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OBJECTIVE: To investigate overall survival (OS) and health-related quality of life (HRQOL) of first-line isolated hepatic perfusion (IHP) compared to best alternative care (BAC) for patients with uveal melanoma liver metastases. SUMMARY BACKGROUND DATA: Approximately half of patients with uveal melanoma develop metastatic disease, most commonly in the liver and systemic treatment options are limited. Isolated hepatic perfusion (IHP) is a locoregional therapy with high response rates but with unclear effect on overall survival (OS). METHODS: In this phase III randomized controlled multicenter trial (the SCANDIUM trial) patients with previously untreated isolated uveal melanoma liver metastases were included between 2013-2021, with at least 24 months of follow-up. The planned accrual was 90 patients randomized 1:1 to receive a one-time treatment with IHP or BAC. Crossover to IHP was not allowed. The primary endpoint was the 24-month OS rate, with the hypothesis of a treatment effect leading to a 50% OS rate in the IHP group compared to 20% in the control group. HRQOL was measured by the EuroQol 5-domains 3-levels (EQ-5D-3L) questionnaire over 12 months. RESULTS: The intention-to-treat (ITT) population included 87 patients randomized to the IHP group (43 patients; 41 [89%] received IHP) or the control group (44 patients). The control group received chemotherapy (49%), immunotherapy (39%), or localized interventions (9%). In the ITT population, the median PFS was 7.4 months in the IHP group compared with 3.3 months in the control group, with a hazard ratio of 0.21 (95% CI, 0.12-0.36). The 24-month OS rate was 46.5% in the IHP group versus 29.5% in the control group (P=0.12). The median OS was 21.7 months versus 17.6 months, with a hazard ratio of 0.64 (95% CI, 0.37-1.10). EQ-5D-3L showed a sustained high health status for the IHP group over 12 months, compared to a deteriorating trend in the control group. CONCLUSIONS: For patients with liver metastases from uveal melanoma, IHP offers high response rates translating to a benefit in PFS including a trend of better HRQOL compared to the control group. However, the primary endpoint of OS at 24 months was not met.
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Background Colon cancer incidence is rising globally, and factors pertaining to urbanization have been proposed involved in this development. Traffic noise may increase colon cancer risk by causing sleep disturbance and stress, thereby inducing known colon cancer risk-factors, e.g. obesity, diabetes, physical inactivity, and alcohol consumption, but few studies have examined this. Objectives The objective of this study was to investigate the association between traffic noise and colon cancer (all, proximal, distal) in a pooled population of 11 Nordic cohorts, totaling 155,203 persons. Methods We identified residential address history and estimated road, railway, and aircraft noise, as well as air pollution, for all addresses, using similar exposure models across cohorts. Colon cancer cases were identified through national registries. We analyzed data using Cox Proportional Hazards Models, adjusting main models for harmonized sociodemographic and lifestyle data. Results During follow-up (median 18.8 years), 2757 colon cancer cases developed. We found a hazard ratio (HR) of 1.05 (95% confidence interval (CI): 0.99-1.10) per 10-dB higher 5-year mean time-weighted road traffic noise. In sub-type analyses, the association seemed confined to distal colon cancer: HR 1.06 (95% CI: 0.98-1.14). Railway and aircraft noise was not associated with colon cancer, albeit there was some indication in sub-type analyses that railway noise may also be associated with distal colon cancer. In interaction-analyses, the association between road traffic noise and colon cancer was strongest among obese persons and those with high NO2-exposure. Discussion A prominent study strength is the large population with harmonized data across eleven cohorts, and the complete address-history during follow-up. However, each cohort estimated noise independently, and only at the most exposed façade, which may introduce exposure misclassification. Despite this, the results of this pooled study suggest that traffic noise may be a risk factor for colon cancer, especially of distal origin.
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Poluição do Ar , Neoplasias do Colo , Ruído dos Transportes , Humanos , Estudos de Coortes , Fatores de Risco , Exposição Ambiental/análise , Dinamarca/epidemiologiaRESUMO
OBJECTIVES: To investigate the association between occupational noise exposure and stroke incidence in a pooled study of five Scandinavian cohorts (NordSOUND). METHODS: We pooled and harmonised data from five Scandinavian cohorts resulting in 78 389 participants. We obtained job data from national registries or questionnaires and recoded these to match a job-exposure matrix developed in Sweden, which specified the annual average daily noise exposure in five exposure classes (LAeq8h): <70, 70-74, 75-79, 80-84, ≥85 dB(A). We identified residential address history and estimated 1-year average road traffic noise at baseline. Using national patient and mortality registers, we identified 7777 stroke cases with a median follow-up of 20.2 years. Analyses were conducted using Cox proportional hazards models adjusting for individual and area-level potential confounders. RESULTS: Exposure to occupational noise at baseline was not associated with overall stroke in the fully adjusted models. For ischaemic stroke, occupational noise was associated with HRs (95% CI) of 1.08 (0.98 to 1.20), 1.09 (0.97 to 1.24) and 1.06 (0.92 to 1.21) in the 75-79, 80-84 and ≥85 dB(A) exposure groups, compared with <70 dB(A), respectively. In subanalyses using time-varying occupational noise exposure, we observed an indication of higher stroke risk among the most exposed (≥85 dB(A)), particularly when restricting analyses to people exposed to occupational noise within the last year (HR: 1.27; 95% CI: 0.99 to 1.63). CONCLUSIONS: We found no association between occupational noise and risk of overall stroke after adjustment for confounders. However, the non-significantly increased risk of ischaemic stroke warrants further investigation.
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OBJECTIVE: Increasing evidence indicates aggravation of immune-mediated diseases due to physiological and psychological stress. Noise is a stressor, however, little is known about its effects on children's respiratory health. This study investigates the association between pre- or postnatal road traffic or occupational noise exposure and asthma as well as related symptoms from infancy to adolescence. METHODS: The study was conducted in the Swedish birth cohort BAMSE, including over 4000 participants followed with repeated questionnaires and clinical tests until 16 years of age. Pre- and postnatal residential road traffic noise was assessed by estimating time-weighted average noise levels at the most exposed façade. Maternal occupational noise exposure during pregnancy was evaluated using a job-exposure-matrix. The associations between noise exposure and asthma-related outcomes were explored using logistic regression and generalised estimating equations. RESULTS: We observed non-significant associations for asthma ever up to 16 years with residential road traffic noise exposure in infancy ≥55 dBLden (adjusted OR = 1.22; 95% CI 0.90-1.65), as well as prenatal occupational noise exposure ≥80 dBLAeq,8h (1.18, 0.85-1.62). In longitudinal analyses, however, no clear associations between pre- or postnatal exposure to residential road traffic noise, or average exposure to noise since birth, were detected in relation to asthma or wheeze until 16 years. CONCLUSION: We did not find a clear overall association between exposure to noise during different time periods and asthma or wheeze up to adolescence.
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Asma , Ruído dos Transportes , Adolescente , Asma/epidemiologia , Asma/etiologia , Criança , Estudos de Coortes , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Gravidez , Suécia/epidemiologiaRESUMO
BACKGROUND: While recent years have seen a revolution in the treatment of metastatic cutaneous melanoma, no treatment has yet been able to demonstrate any prolonged survival in metastatic uveal melanoma. Thus, metastatic uveal melanoma remains a disease with an urgent unmet medical need. Reports of treatment with immune checkpoint inhibitors have thus far been disappointing. Based on animal experiments, it is reasonable to hypothesize that the effect of immunotherapy may be augmented by epigenetic therapy. Proposed mechanisms include enhanced expression of HLA class I and cancer antigens on cancer cells, as well as suppression of myeloid suppressor cells. METHODS: The PEMDAC study is a multicenter, open label phase II study assessing the efficacy of concomitant use of the PD1 inhibitor pembrolizumab and the class I HDAC inhibitor entinostat in adult patients with metastatic uveal melanoma. Primary endpoint is objective response rate. Eligible patients have histologically confirmed metastatic uveal melanoma, ECOG performance status 0-1, measurable disease as per RECIST 1.1 and may have received any number of prior therapies, with the exception of anticancer immunotherapy. Twenty nine patients will be enrolled. Patients receive pembrolizumab 200 mg intravenously every third week in combination with entinostat 5 mg orally once weekly. Treatment will continue until progression of disease or intolerable toxicity or for a maximum of 24 months. DISCUSSION: The PEMDAC study is the first trial to assess whether the addition of an HDAC inhibitor to anti-PD1 therapy can yield objective anti-tumoral responses in metastatic UM. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT02697630 . (Registered 3 March 2016). EudraCT registration number: 2016-002114-50.
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Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Benzamidas/administração & dosagem , Melanoma/tratamento farmacológico , Piridinas/administração & dosagem , Neoplasias Uveais/tratamento farmacológico , Administração Intravenosa , Administração Oral , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzamidas/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Masculino , Estudos Prospectivos , Piridinas/uso terapêutico , Projetos de Pesquisa , Resultado do TratamentoRESUMO
BACKGROUND: There is limited evidence from longitudinal studies on transportation noise from different sources and development of ischaemic heart disease (IHD) and stroke. OBJECTIVES: This cohort study assessed associations between exposure to noise from road traffic, railway or aircraft and incidence of IHD and stroke. METHODS: In a cohort of 20 012 individuals from Stockholm County, we estimated long-term residential exposure to road traffic, railway and aircraft noise. National Patient and Cause-of-Death Registers were used to identify IHD and stroke events. Information on risk factors was obtained from questionnaires and registers. Adjusted HR for cardiovascular outcomes related to source-specific noise exposure were computed using Cox proportional hazards regression. RESULTS: No clear or consistent associations were observed between transportation noise and incidence of IHD or stroke. However, noise exposure from road traffic and aircraft was related to IHD incidence in women, with HR of 1.11 (95% CI 1.00 to 1.22) and 1.25 (95% CI 1.09 to 1.44) per 10 dB Lden, respectively. For both sexes taken together, we observed a particularly high risk of IHD in those exposed to all three transportation noise sources at≥45 dB Lden, with a HR of 1.57 (95% CI 1.06 to 2.32), and a similar tendency for stroke (HR 1.42; 95% CI 0.87 to 2.32). CONCLUSION: No overall associations were observed between transportation noise exposure and incidence of IHD or stroke. However, there appeared to be an increased risk of IHD in women exposed to road traffic or aircraft noise as well as in those exposed to multiple sources of transportation noise.
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Incidência , Isquemia Miocárdica/epidemiologia , Ruído dos Transportes/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/etiologia , Ruído/efeitos adversos , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Suécia/epidemiologiaRESUMO
BACKGROUND: There is growing evidence that traffic noise exposure is associated with adiposity among adults but data in children are limited. OBJECTIVE: This longitudinal study examined whether pre- and postnatal noise exposure is associated with body mass index (BMI) between birth and adolescence or with adverse birth outcomes. METHODS: The study was conducted using data from the BAMSE birth cohort, which included 4089 children born in Stockholm County, Sweden. Data on BMI from birth to adolescence were collected via questionnaires, clinical examinations and health care records. A national register provided information on birth outcomes. Road traffic noise levels at the most exposed façade were estimated for all residences of the children during follow-up, as well as of their mothers during pregnancy, and time-weighted average exposure was calculated for different time windows. Maternal occupational noise exposure was obtained from a job-exposure-matrix. Logistic- and quantile regression models were used to estimate associations between noise exposure and health outcomes. RESULTS: We found residential road traffic noise exposure to be associated with increases in BMI from school age to adolescence, but not at earlier ages. In the age groups 8-11 years and 12-16 years the BMI increments were 0.11â¯kg/m2 per 10â¯dBâ¯Lden (95% CI 0.08-0.13) and 0.20â¯kg/m2 per 10â¯dBâ¯Lden (95% CI 0.17-0.22), respectively. Maternal noise exposure during pregnancy was generally unrelated to adverse birth outcomes and BMI from birth to adolescence in the children, however, traffic noise exposure was associated with a decreased risk of preterm birth CONCLUSION: Residential road traffic noise exposure was associated with BMI increases from school age to adolescence, but not at earlier ages. Maternal occupational noise exposure or exposure from road traffic during pregnancy were not consistently related to birth outcomes or BMI from birth to adolescence.
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Exposição Ambiental/estatística & dados numéricos , Ruído dos Transportes , Adolescente , Adulto , Criança , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Estudos Longitudinais , Gravidez , SuéciaRESUMO
Glycoprotein C (gC) mediates the attachment of HSV-1 to susceptible host cells by interacting with glycosaminoglycans (GAGs) on the cell surface. gC contains a mucin-like region located near the GAG-binding site, which may affect the binding activity. Here, we address this issue by studying a HSV-1 mutant lacking the mucin-like domain in gC and the corresponding purified mutant protein (gCΔmuc) in cell culture and GAG-binding assays, respectively. The mutant virus exhibited two functional alterations as compared with native HSV-1 (i.e. decreased sensitivity to GAG-based inhibitors of virus attachment to cells and reduced release of viral particles from the surface of infected cells). Kinetic and equilibrium binding characteristics of purified gC were assessed using surface plasmon resonance-based sensing together with a surface platform consisting of end-on immobilized GAGs. Both native gC and gCΔmuc bound via the expected binding region to chondroitin sulfate and sulfated hyaluronan but not to the non-sulfated hyaluronan, confirming binding specificity. In contrast to native gC, gCΔmuc exhibited a decreased affinity for GAGs and a slower dissociation, indicating that once formed, the gCΔmuc-GAG complex is more stable. It was also found that a larger number of gCΔmuc bound to a single GAG chain, compared with native gC. Taken together, our data suggest that the mucin-like region of HSV-1 gC is involved in the modulation of the GAG-binding activity, a feature of importance both for unrestricted virus entry into the cells and release of newly produced viral particles from infected cells.
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Glicosaminoglicanos/metabolismo , Herpesvirus Humano 1/fisiologia , Mucinas/metabolismo , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/metabolismo , Animais , Linhagem Celular , Herpesvirus Humano 1/ultraestrutura , Humanos , Cinética , Microscopia de Fluorescência , Proteínas Mutantes/metabolismo , Mutação , Neuraminidase/metabolismo , Concentração Osmolar , Ligação Proteica , Estrutura Terciária de Proteína , Ressonância de Plasmônio de Superfície , Vírion/metabolismoRESUMO
Herpes simplex encephalitis (HSE), targeting the limbic system, is the most common cause of viral encephalitis in the Western world. Two pathways for viral entry to the central nervous system (CNS) in HSE have been suggested: either via the trigeminal nerve or via the olfactory tract. This question remains unsettled, and studies of viral spread between the two brain hemispheres are scarce. Here, we investigated the olfactory infection as a model of infection and tropism of herpes simplex virus 1 (HSV-1), the causative agent of HSE, in the CNS of rats. Rats were instilled with HSV-1 in the right nostril and sacrificed 1-6 days post-infection, and tissues were analysed for viral spread using immunohistochemistry and quantitative PCR (qPCR). After nasal instillation, HSV-1 infected mitral cells of the olfactory bulb (OB) on the right side only, followed by limbic encephalitis. As a novel finding, the anterior commissure (AC) conveyed a rapid transmission of virus between the right and the left OB, acting as a shortcut also between the olfactory cortices. The neuronal cell population that conveyed the viral infection via the AC was positive for the water channel protein aquaporin 9 (AQP9) by immunohistochemistry. Quantification of AQP9 in cerebrospinal fluid samples of HSE patients showed increment as compared to controls. We conclude that the olfactory route and the AC are important for the spread of HSV-1 within the olfactory/limbic system of rats and furthermore, we suggest that AQP9 is involved in viral tropism and pathogenesis of HSE.
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Comissura Anterior/virologia , Aquaporinas/metabolismo , Encefalite por Herpes Simples/virologia , Herpesvirus Humano 1/patogenicidade , Mucosa Olfatória/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Comissura Anterior/metabolismo , Modelos Animais de Doenças , Encefalite por Herpes Simples/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neurônios/metabolismo , Neurônios/virologia , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo RealRESUMO
OBJECTIVES: Limited evidence suggests adverse effects of traffic noise exposure on the metabolic system. This study investigates the association between road traffic noise and obesity markers as well as the role of combined exposure to multiple sources of traffic noise. METHODS: In a cross-sectional study performed in 2002-2006, we assessed exposure to noise from road traffic, railways and aircraft at the residences of 5075 Swedish men and women, primarily from suburban and semirural areas of Stockholm County. A detailed questionnaire and medical examination provided information on markers of obesity and potential confounders. Multiple linear and logistic regression models were used to assess associations between traffic noise and body mass index (BMI), waist circumference and waist-hip ratio using WHO definitions of obesity. RESULTS: Road traffic noise was significantly related to waist circumference with a 0.21 cm (95% CI 0.01 to 0.41) increase per 5 dB(A) rise in L(den). The OR for central obesity among those exposed to road traffic noise ≥ 45 dB(A) was 1.18 (95% CI 1.03 to 1.34) in comparison to those exposed below this level. Similar results were seen for waist-hip ratio (OR 1.29; 95% CI 1.14 to 1.45) but not for BMI (OR 0.89; 95% CI 0.76 to 1.04). Central obesity was also associated with exposure to railway and aircraft noise, and a particularly high risk was seen for combined exposure to all three sources of traffic noise (OR 1.95; 95% CI 1.24 to 3.05). CONCLUSIONS: Our results suggest that traffic noise exposure can increase the risk of central obesity. Combined exposure to different sources of traffic noise may convey a particularly high risk.
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Índice de Massa Corporal , Exposição Ambiental/efeitos adversos , Ruído dos Transportes/efeitos adversos , Obesidade Abdominal/etiologia , Meios de Transporte , Circunferência da Cintura , Relação Cintura-Quadril , Adulto , Aeronaves , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Veículos Automotores , Razão de Chances , FerroviasRESUMO
BACKGROUND: Noise has been found to be associated with endocrine changes and cardiovascular disease. Increased cortisol levels and chronic sleep problems due to noise may increase the risk of obesity. OBJECTIVES: We investigated the relationship between road traffic noise and obesity markers. Furthermore, we explored the modifying role of noise sensitivity, noise annoyance, and sleep disturbances. METHODS: We used data from a population-based study, HUBRO (N=15,085), and its follow-up study HELMILO (N=8410) conducted in Oslo, Norway. Measurements were used to define body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), and these binary outcomes: BMI≥30kg/m(2), WC≥102cm (men)/88cm (women), and WHR≥0.90 (men)/0.85 (women). Modelled levels of road traffic noise (Lden) were assigned to each participant's home address. Linear and logistic regression models were used to examine the associations. RESULTS: The results indicated no significant associations between road traffic noise and obesity markers in the total populations. However, in highly noise sensitive women (n=1106) a 10dB increase in noise level was associated with a slope (=beta) of 1.02 (95% confidence interval (CI): 1.01, 1.03) for BMI, 1.01 (CI: 1.00, 1.02) for WC, and an odds ratio (OR) of 1.24 (CI: 1.01, 1.53) for WHR ≥0.85. The associations appeared weaker in highly noise sensitive men. We found no effect modification of noise annoyance or sleep disturbances. In a sub-population with bedroom facing a road, the associations increased in men (e.g. an OR of 1.25 (CI: 0.88, 1.78) for BMI ≥30kg/m(2)), but not in women. Among long-term residents the associations increased for BMI ≥30kg/m(2) (OR of 1.07 (CI: 0.93, 1.24) in men and 1.10 (CI: 0.97, 1.26) in women), but not for the other outcomes. CONCLUSION: In an adult urban Scandinavian population, road traffic noise was positively associated with obesity markers among highly noise sensitive women. The associations appeared stronger among men with bedroom facing a street, representing a population with more accurately assigned exposure.
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Exposição Ambiental , Ruído dos Transportes/efeitos adversos , Obesidade/diagnóstico , Obesidade/epidemiologia , Transtornos do Sono-Vigília/epidemiologia , Adulto , Idoso , Índice de Massa Corporal , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Obesidade/etiologia , Obesidade Abdominal/epidemiologia , Obesidade Abdominal/etiologia , Transtornos do Sono-Vigília/etiologia , Circunferência da Cintura , Razão Cintura-EstaturaRESUMO
BACKGROUND: Emerging evidence shows that long-term exposure to air pollution, road traffic noise, and greenness can each be associated with cardiovascular disease, but only few studies combined these exposures. In this study, we assessed associations of multiple environmental exposures and incidence of myocardial infarction using annual time-varying predictors. MATERIALS AND METHODS: In a population-based cohort of 20,407 women in Sweden, we estimated a five-year moving average of residential exposure to air pollution (PM2.5, PM10 and NO2), road traffic noise (Lden), and greenness (normalized difference vegetation index, NDVI in 500 m buffers), from 1998 to 2017 based on annually varying exposures and address history. We used adjusted time-varying Cox proportional hazards regressions to estimate hazard ratios (HR) and 95 % confidence intervals (95 % CI) of myocardial infarction per interquartile range (IQR). Furthermore, we investigated interactions between the exposures and explored potential vulnerable subgroups. RESULTS: In multi-exposure models, long-term exposure to greenness was inversely associated with incidence of myocardial infarction (HR 0.89; 95 % CI 0.80, 0.99 per IQR NDVI increase). Stronger associations were observed in some subgroups, e.g. among women with low attained education and in overweight (BMI ≥ 25 kg/m2) compared to their counterparts. For air pollution, we observed a tendency of an increased risk of myocardial infarction in relation to PM2.5 (HR 1.07; 95 % CI 0.93, 1.23) and the association appeared stronger in women with low attained education (HR 1.30; 95 % CI 1.06, 1.58). No associations were observed for PM10, NO2 or road traffic noise. Furthermore, there were no clear interaction patterns between the exposures. CONCLUSION: Over a 20-year follow-up period, in multi-exposure models, we found an inverse association between residential greenness and risk of myocardial infarction among women. Furthermore, we observed an increased risk of myocardial infarction in relation to PM2.5 among women with low attained education. Road traffic noise was not associated with myocardial infarction.
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Background: Available evidence suggests a link between exposure to transportation noise and an increased risk of obesity. We aimed to assess exposure-response functions for long-term residential exposure to road traffic, railway and aircraft noise, and markers of obesity. Methods: Our cross-sectional study is based on pooled data from 11 Nordic cohorts, including up to 162,639 individuals with either measured (69.2%) or self-reported obesity data. Residential exposure to transportation noise was estimated as a time-weighted average Lden 5 years before recruitment. Adjusted linear and logistic regression models were fitted to assess beta coefficients and odds ratios (OR) with 95% confidence intervals (CI) for body mass index, overweight, and obesity, as well as for waist circumference and central obesity. Furthermore, natural splines were fitted to assess the shape of the exposure-response functions. Results: For road traffic noise, the OR for obesity was 1.06 (95% CI = 1.03, 1.08) and for central obesity 1.03 (95% CI = 1.01, 1.05) per 10 dB Lden. Thresholds were observed at around 50-55 and 55-60 dB Lden, respectively, above which there was an approximate 10% risk increase per 10 dB Lden increment for both outcomes. However, linear associations only occurred in participants with measured obesity markers and were strongly influenced by the largest cohort. Similar risk estimates as for road traffic noise were found for railway noise, with no clear thresholds. For aircraft noise, results were uncertain due to the low number of exposed participants. Conclusion: Our results support an association between road traffic and railway noise and obesity.
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Health effects have repeatedly been associated with residential levels of air pollution. However, it is difficult to disentangle effects of long-term exposure to locally generated and long-range transported pollutants, as well as to exhaust emissions and wear particles from road traffic. We aimed to investigate effects of exposure to particulate matter fractions on respiratory health in the Swedish adult population, using an integrated assessment of sources at different geographical scales. The study was based on a nationwide environmental health survey performed in 2007, including 25,851 adults aged 18-80 years. Individual exposure to particulate matter at residential addresses was estimated by dispersion modelling of regional, urban and local sources. Associations between different size fractions or source categories and respiratory outcomes were analysed using multiple logistic regression, adjusting for individual and contextual confounding. Exposure to locally generated wear particles showed associations for blocked nose or hay fever, chest tightness or cough, and restricted activity days with odds ratios of 1.5-2 per 10-µg·m(-3) increase. Associations were also seen for locally generated combustion particles, which disappeared following adjustment for exposure to wear particles. In conclusion, our data indicate that long-term exposure to locally generated road wear particles increases the risk of respiratory symptoms in adults.
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Poluentes Atmosféricos/efeitos adversos , Transtornos Respiratórios/induzido quimicamente , Emissões de Veículos/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cidades , Tosse/etiologia , Estudos Transversais , Exposição Ambiental , Feminino , Geografia , Inquéritos Epidemiológicos , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Razão de Chances , Material Particulado/efeitos adversos , Análise de Regressão , Transtornos Respiratórios/epidemiologia , Rinite Alérgica Sazonal/etiologia , Suécia , Adulto JovemRESUMO
Land Use Regression (LUR) models have been used to describe and model spatial variability of annual mean concentrations of traffic related pollutants such as nitrogen dioxide (NO2), nitrogen oxides (NOx) and particulate matter (PM). No models have yet been published of elemental composition. As part of the ESCAPE project, we measured the elemental composition in both the PM10 and PM2.5 fraction sizes at 20 sites in each of 20 study areas across Europe. LUR models for eight a priori selected elements (copper (Cu), iron (Fe), potassium (K), nickel (Ni), sulfur (S), silicon (Si), vanadium (V), and zinc (Zn)) were developed. Good models were developed for Cu, Fe, and Zn in both fractions (PM10 and PM2.5) explaining on average between 67 and 79% of the concentration variance (R(2)) with a large variability between areas. Traffic variables were the dominant predictors, reflecting nontailpipe emissions. Models for V and S in the PM10 and PM2.5 fractions and Si, Ni, and K in the PM10 fraction performed moderately with R(2) ranging from 50 to 61%. Si, NI, and K models for PM2.5 performed poorest with R(2) under 50%. The LUR models are used to estimate exposures to elemental composition in the health studies involved in ESCAPE.
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Poluição do Ar/análise , Modelos Teóricos , Material Particulado/análise , Poluição do Ar/estatística & dados numéricos , Cobre/análise , Europa (Continente) , Sistemas de Informação Geográfica , Níquel/análise , Dióxido de Nitrogênio/análise , Óxidos de Nitrogênio/análise , Potássio/análise , Análise de Regressão , Silício/análise , Enxofre/análise , Vanádio/análise , Zinco/análiseRESUMO
Background: Recent evidence suggests environmental health inequalities both within and between European countries and socially deprived groups may be more susceptible to pollution. However, evidence is still inconclusive and additional studies are warranted. This study aims to investigate sociodemographic inequalities in long-term residential exposure to air pollution, road traffic noise, and greenness, taking lifestyle and degree of urbanization into account. Methods: In total 20,407 women, born 1914-48 residing in Uppsala County, Sweden, were followed between 1997 and 2017. Time-varying sociodemographic variables were obtained from registers, and questionnaires provided lifestyle information. Generalized estimating equations were used to compute beta-coefficients (ß) and 95% confidence intervals (95% CI) for associations between sociodemographic and lifestyle variables and spatial-temporal modeled particulate matter (PM2.5, PM10), nitrogen dioxide (NO2), road traffic noise and greenness. All models were additionally stratified by urbanization type. Results: Urban area residency was the most important predictor of high exposure to air pollution and noise, and to low greenness. For instance, ß for NO2 was -2.92 (95% CI = -3.00, -2.83) and -3.10 (95% CI = -3.18, -3.01) µg/m3 in suburban and rural areas, respectively, compared with urban areas. For greenness, the opposite held true with corresponding ß of 0.059 (95% CI = 0.056, 0.062) and 0.095 (95% CI = 0.092, 0.098). Within urban areas, elderly, unmarried and well-educated women had the highest environmental burden. However, less pronounced, and even reversed associations were found in suburban and rural areas. Conclusion: This study provides evidence of a mixed pattern of environmental health inequalities across sociodemographic groups in urban areas.
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BACKGROUND: Transportation noise may induce cardiovascular disease, but the public health implications are unclear. OBJECTIVES: The study aimed to assess exposure-response relationships for different transportation noise sources and ischemic heart disease (IHD), including subtypes. METHODS: Pooled analyses were performed of nine cohorts from Denmark and Sweden, together including 132,801 subjects. Time-weighted long-term exposure to road, railway, and aircraft noise, as well as air pollution, was estimated based on residential histories. Hazard ratios (HRs) were calculated using Cox proportional hazards models following adjustment for lifestyle and socioeconomic risk factors. RESULTS: A total of 22,459 incident cases of IHD were identified during follow-up from national patient and mortality registers, including 7,682 cases of myocardial infarction. The adjusted HR for IHD was 1.03 [95% confidence interval (CI) 1.00, 1.05] per 10 dB Lden for both road and railway noise exposure during 5 y prior to the event. Higher risks were indicated for IHD excluding angina pectoris cases, with HRs of 1.06 (95% CI: 1.03, 1.08) and 1.05 (95% CI: 1.01, 1.08) per 10 dB Lden for road and railway noise, respectively. Corresponding HRs for myocardial infarction were 1.02 (95% CI: 0.99, 1.05) and 1.04 (95% CI: 0.99, 1.08). Increased risks were observed for aircraft noise but without clear exposure-response relations. A threshold at around 55 dB Lden was suggested in the exposure-response relation for road traffic noise and IHD. DISCUSSION: Exposure to road, railway, and aircraft noise in the prior 5 y was associated with an increased risk of IHD, particularly after exclusion of angina pectoris cases, which are less well identified in the registries. https://doi.org/10.1289/EHP10745.
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Infarto do Miocárdio , Isquemia Miocárdica , Ruído dos Transportes , Humanos , Ruído dos Transportes/efeitos adversos , Exposição Ambiental , Isquemia Miocárdica/epidemiologia , Infarto do Miocárdio/epidemiologia , Angina PectorisRESUMO
BACKGROUND: Environmental noise is an important environmental exposure that can affect health. An association between transportation noise and breast cancer incidence has been suggested, although current evidence is limited. We investigated the pooled association between long-term exposure to transportation noise and breast cancer incidence. METHODS: Pooled data from eight Nordic cohorts provided a study population of 111,492 women. Road, railway, and aircraft noise were modelled at residential addresses. Breast cancer incidence (all, estrogen receptor (ER) positive, and ER negative) was derived from cancer registries. Hazard ratios (HR) were estimated using Cox Proportional Hazards Models, adjusting main models for sociodemographic and lifestyle variables together with long-term exposure to air pollution. RESULTS: A total of 93,859 women were included in the analyses, of whom 5,875 developed breast cancer. The median (5th-95th percentile) 5-year residential road traffic noise was 54.8 (40.0-67.8) dB Lden, and among those exposed, the median railway noise was 51.0 (41.2-65.8) dB Lden. We observed a pooled HR for breast cancer (95 % confidence interval (CI)) of 1.03 (0.99-1.06) per 10 dB increase in 5-year mean exposure to road traffic noise, and 1.03 (95 % CI: 0.96-1.11) for railway noise, after adjustment for lifestyle and sociodemographic covariates. HRs remained unchanged in analyses with further adjustment for PM2.5 and attenuated when adjusted for NO2 (HRs from 1.02 to 1.01), in analyses using the same sample. For aircraft noise, no association was observed. The associations did not vary by ER status for any noise source. In analyses using <60 dB as a cutoff, we found HRs of 1.08 (0.99-1.18) for road traffic and 1.19 (0.95-1.49) for railway noise. CONCLUSIONS: We found weak associations between road and railway noise and breast cancer risk. More high-quality prospective studies are needed, particularly among those exposed to railway and aircraft noise before conclusions regarding noise as a risk factor for breast cancer can be made.
Assuntos
Neoplasias da Mama , Ruído dos Transportes , Humanos , Feminino , Ruído dos Transportes/efeitos adversos , Estudos de Coortes , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Fatores de Risco , Estudos Prospectivos , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análiseRESUMO
PURPOSE: About half of patients with metastatic uveal melanoma present with isolated liver metastasis, in whom the median survival is 6-12 months. The few systemic treatment options available only moderately prolong survival. Isolated hepatic perfusion (IHP) with melphalan is a regional treatment option, but prospective efficacy and safety data are lacking. METHODS: In this multicenter, randomized, open-label, phase III trial, patients with previously untreated isolated liver metastases from uveal melanoma were randomly assigned to receive a one-time treatment with IHP with melphalan or best alternative care (control group). The primary end point was overall survival at 24 months. Here, we report the secondary outcomes of response according to RECIST 1.1 criteria, progression-free survival (PFS), hepatic PFS (hPFS), and safety. RESULTS: Ninety-three patients were randomly assigned, and 87 patients were assigned to either IHP (n = 43) or a control group receiving the investigator's choice of treatment (n = 44). In the control group, 49% received chemotherapy, 39% immune checkpoint inhibitors, and 9% locoregional treatment other than IHP. In an intention-to-treat analysis, the overall response rates (ORRs) were 40% versus 4.5% in the IHP and control groups, respectively (P < .0001). The median PFS was 7.4 months versus 3.3 months (P < .0001), with a hazard ratio of 0.21 (95% CI, 0.12 to 0.36), and the median hPFS was 9.1 months versus 3.3 months (P < .0001), both favoring the IHP arm. There were 11 treatment-related serious adverse events in the IHP group compared with seven in the control group. There was one treatment-related death in the IHP group. CONCLUSION: IHP treatment resulted in superior ORR, hPFS, and PFS compared with best alternative care in previously untreated patients with isolated liver metastases from primary uveal melanoma.