Straight metalworking fluids have been linked to cardiovascular mortality in analyses using binary exposure metrics, accounting for healthy worker survivor bias by using g-estimation of accelerated ...failure time models. A cohort of 38,666 Michigan autoworkers was followed (1941-1994) for mortality from all causes and ischemic heart disease. The structural model chosen here, using continuous exposure, assumes that increasing exposure from 0 to 1 mg/m(3) in any single year would decrease survival time by a fixed amount. Under that assumption, banning the fluids would have saved an estimated total of 8,468 (slope-based 95% confidence interval: 2,262, 28,563) person-years of life in this cohort. On average, 3.04 (slope-based 95% confidence interval: 0.02, 25.98) years of life could have been saved for each exposed worker who died from ischemic heart disease. Estimates were sensitive to both model specification for predicting exposure (multinomial or logistic regression) and characterization of exposure as binary or continuous in the structural model. Our results provide evidence supporting the hypothesis of a detrimental relationship between straight metalworking fluids and mortality, particularly from ischemic heart disease, as well as an instructive example of the challenges in obtaining and interpreting results from accelerated failure time models using a continuous exposure in the presence of competing risks.
Alcohol consumption interacts with tobacco use to increase the risk of head and neck squamous cell carcinoma (HNSCC). Alcohol is eliminated through oxidation by alcohol dehydrogenase (ADH). The ADH1C ...gene is polymorphic and the ADH1C*1 allele metabolizes ethanol to acetaldehyde at a higher rate than the variant ADH1C*2 allele. This polymorphism has been reported to alter the risk of HNSCC associated with alcohol use, although the literature differs in the estimates of both the magnitude and direction of this effect modification. We have investigated the association between the established risk factors for HNSCC and variant genotypes of ADH1C in a case-control study in the greater Boston area. ADH1C genotypes were determined from 521 cases and 599 population-based controls. The odds ratio (OR) for HNSCC associated with >26 drinks per week was 3.7 95% confidence interval (95% CI), 2.4-5.7, whereas the OR for smoking >58 pack-years was 5.6 (95% CI, 3.8-8.4). The combination of heavy smoking and heavy drinking significantly interacted to produce an OR of 17.3 (95% CI, 7.8-38.3). In cases and controls, respectively, 16% and 14% were ADH1C*1-1, 46% and 46% were ADH1C*1-2 and 38% and 40% were ADH1C*2-2. There was a significant interaction of alcohol use and genotype (P = 0.05), with an estimated oral cancer risk in heavy drinkers of 7.1 (95% CI, 2.3-22.0) for homozygous variants compared with an OR of 2.3 (95% CI, 1.4-3.8) for ADH1C homozygous wild type or heterozygous individuals (controlling for smoking, age, race, and gender). These findings suggest that the ADH1C*2-2 genotype is associated with susceptibility to smoking and drinking-related HNSCC by modifying the biologically effective dose of alcohol.
The recently revised ACGIH TLV for Hand Activity (TLV2018) is a widely used tool for assessing risk for upper limb musculoskeletal disorders. The purpose of this analysis was to compare the strength ...of the exposure-response relationships between the TLV2018 and carpal tunnel syndrome (CTS) between men and women and across age strata. Heterogeneity of the effect size by sex or age would be important to specialists using the method for prevention of CTS among working populations. Data from two large prospective studies were combined to allow for stratification of exposure-response models assessing the association between the TLV2018 and CTS by gender and age. Results show greater risk for women than men and for younger workers than older workers for TLV2018 values above the action limit. Although the TLV2018 is an effective surveillance tool for estimating increased risk of CTS with increasing exposure, these analyses show that such increase are not homogeneous across sex and age.
In this paper, we review available methods for determination of the functional form of the relation between a covariate and the log hazard ratio for a Cox model. We pay special attention to the ...detection of influential observations to the extent that they influence the estimated functional form of the relation between a covariate and the log hazard ratio. Our paper is motivated by a data set from a cohort study of lung cancer and silica exposure, where the nonlinear shape of the estimated log hazard ratio for silica exposure plotted against cumulative exposure and hereafter referred to as the exposure-response curve was greatly affected by whether or not two individuals with the highest exposures were included in the analysis. Formal influence diagnostics did not identify these two individuals but did identify the three highest exposed cases. Removal of these three cases resulted in a biologically plausible exposure-response curve.
Aims: To illustrate the contribution of smoothing methods to modelling exposure-response data, Cox models with penalised splines were used to reanalyse lung cancer risk in a cohort of workers exposed ...to silica in California’s diatomaceous earth industry. To encourage application of this approach, computer code is provided. Methods: Relying on graphic plots of hazard ratios as smooth functions of exposure, the sensitivity of the curve to amount of smoothing, length of the exposure lag, and the influence of the highest exposures was evaluated. Trimming and data transformations were used to down-weight influential observations. Results: The estimated hazard ratio increased steeply with cumulative silica exposure before flattening and then declining over the sparser regions of exposure. The curve was sensitive to changes in degrees of freedom, but insensitive to the number or location of knots. As the length of lag increased, so did the maximum hazard ratio, but the shape was similar. Deleting the two highest exposed subjects eliminated the top half of the range and allowed the hazard ratio to continue to rise. The shape of the splines suggested a parametric model with log hazard as a linear function of log transformed exposure would fit well. Conclusions: This flexible statistical approach reduces the dependence on a priori assumptions, while pointing to a suitable parametric model if one exists. In the absence of an appropriate parametric form, however, splines can provide exposure-response information useful for aetiological research and public health intervention.
In order to evaluate chronic effects of long-term exposure to cotton dust on respiratory health, and the role of dust and endotoxin, longitudinal changes in lung function and respiratory symptoms ...were observed prospectively from 1981 to 2001 in 447 cotton textile workers, along with 472 silk textile controls. The results from five surveys conducted over the 20-yr period are reported, including standardised questionnaires, pre- and post-shift spirometric measurements, work-area inhalable dust sample collections and airborne Gram-bacterial endotoxin analysis. Cotton workers had more persistent respiratory symptoms and greater annual declines in forced expiratory volume in one second (FEV1) and forced vital capacity as compared with silk workers. After exposure cessation, in the final 5-yr period, the rate of FEV1 decline tended to slow in nonsmoking males, but not in nonsmoking females. Workers who reported byssinotic symptoms more persistently suffered greater declines in FEV1. Chronic loss in lung function was more strongly associated with exposure to endotoxin than to dust. In conclusion, the current study suggests that long-term exposure to cotton dust, in which airborne endotoxin appears to play an important role, results in substantial adverse chronic respiratory effects.
Background: Workers with acute hand injuries account for over 1 000 000 emergency department visits annually in the United States. Aims: To determine potential transient risk factors for occupational ...acute hand injury. Methods: Subjects were recruited from 23 occupational health clinics in five northeastern states in the USA. In a telephone interview, subjects were asked to report the occurrence of seven potential risk factors within a 90-minute time period before an acute hand injury. Each case also provided control information on exposures during the month before the injury. The self-matched feature of the study design controlled for stable between-person confounders. Results: A total of 1166 subjects were interviewed (891 men, 275 women), with a mean age (SD) of 37.2 years (11.4). The median time interval between injury and interview was 1.3 days. Sixty three per cent of subjects had a laceration. The relative risk of a hand injury was increased when working with equipment, tools, or work pieces not performing as expected (11.0, 95% CI 9.4 to 12.8), or when using a different work method to do a task (10.5, 95% CI 8.7 to 12.7). Other transient factors in decreasing order of relative risk were doing an unusual task, being distracted, and being rushed. Wearing gloves reduced the relative risk by 60% (0.4, 95% CI 0.3 to 0.5). Occupational category, job experience, and safety training were found to alter several of these effects. Conclusion: The results suggest the importance of these transient, potentially modifiable factors in the aetiology of acute hand injury at work. Attempts to modify these exposures by various strategies may reduce the incidence of acute hand injury at work.
Background Uncontrolled confounding by personal exposures like smoking can limit the inferential power of occupational cohort studies. We developed and demonstrate a refinement of an existing type of ...sensitivity analysis, indirect adjustment, for evaluating the potential magnitude of confounding by alcohol and tobacco. Results of a large retrospective cohort study of laryngeal cancer and exposure to metalworking fluids (MWF) are used to illustrate the methods. Methods Data on smoking and drinking habits representative of the study cohort were obtained from a sample of US manufacturing workers from the 1977 National Health Interview Survey (NHIS). Two different mechanisms were assumed to affect the distribution of confounding factors between MWF exposure groups: socially determined and chance differences. Chance variation was investigated with Monte Carlo sampling from the NHIS survey distribution of smoking and drinking. An upper bound on systematic differences in smoking and drinking was set by assuming that differences between exposure groups within the same unionized blue collar workforce were very unlikely to be larger than differences between blue and white collar manufacturing workers in the NHIS data. Results Under plausibly large differences in smoking and drinking habits among MWF exposure groups occurring by either mechanism, the exposure–risk association was unlikely to have been over- or under-estimated by as much as 20%. Conclusions When comparing exposure groups within the same working population, it is unlikely that either systematic or chance differences in smoking and drinking habits will cause as much as a 20% change in the relative risk in large studies. While this study focused on an occupational exposure and laryngeal cancer, there are many situations in which epidemiologists are concerned that unmeasured ‘lifestyle factors’ may differ among exposure groups, and it would appear that the likely confounding effect of such differences will often be modest.
Low level effects of granite dust on one-second forced expiratory volume (FEV1) are estimated in 618 Vermont granite workers followed for 5 years with annual pulmonary function tests. Reduced ...pulmonary function has already been reported for the subset of subjects lost to follow-up (dropouts) suggesting possible bias in analyses based only on survivors.
Healthy worker selection bias is directly assessed by comparing the dose-response associations between survivors who remained in the study for the full 5-year observation period and the dropouts.
The 353 survivors had an FEV1 of 96% of predicted at baseline and were losing FEV1 at an average rate of 44 ml/yr. No association was found in this group between the rate of FEV1 decline and lifetime dust exposure. However, the 265 workers with incomplete follow-up, 'dropouts', had a lower FEV1 at baseline (94%) and were losing FEV1 at an average rate of 69 ml/yr. The dose-response parameter in this group was estimated to be 4 ml/yr loss per mg/m3-year and was statistically significant.
These results provide an illustration of bias due to the healthy worker effect and an example of the failure to detect a true work-related health effect in a study based only on a 'survivor' population.
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