Yes / Born in Bradford is a prospective pregnancy and birth cohort in the UKs 6th largest city. Between 2007 and 2011 12,453 women (13,776 pregnancies), 3,448 of their partners and 13,818 babies were recruited. Half of families are in the poorest fifth of deprivation for England and Wales, and 45% are of Pakistani origin. Recruitment was in one Metropolitan District. This allows consideration of the impact of local circumstances, including service provision and policy choices, and engagement with the local community to implement evidence based responses to study findings. The introduction of a large study into a local health economy contributed to organizational changes including the development of a paperless maternity data system and better links between primary, secondary, and child health services. Embedding research in practice can lead to improved quality of routine data collected, for example on infant growth, and make routine data available for research, enhancing its cost effectiveness. Early adoption of research findings locally includes the introduction of routine vitamin D supplementation and an oral glucose tolerance test for all pregnant women. Findings that consanguinity was associated with a doubling of risk for congenital anomaly and that 30% of all anomalies in children of Pakistani origin could be attributed to consanguinity reinforced local commitment to community education about genetics and targeted genetic counselling. These findings also led to the establishment of a regional congenital anomalies register. In partnership with the European ESCAPE consortium (14 cohorts in 12 countries) a significant association was found between fetal growth and air pollution. The European Environmental Agency Director stated that this evidence is sufficient to trigger changes in EU regulations. Some findings can be quickly embedded in local provision, some have a resonance that prompts regional changes, some are generated with collaborators and can lead to policy change at international level.

Type 2 diabetes mellitus (T2DM) is associated with a high mortality risk, although the magnitude of this association remains unknown in Latin America (LA). We aimed to assess the strength of the association between T2DM and all-cause and cause-specific mortality in population-based cohort studies in LA. Systematic review and meta-analysis: inclusion criteria were (1) men and women 18 years old and above with T2DM; (2) study outcomes all-cause and/or cause-specific mortality; and (3) using people without T2DM as comparison group. Five databases (Scopus, Medline, Embase, Global Health, and LILACS) were searched. Risk of bias was evaluated with the ROBINS-I criteria. Initially, there were 979 identified studies, of which 17 were selected for qualitative synthesis; 14 were included in the meta-analysis (N = 416 821). Self-reported T2DM showed a pooled relative risk (RR) of 2.49 for all-causes mortality (I-squared [I 2 ] = 85.7%, p < 0.001; 95% confidence interval [CI], 1.96-3.15). T2DM based on a composite definition was associated with a 2.26-fold higher all-cause mortality (I 2 = 93.9%, p < 0.001; 95% CI, 1.36-3.74). The pooled risk estimates were similar between men and women, although higher at younger ages. The pooled RR for cardiovascular mortality was 2.76 (I 2 = 59.2%; p < 0.061; 95% CI, 1.99-3.82) and for renal mortality 15.85 (I 2 = 0.00%; p < 0.645; 95% CI, 9.82-25.57). Using available population-based cohort studies, this work has identified and estimated the strength of the association between T2DM and mortality in LA. The higher mortality risk compared with high-income countries deserves close attention from health policies makers and clinicians to improve diabetes care and control hence preventing complications and delaying death. / Revisión por pares

This thesis examined associations between ecological indicators of residential radon and fine particulate matter air pollution (PM2.5) and lung cancer mortality using data from the American Cancer Society Cancer Prevention Study-II (CPS-II) prospective cohort. Nearly 1.2 million CPS-II participants were recruited in 1982. Mean county-level residential radon concentrations were linked to study participants according to ZIP code information at enrollment (mean (SD) = 53.5 (38.0) Bq/m3). Cox proportional hazards regression models were used to obtain adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for lung cancer mortality associated with radon. After necessary exclusions, a total of 811,961 participants in 2,754 counties were retained for analysis. A significant positive linear trend was observed between categories of radon concentrations and lung cancer mortality (p = 0.02). A 15% (95% CI 1 - 31%) increase in the risk of lung cancer mortality was observed per each 100 Bq/m3 radon. Radon was also positively associated with chronic obstructive pulmonary disease mortality (HR per each 100 Bq/m3 = 1.13, 95% CI 1.05 - 1.21). No clear associations were observed between radon and non-respiratory mortality. In lifelong never smokers (n = 188,699), each 10 µg/m3 increase in mean metropolitan statistical area PM2.5 concentrations was associated with a 15-27% increase in the risk of lung cancer death which strengthened among individuals with a history of asthma or any prevalent chronic lung disease at enrollment (p for interaction < 0.05). There was no association between PM2.5 and mortality from non-malignant respiratory disease. In conclusion, this thesis observed significant positive associations between ecological indicators of residential radon and PM2.5 concentrations and lung cancer mortality. These findings further support efforts to reduce radon concentrations in homes to the lowest possible level and strengthens the evidence that ambient concentrations of PM2.5 measured in recent decades are associated with small but measurable increases in lung cancer mortality. Further research is needed to better understand possible complex inter-relationships between environmental risk factors, chronic lung disease, and lung cancer.

This thesis examined associations between ecological indicators of residential radon and fine particulate matter air pollution (PM2.5) and lung cancer mortality using data from the American Cancer Society Cancer Prevention Study-II (CPS-II) prospective cohort. Nearly 1.2 million CPS-II participants were recruited in 1982. Mean county-level residential radon concentrations were linked to study participants according to ZIP code information at enrollment (mean (SD) = 53.5 (38.0) Bq/m3). Cox proportional hazards regression models were used to obtain adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for lung cancer mortality associated with radon. After necessary exclusions, a total of 811,961 participants in 2,754 counties were retained for analysis. A significant positive linear trend was observed between categories of radon concentrations and lung cancer mortality (p = 0.02). A 15% (95% CI 1 - 31%) increase in the risk of lung cancer mortality was observed per each 100 Bq/m3 radon. Radon was also positively associated with chronic obstructive pulmonary disease mortality (HR per each 100 Bq/m3 = 1.13, 95% CI 1.05 - 1.21). No clear associations were observed between radon and non-respiratory mortality. In lifelong never smokers (n = 188,699), each 10 µg/m3 increase in mean metropolitan statistical area PM2.5 concentrations was associated with a 15-27% increase in the risk of lung cancer death which strengthened among individuals with a history of asthma or any prevalent chronic lung disease at enrollment (p for interaction < 0.05). There was no association between PM2.5 and mortality from non-malignant respiratory disease. In conclusion, this thesis observed significant positive associations between ecological indicators of residential radon and PM2.5 concentrations and lung cancer mortality. These findings further support efforts to reduce radon concentrations in homes to the lowest possible level and strengthens the evidence that ambient concentrations of PM2.5 measured in recent decades are associated with small but measurable increases in lung cancer mortality. Further research is needed to better understand possible complex inter-relationships between environmental risk factors, chronic lung disease, and lung cancer.

During the past decades, the incidence of osteoporotic fractures has increased dramatically in the Western world. Consumption of coffee and intake of caffeine have in some studies been found to be associated with increased risk of osteoporotic fractures, but overall results from previous research are inconsistent. Despite weak evidence, some osteoporosis organisations recommend limiting daily coffee or caffeine intake. The primary aim of this thesis was to study the association between long-term consumption of coffee and bone mineral density (BMD), incidence of osteoporosis and fractures. A secondary aim was to study the relation between tea consumption and fracture risk. An increased risk of osteoporotic fractures in individuals who consumed ≥ 4 cups of coffee vs &lt; 1 cup coffee per day was demonstrated in a study of 31,257 Swedish middle-aged and elderly women (a part of the Swedish Mammography Cohort - SMC) when calcium intake was low (&lt; 700 mg/day). However, no higher risks of osteoporosis or fractures were observed in the full SMC with increasing coffee consumption. In the full SMC (n = 61,433) the follow-up was longer and the number of fractures was higher. Similarly, no statistically significant associations between consumption of coffee (≥ 4 cups of coffee vs &lt; 1 cup) and incidence of osteoporotic fractures were observed in the Cohort of Swedish Men (COSM), including 45,339 men. Calcium intake did not modify the results from the investigations performed in the full SMC or COSM. Nonetheless, a 2 - 4% lower BMD at measured sites was observed in men participating in the PIVUS cohort and in women from a sub-cohort of the SMC who consumed ≥ 4 cups of coffee vs &lt; 1 cup daily. Individuals with high coffee intake and rapid metabolism of caffeine had lower BMD at the femoral neck. No association between tea consumption and risk of fractures was found in the studies. In conclusion, the findings presented in this thesis demonstrate that high consumption of coffee may be associated with a modest decrease in BMD. However, there was no evidence of a substantially increased incidence of osteoporosis or fractures typically associated with osteoporosis.

Earlier retrospective noise exposure assessments for use in epidemiological research were not adequately characterized because they did not properly account for use of hearing protection devices (HPD) which would result in potential misclassification. Exposure misclassification has been shown to attenuate exposure-outcomes relations. In the case of already subtle relationships such as noise and cardiovascular diseases, this would potentially annihilate any association. We investigated two approaches using Workers’ Compensation Board (WorkSafe BC) audiometric surveillance data to (i) re-assess the noise exposure in a cohort of lumber mill workers in British Columbia using data on the use of HPD and the determinants of their use available through WorkSafe BC, and (ii) test the validity of the new exposure measures by testing their predictions of noise-induced hearing loss, a well-established association. Work history, noise exposure measurements, and audiometric surveillance data were merged together, forming job-exposure-audiometric information for each of 13,147 lumber mill workers. Correction factors specific to each type and class of HPD were determined based on research and standards. HPD-relevant correction factors were created using 1) deterministic methods and self-reported HPD use after filling gaps in the exposure history, or 2) a model of the determinants of use of HPD, then adjusting noise estimates according to the methods’ predictions and attenuation factors. For both methods, the HPD-adjusted and unadjusted noise exposure estimates were cumulated across all jobs each worker held in a cohort-participating lumber mill. Finally, these noise metrics were compared by examining how well each predicted hearing loss. Analyses controlled for gender, age, race as well as medical and non-occupational risk factors. Both methods led to a strengthening of the noise-hearing loss relationships compared to methods using HPD-unadjusted noise estimates. The method based on the modeling of HPD use had the best performance with a four-fold increase in the slope compared to the unadjusted noise-hearing loss slope. Accounting for HPD use in noise exposure assessment is necessary since we have shown that misclassification attenuated the exposure-response relationships. Exposure-response analyses subsequent to exposure reassessment provide predictive validity and gives confidence in the exposure adjustment methods.

This thesis examined associations between ecological indicators of residential radon and fine particulate matter air pollution (PM2.5) and lung cancer mortality using data from the American Cancer Society Cancer Prevention Study-II (CPS-II) prospective cohort. Nearly 1.2 million CPS-II participants were recruited in 1982. Mean county-level residential radon concentrations were linked to study participants according to ZIP code information at enrollment (mean (SD) = 53.5 (38.0) Bq/m3). Cox proportional hazards regression models were used to obtain adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for lung cancer mortality associated with radon. After necessary exclusions, a total of 811,961 participants in 2,754 counties were retained for analysis. A significant positive linear trend was observed between categories of radon concentrations and lung cancer mortality (p = 0.02). A 15% (95% CI 1 - 31%) increase in the risk of lung cancer mortality was observed per each 100 Bq/m3 radon. Radon was also positively associated with chronic obstructive pulmonary disease mortality (HR per each 100 Bq/m3 = 1.13, 95% CI 1.05 - 1.21). No clear associations were observed between radon and non-respiratory mortality. In lifelong never smokers (n = 188,699), each 10 µg/m3 increase in mean metropolitan statistical area PM2.5 concentrations was associated with a 15-27% increase in the risk of lung cancer death which strengthened among individuals with a history of asthma or any prevalent chronic lung disease at enrollment (p for interaction < 0.05). There was no association between PM2.5 and mortality from non-malignant respiratory disease. In conclusion, this thesis observed significant positive associations between ecological indicators of residential radon and PM2.5 concentrations and lung cancer mortality. These findings further support efforts to reduce radon concentrations in homes to the lowest possible level and strengthens the evidence that ambient concentrations of PM2.5 measured in recent decades are associated with small but measurable increases in lung cancer mortality. Further research is needed to better understand possible complex inter-relationships between environmental risk factors, chronic lung disease, and lung cancer.

The primary function of vitamin D in humans is to maintain sufficient circulating calcium concentrations. Low vitamin D levels could result in excessive calcium resorption from bone. Vitamin deficiency may therefore decrease bone mineral density (BMD), resulting in an increased risk of fracture. This thesis sought to determine the association between vitamin D intake and bone health and to estimate circulating levels of vitamin D optimal for bone health without increasing the risk for non-bone disease. Furthermore, the thesis assessed the difference in performance between common serum vitamin D assays and the genetic influence of vitamin D status. In prospective population-based cohorts, blood concentrations &lt;40 nmol/L (lowest 5%) increased the risk of fracture in elderly men. Low levels were further associated with a slight decrease in lumbar spine BMD. Both high (&gt;98 nmol/L) and low (&lt;46 nmol/L) vitamin D levels were associated with higher cancer and overall mortality. In another cohort, also of older men and women, no association was found between vitamin D levels and fracture. Low vitamin D levels were weakly associated with decreased total body BMD in men but not in women. Dietary intake of vitamin D over a 20-year period in more than 60,000 Swedish women was not associated with osteoporosis or fracture, regardless of calcium intake. During summer, dietary vitamin D intake and other life style habits are of minor importance for the variation in vitamin D levels relative to sun exposure and genes. In summer time, genes explain about half  of the variation in vitamin D levels, but none of the variance in winter time. The variability between vitamin D assays was substantial. Three assays classified 8, 22 and 43% of the same study population as vitamin D insufficient if &lt;50 nmol/L was set as the insufficiency level. Based on the results in this thesis, low 25(OH)D levels and low dietary vitamin D intake are not a major cause of fractures in community-dwelling elderly Swedish women and men. Differences in assay performance and potential negative health outcomes of high 25(OH)D levels need to be considered.

Earlier retrospective noise exposure assessments for use in epidemiological research were not adequately characterized because they did not properly account for use of hearing protection devices (HPD) which would result in potential misclassification. Exposure misclassification has been shown to attenuate exposure-outcomes relations. In the case of already subtle relationships such as noise and cardiovascular diseases, this would potentially annihilate any association. We investigated two approaches using Workers’ Compensation Board (WorkSafe BC) audiometric surveillance data to (i) re-assess the noise exposure in a cohort of lumber mill workers in British Columbia using data on the use of HPD and the determinants of their use available through WorkSafe BC, and (ii) test the validity of the new exposure measures by testing their predictions of noise-induced hearing loss, a well-established association. Work history, noise exposure measurements, and audiometric surveillance data were merged together, forming job-exposure-audiometric information for each of 13,147 lumber mill workers. Correction factors specific to each type and class of HPD were determined based on research and standards. HPD-relevant correction factors were created using 1) deterministic methods and self-reported HPD use after filling gaps in the exposure history, or 2) a model of the determinants of use of HPD, then adjusting noise estimates according to the methods’ predictions and attenuation factors. For both methods, the HPD-adjusted and unadjusted noise exposure estimates were cumulated across all jobs each worker held in a cohort-participating lumber mill. Finally, these noise metrics were compared by examining how well each predicted hearing loss. Analyses controlled for gender, age, race as well as medical and non-occupational risk factors. Both methods led to a strengthening of the noise-hearing loss relationships compared to methods using HPD-unadjusted noise estimates. The method based on the modeling of HPD use had the best performance with a four-fold increase in the slope compared to the unadjusted noise-hearing loss slope. Accounting for HPD use in noise exposure assessment is necessary since we have shown that misclassification attenuated the exposure-response relationships. Exposure-response analyses subsequent to exposure reassessment provide predictive validity and gives confidence in the exposure adjustment methods.

Diss. Stockholm : Karol. inst., 2002. / S. 1-56: sammanfattning, s. 59-127: 5 uppsatser.