Socio-economic functioning in patients with bipolar disorder and their unaffected siblings - results from a nation-wide population-based longitudinal study.

BACKGROUND: Few studies have reported real-life data on socio-economic functioning in patients with bipolar disorder and their unaffected first-degree relatives. METHODS: We used Danish nation-wide population-based longitudinal register linkage to investigate socio-economic functioning in 19 955 patients with bipolar disorder, their 13 923 siblings and 20 sex, age and calendar-matched control individuals from the general population. Follow-up was from 1995 to 2017. RESULTS: Patients with a diagnosis of bipolar disorder had lower odds of having achieved the highest educational level [OR 0.75 (95% confidence interval (CI) 0.73-0.77)], being employed [OR 0.16 (95% CI 0.159-0.168)], having achieved the 80% highest quartile of income [OR 0.33 (95% CI 0.32-0.35)], cohabitating [OR 0.44 (95% CI 0.43-0.46)] and being married [OR 0.54 (95% CI 0.52-0.55)] at first contact to hospital psychiatry as inpatient or outpatient compared with control individuals from the general population. Similarly, siblings to patients with bipolar disorder had a lower functioning within all five socio-economic areas than control individuals. Furthermore, patients and partly siblings showed substantially decreased ability to enhance their socio-economic functioning during the 23 years follow-up compared to controls. CONCLUSIONS: Socio-economic functioning is substantially decreased in patients with bipolar disorder and their siblings and does not improve during long-term follow-up after the initial hospital contact, highlighting a severe and overlooked treatment gap.

Inference for transition probabilities in non-Markov multi-state models.

Multi-state models are frequently used when data come from subjects observed over time and where focus is on the occurrence of events that the subjects may experience. A convenient modeling assumption is that the multi-state stochastic process is Markovian, in which case a number of methods are available when doing inference for both transition intensities and transition probabilities. The Markov assumption, however, is quite strict and may not fit actual data in a satisfactory way. Therefore, inference methods for non-Markov models are needed. In this paper, we review methods for estimating transition probabilities in such models and suggest ways of doing regression analysis based on pseudo observations. In particular, we will compare methods using land-marking with methods using plug-in. The methods are illustrated using simulations and practical examples from medical research.

Social, demographic and health characteristics of men fathering children at different ages.

The aim of this study was to examine associations between selected sociodemographic, socioeconomic, and health characteristics and the rates of fatherhood in different age groups. We investigated rates between 2011 and 2015 in a population-based register study including all men born from 1945 to 1995 residing in Denmark in 2011. The study population consisted of 1,867,108 men who fathered 268,612 children during the follow-up. The associations were quantified as incidence rate ratios using Poisson regression. Young men had higher rates of fathering a child if they lived outside the Capital Region, had a relatively high income, were previously diagnosed with cardiovascular disease, psychoactive substance abuse, personality disorders, schizophrenia or behavioural and emotional disorders. Men of advanced age had higher rates of fathering a child when born outside Denmark, living in the Capital Region, were in the lower or upper 10th percentile income group, were self-employed or unemployed or previously diagnosed with depression. Men of advanced age had lower rates of fathering a child if previously diagnosed with somatic diseases, psychoactive substance abuse or mental retardation. The findings highlight the importance of consideration of various sociodemographic, socioeconomic, and health characteristics when studying associations between paternal age and offspring health.

Ethnic differences in the risk of caesarean section: a Danish population-based register study 2004-2015.

BACKGROUND: Studies have shown differences in the risk of caesarean section (CS) between ethnic minority groups. This could be a marker of unequal health care. The aim of this study was to investigate differences in the risk of CS between immigrants of various origins in Denmark, where all health care is free and easy to access, and Danish-born women. A further aim was to determine the possible influence of known risk factors for CS. METHODS: The design was a population-based register study using national Danish registers and included all live- and stillborn singleton deliveries by primiparous women in Denmark from 2004 to 2015. The total study population consisted of 298,086 births, including 25,198 births to women from the 19 largest immigrant groups in Denmark. Multinomial logistic regression analysis was used to estimate relative risk ratios (RRR) of emergency and planned CS, using vaginal delivery (VD) as reference, in immigrant women compared to Danish-born women. A number of known risk factors were included separately. RESULTS: Women from Turkey, the Philippines, Thailand, Somalia, Vietnam, Iran and Afghanistan had a statistically significant elevated risk ratio of emergency CS vs. VD compared to Danish-born women; adjusted RRR's ranging 1.15-2.19. The risk ratio of planned CS vs. VD was lower among the majority of immigrant groups, however higher among women from Poland, Thailand and Iran, when compared to Danish-born women. None of the studied explanatory variables affected the risk ratio of planned CS vs. VD, whereas maternal height contributed with varying strength to the risk ratio of emergency CS vs. VD for all immigrant groups. CONCLUSION: Substantial variations in CS risks by maternal country of birth were documented. Some of the disparities in emergency CS seem to be explained by maternal height.

A Note on the Measurement of Socioeconomic Inequalities in Life Years Lost by Cause of Death.

Quantifying socioeconomic inequalities in health in absolute terms is of prime interest for decision-making and for international comparisons. The Slope Index of Inequality (SII), an index that quantifies absolute socioeconomic inequalities, was recently formalized, particularly in the context of mortality differences measured in the rate or hazard scale. However, absolute inequalities using either rates or hazards do not translate into a time dimension, which makes their interpretation difficult for policymakers. We propose an extension of the (Equation is included in full-text article.)in terms of the expected number of life years lost before an upper age, as well as its decomposition by cause of death. The (Equation is included in full-text article.)in the life years lost metric quantifies the extent to which life expectancy is shortened when comparing the higher and lower ends of the socioeconomic scale. The methodology proposed builds on recent developments in survival analysis for decomposing the number of life years lost according to cause of death using a pseudo-value approach. We illustrate our proposal using a representative 1% sample of the French population. On average, the least educated men lost 7 years of life from age 30 up to age 90 compared to the most educated. The loss for women is twice as much with 3.5 years. The (Equation is included in full-text article.)in the life years lost metric is easily understood, and the decomposition of the all-cause mortality (Equation is included in full-text article.)into parts attributable to given causes provides a sound estimation of the burden of different causes of death on absolute socioeconomic inequalities in mortality.

Goodness of fit tests for estimating equations based on pseudo-observations.

We study regression models for mean value parameters in survival analysis based on pseudo-observations. Such parameters include the survival probability and the cumulative incidence in a single point as well as the restricted mean life time and the cause-specific number of years lost. Goodness of fit techniques for such models based on cumulative sums of pseudo-residuals are derived including asymptotic results and Monte Carlo simulations. Practical examples from liver cirrhosis and bone marrow transplantation are also provided.

Delayed age at transfer of adoptees to adoptive parents is associated with increased mortality irrespective of social class of the adoptive parents: a cohort study.

BACKGROUND: Adverse early life experience and development may have long-term health consequences, but later environmental conditions may perhaps protect against the effects of such early life adversities. The aim was to investigate whether cause-specific and overall mortality rates among adoptees are associated with the age at which they were transferred to the adoptive family and whether the social class of the adoptive family modifies this association. METHODS: A cohort of 10,592 non-familial adoptions (biologically unrelated adoptee and adoptive parents) of Danish-born children formally granted in 1924-47 and with follow-up of total and cause-specific mortality through ages up to 85 years. The rates of death after the age of 16 from all causes combined, all natural causes, all external causes, and suicide were compared according to the age at which adoptees were transferred to their adoptive family by estimating hazard ratios in Cox regression models. RESULTS: Death rates from all causes were significantly higher in adoptees transferred between age 1 month and 4 years compared to those transferred immediately after birth with the hazard ratio peaking at 1.19 (95% confidence limit: 1.08 to 1.32) for adoptees transferred between 6 and 11 months. This result was primarily driven by a similar pattern for natural causes of death. For death from external causes and for suicide the hazard ratios were increasing with increasing age at transfer, and tests for trend were statistically significant. The social class of the adoptive family did not significantly modify these associations. CONCLUSIONS: Transfer to an adoptive family later than at the time of birth may have adverse long-term consequences affecting overall and cause-specific mortality. These effects were not modified by the environment provided by the adoptive family as indicated by the social class of these families.

Life years lost among patients with a given disease.

A number of suggested measures of life years lost among patients with a given disease are reviewed, and some new ones are proposed. The methods are all phrased in the framework of a (Markov or non-Markov) illness-death model in combination with a population life table. The methods are illustrated using data on Danish male patients with bipolar disorder, and some recommendations are given. Copyright © 2017 John Wiley & Sons, Ltd.

Socioeconomic disparities in birth weight and body mass index during infancy through age 7†years: a study within the Danish National Birth Cohort.

BACKGROUND: Socioeconomic inequalities in birth weight and in body mass index (BMI) later in childhood are in opposite directions, which raises questions about when during childhood the change in direction happens. We examined how maternal and paternal education and household income were associated with birthweight z-scores and with BMI z-scores at age 5 and 12 months and 7 years, and we examined the socioeconomic differences in the tracking of these z-scores across infancy and childhood. METHODS: The associations were studied in a cohort of children in the Danish National Birth Cohort, single born between 1997 and 2003, for whom information on body size from at least 1 of 4 time points (n=85 062) was recorded. We examined the associations using linear mixed-effects modelling. RESULTS: Children from families with a low maternal and paternal educational level changed their body size z-scores upwards between birth and age 7 years. At age 5 and 12 months, there were no educational gradient. A low maternal educational level was associated with lower birth weight for gestational age z-scores at birth for boys (-0.199; 95% CI -0.230 to -0.169) and girls (-0.198; 95% CI -0.229 to -0.167) and higher BMI z-scores at age 7 for boys (0.198; 95% CI 0.154 to 0.242) and girls (0.218; 95% CI 0.173 to 0.264). There was not a similarly clear pattern in the tracking between different household income groups. However, a low household income level was associated with higher z-scores of both birth weight and BMI at age 7 years, but with a much weaker gradient at 5 and 12 months. CONCLUSIONS: The educational gradient shifts from positive with birth weight, to none during infancy to inverse with BMI at age 7 years. In contrast, the income gradient was positive at birth and at 7 years and much weaker during infancy.

Nationwide and population-based prescription patterns in bipolar disorder.

OBJECTIVES: The aim of the present study was to describe prescription patterns and changes in these patterns over the last decade for patients diagnosed with bipolar disorder in mental healthcare, using population-based and nationwide data, and to relate the findings to recommendations from international guidelines. METHODS: A population-based, nationwide study was carried out. It included register-based longitudinal data on all patients with a first-ever contact with mental healthcare with a diagnosis of mania/bipolar disorder from the entire Danish population, and all prescription data for this population during the decade from 2000 to 2011, inclusive. RESULTS: A total of 3,205 patients were included in the study. Lithium was prescribed less, and antiepileptic and atypical antipsychotic agents were prescribed substantially more during the study period. Lithium went from being the first drug prescribed to being the last, and was replaced by atypical antipsychotic agents. Antiepileptic agents went from being the fourth to the second drug class prescribed, and the prescription of antidepressants was virtually unchanged, at a high level, during the decade (one-year value 40-60%). The prescription of lamotrigine and quetiapine increased substantially. Combination therapy increased for all drug combinations, except for lithium combined with antidepressants. CONCLUSIONS: Major changes took place in drug prescriptions during the study period. The decrease in the use of lithium and the constant high use of antidepressants do not align with recommendations from international guidelines.

Socio-economic position and time trends in invasive management and case fatality after acute myocardial infarction in Denmark.

BACKGROUND: Lower case fatality and increased use of evidence-based invasive management incl. coronary angiography (CAG) have been reported for patients admitted with acute myocardial infarction (AMI) in the last 25 years. This article seeks to investigate whether these advances have benefitted patients in all socio-economic groups and how this has impacted on inequality in case fatality. METHODS: Forty three thousand eight hundred and forty three patients admitted with AMI in the period from 2001 to 2009 were included. Socio-economic position was measured using individual information on education. Age-standardized cumulative incidence of CAG within 1, 3 and 30 days along with age-standardized case fatality within 30 and 365 days were estimated. Cox regression models were used to model the relative inequality over time. RESULTS: Use of CAG within 1, 3 and 30 days increased for all educational groups over time and the inequality in CAG within 1 and 3 days seen in the beginning of the time frame was eliminated. Case fatality decreased in all educational groups and the relative inequality in 30 days case fatality decreased for women but not 365 days case fatality. No change was seen for inequality in case fatality for men. CONCLUSION: Increased use of CAG within the evidence based time frame was observed along with a decrease in inequality. However, a reduction in inequality was only observed for short term case fatality, and only for women. These results suggest that inequality in case fatality is not primarily driven by inequality in invasive management of AMI.

Does access to invasive examination and treatment influence socioeconomic differences in case fatality for patients admitted for the first time with non-ST-elevation myocardial infarction or unstable angina?

AIMS: Our aim was to investigate whether there is social inequality in access to invasive examination and treatment, and whether access explains social inequality in case fatality in a nationwide sample of patients admitted for the first time with unstable angina or non-ST-elevation myocardial infarction (NSTEMI) in Denmark. METHODS AND RESULTS: All patients admitted for the first time with NSTEMI (n=16,625) or unstable angina (n=8,800) from 2001 to 2009 in Denmark were included. We measured time from admission to coronary angiography (CAG), percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). The outcomes were 30-day and one-year case fatality. We found social inequality in access to CAG and one-year case fatality for both NSTEMI and unstable angina patients, but the time waited for CAG did not explain the social inequality in case fatality. CONCLUSIONS: Despite nominal equal access to health care, social inequality in case fatality after NSTEMI and unstable angina exists in Denmark. The patients with the shortest education waited longer for angio-graphy; however, this did not seem to explain inequality in case fatality. This register-based study was approved by the Danish Data Protection Agency (Approval number 2010-41-5263). Register-based studies do not need approval by a medical ethics committee in Denmark.

Cohort profile: the Social Inequality in Cancer (SIC) cohort study.

The Social Inequality in Cancer (SIC) cohort study was established to determine pathways through which socioeconomic position affects morbidity and mortality, in particular common subtypes of cancer. Data from seven well-established cohort studies from Denmark were pooled. Combining these cohorts provided a unique opportunity to generate a large study population with long follow-up and sufficient statistical power to develop and apply new methods for quantification of the two basic mechanisms underlying social inequalities in cancer-mediation and interaction. The SIC cohort included 83 006 participants aged 20-98 years at baseline. A wide range of behavioural and biological risk factors such as smoking, physical inactivity, alcohol intake, hormone replacement therapy, body mass index, blood pressure and serum cholesterol were assessed by self-administered questionnaires, physical examinations and blood samples. All participants were followed up in nationwide demographic and healthcare registries. For those interested in collaboration, further details can be obtained by contacting the Steering Committee at the Department of Public Health, University of Copenhagen, at inan@sund.ku.dk.

Are familial factors underlying the association between socioeconomic position and prescription medicine? A register-based study on Danish twins.

OBJECTIVES: Although well established, the association between socioeconomic position and health and health behaviour is not clearly understood, and it has been speculated that familial factors, for example, dispositional factors or exposures in the rearing environment, may be underlying the association. The objective was to compare prescription fillings within twin pairs who are partly or fully genetically identical and share childhood exposures. DESIGN: Twin cohort study. SETTING: Denmark. PARTICIPANTS: Data from the Danish Twin Registry were linked to registers in Statistics Denmark and the Danish Registry of Medicinal Product statistics. A total of 8582 monozygotic (MZ) and 15 788 dizygotic same sex (DZSS) twins were included. OUTCOME MEASURES: Number of prescription fillings during follow-up (1995-2005) was analysed according to education and income. Results of unpaired and intrapair analyses were compared. RESULTS: An inverse social gradient in filling of prescriptions for all-purpose and system-specific drugs was observed in the unpaired analyses. In the intrapair analyses, associations were attenuated some in DZSS and more in MZ twins. Filling of drugs targeting the nervous system was still strongly associated with income in the intrapair analyses. CONCLUSIONS: Familial factors seem to account for part of the observed social inequality in filling of prescription medicine.

Does shared family background influence the impact of educational differences on early mortality?

The mechanisms behind social differences in mortality rates have been debated. The authors examined the extent to which shared family background and health in early life could explain the association between educational status and all-cause mortality rates using a sibling design. The study was register-based and included all individuals born in Denmark between 1950 and 1979 who had at least 1 full sibling born in the same time period (n = 1,381,436). All individuals were followed from 28 years of age until death, emigration, or December 2009. The authors used Cox regression analyses to estimate hazard ratios for mortality according to educational level. Conventional cohort and intersibling analyses were carried out and conducted separately for deaths occurring before and after the age of 45 years, respectively. The cohort analyses showed an inverse association between educational status and all-cause mortality that was strongest for males, increased with younger birth cohorts, and tended to be strongest in the analyses of death before 45 years of age. The associations were attenuated slightly in the intersibling analyses and after adjustment for serious health conditions in early life. Hence, health selection and confounding by factors shared by siblings explained only a minor part of the association between educational level and all-cause mortality.

Risk for hepatocellular carcinoma in patients with alcoholic cirrhosis: a Danish nationwide cohort study.

BACKGROUND: Patients with alcoholic cirrhosis are at higher risk for hepatocellular carcinoma (HCC). The role of HCC surveillance for these patients is undefined. OBJECTIVE: To provide population-based estimates of HCC incidence and comparisons of HCC-related mortality and total mortality among patients with alcoholic cirrhosis as a basis for assessing the role of HCC surveillance. DESIGN: Nationwide, registry-based, historical cohort study. SETTING: Denmark. PATIENTS: All Danish citizens with a first-time hospital diagnosis of alcoholic cirrhosis from 1993 to 2005. MEASUREMENTS: Hepatocellular carcinoma incidence and mortality starting 1 year after diagnosis of alcoholic cirrhosis through 2009; ratio of HCC-related mortality to total mortality. RESULTS: Among 8482 patients, 169 developed HCC. A total of 5734 patients died, 151 of whom had developed HCC. Five-year cumulative HCC risk was 1.0% (95% CI, 0.8% to 1.3%), and 5-year cumulative mortality was 43.7% (CI, 42.6% to 44.7%). Only 1.8% of all deaths were HCC-related. In sensitivity analyses that included all possible HCC diagnoses and a subpopulation of patients who were followed by hepatologists, the highest 5-year HCC risk was 1.9% (CI, 0.8% to 3.9%). These patients did not have higher mortality than patients in the nationwide cohort. LIMITATION: Cirrhosis and HCC diagnoses were made by hospital physicians without uniform clinical criteria, and use of registry data precluded detailed information on clinical care of patients, including HCC surveillance. CONCLUSION: Danish patients with alcoholic cirrhosis have a low risk for HCC, and HCC contributes little to their high mortality. On the basis of these data, HCC surveillance would be expected to have a minimal effect on mortality and is unlikely to be cost-effective.

Interpretability and importance of functionals in competing risks and multistate models.

The basic parameters in both survival analysis and more general multistate models, including the competing risks model and the illness-death model, are the transition hazards. It is often necessary to supplement the analysis of such models with other model parameters, which are all functionals of the transition hazards. Unfortunately, not all such functionals are equally meaningful in practical contexts, even though they may be mathematically well defined. We have found it useful to check whether the functionals satisfy three simple principles, which may be used as criteria for practical interpretability.

How do macro-level contexts and policies affect the employment chances of chronically ill and disabled people? Part II: The impact of active and passive labor market policies.

The authors investigate three hypotheses on the influence of labor market deregulation, decommodification, and investment in active labor market policies on the employment of chronically ill and disabled people. The study explores the interaction between employment, chronic illness, and educational level for men and women in Canada, Denmark, Norway, Sweden, and the United Kingdom, countries with advanced social welfare systems and universal health care but with varying types of active and passive labor market policies. People with chronic illness were found to fare better in employment terms in the Nordic countries than in Canada or the United Kingdom. Their employment chances also varied by educational level and country. The employment impact of having both chronic illness and low education was not just additive but synergistic. This amplification was strongest for British men and women, Norwegian men, and Danish women. Hypotheses on the disincentive effects of tighter employment regulation or more generous welfare benefits were not supported. The hypothesis that greater investments in active labor market policies may improve the employment of chronically ill people was partially supported. Attention must be paid to the differential impact of macro-level policies on the labor market participation of chronically ill and disabled people with low education, a group facing multiple barriers to gaining employment.

Does educational status impact adult mortality in Denmark? A twin approach.

To disentangle an independent effect of educational status on mortality risk from direct and indirect selection mechanisms, the authors used a discordant twin pair design, which allowed them to isolate the effect of education by means of adjustment for genetic and environmental confounding per design. The study is based on data from the Danish Twin Registry and Statistics Denmark. Using Cox regression, they estimated hazard ratios for mortality according to the highest attained education among 5,260 monozygotic and 11,088 dizygotic same-sex twin pairs born during 1921-1950 and followed during 1980-2008. Both standard cohort and intrapair analyses were conducted separately for zygosity, gender, and birth cohort. Educational differences in mortality were demonstrated in the standard cohort analyses but attenuated in the intrapair analyses in all subgroups but men born during 1921-1935, and no effect modification by zygosity was observed. Hence, the results are most compatible with an effect of early family environment in explaining the educational inequality in mortality. However, large educational differences were still reflected in mortality risk differences within twin pairs, thus supporting some degree of independent effect of education. In addition, the effect of education may be more pronounced in older cohorts of Danish men.

Socioeconomic status and survival of cirrhosis patients: a Danish nationwide cohort study.

BACKGROUND: Low socioeconomic status is a risk factor for liver cirrhosis, but it is unknown whether it is a prognostic factor after cirrhosis diagnosis. We examined whether marital status, employment, and personal income were associated with the survival of cirrhosis patients. METHODS: Using registry-data we conducted a population-based cohort study of 1,765 Danish cirrhosis patients diagnosed in 1999-2001 at age 45-59 years. Follow-up ended on 31 December 2003. With Cox regression we examined the associations between marital status (never married, divorced, married), employment (employed, disability pensioner, unemployed), personal income (0-49, 50-99, 100+ percent of the national average) and survival, controlling for gender, age, cirrhosis severity, comorbidity, and substance abuse. RESULTS: Five-year survival was higher for married patients (48%) than for patients who never married (40%) or were divorced (34%), but after adjustment only divorced patients had poorer survival than married patients (adjusted hazard ratio for divorced vs. married = 1.22, 95% CI 1.04-1.42). Five-year survival was lower for disability pensioners (31%) than for employed (46%) or unemployed patients (48%), also after adjustment (adjusted hazard ratio for disability pensioners vs. employed = 1.35, 95% CI 1.09-1.66). Personal income was not associated with survival. CONCLUSION: Marital status and employment were associated with the survival of cirrhosis patients. Specifically, divorced cirrhosis patients and cirrhosis patients who never married had a poorer survival than did married cirrhosis patients, and cirrhosis patients who were disability pensioners had a poorer survival than did employed or unemployed cirrhosis patients. The poorer survival for the divorced and for the disability pensioners could not be explained by differences in other socioeconomic factors, gender, age, cirrhosis severity, substance abuse, or comorbidity. Personal income was not associated with survival.