RESUMEN
PURPOSE: To retrospectively evaluate the tislelizumab-based chemoimmunotherapy combined with gemcitabine/cisplatin for bladder-sparing in patients with muscle-invasive bladder cancer (MIBC). METHODS: Forty-five patients who received bladder-sparing treatment or radical cystectomy (RC) for MIBC (cT2-T4a, NxM0) were retrospectively enrolled. All patients received maximal transurethral resection of bladder tumor (mTURBT), followed by four cycles of chemo-immunotherapy with tislelizumab (PD-L1 inhibitor), gemcitabine, and cisplatin. Clinical efficacy was evaluated to compare the benefit of bladder-sparing treatment on clinical CR (cCR) and RC for non-cCR patients. The primary outcomes were bladder intact disease-free survival (BIDFS) and overall survival (OS), and the secondary outcomes were adverse effects. The PD-L1 status and molecular subtypes of tumors were analyzed. RESULTS: The overall survival rate was 88.8% (95%CI: 79.6%, 98.0%) at 12 months, 85.7% (95%CI: 74.9%, 96.5%) at 18 months, and 66.6% (95%CI: 45.2%, 88.0%) at 24 months. Twenty-nine patients (64.4%) achieved cCR and their OS rate was 96.6% (95%CI: 89.9%, 100%). Sixteen patients were in the non-cCR group, and their OS rate was 75.0% (95%CI: 53.8%, 96.2%) at 12 months, 65.6% (95%CI: 40.3%, 90.9%) at 18 months, and 52.5% (95%CI: 21.9%, 83.1%) at 24 months. The BIDFS rate for patients who received bladder-sparing treatment was 96.0% (95%CI: 88.4%, 100%) from 12 to 24 months. Four patients (8.8%) were PD-L1 positive and 41 patients (91.2%) were PD-L1 negative. CONCLUSIONS: Our retrospective study of patients with MIBC suggests that tislelizumab-based neoadjuvant therapy was a safe and effective bladder-sparing treatment.
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Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Cistectomía , Desoxicitidina , Gemcitabina , Invasividad Neoplásica , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/mortalidad , Masculino , Femenino , Estudios Retrospectivos , Anciano , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Tratamientos Conservadores del Órgano/métodos , Tasa de Supervivencia , Adulto , Anciano de 80 o más AñosRESUMEN
PURPOSE: As a non-invasive treatment, stereotactic body radiation therapy (SBRT) has been an emerging and effective option for patients with unresectable intrahepatic cholangiocarcinoma (ICC). The Cyber Knife has an SBRT system, which can realize real-time tracking of tumors during treatment. It can protect the surrounding normal liver tissue while the tumor gets the therapeutic dose. The purpose of this study was to evaluate the factors affecting the local control rate for patients after SBRT treatment, and to predict the factors affecting survival rates, then to report the 3-year actual survival rates after treatment and identify the influencing factors of 3-year survival rate. MATERIALS AND METHODS: We conducted a long-term follow-up of 43 patients with unresectable intrahepatic cholangiocarcinoma who underwent Cyber Knife in our hospital from January 2016 to December 2018. Regular medical check-ups were performed every 2-3 months after SBRT to evaluated the effect of treatment. RESULTS: The median follow-up time was 15 months (4-78 months), and the median progression-free survival (PFS) was 6 months (95% CI, 2.788-9.212) and the median overall survival (OS) was 12 months (95% CI, 3.434-20.566), respectively. Based on modified Response Evaluation and Criteria in Solid Tumor (mRECIST), response rate (RR) and disease control rate (DCR) of SBRT in unresectable ICC were 55.2% and 86%. The 1-, 2- and 3-years OS rate were 51.2%, 32.6% and 23.3%. Multivariate analysis based on competing risk survival analysis identified that patients with multiple nodules, large diameter, high level of CA199 and CEA, poor ECOG performance status had worse overall survival (p < 0.05). Patients who survived ≥3 years had significantly lower levels of CEA, CA199, smaller tumor diameters and lower number of lesions (p < 0.05). CONCLUSION: The SBRT might be a candidate option for patients who unable to perform surgery. The rate of 3-year survival after SBRT for unresectable ICC can be expected with 23.3%.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Radiocirugia , Humanos , Radiocirugia/efectos adversos , Resultado del Tratamiento , Colangiocarcinoma/radioterapia , Colangiocarcinoma/cirugía , Conductos Biliares Intrahepáticos/patología , Conductos Biliares Intrahepáticos/efectos de la radiación , Neoplasias de los Conductos Biliares/patología , Estudios RetrospectivosRESUMEN
OBJECTIVES: To determine whether the Child Opportunity Index (COI), a nationally available measure of relative educational, health/environmental, and social/economic opportunity across census tracts within metropolitan areas, is associated with population- and patient-level asthma morbidity. STUDY DESIGN: This population-based retrospective cohort study was conducted between 2011 and 2013 in a southwest Ohio county. Participants included all children aged 1-16 years with hospitalizations or emergency department visits for asthma or wheezing at a major pediatric hospital. Patients were identified using discharge diagnosis codes and geocoded to their home census tract. The primary population-level outcome was census tract asthma hospitalization rate. The primary patient-level outcome was rehospitalization within 12 months of the index hospitalization. Census tract opportunity was characterized using the COI and its educational, health/environmental, and social/economic domains. RESULTS: Across 222 in-county census tracts, there were 2539 geocoded hospitalizations. The median asthma-related hospitalization rate was 5.0 per 1000 children per year (IQR, 1.9-8.9). Median hospitalization rates in very low, low, moderate, high, and very high opportunity tracts were 9.1, 7.6, 4.6, 2.1, and 1.8 per 1000, respectively (P < .0001). The social/economic domain had the most variables significantly associated with the outcome at the population level. The adjusted patient-level analyses showed that the COI was not significantly associated with a patient's risk of rehospitalization within 12 months. CONCLUSIONS: The COI was associated with population-level asthma morbidity. The details provided by the COI may inform interventions aimed at increasing opportunity and reducing morbidity across regions.
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Asma/epidemiología , Disparidades en el Estado de Salud , Hospitalización/estadística & datos numéricos , Clase Social , Salud Urbana/estadística & datos numéricos , Adolescente , Asma/economía , Asma/etiología , Asma/terapia , Niño , Preescolar , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Lactante , Modelos Logísticos , Masculino , Ohio/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Salud Urbana/economíaRESUMEN
OBJECTIVES: To assess whether population-level violent (and all) crime rates were associated with population-level child asthma utilization rates and predictive of patient-level risk of asthma reutilization after a hospitalization. STUDY DESIGN: A retrospective cohort study of 4638 pediatric asthma-related emergency department visits and hospitalizations between 2011 and 2013 was completed. For population-level analyses, census tract asthma utilization rates were calculated by dividing the number of utilization events within a tract by the child population. For patient-level analyses, hospitalized patients (n = 981) were followed until time of first asthma-related reutilization. The primary predictor was the census tract rate of violent crime as recorded by the police; the all crime (violent plus nonviolent) rate was also assessed. RESULTS: Census tract-level violent and all crime rates were significantly correlated with asthma utilization rates (both P < .0001). The violent crime rate explained 35% of the population-level asthma utilization variance and remained associated with increased utilization after adjustment for census tract poverty, unemployment, substandard housing, and traffic exposure (P = .002). The all crime rate explained 28% of the variance and was similarly associated with increased utilization after adjustment (P = .02). Hospitalized children trended toward being more likely to reutilize if they lived in higher violent (P = .1) and all crime areas (P = .01). After adjustment, neither relationship was significant. CONCLUSIONS: Crime data could help facilitate early identification of potentially toxic stressors relevant to the control of asthma for populations and patients.
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Asma/epidemiología , Crimen/estadística & datos numéricos , Exposición a la Violencia/estadística & datos numéricos , Niño , Preescolar , Estudios de Cohortes , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Ohio/epidemiología , Policia , Estudios RetrospectivosRESUMEN
OBJECTIVES: Limited information is available concerning the post-treatment neutrophil-lymphocyte ratio in critical limb ischemia patients who receive conservative therapy. Accordingly, this study was designed to evaluate the predictive value of the post-treatment neutrophil-lymphocyte ratio in critical limb ischemia patients without surgery. METHOD: From January 2009 to January 2011, critical limb ischemia patients were admitted to a vascular center. The demographic data, patient histories, comorbidities and risk factors were documented, and the differential cell count was determined at admission and seven days later after conservative therapy. The cutoff value of the post-treatment neutrophil-lymphocyte ratio was determined by an ROC curve. Patients were divided into groups A and B according to the cutoff value. Amputation-free survival was compared between groups. Univariate and multivariate analyses were used to identify independent risk factors. RESULT: A total of 172 patients were identified with a mean age 71.98±10.09 years; among them, 122 were male. A value of 3.8 was identified as the cutoff value of the post-treatment neutrophil-lymphocyte ratio. Groups A (post-treatment neutrophil-lymphocyte ratio ≥3.8) and B (post-treatment neutrophil-lymphocyte ratio <3.8) showed a significant difference in amputation-free survival (P<0.001). The 1-year, 2-year and 3-year amputation-free survival rates were 79.6%, 55.6% and 46.3%, respectively, in group A; however, in group B, these values were 89.7%, 79.3% and 75.9%, respectively. The post-treatment neutrophil-lymphocyte ratio was identified as an independent predictive factor for amputation in critical limb ischemia patients (P<0.001). CONCLUSION: The post-treatment neutrophil-lymphocyte ratio is an independent predictive factor for amputation in critical limb ischemia patients. Patients with a post-treatment neutrophil-lymphocyte ratio ≥3.8 are likely to suffer from amputation; amputation-free survival usually occurs in patients with a post-treatment neutrophil-lymphocyte ratio <3.8.
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Amputación Quirúrgica , Extremidades/irrigación sanguínea , Isquemia/sangre , Isquemia/terapia , Linfocitos , Neutrófilos , Anciano , Anciano de 80 o más Años , Enfermedad Crítica , Métodos Epidemiológicos , Femenino , Humanos , Isquemia/mortalidad , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Pronóstico , Valores de Referencia , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
OBJECTIVES: Limited information is available concerning the post-treatment neutrophil-lymphocyte ratio in critical limb ischemia patients who receive conservative therapy. Accordingly, this study was designed to evaluate the predictive value of the post-treatment neutrophil-lymphocyte ratio in critical limb ischemia patients without surgery. METHOD: From January 2009 to January 2011, critical limb ischemia patients were admitted to a vascular center. The demographic data, patient histories, comorbidities and risk factors were documented, and the differential cell count was determined at admission and seven days later after conservative therapy. The cutoff value of the post-treatment neutrophil-lymphocyte ratio was determined by an ROC curve. Patients were divided into groups A and B according to the cutoff value. Amputation-free survival was compared between groups. Univariate and multivariate analyses were used to identify independent risk factors. RESULT: A total of 172 patients were identified with a mean age 71.98±10.09 years; among them, 122 were male. A value of 3.8 was identified as the cutoff value of the post-treatment neutrophil-lymphocyte ratio. Groups A (post-treatment neutrophil-lymphocyte ratio ≥3.8) and B (post-treatment neutrophil-lymphocyte ratio <3.8) showed a significant difference in amputation-free survival (P<0.001). The 1-year, 2-year and 3-year amputation-free survival rates were 79.6%, 55.6% and 46.3%, respectively, in group A; however, in group B, these values were 89.7%, 79.3% and 75.9%, respectively. The post-treatment neutrophil-lymphocyte ratio was identified as an independent predictive factor for amputation in critical limb ischemia patients (P<0.001). CONCLUSION: The post-treatment neutrophil-lymphocyte ratio is an independent predictive factor for amputation in critical limb ischemia patients. Patients with a post-treatment neutrophil-lymphocyte ratio ≥3.8 are likely to suffer from ...
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Adolescente , Preescolar , Femenino , Humanos , Masculino , Síndrome de Down/diagnóstico , Pérdida Auditiva/diagnóstico , Trastornos del Desarrollo del Lenguaje/diagnóstico , Trastornos del Habla/diagnóstico , Trastornos de la Articulación/diagnóstico , Comorbilidad , Comprensión , Lectura , Estudios Retrospectivos , Medición de la Producción del Habla , Conducta Verbal , VocabularioRESUMEN
OBJECTIVE: To examine the association between exposure to traffic-related air pollution (TRAP) and hospital readmission for asthma or bronchodilator-responsive wheezing. STUDY DESIGN: A population-based cohort of 758 children aged 1-16 years admitted for asthma or bronchodilator-responsive wheezing was assessed for asthma readmission within 12 months. TRAP exposure was estimated with a land use regression model using the home address at index admission, with TRAP dichotomized at the sample median (0.37 µg/m3). Covariates included allergen-specific IgE, tobacco smoke exposure, and social factors obtained at enrollment. Associations between TRAP exposure and readmission were assessed using logistic regression and Cox proportional hazards models. RESULTS: The study cohort was 58% African American and 32% white; 19% of the patients were readmitted within 12 months of the original admission. Higher TRAP exposure was associated with a higher readmission rate (21% vs. 16%; P = .05); this association was not significant after adjusting for covariates (aOR, 1.4; 95% CI, 0.9-2.2). Race modified the observed association; white children with high TRAP exposure had 3-fold higher odds of asthma readmission (OR, 3.0; 95% CI, 1.1-8.1), compared with white children with low TRAP exposure. In African American children, TRAP exposure was not associated with increased readmission (OR, 1.1; 95% CI, 0.6-1.8). In children with high TRAP exposure, TRAP exposure was associated with decreased time to readmission in white children (hazard ratio, 3.2; 95% CI, 1.5-6.7) compared with African American children (hazard ratio, 1.0; 95% CI, 0.7-1.4). African American children had a higher readmission rate overall. CONCLUSION: TRAP exposure is associated with increased odds of hospital readmission in white children, but not in African American children.
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Contaminantes Atmosféricos/efectos adversos , Asma/epidemiología , Exposición a Riesgos Ambientales/efectos adversos , Readmisión del Paciente/estadística & datos numéricos , Emisiones de Vehículos/toxicidad , Adolescente , Asma/etiología , Asma/terapia , Causalidad , Niño , Preescolar , Estudios de Cohortes , Monitoreo del Ambiente/métodos , Femenino , Gasolina/toxicidad , Hospitalización/estadística & datos numéricos , Humanos , Incidencia , Lactante , Modelos Logísticos , Estudios Longitudinales , Masculino , Material Particulado/efectos adversos , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Medición de Riesgo , Factores SocioeconómicosRESUMEN
OBJECTIVES: To characterize variation and inequalities in neighborhood child asthma admission rates and to identify associated community factors within one US county. STUDY DESIGN: This population-based prospective, observational cohort study consisted of 862 sequential child asthma admissions among 167â653 eligible children ages 1-16 years in Hamilton County, Ohio. Admissions occurred at a tertiary-care pediatric hospital and accounted for nearly 95% of in-county asthma admissions. Neighborhood admission rates were assessed by geocoding addresses to city- and county-defined neighborhoods. The 2010 US Census provided denominator data. Neighborhood admission distribution inequality was assessed by the use of Gini and Robin Hood indices. Associations between neighborhood rates and socioeconomic and environmental factors were assessed using ANOVA and linear regression. RESULTS: The county admission rate was 5.1 per 1000 children. Neighborhood rates varied significantly by quintile: 17.6, 7.7, 4.9, 2.2, and 0.2 admissions per 1000 children (P < .0001). Fifteen neighborhoods containing 8% of the population had zero admissions. The Gini index of 0.52 and Robin Hood index of 0.38 indicated significant inequality. Neighborhood-level educational attainment, car access, and population density best explained variation in neighborhood admission rates (R(2) = 0.55). CONCLUSION: In a single year, asthma admission rates varied 88-fold across neighborhood quintiles in one county; a reduction of the county-wide admission rate to that of the bottom quintile would decrease annual admissions from 862 to 34. A rate of zero was present in 15 neighborhoods, which is evidence of what may be attainable.
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Asma/terapia , Disparidades en Atención de Salud/estadística & datos numéricos , Admisión del Paciente/estadística & datos numéricos , Adolescente , Asma/epidemiología , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Masculino , Ohio , Estudios Prospectivos , Factores SocioeconómicosRESUMEN
OBJECTIVES: Since pubertal maturation is an important covariate in studies that evaluate physical and social changes that occur during the teen years, we examined pubertal parameters in a group of US girls. STUDY DESIGN: Black and white girls recruited at age 9 were followed annually for 10 years. Preece-Baines model 1 was used to estimate tempo and growth parameters. The temporal trend between age of menarche and onset of puberty was calculated. RESULTS: The study included 615 (77.2% prepubertal) white and 541 (49.4% prepubertal) black participants. Mean onset of puberty was 10.2 and 9.6 years in white and black girls, respectively, menarche was 12.6 and 12.0, achievement of Tanner growth stage 5 was 14.3 and 13.6, and achievement of adult height was 17.1 and 16.5 years. The Pearson's correlation coefficient between menarche and onset of puberty was .37. CONCLUSIONS: Menarche is often used as a marker for onset of puberty and for timing of puberty. Data gathered over the past 20 years suggest only moderate correlation between menarche and onset of puberty (.37-.38), which has decreased significantly during the last 50 years. This suggests the existence of both similar and unique factors that impact the age at onset of puberty and age at menarche.
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Población Negra , Pubertad/etnología , Población Blanca , Adolescente , Distribución por Edad , Distribución de la Grasa Corporal , Estatura , Niño , Femenino , Humanos , Estudios Longitudinales , Menarquia/etnología , Análisis de Regresión , Estados UnidosRESUMEN
OBJECTIVE: To determine prevalence of metabolic syndrome (MS) among adolescents by using definitions from the National Cholesterol Education Program Adult Treatment Panel III (NCEP) and World Health Organization (WHO) guidelines and to compare the populations identified by these definitions. STUDY DESIGN: School-based, cross-sectional study of 1513 black, white, and Hispanic teens who had a fasting morning blood sample drawn and a physical examination. RESULTS: Overall, the prevalence of NCEP-defined MS was 4.2% and of WHO-defined MS was 8.4%. MS was found almost exclusively among obese teens, for whom prevalence of NCEP-defined MS was 19.5% and prevalence of WHO-defined MS was 38.9%. Agreement between definitions was poor (kappa statistic=0.41). No race or sex differences were present for NCEP-defined MS. However, nonwhite teens were more likely to have MS by WHO criteria (RR, 1.40; 95% CI, 1.04, 1.87), and MS was more common among girls if the WHO-based definition was used (RR, 1.26; 95% CI, 1.08, 1.88). CONCLUSIONS: Among adolescents, obesity is a powerful risk for MS. Important demographic and clinical differences exist in the typology of MS, depending on the definition. Such discrepancies suggest that the concept of a common pathologic syndrome or etiologic mechanism underlying MS as defined by these guidelines may be flawed.
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Población Negra , Hispánicos o Latinos , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/etnología , Población Blanca , Adolescente , Adulto , Niño , Estudios de Cohortes , Femenino , Humanos , Masculino , Guías de Práctica Clínica como Asunto , Prevalencia , Factores de Riesgo , Organización Mundial de la SaludRESUMEN
Chronic exposure to inorganic arsenic (In-As) from drinking water is associated with different health effects, including skin, lung, bladder, and kidney cancer as well as vascular and possibly reproductive effects. In-As is metabolized through the process of methylation, resulting in the production and excretion of methylated species, mainly monomethylarsenate (MMA) and dimethylarsenate (DMA). Because a large percentage of the dose is excreted in urine, the distribution of urinary In-As, MMA, and DMA is considered a useful indicator of methylation patterns in human populations. Several factors affect these patterns, including sex and exposure level. In this study, we investigated the profile of urinary In-As, MMA, and DMA of pregnant women. Periodic urine samples were collected from early to late pregnancy among 29 pregnant women living in Antofagasta, Chile, who drank tap water containing 40 micro g/L In-As. The total urinary arsenic across four sampling periods increased with increasing weeks of gestation, from an initial mean value of 36.1 to a final value of 54.3 micro g/L. This increase was mainly due to an increase in DMA, resulting in lower percentages of In-As and MMA and a higher percentage of DMA. Our findings indicate that among women exposed to moderate arsenic from drinking water during pregnancy, changes occur in the pattern of urinary arsenic excretion and metabolite distribution. The toxicologic significance of this is not clear, given recent evidence suggesting that intermediate methylated species may be highly toxic. Nevertheless, this study suggests that arsenic metabolism changes throughout the course of pregnancy, which in turn may have toxicologic effects on the developing fetus. Key words: arsenic, arsenic metabolism, arsenic methylation, Chile, pregnancy, urinary arsenic.
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Arsénico/análisis , Arsénico/orina , Monitoreo del Ambiente/métodos , Embarazo/orina , Contaminantes Químicos del Agua/análisis , Abastecimiento de Agua/análisis , Adulto , Chile , Creatinina/orina , Femenino , Edad Gestacional , Humanos , Metilación , Embarazo/metabolismo , Complicaciones del Embarazo/orina , Trimestres del Embarazo/orina , Fumar/orinaRESUMEN
OBJECTIVE: To determine whether the socioeconomic context of the school environment is associated with adolescent depressive symptoms independent of individual household income. Study design Data were drawn from a 1995 nationally representative study of 7th to 12th grade students. Multivariable linear regression at the school and individual levels assessed the relation between income and depressive symptoms. Multilevel modeling techniques were then used to understand how these factors are jointly associated with adolescent depressive symptoms. PARTICIPANTS: Adolescents (n=13,235) in grades 7 through 12 from 132 schools whose parent provided income information. RESULTS: Linear regression analyses indicated that lower household income, average school income, and increasing school-level income inequality were significantly (P<.001) associated with depressive symptoms. Further examination of these relations through multilevel modeling indicated that both household income (P<.01) and average school income (P<.05) were significantly related to depressive symptoms after adjusting for covariates, with evidence for an interaction between the two. The impact of lower household income on depressive symptoms was approximately 2-fold greater for students attending a poor versus a rich school. CONCLUSIONS: School context is associated with adolescents' depressive symptoms, even after adjusting for individual-level factors. The school environment may partially buffer the adverse influence of lower household income on adolescent depressive symptoms.
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Depresión/epidemiología , Renta , Salud Mental , Adolescente , Adulto , Niño , Femenino , Humanos , Modelos Lineales , Masculino , Análisis de Regresión , Clase SocialRESUMEN
BACKGROUND: Arsenic exposures from drinking water increase the risk of various cancers and noncancer health endpoints. Limited evidence suggests that arsenic may have adverse human reproductive effects. We investigated the association between drinking water arsenic exposure and fetal growth, as manifest in birth weight. METHODS: We conducted a prospective cohort study in two Chilean cities with contrasting drinking water arsenic levels: Antofagasta (40 micro g/L) and Valparaíso (<1 micro g/L). Study subjects completed in-depth interviews and provided urine samples for exposure analysis. We obtained pregnancy and birth information from medical records. The birth weight analysis was restricted to liveborn, singleton infants born between December 1998 and February 2000. RESULTS: The final study group consisted of 424 infants from Antofagasta and 420 from Valparaíso. After controlling for confounders, results of the multivariable analysis indicated that Antofagasta infants had lower mean birth weight (-57 g; 95% confidence interval = -123 to 9). CONCLUSION: This study suggests that moderate arsenic exposures from drinking water (<50 micro g/L) during pregnancy are associated with reduction in birth weight, similar in magnitude to that resulting from other environmental exposures such as environmental tobacco smoke and benzene.