Air pollution and myocardial infarction; effect modification by sociodemographic and environmental factors. A cohort study from Denmark.

Air pollution is associated with increased risk of myocardial infarction (MI), but it is unresolved to what extent the association is modified by factors such as socioeconomic status, comorbidities, financial stress, residential green space, or road traffic noise. We formed a cohort of all (n = 1,964,702) Danes, aged 50-85 years, with 65,311 cases of MI during the followed-up period 2005-2017. For all participants we established residential five-year running average exposure to particulate matter <2.5 µm (PM2.5), ultrafine particles (UFP, <0.1 µm), elemental carbon (EC) and nitrogen dioxide (NO2). We evaluated risk in population strata, using Aalen additive hazards models to estimate absolute risk and Cox proportional hazards models to estimate relative risk of MI with 95% confidence intervals (CI). PM2.5 and the other pollutant were associated with MI. Lower education and lower income were associated with higher absolute risks of MI from air pollution, whereas no clear effect modification was apparent for relative risk estimates. For example, 5 µg/m3 higher PM2.5 was associated with HR for MI of 1.16 (95% CI: 1.10-1.22) among those with only mandatory education and 1.13 (95% CI: 1.03-1.24) among those with long education. The corresponding rate differences per 100,000 person years were 243 (95% CI: 216-271) and 358 (95% CI: 338-379), respectively. Higher level of comorbidity was consistently across all four pollutants associated with both higher absolute and relative risk of MI. In conclusion, people with comorbid conditions or of lower SES appeared more vulnerable to long-term exposure to air pollution and more cases of MI may be prevented by focused interventions in these groups.

Effects of Sociodemographic Characteristics, Comorbidity, and Coexposures on the Association between Air Pollution and Type 2 Diabetes: A Nationwide Cohort Study.

BACKGROUND: Exposure to air pollution has been associated with a higher risk of type 2 diabetes (T2D), but studies investigating whether deprived groups are more susceptible to the harmful effects of air pollution are inconsistent. OBJECTIVES: We aimed to investigate whether the association between air pollution and T2D differed according to sociodemographic characteristics, comorbidity, and coexposures. METHODS: We estimated residential exposure to PM2.5, ultrafine particles (UFP), elemental carbon, and NO2 for all persons living in Denmark in the period 2005-2017. In total, 1.8 million persons 50-80 y of age were included for main analyses of whom 113,985 developed T2D during follow-up. We conducted additional analyses on 1.3 million persons age 35-50 y. Using Cox proportional hazards model (relative risk) and Aalens additive hazard model (absolute risk), we calculated associations between 5-y time-weighted running means of air pollution and T2D in strata of sociodemographic variables, comorbidity, population density, road traffic noise, and green space proximity. RESULTS: Air pollution was associated with T2D, especially among people age 50-80 y, with hazard ratios of 1.17 [95% confidence interval (CI): 1.13, 1.21] per 5 µg/m3 PM2.5 and 1.16 (95% CI: 1.13, 1.19) per 10,000 UFP/cm3. In the age 50-80 y population, we found higher associations between air pollution and T2D among men in comparison with women, people with lower education vs. individuals with high education, people with medium income vs. those with low or high income, people cohabiting vs. those living alone, and people with comorbidities vs. those without comorbidities. We observed no marked changes according to occupation, population density, road noise, or surrounding greenness. In the age 35-50 y population, similar tendencies were observed, except in relation to sex and occupation, where we observed associations with air pollution only among women and blue-collar workers. DISCUSSION: We found stronger associations between air pollution and T2D among people with existing comorbidities and weaker associations among people with high socioeconomic status in comparison with those with lower socioeconomic status. https://doi.org/10.1289/EHP11347.

Cognitive-behavioural therapy reduces psychological distress in younger patients with cardiac disease: a randomized trial.

AIMS: To test whether usual outpatient cardiac rehabilitation (CR) supplemented by a cognitive-behavioural therapy (CBT) intervention may reduce anxiety and depression compared with usual CR. METHODS AND RESULTS: In this multicentre randomized controlled trial, 147 cardiac patients (67% men, mean age 54 years, 92% with coronary artery disease) with psychological distress defined as a hospital anxiety and depression scale (HADS) anxiety or depression score ≥8 were randomized to five sessions of group CBT plus usual CR (intervention, n = 74) or CR alone (control, n = 73). Patients with severe distress or a psychiatric diagnosis were excluded. The intervention was delivered by cardiac nurses with CBT training and supervised by a psychologist. A reference, non-randomized group (background, n = 41) of consecutive patients without psychological distress receiving usual CR was included to explore the effect of time on HADS score. The primary outcome, total HADS score after 3 months, improved more in the intervention than in the control group [the mean total HADS score improved by 8.0 (standard deviation 5.6) vs. 4.1 (standard deviation 7.8), P < 0.001]. Significant between-group differences were maintained after 6 months. Compared with the control group, the intervention group also had greater adherence to CR (P = 0.003), more improvement in the heart-related quality of life (HeartQoL) at 6 months (P < 0.01), and a significant reduction in cardiac readmissions at 12 months (P < 0.01). The background group had no significant change in HADS score over time. CONCLUSION: Brief CBT provided by cardiac nurses in relation to CR reduced anxiety and depression scores, improved HeartQoL and adherence to CR, and reduced cardiovascular readmissions. The programme is simple and may be implemented by CR nurses.

Intensive group-based cognitive therapy in patients with cardiac disease and psychological distress-a randomized controlled trial protocol.

BACKGROUND: Many patients with coronary artery disease (CAD) and valvular heart disease (VHD) suffer from psychological distress. Such stress is associated with increased morbidity, reduced quality of life and delayed return to work. European guidelines emphasize recognition and intervention, but evidence-based treatment options are limited and perceived as costly. The present study will test the effect of brief, group-based cognitive therapy as an adjunct to usual cardiac rehabilitation in a randomized design. METHODS: A total of 148 patients with CAD and/or VHD after surgical intervention and concomitant psychological distress (defined as HADS anxiety (A) or depression (D) score ≥8) will be randomized to either usual out-patient cardiac rehabilitation (CR) comprising an 8-week multidisciplinary programme or usual care supplemented by five group-based cognitive therapy sessions performed by trained CR nurses. A structured, standardized treatment manual will be used. Patients will be randomized 1:1 at three different sites. Additionally, a non-randomized sub-group of 40 matched patients without signs of psychological distress will be followed to investigate spontaneous variation in HADS. The primary outcome is Hospital Anxiety and Depression Score (HADS). Secondary outcomes are adherence to cardiac rehabilitation (CR), health-related quality of life measured by HeartQoL, time to return to work, adherence to lifestyle interventions and cardiovascular readmissions. Patients are followed up for 12 months. DISCUSSION: To our knowledge, this is the first randomized controlled trial (RCT) on patients with cardiac disease with an intensive group-based programme of cognitive therapy performed by CR nurses, which makes it affordable and widely implementable. The outcome will elucidate the feasibility and effect of cognitive therapy as an adjunct to CR in patients with post-surgery CAD and/or VHD and psychological distress and could possibly benefit patients with other heart conditions as well. The clinical trial complies with the Declaration of Helsinki. The trial has been approved by The Regional Research Ethics Committee (file number H-16042832) and The Danish Data Protection Agency. The results will be disseminated as original research in peer-reviewed manuscripts. TRIAL REGISTRATION: www.clinicaltrials.gov NCT04254315 . Retrospectively registered on 30 January 2020.

Occupational and recreational physical activity and Parkinson's disease in Denmark.

Objectives This study aimed to examine whether occupational and physical activity (PA) at different ages contribute to Parkinson's disease (PD) risk in a large population-based case-control study in Denmark. Methods We identified 1828 PD patients from the Danish National Hospital Register and recruited 1909 gender and year of birth matched controls from the Danish Central Population Register. Occupational and leisure-time PA were determined from a job exposure matrix based on occupational history and self-reported leisure-time information. Results No association was found for occupational PA alone in men, but higher leisure-time PA (≥5 hours/week of strenuous activities) in young adulthood (15-25 years) was associated with a lower PD risk (adjusted odds ratio (OR adj) 0.75, 95% confidence interval (95% CI) 0.62-0.90); men who engaged in high occupational and high leisure-time PA in young adulthood had the lowest PD risk (OR adj0.58, 95% CI 0.41-0.81). Among women, inverse associations were found for occupation PA before age 50 (highest vs lowest, OR adj0.75, 95% CI 0.55-1.06) and strenuous leisure-time PA after age 50 (OR adj0.65, 95% CI 0.87-0.99); no clear pattern was seen for leisure and occupational PA combined. Conclusions We observed gender-specific inverse associations between occupational and leisure-time PA and PD risk; however, we cannot preclude reverse causation especially in older ages since PD has a long prodromal stage that might lead to a reduction of PA years before motor symptom onset and PD diagnosis.

Clinical Features in a Danish Population-Based Cohort of Probable Multiple System Atrophy Patients.

BACKGROUND: Multiple system atrophy (MSA) is a rare, sporadic and progressive neurodegenerative disorder. We aimed to describe the clinical features of Danish probable MSA patients, evaluate their initial response to dopaminergic therapy and examine mortality. METHODS: From the Danish National Patient Registry, we identified 782 patients diagnosed with conditions potentially compatible with probable MSA (International Classification of Diseases, version 10 (ICD-10) codes G23.2, G23.8 and G23.9) during 1994-2009. Through medical record review, we narrowed our sample to 115 patients who fulfilled the criteria for probable MSA. We recorded clinical features, examined differences by MSA subtype and used Kaplan-Meier survival analysis to examine mortality. RESULTS: The mean age at onset of patients with probable MSA was 60.2 years (range 36-75 years) and mean time to wheelchair dependency was 4.7 years (range 0-15 years). One-third of patients experienced a transient improvement in motor symptoms with use of levodopa. Median survival from disease onset was 6.9 years (range 1-16 years, 95% CI 6.3-7.5) with no apparent variation according to gender or subtype. CONCLUSIONS: Our nationwide approach corroborated that MSA is associated with diverse and grave symptoms, only limited response to levodopa, and poor prognosis.

Traffic-Related Air Pollution and Parkinson's Disease in Denmark: A Case-Control Study.

BACKGROUND: Very little is currently known about air pollutants' adverse effects on neurodegenerative diseases even though recent studies have linked particulate exposures to brain pathologies associated with Parkinson's and Alzheimer's disease. OBJECTIVE: In the present study, we investigated long-term exposure to traffic-related air pollution and Parkinson's disease. METHODS: In a case-control study of 1,696 Parkinson's disease (PD) patients identified from Danish hospital registries and diagnosed 1996-2009 and 1,800 population controls matched by sex and year of birth, we assessed long-term traffic-related air pollutant exposures (represented by nitrogen dioxide; NO2) from a dispersion model, using residential addresses from 1971 to the date of diagnosis or first cardinal symptom for cases and the corresponding index date for their matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with logistic regression, adjusting for matching factors and potential confounders. RESULTS: We found ambient air pollution from traffic sources to be associated with risk of PD, with a 9% higher risk (95% CI: 3, 16.0%) per interquartile range increase (2.97 µg/m(3)) in modeled NO2. For participants living for ≥ 20 years in the capital city, ORs were larger (OR = 1.21; 95% CI: 1.11, 1.31) than in provincial towns (OR = 1.10; 95% CI: 0.97, 1.26), whereas there was no association among rural residents. CONCLUSIONS: Our findings raise concerns about potential effects of air pollution from traffic and other sources on the risk of PD, particularly in populations with high or increasing exposures.

Dependency and transfer incomes in idiopathic Parkinson's disease.

INTRODUCTION: Idiopathic Parkinson's disease (IPD) is a progressive neurodegenerative disorder affecting approximately 1% of the population above 65 years of age. The aim of this study was to define the estimated Danish IPD population and to elucidate source of income and labour market affiliation for working-age IPD patients. MATERIAL AND METHODS: IPD cases were included through the Danish Register of Medicinal Product Statistics. The participants had to be alive by the end of 2010 and at least twice have cashed in prescriptions on IPD medication in the 2009-2010 period. Information on employment status and transfer income was retrieved through the DREAM database under the Danish Ministry of Employment. RESULTS: A total of 7,033 estimated IPD patients were identified. The mean age at time of registration (2010, week 50) was 72 years. Overall, 7% of the IPD patients were employed and 5% were self-supportive. In the working age range (18-64 years), 25% were employed and 10% enrolled in supported employment. Compared with the age-adjusted general population, twice as many IPD patients were outside the ordinary labour market and, furthermore, the proportion receiving anticipatory pension was increased threefold. The majority (89%) of the patients were living at home with a spouse (59%). 11% were nursing home residents. CONCLUSION: The working age IPD population was more prone to be outside employment and to receive public transfer income than an age-adjusted population sample. FUNDING: The study was funded by the Danish Parkinson Association. TRIAL REGISTRATION: not relevant.

The use of antidepressant medication in Parkinson's disease patients is not affected by the type of antiparkinson medication.

Previous studies have suggested that dopamine agonists have an antidepressant effect in Parkinson's disease (PD) patients. We examined whether fewer PD patients used antidepressant medication, when they were first treated with a dopamine agonist compared to other PD medications. PD patients diagnosed in Denmark were identified, and the diagnosis was confirmed by a review of the medical record. Antidepressant medication was assessed using the Danish National Prescription Registry. We used Cox proportional hazards regression to model the association between PD medications and time to antidepressant prescription. The type of PD medication first prescribed did not affect the subsequent use of antidepressants.

[Shift work and risk of cancer and coronary heart diseases]. / Skifteholdsarbejde og risiko for kræftog hjerte-kar-sygdom.

Shift and night work are among the most frequent occupational exposures. Such work schedules involve exposure to light-at-night, which may reduce normal nocturnal melatonin production, create circadian rhythm disruption, sleep deprivation and unhealthy lifestyle. There is strong experimental evidence that light-at-night and circadian disruption may increase the risk of cancer and coronary heart diseases. There is emerging, but limited epidemiologic evidence that night shift work may increase breast cancer and certain cardiovascular diseases.

Parkinson's disease and other neurodegenerative disorders among welders: a Danish cohort study.

It has been hypothesized that welders are at increased risk for neurological disorders, including Parkinson's disease, but few well-designed cohort studies have been conducted. The risk for Parkinson's disease and other neurodegenerative disorders was examined in an updated follow-up study based on a previous cohort of 5867 Danish welders and 1735 nonwelding metal workers exposed to welding fume. Occupational history and information on smoking were obtained from questionnaires, supplemented by information from the compulsory Danish Supplementary Pension Fund. Hospital contacts, including outpatient data from 1994, for Parkinson's disease and other neurological disorders were ascertained from the Danish National Hospital Register. Based on first-time hospital contacts, standardized hospitalization ratios (SHRs) were calculated for the entire cohort and for welders, metal workers, and nonresponders separately and for the general Danish population in 1987-2008. In an internal analysis of welders, Cox proportional hazard models were used to estimate hospitalization rate ratios (HRRs) for Parkinson's disease associated with lifelong exposure to welding. Overall, 45 cohort members had a hospital contact for Parkinson's disease (SHR, 1.12; 95% confidence interval [CI], 0.82-1.50), of whom 25 were welders (standardized incidence rate ratio, 1.05; 95% CI, 0.68-1.55). When duration of welding was compared among 5736 welders, the HRR was 0.83 (95% CI, 0.59-1.16) per 10 years' welding, after adjustment for smoking. The results of this study do not support the hypothesis that welders are at increased risk for Parkinson's disease; these findings are consistent with those of our previously published analysis. © 2012 Movement Disorder Society.

Validation of hospital register-based diagnosis of Parkinson's disease.

INTRODUCTION: Denmark has a long-standing tradition of maintaining one of the world's largest health science specialized register data bases as the National Hospital Register (NHR). To estimate the prevalence and incidence of diseases, the correctness of the diagnoses recorded is critical. Parkinson's disease (PD) is a neurodegenerative disorder and only 75-80% of patients with parkinsonism will have idiopathic PD (iPD). It is necessary to follow patients in order to determine if some of them will develop other neurodegenerative diseases and a one-time-only diagnostic code for iPD reported in the register may be incorrect. MATERIAL AND METHODS: This was a large nationwide population-based study of risk factors for iPD, called Parkinson's disease in Denmark (PASIDA). We evaluated the iPD diagnosis reported in the NHR. Medical records with primary diagnoses of iPD from six neurological departments were collected and abstracted using a standardized system to review the diagnostic accuracy of the ICD codes. RESULTS: Among the 1,040 medical records abstracted, 857 (82.4%) patients met our criteria for iPD. 183(17.6%) of the patients suffered from other diagnoses such as atypical PD (66 patients), secondary PD (60 patients) and other diagnoses (46 patients). CONCLUSION: Possibly only about 82% of the patients with the primary diagnosis of iPD in the Danish NHR actually suffered from iPD. To improve diagnostic validity, we appeal to update the ICD code and to identify the correct parkinsonian phenotype to reduce biased case sampling in register-based studies and appropriate treatment for these rare diseases. FUNDING: This study was supported by a grant from the National Institutes of Environmental Health Sciences, USA (grant No R01 ES013717). The funding source had no role in the design or analysis of the study or in the decision to submit the manuscript for publication. TRIAL REGISTRATION: Ethical approval: The study protocol was approved by the Danish Data Protection Agency (No 2006-41-7323) and by UCLA-IRB.

Malignant melanoma, breast cancer and other cancers in patients with Parkinson's disease.

Previous studies report an atypical cancer pattern among patients with Parkinson's disease. Here, we evaluate the cancer pattern among people diagnosed with Parkinson's disease in an extension of our previous cohort study. For this Danish population-based cohort study, we identified 20,000 people with Parkinson's disease diagnosed in 1977-2006, from the National Danish Hospital Register. Cohort members were followed up for cancer in the Danish Cancer Registry until December 31, 2008, and their incidence rates of cancer were compared to age-, sex- and calendar period-specific rates in the general population as standardized incidence rate ratios (SIRs). In subanalyses, we estimated the risk for cancer among patients with early onset Parkinson's disease and we also compared breast tumor characteristics among women with Parkinson's disease to that of a control group. The overall cancer risk in our cohort was decreased [SIR = 0.86; 95% confidence interval (CI) = 0.83-0.90], as were those for smoking-related (SIR = 0.65; 95% CI = 0.60-0.70) and nonsmoking-related cancers (SIR = 0.79; 95% CI = 0.71-0.86). The cohort had increased risks for malignant melanoma (SIR = 1.41; 95% CI = 1.09-1.80), nonmelanoma skin cancer (SIR = 1.29; 95% CI = 1.18-1.39) and female breast cancer (SIR = 1.17; 95% CI = 1.02-1.34). Among patients with early onset Parkinson's disease, the risk for cancer was comparable to that of the general population. Of breast tumor characteristics, only grade of malignancy differed between Parkinson's disease women and controls. This study confirms a lower cancer risk among people with Parkinson's disease. Increased risks for malignant melanoma, nonmelanoma skin cancer and breast cancer might be due to shared risk factors with Parkinson's disease.

Does computer use affect the incidence of distal arm pain? A one-year prospective study using objective measures of computer use.

PURPOSE: To study how objectively recorded mouse and keyboard activity affects distal arm pain among computer workers. METHODS: Computer activities were recorded among 2,146 computer workers. For 52 weeks mouse and keyboard time, sustained activity, speed and micropauses were recorded with a software program installed on the participants' computers. Participants reported weekly pain scores via the software program for elbow, forearm and wrist/hand as well as in a questionnaire at baseline and 1-year follow up. Associations between pain development and computer work were examined for three pain outcomes: acute, prolonged and chronic pain. RESULTS: Mouse time, even at low levels, was associated with acute pain in a similar way for all the examined regions. There were no exposure-response threshold patterns. Keyboard time had no effect. Mouse and keyboard sustained activity, speed and micropauses were not risk factors for acute pain, nor did they modify the effects of mouse or keyboard time. Computer usage parameters were not associated with prolonged or chronic pain. A major limitation of the study was low keyboard times. CONCLUSION: Computer work was not related to the development of prolonged or chronic pain. Mouse time was associated with acute distal arm pain, but the impact was quite small.

Parkinson's disease among gardeners exposed to pesticides--a Danish cohort study.

OBJECTIVE: Several studies have found positive associations between exposure to pesticides and Parkinson's disease. As Danish gardeners have had frequent, intensive exposure to pesticides, the aim of this study was to investigate their risk for Parkinson's disease. METHODS: The cohort was comprised of 3124 male members of the Danish Union of Gardeners on 1 April 1975. Hospital register data were used to follow them for a primary diagnosis of Parkinson's disease during 1977-2008 and to calculate standardized hospitalization rate ratios (SHR) for this disease among gardeners and the general Danish population for comparison. Data from the Danish Cancer Registry were used to calculate standardized incidence rate ratios (SIR) for smoking-related cancers among gardeners and the general population. RESULTS: The SHR for Parkinson's disease among gardeners was close to that of the general population [1.14, 95% confidence interval (95% CI) 0.76-1.65]. In a birth cohort analysis, a downward trend was observed, with the highest risk among gardeners born before 1915 (SHR 1.55, 95% CI 0.77-2.77). The SIR for smoking-related cancers did not differ from that of the general population. CONCLUSION: The results indicate a weak but dose-related association between exposure to pesticides and risk for Parkinson's disease; however, the results were based on 28 cases and the possibility of no association cannot be ruled out.

The Supplementary Pension Fund Register.

INTRODUCTION: Information on individual long-term work history is often required in occupational studies of diseases. CONTENT: The Supplementary Pension Fund Register has kept individual information on all employments, including start and end, on a company level backdating to 1964 for all wage earners in Denmark. Based on the computerised information, which also includes the unique personal identification number, it is possible to link information on employment history to information on individuals in nationwide registers of diseases. VALIDITY AND COVERAGE: Membership is compulsory and controlled by the Danish authorities, therefore information is considered to be accurate and complete. CONCLUSION: This register is unique and of high value in occupational epidemiology.

Occupation and cancer risk by use of Danish registers.

INTRODUCTION: Based on evidence from animal experiments and case reports, certain occupational exposures may contribute to yet undetected cancer risk in humans. Since traditional epidemiological studies are time consuming, the use of existing information from registers may facilitate the research process. Due to the existence of a unique personal identification number (CPR-number), a national cancer register operating since 1943, a nationwide pension fund scheme with compulsory membership for all employees covering long-term individual employment history, and sometimes with addition of information from external sources, e.g. interviews or job exposure matrices, it is possible to conduct large nationwide studies of occupational exposures and cancer risk in Denmark. RESEARCH TOPICS: In this review we give three examples of cancer studies of widespread occupational exposures: formaldehyde, night shift work, and bitumen. CONCLUSION: Results from register-based studies have contributed to the now-existing evidence on occupational exposures and risk of cancer.

Exposure assessment for a nested case-control study of lung cancer among European asphalt workers.

OBJECTIVE: Development of a method for retrospective assessment of exposure to bitumen fume, bitumen condensate, organic vapour, polycyclic aromatic hydrocarbons, and co-exposures to known or suspected lung carcinogens for a nested case-control study of lung cancer mortality among European asphalt workers. METHODS: Company questionnaires and structured questionnaires used in interviews and industry-specific job-exposure matrices (JEMs) were elaborated and applied. Three sources of information were eventually used for exposure assessment and assignment: (i) data obtained in cohort phase, (ii) data from living subjects, next-of-kin, and fellow-workers questionnaires, and (iii) JEMs for bitumen exposure by inhalation and via skin and co-exposures to known or suspected lung carcinogens within and outside cohort companies. Inhalation and dermal exposure estimates for bitumen were adjusted for time trends, time spent in a job, and other determinants of exposure (e.g. oil gravel paving). Clothing patterns, personal protective devices, and personal hygiene were taken into consideration while estimating dermal exposure. RESULTS: Occupational exposures could be assessed for 433 cases and 1253 controls for relevant time periods. Only 43% of work histories were spent inside original asphalt and construction companies. A total of 95.8% of job periods in cohort companies could be coded at a more detailed level. Imputation of work time and 'hygienic behaviour' multipliers was needed for <10% of work history years. Overall, downward trends in exposure were present and differences existed between countries and companies. As expected, correlations were strongest (r > 0.7) among bitumen-related agents, while correlations between coal tar, bitumen-related agents, and established lung carcinogens were weaker (r < 0.4). CONCLUSIONS: A systematic and detailed approach was developed to estimate inhalation and dermal exposure for a nested case-control study among asphalt workers.