–1.18), 4–8 years after BP was 1.09 (95% CI 1.05–1.14) and 9+ years since BP was 1.09 (95% CI 1.05–1.12). In women, the IRR same year as BP was 1.45 (95% CI 1.26–1.66), the year after BP was 1.30 (95% CI 1.14–1.50), 2–3 years after BP was 1.26 (95% CI 1.13–1.39), 4–8 years after BP was 1.17 (95% CI 1.08–1.26) and 9+ years since BP was 1.24 (95% CI 1.17–1.32).Conclusions We found both a short-term elevated risk of first time MI following BP and a weaker long-term elevated risk, in both men and women. [ABSTRACT FROM PUBLISHER]

Background In studies of all-cause mortality, the fundamental epidemiological concepts of rate and risk are connected through a well-defined one-to-one relation. An important consequence of this relation is that regression models such as the proportional hazards model that are defined through the hazard (the rate) immediately dictate how the covariates relate to the survival function (the risk).Methods This introductory paper reviews the concepts of rate and risk and their one-to-one relation in all-cause mortality studies and introduces the analogous concepts of rate and risk in the context of competing risks, the cause-specific hazard and the cause-specific cumulative incidence function.Results The key feature of competing risks is that the one-to-one correspondence between cause-specific hazard and cumulative incidence, between rate and risk, is lost. This fact has two important implications. First, the naïve Kaplan–Meier that takes the competing events as censored observations, is biased. Secondly, the way in which covariates are associated with the cause-specific hazards may not coincide with the way these covariates are associated with the cumulative incidence. An example with relapse and non-relapse mortality as competing risks in a stem cell transplantation study is used for illustration.Conclusion The two implications of the loss of one-to-one correspondence between cause-specific hazard and cumulative incidence should be kept in mind when deciding on how to make inference in a competing risks situation. [ABSTRACT FROM AUTHOR]

The risk of recurrence in affective disorder is influenced by the number of prior episodes and by a person's tendency toward recurrence. Newly developed frailty models were used to estimate the effect of the number of episodes on the rate of recurrence, taking into account individual frailty toward recurrence. The study base was the Danish psychiatric case register of all hospital admissions for primary affective disorder in Denmark during 1971–1993. A total of 20, 350 first-admission patients were discharged with a diagnosis of major affective disorder. For women with unipolar disorder and for all kinds of patients with bipolar disorder, the rate of recurrence was affected by the number of prior episodes even when the effect was adjusted for individual frailty toward recurrence. No effect of episodes but a large effect of the frailty parameter was found for unipolar men. The authors concluded that the risk of recurrence seems to increase with the number of episodes of bipolar affective disorder in general and for women with unipolar disorder. Am J Epidemiol 1999; 149: 404–11. [ABSTRACT FROM AUTHOR]

. Purpose: To investigate whether normal tension glaucoma (NTG) is associated with increased risk of developing dementia/Alzheimer disease (AD). Methods: A total of 69 patients with NTG were identified in the case note files in the Glaucoma Clinic, University Hospital of Copenhagen (Rigshospitalet), Denmark from 1980 to 2001. The rate of a subsequent diagnosis of dementia as recorded in nationwide health care registers from 1980 to 2005 was estimated and compared with the rate for the general population [standard mortality rate (SMR) = observed number of cases of dementia/expected number of cases of dementia]. Results: The 69 patients had a median age of 64 years (quartiles 57 and 73) at the time of the diagnosis, and the average follow-up period was 12.7 years. The SMRdementia was 0.20 (95% CI 0.01-1.11). No patient developed AD. Conclusion: Normal tension glaucoma was not associated with an increased risk of developing dementia/AD. [ABSTRACT FROM AUTHOR]

Abstract: The risk estimates obtained in studies of genetic polymorphisms and lung cancer differ markedly between studies, which might be due to chance or differences in study design, in particular the stratification/match of comparison group. The effect of different strategies for stratification and adjustment for smoking on the estimated effect of polymorphisms on lung cancer risk was explored in the case-cohort design. We used an empirical and a statistical simulation approach. The stratification strategies were: no smoking stratification, stratification for smoking status and stratification for smoking duration. The study base was a prospective follow-up study with 57,053 participants. In the simulation approach the glutathione S-transferase T1 null polymorphism, as a model of any polymorphism, was added to simulated data in two different ways, assuming either absence or presence of association with smoking. In the empirical approach the risk estimates of the investigated polymorphisms differed between the three different stratification strategies. Simulated data with neither stratification nor adjustment for smoking resulted in low biases and narrow confidence intervals (CI) in the absence of a genotype-smoking association and markedly higher biases in the presence of a genotype-smoking association. In study designs stratified by smoking, low biases and narrow CI spans were found, regardless of a genotype-smoking association. Stratification for smoking seems to be advantageous in case-cohort studies of genetic polymorphisms and lung cancer. [Copyright &y& Elsevier]

Background: Knowledge of risk factors of treatment-resistant depression (TRD) contributes to understand the underlying mechanisms and to identify patients at risk. However, there is still a lack of studies on how different risk factors associate with TRD. The objective of this study was to determine the independent association of several socio-demographic and clinical risk factors with TRD.Methods: 194.074 patients with a first-time hospital contact for depression identified in the Danish National Patient Registry (DNPR) from 1996 through 2014 were followed for TRD for 12 months after diagnosis. Socio-demographic and clinical risk factors were identified in nation-wide registries. Data were analyzed using Cox Proportional Hazard Regression and Fine-Gray model for competing mortality risk.Results: Indicators of disease severity (recurrent depression (adjusted HR (aHR) 1.17 (1.14-1.20)), severity of depression (aHR 2.01 (1.95-2.08)), admission to a psychiatric ward (aHR 2.03 (1.96, 2.10)) were strong risk factors. Aged 65-84 (aHR 1.96 (1.83-2.10)), lost labor market affiliation ((aHR 1.12 (1.08, 1.16)), cohabiting (aHR 1.27 (1.23, 1.30)), comorbid anxiety (aHR 1.18 (1.10-1.27)), insomnia (aHR 1.27 (1.06-1.51)), migraine (aHR 1.42 (1.16-1.73)) and use of psychotropic drugs was also associated with higher rates of TRD.Limitations: Information on drug use during hospitalization was not available. Information on rating scales could have provided a more precise assessment of symptom severity and treatment response.Conclusions: Besides indicators of disease severity, other important risk factors associated with TRD are age, lost labor market affiliation, cohabiting with a partner as well as anxiety, insomnia, migraine and the use of psychotropic medications. [ABSTRACT FROM AUTHOR]