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OBJECTIVE: Neurofilament light chains (NfL) and phosphorylated neurofilament heavy chains (pNfH), established as diagnostic and prognostic biomarkers in hospital-based amyotrophic lateral sclerosis (ALS) cohorts, are now surrogate markers in clinical trials. This study extends their evaluation to a population level, with the aim of advancing their full establishment and assessing the transferability of biomarker findings from controlled cohorts to real-world ALS populations. METHODS: We measured serum NfL and pNfH levels in all ALS patients (n = 790) and general population controls (n = 570) with available baseline samples participating in the epidemiological ALS Registry Swabia, providing platform-specific (ELLA™) reference data and Z-scores for controls, as well as reference data, disease-specific Z-scores and longitudinal data in ALS. We evaluated the diagnostic and prognostic utility of neurofilaments and quantified the impact of ALS-related factors and non-ALS confounders. RESULTS: Neurofilaments showed high diagnostic and prognostic utility at the population level, with NfL superior to pNfH. The novel concept of a population-based ALS Z-score significantly improved the prognostic utility compared to absolute raw values. Both biomarkers increased more strongly with age in controls than in ALS, and age adjustment improved diagnostic accuracy. Our data show that disease progression rates, ALS phenotype, body mass index (BMI), and renal function need to be considered when interpreting neurofilament levels; longitudinal neurofilament levels were generally stable in individual patients, especially when adjusted for age and baseline levels. INTERPRETATION: Population-based assessment enhances the utility of particularly serum NfL as a diagnostic and prognostic biomarker in ALS and improves the translation of findings from controlled cohorts to real-world populations. ANN NEUROL 2024.
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End-stage kidney disease (ESKD) poses a high burden on patients and health systems. While numerous studies indicate an association between air pollution and chronic kidney disease, studies on ESKD are rare. We investigated the association of long-term exposure to nitrogen dioxide (NO2), fine particulate matter (PM2.5), black carbon (BC) and ozone (O3) with ESKD incidence in two large population-based European cohorts. We followed individuals in the Austrian Vorarlberg Health Monitoring and Promotion Program (VHM&PP) and the Italian Rome Longitudinal Study (RoLS) using dialysis and kidney transplant registries. Long-term exposure to pollutants was estimated at the home address using Europe-wide land use regression models at 100x100m scale. Hazard ratios (HR) were determined from Cox-proportional hazard models adjusted for individual and neighbourhood level confounders. We observed 501 events among 136,823 individuals in VHM&PP (mean age 42.1 years; crude incidence rate (IR) 0.14 per 1000 person-years) and 3231 events among 1,939,461 individuals in RoLS (mean age 52.4 years; IR 0.22 per 1000 person-years). In VHM&PP, there was no evidence of an association between PM2.5 or O3 and ESKD. There were elevated HRs but with large confidence intervals for BC (HR 1.17 [95 % confidence interval (CI): 0.98, 1.39] for 0.5*10-5/m), and for NO2 (HR 1.14 [95%CI: 0.96, 1.35] for 10 µg/m3). In RoLS, ESKD was associated with PM2.5 (HR 1.37 [95 % CI: 1.06, 1.76] for an increase of 5 µg/m3), while there was no evidence of association with BC, NO2, or O3 exposure. Our study suggests an association of air pollution with ESKD incidence, which differed between the two cohorts and may possibly be influenced by respective air pollution mixtures.
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Poluentes Atmosféricos , Poluição do Ar , Falência Renal Crônica , Material Particulado , Falência Renal Crônica/epidemiologia , Humanos , Poluição do Ar/estatística & dados numéricos , Incidência , Material Particulado/análise , Poluentes Atmosféricos/análise , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Exposição Ambiental/estatística & dados numéricos , Dióxido de Nitrogênio/análise , Ozônio/análise , Estudos de Coortes , Itália/epidemiologia , Europa (Continente)/epidemiologia , Estudos LongitudinaisRESUMO
The integrity of the blood-CSF barrier plays a major role in inflammation, but also in shielding the central nervous system from external and systemic - potentially toxic - factors. Here we report results of measurements of the albumin quotient - which is thought to mirror the integrity of the blood/CSF barrier - in 1059 amyotrophic lateral sclerosis patients. The results were compared with groups of patients suffering from Alzheimer´s disease, facial palsy and tension headache. The albumin quotient, an accepted measure of the blood/CSF barrier integrity, was not significantly different from control populations. In addition, we found that the albumin quotient correlated with survival of the patients; this effect was mainly driven by male patients and influenced by age, BMI and diabetes mellitus. We conclude that the blood/CSF barrier is intact in this large cohort of ALS patients and that the albumin quotient correlates with survival. Whether this is important for the pathogenesis of the disease, requires mechanistic studies.
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Background: Amyotrophic lateral sclerosis (ALS) is a fatal disorder, which imposes a severe emotional burden on patients. Appropriate coping mechanisms may alleviate this burden and facilitate wellbeing, with social support known to be a successful coping strategy. This observational study aimed to determine the interplay of general coping traits of hope for success and fear of failure, coping behavior of social activity, and patients' wellbeing. Methods: In this cross-sectional study, patients with ALS from a clinical-epidemiological registry in Southwestern Germany were interviewed regarding coping traits (achievement-motivated behavior: hope for success and fear of failure), coping behavior of social activity, and psychosocial adjustment, determined using measures of depressiveness, anxiety [both measured by Hospital Anxiety and Depression Scale (HADS)], and quality of life [Anamnestic Comparative Self-Assessment (ACSA)]. Demographics, clinical [ALS Functional Rating Scale revised version (ALSFRS-R)], and survival data were recorded. Results: A total of 868 patients [60.70% male patients, mean age: 64.70 (±10.83) years, mean ALSFRS-R: 37.36 ± 7.07] were interviewed. Anxiety in patients was found to be associated with a high fear of failure. In contrast, a generally positive attitude in patients exemplified in high hopes for success was associated with better wellbeing. Finally, coping behavior of social activity explained up to 65% of the variance of depressiveness among the patients with ALS. Conclusion: In this study, we present evidence that the wellbeing of patients with ALS is not an immediate fatalistic consequence of physical degradation but rather determined by coping traits and behavior, which may be trained to substantially increase the wellbeing of patients with ALS.
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BACKGROUND: whether screening for skin cancer affects melanoma-specific mortality in a population-based setting remains unclear. METHODS: in this population-based cohort study, we characterized and evaluated a skin cancer prevention program following a targeted screening approach conducted in 1989-1994 in the Austrian province Vorarlberg, with follow-up until 2019. The general population and attendees of a health examination program served for comparison. RESULTS: in the screening program including full follow-up until 2019, 207 invasive and 187 in situ melanomas were identified in 8997 individuals. Incidences of invasive and in situ melanomas were elevated compared to the general population (IRR 2.92, 95%-CI 2.49-3.41, and IRR 4.13, 95%-CI 3.53-4.83, respectively) and the health examination program (HR 3.02, 95%-CI 2.59-3.52, and HR 3.90, 95%-CI 3.30-4.61, respectively). Breslow thickness and Clark's level at time of invasive diagnosis were significantly lower in 1989-2019, but the tumor characteristics of the melanomas diagnosed during 1989-1994 did not differ from the comparison groups. Moreover, melanoma mortality was significantly elevated in the screening program (IRR 1.66, 95%-CI 1.00-2.75 vs. the general population, HR 2.12, 95%-CI 1.25-3.61 vs. the health examination cohort). Melanoma mortality in Vorarlberg declined until 2004, though statistically non-significantly. CONCLUSIONS: given the uncertain effectiveness and high public expenditures of population-wide mass screening programs, primary prevention and targeted risk-based skin cancer screening might be promising alternatives.
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Despite the known link between air pollution and cause-specific mortality, its relation to chronic kidney disease (CKD)-associated mortality is understudied. Therefore, we investigated the association between long-term exposure to air pollution and CKD-related mortality in a large multicentre population-based European cohort. Cohort data were linked to local mortality registry data. CKD-death was defined as ICD10 codes N18-N19 or corresponding ICD9 codes. Mean annual exposure at participant's home address was determined with fine spatial resolution exposure models for nitrogen dioxide (NO2), black carbon (BC), ozone (O3), particulate matter ≤2.5 µm (PM2.5) and several elemental constituents of PM2.5. Cox regression models were adjusted for age, sex, cohort, calendar year of recruitment, smoking status, marital status, employment status and neighbourhood mean income. Over a mean follow-up time of 20.4 years, 313 of 289,564 persons died from CKD. Associations were positive for PM2.5 (hazard ratio (HR) with 95% confidence interval (CI) of 1.31 (1.03-1.66) per 5 µg/m3, BC (1.26 (1.03-1.53) per 0.5 × 10- 5/m), NO2 (1.13 (0.93-1.38) per 10 µg/m3) and inverse for O3 (0.71 (0.54-0.93) per 10 µg/m3). Results were robust to further covariate adjustment. Exclusion of the largest sub-cohort contributing 226 cases, led to null associations. Among the elemental constituents, Cu, Fe, K, Ni, S and Zn, representing different sources including traffic, biomass and oil burning and secondary pollutants, were associated with CKD-related mortality. In conclusion, our results suggest an association between air pollution from different sources and CKD-related mortality.
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Poluentes Atmosféricos , Poluição do Ar , Exposição Ambiental , Insuficiência Renal Crônica , Humanos , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/induzido quimicamente , Masculino , Feminino , Europa (Continente)/epidemiologia , Pessoa de Meia-Idade , Idoso , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/efeitos adversos , Estudos de Coortes , Exposição Ambiental/efeitos adversos , Material Particulado/análise , Material Particulado/efeitos adversos , AdultoRESUMO
Air pollution has been shown to significantly impact human health including cancer. Gastric and upper aerodigestive tract (UADT) cancers are common and increased risk has been associated with smoking and occupational exposures. However, the association with air pollution remains unclear. We pooled European subcohorts (N = 287,576 participants for gastric and N = 297,406 for UADT analyses) and investigated the association between residential exposure to fine particles (PM2.5), nitrogen dioxide (NO2), black carbon (BC) and ozone in the warm season (O3w) with gastric and UADT cancer. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level. During 5,305,133 and 5,434,843 person-years, 872 gastric and 1139 UADT incident cancer cases were observed, respectively. For gastric cancer, we found no association with PM2.5, NO2 and BC while for UADT the hazard ratios (95% confidence interval) were 1.15 (95% CI: 1.00-1.33) per 5 µg/m3 increase in PM2.5, 1.19 (1.08-1.30) per 10 µg/m3 increase in NO2, 1.14 (1.04-1.26) per 0.5 × 10-5 m-1 increase in BC and 0.81 (0.72-0.92) per 10 µg/m3 increase in O3w. We found no association between long-term ambient air pollution exposure and incidence of gastric cancer, while for long-term exposure to PM2.5, NO2 and BC increased incidence of UADT cancer was observed.
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Poluentes Atmosféricos , Poluição do Ar , Neoplasias Gástricas , Humanos , Material Particulado/efeitos adversos , Material Particulado/análise , Dióxido de Nitrogênio/efeitos adversos , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologia , Incidência , Exposição Ambiental/efeitos adversos , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análiseRESUMO
Blood pressure (BP) varies over a lifetime. This cardiovascular observation study (OS) compared the predictive value of earlier- and later-in-life blood pressure (BP) in 1,497 cardiovascular disease patients utilizing readings taken during a health survey (HS) and 15 years later from the same subjects at the baseline of this OS. Prediction of the cardiovascular risk during the OS follow-up (21 years) was significantly more effective if the earlier BP readings at HS were used instead of recent OS readings (NRI = 0.30, p < 0.001). For HS readings, each 10 mm Hg increase of systolic and diastolic BP was associated with a 17% and 20% higher risk, respectively. At OS, systolic BP lost significance and diastolic BP reversed its association. Noteworthy, different BP categorizations (European vs. US guidelines) yielded similar results. This study highlights the poor predictive power of BP readings in elderly cardiovascular disease patients but emphasizes the significant prognostic value of earlier-in-life BP.
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It is unclear whether cancers of the upper aerodigestive tract (UADT) and gastric cancer are related to air pollution, due to few studies with inconsistent results. The effects of particulate matter (PM) may vary across locations due to different source contributions and related PM compositions, and it is not clear which PM constituents/sources are most relevant from a consideration of overall mass concentration alone. We therefore investigated the association of UADT and gastric cancers with PM2.5 elemental constituents and sources components indicative of different sources within a large multicentre population based epidemiological study. Cohorts with at least 10 cases per cohort led to ten and eight cohorts from five countries contributing to UADT- and gastric cancer analysis, respectively. Outcome ascertainment was based on cancer registry data or data of comparable quality. We assigned home address exposure to eight elemental constituents (Cu, Fe, K, Ni, S, Si, V and Zn) estimated from Europe-wide exposure models, and five source components identified by absolute principal component analysis (APCA). Cox regression models were run with age as time scale, stratified for sex and cohort and adjusted for relevant individual and neighbourhood level confounders. We observed 1139 UADT and 872 gastric cancer cases during a mean follow-up of 18.3 and 18.5 years, respectively. UADT cancer incidence was associated with all constituents except K in single element analyses. After adjustment for NO2, only Ni and V remained associated with UADT. Residual oil combustion and traffic source components were associated with UADT cancer persisting in the multiple source model. No associations were found for any of the elements or source components and gastric cancer incidence. Our results indicate an association of several PM constituents indicative of different sources with UADT but not gastric cancer incidence with the most robust evidence for traffic and residual oil combustion.
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Poluentes Atmosféricos , Poluição do Ar , Neoplasias Gástricas , Humanos , Material Particulado/análise , Neoplasias Gástricas/induzido quimicamente , Neoplasias Gástricas/epidemiologia , Incidência , Exposição Ambiental/análise , Poluição do Ar/análise , Poluentes Atmosféricos/análiseRESUMO
BACKGROUND: Insulin resistance is a hypothesised biological mechanism linking obesity with prostate cancer (PCa) death. Data in support of this hypothesis is limited. METHODS: We included 259,884 men from eight European cohorts, with 11,760 incident PCa's and 1784 PCa deaths during follow-up. We used the triglyceride-glucose (TyG) index as indicator of insulin resistance. We analysed PCa cases with follow-up from PCa diagnosis, and the full cohort with follow-up from the baseline cancer-free state, thus incorporating both PCa incidence and death. We calculated hazard ratios (HR) and the proportion of the total effect of body mass index (BMI) on PCa death mediated through TyG index. RESULTS: In the PCa-case-only analysis, baseline TyG index was positively associated with PCa death (HR per 1-standard deviation: 1.11, 95% confidence interval (CI); 1.01-1.22), and mediated a substantial proportion of the baseline BMI effect on PCa death (HRtotal effect per 5-kg/m2 BMI: 1.24; 1.14-1.35, of which 28%; 4%-52%, mediated). In contrast, in the full cohort, the TyG index was not associated with PCa death (HR: 1.03; 0.94-1.13), hence did not substantially mediate the effect of BMI on PCa death. CONCLUSIONS: Insulin resistance could be an important pathway through which obesity accelerates PCa progression to death.
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Resistência à Insulina , Neoplasias da Próstata , Masculino , Humanos , Índice de Massa Corporal , Análise de Mediação , Glucose , Obesidade/complicações , Obesidade/epidemiologia , Triglicerídeos , Glicemia , Fatores de Risco , BiomarcadoresRESUMO
Leukemia and lymphoma are the two most common forms of hematologic malignancy, and their etiology is largely unknown. Pathophysiological mechanisms suggest a possible association with air pollution, but little empirical evidence is available. We aimed to investigate the association between long-term residential exposure to outdoor air pollution and risk of leukemia and lymphoma. We pooled data from four cohorts from three European countries as part of the "Effects of Low-level Air Pollution: a Study in Europe" (ELAPSE) collaboration. We used Europe-wide land use regression models to assess annual mean concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC) and ozone (O3) at residences. We also estimated concentrations of PM2.5 elemental components: copper (Cu), iron (Fe), zinc (Zn); sulfur (S); nickel (Ni), vanadium (V), silicon (Si) and potassium (K). We applied Cox proportional hazards models to investigate the associations. Among the study population of 247,436 individuals, 760 leukemia and 1122 lymphoma cases were diagnosed during 4,656,140 person-years of follow-up. The results showed a leukemia hazard ratio (HR) of 1.13 (95% confidence intervals [CI]: 1.01-1.26) per 10 µg/m3 NO2, which was robust in two-pollutant models and consistent across the four cohorts and according to smoking status. Sex-specific analyses suggested that this association was confined to the male population. Further, the results showed increased lymphoma HRs for PM2.5 (HR = 1.16; 95% CI: 1.02-1.34) and potassium content of PM2.5, which were consistent in two-pollutant models and according to sex. Our results suggest that air pollution at the residence may be associated with adult leukemia and lymphoma.
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Poluentes Atmosféricos , Poluição do Ar , Poluentes Ambientais , Leucemia , Linfoma , Adulto , Feminino , Humanos , Masculino , Dióxido de Nitrogênio/análise , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Material Particulado/análise , Poluentes Ambientais/análise , Leucemia/induzido quimicamente , Leucemia/epidemiologia , Linfoma/induzido quimicamente , Linfoma/epidemiologia , Potássio/análise , Poluentes Atmosféricos/análiseRESUMO
INTRODUCTION: Demographics are important prognostic factors in malignant diseases. A nationwide analysis concerning the prognostic impact of demographics in head and neck cancer (HNC) patients (HNCP) has not been performed previously. METHODS: A retrospective analysis of data from the Center for Cancer Registry Data (ZfKD) and the Federal Statistical Office (Destatis) between 2002 and 2017 was performed. A total of 212'920 HNCP were included. Incidence, tumor stage, age development, sex distribution, age-, residence-, and diagnosis-time-specific survival were examined. RESULTS: Mean age of HNCP increased more rapidly than in the general population (slope coefficient: 0.29 vs. 0.20; p < 0.0001). Higher age and male sex were associated with a worse prognosis. Whereas overall survival (OS) increased from the early to the later observation period for HNCP <70 years, no OS improvement for HNCP >70 years was found. Furthermore, an OS disadvantage was observed for East Germany compared to West Germany (median 47 vs. 60 months; p < 0.0001). This disparity was associated with a disproportionately high ratio of men in East Germany (men/women: 4.4 vs. 3.1; p < 0.0001) and a lower mean age (61 vs. 63 years; p < 0.0001). In addition to stage, age and sex, residence in East Germany were confirmed as an independent factor for OS in a multivariate analysis. CONCLUSION: Finally, three decades after the German reunion, a survival disadvantage for patients in East Germany still exists. This discrepancy may be a result of socioeconomic disparities.
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Neoplasias de Cabeça e Pescoço , Humanos , Masculino , Feminino , Estudos Retrospectivos , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/terapia , Alemanha/epidemiologia , Prognóstico , Distribuição por SexoRESUMO
Kidney function as part of metabolic changes could be associated with amyotrophic lateral-sclerosis (ALS). We investigated the associations between estimated chronic kidney disease (CKD), based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C equation, and the risk at onset and prognostic value of CKD for ALS. Between October 2010 and June 2014, 362 ALS cases (59.4% men, mean age 65.7 years) and 681 controls (59.5% men, means age 66.3 years) were included in a population-based case-control study based on the ALS registry Swabia in Southern Germany. All ALS cases were followed-up (median 89.7 months), 317 died. Serum samples were measured for cystatin C to estimate the glomerular filtration rate (eGFR) according to the CKD-EPI equation. Information on covariates were assessed by an interview-based standardized questionnaire. Conditional logistic regression models were applied to calculate odds ratios (OR) for risk of ALS associated with eGFR/CKD stages. Time-to-death associated with renal parameters at baseline was assessed in ALS cases only. ALS cases were characterized by lower body mass index, slightly lower smoking prevalence, more intense occupational work and lower education than controls. Median serum cystatin-C based eGFR concentrations were lower in ALS cases than in controls (54.0 vs. 59.5 mL/min pro 1.73 m2). The prevalence of CKD stage ≥ 3 was slightly higher in ALS cases than in controls (14.1 vs. 11.0%). In the adjusted models, CKD stage 2 (OR 1.82, 95% CI 1.32, 2.52) and stage 3 (OR 2.34, 95% CI 1.38, 3.96) were associated with increased ALS risk. In this cohort of ALS cases, eGFR and CKD stage ≥ 3 (HR 0.94; 95% CI 0.64, 1.38) were not associated with prognosis. In this case-control study, higher CKD stages were associated with increased ALS risk, while in the prospective cohort of ALS cases, no indication of an association of CysC-based CKD on mortality was seen. In addition, our work strengthens the importance to evaluate renal function using a marker independent of muscle mass in ALS patients.
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Esclerose Lateral Amiotrófica , Insuficiência Renal Crônica , Masculino , Humanos , Idoso , Feminino , Prognóstico , Estudos de Casos e Controles , Estudos Prospectivos , Cistatina C , Insuficiência Renal Crônica/complicações , Taxa de Filtração Glomerular , Sistema de Registros , Creatinina , BiomarcadoresRESUMO
BACKGROUND: Air pollution is a growing concern worldwide, with significant impacts on human health. Multiple myeloma is a type of blood cancer with increasing incidence. Studies have linked air pollution exposure to various types of cancer, including leukemia and lymphoma, however, the relationship with multiple myeloma incidence has not been extensively investigated. METHODS: We pooled four European cohorts (N = 234,803) and assessed the association between residential exposure to nitrogen dioxide (NO2), fine particles (PM2.5), black carbon (BC), and ozone (O3) and multiple myeloma. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level. RESULTS: During 4,415,817 person-years of follow-up (average 18.8 years), we observed 404 cases of multiple myeloma. The results of the fully adjusted linear analyses showed hazard ratios (95% confidence interval) of 0.99 (0.84, 1.16) per 10 µg/m³ NO2, 1.04 (0.82, 1.33) per 5 µg/m³ PM2.5, 0.99 (0.84, 1.18) per 0.5 10-5 m-1 BCE, and 1.11 (0.87, 1.41) per 10 µg/m³ O3. CONCLUSIONS: We did not observe an association between long-term ambient air pollution exposure and incidence of multiple myeloma.
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Poluentes Atmosféricos , Poluição do Ar , Mieloma Múltiplo , Humanos , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Estudos de Coortes , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Mieloma Múltiplo/induzido quimicamente , Mieloma Múltiplo/epidemiologia , Dióxido de Nitrogênio/toxicidade , Dióxido de Nitrogênio/análise , Material Particulado/análiseRESUMO
BACKGROUND: Demographic development in rural and urban areas differs substantially. Demographics and access to specialized head and neck cancer centers may affect head and neck cancer patients' (HNCP) outcomes. Here, we compare epidemiological indicators and outcomes of HNCP in rural and urban Germany. PATIENTS AND METHODS: In a retrospective analysis of data from the Center for Cancer Registry Data (ZfKD) between 2002 and 2017, 212,920 HNCP were included. Incidence, demographics, travel distance to specialized centers, and ground values were compared between rural and urban areas with a focus on their association with patient outcomes. RESULTS: The mean age of HNCP was significantly higher in urban areas (mean difference = 1.4 years; p < 0.0001), but increased at a comparable rate (p = 0.26) in rural and urban areas during the observation period. Gender imbalance was higher in rural areas (mean ratio of men/women: 4.1 vs. 3.1; p < 0.0001), but showed a comparable trend toward equilibration in both, rural and urban districts (p = 0.46). The portion of HNCP of the entire HNCP population living in urban areas increased from 55.9% in the year 2002 to 76.4% in the year 2017. There was no significant difference or change in the ratio of advanced to low UICC stage during the observation period (p = 0.26). However, travel distances to medical centers were higher in rural areas, especially (p < 0.0001) in East Germany. Median survival of HNCP in rural areas was significantly lower than in urban areas (42 months [SEM = 0.7; CI: 40.5-43.5] vs. 54 months [SEM = 1.2; CI: 51.7-56.3]; p < 0.0001) in East Germany, whereas in West Germany no significant difference was observed (59 months [SEM = 0.8; CI: 57.4-60.6] vs. 60 months [SEM = 0.5; CI: 59.0-61.0]; p = 0.15). CONCLUSIONS: Place of residence contributes to survival outcome of HNCP. Access to specialized care and socioeconomic factors could be improved in East Germany.
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BACKGROUND: Risk factors for malignant tumours of the central nervous system (CNS) are largely unknown. METHODS: We pooled six European cohorts (N = 302,493) and assessed the association between residential exposure to nitrogen dioxide (NO2), fine particles (PM2.5), black carbon (BC), ozone (O3) and eight elemental components of PM2.5 (copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc) and malignant intracranial CNS tumours defined according to the International Classification of Diseases ICD-9/ICD-10 codes 192.1/C70.0, 191.0-191.9/C71.0-C71.9, 192.0/C72.2-C72.5. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level. RESULTS: During 5,497,514 person-years of follow-up (average 18.2 years), we observed 623 malignant CNS tumours. The results of the fully adjusted linear analyses showed a hazard ratio (95% confidence interval) of 1.07 (0.95, 1.21) per 10 µg/m³ NO2, 1.17 (0.96, 1.41) per 5 µg/m³ PM2.5, 1.10 (0.97, 1.25) per 0.5 10-5m-1 BC, and 0.99 (0.84, 1.17) per 10 µg/m³ O3. CONCLUSIONS: We observed indications of an association between exposure to NO2, PM2.5, and BC and tumours of the CNS. The PM elements were not consistently associated with CNS tumour incidence.
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Poluentes Atmosféricos , Poluição do Ar , Neoplasias Encefálicas , Ozônio , Humanos , Material Particulado/efeitos adversos , Dióxido de Nitrogênio , Exposição Ambiental/efeitos adversos , Poluição do Ar/efeitos adversos , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/etiologia , Poluentes Atmosféricos/efeitos adversosRESUMO
Gamma glutamyl transferase (GGT) is related to oxidative stress and an indicator for liver damage. We investigated the association between air pollution and GGT in a large Austrian cohort (N = 116,109) to better understand how air pollution affects human health. Data come from voluntary prevention visits that were routinely collected within the Vorarlberg Health Monitoring and Prevention Program (VHM&PP). Recruitment was ongoing from 1985 to 2005. Blood was drawn and GGT measured centralized in two laboratories. Land use regression models were applied to estimate individuals' exposure at their home address for particulate matter (PM) with a diameter of <2.5 µm (PM2.5), <10 µm (PM10), fraction between 10 µm and 2.5 µm (PMcoarse), as well as PM2.5 absorbance (PM2.5abs), NO2, NOx and eight components of PM. Linear regression models, adjusting for relevant individual and community-level confounders were calculated. The study population was 56 % female with a mean age of 42 years and mean GGT was 19.0 units. Individual PM2.5 and NO2 exposures were essentially below European limit values of 25 and 40 µg/m3, respectively, with means of 13.58 µg/m3 for PM2.5 and 19.93 µg/m3 for NO2. Positive associations were observed for PM2.5, PM10, PM2.5abs, NO2, NOx, and Cu, K, S in PM2.5 and PM10 fractions and Zn mainly in PM2.5 fraction. The strongest association per interquartile range observed was an increase of serum GGT concentration by 1.40 % (95 %-CI: 0.85 %; 1.95 %) per 45.7 ng/m3 S in PM2.5. Associations were robust to adjustments for other biomarkers, in two-pollutant models and the subset with a stable residential history. We found that long-term exposure to air pollution (PM2.5, PM10, PM2.5abs, NO2, NOx) as well as certain elements, were positively associated with baseline GGT levels. The elements associated suggest a role of traffic emissions, long range transport and wood burning.
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Poluentes Atmosféricos , Poluição do Ar , Humanos , Feminino , Adulto , Masculino , Poluentes Atmosféricos/análise , Dióxido de Nitrogênio , Áustria , gama-Glutamiltransferase , Exposição Ambiental/análise , Poluição do Ar/análise , Material Particulado/análiseRESUMO
BACKGROUND: To date, the role of blood lipid levels and their association with the onset and prognosis of ALS is controversial. We explored these associations in a large, population-based case-control study. METHODS: Between October 2010 and June 2014, 336 ALS patients (mean age 65.7 ± 10.7; 57.7% male) and 487 sex- and age-matched controls from the same geographic region were recruited within the ALS registry in Southwest Germany. Triglycerides and cholesterol (high-density lipoprotein (HDL), low-density lipoprotein (LDL), total) were measured. The ALS cohort was followed up for vital status. Conditional logistic regression models were applied to calculate odds ratio (OR) for risk of ALS associated with serum lipid concentrations. In ALS patients only, survival models were used to appraise the prognostic value. RESULTS: High concentration of total cholesterol (OR 1.60, 95% confidence interval (CI) 1.03-2.49, top vs. bottom quartile), but not HDL, LDL, LDL-HDL ratio, or triglycerides, was positively associated with the risk of ALS. During the median follow-up time of 88.9 months, 291 deaths occurred among 336 ALS patients. In the adjusted survival analysis, higher HDL (HR 1.72, 95% CI 1.19-2.50) and LDL cholesterol levels (HR 1.58, 95% CI 1.11-2.26) were associated with higher mortality in ALS patients. In contrast, higher triglyceride levels were associated with lower mortality (HR 0.68, 95% CI 0.48-0.96). CONCLUSION: The results highlight the importance to distinguish cholesterol from triglycerides when considering the prognostic role of lipid metabolism in ALS. It further strengthens the rationale for a triglyceride-rich diet, while the negative impact of cholesterol must be further explored.