It is usually preferable to model and estimate prevalence ratios instead of odds ratios in cross-sectional studies when diseases or injuries are not rare. Problems with existing methods of modeling ...prevalence ratios include lack of convergence, overestimated standard errors, and extrapolation of simple univariate formulas to multivariable models. We compare two of the newer methods using simulated data and real data from SAS online examples.
The Robust Poisson method, which uses the Poisson distribution and a sandwich variance estimator, is compared to the log-binomial method, which uses the binomial distribution to obtain maximum likelihood estimates, using computer simulations and real data.
For very high prevalences and moderate sample size, the Robust Poisson method yields less biased estimates of the prevalence ratios than the log-binomial method. However, for moderate prevalences and moderate sample size, the log-binomial method yields slightly less biased estimates than the Robust Poisson method. In nearly all cases, the log-binomial method yielded slightly higher power and smaller standard errors than the Robust Poisson method.
Although the Robust Poisson often gives reasonable estimates of the prevalence ratio and is very easy to use, the log-binomial method results in less bias in most common situations, and because it fits the correct model and obtains maximum likelihood estimates, it generally results in slightly higher power, smaller standard errors, and, unlike the Robust Poisson, it always yields estimated prevalences between zero and one.
The purpose of this study was to estimate the incidence and prevalence of hearing loss for noise-exposed U.S. workers by industry sector and 5-year time period, covering 30 years.
Audiograms for 1.8 ...million workers from 1981-2010 were examined. Incidence and prevalence were estimated by industry sector and time period. The adjusted risk of incident hearing loss within each time period and industry sector as compared with a reference time period was also estimated.
The adjusted risk for incident hearing loss decreased over time when all industry sectors were combined. However, the risk remained high for workers in Healthcare and Social Assistance, and the prevalence was consistently high for Mining and Construction workers.
While progress has been made in reducing the risk of incident hearing loss within most industry sectors, additional efforts are needed within Mining, Construction and Healthcare and Social Assistance.
Dosimetry for toxicology studies involving carbon nanotubes (CNT) is challenging because of a lack of detailed occupational exposure assessments. Therefore, exposure assessment findings, measuring ...the mass concentration of elemental carbon from personal breathing zone (PBZ) samples, from 8 U.S.-based multi-walled CNT (MWCNT) manufacturers and users were extrapolated to results of an inhalation study in mice.
Upon analysis, an inhalable elemental carbon mass concentration arithmetic mean of 10.6 μg/m3 (geometric mean 4.21 μg/m3) was found among workers exposed to MWCNT. The concentration equates to a deposited dose of approximately 4.07 μg/d in a human, equivalent to 2 ng/d in the mouse. For MWCNT inhalation, mice were exposed for 19 d with daily depositions of 1970 ng (equivalent to 1000 d of a human exposure; cumulative 76 yr), 197 ng (100 d; 7.6 yr), and 19.7 ng (10 d; 0.76 yr) and harvested at 0, 3, 28, and 84 d post-exposure to assess pulmonary toxicity. The high dose showed cytotoxicity and inflammation that persisted through 84 d after exposure. The middle dose had no polymorphonuclear cell influx with transient cytotoxicity. The low dose was associated with a low grade inflammatory response measured by changes in mRNA expression. Increased inflammatory proteins were present in the lavage fluid at the high and middle dose through 28 d post-exposure. Pathology, including epithelial hyperplasia and peribronchiolar inflammation, was only noted at the high dose.
These findings showed a limited pulmonary inflammatory potential of MWCNT at levels corresponding to the average inhalable elemental carbon concentrations observed in U.S.-based CNT facilities and estimates suggest considerable years of exposure are necessary for significant pathology to occur at that level.
New approaches to ovarian cancer are needed to improve survival. Wilms' tumour 1 (WT1) is a tumour-associated antigen expressed in many ovarian cancers. P53 is also often altered. The clinical ...significance of the combined expression of these two transcription factors has not been studied.
One hundred ninety-six ovarian tumours were classified histopathologically. Tumours were stained for WT1 and p53 immunohistochemically. Stains were analysed according to tumour type, grade and FIGO stage. Kaplan-Meier analyses on 96 invasive carcinomas determined whether categorical variables were related to survival.
WT1 and p53 were related to ovarian tumour type, grade, FIGO stage and patient survival. Uniform nuclear p53 expression was associated with invasion and WT1 expression was associated with advanced grade, FIGO stage and poor survival. When WT1 and p53 were both in the age-adjusted Cox model, WT1 was significant while p53 was not. When we combined tumours expressing WT1 and p53, then adjusted for age and tumour subtype, the hazard ratio compared to tumours without WT1 and with normal p53 was 2.70; when adjusted for age and FIGO stage, the hazard ratio was 2.40.
WT1, an antigen target, is a biomarker for poor prognosis, particularly when combined with altered p53.
ObjectivesThe US Occupational Safety and Health Administration (OSHA) recently proposed a permissible exposure limit of 0.2 µg/m3 for beryllium, based partly on extrapolated estimates of lung cancer ...risk from a pooled occupational cohort. The purpose of the present analysis was to evaluate whether cohort members exposed at lower levels to mainly insoluble forms of beryllium exhibit increased risk of lung cancer.MethodsWe conducted Cox proportional hazards regression analyses among 75 lung cancer cases in age-based risk sets within two lower exposure plants in the pooled cohort followed from 1940 to 2005. We used categorical and power models to evaluate exposure–response patterns for mean and cumulative beryllium exposures in the two-plant cohort, comparing findings with the full pooled cohort. We also evaluated the distribution of exposure-years in each cohort by solubility class (soluble, insoluble and mixed).Results98% of workers in the two-plant cohort were hired between 1955 and 1969. The mean beryllium exposure averaged 1.3 µg/m3 and the predominant form was insoluble. Adjusting for confounders, we observed a monotonic increase in lung cancer mortality across exposure categories in the two-plant cohort. The exposure–response coefficients (per unit ln exposure) were 0.270 (p=0.061) for mean exposure and 0.170 (p=0.033) for cumulative exposure, compared with 0.155 and 0.094 (respectively) in the full cohort.ConclusionThe low-exposure levels at these two plants and the predominance of insoluble beryllium suggest that the overall pooled cohort findings on which OSHA’s lung cancer risk assessment is based are relevant for current workers exposed to any form of beryllium.
Objectives To quantify the risk for carpal tunnel syndrome (CTS) from workplace physical factors, particularly hand activity level and forceful exertion, while taking into account individual factors ...including age, gender, body mass index (BMI), and pre-existing medical conditions. Methods Three healthcare and manufacturing workplaces were selected for inclusion on the basis of range of exposure to hand activity level and forceful exertion represented by their jobs. Each study participant's job tasks were observed and evaluated onsite and videotaped for further analysis, including frequency and duration of exertion and postural deviation. Individual health assessment entailed electrodiagnostic testing of median and ulnar nerves, physical examination and questionnaires at baseline with annual follow-up for 2 years. Results The incidence of dominant hand CTS during the study was 5.11 per 100 person-years (29 cases). Adjusted HRs for dominant hand CTS were as follows: working with forceful exertion ≥20% but <60% of the time: 2.83 (1.18, 6.79) and ≥60% of the time vs <20%: 19.57 (5.96, 64.24), BMI ≥30 kg/m2 (obesity): 3.19 (1.28, 7.98). The American Conference for Governmental Industrial Hygienists (ACGIH) Threshold Limit Value (TLV) for hand activity level also predicted CTS, HR=1.40 (1.11, 1.78) for each unit increase in the TLV ratio, controlling for obesity and job strain. Conclusions Workplace and individual risk factors both contribute to the risk for CTS. Time spent in forceful exertion can be a greater risk for CTS than obesity if the job exposure is high. Preventive workplace efforts should target forceful exertions.
Little is known on environmental risk factors for cryptorchidism and hypospadias, which are among the most frequent congenital abnormalities. The aim of our study was to identify risk factors for ...cryptorchidism and hypospadias, with a focus on potential endocrine disruptors in parental diet and occupation. In a case-control study nested within a cohort of 8,698 male births, we compared 78 cryptorchidism cases and 56 hypospadias cases with 313 controls. The participation rate was 85% for cases and 68% for controls. Through interviews, information was collected on pregnancy aspects and personal characteristics, lifestyle, occupation, and dietary phytoestrogen intake of both parents. Occupational exposure to potential endocrine disruptors was classified based on self-reported exposure and ratings of occupational hygienists based on job descriptions. Our findings indicate that paternal pesticide exposure was associated with cryptorchidism odds ratio (OR) = 3.8; 95% confidence interval (95% CI), 1.1-13.4. Smoking of the father was associated with hypospadias (OR = 3.8; 95% CI, 1.8-8.2). Maternal occupational, dietary, and lifestyle exposures were not associated with either abnormality. Both abnormalities were associated with suboptimal maternal health, a lower maternal education, and a Turkish origin of the parents. Being small for gestational age was a risk factor for hypospadias, and preterm birth was a risk factor for cryptorchidism. Because paternal pesticide exposure was significantly associated with cryptorchidism and paternal smoking was associated with hypospadias in male offspring, paternal exposure should be included in further studies on cryptorchidism and hypospadias risk factors.
Melanoma is a disease that primarily arises in the skin but is a derivative of the neural crest. Eukaryotic translation initiation factor 4E (eIF4E) regulates translation of multiple ...malignancy-associated mRNAs and is overexpressed in many epithelial tumours. However, expression in human tumours derived from the neural crest is unknown. Here, we determined the association of eIF4E and phospho-eIF4E expression in melanocytic lesions with malignant conversion, metastatic potential and patient survival.
Archived formalin-fixed, paraffin-embedded surgical specimens from 114 patients with melanocytic lesions were stained immunohistochemically for eIF4E and phospho-eIF4E and evaluated semiquantitatively. The relationship between cytoplasmic and nuclear eIF4E and phospho-eIF4E protein expression, melanocytic lesion subtype and tumour progression was determined. Kaplan-Meier survival analyses and Cox proportional hazard regression were performed.
Increased eIF4E and phospho-eIF4E expression was highly associated with malignancy (P<0.0001). High nuclear phospho-eIF4E was associated with synchronous or future metastasis (P=0.0059). Kaplan-Meier analyses demonstrated highly significant associations between high histoscores for cytoplasmic and nuclear phospho-eIF4E and reduced survival in all patients (P=0.0003 and 0.0009, respectively).
Increased melanoma expression of eIF4E and phospho-eIF4E is associated with metastatic potential, reduced survival and increased risk of death.
Dose-response modeling in occupational epidemiology is usually motivated by questions of causal inference (eg, is there a monotonic increase of risk with increasing exposure?) or risk assessment (eg, ...how much excess risk exists at any given level of exposure?). We focus on several approaches to dose-response in occupational cohort studies. Categorical analyses are useful for detecting the shape of dose-response. However, they depend on the number and location of cutpoints and result in step functions rather than smooth curves. Restricted cubic splines and penalized splines are useful parametric techniques that provide smooth curves. Although splines can complement categorical analyses, they do not provide interpretable parameters. The shapes of these curves will depend on the degree of "smoothing" chosen by the analyst. We recommend combining categorical analyses and some type of smoother, with the goal of developing a reasonably simple parametric model. A simple parametric model should serve as the goal of dose-response analyses because (1) most "true" exposure response curves in nature may be reasonably simple, (2) a simple parametric model is easily communicated and used by others, and (3) a simple parametric model is the best tool for risk assessors and regulators seeking to estimate individual excess risks per unit of exposure. We discuss these issues and others, including whether the best model is always the one that fits the best, reasons to prefer a linear model for risk in the low-exposure region when conducting risk assessment, and common methods of calculating excess lifetime risk at a given exposure from epidemiologic results (eg, from rate ratios). Points are illustrated using data from a study of dioxin and cancer.
PDF
