The impact of socioeconomic status and multimorbidity on mortality: a population-based cohort study.

OBJECTIVE: Multimorbidity (MM) is more prevalent among people of lower socioeconomic status (SES), and both MM and SES are associated with higher mortality rates. However, little is known about the relationship between SES, MM, and mortality. This study investigates the association between educational level and mortality, and to what extent MM modifies this association. METHODS: We followed 239,547 individuals invited to participate in the Danish National Health Survey 2010 (mean follow-up time: 3.8 years). MM was assessed by using information on drug prescriptions and diagnoses for 39 long-term conditions. Data on educational level were provided by Statistics Denmark. Date of death was obtained from the Civil Registration System. Information on lifestyle factors and quality of life was collected from the survey. The main outcomes were overall and premature mortality (death before the age of 75). RESULTS: Of a total of 12,480 deaths, 6,607 (9.5%) were of people with low educational level (LEL) and 1,272 (2.3%) were of people with high educational level (HEL). The mortality rate was higher among people with LEL compared with HEL in groups of people with 0-1 disease (hazard ratio: 2.26, 95% confidence interval: 2.00-2.55) and ≥4 diseases (hazard ratio: 1.14, 95% confidence interval: 1.04-1.24), respectively (adjusted model). The absolute number of deaths was six times higher among people with LEL than those with HEL in those with ≥4 diseases. The 1-year cumulative mortality proportions for overall death in those with ≥4 diseases was 5.59% for people with HEL versus 7.27% for people with LEL, and 1-year cumulative mortality proportions for premature death was 2.93% for people with HEL versus 4.04% for people with LEL. Adjusting for potential mediating factors such as lifestyle and quality of life eliminated the statistical association between educational level and mortality in people with MM. CONCLUSION: Our study suggests that LEL is associated with higher overall and premature mortality and that the association is affected by MM, lifestyle factors, and quality of life.

The association of unipolar depression with thirty-day mortality after hospitalization for infection: A population-based cohort study in Denmark.

OBJECTIVE: While depression is associated with higher risk of death due to chronic medical conditions, it is unknown if depression increases mortality following serious infections. We sought to determine if pre-existing unipolar depression is associated with increased mortality within 30days after hospitalization for a serious infection. METHODS: We conducted a population-based cohort study of all adults hospitalized for an infection in Denmark between 2005 and 2013. Pre-existing unipolar depression was ascertained via psychiatrist diagnoses or at least two antidepressant prescription redemptions within a six month period. Our primary outcome was all-cause mortality within 30days after infection-related hospitalization. We also studied death due to infection within 30days after admission. RESULTS: We identified 589,688 individuals who had a total of 703,158 hospitalizations for infections. After adjusting for demographics, infectious diagnosis and time since infection, socioeconomic factors and comorbidities, pre-existing unipolar depression was associated with slightly increased risk of all-cause mortality within 30days after infection-related hospitalization (Mortality Rate Ratio [MRR]: 1.07, 95% Confidence Interval [95% CI]: 1.05, 1.09). The association was strongest among persons who initiated antidepressant treatment within one year before the infection (MRR: 1.30, 95% CI: 1.25, 1.35). Pre-existing unipolar depression was associated with increased risk of death due to sepsis (MRR: 1.30, 95% CI: 1.17, 1.44), pneumonia (MRR: 1.23, 95% CI: 1.16, 1.29) and urinary tract infection (MRR: 1.25, 95% CI: 1.08, 1.44) after adjusting for demographics, infectious diagnosis at admission and time since infection. CONCLUSIONS: Pre-existing unipolar depression is associated with slightly increased mortality following hospitalization for an infection.

Long-term risk of atrial fibrillation after the death of a partner.

OBJECTIVES: Severe psychological stress is generally associated with an increased risk of acute cardiovascular diseases, such as myocardial infarction, but it remains unknown whether it also applies to atrial fibrillation. We conducted a population-based case-control study using nationwide Danish health registers to examine the risk of atrial fibrillation after the death of a partner. METHODS: From 1995 through 2014, we identified 88 612 cases with a hospital diagnosis of atrial fibrillation and 886 120 age-matched and sex-matched controls based on risk-set sampling. The conditional logistic regression model was used to calculate adjusted ORs of atrial fibrillation with 95% CIs. RESULTS: Partner bereavement was experienced by 17 478 cases and 168 940 controls and was associated with a transiently higher risk of atrial fibrillation; the risk was highest 8-14 days after the loss (1.90; 95% CI 1.34 to 2.69), after which it gradually declined. One year after the loss, the risk was almost the same as in the non-bereaved population. Overall, the OR of atrial fibrillation within 30 days after bereavement was 1.41 (95% CI 1.17 to 1.70), but it tended to be higher in persons below the age of 60 years (2.34; 95% CI 1.02 to 5.40) and in persons whose partner had a low predicted mortality 1 month before the death, that is, ≤5 points on the age-adjusted Charlson Comorbidity Index (1.57; 95% CI 1.13 to 2.17). CONCLUSIONS: The severely stressful life event of losing a partner was followed by a transiently increased risk of atrial fibrillation lasting for 1 year, especially for the least predicted losses.

Depression and risk of hospitalisations and rehospitalisations for ambulatory care-sensitive conditions in Denmark: a population-based cohort study.

OBJECTIVE: Hospitalisations for ambulatory care-sensitive conditions (ACSCs), a group of chronic and acute illnesses considered not to require inpatient treatment if timely and appropriate ambulatory care is received, and early rehospitalisations are common and costly. We sought to determine whether individuals with depression are at increased risk of hospitalisations for ACSCs, and rehospitalisation for the same or another ACSC, within 30 days. DESIGN: National, population-based cohort study. SETTING: Denmark. PARTICIPANTS: 5,049,353 individuals ≥ 18 years of age between 1 January 2005 and 31 December 2013. MEASUREMENTS: Depression was ascertained via psychiatrist diagnoses in the Danish Psychiatric Central Register or antidepressant prescription redemption from the Danish National Prescription Registry. Hospitalisations for ACSCs and rehospitalisations within 30 days were identified using the Danish National Patient Register. RESULTS: Overall, individuals with depression were 2.35 times more likely to be hospitalised for an ACSC (95% CI 2.32 to 2.37) versus those without depression after adjusting for age, sex and calendar period, and 1.45 times more likely after adjusting for socioeconomic factors, comorbidities and primary care utilisation (95% CI 1.43 to 1.46). After adjusting for ACSC-predisposing comorbidity, depression was associated with significantly greater risk of hospitalisations for all chronic (eg, angina, diabetes complications, congestive heart failure exacerbation) and acute ACSCs (eg, pneumonia) compared to those without depression. Compared to those without depression, persons with depression were 1.21 times more likely to be rehospitalised within 30 days for the same ACSC (95% CI 1.18 to 1.24) and 1.19 times more likely to be rehospitalised within 30 days for a different ACSC (95% CI 1.15 to 1.23). CONCLUSIONS: Individuals with depression are at increased risk of hospitalisations for ACSCs, and once discharged are at elevated risk of rehospitalisations within 30 days for ACSCs.

Incidence of Suicide Among Persons Who Had a Parent Who Died During Their Childhood: A Population-Based Cohort Study.

IMPORTANCE: Parental death from suicide is associated with increased risk of suicide in the bereaved child, but little is known about the long-term risks of suicide after parental death from other causes. A better understanding of this association may improve suicide prevention efforts. OBJECTIVE: To examine the long-term risks of suicide after parental death and how the risk trajectories differed by cause of parental death while accounting for major potential confounding variables. DESIGN, SETTING, AND PARTICIPANTS: A population-based matched cohort study was performed using information from nationwide registers (data from 1968 to 2008) in 3 Scandinavian countries (for a total of 7,302,033 persons). We identified 189,094 children (2.6%) who had a parent who died before the child reached 18 years of age (ie, the bereaved cohort). Each bereaved child was matched by sex and age to 10 children who did not have a parent who died before they reached 18 years of age (for a total of 1,890,940 children) (ie, the reference cohort). Both cohorts were followed for up to 40 years. Poisson regression was used to calculate the incidence rate ratio (IRR), while accounting for age at parental death, sex, time since bereavement, maternal/paternal death, birth order, family history of psychiatric illness, and socioeconomic status. Data analyses were finalized June 24, 2015. EXPOSURE: The main exposure was death of a parent within the first 18 years of life. MAIN OUTCOMES AND MEASURES: Incidence of suicide among persons who had a parent who died during their childhood. RESULTS: During follow-up, 265 bereaved persons (0.14%) and 1342 nonbereaved persons (0.07%) died of suicide (IRR = 2.02 [95% CI, 1.75-2.34]); IRR = 3.44 (95% CI, 2.61-4.52) for children who had a parent who died of suicide, and IRR = 1.76 (95% CI, 1.49-2.09) for children who had a parent who died of other causes. The IRR tended to be higher for children who had a parent who died before they reached 6 years of age, and the IRR remained high for at least 25 years. During 25 years of follow-up, the absolute risk of suicide was 4 in 1000 persons for boys who experienced parental death and 2 in 1000 persons for girls who experienced parental death. CONCLUSIONS AND RELEVANCE: Parental death in childhood is, irrespective of cause, associated with an increased long-term risk of suicide. The consequences of parental death in childhood are far-reaching, and suicide risk trajectories may be influenced by early-life conditions. Future public health efforts should consider helping highly distressed children to cope with bereavement.

Apgar-score in children prenatally exposed to antiepileptic drugs: a population-based cohort study.

OBJECTIVES: It is unknown if prenatal exposure to antiepileptic drugs (AEDs) increases the risk of low Apgar score in offspring. SETTING: Population-based study using health registers in Denmark. PARTICIPANTS: We identified all 677 021 singletons born in Denmark from 1997 to 2008 and linked the Apgar score from the Medical Birth Register with information on the women's prescriptions for AEDs during pregnancy from the Danish Register of Medicinal Product Statistics. We used the Danish National Hospital Registry to identify mothers diagnosed with epilepsy before birth of the child. Results were adjusted for smoking and maternal age. RESULTS: Among 2906 children exposed to AEDs, 55 (1.9%) were born with an Apgar score ≤7 as compared with 8797 (1.3%) children among 674 115 pregnancies unexposed to AEDs (adjusted relative risk (aRR)=1.41 (95% CI 1.07 to 1.85). When analyses were restricted to the 2215 children born of mothers with epilepsy, the aRR of having a low Apgar score associated with AED exposure was 1.34 (95% CI 0.90 to 2.01) When assessing individual AEDs, we found increased, unadjusted RR for exposure to carbamazepine (RR=1.86 (95% CI 1.01 to 3.42)), valproic acid (RR=1.85 (95% CI 1.04 to 3.30)) and topiramate (RR=2.97 (95% CI 1.26 to 7.01)) when compared to unexposed children. CONCLUSIONS: Prenatal exposure to AEDs was associated with increased risk of being born with a low Apgar score, but the absolute risk of a low Apgar score was <2%. Risk associated with individual AEDs indicate that the increased risk is not a class effect, but that there may be particularly high risks of a low Apgar score associated with certain AEDs.

Use of primary health care prior to a postpartum psychiatric episode.

OBJECTIVE: Childbirth is a strong trigger of psychiatric episodes. Nevertheless, use of primary care before these episodes is not quantified. The aim was to study the use of general practice in Denmark from two years before to one year after childbirth in women who developed postpartum psychiatric disorders. DESIGN: A matched cohort study was conducted including women who gave birth in the period 1996-2010. Women were divided into four groups: (i) all mothers with postpartum psychiatric episodes 0-3 months after birth, n = 939; 2: All mothers with a postpartum psychiatric episode 3-12 months after birth, n = 1 436; and (iii) two comparison groups of mothers, total n = 6 630 among 320 620 eligible women. SETTING: Denmark. SUBJECTS: Women born in Denmark after 1 January 1960, restricting the cohort to women who gave birth to their first singleton child between 1 January 1996 and 20 October 2010. MAIN OUTCOME MEASURES: The main outcome measures were consultation rates, consultation rate ratios, and rate differences. RESULTS: Women who developed a psychiatric episode after childbirth had higher GP consultation rates before, during, and after the pregnancy. Women with a psychiatric episode 0-3 months postpartum had 6.89 (95% CI 6.60; 7.18) mean number of consultations during pregnancy, corresponding to 1.52 (95% CI 1.22; 1.82) more visits than the comparison group. CONCLUSION: Women with a postpartum psychiatric episode had higher use of GP-based primary health care services years before the childbirth, and in this specific group of patients childbirth itself triggered a marked increase in the number of GP contacts postpartum.

Risk of Fetal Death after Treatment with Antipsychotic Medications during Pregnancy.

BACKGROUND: Antipsychotic medications are increasingly used during pregnancy. Nevertheless, fetal risks are still not fully studied. It is currently unclear whether the antipsychotic treatment might induce a higher risk of fetal death. We aimed to determine if use of antipsychotic medication during pregnancy is associated with an increased risk of spontaneous abortion or stillbirth. METHODS: In a historical cohort study, we identified all clinically recognized pregnancies registered in the nationwide Danish registries from 1997 to 2008 (N = 1,005,319). Exposure was defined as any prescription of antipsychotic medications redeemed by the pregnant women during the exposure window, and recorded in the Danish National Prescription Register. Outcome was defined as any spontaneous abortion or stillbirth recorded in the Danish National Hospital Register and the Danish Medical Birth Register respectively. RESULTS: Women exposed to antipsychotic medications during pregnancy had a 34% higher risk of spontaneous abortion (adjusted relative risk = 1.34; 95% confidence interval = 1.22; 1.46) compared to unexposed women, but a similar risk compared to women exposed prior to (but not during) pregnancy (adjusted relative risk = 1.04; 95% confidence interval = 0.93; 1.17). The risk of spontaneous abortion was not increased in exposed pregnancies when compared to unexposed pregnancies in the same women (adjusted hazard ratio = 1.11; 95% CI = 0.94; 1.31). A twofold higher risk of stillbirth was found in women exposed to antipsychotic medications compared with unexposed women (relative risk = 2.27; 95% confidence interval = 1.45; 3.55) and compared with women exposed only prior to pregnancy (relative risk = 2.06; 95% confidence interval = 1.01; 4.19). CONCLUSIONS: The increased risk of spontaneous abortion found in women treated with antipsychotic medications during pregnancy is most likely due to confounding factors. The risk of stillbirth was twofold higher in pregnancies exposed to antipsychotic medication during pregnancy. Treatment with antipsychotic medications during pregnancy requires careful consideration.

Effect of depression and diabetes mellitus on the risk for dementia: a national population-based cohort study.

IMPORTANCE: Although depression and type 2 diabetes mellitus (DM) may independently increase the risk for dementia, no studies have examined whether the risk for dementia among people with comorbid depression and DM is higher than the sum of each exposure individually. OBJECTIVE: To examine the risk for all-cause dementia among persons with depression, DM, or both compared with persons with neither exposure. DESIGN, SETTING, AND PARTICIPANTS: We performed a national population-based cohort study of 2 454 532 adults, including 477 133 (19.4%) with depression, 223 174 (9.1%) with DM, and 95 691 (3.9%) with both. We included all living Danish citizens 50 years or older who were free of dementia from January 1, 2007, through December 31, 2013 (followed up through December 31, 2013). Dementia was ascertained by physician diagnosis from the Danish National Patient Register or the Danish Psychiatric Central Register and/or by prescription of a cholinesterase inhibitor or memantine hydrochloride from the Danish National Prescription Registry. Depression was ascertained by psychiatrist diagnosis from the Danish Psychiatric Central Research Register or by prescription of an antidepressant from the Danish National Prescription Registry. Diabetes mellitus was identified using the National Diabetes Register. MAIN OUTCOMES AND MEASURES: We estimated the risk for all-cause dementia associated with DM, depression, or both using Cox proportional hazards regression models that adjusted for potential confounding factors (eg, demographics) and potential intermediates (eg, medical comorbidities). RESULTS: During 13 834 645 person-years of follow-up, 59 663 participants (2.4%) developed dementia; of these, 6466 (10.8%) had DM, 15 729 (26.4%) had depression, and 4022 (6.7%) had both. The adjusted hazard ratio for developing all-cause dementia was 1.83 (95% CI, 1.80-1.87) for persons with depression, 1.20 (95% CI, 1.17-1.23) for persons with DM, and 2.17 (95% CI, 2.10-2.24) for those with both compared with persons who had neither exposure. The excess risk for all-cause dementia observed for individuals with comorbid depression and DM surpassed the summed risk associated with each exposure individually, especially for persons younger than 65 years (hazard ratio, 4.84 [95% CI, 4.21-5.55]). The corresponding attributable proportion due to the interaction of comorbid depression and DM was 0.25 (95% CI, 0.13-0.36; P < .001) for those younger than 65 years and 0.06 (95% CI, 0.02-0.10; P = .001) for those 65 years or older. CONCLUSIONS AND RELEVANCE: Depression and DM were independently associated with a greater risk for dementia, and the combined association of both exposures with the risk for all-cause dementia was stronger than the additive association.

Use of antiepileptic drugs during pregnancy and risk of spontaneous abortion and stillbirth: population based cohort study.

OBJECTIVE: To determine whether use of antiepileptic drugs during pregnancy may increase the risk of spontaneous abortion or stillbirth. DESIGN: Population based cohort study. SETTING: Register based study in Denmark, 1997-2008. PARTICIPANTS: 983,305 pregnancies identified in the Danish medical birth register and the Danish national hospital discharge register from 1 February 1997 to 31 December 2008 were linked to the Danish Register of Medicinal Product Statistics to obtain information on use of antiepileptic drugs. MAIN OUTCOME MEASURES: Risk ratio of spontaneous abortion and stillbirth after use of antiepileptic drugs during pregnancy, estimated by using binomial regression adjusting for potential confounders of maternal age, cohabitation, income, education, history of severe mental disorder, and history of drug misuse. RESULTS: Antiepileptic drugs were used in a total of 4700 (0.5%) pregnancies. 16 out of 100 pregnant women using antiepileptics and 13 out of 100 pregnant women not using antiepileptics experienced a spontaneous abortion. After adjusting for potential confounders pregnant women using antiepileptics had a 13% higher risk of spontaneous abortions than pregnant women not using antiepileptics (adjusted risk ratio 1.13, 95% confidence interval 1.04 to 1.24). However, the risk of spontaneous abortion was not increased in women with an epilepsy diagnosis (0.98, 0.87 to 1.09), only in women without a diagnosis of epilepsy (1.30, 1.14 to 1.49). In an analysis including women with at least two pregnancies with discordant antiepileptic drug use (for example, use in the first pregnancy but not in the second), the adjusted hazard ratio for spontaneous abortion was 0.83 (0.69 to 1.00) for exposed pregnancies compared with unexposed pregnancies. Stillbirth was identified in 18 women who used antiepileptic drugs (unadjusted risk ratio 1.29, 0.80 to 2.10). CONCLUSION: Among women with epilepsy and when analysing the risk in antiepileptic drug discordant pregnancies in the same woman, we found no overall association between the use of antiepileptic drugs during pregnancy and spontaneous abortions. Therefore unmeasured confounding may explain the slight increased risk for spontaneous abortion with any antiepileptic drug use (among women both with and without epilepsy). We found no association between antiepileptic drug use during pregnancy and stillbirth, but the statistical precision was low.