Risk of Suicide Across Medical Conditions and the Role of Prior Mental Disorder.

Importance: According to the World Health Organization, more than 700 000 individuals worldwide die by suicide each year. Medical conditions likely increase the risk of suicide. Objective: To (1) provide age- and sex-specific pairwise estimates of the risk of suicide across a comprehensive range of medical conditions, (2) investigate whether there is a dose-response-like relationship at play (ie, the higher the disability burden due to medical morbidity, the higher the risk of suicide), and (3) determine if the risk of suicide with medical conditions is particularly pronounced among those who had mental disorder preceding the medical conditions. Design, Setting, and Participants: This cohort study was an observational study of population-based data for all individuals living in Denmark at some point between 2000 and 2020. The data analysis took place from September 2023 to May 2024. Exposures: Thirty-one specific medical conditions as well as prior mental disorder. Main Outcomes and Measures: The main outcome was suicide. Associations between the 31 specific medical conditions, nested within 9 categories, and suicide were examined via Poisson regression, yielding incidence rate ratios (IRRs). Subsequent analyses included an interaction term to assess whether a previous hospital-treated mental disorder modified the associations. Finally, the association between the disability burden of medical conditions and suicide was examined for those with and without prior mental disorder, respectively. Results: A total of 6 635 857 individuals (3 337 613 females and 3 298 244 males) were included in the analyses of the associations between medical conditions and suicide. Except for endocrine disorders, all categories of medical conditions were associated with a statistically significant increased risk of suicide (which was most pronounced for gastrointestinal conditions [IRR, 1.7; 95% CI,1.5-1.8], cancer [IRR, 1.5; 95% CI, 1.4-1.6], and hematological conditions [IRR, 1.5; 95% CI, 1.3-1.6]). Interaction between mental disorder and individual medical conditions did not seem to play a major role for suicide risk. For those without but not for those with mental disorder, there was a dose-response-like relationship between the disability burden of medical conditions and suicide. Conclusions and Relevance: Medical conditions are generally associated with increased risk of suicide in a dose-response-like manner. Individuals with hospital-treated mental disorder appear to be at such elevated risk of suicide that additional disability associated with medical conditions has little impact in this regard.

Associations between physical diseases and subsequent mental disorders: a longitudinal study in a population-based cohort.

People with physical diseases are reported to be at elevated risk of subsequent mental disorders. However, previous studies have considered only a few pairs of conditions, or have reported only relative risks. This study aimed to systematically explore the associations between physical diseases and subsequent mental disorders. It examined a population-based cohort of 7,673,978 people living in Denmark between 2000 and 2021, and followed them for a total of 119.3 million person-years. The study assessed nine broad categories of physical diseases (cardiovascular, endocrine, respiratory, gastrointestinal, urogenital, musculoskeletal, hematological and neurological diseases, and cancers), encompassing 31 specific diseases, and the subsequent risk of mental disorder diagnoses, encompassing the ten ICD-10 groupings (organic, including symptomatic, mental disorders; mental disorders due to psychoactive substance use; schizophrenia and related disorders; mood disorders; neurotic, stress-related and somatoform disorders; eating disorders; personality disorders; intellectual disabilities; pervasive developmental disorders; and behavioral and emotional disorders with onset usually occurring in childhood and adolescence). Using Poisson regression, the overall and time-dependent incidence rate ratios (IRRs) for pairs of physical diseases and mental disorders were calculated, adjusting for age, sex and calendar time. Absolute risks were estimated with the Aalen-Johansen estimator. In total, 646,171 people (8.4%) were identified as having any mental disorder during follow-up. All physical diseases except cancers were associated with an elevated risk of any mental disorder. For the nine broad pairs of physical diseases and mental disorders, the median point estimate of IRR was 1.51 (range: 0.99-1.84; interquartile range: 1.29-1.59). The IRRs ranged from 0.99 (95% CI: 0.98-1.01) after cancers to 1.84 (95% CI: 1.83-1.85) after musculoskeletal diseases. Risks varied over time after the diagnosis of physical diseases. The cumulative mental disorder incidence within 15 years after diagnosis of a physical disease varied from 3.73% (95% CI: 3.67-3.80) for cancers to 10.19% (95% CI: 10.13-10.25) for respiratory diseases. These data document that most physical diseases are associated with an elevated risk of subsequent mental disorders. Clinicians treating physical diseases should constantly be alert to the possible development of secondary mental disorders.

Inpatient admissions and mortality of anorexia nervosa patients according to their preceding psychiatric and somatic diagnoses.

OBJECTIVE: Anorexia nervosa (AN) is associated with increased risk of mortality, but little is known about the risk of inpatient admissions and mortality outcomes in individuals with diagnoses of both AN and other psychiatric and somatic conditions. We aimed to investigate the inpatient admissions and mortality among people with AN and other diagnosed conditions using Danish national registers. METHOD: This retrospective cohort study included individuals diagnosed with AN in Denmark, born 1977-2010. We identified other mental and somatic conditions in this population. We used Cox proportional hazards regression to estimate the risk of inpatient admission and mortality, focusing on (i) the number of other diagnosed conditions, and (ii) specific combinations of conditions diagnosed prior to the AN diagnosis. Categories of inpatient admissions considered were due to: (i) AN, (ii) any psychiatric disorder, and (iii) any somatic disorder. Additionally, competing risks survival analysis was used to calculate the cumulative incidence of inpatient admission and all-cause mortality over the follow-up period. RESULTS: The study population included 11,489 individuals. The most common conditions individuals had prior to their AN diagnosis were other eating disorders (34.5%) and anxiety disorders (32.7%). During the follow-up, 3184 (27.7%), 4604 (40.1%), and 6636 (57.8%) individuals were admitted for AN, any psychiatric disorder, and any somatic disorder, respectively; and in total 106 (0.9%) died. The risk of all outcomes was highest among those who had received a higher number of other diagnoses. For most combinations, the risks of admission and mortality were increased. DISCUSSION: Our study presents the prevalence of other conditions in patients with AN in Denmark and elucidates their association with higher rates of inpatient admission and mortality. Our findings highlight the need for comprehensive, multidisciplinary care of patients with AN considering the spectrum of other diagnosed conditions to improve health outcomes.

The Role of Socioeconomic Position in the Association Between Mental Disorders and Mortality: A Systematic Review and Meta-Analysis.

Importance: Studies are lacking summarizing how the association between mental disorders and mortality varies by socioeconomic position (SEP), particularly considering different aspects of SEP, specific types of mental disorders, and causes of death. Objective: To investigate the role of SEP in the association between mental disorders and mortality and the association between SEP and mortality among people with mental disorders. Data Sources: MEDLINE, Embase, PsycINFO, and Web of Science were searched from January 1, 1980, through April 3, 2023, and a snowball search of reference and citation lists was conducted. Study Selection: Inclusion criteria were observational studies estimating the associations between different types of mental disorders and mortality, stratified by SEP and between SEP and mortality in people with mental disorders. Data Extraction and Synthesis: Pairs of reviewers independently extracted data using a predefined data extraction form and assessed the risk of bias using the adapted Newcastle-Ottawa scale. Graphical analyses of the dose-response associations and random-effects meta-analyses were performed. Heterogeneity was explored through meta-regressions and sensitivity analyses. Main Outcomes and Measures: All-cause and cause-specific mortality. Results: Of 28 274 articles screened, 71 including more than 4 million people with mental disorders met the inclusion criteria (most of which were conducted in high-income countries). The relative associations between mental disorders and mortality were similar across SEP levels. Among people with mental disorders, belonging to the highest rather than the lowest SEP group was associated with lower all-cause mortality (pooled relative risk [RR], 0.79; 95% CI, 0.73-0.86) and mortality from natural causes (RR, 0.73; 95% CI, 0.62-0.85) and higher mortality from external causes (RR, 1.18; 95% CI, 0.99-1.41). Heterogeneity was high (I2 = 83% to 99%). Results from subgroup, sensitivity, and meta-regression analyses were consistent with those from the main analyses. Evidence on absolute scales, specific diagnoses, and specific causes of death was scarce. Conclusion and Relevance: This study did not find a sufficient body of evidence that SEP moderated the relative association between mental disorders and mortality, but the underlying mortality rates may differ by SEP group, despite having scarcely been reported. This information gap, together with our findings related to SEP and a possible differential risk between natural and external causes of death in individuals with specific types of mental disorders, warrants further research.

Global, regional and national burdens of non-melanoma skin cancer attributable to occupational exposure to solar ultraviolet radiation for 183 countries, 2000-2019: A systematic analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.

BACKGROUND: A World Health Organization (WHO) and International Labour Organization (ILO) systematic review reported sufficient evidence for higher risk of non-melanoma skin cancer (NMSC) amongst people occupationally exposed to solar ultraviolet radiation (UVR). This article presents WHO/ILO Joint Estimates of global, regional, national and subnational occupational exposures to UVR for 195 countries/areas and the global, regional and national attributable burdens of NMSC for 183 countries, by sex and age group, for the years 2000, 2010 and 2019. METHODS: We calculated population-attributable fractions (PAFs) from estimates of the population occupationally exposed to UVR and the risk ratio for NMSC from the WHO/ILO systematic review. Occupational exposure to UVR was modelled via proxy of occupation with outdoor work, using 166 million observations from 763 cross-sectional surveys for 96 countries/areas. Attributable NMSC burden was estimated by applying the PAFs to WHO's estimates of the total NMSC burden. Measures of inequality were calculated. RESULTS: Globally in 2019, 1.6 billion workers (95 % uncertainty range [UR] 1.6-1.6) were occupationally exposed to UVR, or 28.4 % (UR 27.9-28.8) of the working-age population. The PAFs were 29.0 % (UR 24.7-35.0) for NMSC deaths and 30.4 % (UR 29.0-31.7) for disability-adjusted life years (DALYs). Attributable NMSC burdens were 18,960 deaths (UR 18,180-19,740) and 0.5 million DALYs (UR 0.4-0.5). Men and older age groups carried larger burden. Over 2000-2019, attributable deaths and DALYs almost doubled. CONCLUSIONS: WHO and the ILO estimate that occupational exposure to UVR is common and causes substantial, inequitable and growing attributable burden of NMSC. Governments must protect outdoor workers from hazardous exposure to UVR and attributable NMSC burden and inequalities.

Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management.

Populations with common physical diseases - such as cardiovascular diseases, cancer and neurodegenerative disorders - experience substantially higher rates of major depressive disorder (MDD) than the general population. On the other hand, people living with MDD have a greater risk for many physical diseases. This high level of comorbidity is associated with worse outcomes, reduced adherence to treatment, increased mortality, and greater health care utilization and costs. Comorbidity can also result in a range of clinical challenges, such as a more complicated therapeutic alliance, issues pertaining to adaptive health behaviors, drug-drug interactions and adverse events induced by medications used for physical and mental disorders. Potential explanations for the high prevalence of the above comorbidity involve shared genetic and biological pathways. These latter include inflammation, the gut microbiome, mitochondrial function and energy metabolism, hypothalamic-pituitary-adrenal axis dysregulation, and brain structure and function. Furthermore, MDD and physical diseases have in common several antecedents related to social factors (e.g., socioeconomic status), lifestyle variables (e.g., physical activity, diet, sleep), and stressful live events (e.g., childhood trauma). Pharmacotherapies and psychotherapies are effective treatments for comorbid MDD, and the introduction of lifestyle interventions as well as collaborative care models and digital technologies provide promising strategies for improving management. This paper aims to provide a detailed overview of the epidemiology of the comorbidity of MDD and specific physical diseases, including prevalence and bidirectional risk; of shared biological pathways potentially implicated in the pathogenesis of MDD and common physical diseases; of socio-environmental factors that serve as both shared risk and protective factors; and of management of MDD and physical diseases, including prevention and treatment. We conclude with future directions and emerging research related to optimal care of people with comorbid MDD and physical diseases.

The prevalences and levels of occupational exposure to dusts and/or fibres (silica, asbestos and coal): A systematic review and meta-analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.

BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing joint estimates of the work-related burden of disease and injury (WHO/ILO Joint Estimates), with contributions from a large number of individual experts. Evidence from human, animal and mechanistic data suggests that occupational exposure to dusts and/or fibres (silica, asbestos and coal dust) causes pneumoconiosis. In this paper, we present a systematic review and meta-analysis of the prevalences and levels of occupational exposure to silica, asbestos and coal dust. These estimates of prevalences and levels will serve as input data for estimating (if feasible) the number of deaths and disability-adjusted life years that are attributable to occupational exposure to silica, asbestos and coal dust, for the development of the WHO/ILO Joint Estimates. OBJECTIVES: We aimed to systematically review and meta-analyse estimates of the prevalences and levels of occupational exposure to silica, asbestos and coal dust among working-age (≥ 15 years) workers. DATA SOURCES: We searched electronic academic databases for potentially relevant records from published and unpublished studies, including Ovid Medline, PubMed, EMBASE, and CISDOC. We also searched electronic grey literature databases, Internet search engines and organizational websites; hand-searched reference lists of previous systematic reviews and included study records; and consulted additional experts. STUDY ELIGIBILITY AND CRITERIA: We included working-age (≥ 15 years) workers in the formal and informal economy in any WHO and/or ILO Member State but excluded children (< 15 years) and unpaid domestic workers. We included all study types with objective dust or fibre measurements, published between 1960 and 2018, that directly or indirectly reported an estimate of the prevalence and/or level of occupational exposure to silica, asbestos and/or coal dust. STUDY APPRAISAL AND SYNTHESIS METHODS: At least two review authors independently screened titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, then data were extracted from qualifying studies. We combined prevalence estimates by industrial sector (ISIC-4 2-digit level with additional merging within Mining, Manufacturing and Construction) using random-effects meta-analysis. Two or more review authors assessed the risk of bias and all available authors assessed the quality of evidence, using the ROB-SPEO tool and QoE-SPEO approach developed specifically for the WHO/ILO Joint Estimates. RESULTS: Eighty-eight studies (82 cross-sectional studies and 6 longitudinal studies) met the inclusion criteria, comprising > 2.4 million measurements covering 23 countries from all WHO regions (Africa, Americas, Eastern Mediterranean, South-East Asia, Europe, and Western Pacific). The target population in all 88 included studies was from major ISCO groups 3 (Technicians and Associate Professionals), 6 (Skilled Agricultural, Forestry and Fishery Workers), 7 (Craft and Related Trades Workers), 8 (Plant and Machine Operators and Assemblers), and 9 (Elementary Occupations), hereafter called manual workers. Most studies were performed in Construction, Manufacturing and Mining. For occupational exposure to silica, 65 studies (61 cross-sectional studies and 4 longitudinal studies) were included with > 2.3 million measurements collected in 22 countries in all six WHO regions. For occupational exposure to asbestos, 18 studies (17 cross-sectional studies and 1 longitudinal) were included with > 20,000 measurements collected in eight countries in five WHO regions (no data for Africa). For occupational exposure to coal dust, eight studies (all cross-sectional) were included comprising > 100,000 samples in six countries in five WHO regions (no data for Eastern Mediterranean). Occupational exposure to silica, asbestos and coal dust was assessed with personal or stationary active filter sampling; for silica and asbestos, gravimetric assessment was followed by technical analysis. Risk of bias profiles varied between the bodies of evidence looking at asbestos, silica and coal dust, as well as between industrial sectors. However, risk of bias was generally highest for the domain of selection of participants into the studies. The largest bodies of evidence for silica related to the industrial sectors of Construction (ISIC 41-43), Manufacturing (ISIC 20, 23-25, 27, 31-32) and Mining (ISIC 05, 07, 08). For Construction, the pooled prevalence estimate was 0.89 (95% CI 0.84 to 0.93, 17 studies, I2 91%, moderate quality of evidence) and the level estimate was rated as of very low quality of evidence. For Manufacturing, the pooled prevalence estimate was 0.85 (95% CI 0.78 to 0.91, 24 studies, I2 100%, moderate quality of evidence) and the pooled level estimate was rated as of very low quality of evidence. The pooled prevalence estimate for Mining was 0.75 (95% CI 0.68 to 0.82, 20 studies, I2 100%, moderate quality of evidence) and the pooled level estimate was 0.04 mg/m3 (95% CI 0.03 to 0.05, 17 studies, I2 100%, low quality of evidence). Smaller bodies of evidence were identified for Crop and animal production (ISIC 01; very low quality of evidence for both prevalence and level); Professional, scientific and technical activities (ISIC 71, 74; very low quality of evidence for both prevalence and level); and Electricity, gas, steam and air conditioning supply (ISIC 35; very low quality of evidence for both prevalence and level). For asbestos, the pooled prevalence estimate for Construction (ISIC 41, 43, 45,) was 0.77 (95% CI 0.65 to 0.87, six studies, I2 99%, low quality of evidence) and the level estimate was rated as of very low quality of evidence. For Manufacturing (ISIC 13, 23-24, 29-30), the pooled prevalence and level estimates were rated as being of very low quality of evidence. Smaller bodies of evidence were identified for Other mining and quarrying (ISIC 08; very low quality of evidence for both prevalence and level); Electricity, gas, steam and air conditioning supply (ISIC 35; very low quality of evidence for both prevalence and level); and Water supply, sewerage, waste management and remediation (ISIC 37; very low quality of evidence for levels). For coal dust, the pooled prevalence estimate for Mining of coal and lignite (ISIC 05), was 1.00 (95% CI 1.00 to 1.00, six studies, I2 16%, moderate quality of evidence) and the pooled level estimate was 0.77 mg/m3 (95% CI 0.68 to 0.86, three studies, I2 100%, low quality of evidence). A small body of evidence was identified for Electricity, gas, steam and air conditioning supply (ISIC 35); with very low quality of evidence for prevalence, and the pooled level estimate being 0.60 mg/m3 (95% CI -6.95 to 8.14, one study, low quality of evidence). CONCLUSIONS: Overall, we judged the bodies of evidence for occupational exposure to silica to vary by industrial sector between very low and moderate quality of evidence for prevalence, and very low and low for level. For occupational exposure to asbestos, the bodies of evidence varied by industrial sector between very low and low quality of evidence for prevalence and were of very low quality of evidence for level. For occupational exposure to coal dust, the bodies of evidence were of very low or moderate quality of evidence for prevalence, and low for level. None of the included studies were population-based studies (i.e., covered the entire workers' population in the industrial sector), which we judged to present serious concern for indirectness, except for occupational exposure to coal dust within the industrial sector of mining of coal and lignite. Selected estimates of the prevalences and levels of occupational exposure to silica by industrial sector are considered suitable as input data for the WHO/ILO Joint Estimates, and selected estimates of the prevalences and levels of occupational exposure to asbestos and coal dust may perhaps also be suitable for estimation purposes. Protocol identifier: https://doi.org/10.1016/j.envint.2018.06.005. PROSPERO registration number: CRD42018084131.

New global indicator for workers' health: mortality rate from diseases attributable to selected occupational risk factors.

Through sustainable development goals 3 and 8 and other policies, countries have committed to protect and promote workers' health by reducing the work-related burden of disease. To monitor progress on these commitments, indicators that capture the work-related burden of disease should be available for monitoring workers' health and sustainable development. The World Health Organization and the International Labour Organization estimate that only 363 283 (19%) of 1 879 890 work-related deaths globally in 2016 were due to injuries, whereas 1 516 607 (81%) deaths were due to diseases. Most monitoring systems focusing on workers' health or sustainable development, such as the global indicator framework for the sustainable development goals, include an indicator on the burden of occupational injuries. Few such systems, however, have an indicator on the burden of work-related diseases. To address this gap, we present a new global indicator: mortality rate from diseases attributable to selected occupational risk factors, by disease, risk factor, sex and age group. We outline the policy rationale of the indicator, describe its data sources and methods of calculation, and report and analyse the official indicator for 183 countries. We also provide examples of the use of the indicator in national workers' health monitoring systems and highlight the indicator's strengths and limitations. We conclude that integrating the new indicator into monitoring systems will provide more comprehensive and accurate surveillance of workers' health, and allow harmonization across global, regional and national monitoring systems. Inequalities in workers' health can be analysed and the evidence base can be improved towards more effective policy and systems on workers' health.

Par le biais des objectifs de développement durable 3 et 8 ainsi que d'autres mesures, plusieurs pays se sont engagés à protéger et promouvoir la santé des travailleurs en réduisant l'impact des maladies liées au travail. Mais pour évaluer leurs progrès en la matière, il convient de mettre en place des indicateurs estimant l'impact des maladies liées au travail afin de placer le développement durable et la santé des travailleurs sous surveillance. D'après l'Organisation mondiale de la Santé et l'Organisation internationale du Travail, seulement 363 283 (19%) des 1 879 890 décès liés au travail dans le monde en 2016 découlaient de blessures, tandis que 1 516 607 (81%) d'entre eux étaient causés par des maladies. La plupart des systèmes de surveillance qui s'intéressent à la santé des travailleurs ou au développement durable, comme le cadre mondial d'indicateurs pour les objectifs de développement durable, comportent un indicateur relatif à l'impact des accidents de travail. Cependant, rares sont ceux qui possèdent un indicateur concernant l'impact des maladies professionnelles. Pour combler cette lacune, nous dévoilons un nouvel indicateur mondial: le taux de mortalité dû aux maladies attribuables à certains facteurs de risque professionnels classé par maladie, facteur de risque, sexe et catégorie d'âge. Nous exposons le motif politique de l'indicateur, décrivons l'origine des données et les méthodes de calcul, et communiquons et analysons l'indicateur officiel pour 183 pays. Nous fournissons également des exemples de la façon dont l'indicateur peut être utilisé dans des systèmes nationaux de surveillance de la santé des travailleurs et soulignons ses forces et faiblesses. Nous concluons en affirmant que l'intégration de ce nouvel indicateur dans les systèmes de surveillance offrira un suivi plus complet et précis de la santé des travailleurs et ouvrira la voie à une harmonisation des systèmes mondiaux, nationaux et régionaux. Il est possible d'analyser les inégalités en matière de santé des travailleurs et d'en améliorer les bases factuelles afin d'établir des politiques et systèmes plus efficaces dans ce domaine.

A través de los objetivos de desarrollo sostenible 3 y 8 y de otras políticas, los países se han comprometido a proteger y promover la salud de los trabajadores reduciendo la carga de morbilidad relacionada con el trabajo. Para supervisar los avances en el cumplimiento de estos compromisos, debería disponerse de indicadores que reflejen la carga de morbilidad relacionada con el trabajo, a fin de controlar la salud de los trabajadores y el desarrollo sostenible. La Organización Mundial de la Salud y la Organización Internacional del Trabajo estiman que solo 363 283 (19%) de las 1 879 890 muertes relacionadas con el trabajo a nivel mundial en 2016 se debieron a lesiones, mientras que 1 516 607 (81%) muertes se debieron a enfermedades. La mayoría de los sistemas de vigilancia centrados en la salud de los trabajadores o el desarrollo sostenible, como el marco de indicadores mundiales para los objetivos de desarrollo sostenible, incluyen un indicador sobre la carga de las lesiones laborales. No obstante, pocos de estos sistemas cuentan con un indicador sobre la carga de las enfermedades relacionadas con el trabajo. Para subsanar esta carencia, presentamos un nuevo indicador mundial: la tasa de mortalidad por enfermedades atribuibles a factores de riesgo laborales seleccionados, por enfermedad, factor de riesgo, sexo y grupo de edad. Describimos la justificación política del indicador, describimos sus fuentes de datos y métodos de cálculo, e informamos y analizamos el indicador oficial para 183 países. También proporcionamos ejemplos del uso del indicador en los sistemas nacionales de vigilancia de la salud de los trabajadores y destacamos las ventajas y las limitaciones del indicador. Concluimos que la integración del nuevo indicador en los sistemas de vigilancia proporcionará una vigilancia más exhaustiva y precisa de la salud de los trabajadores, y permitirá la armonización entre los sistemas de vigilancia mundiales, regionales y nacionales. Se podrán analizar las desigualdades en la salud de los trabajadores y se podrá mejorar la base de evidencias para lograr políticas y sistemas más eficaces en materia de salud de los trabajadores.

Agreement between survey- and register-based measures of depression in Denmark.

BACKGROUND: Register-based studies of major depressive disorder (MDD) do not capture all prevalent cases, as untreated cases and diagnoses made by general practitioners are not recorded in the registers. We examined the prevalence and agreement of survey- and register-based measures of depression, and explored sociodemographic and health-related factors that may have influenced this agreement. METHODS: All 32,407 participants in the 2017 Central Denmark Region How are you? survey were linked to hospital and prescription records. A checklist for depressive symptoms within the last 14 days (Major Depression Inventory; MDI) from the survey was compared with register-based assessment of hospital-diagnosed MDD and/or prescriptions for antidepressants. We estimated agreement between survey-based and register-based measures for depression and used logistic regression models to explore selected associated factors. RESULTS: In total, 5.9% of How are you? survey participants screened positive for current depression on the MDI. Of these, 51.3% (95% confidence interval (CI): 49.0-53.6) filled a prescription for an antidepressant medication during the 10 years prior or 2 years following the administration of the survey, and 14.5% (95% CI: 12.9-16.2) were treated for MDD in a psychiatric hospital-based setting. When using a higher threshold of the MDI indicating more severe current depression, 22.8% (95% CI: 19.6-26.1) of those who screened positive also received an MDD diagnosis and 63.4% (95% CI: 59.7-67.2) were prescribed antidepressants during this 12-year period. Among those with current depression, female sex, older age, chronic diseases, hospital-treated self-harm, and being permanently outside the workforce were associated with having a register-based MDD diagnosis or antidepressant prescription. Among those with a register-based depression record, female sex, younger age, hospital-treated self-harm, stress, and severe loneliness were associated with current depression. CONCLUSION: We found that as few as 15% of individuals with current depression in the general Danish population were captured by the psychiatric hospital register, while 51% of these individuals were identifiable in the prescription register. These findings demonstrate that register-based measures significantly underestimate the true prevalence of depression by identifying only the cases that are most severe.

Maternal antipsychotic use during pregnancy and congenital malformations.

BACKGROUND: Existing data may underestimate the potential teratogenic effects of prenatal antipsychotic exposure because of lacking data on miscarriages and induced abortions. OBJECTIVE: This study aimed to present a comprehensive analysis based on information on pregnancies ending in termination, miscarriage, stillbirth, and live birth. STUDY DESIGN: We conducted a population-based cohort study in Denmark of clinically recognized singleton pregnancies with the first-trimester scan performed from 2008 to 2017. We compared the risk of major malformations between pregnancies exposed to antipsychotics in the first trimester and unexposed pregnancies. In secondary analyses, the comparison was made with pregnancies of women who used antipsychotics before but not during pregnancy (discontinuers). We used weighted log-binomial regression to estimate adjusted prevalence ratios and propensity score fine stratifications for confounding control. We performed 4 sensitivity analyses, including a sibling-controlled analysis. RESULTS: Of the 503,158 pregnancies, 1252 (0.2%) were of women who filled an antipsychotic prescription in the first trimester. Major malformations were present in 7.3% of antipsychotic-exposed pregnancies, 5.1% of unexposed pregnancies, and 6.0% of discontinuers' pregnancies. The adjusted prevalence ratio was 1.23 (95% confidence interval, 1.01-1.50) among exposed pregnancies compared with unexposed pregnancies. The prevalence ratio was attenuated to 1.14 (95% confidence interval, 0.88-1.48) compared with discontinuers and 1.08 (95% confidence interval, 0.47-2.49) in the sibling analysis. Similar findings were observed with cardiac malformations. Results were consistent for classes and individual antipsychotics, and remained robust across the 4 sensitivity analyses. CONCLUSION: Our findings suggest limited or no overall teratogenic effect of first-trimester antipsychotic exposure. For individual antipsychotics, with estimations based on very few cases, further studies with sufficient sample sizes are warranted.

In utero exposure to ADHD medication and long-term offspring outcomes.

Attention Deficit Hyperactivity Disorder (ADHD) medication is increasingly being used during pregnancy. Concerns have been raised as to whether ADHD medication has long-term adverse effects on the offspring. The authors investigated whether in utero exposure to ADHD medication was associated with adverse long-term neurodevelopmental and growth outcomes in offspring. The population-based cohort study in the Danish national registers included 1,068,073 liveborn singletons from 1998 to 2015 followed until any developmental diagnosis, death, emigration, or December 31, 2018. Children of mothers who continued ADHD medication (methylphenidate, amphetamine, dexamphetamine, lisdexamphetamine, modafinil, atomoxetine, clonidine) during pregnancy and children of mothers who discontinued ADHD medication before pregnancy were compared using Cox regression. Main outcomes were neurodevelopmental psychiatric disorders, impairments in vision or hearing, epilepsy, seizures, or growth impairment during childhood or adolescence. In total, 898 children were exposed to ADHD medication during pregnancy compared to 1270 children whose mothers discontinued ADHD medication before pregnancy. After adjustment for demographic and psychiatric characteristics of the mother, no increased risk of any offspring developmental disorders was found combined (aHR 0.97, 95% CI 0.81 to 1.17) or for separate subcategories. Similarly, no increased risk was found for any sub-categories of outcomes in the negative control or sibling controlled analyses. Neurodevelopment and growth in offspring do not differ based on antenatal exposure to ADHD medication. These findings provide reassurance for women with ADHD who depend on ADHD medication for daily functioning and who consider continuing medication in pregnancy.

The health care cost of comorbidity in individuals with mental disorders: A Danish register-based study.

AIM: The aim of the study was to estimate the annual health care cost by number of comorbid mental and somatic disorders in persons with a mental disorder. METHODS: All persons living in Denmark between 2004 and 2017 with a hospital diagnosis of a mental disorder were identified. We investigated the cost of different health care services: psychiatric hospitals, somatic hospitals, primary health care (e.g. general practitioners, psychologists and so on) and subsidised prescriptions. Within those with at least one mental disorder, we examined the costs for people with (a) counts of different types of mental disorders (e.g. exactly 1, exactly 2 and so on up to 8 or more) and (b) counts of different types of somatic disorders (e.g. no somatic disorders, exactly 1, exactly 2 and so on up to 15 or more). The estimates are reported in average cost per case and nationwide annual cost in Euro 2017. RESULTS: In total, 447,209 persons (238,659 females and 208,550 males) were diagnosed with at least one mental disorder in the study period. The average annual health care cost per case and nationwide cost was 4471 Euros and 786 million Euro, respectively, for persons with exactly one mental disorder, and 33,273 Euro and 3.6 million Euro for persons with eight or more mental disorders. The annual health care cost was 4613 Euro per case and 386 million Euro for persons without any somatic disorders, while the cost per case was 16,344 Euro and 0.7 million Euro in nationwide cost for persons with 15 or more disorders. The amount and proportion of the different health care costs varied by type of comorbidity and count of disorders. CONCLUSIONS: The annual health care cost per case was higher with increasing number of comorbid mental and somatic disorders, while the nationwide annual health care cost was lower with increasing number of comorbid disorders for persons with a mental disorder in Denmark.

Bidirectional Associations Between Asthma and Types of Mental Disorders.

BACKGROUND: Asthma and mental disorders frequently co-occur. Studies of their comorbidity have generally focused on associations related to a subset of mental disorders. OBJECTIVE: To estimate bidirectional associations between asthma and 10 broad types of mental disorders. METHODS: In a population-based cohort study, including all individuals born in Denmark between 1955 and 2011 (N = 5,053,471), we considered diagnoses of comorbid mental disorders among those with asthma, and vice versa, between 2000 and 2016. We used Cox regression models to calculate overall and time-dependent hazard ratios for mental disorder-asthma pairs and competing-risks survival analyses to estimate absolute risks. RESULTS: Altogether, 376,756 individuals were identified as having an incident mental disorder and 364,063 incident asthma during follow-up. An increased risk was seen for all bidirectional mental disorder-asthma pairs. Following an asthma diagnosis, adjusted hazard ratios for different subsequent mental disorders ranged from 1.75 (95% CI, 1.64-1.87) for organic disorders to 2.75 (95% CI, 2.69-2.81) for personality disorders. Following a prior mental disorder diagnosis, hazard ratios for asthma ranged from 1.06 (95% CI, 1.00-1.12) for developmental disorders to 2.33 (95% CI, 2.28-2.39) for substance use disorders. Risks varied with time since prior disorder diagnosis but remained elevated. Cumulative incidence of (1) asthma after a mental disorder and (2) a mental disorder after asthma was higher in those with prior disorders than in matched reference groups. CONCLUSIONS: Our findings provide evidence of bidirectional associations between asthma and each of the mental disorder types, suggesting possible shared etiological factors or pathophysiologic processes.

Estimating the population exposed to a risk factor over a time window: A microsimulation modelling approach from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.

OBJECTIVES: Burden of disease estimation commonly requires estimates of the population exposed to a risk factor over a time window (yeart to yeart+n). We present a microsimulation modelling approach for producing such estimates and apply it to calculate the population exposed to long working hours for one country (Italy). METHODS: We developed a three-model approach: Model 1, a multilevel model, estimates exposure to the risk factor at the first year of the time window (yeart). Model 2, a regression model, estimates transition probabilities between exposure categories during the time window (yeart to yeart+n). Model 3, a microsimulation model, estimates the exposed population over the time window, using the Monte Carlo method. The microsimulation is carried out in three steps: (a) a representative synthetic population is initiated in the first year of the time window using prevalence estimates from Model 1, (b) the exposed population is simulated over the time window using the transition probabilities from Model 2; and (c) the population is censored for deaths during the time window. RESULTS: We estimated the population exposed to long working hours (i.e. 41-48, 49-54 and ≥55 hours/week) over a 10-year time window (2002-11) in Italy. We populated all three models with official data from Labour Force Surveys, United Nations population estimates and World Health Organization life tables. Estimates were produced of populations exposed over the time window, disaggregated by sex and 5-year age group. CONCLUSIONS: Our modelling approach for estimating the population exposed to a risk factor over a time window is simple, versatile, and flexible. It however requires longitudinal exposure data and Model 3 (the microsimulation model) is stochastic. The approach can improve accuracy and transparency in exposure and burden of disease estimations. To improve the approach, a logical next step is changing Model 3 to a deterministic microsimulation method, such as modelling of microflows.

The effect of occupational exposure to welding fumes on trachea, bronchus and lung cancer: A systematic review and meta-analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.

BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) are the producers of the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury (WHO/ILO Joint Estimates). Welding fumes have been classified as carcinogenic to humans (Group 1) by the WHO International Agency for Research on Cancer (IARC) in IARC Monograph 118; this assessment found sufficient evidence from studies in humans that welding fumes are a cause of lung cancer. In this article, we present a systematic review and meta-analysis of parameters for estimating the number of deaths and disability-adjusted life years from trachea, bronchus, and lung cancer attributable to occupational exposure to welding fumes, to inform the development of WHO/ILO Joint Estimates on this burden of disease (if considered feasible). OBJECTIVES: We aimed to systematically review and meta-analyse estimates of the effect of any (or high) occupational exposure to welding fumes, compared with no (or low) occupational exposure to welding fumes, on trachea, bronchus, and lung cancer (three outcomes: prevalence, incidence, and mortality). DATA SOURCES: We developed and published a protocol, applying the Navigation Guide as an organizing systematic review framework where feasible. We searched electronic databases for potentially relevant records from published and unpublished studies, including Medline, EMBASE, Web of Science, CENTRAL and CISDOC. We also searched grey literature databases, Internet search engines, and organizational websites; hand-searched reference lists of previous systematic reviews; and consulted additional experts. STUDY ELIGIBILITY AND CRITERIA: We included working-age (≥15 years) workers in the formal and informal economy in any Member State of WHO and/or ILO but excluded children (<15 years) and unpaid domestic workers. We included randomized controlled trials, cohort studies, case-control studies, and other non-randomized intervention studies with an estimate of the effect of any (or high) occupational exposure to welding fumes, compared with occupational exposure to no (or low) welding fumes, on trachea, bronchus, and lung cancer (prevalence, incidence, and mortality). STUDY APPRAISAL AND SYNTHESIS METHODS: At least two review authors independently screened titles and abstracts against the eligibility criteria at a first review stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. If studies reported odds ratios, these were converted to risk ratios (RRs). We combined all RRs using random-effects meta-analysis. Two or more review authors assessed the risk of bias, quality of evidence, and strength of evidence, using the Navigation Guide tools and approaches adapted to this project. Subgroup (e.g., by WHO region and sex) and sensitivity analyses (e.g., studies judged to be of "high"/"probably high" risk of bias compared with "low"/"probably low" risk of bias) were conducted. RESULTS: Forty-one records from 40 studies (29 case control studies and 11 cohort studies) met the inclusion criteria, comprising over 1,265,512 participants (≥22,761 females) in 21 countries in three WHO regions (Region of the Americas, European Region, and Western Pacific Region). The exposure and outcome were generally assessed by job title or self-report, and medical or administrative records, respectively. Across included studies, risk of bias was overall generally probably low/low, with risk judged high or probably high for several studies in the domains for misclassification bias and confounding. Our search identified no evidence on the outcome of having trachea, bronchus, and lung cancer (prevalence). Compared with no (or low) occupational exposure to welding fumes, any (or high) occupational exposure to welding fumes increased the risk of acquiring trachea, bronchus, and lung cancer (incidence) by an estimated 48 % (RR 1.48, 95 % confidence interval [CI] 1.29-1.70, 23 studies, 57,931 participants, I2 24 %; moderate quality of evidence). Compared with no (or low) occupational exposure to welding fumes, any (or high) occupational exposure to welding fumes increased the risk dying from trachea, bronchus, and lung cancer (mortality) by an estimated 27 % (RR 1.27, 95 % CI 1.04-1.56, 3 studies, 8,686 participants, I2 0 %; low quality of evidence). Our subgroup analyses found no evidence for difference by WHO region and sex. Sensitivity analyses supported the main analyses. CONCLUSIONS: Overall, for incidence and mortality of trachea, bronchus, and lung cancer, we judged the existing body of evidence for human data as "sufficient evidence of harmfulness" and "limited evidence of harmfulness", respectively. Occupational exposure to welding fumes increased the risk of acquiring and dying from trachea, bronchus, and lung cancer. Producing estimates for the burden of trachea, bronchus, and lung cancer attributable to any (or high) occupational exposure to welding fumes appears evidence-based, and the pooled effect estimates presented in this systematic review could be used as input data for the WHO/ILO Joint Estimates. PROTOCOL IDENTIFIER: https://doi.org/10.1016/j.envint.2020.106089.