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.

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.

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.

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.

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.

Sex of the first-born and obstetric complications in the subsequent birth. A study of 2.3 million second births from Denmark, Finland, Norway, and Sweden.

INTRODUCTION: Studies have shown associations between a first-born boy and increased risks of pregnancy loss, stillbirth, decreased birthweight, and preterm birth in subsequent pregnancies, but with limited precision. MATERIAL AND METHODS: We examined associations between sex of the first-born and obstetric complications in second births. We calculated the relative risks (RR)s of preeclampsia/eclampsia, placental abruption, stillbirth, and preterm birth in approximately 2.3 million second births comparing women with a preceding first-born boy to those with a first-born girl using the Medical Birth Registries of Denmark, Finland, Norway, and Sweden 1980-2008. RESULTS: In second births following a first-born boy rather than a girl, the RR was 4% higher for preeclampsia/eclampsia (RR = 1.04, 95% CI 1.02-1.06), 9% higher for placental abruption (RR = 1.09, 95% CI 1.05-1.13), 9% higher for stillbirth (RR = 1.09, 95% CI 1.04-1.14), and 8% higher for preterm birth (RR = 1.08, 95% CI 1.07-1.09). The population attributable risks ranged from 2% to 4.5%. CONCLUSIONS: Male sex of the first-born is associated with small increases in risks of obstetric complications in the second birth. Exploration of the underlying mechanisms is needed to increase our knowledge and treatment options for these serious obstetric complications.

The stillbirth sex ratio as a marker of population health among live-born males in Denmark, 1835-1923.

OBJECTIVES: We know little about whether an elevated stillbirth sex ratio (ratio of male to female stillbirths) gauges stronger selection in utero against frail male gestations and therefore predicts greater male infant survival. An alternative scenario could involve a "low endowment" case in which pregnancy cohorts show both excess male stillbirths and elevated mortality risk among male live births. We exploit the longest sex-specific stillbirth series (Denmark, 1835-1923) to explore whether annual deviations in age-specific male mortality vary with the annual cohort's stillbirth sex ratio. METHODS: We applied autoregressive, integrated, moving average time series methods to annual counts of age-specific male mortality in Denmark. We derived the independent variable, the stillbirth sex ratio, from only late stillbirths (ie, 28th week and thereafter) owing to data availability. Methods control for secular patterns as well as shared antecedents of male and female mortality. RESULTS: Cohort male infant mortality varies positively with the stillbirth sex ratio (coef = 0.0081, standard error [SE] = 0.0019, P < 0.001). This positive relation persists into childhood (ie, ages 1-4.99 years) but attenuates with age. DISCUSSION: We infer support for the "low endowment" argument in that high stillbirth sex ratios predict a relatively greater risk of mortality among males which ultimately survive to birth. These findings provide evidence that the stillbirth sex ratio may serve as a marker of population health among male cohorts.

Social and demographic drivers of trend and seasonality in elective abortions in Denmark.

BACKGROUND: Elective abortions show a secular decline in high income countries. That general pattern, however, may mask meaningful differences-and a potentially rising trend-among age, income, and other racial/ethnic groups. We explore these differences in Denmark, a high-income, low-fertility country with excellent data on terminations and births. METHODS: We examined monthly elective abortions (n = 225,287) from 1995 to 2009, by maternal age, parity, income level and mother's country of origin. We applied time-series methods to live births as well as spontaneous and elective abortions to approximate the denominator of pregnancies at risk of elective abortion. We used linear regression methods to identify trend and seasonal patterns. RESULTS: Despite an overall declining trend, teenage women show a rising proportion of pregnancies that end in an elective termination (56% to 67%, 1995 to 2009). Non-Western immigrant women also show a slight increase in incidence. Heightened economic disadvantage among non-Western immigrant women does not account for this rise. Elective abortions also show a sustained "summer peak" in June, July and August. Low-income women show the most pronounced summer peak. CONCLUSIONS: Identification of the causes of the increase over time in elective abortion among young women, and separately among non-Western immigrant women, represents key areas of further inquiry. The unexpected increase over time in elective abortions among teens and non-Western immigrants in Denmark may signal important social and cultural impediments to contraception. The summer peak in abortions among low-income women, moreover, conflicts with the conventional assumption that the social and demographic composition of mothers who electively end their pregnancy remains stable within a calendar year.

Spontaneous Pregnancy Loss in Denmark Following Economic Downturns.

An estimated 11%-20% of clinically recognized pregnancies result in spontaneous abortion. The literature finds elevated risk of spontaneous abortion among women who report adverse financial life events. This work suggests that, at the population level, national economic decline-an ambient and plausibly unexpected stressor-will precede an increase in spontaneous abortion. We tested this hypothesis using high-quality information on pregnancy and spontaneous loss for all women in Denmark. We applied time-series methods to monthly counts of clinically detected spontaneous abortions (n = 157,449) and the unemployment rate in Denmark beginning in January 1995 and ending in December 2009. Our statistical methods controlled for temporal patterns in spontaneous abortion (e.g., seasonality, trend) and changes in the population of pregnancies at risk of loss. Unexpected increases in the unemployment rate preceded by 1 month a rise in the number of spontaneous abortions (ß = 33.19 losses/month, 95% confidence interval: 8.71, 57.67). An attendant analysis that used consumption of durable household goods as an indicator of financial insecurity supported the inference from our main test. Changes over time in elective abortions and in the cohort composition of high-risk pregnancies did not account for results. It appears that in Denmark, ambient stressors as common as increasing unemployment may precede a population-level increase in spontaneous abortion.

Shared risk aversion in spontaneous and induced abortion.

STUDY QUESTION: Does the incidence of spontaneous abortion correlate positively over conception cohorts with the incidence of non-clinically indicated induced abortion as predicted by shared risk aversion? SUMMARY ANSWER: We find that the number of spontaneous and non-clinically indicated induced abortions correlates in conception cohorts, suggesting that risk aversion affects both the conscious and non-conscious mechanisms that control parturition. WHAT IS KNOWN ALREADY: Much literature speculates that natural selection conserved risk aversion because the trait enhanced Darwinian fitness. Risk aversion, moreover, supposedly influences all decisions including those that individuals can and cannot report making. We argue that these circumstances, if real, would manifest in conscious and non-conscious decisions to invest in prospective offspring, and therefore affect incidence of induced and spontaneous abortion over time. STUDY DESIGN, SIZE, DURATION: Using data from Denmark, we test the hypothesis that monthly conception cohorts yielding unexpectedly many non-clinically indicated induced abortions also yield unexpectedly many spontaneous abortions. The 180 month test period (January 1995 through December 2009), yielded 1 351 800 gestations including 156 780 spontaneous as well as 233 280 induced abortions 9100 of which were clinically indicated. PARTICIPANTS/MATERIALS, SETTING, METHODS: We use Box-Jenkins transfer functions to adjust the incidence of spontaneous and non-clinically indicated induced abortions for autocorrelation (including seasonality), cohort size, and fetal as well as gestational anomalies over the 180-month test period. We use cross-correlation to test our hypothesized association. MAIN RESULTS AND THE ROLE OF CHANCE: We find a positive association between spontaneous and non-clinically indicated induced abortions. This suggests, consistent with our theory, that mothers of conception cohorts that yielded more spontaneous abortions than expected opted more frequently than expected for non-clinically indicated induced abortion. LIMITATIONS, REASONS FOR CAUTION: Limitations of our work include that even the world's best registration system will not capture all spontaneous abortions and that results may not generalize beyond Denmark. WIDER IMPLICATIONS OF THE FINDINGS: Our findings imply that abortion, intentional or 'spontaneous,' follows from a woman's estimate, made consciously or otherwise, of the costs and benefits of extending gestation given characteristics of the prospective offspring, likely environmental circumstances at birth, and maternal resources. STUDY FUNDING/COMPETING INTERESTS: The Robert Wood Johnson Health and Society Scholars Program funded the research described in this manuscript. None of the authors has any conflict of interest to declare.

Differences in perinatal and infant mortality in high-income countries: artifacts of birth registration or evidence of true differences?

BACKGROUND: Variation in birth registration criteria may compromise international comparisons of fetal and infant mortality. We examined the effect of birth registration practices on fetal and infant mortality rates to determine whether observed differences in perinatal and infant mortality rates were artifacts of birth registration or reflected true differences in health status. METHODS: A retrospective population-based cohort study was done using data from Canada, United States, Denmark, Finland, Iceland, Norway, and Sweden from 1995-2005. Main outcome measures included live births by gestational age and birth weight; gestational age-and birth weight-specific stillbirth rates; neonatal, post-neonatal, and cause-specific infant mortality. RESULTS: Proportion of live births <22 weeks varied substantially: Sweden (not reported), Iceland (0.00%), Finland (0.001%), Denmark (0.01%), Norway (0.02%), Canada (0.07%) and United States (0.08%). At 22-23 weeks, neonatal mortality rates were highest in Canada (892.2 per 1000 live births), Denmark (879.3) and Iceland (1000.0), moderately high in the United States (724.1), Finland (794.3) and Norway (739.0) and low in Sweden (561.2). Stillbirth:live birth ratios at 22-23 weeks were significantly lower in the United States (79.2 stillbirths per 100 live births) and Finland (90.8) than in Canada (112.1), Iceland (176.2) and Norway (173.9). Crude neonatal mortality rates were 83% higher in Canada and 96% higher in the United States than Finland. Neonatal mortality rates among live births ≥ 28 weeks were lower in Canada and United States compared with Finland. Post-neonatal mortality rates were higher in Canada and United States than in Nordic countries. CONCLUSIONS: Live birth frequencies and stillbirth and neonatal mortality patterns at the borderline of viability are likely due to differences in birth registration practices, although true differences in maternal, fetal and infant health cannot be ruled out. This study emphasises the need for further standardisations, in order to enhance the relevance of international comparisons of infant mortality.

Modelling the spatial risk pattern of dementia in Denmark using residential location data: A registry-based national cohort.

Dementia is a major global public health concern that is increasingly leading to morbidity and mortality among older adults. While studies have focused on the risk factors and care provision, there is currently limited knowledge about the spatial risk pattern of the disease. In this study, we employ Bayesian spatial modelling with a stochastic partial differential equation (SPDE) approach to model the spatial risk using complete residential history data from the Danish population and health registers. The study cohort consisted of 1.6 million people aged 65 years and above from 2005 to 2018. The results of the spatial risk map indicate high-risk areas in Copenhagen, southern Jutland and Funen. Individual socioeconomic factors and population density reduce the intensity of high-risk patterns across Denmark. The findings of this study call for the critical examination of the contribution of place of residence in the susceptibility of the global ageing population to dementia.

Association of Tumor Necrosis Factor-α Inhibitors with Incident Dementia: Analysis Based on Population-Based Cohort Studies.

BACKGROUND AND OBJECTIVE: Preliminary evidence suggests a possible preventive effect of tumor necrosis factor-α inhibitors (TNFi) on incident dementia. The objective of the analysis was to investigate the association between TNFi and the risk of incident dementia in a population undergoing treatment for rheumatological disorders. METHODS: We followed patients aged ≥ 65 years with dementia and rheumatological conditions in two cohort studies, DANBIO (N = 21,538), a Danish clinical database, and AOK PLUS (N = 7112), a German health insurance database. We defined incident dementia using diagnostic codes and/or medication use and used Cox regression to compare the associations of TNFi with other rheumatological therapies on the risk of dementia. To ensure that the patients were receiving long-term medication, we included patients with rheumatic diseases and systemic therapies. RESULTS: We observed similar trends towards a lower risk of dementia associated with TNFi versus other anti-inflammatory agents in both cohorts (hazard ratios were 0.92 [95% confidence interval 0.76, 1.10] in DANBIO and 0.89 [95% confidence interval 0.63, 1.24] in AOK PLUS, respectively). CONCLUSIONS: Tumor necrosis factor-α inhibitors may decrease the risk of incident dementia although the association did not reach statistical significance in this analysis. Further research, ideally with randomization, is needed to gauge the potential of repurposing TNFi for dementia prevention and/or treatment.

Long-Term Exposure to Air Pollution and Risk of Acute Lower Respiratory Infections in the Danish Nurse Cohort.

RATIONALE: Air pollution is a major risk factor for chronic cardiorespiratory diseases, affecting both the immune and respiratory systems' functionality, while the epidemiological evidence on respiratory infections remains sparse. OBJECTIVE: We aimed to assess the association of long-term exposure to ambient air pollution with risk of developing new and recurrent ALRIs that characterized by persistently severe symptoms necessitating hospital contact, and identify the potential susceptible populations by socio-economic status (SES), smoking, physical activity status, overweight, and co-morbidity with chronic lung disease. METHODS: We followed 23,912 female nurses from the Danish Nurse Cohort (> 44 years) from baseline (1993 or 1999) until 2018 for the incident and recurrent ALRIs defined by hospital contact (in-, outpatient, and emergency room) data from the National Patient Register. Residential annual mean concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), and black carbon (BC) were modelled using Danish DEHM/UBM/AirGIS system. We used marginal Cox models with time-varying exposures to assess the association of 3-year running-mean air pollution with incident and recurrent ALRIs and examine effect modification by age, socio-economic status (SES), smoking, physical activity, body mass index, and comorbidity with asthma or chronic obstructive pulmonary disease (COPD). RESULTS: During a 21.3 years mean follow-up, 4,746 ALRIs were observed, of which 2,553 were incident. We observed strong positive associations of all three pollutants with incident ALRIs, with hazard ratios and 95% confidence intervals of 1.19 (1.08-1.31) per 2.5 µg/m3 for PM2.5, 1.17 (1.11-1.24) per 8.0 µg/m3 for NO2, and 1.09 (1.05-1.12) per 0.3 µg/m3 for BC, and slightly stronger associations with recurrent ALRIs. Associations were strongest in COPD patients and nurses with low physical activity. CONCLUSION: Long-term exposure to air pollution at low levels was associated with risk of new and recurrent ALRIs, with COPD patients and physically inactive subjects most vulnerable. Primary Source of Funding: This study was supported by the Novo Nordisk Foundation Challenge Programme (NNF17OC0027812).