Abstract: BACKGROUND: There is limited evidence for the role of air pollution in the development and triggering of wheezing symptoms in young children. A study was undertaken to examine the effect of exposure to air pollution on wheezing symptoms in children under the age of 3 years with genetic susceptibility to asthma. METHODS: Daily recordings of symptoms were obtained for 205 children participating in the birth cohort study Copenhagen Prospective Study on Asthma in Children and living in Copenhagen for the first 3 years of life. Daily air pollution levels for particulate matter <10 microm in diameter (PM(10)) and the concentrations of ultrafine particles, nitrogen dioxide (NO(2)), nitrogen oxide (NO(x)) and carbon monoxide (CO) were available from a central background monitoring station in Copenhagen. The association between incident wheezing symptoms and air pollution on the concurrent and previous 4 days was estimated by a logistic regression model (generalised estimating equation) controlling for temperature, season, gender, age, exposure to smoking and paternal history of asthma. RESULTS: Significant positive associations were found between concentrations of PM(10), NO(2), NO(x), CO and wheezing symptoms in infants (aged 0-1 year) with a delay of 3-4 days. Only the traffic-related gases (NO(2), NO(x)) showed significant effects throughout the 3 years of life, albeit attenuating after the age of 1 year. CONCLUSIONS: Air pollution related to traffic is significantly associated with triggering of wheezing symptoms in the first 3 years of life.
Abstract: We investigated the effects of socioeconomic, demographic and health-related indicators on the incidence of and survival from mouth, pharynx and larynx cancers diagnosed in 1994-2003 with follow-up through 2006 in Denmark using information from nationwide registers. The analyses were based on data on 3058 patients with mouth and pharynx cancer and 1799 with larynx cancer in a cohort of 3.22 million persons born between 1925 and 1973 and aged >or=30 years. The incidences of all the three cancers increased with decreasing socioeconomic position, measured as disposable income, work market affiliation, social class, housing tenure, cohabiting status and type of district. Similar differences in survival persisted for all 5 years observed. Immigrants had better survival from larynx cancer than native Danes. We could not determine the effects of differences in tobacco and alcohol consumption or their multiplicative interactions.
Abstract: OBJECTIVES: To study the association between short-term exposure to ultrafine particles and morbidity in Copenhagen, Denmark. METHODS: We studied the association between urban background levels of the total number concentration of particles (NC(tot), 6-700 nm in diameter) measured at a single site (15 May 2001 to 31 December 2004) and hospital admissions due to cardiovascular (CVD) and respiratory disease (RD) in the elderly (age >or=65 years), and due to asthma in children (age 5-18 years). We examined these associations in the presence of PM(10), PM(2.5) (particulate matter <10 and 2.5 microm in diameter, respectively) and ambient gasses. We utilised data on size distribution to calculate NC(tot) for four modes with median diameters 12, 23, 57 and 212 nm, and NC(100) (number concentration of particles <100 nm in diameter) and examined their associations with health outcomes. We used a time series Poisson generalised additive model adjusted for overdispersion, season, day of the week, public holidays, school holidays, influenza, pollen and meteorology, with up to 5 days' lagged exposure. RESULTS AND CONCLUSIONS: The adverse health effects of particulate matter on CVD and RD hospital admissions in the elderly were mainly mediated by PM(10) and accumulation mode particles with lack of effects for NC(100). For paediatric asthma, accumulation mode particles, NC(100) and nitrogen oxides (mainly from traffic related sources) were relevant, whereas PM(10) appeared to have little effect. Our results suggest that particle volume/mass from long-range transported air pollution is relevant for CVD and RD admissions in the elderly, and possibly particle numbers from traffic sources for paediatric asthma.
Abstract: An association between particulate air pollution and morbidity and mortality is well established. However, little is known about which sources of particulate matter contribute most to the adverse health effects. Identification of responsible sources would merit more efficient control. For a 6-year period (01 January 1999 to 31 December 2004), we examined associations between urban background PM(10) in the presence of gaseous pollutants (CO, NO(2)) and hospital admissions due to cardiovascular and respiratory disease in the elderly (age>/=65), and asthma in children (age 5-18) in Copenhagen, Denmark. We further studied associations between fractions of PM(10) assigned to six sources (biomass, secondary, oil, crustal, sea salt, and vehicle) and admissions during a 1(1/2) -year campaign. We used Poisson generalized additive time-series model adjusted for season, day of the week, public holidays, influenza epidemics, grass pollen, school holidays, and meteorology, with up to 5 days lagged air pollution exposure. We found positive associations between PM(10) and the three health outcomes, with strongest associations for asthma. The PM(10) effect remained robust in the presence of CO and NO(2). We found different PM(10) sources to be variably associated with different outcomes: crustal and secondary sources showed strongest associations with cardiovascular, biomass with respiratory, and vehicle with asthma admissions. These novel results may merit future research of potential mechanism, whereas at present, no single PM(10) source can be attributed to all morbidity.
Abstract: Randomised clinical trials find no protection against development of ischaemic heart disease by use of Hormone Therapy (HT) after the age of 50 years. Observational studies suggest that early menopause is a risk factor for ischaemic heart disease. Yet, a clinical very relevant question is whether HT reduces this risk associated with early menopause. OBJECTIVE: To analyse whether early menopause based on various causes are independent risk factors for ischaemic heart disease, and to investigate whether the risks are modified by use of HT. METHODS: In a prospective cohort study questionnaires were mailed to Danish female nurses above 44 years of age in 1993. Information on menopause, use of HT and lifestyle was obtained. In total 19,898 (86%) nurses fulfilled the questionnaire, among them 10.533 were postmenopausal with definable menopausal age, free of previous ischaemic heart disease, stroke or cancer. Through individual linkage to national register incident cases of ischaemic heart disease were identified until end of 1998. RESULTS: Menopause below both age 40 and 45 was associated with an increased risk of ischaemic heart disease, seeming most pronounced for women who had an early ovariectomy but also among spontaneous menopausal women. Generally HT did not reduce the risk except for the early-ovariectomised women, where no increased risk of ischaemic heart disease for HT users was found. CONCLUSION: We found an increased risk of ischaemic heart disease associated with early removal of the ovaries that might be reduced with HT. The present study need confirmation from other studies but suggests that early ovariectomised women could benefit from HT.
Abstract: BACKGROUND: Although survival is traditionally modeled using Cox proportional hazards modeling, this approach may be inappropriate in sepsis, in which the proportional hazards assumption does not hold. Newer, more flexible models, such as Gray's model, may be more appropriate. OBJECTIVES: To construct and compare Gray's model and two different Cox models in a large sepsis cohort. To determine whether hazards for death after sepsis were nonproportional. To explore how well the different survival modeling approaches describe these data. DESIGN: Analysis of combined data from the treatment and placebo arms of a large, negative, sepsis trial. SETTING: Intensive care units at 136 U.S. medical centers. SUBJECTS: A total of 1090 adults aged 18 yrs or older with signs and symptoms of severe sepsis and documented or probable Gram-negative infection. MEASUREMENTS: We considered 27 potential baseline risk factors and modeled survival over the 28 days after the onset of sepsis. We tested proportionality in single-variable Cox analysis using Schoenfeld residuals and log-log plots. We constructed a traditional multivariable Cox model, a multivariable Cox model with time-varying covariates, and a multivariable Gray's model. RESULTS: In single-variable analyses, 20 of the 27 potential factors were significantly associated with mortality, and 10 of 20 had nonproportional hazards. In multivariate analysis, all three models retained a very similar set of significant covariates (two models retained the identical set of nine variables, and the third differed only in that it retained the same nine plus a tenth variable). Four of the nine common covariates had nonproportional hazards. Of the three models, Gray's model best captured these changing hazard ratios over time. CONCLUSION: We confirm that many of the important predictors of mortality in severe sepsis are nonproportional and find that Gray's model seems best suited for modeling survival in this condition.
Abstract: Epidemiologic studies have shown an increased risk of breast cancer following hormone replacement therapy (HRT). The aim of this study was to investigate whether different treatment regimens or the androgenecity of progestins influence the risk of breast cancer differently. The Danish Nurse Cohort was established in 1993, where all female nurses aged 45 years and above received a mailed questionnaire (n = 23,178). A total of 19,898 women returned the questionnaire (86%). The questionnaire included information on HRT types and regimens, reproductive history and lifestyle-related factors. Breast cancer cases were ascertained using nationwide registries. The follow-up ended on 31 December 1999. Women with former cancer diagnoses, women with missing information on HRT, surgical menopause, premenopausal, as well as hysterectomized women were excluded, leaving 10,874 for analyses. Statistical analyses were performed using Cox proportional hazards model. A total of 244 women developed breast cancer during follow-up. After adjustment for confounding factors, an increased risk of breast cancer was found for the current use of estrogen only (RR = 1.96; 95% CI = 1.16-3.35), for the combined use of estrogen and progestin (RR = 2.70; 95% CI = 1.96-3.73) and for current users of tibolone (RR = 4.27; 95% CI = 1.74-10.51) compared to the never use of HRT. In current users of combined HRT with testosterone-like progestins, the continuous combined regimens were associated with a statistically significant higher risk of breast cancer than the cyclical combined regimens (RR = 4.16, 95% CI = 2.56-6.75, and RR = 1.94, 95% CI = 1.26-3.00, respectively). An increased risk of breast cancer was noted with longer durations of use for the continuous combined regimens (p for trend = 0.048). The European traditional HRT regimens were associated with an increased risk of breast cancer. The highest risk was found for the use of continuous combined estrogen and progestin.
Abstract: The aim of this study is to investigate the risk of developing prognostic different types of breast cancer in women using hormone replacement therapy (HRT). A total of 10 874 postmenopausal Danish Nurses were followed since 1993. Incident breast cancer cases and histopathological information were retrieved through the National Danish registries. The follow-up ended on 31 December 1999. Breast cancer developed in 244 women, of whom 172 were invasive ductal carcinomas. Compared to never users, current users of HRT had an increased risk of a hormone receptor-positive breast cancer, but a neutral risk of receptor-negative breast cancer, relative risk (RR) 3.29 (95% confidence interval (CI): 2.27-4.77) and RR 0.99 (95% CI: 0.42-2.36), respectively (P for difference=0.013). The risk of being diagnosed with low histological malignancy grade was higher than high malignancy grade with RR 4.13 (95% CI: 2.43-7.01) and RR 2.17 (95% CI: 1.42-3.30), respectively (P=0.063). For breast cancers with other prognostic characteristics, the risk was increased equally for the favourable and non favourable types. Current users of HRT experience a two- to four-fold increased risk of breast cancer with various prognostic characteristics, both the favourable and non favourable types. For receptor status, the risk with HRT was statistically significantly higher for hormone receptor-positive breast cancer compared to receptor-negative breast cancer.
Abstract: This study identified the underlying demographic and socioeconomic factors associated with insurance status among nonelderly Americans (age 19-64), as well as compared health care utilization between insured and uninsured. Data from the Community Tracking Study 1996-1997 Household Survey were analyzed. Approximately 74 percent of uninsured Americans are nonelderly Americans. Among the nonelderly Americans, about 17 percent are uninsured. Our findings show that insurance status varies significantly by region, age, race, gender, marital status, income, education, employment status, and health status. Also, the insured nonelderly Americans were found to have better access to health care than the uninsured nonelderly.
Abstract: OBJECTIVE: To investigate the risk of ischaemic heart disease and myocardial infarction among women using hormone replacement therapy, especially the potential modifying effect of cardiovascular risk factors. DESIGN: Prospective observational study. SETTING: Denmark. PARTICIPANTS: 19 898 nurses aged 45 and over completing a questionnaire on lifestyle and use of hormone replacement therapy in 1993. MAIN OUTCOME MEASURES: All cases of death and incident cases of ischaemic heart disease and myocardial infarction until the end of 1998. RESULTS: Current users of hormone replacement therapy smoked more, consumed more alcohol, had lower self rated health, but were slimmer and had a lower prevalence of diabetes than never users. In current users compared with never users, hormone replacement therapy had no protective effect on ischaemic heart disease (hazard ratio 1.2, 0.9 to 1.7) or myocardial infarction (1.0, 0.6 to 1.7), whereas current users with diabetes had an increased risk of death (3.2, 1.4 to 7.5), ischaemic heart disease (4.2, 1.4 to 12.5), and myocardial infarction (9.2, 2.0 to 41.4) compared with never users with diabetes. CONCLUSION: Hormone replacement therapy showed no protective effect on ischaemic heart disease, but there was a significantly increased risk of death from all causes and ischaemic heart disease among women with diabetes.
Abstract: BACKGROUND: Recent randomized clinical trials suggest an increased risk of stroke with hormone therapy (HT), whereas observational studies have suggested mixed results. Differences in design, definitions of HT exposure, and stroke outcome may explain these discrepancies. Little attention has been paid to identifying subgroups of women who are particularly sensitive to HT. OBJECTIVES: To investigate the risk of various stroke outcomes among women using HT based primarily on estradiol-17beta (unopposed or combined with norethisterone acetate) and to assess the potential modifying effect by presence of risk factors for stroke. DESIGN: Prospective cohort study. SETTING: In 1993, the Danish Nurse Study was established, and questionnaires on lifestyle and HT use were sent to all Danish nurses older than 44 years, of whom 19,898 (85.8%) replied. PARTICIPANTS: Postmenopausal women (n = 13,122) free of previous major cardiovascular and cerebrovascular disease and cancer. MAIN OUTCOME MEASURE: Ischemic or hemorrhagic stroke (n = 144) identified in the national registries of hospital discharges and cause of deaths in the total follow-up through December 31, 1998. RESULTS: In 1993, 28.0% of the 13 122 were current HT users, 14.3% were past users, and 57.7% were never users. Overall, HT exposure was not consistently associated with stroke. However, subdivision based on the presence of hypertension showed a significantly increased risk of stroke among hypertensive women. Compared with hypertensive never HT users, an increased risk of total stroke was found with current use (hazard ratio, 2.35; 95% confidence interval, 1.16-4.74) and especially with current use of estrogen-progestin (hazard ratio, 3.00; 95% confidence interval, 1.33-6.76). Normotensive women had no increased risk of stroke with HT. CONCLUSIONS: We found an increased risk of stroke among hypertensive but not normotensive women using HT. The present study suggests that HT should be avoided in hypertensive women.
