Exposure to air pollution and risk of respiratory tract infections in the adult Danish population-a nationwide study.

OBJECTIVES: The association between air pollution and risk of respiratory tract infection (RTI) in adults needs to be clarified in settings with low to moderate levels of air pollution. We investigated this in the Danish population between 2004 and 2016. METHODS: We included 3 653 490 persons aged 18-64 years in a nested case-control study. Exposure was defined as the average daily concentration at the individual's residential address of CO, NOX, NO2, O3, SO2, NH3, PPM2.5, black carbon, organic carbon, mineral dust, sea salt, secondary inorganic aerosols, SO42-, NO3-, NH4+, secondary organic aerosols, PM2.5, and PM10 during a 3-month exposure window. RTIs were defined by hospitalization for RTIs. Incidence rate ratios (IRRs) and 95% CIs were estimated comparing highest with lowest decile of exposure using conditional logistic regression models. RESULTS: In total, 188 439 incident cases of RTI were identified. Exposure to most air pollutants was positively associated with risk of RTI. For example, NO2 showed an IRR of 1.52 (CI: 1.48-1.55), and PM2.5 showed an IRR of 1.45 (CI: 1.40-1.50). In contrast, exposure to sea salt, PM10, NH3, and O3 was negatively associated with a risk of RTIs. DISCUSSION: In this nationwide study comprising adults, exposure to air pollution was associated with risk of RTIs and subgroups hereof. Sea salt, PM10, NH3, and O3 may be proxies for rural areas, as the levels of these species in Denmark are higher near the western coastlines and/or in rural areas with fewer combustion sources.

Schizophrenia spectrum disorders in Denmark between 2000 and 2018: Incidence and early diagnostic transition.

BACKGROUND: Schizophrenia spectrum disorders (SSD) comprise a group of related mental disorders, which share clinical features and common genetic disposition, but it is unknown if there is a diagnostic transition between these disorders over time. We aimed to study the incidence at the first SSD diagnosis between 2000 and 2018, defined as schizophrenia, schizotypal or schizoaffective disorder, and the early diagnostic transition between these disorders. METHODS: Using Danish nationwide healthcare registers, we identified all individuals aged 15-64 years during the period from 2000 to 2018 in Denmark and calculated the yearly incidence rates for the specific SSDs. We studied the diagnostic pathways from the first ever diagnosis of an SSD across the subsequent two treatment courses with an SSD diagnosis to evaluate early diagnostic stability, and explore potential changes over time. RESULTS: Among 21,538 patients, yearly incidence rates per 10,000 individuals were similar during the observation period for schizophrenia (2000: 1.8; 2018: 1.6), lower for schizoaffective disorder (2000: 0.3; 2018: 0.1) and increasing for schizotypal disorder (2000: 0.7; 2018: 1.3). Among the subgroup of 13,417 individuals with three separate treatment courses, early diagnostic stability was present among 89.9% which differed between the disorders (schizophrenia: 95.4%; schizotypal disorder: 78.0%; schizoaffective disorder: 80.5%). Among 1352 (10.1%) experiencing an early diagnostic transition, 398 (3.0%) were diagnosed with schizotypal disorder after a schizophrenia or schizoaffective disorder diagnosis. CONCLUSION: This study provides comprehensive incidence rates for SSDs. The majority of patients experienced early diagnostic stability, but sizable proportions of people with initial schizophrenia or schizoaffective disorder are subsequently diagnosed with schizotypal disorder.

Towards more comprehensive nationwide familial aggregation studies in Denmark: The Danish Civil Registration System versus the lite Danish Multi-Generation Register.

AIM: Linking information on family members in the Danish Civil Registration System (CRS) with information in Danish national registers provides unique possibilities for research on familial aggregation of diseases, health patterns, social factors and demography. However, the CRS is limited in the number of generations that it can identify. To allow more complete familial linkages, we introduce the lite Danish Multi-Generation Register (lite MGR) and the future full Danish MGR that is currently being developed. METHODS: We generated the lite MGR by linking the current version of the CRS with historical versions stored by the Danish National Archives in the early 1970s, which contain familial links not saved in the current CRS. We describe and compare the completeness of familial links in the lite MGR and the current version of the CRS. We also describe planned procedures for generating the full MGR by linking the current CRS with scanned archived records from Parish Registers. RESULTS: Among people born in Denmark in 1960 or later, the current CRS contains information on both parents. However, it has limited parental information for people born earlier. Among the 732,232 people born in Denmark during 1950-1959, 444,084 (60.65%) had information on both parents in the CRS. In the lite MGR, it was 560,594 (76.56%). CONCLUSIONS: The lite MGR offers more complete information on familial relationships than the current CRS. The lite and full MGR will offer an infrastructure tying together existing research infrastructures, registers and biobanks, raising their joint research value to an unparalleled level.

Multilevel interactions between family and neighbourhood socioeconomic indices in childhood and later risks of self-harm and violent criminality in Denmark: a national cohort study.

BACKGROUND: A socioeconomically disadvantaged childhood has been associated with elevated self-harm and violent criminality risks during adolescence and young adulthood. However, whether these risks are modified by a neighbourhood's socioeconomic profile is unclear. The aim of our study was to compare risks among disadvantaged young people residing in deprived areas versus risks among similarly disadvantaged individuals residing in affluent areas. METHODS: We did a national cohort study, using Danish interlinked national registers, from which we delineated a longitudinal cohort of people born in Denmark between Jan 1, 1981, and Dec 31, 2001, with two Danish-born parents, who were alive and residing in the country when they were aged 15 years, who were followed up for a hospital-treated self-harm episode or violent crime conviction. A neighbourhood affluence indicator was derived based on nationwide income quartiles, with parental income and educational attainment indicating the socioeconomic position of each cohort member's family. Bayesian multilevel survival analyses were done to examine the moderating influences of neighbourhood affluence on associations between family socioeconomic position and sex-specific risks for the two adverse outcomes. FINDINGS: 1 084 047 cohort members were followed up for 12·8 million person-years in aggregate. Individuals of a low socioeconomic position residing in deprived neighbourhoods had a higher incidence of both self-harm and violent criminality compared with equivalently disadvantaged peers residing in affluent areas. Women from a low-income background residing in affluent areas had, on average, 95 (highest density interval 76-118) fewer self-harm episodes and 25 (15-41) fewer violent crime convictions per 10 000 person-years compared with women of an equally low income residing in deprived areas, whereas men of a low income residing in affluent areas had 61 (39-81) fewer self-harm episodes and 88 (56-191) fewer violent crime convictions per 10 000 person-years than men of a low income residing in deprived areas. INTERPRETATION: Even in a high-income European country with comprehensive social welfare and low levels of poverty and inequality, individuals residing in affluent neighbourhoods have lower risks of self-harm and violent criminality compared with individuals residing in deprived neighbourhoods. More research is needed to explore the potential of neighbourhood policies and interventions to reduce the harmful effects of growing up in socioeconomically deprived circumstances on later risk of self-harm and violent crime convictions. FUNDING: European Research Council, Lundbeck Foundation Initiative for Integrative Psychiatric Research, and BERTHA, the Danish Big Data Centre for Environment and Health funded by the Novo Nordisk Foundation Challenge Programme.

The complexities of suicide: a multilevel survival analysis examining individual, familial and neighbourhood determinants of suicide risk using Danish register-based data.

BACKGROUND: Suicide risk is complex and nuanced, and how place impacts suicide risk when considered alongside detailed individual risk factors remains uncertain. We aimed to examine suicide risk in Denmark with both individual and neighbourhood level risk factors. METHODS: We used Danish register-based data to identify individuals born in Denmark from 1972, with full parental information and psychiatric diagnosis history. We fitted a two-level survival model to estimate individual and neighbourhood determinants on suicide risk. RESULTS: We identified 1723 cases of suicide in Denmark during the follow-up period from 1982 to 2015. Suicide risk was explained mainly by individual determinants. Parental comorbidities, particularly maternal schizophrenia [incidence rate ratio (IRR): 2.29, 95% CI 1.56-3.16] and paternal death (2.29, 95% CI 1.31-3.72) partly explained suicide risk when adjusted for all other determinants. The general contextual effect of suicide risk across neighbourhoods showed a median incidence rate ratio (MRR) of 1.13 (1.01-1.28), which was further reduced with full adjustment. Suicide risk increased in neighbourhoods with a higher proportion of manual workers (IRR: 1.08; 1.03-1.14), and decreased with a higher population density (IRR: 0.89; 0.83-0.96). CONCLUSION: Suicide risk varies mainly between individuals, with parental comorbidities having the largest effect on suicide risk. Suicide risk was less impacted by neighbourhood, though, albeit to a lesser extent than individual determinants, some characteristics were associated with suicide risk. Suicide prevention policies might consider targeting interventions towards individuals more vulnerable due to particular parental comorbidities, whilst taking into account that some neighbourhood characteristics might exacerbate this risk further.

PM2.5 air pollution components and mortality in Denmark.

BACKGROUND: Ambient fine particulate matter (PM2.5) causes millions of deaths every year worldwide. Identification of the most harmful types of PM2.5 would facilitate efficient prevention strategies. OBJECTIVES: The aim of this study was to investigate associations between components of PM2.5 and mortality in a nation-wide Danish population. METHODS: Our study base was Danes born 1921-1985 and aged 30-85 years, who were followed up for mortality from 1991 to 2015. We included 678,465 natural cause mortality cases and selected five age, sex and calendar time matched controls to each case from the study base. We retrieved the address history of the study population from Danish registries and assessed five-year average concentrations of eight PM2.5 components using deterministic Chemistry-Transport Models air pollution models. We estimated mortality rate ratios (MRRs) by conditional logistic regression and adjusted for socio-demographical factors at individual and neighborhood level. RESULTS: Single pollutant models showed the strongest associations between natural cause mortality and an interquartile increase in sulfate particles (SO4--) (MRR: 1.123; 95 % CI: 1.100-1.147 per 1.5 µg/m3) and secondary organic aerosol (SOA) (MRR: 1.054; 95 % CI: 1.048-1.061 per 0.050 µg/m3). Two-pollutant models showed robust associations between SO4-- and SOA and natural cause mortality. Elemental carbon and mineral dust showed robust associations with higher respiratory and lung cancer mortality. CONCLUSION: This nation-wide study found robust associations between natural cause mortality and SO4-- particles and SOA, which is in line with the results of previous studies. Elemental carbon and mineral dust showed robust associations with higher respiratory and lung cancer mortality.

School performance and genetic propensities for educational attainment and depression in the etiology of self-harm: a Danish population-based study.

BACKGROUND: Poor school performance is linked to higher risks of self-harm. The association might be explained through genetic liabilities for depression or educational attainment. We investigated the association between school performance and self-harm in a population-based sample while assessing the potential influence of polygenic risk scores (PRSs) for depression (PRSMDD) and for educational attainment (PRSEDU). METHOD: We conducted a follow-up study of individuals born 1987-98 and followed from age 18 until 2016. The total sample consisted of a case group (23,779 diagnosed with mental disorders; schizophrenia, bipolar disorder, depression, autism, and attention deficit hyperactivity disorder (ADHD) and a randomly sampled comparison group (n = 10,925). Genome-wide data were obtained from the Neonatal Screening Biobank and information on school performance, family psychiatric history, and socioeconomic status from national administrative registers. RESULTS: Individuals in the top PRSMDD decile were at higher self-harm risk in the case group (IRR: 1.30; 95% CI 1.15-1.46), whereas individuals in the top PRSEDU decile were at lower self-harm risk (IRR: 0.63; 95% CI: 0.55-0.74). Poorer school performance was associated with higher self-harm risk in persons diagnosed with any mental disorder (IRR: 1.69; 95% CI: 1.44-1.99) and among the comparison group (IRR: 7.93; 95% CI: 4.47-15.18). Observed effects of PRSMDD and PRSEDU on self-harm risk were strongest for individuals with poor school performance. CONCLUSION: Associations between PRSMDD and self-harm risk and between PRSEDU and self-harm risk were found. Nevertheless, these polygenic scores seem currently of limited clinical utility for identifying individuals at high self-harm risk.

Maternal Epilepsy and Long-term Offspring Mortality: A Nationwide Cohort Study.

OBJECTIVE: We examined how maternal epilepsy and use of antiseizure medications in pregnancy was associated with offspring mortality. METHODS: This population-based cohort study included all live- and stillborn singletons in Denmark between 1981 and 2016. We used nation-wide registers to retrieve information on pregnancy characteristics, epilepsy diagnoses, use of antiseizure medications, and mortality. Adjusted mortality rate ratios (MRR) were estimated using log-linear Poisson regression. RESULTS: The cohort consisted of 1,862,474 children. In total, 12,026 live-born children died during follow-up, of whom 170 (1.4%) were offspring of mothers with epilepsy. Overall mortality was increased in offspring of mothers with epilepsy compared to offspring of mothers without epilepsy (MRR = 1.46, 95% CI: 1.23-1.71), driven by an excess mortality only in the first year of life. Mortality was increased for natural deaths (MRR = 1.50, 95% CI: 1.25-1.78) but not from unnatural deaths (MRR = 1.38, 95% CI: 0.84-2.14), and only in offspring of women with epilepsy who used antiseizure medications during pregnancy (MRR = 1.51, 95% CI: 1.00-2.17), but not in offspring of women with epilepsy who did not use antiseizure medications while pregnant (MRR = 0.97, 95% CI: 0.69-1.31). When analyses were restricted to children born from 2000 and onwards, the excess mortality that was observed in the first year of life among children of mothers with epilepsy, was no longer evident. INTERPRETATION: During the 1981 to 1999 epoch, offspring of women with epilepsy were at increased risk of dying in the first year of life. However, this risk did not extend to children born after 2000. Future retrospective studies of the effects of maternal epilepsy on the health of the offspring should take this difference into account. ANN NEUROL 2022;91:455-465.

Exposure to ambient air pollution during childhood and subsequent risk of self-harm: A national cohort study.

A growing body of evidence indicates that exposure to air pollution not only impacts on physical health but is also linked with a deterioration in mental health. We conducted the first study to investigate exposure to ambient particulate matter with an aerodynamic diameter of less than 2.5 µm (PM2.5) and nitrogen dioxide (NO2) during childhood and subsequent self-harm risk. The study cohort included persons born in Denmark between January 1, 1979 and December 31, 2006 (N = 1,424,670), with information on daily exposures to PM2.5 and NO2 at residence from birth to 10th birthday. Follow-up began from 10th birthday until first hospital-presenting self-harm episode, death, or December 31, 2016, whichever came first. Incidence rate ratios estimated by Poisson regression models revealed a dose relationship between increasing PM2.5 exposure and rising self-harm risk. Exposure to 17-19 µg/m3 of PM2.5 on average per day from birth to 10th birthday was associated with a 1.45 fold (95% CI 1.37-1.53) subsequently elevated self-harm risk compared with a mean daily exposure of <13 µg/m3, whilst those exposed to 19 µg/m3 or above on average per day had a 1.59 times (1.45-1.75) elevated risk. Higher mean daily exposure to NO2 during childhood was also linked with increased self-harm risk, but the dose-response relationship observed was less evident than for PM2.5. Covariate adjustment attenuated the associations, but risk remained independently elevated. Although causality cannot be assumed, these novel findings indicate a potential etiological involvement of ambient air pollution in the development of mental ill health.

Adverse Childhood Experiences and Risk of Subsequently Engaging in Self-Harm and Violence towards Other People-"Dual Harm".

The etiology of "dual harm" (the co-occurrence of self-harm and externalized violence in the same individual) is under-researched. Risk factors have mostly been investigated for each behavior separately. We aimed to examine adversities experienced between birth and age 15 years among adolescents and young adults with histories of self-harm and violent criminality, with a specific focus on dual harm. Three nested case-control studies were delineated using national interlinked Danish registers; 58,409 cases in total aged 15-35 were identified: 28,956 with a history of violent criminality (but not self-harm), 25,826 with a history of self-harm (but not violent criminality), and 3987 with dual-harm history. Each case was matched by date of birth and gender to 20 controls who had not engaged in either behavior. We estimated exposure prevalence for cases versus controls for each of the three behavior groups, and incidence rate ratios (IRRs). Experiencing five or more childhood adversities was more prevalent among individuals with dual-harm history (19.3%; 95% CI 18.0, 20.8%) versus self-harm (10.9%; 10.5, 11.3%) and violence (11.4%; 11.0%, 11.8%) histories. The highest IRRs for dual harm were linked with parental unemployment (5.15; 95% CI 4.71, 5.64), parental hospitalization following self-harm (4.91; 4.40, 5.48) or assault (5.90; 5.07, 6.86), and parental violent criminality (6.11; 5.57, 6.70). Growing up in environments that are characterized by poverty, violence, and substance misuse, and experiencing multiple adversities in childhood, appear to be especially strongly linked with elevated dual-harm risk. These novel findings indicate potential etiologic pathways to dual harm.

Long-term exposure to air pollution and mortality in the Danish population a nationwide study.

BACKGROUND: Studies have shown higher mortality in association with exposure to air pollution. We investigated this association with focus on differences between socioeconomic groups. METHODS: We included all Danes born between 1921 and 1985 aged 30-85 years from 1991 to 2015 (N = 4,401,348). We applied a nested case-control design and identified those who died during follow-up and selected five controls per case. We modelled NO2, fine particulate matter (PM2·5), black carbon (BC) particles, and ozone (O3) as five-year average concentrations at the residential addresses of 672,895 all natural cause mortality cases and 3,426,533 controls in conditional logistic regression with adjustment for individual and neighbourhood level socio-demographic variables. FINDINGS: In single pollutant models, a 10 µg/m3 (BC: 1 µg/m3) increase in NO2, PM2·5, BC, and O3 was associated with natural cause mortality rate ratios (MRR) of 1·05 (95% confidence interval 1·04-1·06), 1·08 (1·04-1·13), 1·05 (1·02-1·08), and 0·96 (0·95-0·97), respectively. The patterns were similar for respiratory disease and lung cancer mortality. O3 was associated with higher risk of CVD mortality. The rate differences for a unit increase in PM2·5, NO2, and BC were largest among those with the lowest income; this pattern was not detected when considering the relative risk measure, MRR. INTERPRETATION: Long-term concentration of air pollution at the residence was associated with higher natural cause mortality in the Danish population and the strength of the association differed by socioeconomic group. We recommend that future studies express socioeconomic differences in absolute rather than relative risk.

Exposure to air pollution during childhood and risk of developing schizophrenia: a national cohort study.

BACKGROUND: Ambient air pollution affects neurological function, but its association with schizophrenia risk is unclear. We investigated exposure to nitrogen oxides (NOX) as a whole and nitrogen dioxide (NO2) specifically, as well as PM10, and PM2·5, during childhood and subsequent schizophrenia risk. METHODS: People born in Denmark from 1980 to 1984 (N=230 844), who were residing in the country on their tenth birthday, and who had two Danish-born parents were followed-up from their tenth birthday until schizophrenia diagnosis or Dec 31, 2016. Mean daily exposure to each pollutant (NO2, NOX, PM10, and PM2·5) at all of an individual's residential addresses from birth to their tenth birthday was modelled. Incidence rate ratios, cumulative incidence, and population attributable risks were calculated using survival analysis techniques. FINDINGS: We analysed data between Aug 1, 2018, and Nov 15, 2019. Of 230 844 individuals included, 2189 cohort members were diagnosed with schizophrenia during follow-up. Higher concentrations of residential NO2 and NOX exposure during childhood were associated with subsequent elevated schizophrenia risk. People exposed to daily mean concentrations of more than 26·5 µg/m3 NO2 had a 1·62 (95% CI 1·41-1·87) times increased risk compared with people exposed to a mean daily concentration of less than 14·5 µg/m3. The absolute risks of developing schizophrenia by the age of 37 years when exposed to daily mean concentrations of more than 26·5 µg/m3 NO2 between birth and 10 years were 1·45% (95% CI 1·30-1·62%) for men and 1·03% (0·90-1·17) for women, whereas when exposed to a mean daily concentration of less than 14·5 µg/m3, the risk was 0·80% (95% CI 0·69-0·92%) for men and 0·67% (0·57-0·79) for women. Associations between exposure to PM2·5 or PM10 and schizophrenia risk were less consistent. INTERPRETATION: If the association between air pollution and schizophrenia is causal, reducing ambient air pollution including NO2 and NOX could have a potentially considerable effect on lowering schizophrenia incidence at the population level. Further investigations are necessary to establish a causal relationship. FUNDING: Lundbeck Foundation, Stanley Medical Research Institute, European Research Council, NordForsk, Novo Nordisk Foundation, National Health and Medical Research Council, Danish National Research Foundation.

Temporal trends in incidence of hospital-treated self-harm among adolescents in Denmark: national register-based study.

BACKGROUND: Studies conducted in the UK and in Ireland have reported increased rates of self-harm in adolescent females from around the time of the 2008 economic recession and through periods of subsequent national austerity programme implementation. It is not known if incidence rates have increased similarly in other Western European countries during this period. METHODS: Data from interlinked national administrative registers were extracted for individuals born in Denmark during 1981-2006. We estimated gender- and age-specific incidence rates (IRs) per 10,000 person-years at risk for hospital-treated non-fatal self-harm during 2000-2016 at ages 10-19 years. RESULTS: Incidence of self-harm peaked in 2007 (IR 25.1) and then decreased consistently year on year to 13.8 in 2016. This pattern was found in all age groups, in both males and females and in each parental income tertile. During the last 6 years of the observation period, 2011-2016, girls aged 13-16 had the highest incidence rates whereas, among boys, incidence was highest among 17-19 year olds throughout. CONCLUSIONS: The temporal increases in incidence rates of self-harm among adolescents observed in some Western European countries experiencing major economic recession were not observed in Denmark. Restrictions to sales of analgesics, access to dedicated suicide prevention clinics, higher levels of social spending and a stronger welfare system may have protected potentially vulnerable adolescents from the increases seen in other countries. A better understanding of the specific mechanisms behind the temporal patterns in self-harm incidence in Denmark is needed to help inform suicide prevention in other nations.

Association of Childhood Exposure to Nitrogen Dioxide and Polygenic Risk Score for Schizophrenia With the Risk of Developing Schizophrenia.

Importance: Schizophrenia is a highly heritable psychiatric disorder, and recent studies have suggested that exposure to nitrogen dioxide (NO2) during childhood is associated with an elevated risk of subsequently developing schizophrenia. However, it is not known whether the increased risk associated with NO2 exposure is owing to a greater genetic liability among those exposed to highest NO2 levels. Objective: To examine the associations between childhood NO2 exposure and genetic liability for schizophrenia (as measured by a polygenic risk score), and risk of developing schizophrenia. Design, Setting, and Participants: Population-based cohort study including individuals with schizophrenia (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code F20) and a randomly selected subcohort. Using national registry data, all individuals born in Denmark between May 1, 1981, and December 31, 2002, were followed up from their 10th birthday until the first occurrence of schizophrenia, emigration, death, or December 31, 2012, whichever came first. Statistical analyses were conducted between October 24, 2018, and June 17, 2019. Exposures: Individual exposure to NO2 during childhood estimated as mean daily exposure to NO2 at residential addresses from birth to the 10th birthday. Polygenic risk scores were calculated as the weighted sum of risk alleles at selected single-nucleotide polymorphisms based on genetic material obtained from dried blood spot samples from the Danish Newborn Screening Biobank and on the Psychiatric Genomics Consortium genome-wide association study summary statistics file. Main Outcomes and Measures: The main outcome was schizophrenia. Weighted Cox proportional hazards regression models were fitted to estimate adjusted hazard ratios (AHRs) for schizophrenia with 95% CIs according to the exposures. Results: Of a total of 23 355 individuals, 11 976 (51.3%) were male and all had Danish-born parents. During the period of the study, 3531 were diagnosed with schizophrenia. Higher polygenic risk scores were correlated with higher childhood NO2 exposure (ρ = 0.0782; 95% CI, 0.065-0.091; P < .001). A 10-µg/m3 increase in childhood daily NO2 exposure (AHR, 1.23; 95% CI, 1.15-1.32) and a 1-SD increase in polygenic risk score (AHR, 1.29; 95% CI, 1.23-1.35) were independently associated with increased schizophrenia risk. Conclusions and Relevance: These findings suggest that the apparent association between NO2 exposure and schizophrenia is only slightly confounded by a higher polygenic risk score for schizophrenia among individuals living in areas with greater NO2. The findings demonstrate the utility of including polygenic risk scores in epidemiologic studies.

Environmental pollution is associated with increased risk of psychiatric disorders in the US and Denmark.

The search for the genetic factors underlying complex neuropsychiatric disorders has proceeded apace in the past decade. Despite some advances in identifying genetic variants associated with psychiatric disorders, most variants have small individual contributions to risk. By contrast, disease risk increase appears to be less subtle for disease-predisposing environmental insults. In this study, we sought to identify associations between environmental pollution and risk of neuropsychiatric disorders. We present exploratory analyses of 2 independent, very large datasets: 151 million unique individuals, represented in a United States insurance claims dataset, and 1.4 million unique individuals documented in Danish national treatment registers. Environmental Protection Agency (EPA) county-level environmental quality indices (EQIs) in the US and individual-level exposure to air pollution in Denmark were used to assess the association between pollution exposure and the risk of neuropsychiatric disorders. These results show that air pollution is significantly associated with increased risk of psychiatric disorders. We hypothesize that pollutants affect the human brain via neuroinflammatory pathways that have also been shown to cause depression-like phenotypes in animal studies.

The Danish in-hospital cardiac arrest registry (DANARREST).

Aim of database: The aim of DANARREST is to collect data on processes of care and outcomes for patients with in-hospital cardiac arrest in Denmark, and thereby facilitate and monitor quality and quality improvement initiatives. Study population: In-hospital cardiac arrest patients with a clinical indication for cardiopulmonary resuscitation in Denmark. Main variables: DANARREST includes a number of descriptive variables as well as seven quality of care indicators; four related to processes of care and three related to clinical outcomes. The four process measures are related to whether the cardiac arrest was witnessed, whether the cardiac arrest was ECG-monitored, the timing of cardiopulmonary resuscitation, and the timing of the first rhythm analysis. The three outcomes measures include return of spontaneous circulation, 30-day survival, and 1-year survival. Database status: DANARREST started in 2013, and the coverage has increased steadily since. As of 2017, 95% of relevant hospitals are reporting data with an estimated coverage rate of approximately 80%. Conclusion: DANARREST is a relatively new national registry of in-hospital cardiac arrests in Denmark, with a high coverage rate. The registry provides an opportunity to monitor and improve quality of care for patients with in-hospital cardiac arrest.

Multiple adverse outcomes following first discharge from inpatient psychiatric care: a national cohort study.

BACKGROUND: Discharged psychiatric inpatients are at elevated risk of serious adverse outcomes, but no previous study has comprehensively examined an array of multiple risks in a single cohort. METHODS: We used data from the Danish Civil Registration System to delineate a cohort of all individuals born in Denmark in 1967-2000, who were alive and residing in Denmark on their 15th birthday, and who had been discharged from their first inpatient psychiatric episode at age 15 years or older. Each individual in the discharged cohort was matched on age and sex with 25 comparators without a history of psychiatric admission. Data linked to each individual were also obtained from the Psychiatric Central Research Register, Register of Causes of Death, National Patient Register, and the National Crime Register. We used survival analysis techniques to estimate absolute and relative risks of all-cause mortality, suicide, accidental death, homicide victimisation, homicide perpetration, non-fatal self-harm, violent criminality, and hospitalisation following violence, until Dec 31, 2015. FINDINGS: We included 62 922 individuals in the discharged cohort, and 1 573 050 matched comparators. Risks for each of all eight outcomes examined were markedly elevated in the discharged cohort relative to the comparators. Within 10 years of first discharge, the cumulative incidence of death, self-harm, committing a violent crime, or hospitalisation due to interpersonal violence was 32·0% (95% CI 31·6-32·5) in the discharged cohort (37·1% [36·5-37·8] in men and 27·2% [26·7-27·8] in women). Absolute risk of at least one adverse outcome occurring within this timeframe were highest in people diagnosed with a psychoactive substance use disorder at first discharge (cumulative incidence 49·4% [48·4-50·4]), and lowest in those diagnosed with a mood disorder (24·4% [23·6-25·2]). For suicide and non-fatal self-harm, risks were especially high during the first 3 months post-discharge, whereas risks for accidental death, violent criminality, and hospitalisation due to violence were more constant throughout the 10-year follow-up. INTERPRETATION: People discharged from inpatient psychiatric care are at higher risk than the rest of the population for a range of serious fatal and non-fatal adverse outcomes. Improved inter-agency liaison, intensive follow-up immediately after discharge, and longer-term social support are indicated. FUNDING: Medical Research Council, European Research Council, and Wellcome Trust.

Risk of dying unnaturally among people aged 15-35 years who have harmed themselves and inflicted violence on others: a national nested case-control study.

BACKGROUND: Self-harm and violent criminality have overlapping causes, but people who engage in these behaviours are typically studied as two discrete populations. In this study, we aimed to examine the risk of unnatural death (ie, death from external causes such as accidents, suicide, and undetermined causes) among people with a history of self-harm and violent crime, focusing specifically on those with co-occurring behaviours. METHODS: For this population-based nested case-control study, we used national interlinked Danish registers. Individuals aged 35 years or younger, who were alive and residing in the country on their 15th birthday, and who died from external causes (cases) were matched by age and gender to living people (controls). We compared risks of suicide, accidental death, and any death by external causes among those with a history of hospital-treated self-harm, violent criminality, or both behaviours with those in individuals without histories of either behaviour. We estimated incidence rate ratios (IRRs), adjusted for age and gender, to compare risks. FINDINGS: We identified 2246 individuals who died from external causes, whom we matched to 44 920 living controls. 1499 (66·7%) of 2246 individuals died from accidental causes and 604 (26·9%) died by suicide. The risk of unnatural death was elevated for individuals with a history of violence (IRR 5·19, 95% CI 4·45-6·06) or self-harm (12·65, 10·84-14·77), but the greatest risk increase was among those with histories of both behaviours (29·37, 23·08-37·38). Substance misuse disorders, particularly multiple drug use, was more prevalent among individuals with co-occurring self-harm and violence than among those engaging in just one of these behaviours. Psychiatric disorders seemed to account for some of the excess risk of unnatural death among people with dual-harm histories, but excess risk, particularly of accidental death, persisted in the multivariable models. INTERPRETATION: Among individuals with co-occurring self-harm and violence, the risk of accidental death, particularly accidental self-poisoning, should be considered to be as important as the risk of suicide. People with a history of both behaviours who also have a substance misuse disorder are at particularly high risk of dying from external causes. Strategies should be designed to be accessible for people facing turbulent lives with multiple problems. Individuals in this group with both behaviours are likely to be treated by health-care services for self-harm and have contact with criminal justice services, providing multiple opportunities for proactive intervention. FUNDING: European Research Council.

Family income inequalities and trajectories through childhood and self-harm and violence in young adults: a population-based, nested case-control study.

BACKGROUND: Childhood poverty is associated with elevated later risks for self-directed and externalised violence, but how risks are modified by parental socioeconomic mobility remains unclear. We investigated parental income trajectories during childhood and subsequent risks of self-harm and violent criminality in young adulthood. METHODS: Using Danish national registers, we delineated a nested case-control study of Danish citizens born from Jan 1, 1982, to Dec 31, 2000, with first hospital-treated self-harm episodes and first violent crime convictions at ages 15-33 years. Each case was matched on age and gender to 25 randomly selected controls. Parental income was assessed in birth-year and at ages 5 years, 10 years, and 15 years. We considered parental age, the child's number of siblings, parental mental health, and parental education to be covariates. We estimated incidence rate ratios (IRRs) by conditional logistic regression inherently adjusted for age, gender, and calendar year; we then made additional adjustments for the covariates considered. FINDINGS: We identified 21 267 first episodes of hospital-treated self-harm, to which we matched 531 675 controls, and 23 724 first violent crime convictions, to which we matched 593 100 controls. We observed inverse relationships between parental income and risks for the two outcomes for each of the ages parental income was measured. The longer a child lived in poorer circumstances, the higher their subsequent risks for self-harm and violent criminality, and vice versa for time spent living in affluent conditions. Associations were stronger for violent criminality than for self-harm. Compared with individuals who were born and remained in the most affluent families, all other income trajectories were associated with elevated risks for both outcomes. Those who remained in the least affluent quintile showed the highest risks for self-harm (IRR 7·2, 95% CI 6·6-7·9; 1174 [6%] cases) and for violent criminality (IRR 13·0; 95% CI 11·9-14·1; 1640 [7%] cases). The risk patterns were attenuated, but essentially persisted, after covariate adjustment. For any parental income level at birth, being upwardly mobile was associated with lower risk compared with downward mobility. INTERPRETATION: Parental income represents a multitude of unmeasured familial sociodemographic indices. Tackling the causes of inequality and associated psychosocial and sociocultural challenges to enable upwards socioeconomic mobility could potentially reduce risks for self-directed and externalised violence. FUNDING: European Research Council.

Suicide Methods and Specific Types of Accidental Death and Fatal Poisoning Among Discharged Psychiatric Patients: A National Cohort Study.

OBJECTIVE: Persons discharged from inpatient psychiatric units are at greatly elevated risk of dying unnaturally. We conducted a comprehensive examination of specific causes of unnatural death post-discharge in a national register-based cohort. METHOD: A cohort of 1,683,645 Danish residents born 1967-1996 was followed from their 15th birthday until death, emigration, or December 31, 2011, whichever came first. Survival analysis techniques were used to estimate incidence rate ratios (IRRs) comparing risk for persons with and without psychiatric admission history in relation to (a) suicide method, (b) accidental death type, (c) fatal poisoning type, and (d) homicide. RESULTS: More than half (52.5%, n = 711) of all unnatural deaths post-discharge were fatal poisonings, compared with less than a fifth (17.0%, n = 1,012) among persons in the general population not admitted. Just 6.8% (n = 92) of all unnatural deaths post-discharge were due to transport accidents-the most common unnatural death type in the general population (53.4%, n = 3,184). Suicide risk was 32 times higher among discharged patients (IRR 32.3; 95% CI, 29.2-35.8) and was even higher during the first year post-discharge (IRR 70.4; 95% CI, 59.7-83.0). Among the suicide methods examined, relative risk values were significantly larger for intentional self-poisoning (IRR 40.8; 95% CI, 33.9-49.1) than for "violent" suicide methods (IRR 29.4; 95% CI, 26.1-33.2). The greatest relative risk observed was for fatal poisoning (irrespective of intent) by psychotropic medication (IRR 93.7; 95% CI, 62.5-140.5). The highest post-discharge mortality rate was for accidental self-poisoning among persons diagnosed with a psychoactive substance abuse disorder: 290.1 per 100,000 person-years. CONCLUSIONS: Closer liaison between inpatient services and community care, more effective early treatment for comorbid substance abuse, enhanced psychosocial assessment following self-harm, and tighter medication surveillance could decrease risk of unnatural death post-discharge.