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Biomedical subjects

Gary M Marsh

Publications and source records attributed to Gary M Marsh.

14 recordsLinked to original sources

Mortality patterns among workers in a US pharmaceutical production plant.

PURPOSE: To examine mortality among workers in a pharmaceutical production plant and to address community concerns about 1980 to 1990 increases in local county cancer mortality rates. METHODS: Subjects were 1999 workers with some full-time employment during the period between 1970 and 1996. We identified deaths through the year 2000 and reconstructed exposures to nine chemical agents with available exposure measurements. Data analyses included standardized mortality ratios (SMRs) and time trends in local cancer mortality rates. RESULTS: We observed deficits in deaths from all causes combined, all cancers combined, and most cause of death categories examined. Male workers with potential plant exposure had excesses in deaths from all lymphatic-hematopoietic tissue cancers (LHTC), in particular non-Hodgkin's lymphoma (NHL), and respiratory system cancers (RSC) that were larger among long-term workers, but the pattern of findings suggested the excesses were probably not related to occupational factors at the plant. The increase in local county cancer mortality rates was simply the upward cycle of a periodic trend that peaked in 1990 and returned to 1980 levels in 2000. CONCLUSIONS: With the possible exceptions of LHTC, in particular NHL, and RSC, this study provided no evidence of elevated total or cause-specific cohort mortality risks. It does not appear that plant factors played a role in the 1980 to 1990 increases in local county cancer mortality rates.

Adult↗

A method for imputing missing data in longitudinal studies.

PURPOSE: In a cohort in which racial data are unknown for some persons, race-specific persons and person-years are imputed using a model-based iterative allocation algorithm (IAA). METHODS: An EM algorithm-based approach to address misclassification in a censored data regression setting can be adapted to estimate the probability that a person of unknown race is white. The corresponding race-specific person-years are obtained as a by-product of the estimation procedure. Variance estimates are computed using the bootstrap. The proposed approach is compared with the proportional allocation method (PAM). RESULTS: In an occupational cohort where racial data were missing for 41% of the workers, the age-time-race-specific person-years were estimated within a relative variation of approximately 20%, using the IAA. The deaths were less reliably estimated. The standardized mortality ratios (SMRs) for all-cause mortality estimated using the IAA and the PAM were more similar for the non-white workers than for a smaller subgroup of white workers. CONCLUSIONS: The IAA provides a method to reliably estimate race-specific person-year denominators in cohort studies with missing racial data. This method is applicable to other incompletely observed non-time-dependent categorical covariates. Internal cohort rates or SMRs can be computed and modeled, with bootstrap confidence intervals that account for the uncertainty in the determination of race.

Adolescent↗

Reevaluation of mortality risks from leukemia in the formaldehyde cohort study of the National Cancer Institute.

OBJECTIVE: To determine whether the National Cancer Institute's (NCI) recent suggestion of a causal association between formaldehyde exposure and mortality from leukemia and myeloid leukemia (ML) is robust with respect to alternative characterizations and categorizations of formaldehyde exposure and to alternative methods of data analysis. METHODS: The original authors provided the cohort data. We computed US and local county rate-based standardized mortality ratios (SMRs) and internal cohort rate-based relative risks (RR) by categories of four formaldehyde exposure metrics (highest peak, average intensity (AIE), cumulative, and duration), using both NCI categories and an alternative categorization based on tertiles of deaths from all leukemia among exposed subjects. For highest peak exposure, we computed RRs by the duration of time worked in the highest peak category and the time since highest peak exposure. For AIE, we computed RRs by the duration of exposure and the time since first exposure. RESULTS: Our external comparisons revealed that the elevated leukemia and ML RRs and associated trends reported by NCI for highest peak and AIE occurred because null (or slight) to moderate mortality excesses were compared with statistically significant baseline category deficits in deaths. Our alternative categorization of AIE yielded leukemia and ML SMRs close to 1.0 in the highest exposure category, and revealed weaker evidence of a trend in RRs for leukemia and ML. We corroborated NCI's finding of no association for cumulative and duration of formaldehyde exposure. We found no consistent evidence that leukemia or ML risks increased with increasing duration of time spent in a given highest peak exposure (or for AIE, duration of exposure in a given AIE category). We also found no consistent evidence that leukemia or ML risks were greater in the more relevant shorter (less than 20 years) versus longer (20+ years) periods of time from the first highest peak exposure (or for AIE, first exposure). CONCLUSIONS: Our reanalysis provided little evidence to support NCI's suggestion of a causal association between formaldehyde exposure and mortality from leukemia and ML. NCI's key findings for highest peak exposure and AIE do not adequately account for the inordinately large deficits in deaths in the categories used as the baselines for internal rate-based RRs. The NCI findings also do not adequately account for the duration of time subjects spent in the highest peak category (or for AIE, duration of exposure) or the time since their first peak exposure (or for AIE, time since first exposure). Our finding that NCI's suggestion of a causal association is not robust with respect to alternative categorizations of formaldehyde exposure and methods of data analysis casts considerable additional uncertainty regarding the validity of this suggested association.

Cohort Studies↗

Historical cohort study of U.S. man-made vitreous fiber production workers IX: summary of 1992 mortality follow up and analysis of respiratory system cancer among female workers.

We report the 1946-1992 mortality experience of 4008 females employed in any of 10 U.S. fiberglass manufacturing plants between 1945 and 1978 relative to external population rates. We also examine respiratory system cancer (RSC) mortality as a function of estimated exposure to respirable fibers (RFib), formaldehyde (FOR), silica, phenolics, urea, and other agents based on internal cohort comparisons. No statistically significantly elevated standardized mortality ratios were observed for all-cause mortality (930 deaths), any of the 25 nonmalignant causes considered, all malignant neoplasms (266 deaths), or any of the 27 malignant causes considered. Internal cohort comparisons revealed no significant positive associations between RSC mortality (53 cases) and exposure to RFib, FOR, or any of the other agents considered, although exposure levels were generally low. Some demographic subgroups appear to be at relatively increased risk of RSC.

Adult↗

A 50-year historical cohort mortality study of workers in a pharmaceutical plant.

An historical cohort study was conducted of workers at a pharmaceutical manufacturing plant. The cohort mortality experience of workers ever employed at the plant over the period from 1950 to 1999 was examined. The 1958 workers accumulated 44,294 person-years of experience at the plant, and a total of 384 deaths were identified. Our findings from external comparisons based on standardized mortality ratios (SMRs) in the cohort provide no evidence of excess mortality risk from all causes combined (SMR=0.75), all cancers combined (SMR=0.96), or from certain other individual causes of death. No patterns of excess mortality risk were apparent after stratifying on age and sex or job classification. The mortality experience of this cohort was generally more favorable than that of the general population.

Cause of Death↗

A risk assessment for occupational acrylonitrile exposure using epidemiology data.

The extensive data from the Blair et al.((1)) epidemiology study of occupational acrylonitrile exposure among 25460 workers in eight plants in the United States provide an excellent opportunity to update quantitative risk assessments for this widely used commodity chemical. We employ the semiparametric Cox relative risk (RR) regression model with a cumulative exposure metric to model cause-specific mortality from lung cancer and all other causes. The separately estimated cause-specific cumulative hazards are then combined to provide an overall estimate of age-specific mortality risk. Age-specific estimates of the additional risk of lung cancer mortality associated with several plausible occupational exposure scenarios are obtained. For age 70, these estimates are all markedly lower than those generated with the cancer potency estimate provided in the USEPA acrylonitrile risk assessment.((2)) This result is consistent with the failure of recent occupational studies to confirm elevated lung cancer mortality among acrylonitrile-exposed workers as was originally reported by O'Berg,((3)) and it calls attention to the importance of using high-quality epidemiology data in the risk assessment process.

Acrylonitrile↗

The Drake Health Registry Study: findings from fifteen years of continuous bladder cancer screening.

BACKGROUND: The Drake Health Registry Study (DHRS) is an ongoing bladder cancer screening program initiated in 1986 due to workers' probable past exposure to the bladder carcinogen, beta-naphthylamine (BNA). METHODS: At periodic screening visits, a health survey is administered and three screening tests are applied to a urine sample, urinalysis (UA), papanicolaou (PAP), and quantitative fluorescence image analysis (QFIA). Positive screens are eligible for a free bladder cystoscopy with random biopsies. RESULTS: Forty of 51 persons eligible for diagnostic evaluation underwent cystoscopy. One person was diagnosed with carcinoma in situ, two with transitional cell papilloma, 14 with dysplasia, two of which developed transitional cell carcinoma; 26 had bladder abnormalities such as chronic inflammation, chronic cystitis, atypical changes, atypia, hyperplasia, or papillary clusters. CONCLUSIONS: The DHRS continues to identify early stage bladder cancer and other abnormalities among workers exposed to BNA before 1981 and generates useful clinical, psycho-social, and epidemiologic data.

2-Naphthylamine↗

The Drake Health Registry Study: cause-specific mortality experience of workers potentially exposed to beta-naphthylamine.

OBJECTIVE: To examine the cause-specific mortality experience of an occupational cohort with probable past exposure to beta-naphythylamine (BNA). METHODS: Subjects were 374 male and 26 female workers employed at a Pennsylvania chemical plant that produced or used beta-naphthylamine (BNA) between 1940 and 1981. Vital status through 1998 was determined for 97.5% of the cohort and cause of death for 100% of 79 deaths. Limited industrial hygiene data and reports from former employees were used to categorize workers as high, medium, or low risk for BNA exposure. Statistical analyses included US and local county-based standardized mortality ratios (SMRs). RESULTS: We observed statistically significantly elevated county rate-based SMRs for all causes combined (SMR = 1.98, 95% confidence interval (CI) = 1.56-2.49), all malignant neoplasms combined (28 deaths, SMR = 3.08, 95% CI = 2.05-4.46), respiratory system cancer (12 deaths, SMR = 3.91, 95% CI = 2.02-6.83), and bladder cancer (four deaths, SMR = 16.83, 95% CI = 4.59-43.1). Three bladder cancer cases were classified as high risk (SMR = 26.79, 95% CI = 5.53-78.29). Mortality risks were also elevated for most other malignant and non-malignant cause of death categories examined. CONCLUSIONS: Bladder cancer risk remains highly elevated among Drake/Kilsdonk workers and appears to be causally related to past BNA exposure. While lifestyle and behavioral risk factors may explain some of the mortality excesses for non-urological cancers, the possibility remains that BNA exposure may have also played a role in these and other observed cancer excesses.

2-Naphthylamine↗

Factors associated with Medicaid enrollment for low-income children in the United States.

This study analyzes the 1996-1997 Community Tracking Study Household Survey to identify factors associated with Medicaid enrollment for low-income children and to examine the differences between those enrolled in the Medicaid program and those who were eligible but uninsured. We estimated that 17.4% of Medicaid-eligible children were uninsured. Medicaid eligible children who were younger, African American, with single parents, with AFDC eligible parents, with no parent employed full-time were more likely to be enrolled in the Medicaid program. Children with better health status were less likely to be enrolled in Medicaid. In addition, children whose parents were uninsured were more likely not to be enrolled in Medicaid.

Adolescent↗

The role of smoking and exposure to asbestos and man-made vitreous fibers in a questionable case of mesothelioma.

A remaining uncertainty in the U.S. cohort study of man-made vitreous fiber (MMVF) workers is whether asbestos exposure contributed to 10 questionable cases of mesothelioma. We report further details on one case from our previous mesothelioma investigation, including results of a recent lung tissue analysis. Case is a 68 year-old white male employed 1951-54 in a rock/slag wool plant where asbestos-containing products were manufactured. Cause of death was recorded as "mesothelioma, malignant, right pleural cavity" (ICD9: 163.9). Analysis for presence of asbestos bodies identified 18,300 asbestos bodies per gram of wet lung tissue (AB/gm), which greatly exceeds the normal range of 0-20 AB/gm. No MMVFs were identified in this sample. We conclude that this patient's tumor was not a mesothelioma, but a carcinoma possibly arising in the lung or mediastinum, and that this case supports the view that the few suspected mesotheliomas found in the U.S. cohort may have been caused by asbestos exposure.

Aged↗

Bladder cancer among chemical workers exposed to nitrogen products and other substances.

OBJECTIVE: To investigate further bladder cancer mortality excess based on four deaths observed among the internal comparison population of a previous historical cohort study of workers from a chemical plant in Lima, Ohio. The internal population mainly comprised workers from the Nitrogen Products (NP) Division. METHODS: The original Lima cohort was expanded to include all workers (n = 1,841) employed between 1955 and 1996. A subcohort of workers employed mainly in the NP Division (NP Subcohort) was identified and used as the primary study population and as the source of cases and controls for a matched case-control study of bladder cancer. All death records were reviewed for any mention of bladder cancer; all available personnel, medical, and insurance files were reviewed to identify any current or former employees with an existing diagnosis of bladder cancer. A qualitative exposure assessment of all cases and controls was performed to evaluate an exploratory hypothesis that the bladder cancer excess may be associated with work histories involving both NP and urea, specifically, nitric acid and urea. RESULTS: We identified 96 new deaths among the expanded Lima cohort and obtained cause of death for 90. One additional bladder cancer death and one living case were identified and these were members of the original Lima cohort. The bladder cancer standardized mortality ratio (SMR) for the NP Subcohort (SMR = 3.31, 95%CI = 0.90-8.47) fell between the SMRs observed for all workers in the original and expanded Lima cohort (SMR = 3.93, 95%CI = 1.07-10.06 and 3.10, 95%CI = 1.01-7.24, respectively), but was markedly less than the SMR observed for corresponding subcohort of AN-unexposed workers in the original Lima cohort (SMR = 7.01, 95%CI = 1.91-17.96). Sparse data and a high prevalence of exposure among controls precluded an informative statistical analysis of the possible association between work histories involving both nitric acid and urea and bladder cancer risk. CONCLUSIONS: This study confirms that bladder cancer mortality is elevated among persons who worked mainly in the NP Division of the Lima plant, but at a lower, less statistically significant level than indicated by the original cohort study. No occupational risk factors considered to be causally related to the bladder cancer excess could be identified by this intensive investigation; other possible reasons for the excess are suggested by the descriptive data.

Adult↗

Pharyngeal cancer mortality among chemical plant workers exposed to formaldehyde.

OBJECTIVES: To assess the possible relationship between formaldehyde exposure and mortality risk from pharyngeal cancer (PC), in particular nasopharyngeal cancer (NPC). METHODS: Subjects were 7328 workers employed at a plastics-producing plant (1941-1984). Vital status for 98% of the cohort and cause of death for 95% of 2872 deaths were determined. Reconstructed exposures to formaldehyde, particulates and pigment were used to compute several exposure measures. Standardized mortality ratios (SMRs) were computed for several demographic, work history and formaldehyde exposure variables. In a nested case-control study, seven cases of NPC and 15 cases of other PC were matched on race, sex, age and year of birth to four controls from the cohort. Among interviewed subjects, lifetime smoking history was determined using respondents or proxies for all but one control subject. RESULTS: Statistically significant 2.23-fold and fivefold excesses for PC and NPC, respectively, were observed. Fivefold range NPC excesses were observed for both short ( < 1 year) and long-term workers and were concentrated among workers hired during 1947-1956. Only three NPC cases were exposed to formaldehyde for longer than one year, and each had low average intensity of formaldehyde exposure (0.03-0.60 ppm). Only a few exposure measures revealed some evidence of an association with all PC or NPC. For all PC combined, adjustment for smoking and year-of-hire in the case-control study generally corroborated findings from the cohort study. CONCLUSIONS: Overall, the pattern of findings suggests that the large, persistent nasopharyngeal and other PC excesses observed among the Wallingford workforce are not associated with formaldehyde exposure, and may reflect the influence of nonoccupational risk factors or occupational risk factors associated with employment outside the Wallingford plant.

Adult↗

Methodology to improve data quality from chart review in the managed care setting.

BACKGROUND: Because inherent variability may exist in data collected by multiple reviewers or from potential difficulties with data abstraction tools, we developed a standardized method of evaluating interrater reliability (IRR) for clinical studies, HEDIS effectiveness of care measures, and onsite/medical record reviews. OBJECTIVE: To demonstrate the ability of our standardized methods of data collection and analysis of results to determine the extent of agreement between multiple reviewers; identify areas for improvement in data collection procedures; and improve data reliability. STUDY DESIGN: A prospective chart review with concurrent IRR. METHODS: A subsample of patient records included in the Highmark Blue Cross Blue Shield/Keystone Health Plan West basic medical review for each HEDIS measure was selected for the IRR study. An experienced nurse ("gold standard") conducted a blinded concurrent review of these records. Using the kappa statistic (kappa) we evaluated interobserver agreement between results of the onsite reviewers and the "gold standard" from 1997 through 2000. Revised data collection methods and enhanced reviewer training were incorporated for measures showing areas for rater improvement. RESULTS: Results across years showed excellent IRR for most measures; however, each year 1 or 2 measures showed areas for rater improvement (1997 Papanicolaou kappa = 0.50; 1998 well-child visits 3 to 6 years kappa = 0.37; 1999 comprehensive diabetes kappa = 0.73; high blood pressure kappa = 0.73). After reevaluating these measures, the results of the kappa showed excellent interrater agreement in subsequent years. CONCLUSIONS: Standardized methods of data collection and evaluation of IRR results provides health plans increased confidence in data collection, statistical analyses, and in reaching conclusions and deriving relevant recommendations.

Blue Cross Blue Shield Insurance Plans↗