Risk of Major Types of Dementias Following Hospital-Diagnosed Infections and Autoimmune Diseases.

Background: Population-based studies have shown an increased risk of dementia after infections, but weaker links were reported for autoimmune diseases. Evidence is scarce for whether the links may be modified by the dementia or exposure subtype. Objective: We aimed to investigate the association between infections and/or autoimmune diseases and rates of major types of dementias in the short- and long terms. Methods: Nationwide nested case-control study of dementia cases (65+ years) diagnosed in Denmark 2016-2020 and dementia-free controls. Exposures were hospital-diagnosed infections and autoimmune diseases in the preceding 35 years. Two groups of dementia cases were those diagnosed in memory clinics (MC) and those diagnosed outside memory clinics (non-memory clinic cases, NMC). Results: In total, 26,738 individuals were MC and 12,534 were NMC cases. Following any infection, the incidence rate ratio (IRR) for MC cases was 1.23 (95% CI 1.20-1.27) and 1.70 for NMC cases (1.62-1.76). Long-term increased rates were seen for vascular dementia and NMC cases. IRRs for autoimmune diseases were overall statistically insignificant. Conclusions: Cases with vascular dementia and not Alzheimer's disease, and a subgroup of cases identified with poorer health have increased long-term risk following infections. Autoimmune diseases were not associated with any type of dementia. Notably increased risks (attributed to the short term) and for NMC cases may indicate that immunosenescence rather than de novo infection explains the links. Future focus on such groups and on the role of vascular pathology will explain the infection-dementia links, especially in the long term.

A comprehensive analysis of age of onset and cumulative incidence of mental disorders: A Danish register study.

BACKGROUND: The age of onset (AOO), incidence and cumulative incidence of mental disorders are critical epidemiological measures, providing essential insights into the development and course of these disorders across the lifespan. This study aims to provide up-to-date estimates of the AOO, age-specific incidence, and cumulative incidence for a comprehensive range of mental disorders using data from Danish registers. METHODS: We conducted a follow-up study encompassing all Danish residents from January 1, 2004, to December 31, 2021, totaling 91,613,465 person-years. Data were sourced from the Danish Psychiatric Central Research Register, identifying individuals treated for various mental disorders in psychiatric hospitals, outpatient departments, and accident/emergency departments, that is, treated in secondary care settings. We investigated specific categories of mental disorders, including substance abuse disorders, schizophrenia, mood disorders, anxiety, eating disorders, borderline personality disorders, intellectual disabilities, pervasive developmental disorders, and behavioral and emotional disorders. Age-sex-specific incidence rates were estimated using Poisson generalized linear models, and cumulative incidence was calculated using Aalen-Johansen's competing risks model. The study provides estimates of AOO, incidence, and cumulative incidence for various mental disorders, including their age and sex distributions. RESULTS: The cumulative incidence by age 80 years for any mental disorder was 30.72% (95% confidence interval: 30.62%-30.83%) for males and 34.46% (34.35%-34.57%) for females. The most common types of mental disorders were anxiety-related disorders 16.27% (16.19%-16.36%) for males and 23.39% (23.29%-23.50%) for females, and followed by mood disorder 10.34% (10.27%-10.41%) for males and 16.67% (16.58%-16.77%) for females. For those who develop mental disorder, half will have developed their disorder by approximately age 22 years (median and interquartile range: males 21.37 (11.85-36.00); females 22.55 (16.31-36.08)). CONCLUSIONS: Approximately one in three individuals will seek treatment for at least one mental disorder in a secondary care setting by age 80. Given that half of these individuals develop mental disorders before age 22, it is crucial to tailor service planning to meet the specific needs of young individuals. Web-based interactive data-visualization tools are provided for clinical utility.

Absolute and relative risk of violent victimisation and perpetration following onset of mental illness: a Danish register-based study.

Background: Previous research has suggested that people with severe mental illness are at elevated risk of both violence perpetration and violent victimisation, with risk of the latter being perhaps greater than the former. However, few studies have examined risk across both outcomes. Methods: Using a total population approach, the absolute and relative risks of victimisation and perpetration were estimated for young men and women across the full psychiatric diagnostic spectrum. Information on mental disorder status was extracted from national registers and information on violent victimisation and perpetration outcomes from police records. The follow-up was from age 15 to a maximum of 31 years, with most of the person-time at risk pertaining to cohort members aged in their early twenties. Both absolute risk (at 1 and 5 years from onset of illness) and relative risk were estimated. Findings: Both types of violent outcome occurred more frequently amongst those with mental illness than the general population. However, whether risk of one was greater than the other depended on a range of factors, including sex and diagnosis. Men with a mental disorder had higher absolute risks of both outcomes than women [victimisation: Cin (5 year) = 7.15 (6.88-7.42) versus Cin (5 year) = 4.79 (4.61-4.99); perpetration: Cin (5 year) = 8.17 (7.90-8.46) versus Cin (5 year) = 1.86 (1.75-1.98)], as was the case with persons in the general population without a recorded mental illness diagnosis. Women with mental illness had higher absolute risk of victimisation than perpetration, which was also true for men and women without mental illness. However, the opposite was true for men with mental illness. Men and women with diagnoses of personality disorders, substance use disorders, and schizophrenia-spectrum disorders were at highest risk of victimisation and perpetration. Interpretation: Strategies developed to prevent violent victimisation and violence perpetration may need to be tailored for young adults with mental disorders. There may also be a benefit in taking a sex-specific approach to prevention in this group. Funding: This study was supported by an Australian National Health and Medical Research Council Investigator Grant awarded to the first author.

The bidirectional association between psychiatric disorders and sheltered homelessness.

BACKGROUND: Psychiatric disorders and homelessness are related, but temporal associations are unclear. We aimed to explore the overlap between hospital-based psychiatric disorders and sheltered homelessness. METHODS: This population-based cohort study was conducted using the Danish registers e.g., the Danish Homeless Register and the Danish National Patient Register. The study cohort included all individuals aged 15 years or older, living in Denmark at least one day during 2002-2021 (born 1984-2006). First psychiatric diagnosis was used to define psychiatric disorder and first homeless shelter contact to define homelessness. Adjusted incidence rate ratios (IRRs) and cumulative incidences were estimated. RESULTS: Among 1 530 325 individuals accounting for 16 787 562 person-years at risk aged 15-38 years, 11 433 (0.8%) had at least one homeless shelter contact. Among 1 406 410 individuals accounting for 14 131 060 person-years at risk, 210 730 had at least one psychiatric disorder. People with any psychiatric disorder had increased risk of sheltered homelessness relative to individuals with no psychiatric disorder [IRR 9.2, 95% confidence interval (CI) 8.8-9.6]. Ten years after first psychiatric disorder, 3.0% (95% CI 2.9-3.1) had at least one homeless shelter contact. Individuals experiencing homelessness had increased risk of any psychiatric disorder compared to individuals with no homeless shelter contact (IRR 7.0, 95% CI 6.7-7.4). Ten years after first homeless shelter contact, 47.1% (45.3-48.0) had received a hospital-based psychiatric diagnosis. CONCLUSION: Strong bidirectional associations between psychiatric disorders and homelessness were identified. Health and social care professionals should be aware of and address these high risks of accumulated psychiatric and social problems.

Proton pump inhibitors and dementia: A nationwide population-based study.

INTRODUCTION: Proton pump inhibitors (PPIs) may increase dementia risk. However, it is currently unknown whether timing of exposure or age at dementia diagnosis influence the risk. METHODS: We assessed associations between cumulative PPI use and dementia at different ages in a nationwide Danish cohort of 1,983,785 individuals aged 60 to 75 years between 2000 and 2018. RESULTS: During follow-up, there were 99,384 all-cause dementia incidences. Incidence rate ratio (IRR) of dementia with PPI ever-use compared with never-use was 1.36 (95% CI, 1.29 to 1.43) for age 60 to 69 years at diagnosis, 1.12 (1.09 to 1.15) for 70 to 79 years, 1.06 (1.03 to 1.09) for 80 to 89 years, and 1.03 (0.91 to 1.17) for 90+ years. Longer treatment duration yielded increasing IRRs. For cases below 90 years, increased dementia rate was observed regardless of treatment initiation up to >15 years before diagnosis. DISCUSSION: Regardless of timing of treatment initiation, PPI use was associated with increased dementia rate before age 90 years. Dementia rates increased with younger age at diagnosis. HIGHLIGHTS: After following 1,983,785 individuals for a median of 10 years, 99,384 developed dementia PPIs were used by 21.2% of cases and 18.9% of controls PPI use was associated with increased dementia rate regardless of time of treatment onset Magnitude of associations increased with younger age at diagnosis PPI use was not associated with dementia occurring after age 90 years.

Association of maternal and paternal personality disorders with risk of mental disorders in children: A nationwide, register-based cohort study of 1,406,965 children.

BACKGROUND: Knowledge of the association between parental personality disorders and mental disorders in children is limited. To examine the association between parental personality disorders and the risk of mental disorders in offspring. METHODS: We linked Danish health registers to create a cohort of children born from January 1, 1995, to December 31, 2016. Children were followed until their 18th birthday, diagnosis set, emigration, death, or December 31, 2016. Parental personality disorders according to the International Classification of Diseases (ICD) Eighth or 10th Revision. Poisson regression analyses were used to estimate the incidence risk ratio (IRR) and cumulative incidence of ICD 10th mental disorders in offspring (age 0-17). RESULTS: The study cohort included 1,406,965 children. For girls, maternal or paternal personality disorder (MPD/PPD) was associated with mental disorders: MPD girls (IRR, 2.74; 95% CI, 2.59-2.89) and PPD girls (IRR, 2.10; 95% CI, 1.94-2.27). Likewise, the risk was increased for both MPD boys (IRR, 2.44; 95% CI, 2.33-2.56) and PPD boys (IRR, 2.04; 95% CI, 1.91-2.18). For girls and boys combined, exposure to two parents with a personality disorder was associated with the highest risk (IRR, 3.69; 95% CI, 3.15-4.33). At age 18, the cumulative incidence of any mental disorder in children of one or two parents with a personality disorder was 34.1% (95% CI, 33.0-35.1), which was twice the cumulative incidence of mental disorders in nonexposed children (15.2% [95% CI, 15.1-15.3]). CONCLUSION: Children of parents with a personality disorder were at a 2 to 3.5 times higher risk of mental disorders compared with nonexposed offspring. Possible mechanisms of transmission of mental disorders from parent to child involve genetic, environmental, and gene-environment pathways. More research into these mechanisms and research into preventive interventions is warranted.

Healthcare utilization prior to a diagnosis of young-onset Alzheimer's disease: a nationwide nested case-control study.

OBJECTIVE: Our aim was to identify changes in healthcare utilization prior to a young-onset Alzheimer's disease diagnosis. METHODS: In a retrospective incidence density matched nested case-control study using national health registers, we examined healthcare utilization for those diagnosed with young-onset Alzheimer's disease in Danish memory clinics during 2016-2018 compared with age- and sex-matched controls. Negative binomial regression analysis produced contact rate ratios. RESULTS: The study included 1082 young-onset Alzheimer's disease patients and 3246 controls. In the year preceding diagnosis, we found increased contact rate ratios for all types of contacts except physiotherapy. Contact rate ratios for contacts with a general practitioner were significantly increased also > 1-5 and > 5-10 years before diagnosis. The highest contact rate ratios were for psychiatric emergency contacts (8.69, 95% CI 4.29-17.62) ≤ 1 year before diagnosis. INTERPRETATION: Results demonstrate that young-onset Alzheimer's disease patients have increased healthcare utilization from 5 to 10 years prior to diagnosis. Awareness of specific alterations in health-seeking behaviour may help healthcare professionals provide timely diagnoses.

Hospital-Diagnosed Infections, Autoimmune Diseases, and Subsequent Dementia Incidence.

Importance: Systemic inflammation has been suggested to explain reported associations between infections and dementia. Associations between autoimmune diseases and dementia also suggest a role for peripheral systemic inflammation. Objective: To investigate the associations of infections and autoimmune diseases with subsequent dementia incidence and to explore potential shared signals presented by the immune system in the 2 conditions. Design, Setting, and Participants: This nationwide, population-based, registry-based cohort study was conducted between 1978 and 2018 (40-year study period). All Danish residents born 1928 to 1953, alive and in Denmark on January 1, 1978, and at age 65 years were included. Persons with prior registered dementia and those with HIV infections were excluded. Data were analyzed between May 2022 and January 2023. Exposures: Hospital-diagnosed infections and autoimmune diseases. Main Outcomes and Measures: All-cause dementia, defined as the date of a first registered dementia diagnosis after age 65 years in the registries. Poisson regression with person-years at risk as an offset variable was used to analyze time to first dementia diagnosis. Results: A total of 1 493 896 individuals (763 987 women [51%]) were followed for 14 093 303 person-years (677 147 [45%] with infections, 127 721 [9%] with autoimmune diseases, and 75 543 [5%] with dementia). Among individuals with infections, 343 504 (51%) were men, whereas among those with autoimmune diseases, 77 466 (61%) were women. The dementia incidence rate ratio (IRR) following any infection was 1.49 (95% CI, 1.47-1.52) and increased along with increasing numbers of infections in a dose-dependent manner. Dementia rates were increased for all infection sites in the short term, but not always in the long term. The dementia IRR following any autoimmune disease was 1.04 (95% CI, 1.01-1.06), but no dose-dependent increase was observed, and only a few autoimmune conditions showed increased IRRs for dementia. Conclusions and Relevance: These findings may point toward a role for infection-specific processes in the development of dementia, rather than general systemic inflammation, as previously hypothesized. Assessing these 2 conditions in a single setting may allow for additional insights into their roles in dementia and for hypotheses on possible underlying mechanisms.

Risk of homelessness after prison release and recidivism in Denmark: a nationwide, register-based cohort study.

BACKGROUND: Transitional periods between and across services have been linked to homelessness. We aimed to investigate the association of previous history of homelessness and psychiatric disorders with risk of homelessness after release from prison. Additionally, we examined the association between homelessness after release and risk of recidivism. METHODS: We did a nationwide, register-based cohort study of people aged 15 years or older who were released from prison for the first time in Denmark between Jan 1, 2001, and Dec 31, 2021. We obtained data using the Danish Civil Registration System with data linked across other registries (the Danish Central Criminal Register, the Danish Homeless Register, the Danish National Patient Register, and the Danish Psychiatric Central Research Register) on release date, homeless shelter contacts, psychiatric disorders, and new convictions. Outcomes were homelessness after release from prison, defined as first homeless shelter contact following release from first imprisonment, and recidivism within 2 years of release, defined as the first police-recorded criminal conviction after prison release. We calculated incidence rates per 1000 person-years, incidence rate ratios (IRRs) using Poisson regression analysis, and probability of homelessness and recidivism after release. Sex, age, calendar year, country of origin, highest educational level, relationship status, and length of index imprisonment were included as confounders. FINDINGS: The study cohort included 37 382 individuals (34 792 males [93·1%] and 2590 females [6·9%]) aged 15-41 years, who were released from prison between Jan 1, 2001, and Dec 31, 2021, contributing 202 197 person-years at risk. Mean follow-up duration was 5·4 person-years (SD 5·6). Overall, 1843 (4·9%) of 37 382 individuals became homeless. 1 year after release from prison, 788 (2·1%) of 37 382 individuals had at least one homeless shelter contact, and among 1761 individuals with previous history of homelessness before index imprisonment, 357 (20·7%) became homeless. The incidence of homelessness after release was 102·5 cases per 1000 person-years for individuals with previous history of homelessness and 6·7 cases per 1000 person-years in individuals without (IRR 16·4, 95% CI 14·8-18·2; adjusted for sex, age, and calendar year). Individuals who additionally had a mental illness had a higher risk of homelessness (IRR 22·6, 19·7-25·9) compared with those without either previous homelessness or mental illness, and a substantially higher risk was observed for those with previous homelessness and drug use disorder (25·0, 21·6-28·9) compared with those without. Within 2 years of release from prison, the probability of recidivism was 73·2% (95% CI 72·8-73·7). The risk of recidivism was higher among people experiencing homelessness after release from prison than those who did not experience homelessness after release (IRR 1·5, 95% CI 1·3-1·7), adjusted for sex, age, and calendar year. INTERPRETATION: Criminal justice services should review approaches to reduce risk of homelessness, and consider improving liaison with mental health and substance misuse services to prevent adverse outcomes on release from prison. Clinical guidelines applied to criminal justice settings should address the health of individuals who experience homelessness. FUNDING: Lundbeck Foundation.

Are migrants diagnosed with a trauma-related disorder at risk of premature mortality? A register-based cohort study in Denmark.

Background: Mental illness is common among refugees displaced by conflict and war. While evidence points to the relatively good health in terms of longevity of migrants resettled in the destination country, less is known about the mortality of the most vulnerable migrants with a trauma-related diagnosis alone and those with an additional comorbid psychotic disorder. This study aimed to provide an overview of the number and mortality of foreign-born individuals diagnosed with Post-Traumatic Stress Disorder or Enduring Personality Change after a Catastrophic Event (PTSD/EPCACE), a psychotic disorder or both. Methods: A nationwide register-based cohort study, including residents in Denmark, followed from 1 January 1995 to 31 December 2016. The exposure was PTSD/EPCACE and psychotic disorders as well as region of origin. Relative all-cause mortality was estimated using Cox proportional hazards regression models and calculated for migrants with one or both groups of disorders compared to those from the same region without the disorder. Results: During the study period, 6,580,000 individuals (50.4% women) were included in the cohort. Of these 1,249,654 (50.5% women) died during follow-up. For men and women from the former Yugoslavia, the Middle East and Northern Africa, a PTSD/EPCACE diagnosis alone or with comorbid psychotic disorder was not associated with increased mortality after adjusting for region of origin. A psychotic disorder alone, however, was associated with an increased mortality rate. Conclusion: Despite the severity of many refugees' traumatic experiences, a diagnosis of a trauma-related psychiatric disorder did not appear to increase the mortality rates.

Influence of vaccination on adverse health outcomes after SARS-CoV-2 infection among individuals with alcohol use disorder: a population-based study.

BACKGROUND AND AIMS: Alcohol use disorders (AUD) have not been included in the priority groups for early vaccine against SARS-CoV-2. We aimed to determine adverse outcomes after SARS-CoV-2 infection among individuals with AUD and how this is modified by vaccination. DESIGN, SETTING AND PARTICIPANTS: This was a registry-based cohort study carried out in Denmark, 27 February 2020 to 15 October 2021, comprising 2157 individuals with AUD and 237 541 without AUD who had had a polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection during the study period. MEASUREMENTS: The association of AUD with the absolute and relative risk of hospitalization, intensive care and 60-day mortality after SARS-CoV-2 infection and of all-cause mortality throughout the follow-up period were measured. Potential interactions with SARS-CoV-2 vaccination, education and sex were explored in stratified analyses and tested by including interaction terms and using likelihood ratio tests. FINDINGS: Individuals with AUD had an increased absolute and relative risk of adverse outcomes, including hospitalization [incidence rate ratio (IRR) = 1.72, 95% confidence interval (CI) = 1.51-1.95], intensive care (IRR = 1.47, 95% CI = 1.07-2.02) and 60-day mortality [mortality rate ratio (MRR) = 2.35, 95% CI = 1.94-2.85] compared with SARS-CoV-2-positive individuals without AUD. Irrespective of AUD, highest risks of these adverse health outcomes were observed for individuals not vaccinated against SARS-CoV-2 infection, for individuals of low educational level and in males. However, for all-cause mortality throughout the follow-up period, SARS-CoV-2 infection showed a lower relative mortality risk increase, whereas being unvaccinated showed a higher relative mortality risk increase, in individuals with AUD than in the reference population without AUD (P of interaction tests < 0.0001). CONCLUSIONS: Both alcohol use disorder and being unvaccinated for SARS-CoV-2 appear to be independent risk factors for adverse health outcomes following SARS-CoV-2 infection.

Association between SARS-CoV-2 infection and self-harm: Danish nationwide register-based cohort study.

BACKGROUND: Case studies have linked SARS-CoV-2 infection to suicidal behaviour. However, conclusive evidence is lacking. AIMS: To examine whether a history of SARS-CoV-2 infection or SARS-CoV-2-related hospital admission was associated with self-harm in the general population and in high-risk groups. METHOD: A cohort design was applied to nationwide data on all people aged ≥15 years and living in Denmark between 27 February 2020 and 15 October 2021. Exposure was identified as having had a positive SARS-CoV-2 PCR test, and further assessed as SARS-CoV-2-related hospital admission. Rates of probable self-harm were examined using adjusted incidence rate ratios (aIRRs). The following subgroups were identified: (a) lower educational level, (b) chronic medical conditions, (c) disability pension, (d) mental disorders, (e) substance use disorders, and history of (f) homelessness and (g) imprisonment. RESULTS: Among 4 412 248 included individuals, 260 663 (5.9%) had tested positive for SARS-CoV-2. Out of 5453 individuals presenting with self-harm, 131 (2.4%) had been infected. Individuals with a history of a positive SARS-CoV-2 test result had an aIRR for self-harm of 0.86 (95% CI 0.72-1.03) compared with those without. High rates were found after a SARS-CoV-2-related hospital admission (aIRR = 7.68; 95% CI 5.61-10.51) or a non-SARS-CoV-2-related admission (aIRR = 10.27; 95% CI 9.65-10.93) versus non-infected and not admitted. In sensitivity analyses with a more restrictive definition of self-harm, a positive PCR test was associated with lower rates of self-harm. CONCLUSIONS: Individuals with a PCR-confirmed SARS-CoV-2 infection did not have higher rates of self-harm than those without. Hospital admission in general, rather than being SARS-CoV-2 positive. seemed to be linked to elevated rates of self-harm.

The association between mental disorders and subsequent years of working life: a Danish population-based cohort study.

BACKGROUND: Mental disorders can affect workforce participation via a range of mechanisms. In this study, we aimed to estimate the association between different types of mental disorders and working years lost, defined as the number of years not actively working or enrolled in an educational programme. METHODS: In this population-based cohort study, we included all people aged 18-65 years (mean 38·0 [SD 13·9]) in the Danish Civil Registration System from Jan 1, 1995 to Dec 31, 2016. Information on mental disorders was obtained from the Danish Psychiatric Central Research Register and information on labour market characteristics was obtained from administrative registers. Follow-up started at age 18 years, immigration to Denmark, or on Jan 1, 1995, whichever came later; and it ended at age 65 years, death, emigration from Denmark, disability pension, voluntary early retirement, or Dec 31, 2016 (whichever came earlier). As the main outcome, we estimated working years lost for those diagnosed with any mental disorder and 24 types of mental disorders, as well as for the general population of same age and sex. We decomposed total working years lost into periods of unemployment or sick leave, disability pension, voluntary early retirement, or death. Data on ethnicity were not available through administrative registers. FINDINGS: A total of 5 163 321 individuals, 2 642 383 men and 2 520 938 women, were followed up for 65·4 million person-years. Overall, 488 775 (9·47%) individuals were diagnosed with a mental disorder. On average, individuals with mental disorders lost an additional 10·52 (95% CI 10·48-10·57) years of working life compared with the general Danish population. Receiving a disability pension (7·54 [7·49-7·59] years) and longer periods of unemployment (2·24 [2·21-2·27] years) accounted for most of this difference. INTERPRETATION: Our findings foreground the substantial impact of mental disorders on workforce participation. There is a need to invest in programmes that reduce the burden of working years lost and assist people with mental disorders in returning to the workforce. FUNDING: Lundbeck Foundation and Danish National Research Foundation.

Cause-specific mortality and life years lost in people with epilepsy: a Danish cohort study.

Mortality rates are two to three times higher in people with epilepsy than in the general population. This study aimed to quantify how this increased mortality translates into reduced life expectancy and to identify the underlying causes of deaths, thereby offering suggestions for how to reduce mortality associated with epilepsy. In this population-based cohort study, we included all individuals aged 0-94 years who were living in Denmark between 2000 and 2015. Using the nationwide registers, we identified people diagnosed with epilepsy and estimated the excess of life years lost due to 13 overall and nine specific causes of death. Among 6 022 160 people, we identified 129 598 with epilepsy (52.6% males), with a mean age of epilepsy onset of 36.5 years (standard deviation = 26.3 years). During the 16 years of follow-up, 851 087 individuals died, and of these 36 923 had been diagnosed with epilepsy. The average reduction in life expectancy in people with epilepsy was 11.84 years in males (95% confidence interval: 11.66-12.00) and 10.91 years in females (95% confidence interval: 10.70-11.11) compared to the general population. Life expectancy was reduced irrespective of epilepsy aetiology (symptomatic ∼14 years; idiopathic ∼8-10 years), and in particular in people with epilepsy and psychiatric comorbidity (∼13-16 years). Excess mortality was evident across all causes of death including cardiovascular disorders, accidents, and suicide. People with epilepsy experience a substantial reduction in lifespan that can only partly be explained by underlying conditions. Prevention of epilepsy-related deaths should focus on the consequences of psychiatric comorbidity and on modifiable risk factors associated with preventable causes of death such as accidents and neurological and cardiovascular disorders.

Adverse childhood experiences among children of parents who are refugees affected by trauma in Denmark: a register-based cohort study.

BACKGROUND: Children in families who are refugees might experience more adversities than their peers. Adverse childhood experiences (ACEs) are well known risk factors for poorer adulthood health and adjustment. The risk of ACEs for children with a parent who is a refugee affected by trauma is unknown. We aimed to estimate the hazard of individual and cumulative ACEs using a unique sample of children with parents who are refugees affected by and seeking treatment for trauma and population level data. METHODS: This was a register-based cohort study carried out in Denmark. All children aged 0-15 years, residing in Denmark between Jan 1, 1990, and Dec 31, 2016, were followed up from birth or migration into the country to their 15th birthday. We linked data from the Danish Civil Registration System, the Danish National Patient Register, the Danish Psychiatric Central Research Register, the Employment Classification Module, the Register of Causes of Death, and the Income Statistics Register to investigate ten ACE categories (parental: natural and unnatural death, serious mental illness, substance use disorder, somatic illness, and disability; child: residential instability, family disruption, poverty, and stressors) and the cumulative number of ACE categories for children with a parent from a refugee-sending country and children with a parent who is a refugee in treatment for trauma. The main outcome was the hazard ratio (HR) of the individual and cumulative ACEs among children with a parent from a refugee-sending country and children with a parent who is a refugee affected by trauma, compared with the general population of children in Denmark, both adjusted and unadjusted for parental country of origin. FINDINGS: 2 688 794 children were included in the study, 252 310 of whom had parents from refugee-sending countries. 11 603 children had parents affected by trauma and seeking treatment, of whom 1163 (10%) migrated to Denmark before their second birthday and 10 440 (90%) were born in Denmark. Compared with the general population of children in Denmark, the hazard for most ACEs was significantly higher for both children with parents from a refugee-sending country and children with parents who are refugees affected by trauma. For children with a parent from a refugee-sending country, the highest HR was related to the child living in relative poverty for 3 years (3·62 [95% CI 3·52-3·73]). After adjusting for parental country of origin, the hazards for five ACEs were significantly greater for children of parents who are refugees affected by trauma compared with the remaining children of parents from the same countries. The highest HR for this child group was for parental serious mental illness (1·98 [1·85-2·12]). The hazard for experiencing multiple ACEs was significantly higher for both child groups compared with the general population. INTERPRETATION: Our findings suggest that children with parents from refugee-sending countries have a higher rate of several ACEs compared with the general population. Furthermore, having a parent who is a refugee affected by trauma and seeking treatment seems to be an independent risk factor for poorer health and adjustment in adulthood. This study informs decision makers and caregivers that there might be much added value in addressing needs within the whole family, as opposed to only attending to the parent who is seeking treatment. FUNDING: The Lundbeck Foundation.

Hospital-diagnosed sleep disorders and incident dementia: a nationwide observational cohort study.

BACKGROUND AND PURPOSE: Several smaller, community-based studies have suggested a link between sleep disorders and dementia with a focus on sleep as a modifiable risk factor for dementia. Studies on neurodegenerative diseases are prone to reverse causation, and few studies have examined the association with long follow-up time. Our aim was to explore the possible association between sleep disorders and late-onset dementia in an entire population. METHODS: In a nationwide cohort with 40-year follow-up, associations between hospital-based sleep disorder diagnoses and late-onset dementia were assessed. Incidence rate ratios (IRR) were calculated using Poisson regression. RESULTS: The cohort consisted of 1,491,276 people. Those with any sleep disorder had a 17% higher risk of dementia (IRR 1.17, 95% confidence interval [CI] 1.11-1.24) compared to people with no sleep disorder, adjusted for age, sex, calendar year, highest attained educational level at age 50, and somatic and psychiatric comorbidity. The risk of dementia was significantly increased 0-5 years after sleep disorder diagnosis (IRR 1.35, 95% CI 1.25-1.47), whilst the association after 5 years or more was non-significant (1.05, 95% CI 0.97-1.13). CONCLUSIONS: Our findings show an increased short-term risk of dementia following a hospital-based sleep disorder diagnosis, whilst weaker evidence of a long-term risk was found. This could potentially point towards sleep disorders as an early symptom of dementia. Further research is needed to distinguish sleep disorders as an early symptom of dementia, a risk factor, or both.

Adverse SARS-CoV-2-associated outcomes among people experiencing social marginalisation and psychiatric vulnerability: A population-based cohort study among 4,4 million people.

Background: Knowledge of the adverse problems related to SARS-CoV-2 infection in marginalised and deprived groups may help to prioritise more preventive efforts in these groups. We examined adverse outcomes associated with SARS-CoV-2 infection among vulnerable segments of society. Methods: Using health and administrative registers, a population-based cohort study of 4.4 million Danes aged at least 15 years from 27 February 2020 to 15 October 2021 was performed. People with 1) low educational level, 2) homelessness, 3) imprisonment, 4) substance abuse, 5) supported psychiatric housing, 6) psychiatric admission, and 7) severe mental illness were main exposure groups. Chronic medical conditions were included for comparison. COVID-19-related outcomes were: 1) hospitalisation, 2) intensive care, 3) 60-day mortality, and 4) overall mortality. PCR-confirmed SARS-CoV-2 infection and PCR-testing were also studied. Poisson regression analysis was used to compute adjusted incidence and mortality rate ratios (IRRs, MRRs). Findings: Using health and administrative registers, we performed a population-based cohort study of 4,412,382 individuals (mean age 48 years; 51% females). In all, 257,450 (5·8%) individuals had a PCR-confirmed SARS-CoV-2 infection. After adjustment for age, calendar time, and sex, we found that especially people experiencing homelessness had high risk of hospitalisation (IRR 4·36, 95% CI, 3·09-6·14), intensive care (IRR 3·12, 95% CI 1·29-7·52), and death (MRR 8·17, 95% CI, 3·66-18·25) compared with people without such experiences, but increased risk was found for all studied groups. Furthermore, after full adjustment, including for status of vaccination against SARS-CoV-2 infection, individuals with experiences of homelessness and a PCR-confirmed SARS-CoV-2 infection had 41-times (95% CI, 24·84-68·44) higher risk of all-cause death during the study period compared with individuals without. Supported psychiatric housing was linked to almost 3-times higher risk of hospitalisation and 60-day mortality following SARS-CoV-2 infection compared with the general population with other living circumstances. Interpretation: Socially marginalised and psychiatrically vulnerable individuals had substantially elevated risks of adverse health outcomes following SARS-CoV-2 infection. The results highlight that pandemic preparedness should address inequalities in health, including infection prevention and vaccination of vulnerable groups. Funding: Novo Nordisk Foundation.

Analysis of mortality metrics associated with a comprehensive range of disorders in Denmark, 2000 to 2018: A population-based cohort study.

BACKGROUND: The provision of different types of mortality metrics (e.g., mortality rate ratios [MRRs] and life expectancy) allows the research community to access a more informative set of health metrics. The aim of this study was to provide a panel of mortality metrics associated with a comprehensive range of disorders and to design a web page to visualize all results. METHODS AND FINDINGS: In a population-based cohort of all 7,378,598 persons living in Denmark at some point between 2000 and 2018, we identified individuals diagnosed at hospitals with 1,803 specific categories of disorders through the International Classification of Diseases-10th Revision (ICD-10) in the National Patient Register. Information on date and cause of death was obtained from the Registry of Causes of Death. For each of the disorders, a panel of epidemiological and mortality metrics was estimated, including incidence rates, age-of-onset distributions, MRRs, and differences in life expectancy (estimated as life years lost [LYLs]). Additionally, we examined models that adjusted for measures of air pollution to explore potential associations with MRRs. We focus on 39 general medical conditions to simplify the presentation of results, which cover 10 broad categories: circulatory, endocrine, pulmonary, gastrointestinal, urogenital, musculoskeletal, hematologic, mental, and neurologic conditions and cancer. A total of 3,676,694 males and 3,701,904 females were followed up for 101.7 million person-years. During the 19-year follow-up period, 1,034,273 persons (14.0%) died. For 37 of the 39 selected medical conditions, mortality rates were larger and life expectancy shorter compared to the Danish general population. For these 37 disorders, MRRs ranged from 1.09 (95% confidence interval [CI]: 1.09 to 1.10) for vision problems to 7.85 (7.77 to 7.93) for chronic liver disease, while LYLs ranged from 0.31 (0.14 to 0.47) years (approximately 16 weeks) for allergy to 17.05 (16.95 to 17.15) years for chronic liver disease. Adjustment for air pollution had very little impact on the estimates; however, a limitation of the study is the possibility that the association between the different disorders and mortality could be explained by other underlying factors associated with both the disorder and mortality. CONCLUSIONS: In this study, we show estimates of incidence, age of onset, age of death, and mortality metrics (both MRRs and LYLs) for a comprehensive range of disorders. The interactive data visualization site (https://nbepi.com/atlas) allows more fine-grained analysis of the link between a range of disorders and key mortality estimates.

Vaccination against SARS-CoV-2 infection among vulnerable and marginalised population groups in Denmark: A nationwide population-based study.

Background: Social deprivation, psychiatric and medical disorders have been associated with increased risk of infection and severe COVID-19-related health problems. We aimed to study the rates of SARS-CoV-2 vaccination in these high-risk groups. Methods: Using health, vaccination, and administrative registers, we performed a population-based cohort study including all Danish residents aged at least 15 years, December 27, 2020, to October 15, 2021. Population groups were people experiencing: (1) homelessness, (2) imprisonment, (3) substance abuse, (4) severe mental illness, (5) supported psychiatric housing, (6) psychiatric admission, and (7) chronic medical condition. The outcome was vaccine uptake of two doses against SARS-CoV-2 infection. We calculated cumulative vaccine uptake and adjusted vaccination incidence rate ratios (IRRs) relative to the general population by sex and population group. Findings: The cohort included 4,935,344 individuals, of whom 4,277,380 (86·7%) received two doses of vaccine. Lower cumulative vaccine uptake was found for all socially deprived and psychiatrically vulnerable population groups compared with the general population. Lowest uptake was found for people below 65 years experiencing homelessness (54·6%, 95% confidence interval (CI) 53·4-55·8, p<0·0001). After adjustment for age and calendar time, homelessness was associated with markedly lower rates of vaccine uptake (IRR 0·5, 95% CI 0·5-0·6 in males and 0·4, 0·4-0·5 in females) with similar results for imprisonment. Lower vaccine uptake was also found for most of the psychiatric groups with the lower IRR for substance abuse (IRR 0·7, 0·7-0·7 in males and 0·8, 0·8-0·8 in females). Individuals with new-onset severe mental illness and, especially, those in supported psychiatric housing and with chronic medical conditions had the highest vaccine uptake among the studied population groups. Interpretation: Especially, socially deprived population groups, but also individuals with psychiatric vulnerability need higher priority in the implementation of the vaccination strategy to increase equity in immunization uptake. Funding: Novo Nordisk Foundation.