Chemoprevention of lung cancer: the beta-Carotene and Retinol Efficacy Trial (CARET) in high-risk smokers and asbestos-exposed workers.
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Aged↗
Biomedical subjects
S Barnhart
Publications and source records attributed to S Barnhart.
The beta-carotene and retinol efficacy trial (CARET) for chemoprevention of lung cancer in high risk populations: smokers and asbestos-exposed workers.
CARET is a multicenter, two-armed, double-masked randomized chemoprevention trial in Seattle, Portland, San Francisco, Baltimore, Connecticut, and Irvine, to test whether oral administration of beta-carotene (30 mg/day) plus retinyl palmitate (25,000 IU/day) can decrease the incidence of lung cancer in high risk populations, namely, heavy smokers and asbestos-exposed workers. The intervention combines the antioxidant action of beta-carotene and the tumor suppressor mechanism of vitamin A. As of April 30, 1993, CARET had randomized 1,845 participants in the 1985-1988 pilot phase plus 13,260 "efficacy" participants since 1989; of these, 4,000 are asbestos-exposed males and 11,105 are smokers and former smokers (44% female). Accrual is complete everywhere except Irvine, which was the last center added (1991), and the safety profile of the regimen to date has been excellent. With 14,420 smokers, 4,010 asbestos-exposed participants, and 114,100 person-years through February 1998, we expect CARET to be capable of detecting a 23% reduction in lung cancer incidence in the two populations combined and 27, 49, 32, and 35% reductions in the smokers, female smokers, male smokers, and asbestos-exposed subgroups, respectively. CARET is highly complementary to the alpha-tocopherol-beta-carotene study in Finland and the Harvard Physicians Health Study (beta-carotene alone) in the National Cancer Institute portfolio of major cancer chemoprevention trials.
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Outcome of carpal tunnel surgery in Washington State workers' compensation.
All cases of occupational carpal tunnel syndrome (OCTS) who received surgery for this condition in the Washington State workers' compensation system were identified using claim and physician billing databases. One hundred ninety-one incident surgical cases were identified between July 1, 1987 and December 31, 1987, and were followed up a mean of 3 years postoperatively for clinical, disability, and return to work outcomes. Medical record and claim file review was required for clinical and employment information. The mean age of all patients was 36.6 years, 48% were female, and 40% received bilateral surgery. The mean time from claim filing to surgery was 187 days. Ninety-eight percent of cases met the National Institute for Occupational Safety and Health (NIOSH) case definition for OCTS. Relief of pain was complete or modest in 86% (124/145) and only 14% of cases reported no improvement in symptoms. Mean duration of disability (time loss) postoperatively was nearly 4 months, and 8% of cases exceeded 1 year of time loss. The majority of cases returned to their same job (67%) or to a different job (15%). Workers in high risk occupations were less likely to return to the same job after CTS surgery compared to those in lower risk occupations (61% vs. 75%, p = 0.08). In this population, no association was seen between any outcome and age, gender, marital status, or baseline wage. Duration of disability was not significantly related to preoperative severity of OCTS or to more specific case criteria for this condition.(ABSTRACT TRUNCATED AT 250 WORDS)
Absenteeism↗
Statistical design and monitoring of the Carotene and Retinol Efficacy Trial (CARET).
CARET is a chemoprevention trial of beta-carotene and vitamin A with lung cancer as the primary outcome. Participants at high risk for lung cancer are drawn from two populations: asbestos-exposed workers and heavy smokers. The intervention is a daily combination of 30 mg beta-carotene and 25,000 IU vitamin A as retinyl palmitate. Nearly 18,000 participants will be followed for a mean 6 years, yielding over 100,000 person-years of follow-up. We project that this sample size will have 80% power to detect a 23% decrease in the incidence of lung cancer cases. The purpose of this paper is to present the values of the key sample size parameters of CARET; our schemes for monitoring CARET for sample size adequacy, incidence of side effects, and efficacy of the study vitamins; an overview of the data collected; and plans for the primary, secondary, and ancillary analyses to be performed at the end of the trial. These approaches to the design, monitoring, and analysis of CARET are applicable for many other prevention trials.
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Correlation between respiratory symptoms and pulmonary function in asbestos-exposed workers.
Studies of respiratory questionnaire efficacy have emphasized reliability of responses; few have validated symptom response with objective measures of pulmonary function. To determine whether respiratory symptoms are associated with diminished pulmonary function, symptoms reported on the American Thoracic Society (ATS-DLD-78A) questionnaire were correlated cross-sectionally with measured spirometric volumes in 816 asbestos-exposed workers. Cough, phlegm, wheeze, and dyspnea were inversely related to pulmonary function. Cough, phlegm, and chronic bronchitis were associated with a 2 to 8% reduction (p < 0.001) in predicted values for forced vital capacity (FVC) and forced expiratory volume (FEV1); wheeze and dyspnea were clinically more significant, with an 11 to 17% reduction (p < 0.001). Wheeze, dyspnea, and roentgenographic fibrosis were all significant independent predictors of risk for restrictive impairment. These results support the validity of the ATS questionnaire as an epidemiologic tool and emphasize the importance of clinical history in assessing respiratory status.
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Work-related cumulative trauma disorders of the upper extremity.
Cumulative trauma disorders due to performance of repetitive tasks account for more than 50% of all occupational illnesses in the United States today. Employees affected by these disorders frequently experience substantial pain and functional impairment that may require a change in occupation. For the employer, these injuries result in loss of productivity and increased costs in the form of higher medical expenses and disability payments for injured workers. Successful treatment of work-related repetitive tissue injuries depends on early diagnosis and appropriate therapy. Prevention requires identifying sites and tasks that place employees at risk of injury and supporting efforts to develop safer work environments.
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Neuropsychological performance among agricultural pesticide applicators.
To assess the potential effects on neuropsychiatric performance of chronic occupational exposure to organophosphate insecticides, we performed a prospective longitudinal study of a cohort of apple orchard pesticide applicators and a comparison cohort of beef slaughter-house workers. The study group consisted of 49 applicators and 40 comparison subjects who completed both an initial evaluation (preseason) prior to the onset of the approximately 6-month pesticide spraying season and a follow-up evaluation (postseason) about 1 month following the end of spraying season. The applicator cohort had a greater number (n = 22, 45%) of individuals who identified primary preference for Spanish-language testing than did the comparison cohort (n = 5, 13%). Stratification by language preference revealed no significant differences in background characteristics between the two cohorts, except for fewer years of education in the Spanish-language preference applicators versus control subgroups (5.0 +/- 3.1 vs 7.8 +/- 3.7 years, respectively). After controlling for language preference, there were no statistically significant differences between the applicators and control cohorts on neuropsychological subtests of the computerized test battery. Preseason baseline performance on individual tests was a significant predictor of postseason test performance. After controlling for baseline performance, the only statistically significant exposure related across-season changes in neuropsychological performance was for one subtest (Symbol Digit Substitution) and was confined to the Spanish language preference subgroups, with worse adjusted postseason performance among applicators versus controls (P = 0.001). This study found no clear evidence of clinically significant decrements in neuropsychological performance following one 6-month season of pesticide exposure in a cohort of applicators who were felt to have generally low, intermittent, and well-controlled organophosphate exposures.
Adult↗
Organophosphate pesticide exposure in a group of Washington State orchard applicators.
As part of a study to investigate the potential for organophosphates to cause chronic neurologic sequelae, we assessed the pesticide exposure experience of a group of Washington State apple orchard applicators. Seasonal monitoring of cholinesterase activity for 48 regular organophosphate applicators and a control group of 40 slaughterhouse workers was performed. A subset of the pesticide applicators participated in an in-depth exposure assessment. This involved observation of spraying activities during 1 spray day, as well as cholinesterase monitoring and dermal exposure assessment using a fluorescent tracer in the pesticide formulation. Comparison of seasonal red blood cell cholinesterase change in pesticide workers according to exposure level, characterized by frequency of pesticide spraying and protective equipment use, showed lower cholinesterase levels among higher exposed groups compared to lesser exposed groups. In-depth exposure assessment revealed exposure primarily on the head and hand regions. Subclinical changes (less than 15% inhibition) in red cell cholinesterase correlated well with dermal exposure calculations. This study suggests that cholinesterase monitoring may be a useful biological marker for even subclinical organophosphate pesticide effects.
Agricultural Workers' Diseases↗
The 10-year experience of an academically affiliated occupational and environmental medicine clinic.
Occupational and environmental diseases are underrecognized. Among the barriers to the successful diagnosis, treatment, and prevention of these conditions are inadequate consultative and information resources. We describe the 10-year clinical and training experiences of an academically affiliated referral center that has as its primary goal the identification of work-related and other environmental diseases. The University of Washington Occupational and Environmental Medicine Program has evaluated 6,048 patients in its diagnostic and screening clinics. Among the 2,841 seen in the diagnostic clinics, 1,553 (55%) had a work-related condition. The most prevalent diagnoses included asbestos-related lung disease (n = 603), toxic encephalopathy (n = 160), asthma (n = 119), other specific respiratory conditions (n = 197), carpal tunnel syndrome (n = 86), and dermatitis (n = 82). The clinics serve as a training site for fellows in the specialty training program, primary care internal medicine residents, residents from other medical specialties, and students in industrial hygiene, toxicology, and occupational health nursing. The program serves two additional important functions: providing consultative services to community physicians and training specialists and other physicians in this underserved area of medicine.
Adolescent↗
Recruitment for the beta-carotene and retinol efficacy trial (CARET) to prevent lung cancer in smokers and asbestos-exposed workers.
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Asbestos↗
CARET, the beta-carotene and retinol efficacy trial to prevent lung cancer in asbestos-exposed workers and in smokers.
CARET is a two-armed, double-blind, randomized chemo-prevention trial to test the hypothesis that oral administration of beta-carotene 30 mg/day plus retinyl palmitate 25,000 IU/day will decrease the incidence of lung cancer in high-risk populations: heavy smokers and asbestos-exposed workers who have smoked. The agents combine anti-oxidant and nuclear tumor suppressor mechanisms. Fastidious monitoring for possible side effects is facilitated by inclusion of a Vanguard population. As of 31 December 1990, 6,105 participants of the 18,000 needed have been randomized in the trial. Efficacy results are expected in 1999.
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Carpal tunnel syndrome among ski manufacturing workers.
Carpal tunnel syndrome is a common disorder marked by pain and dysesthesias of the upper extremities. As a test of the hypothesis that carpal tunnel syndrome is associated with occupational risk factors, jobs at a ski assembly plant were classified as repetitive and nonrepetitive. The prevalence of carpal tunnel syndrome among 106 employees with repetitive jobs was compared with that among 67 employees with nonrepetitive jobs. The data collection included a questionnaire, a physical examination, and the measurement of distal sensory latencies of the median and ulnar nerves. Carpal tunnel syndrome was present in either or both hands in 15.4% of those workers with repetitive jobs, but only in 3.1% of those workers with nonrepetitive jobs (crude prevalence ratio 4.92, 95% confidence interval 1.17-20.7). The conclusion was drawn that carpal tunnel syndrome is associated with jobs requiring frequent and sustained hand work.
Adult↗
Chronic neuropsychological sequelae of occupational exposure to organophosphate insecticides.
The early (immediate and delayed) neurotoxic effects of acute organophosphate intoxication are well documented in the scientific literature; lack of recognition and inappropriate treatment of occupational poisonings continue. Less well understood is the potential development of chronic neuropsychological sequelae from exposures to insecticides. We undertook two cohort studies to assess chronic neuropsychologic effects of insecticide poisoning. Based, in part, on our clinical evaluation of several patients, these studies included: 1) a retrospective cohort study assessing function at least 1 year following moderate to severe poisonings among farm workers; and 2) a prospective cohort study assessing neuropsychological function before and after a season of organophosphate exposures among pesticide applicators. A typical case description, the study design, methodologic problems, and preliminary findings of these ongoing studies are presented.
Agricultural Workers' Diseases↗
Respiratory mortality among firefighters.
Although firefighters have been shown in some studies to suffer chronic respiratory morbidity from their occupational exposures, an increased risk for dying from non-malignant respiratory diseases has not been documented in any previous retrospective cohort mortality study. In order to assess the possibility that an unusually strong "healthy worker effect" among firefighters might mask this increased risk, a mortality analysis of firefighters was carried out in three cities in relation to the United States population and also to a comparison cohort of police officers. The firefighters were employed between 1945 and 1980 and experienced 886 deaths by 1 January 1984; compared with the United States population they had a significantly reduced risk of dying from all causes (SMR = 82, 95% confidence interval, 77-87), and from non-malignant circulatory diseases (SMR = 81, 95% confidence interval 73-89), but no significant difference in risk of non-malignant respiratory diseases (SMR = 88, 95% confidence interval 66-117). Compared with police, the firefighters experienced a trend toward improved mortality outcomes for all causes investigated (SMR = 82), but they had an excess of deaths from non-malignant respiratory diseases (SMR = 141). The results indicate that firefighters are probably at increased risk for dying from non-malignant respiratory diseases; this increased risk may have been missed in previous studies because of the limitations of using a general reference population.
Adolescent↗
The degree of roentgenographic parenchymal opacities attributable to smoking among asbestos-exposed subjects.
Considerable controversy surrounds the question of whether cigarette smoking has the potential to increase the prevalence of small opacities on chest roentgenographs among asbestos-exposed workers. To compare the relative contribution of smoking with other predictors of the presence of roentgenographic small opacities, we examined 661 men enrolled in a double-blind, randomized trial designed to assess the efficacy of vitamin A and beta-carotene in the prevention of lung cancer among workers with heavy occupational asbestos exposure. Subjects in the study population had a mean latency of 35 yr from first asbestos exposure and a mean of 28 yr in their trade. The prevalence of roentgenographic abnormalities consistent with asbestos exposure was 26% for pleural abnormalities alone, 10% for parenchymal abnormalities alone, and 20% for pleural and parenchymal abnormalities together. We investigated occupation, age, latency from first asbestos exposure, and smoking status as predictors of roentgenographic small opacities. Smoking history, independent of latency, contributed to the prevalence and extent of small opacities, but its effect was less than that of latency. We conclude, that in the setting of heavy occupational exposure to asbestos, cigarette smoking confers added risk for the development of roentgenographic small opacities.
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Evaluation of a proposed NIOSH surveillance. Case definition for occupational asthma.
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Asthma↗
Firefighting acutely increases airway responsiveness.
The acute effects of the products of combustion and pyrolysis on airway responsiveness among firefighters are poorly documented. To study this relationship, spirometry and methacholine challenge testing (MCT) were performed on 18 active Seattle firefighters before and 5 to 24 h after firefighting. Body plethysmography was used to measure changes in specific airway conductance (SGaw), and results of MCT were analyzed using PD35-SGaw, the cumulative dose causing a 35% decrease in SGaw. Subjects who did not react by the end of the protocol were assigned a value of 640 inhalational units, the largest cumulative dose. Fire exposure was defined as the total time (hours) spent without a self-contained breathing apparatus at the firesite and was categorized as mild (less than 1 h, n = 7), moderate (1 to 2 h, n = 5), or severe (greater than 2 h, n = 6). Mean age of the 18 firefighters was 36.7 +/- 6.7 yr (range, 25 to 51), with a mean of 9.1 +/- 7.9 active years in the trade (range, zero to 22). None was known to be asthmatic. After firefighting, FEV1 % predicted (%pred) and FEF25-75 %pred significantly decreased by means of 3.4 +/- 1.1% and 5.6 +/- 2.6%, respectively. The mean decline in PD35-SGaw after firefighting was 184.5 +/- 53.2 units (p = 0.003). This observed decline in PD35-SGaw could not be explained by decrements in prechallenge SGaw, FEV1, or FVC.(ABSTRACT TRUNCATED AT 250 WORDS)
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