Longitudinal metabolite and protein trajectories prior to diabetes mellitus diagnosis in Danish blood donors: a nested case-control study.

AIMS/HYPOTHESIS: Metabolic risk factors and plasma biomarkers for diabetes have previously been shown to change prior to a clinical diabetes diagnosis. However, these markers only cover a small subset of molecular biomarkers linked to the disease. In this study, we aimed to profile a more comprehensive set of molecular biomarkers and explore their temporal association with incident diabetes. METHODS: We performed a targeted analysis of 54 proteins and 171 metabolites and lipoprotein particles measured in three sequential samples spanning up to 11 years of follow-up in 324 individuals with incident diabetes and 359 individuals without diabetes in the Danish Blood Donor Study (DBDS) matched for sex and birth year distribution. We used linear mixed-effects models to identify temporal changes before a diabetes diagnosis, either for any incident diabetes diagnosis or for type 1 and type 2 diabetes mellitus diagnoses specifically. We further performed linear and non-linear feature selection, adding 28 polygenic risk scores to the biomarker pool. We tested the time-to-event prediction gain of the biomarkers with the highest variable importance, compared with selected clinical covariates and plasma glucose. RESULTS: We identified two proteins and 16 metabolites and lipoprotein particles whose levels changed temporally before diabetes diagnosis and for which the estimated marginal means were significant after FDR adjustment. Sixteen of these have not previously been described. Additionally, 75 biomarkers were consistently higher or lower in the years before a diabetes diagnosis. We identified a single temporal biomarker for type 1 diabetes, IL-17A/F, a cytokine that is associated with multiple other autoimmune diseases. Inclusion of 12 biomarkers improved the 10-year prediction of a diabetes diagnosis (i.e. the area under the receiver operating curve increased from 0.79 to 0.84), compared with clinical information and plasma glucose alone. CONCLUSIONS/INTERPRETATION: Systemic molecular changes manifest in plasma several years before a diabetes diagnosis. A particular subset of biomarkers shows distinct, time-dependent patterns, offering potential as predictive markers for diabetes onset. Notably, these biomarkers show shared and distinct patterns between type 1 diabetes and type 2 diabetes. After independent replication, our findings may be used to develop new clinical prediction models.

Cardiovascular disease and the risk of incident falls and mortality among adults aged ≥ 65 years presenting to the emergency department: a cohort study from national registry data in Denmark.

BACKGROUND: Falls cause 58% of injury-related Emergency Department (ED) attendances. Previous research has highlighted the potential role of cardiovascular risk factors for falls. This study investigated the impact of cardiovascular disease (CVD) risk on three-year incident falls, with presentation to the ED, and mortality. METHODS: A matched cohort study design was employed using national registry data from 82,292 adults (33% male) aged ≥ 65 years living in Denmark who attended the ED in 2013. We compared age and gender matched ED attendees presenting with a fall versus another reason. The cohort was followed for three-year incident falls, with presentation to the ED, and mortality. The impact of falls-related CVDs was also examined. RESULTS: Three-year incident falls was twofold higher among age and gender matched ED attendees aged ≥ 65 years presenting with a fall versus another reason at baseline. A presentation of falls with hip fracture had the highest percentage of incident falls in the 65-74 age group (22%) and the highest percentage mortality in all age groups (27-62%). CVD was not a significant factor in presenting with a fall at the ED, nor did it contribute significantly to the prediction of three-year incident falls. CVD was strongly associated with mortality risk among the ED fall group (RR = 1.81, 95% CI: 1.67-1.97) and showed interactions with both age and fall history. CONCLUSION: In this large study of adults aged ≥ 65 years attending the ED utilising data from national administrative registers in Denmark, we confirm that older adults attending the ED with a fall, including those with hip fracture, were at greatest risk for future falls. While CVD did not predict incident falls, it increased the risk of mortality in the three-year follow up with advancing age. This may be informative for the provision of care pathways for older adults attending the ED due to a fall.

Socioeconomic disparities in changes to preterm birth and stillbirth rates during the first year of the COVID-19 pandemic: a study of 21 European countries.

BACKGROUND: Despite concerns about worsening pregnancy outcomes resulting from healthcare restrictions, economic difficulties and increased stress during the COVID-19 pandemic, preterm birth (PTB) rates declined in some countries in 2020, while stillbirth rates appeared stable. Like other shocks, the pandemic may have exacerbated existing socioeconomic disparities in pregnancy, but this remains to be established. Our objective was to investigate changes in PTB and stillbirth by socioeconomic status (SES) in European countries. METHODS: The Euro-Peristat network implemented this study within the Population Health Information Research Infrastructure (PHIRI) project. A common data model was developed to collect aggregated tables from routine birth data for 2015-2020. SES was based on mother's educational level or area-level deprivation/maternal occupation if education was unavailable and harmonized into low, medium and high SES. Country-specific relative risks (RRs) of PTB and stillbirth for March to December 2020, adjusted for linear trends from 2015 to 2019, by SES group were pooled using random effects meta-analysis. RESULTS: Twenty-one countries provided data on perinatal outcomes by SES. PTB declined by an average 4% in 2020 {pooled RR: 0.96 [95% confidence intervals (CIs): 0.94-0.97]} with similar estimates across all SES groups. Stillbirths rose by 5% [RR: 1.05 (95% CI: 0.99-1.10)], with increases of between 3 and 6% across the three SES groups, with overlapping confidence limits. CONCLUSIONS: PTB decreases were similar regardless of SES group, while stillbirth rates rose without marked differences between groups.

Long-term exposure to air pollution and risk of SARS-CoV-2 infection and COVID-19 hospitalisation or death: Danish nationwide cohort study.

BACKGROUND: Early ecological studies have suggested links between air pollution and risk of coronavirus disease 2019 (COVID-19), but evidence from individual-level cohort studies is still sparse. We examined whether long-term exposure to air pollution is associated with risk of COVID-19 and who is most susceptible. METHODS: We followed 3 721 810 Danish residents aged ≥30 years on 1 March 2020 in the National COVID-19 Surveillance System until the date of first positive test (incidence), COVID-19 hospitalisation or death until 26 April 2021. We estimated residential annual mean particulate matter with diameter ≤2.5 µm (PM2.5), nitrogen dioxide (NO2), black carbon (BC) and ozone (O3) in 2019 by the Danish DEHM/UBM model, and used Cox proportional hazards regression models to estimate the associations of air pollutants with COVID-19 outcomes, adjusting for age, sex, individual- and area-level socioeconomic status, and population density. RESULTS: 138 742 individuals were infected, 11 270 were hospitalised and 2557 died from COVID-19 during 14 months. We detected associations of PM2.5 (per 0.53 µg·m-3) and NO2 (per 3.59 µg·m-3) with COVID-19 incidence (hazard ratio (HR) 1.10 (95% CI 1.05-1.14) and HR 1.18 (95% CI 1.14-1.23), respectively), hospitalisations (HR 1.09 (95% CI 1.01-1.17) and HR 1.19 (95% CI 1.12-1.27), respectively) and death (HR 1.23 (95% CI 1.04-1.44) and HR 1.18 (95% CI 1.03-1.34), respectively), which were strongest in the lowest socioeconomic groups and among patients with chronic respiratory, cardiometabolic and neurodegenerative diseases. We found positive associations with BC and negative associations with O3. CONCLUSION: Long-term exposure to air pollution may contribute to increased risk of contracting severe acute respiratory syndrome coronavirus 2 infection as well as developing severe COVID-19 disease requiring hospitalisation or resulting in death.

Effectiveness evaluation of an antenatal care intervention addressing disparities to improve perinatal outcomes in Denmark: A nationwide register-based analysis of a cluster randomised controlled trial (MAMAACT).

OBJECTIVE: To evaluate whether MAMAACT, an antenatal care (ANC) intervention, aimed at reducing ethnic and social disparities in perinatal mortality, affected perinatal health outcomes. DESIGN: Cluster randomised controlled trial. SETTING: Nineteen of 20 maternity wards in Denmark. POPULATION: All newborn children within a pre-implementation period (2014-2017) or an implementation period (2018-2019) (n = 188 658). INTERVENTION: A 6-h training session for midwives in intercultural communication and cultural competence, two follow-up dialogue meetings, and health education materials for pregnant women on warning signs of pregnancy complications in six languages. METHODS: Nationwide register-based analysis of the MAMAACT cluster randomised controlled trial. Mixed-effects logistic regression models were used to estimate the change in outcomes from pre- to post-implementation in the intervention group relative to the control group. Results were obtained for the overall study population and for children born to immigrants from low- to middle-income countries, separately. Models were adjusted for confounders selected a priori. MAIN OUTCOME MEASURES: A composite perinatal mortality and morbidity outcome, including stillbirths, neonatal deaths, Apgar score <7, umbilical arterial pH < 7.0, admissions to a neonatal intensive care unit (NICU) >48 h, and NICU admissions for mechanical ventilation. Additional outcomes were the individual measures. RESULTS: The intervention increased the risk of the composite outcome (adjusted odds ratio [aOR] 1.16, 95% confidence interval [CI] 0.99-1.34), mainly driven by differences in NICU admission risk (composite outcome excluding NICU, aOR 0.98, 95% CI 0.84-1.14). The intervention slightly increased the risk of low Apgar score and decreased the risk of low arterial pH, reflecting, however, small differences in absolute numbers. Other outcomes were unchanged. CONCLUSIONS: Overall, the MAMAACT intervention did not improve the composite perinatal mortality and morbidity outcome (when excluding NICU admissions). The lack of effects may be due to contextual factors including organisational barriers in ANC hindering the midwives from changing practices.

Long-term exposure to elemental components of fine particulate matter and all-natural and cause-specific mortality in a Danish nationwide administrative cohort study.

BACKGROUND: Fine particulate matter (PM2.5) is a well-recognized risk factor for premature death. However, evidence on which PM2.5 components are most relevant is unclear. METHODS: We evaluated the associations between mortality and long-term exposure to eight PM2.5 elemental components [copper (Cu), iron (Fe), zinc (Zn), sulfur (S), nickel (Ni), vanadium (V), silicon (Si), and potassium (K)]. Studied outcomes included death from diabetes, chronic kidney disease (CKD), dementia, and psychiatric disorders as well as all-natural causes, cardiovascular disease (CVD), respiratory diseases (RD), and lung cancer. We followed all residents in Denmark (aged ≥30 years) from January 1, 2000 to December 31, 2017. We used European-wide land-use regression models at a 100 × 100 m scale to estimate the residential annual mean levels of exposure to PM2.5 components. The models were developed with supervised linear regression (SLR) and random forest (RF). The associations were evaluated by Cox proportional hazard models adjusting for individual- and area-level socioeconomic factors and total PM2.5 mass. RESULTS: Of 3,081,244 individuals, we observed 803,373 death from natural causes during follow-up. We found significant positive associations between all-natural mortality with Si and K from both exposure modeling approaches (hazard ratios; 95% confidence intervals per interquartile range increase): SLR-Si (1.04; 1.03-1.05), RF-Si (1.01; 1.00-1.02), SLR-K (1.03; 1.02-1.04), and RF-K (1.06; 1.05-1.07). Strong associations of K and Si were detected with most causes of mortality except CKD and K, and diabetes and Si (the strongest associations for psychiatric disorders mortality). In addition, Fe was relevant for mortality from RD, lung cancer, CKD, and psychiatric disorders; Zn with mortality from CKD, RD, and lung cancer, and; Ni and V with lung cancer mortality. CONCLUSIONS: We present novel results of the relevance of different PM2.5 components for different causes of death, with K and Si seeming to be most consistently associated with mortality in Denmark.

Predicting mortality risk after a fall in older adults using health care spending patterns: a population-based cohort study.

OBJECTIVE: To develop a prognostic model of 1-year mortality for individuals aged 65+ presenting at the emergency department (ED) with a fall based on health care spending patterns to guide clinical decision-making. DESIGN: Population-based cohort study (n = 35,997) included with a fall in 2013 and followed 1 year. METHODS: Health care spending indicators (dynamical indicators of resilience, DIORs) 2 years before admission were evaluated as potential predictors, along with age, sex and other clinical and sociodemographic covariates. Multivariable logistic regression models were developed and internally validated (10-fold cross-validation). Performance was assessed via discrimination (area under the receiver operating characteristic curve, AUC), Brier scores, calibration and decision curve analysis. RESULTS: The AUC of age and sex for mortality was 72.5% [95% confidence interval 71.8 to 73.2]. The best model included age, sex, number of medications and health care spending DIORs. It exhibited high discrimination (AUC: 81.1 [80.5 to 81.6]), good calibration and potential clinical benefit for various threshold probabilities. Overall, health care spending patterns improved predictive accuracy the most while also exhibiting superior performance and clinical benefit. CONCLUSIONS: Patterns of health care spending have the potential to significantly improve assessments on who is at high risk of dying following admission to the ED with a fall. The proposed methodology can assist in predicting the prognosis of fallers, emphasising the added predictive value of longitudinal health-related information next to clinical and sociodemographic predictors.

Long-term Air Pollution Exposure and Pneumonia-related Mortality in a Large Pooled European Cohort.

Rationale: Ambient air pollution exposure has been linked to mortality from chronic cardiorespiratory diseases, while evidence on respiratory infections remains more limited. Objectives: We examined the association between long-term exposure to air pollution and pneumonia-related mortality in adults in a pool of eight European cohorts. Methods: Within the multicenter project ELAPSE (Effects of Low-Level Air Pollution: A Study in Europe), we pooled data from eight cohorts among six European countries. Annual mean residential concentrations in 2010 for fine particulate matter, nitrogen dioxide (NO2), black carbon (BC), and ozone were estimated using Europe-wide hybrid land-use regression models. We applied stratified Cox proportional hazard models to investigate the associations between air pollution and pneumonia, influenza, and acute lower respiratory infections (ALRI) mortality. Measurements and Main Results: Of 325,367 participants, 712 died from pneumonia and influenza combined, 682 from pneumonia, and 695 from ALRI during a mean follow-up of 19.5 years. NO2 and BC were associated with 10-12% increases in pneumonia and influenza combined mortality, but 95% confidence intervals included unity (hazard ratios, 1.12 [0.99-1.26] per 10 µg/m3 for NO2; 1.10 [0.97-1.24] per 0.5 10-5m-1 for BC). Associations with pneumonia and ALRI mortality were almost identical. We detected effect modification suggesting stronger associations with NO2 or BC in overweight, employed, or currently smoking participants compared with normal weight, unemployed, or nonsmoking participants. Conclusions: Long-term exposure to combustion-related air pollutants NO2 and BC may be associated with mortality from lower respiratory infections, but larger studies are needed to estimate these associations more precisely.

Temporal trends in cause-specific mortality in a rural-provincial area of Denmark, Lolland-Falster, 1970-2018.

AIM: In Denmark, rural-provincial Lolland-Falster currently has the highest mortality, caused mainly by the high mortality of in-migrating people. To identify possible preventive measures to combat this excess mortality insight into the underlying diseases is needed. METHODS: We used data from Danish registers to calculate cause-specific mortality for 1970-1979, 1980-1989, 1990-1999, 2000-2009 and 2010-2018 divided into cancer, cardiovascular diseases, respiratory diseases, external causes and other causes (all remaining causes). We calculated age-standardised mortality rates for Lolland-Falster and the rest of Denmark: mortality rate ratios and excess number of deaths per 100,000 person-years for Lolland-Falster distinguishing between long-term residents (10+ years) and in-migrants. RESULTS: In 1970-1979, the age-standardised mortality rates for Lolland-Falster resembled those for rest of Denmark. Over time, age-standardised mortality rates for cardiovascular diseases decreased but more so for the rest of Denmark than for Lolland-Falster. Age-standardised mortality rates for other diseases increased but more so for Lolland-Falster than for the rest of Denmark. The excess mortality in Lolland-Falster derived in particular from in-migrants: in 2010-2018 the mortality rate ratios for this population reached 2.29 (95% confidence interval 1.96-2.69) for external causes and 2.12 (95% confidence interval 1.97-2.29) for other diseases. In-migrants had in total 411 excess deaths per 100,000 person-years. Of these 27% came from tobacco smoking-related causes of death. However, another 25% came from ill-defined, unspecified and a broad range of other, minor causes of deaths. CONCLUSIONS: The excess mortality of in-migrants to Lolland-Falster was attributable to all main causes of deaths, which stresses the complexity in combatting geographical disparities in mortality.

Development of geographic inequality in dental caries and its association with socioeconomic factors over an 18-year period in Denmark.

BACKGROUND: Few studies have examined the development of geographic and socioeconomic inequalities in caries over time or have simultaneously assessed individual-level socioeconomic position (SEP) and neighborhood-level factors as a multi-layered phenomenon influencing caries inequalities. This study examined (i) the trends in geographic inequalities in caries among adolescents in Denmark and (ii) how the association between SEP and caries has progressed over time, when accounting for individual and neighborhood-level confounding factors. METHODS: This nationwide repeated cross-sectional study included 15-year-olds in Denmark from 1995, 2003, and 2013 (n = 149,808). The outcome was caries experience (measured by the decayed, missing, and filled tooth surfaces [DMFS] index). The exposure of interest was SEP, indicated by the previous year's parental education, occupational social class, and (equivalized) disposable household income. Covariates included individual-level factors (immigration status, country of origin, number of children and persons in the family, and household type) and neighborhood (residence municipality)-level factors (Gini index; proportion of unemployed, low-educated, and unmarried/non-cohabiting individuals; proportion of single-parent households and households with overcrowding). Data sources included the Danish national dental and administrative social registers and Statistics Denmark's statistics database (StatBank). Data were analyzed using spatial and spatiotemporal modelling utilizing zero-inflated negative binomial regressions and integrated nested Laplace approximations for Bayesian parametric inference. Observed caries experience geo-maps of the Danish municipalities for 1995, 2003, and 2013 were created. RESULTS: Between 1995 and 2013, caries prevalence in the 15-year-olds declined sharply (1995, 71%; 2013, 45%). Caries experience declined in nearly all socioeconomic subgroups and municipalities. However, geographic inequalities persisted with higher caries levels largely concentrated in the relatively deprived areas of Denmark. Increasing relative socioeconomic inequalities in caries over time were observed with significant graded associations between SEP and caries despite adjustment for the various individual and neighborhood-level covariates and the effect of assessment year (e.g., 15-year-olds with parents having basic education had 1.91-fold [95% CI: 1.86-1.95] higher caries experience than those having parents with high education). CONCLUSIONS: Reducing these enduring inequalities will likely require additional resources and targeted supportive and preventive measures for adolescents from lower SEP backgrounds and those residing in municipalities with higher caries prevalence.

Preterm birth after the introduction of COVID-19 mitigation measures in Norway, Sweden, and Denmark: a registry-based difference-in-differences study.

BACKGROUND: Although some studies have reported a decrease in preterm birth following the start of the COVID-19 pandemic, the findings are inconsistent. OBJECTIVE: This study aimed to compare the incidences of preterm birth before and after the introduction of COVID-19 mitigation measures in Scandinavian countries using robust population-based registry data. STUDY DESIGN: This was a registry-based difference-in-differences study using births from January 2014 through December 2020 in Norway, Sweden, and Denmark. The changes in the preterm birth (<37 weeks) rates before and after the introduction of COVID-19 mitigation measures (set to March 12, 2020) were compared with the changes in preterm birth before and after March 12 from 2014 to 2019. The differences per 1000 births were calculated for 2-, 4-, 8-, 12-, and 16-week intervals before and after March 12. The secondary analyses included medically indicated preterm birth, spontaneous preterm birth, and very preterm (<32 weeks) birth. RESULTS: A total of 1,519,521 births were included in this study. During the study period, 5.6% of the births were preterm in Norway and Sweden, and 5.7% were preterm in Denmark. There was a seasonal variation in the incidence of preterm birth, with the highest incidence during winter. In all the 3 countries, there was a slight overall decline in preterm births from 2014 to 2020. There was no consistent evidence of a change in the preterm birth rates following the introduction of COVID-19 mitigation measures, with difference-in-differences estimates ranging from 3.7 per 1000 births (95% confidence interval, -3.8 to 11.1) for the first 2 weeks after March 12, 2020, to -1.8 per 1000 births (95% confidence interval, -4.6 to 1.1) in the 16 weeks after March 12, 2020. Similarly, there was no evidence of an impact on medically indicated preterm birth, spontaneous preterm birth, or very preterm birth. CONCLUSION: Using high-quality national data on births in 3 Scandinavian countries, each of which implemented different approaches to address the pandemic, there was no evidence of a decline in preterm births following the introduction of COVID-19 mitigation measures.

Stringency of COVID-19 Containment Response Policies and Air Quality Changes: A Global Analysis across 1851 Cities.

The COVID-19 containment response policies (CRPs) had a major impact on air quality (AQ). These CRPs have been time-varying and location-specific. So far, despite having numerous studies on the effect of COVID-19 lockdown on AQ, a knowledge gap remains on the association between stringency of CRPs and AQ changes across the world, regions, nations, and cities. Here, we show that globally across 1851 cities (each more than 300 000 people) in 149 countries, after controlling for the impacts of relevant covariates (e.g., meteorology), Sentinel-5P satellite-observed nitrogen dioxide (NO2) levels decreased by 4.9% (95% CI: 2.2, 7.6%) during lockdowns following stringent CRPs compared to pre-CRPs. The NO2 levels did not change significantly during moderate CRPs and even increased during mild CRPs by 2.3% (95% CI: 0.7, 4.0%), which was 6.8% (95% CI: 2.0, 12.0%) across Europe and Central Asia, possibly due to population avoidance of public transportation in favor of private transportation. Among 1768 cities implementing stringent CRPs, we observed the most NO2 reduction in more populated and polluted cities. Our results demonstrate that AQ improved when and where stringent COVID-19 CRPs were implemented, changed less under moderate CRPs, and even deteriorated under mild CRPs. These changes were location-, region-, and CRP-specific.

The plasticity of late-onset dementia: A nationwide cohort study in Denmark.

INTRODUCTION: The determinants of the secular decline in the incidence of dementia are not clear. The aim of this study was to investigate the influences of four factors-education, wealth, cerebrovascular health, and general health-on the secular decline. METHODS: A cohort study was conducted of all individuals aged ≥65 years in Denmark from 2005 through 2018 (N = 1,757,168). Annual incidence rates of dementia and population attributable risks of the four factors were calculated and birth cohort trends were examined. RESULTS: The incidence of dementia declined by 22.5% in men and 34.2% in women from 2005 through 2018. Population attributable risks of lower education, lower wealth, and stroke likewise declined. Independent of these improvements, the incidence of dementia fell across successive birth cohorts. DISCUSSION: Most of the observed plasticity in late-onset dementia is associated with a risk decline across successive birth cohorts that is independent of improvements in traditional risk factors.

Associations of Cytomegalovirus Infection With All-Cause and Cardiovascular Mortality in Multiple Observational Cohort Studies of Older Adults.

BACKGROUND: Whether latent cytomegalovirus (CMV) infection in older adults has any substantial health consequences is unclear. Here, we sought associations between CMV-seropositivity and IgG titer with all-cause and cardiovascular mortality in 5 longitudinal cohorts. METHODS: Leiden Longevity Study, Prospective Study of Pravastatin in the Elderly at Risk, Longitudinal Study of Aging Danish Twins, and Leiden 85-plus Study were assessed at median (2.8-11.4 years) follow-up . Cox regression and random effects meta-analysis were used to estimate mortality risk dependent on CMV serostatus and/or IgG antibody titer, in quartiles after adjusting for confounders. RESULTS: CMV-seropositivity was seen in 47%-79% of 10 122 white community-dwelling adults aged 59-93 years. Of these, 3519 had died on follow-up (579 from cardiovascular disease). CMV seropositivity was not associated with all-cause (hazard ratio [HR], 1.05; 95% confidence interval [CI], .97-1.14) or cardiovascular mortality (HR, 0.97; 95% CI, .83-1.13). Subjects in the highest CMV IgG quartile group had increased all-cause mortality relative to CMV-seronegatives (HR, 1.16; 95% CI, 1.04-1.29) but this association lost significance after adjustment for confounders (HR, 1.13; 95% CI, .99-1.29). The lack of increased mortality risk was confirmed in subanalyses. CONCLUSIONS: CMV infection is not associated with all-cause or cardiovascular mortality in white community-dwelling older adults.

Long-term air pollution and road traffic noise exposure and COPD: the Danish Nurse Cohort.

BACKGROUND: While air pollution has been linked to the development of chronic obstructive pulmonary disease (COPD), evidence on the role of environmental noise is just emerging. We examined the associations of long-term exposure to air pollution and road traffic noise with COPD incidence. METHODS: We defined COPD incidence for 24 538 female nurses from the Danish Nurse Cohort (age >44 years) as the first hospital contact between baseline (1993 or 1999) and 2015. We estimated residential annual mean concentrations of particulate matter with an aerodynamic diameter <2.5 µm (PM2.5) since 1990 and nitrogen dioxide (NO2) since 1970 using the Danish Eulerian Hemispheric Model/Urban Background Model/Air Geographic Information System modelling system, and road traffic noise (Lden) since 1970 using the Nord2000 model. Time-varying Cox regression models were applied to assess the associations of air pollution and road traffic noise with COPD incidence. RESULTS: 977 nurses developed COPD during a mean of 18.6 years' follow-up. We observed associations with COPD for all three exposures with HRs and 95% CIs of 1.19 (1.01-1.41) per 6.26 µg·m-3 for PM2.5, 1.13 (1.05-1.20) per 8.19 µg·m-3 for NO2 and 1.15 (1.06-1.25) per 10 dB for Lden. Associations with NO2 and Lden attenuated slightly after mutual adjustment, but were robust to adjustment for PM2.5. Associations with PM2.5 were attenuated to null after adjustment for either NO2 or Lden. No potential interaction effect was observed between air pollutants and noise. CONCLUSION: Long-term exposure to air pollution, especially traffic-related NO2, and to road traffic noise were independently associated with COPD.

Differential effects of colorectal cancer screening across sociodemographic groups in Denmark: a register-based study.

INTRODUCTION: Colorectal cancer (CRC) does not affect different sociodemographic groups uniformly. CRC screening programmes could seek to reduce this inequality; however, the screening programmes themselves might be subject to differential participation across sociodemographic groups. This study investigates the sociodemographic inequality at all steps in Denmark's nationwide CRC screening programme: screening participation, faecal immunochemical test (FIT) results, colonoscopy compliance, CRC diagnosis, and cancer stage. MATERIAL AND METHODS: This cohort study includes all first-time invitees from the beginning of the Danish population-based CRC screening programme from 1 March 2014 to 31 December 2017. RESULTS: Sixty-four percent of the invitees participated in the screening programme, and of those 7% were FIT-positive. After being invited to further diagnostic procedures, 90% responded to the invitation, and among those 5% were CRC-positive. Among those diagnosed with CRC, 9% were stage IV. Through multivariable analyses, we identified sociodemographic inequalities in all steps of the screening programme from returning a stool sample to being diagnosed with CRC. Specifically, we identified inequalities across sex, age, migration status, relationship status, the screening status of one's partner, education, income, and use of health services. Women were more likely to participate compared to men (RR = 1.13; 95% CI: 1.12-1.13), but had a lower risk of a positive FIT result (RR = 0.67; 95% CI: 0.66-0.68) and of a CRC diagnosis (RR = 0.88; 95% CI: 0.82-0.93) compared to men. The likelihood of participating as well as the risk of positive FIT results and CRC diagnosis increased with age. CONCLUSION: All steps of the screening programme were subject to sociodemographic inequalities. Interventions are needed to target groups identified as having lower uptake as well as high-risk of being FIT- and/or CRC-positive. These groups include males, individuals aged 60+ years and individuals who do not visit their GP regularly.

Outdoor light at night and breast cancer incidence in the Danish Nurse Cohort.

BACKGROUND: Knowledge of the role of melatonin, xenograft experiments, and epidemiological studies suggests that exposure to light at night (LAN) may disturb circadian rhythms, possibly increasing the risk of developing breast cancer. OBJECTIVES: We examined the association between residential outdoor LAN and the incidence of breast cancer: overall and subtypes classified by estrogen (ER) and progesterone (PR) receptor status. METHODS: We used data on 16,941 nurses from the Danish Nurse Cohort who were followed-up from the cohort baseline in 1993 or 1999 through 2012 in the Danish Cancer Registry for breast cancer incidence and the Danish Breast Cancer Cooperative Group for breast cancer ER and PR status. LAN exposure data were obtained from the U.S. Defense Meteorological Satellite Program (DMSP) available for 1996, 1999, 2000, 2003, 2004, 2006, and 2010 in nW/cm2/sr unit, and assigned to the study participants' residence addresses during the follow-up. Time-varying Cox regression models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between LAN and breast cancer, adjusting for individual characteristics, road traffic noise, and air pollution. RESULTS: Of 16,941 nurses, 745 developed breast cancer in total during 320,289 person-years of follow-up. We found no association between exposure to LAN and overall breast cancer. In the fully adjusted models, HRs for the highest (65.8-446.4 nW/cm2/sr) and medium (22.0-65.7 nW/cm2/sr) LAN tertiles were 0.97 (95% CI: 0.77, 1.23) and 1.09 (95% CI: 0.90, 1.31), respectively, compared to the lowest tertile of LAN exposure (0-21.9 nW/cm2/sr). We found a suggestive association between LAN and ER-breast cancer. CONCLUSION: This large cohort study of Danish female nurses suggests weak evidence of the association between LAN and breast cancer incidence.

Long-term exposure to road traffic noise and stroke incidence: a Danish Nurse Cohort study.

BACKGROUND: Road traffic noise has been linked to increased risk of ischemic heart disease, yet evidence on stroke shows mixed results. We examine the association between long-term exposure to road traffic noise and incidence of stroke, overall and by subtype (ischemic or hemorrhagic), after adjustment for air pollution. METHODS: Twenty-five thousand six hundred and sixty female nurses from the Danish Nurse Cohort recruited in 1993 or 1999 were followed for stroke-related first-ever hospital contact until December 31st, 2014. Full residential address histories since 1970 were obtained and annual means of road traffic noise (Lden [dB]) and air pollutants (particulate matter with diameter < 2.5 µm and < 10 µm [PM2.5 and PM10], nitrogen dioxide [NO2], nitrogen oxides [NOx]) were determined using validated models. Time-varying Cox regression models were used to estimate hazard ratios (HR) (95% confidence intervals [CI]) for the associations of one-, three-, and 23-year running means of Lden preceding stroke (all, ischemic or hemorrhagic), adjusting for stroke risk factors and air pollutants. The World Health Organization and the Danish government's maximum exposure recommendations of 53 and 58 dB, respectively, were explored as potential Lden thresholds. RESULTS: Of 25,660 nurses, 1237 developed their first stroke (1089 ischemic, 148 hemorrhagic) during 16 years mean follow-up. For associations between a 1-year mean of Lden and overall stroke incidence, the estimated HR (95% CI) in the fully adjusted model was 1.06 (0.98-1.14) per 10 dB, which attenuated to 1.01 (0.93-1.09) and 1.00 (0.91-1.09) in models further adjusted for PM2.5 or NO2, respectively. Associations for other exposure periods or separately for ischemic or hemorrhagic stroke were similar. There was no evidence of a threshold association between Lden and stroke. CONCLUSIONS: Long-term exposure to road traffic noise was suggestively positively associated with the risk of overall stroke, although not after adjusting for air pollution.

Do we know the effects of colorectal cancer screening? A short communication on selective uptake and differential effects of colorectal cancer screening in Scandinavia.

Colorectal cancer (CRC) contributes extensively to the overall cancer burden, with substantial and increasing social inequality in both incidence and survival. In several countries, this social inequality in incidence and survival has been increasing over time, and the increase is expected to continue. To overcome this, it is advised to implement nationwide CRC screening programmes, as these are effective in detecting possible signs of CRC, hence identifying earlier-stage cancer and reducing mortality. However, little is known about the distribution of these effects across population groups. It is possible that the outcomes of CRC screening are not equally distributed among participants, but rather that the screening programme serves some population groups better than others. The aim of this short communication based on published data is to describe the status of selective uptake according to sociodemographic and economic factors in CRC screening in Scandinavia. Furthermore, we raise questions that need to be addressed in future research in order to grasp the full effects of the screening programme and ultimately to ensure high uptake as well as participation in subsequent diagnostic procedures across population groups.

Parental education and the risk of cerebral palsy for children: an evaluation of causality.

AIM: To explore whether increasing parental education has a causal effect on risk of cerebral palsy (CP) in the child, or whether unobserved confounding is a more likely explanation. METHOD: We used data from Norwegian registries on approximately 1.5 million children born between 1967 and 2011. We compared results from a traditional cohort design with results from a family-based matched case-control design, in which children with CP were matched to their first cousins without CP. In addition, we performed a simulation study to assess the role of unobserved confounding. RESULTS: In the cohort design, the odds of CP were reduced in children of mothers and fathers with higher education (adjusted odds ratio [OR] 0.67, 95% confidence interval [CI] 0.60-0.75 for maternal education, and adjusted OR 0.75, 95% CI 0.67-0.85 for paternal education). In the family-based case-control design, only an association for maternal education remained (adjusted OR 0.80, 95% CI 0.64-0.99). Results from a simulation study suggested that this association could be explained by unobserved confounding. INTERPRETATION: A causal effect of obtaining higher education on risk of CP in the child is unlikely. Results stress the importance of continued research on the role of genetic and environmental risk factors that vary by parents' educational level. WHAT THIS PAPER ADDS: Children of higher-educated parents had significantly lower odds of cerebral palsy (CP). There was no evidence of difference in risk of CP within first cousins whose mothers or fathers had different educational levels. Association between parental education and odds of CP did not reflect a causal effect.