Brain SPECT: a controlled, blinded assessment of intra-reader and inter-reader agreement.

A detailed assessment of intra- and inter-reader variation in the interpretation of brain SPECT scans has been performed. A random sample was selected from scans performed at a community/teaching hospital in Seattle. Scans were interpreted independently by three experienced readers who were blinded to all patient information. Forty-eight scans were interpreted twice by each reader, for a total of 288 readings. Readers recorded detailed assessments of individual lesions and overall impressions using a standardized reporting form. Intra-observer agreement as reflected in per cent agreement for severity scores ranged from 65% to 100%. Intra-observer agreement on the 'overall impression' was very good for Alzheimer's pattern (kappa=0.73-1.00), and fair to good for the 'heterogeneous pattern' (kappa=0.30-0.63). Inter-observer agreement, as reflected in per cent agreement, ranged from 29% to 100%. Inter-observer agreement about the 'overall impression' was fair to moderate for Alzheimer's pattern (kappa=0.24-0.54) and was poor for the descriptors 'heterogeneous' and 'normal'. It is concluded that brain SPECT has great potential value in many important conditions. This study demonstrates a need for further work in the areas of pattern definition and reduction of observer variation.

Risk factors for adverse health effects following hazardous materials incidents.

To identify risk factors for persistent morbidity, we conducted a prospective study of individuals involved in hazardous materials incidents reported to the Washington Poison Center. Between December 1997 and October 1999, 202 subjects in 87 incidents were surveyed by telephone. Medical symptoms persisting for a minimum of 8 days after the incident were reported in 51 (25%) subjects, and 18 (9%) left work or school for more than 2 days because of the exposure. Medical intervention was reported in 46 (58%) of 79 subjects for whom medical records were available, and objective abnormalities were found in 57 (72%). Multiple logistic regression analysis indicated that subjects with dermal exposures, three or more alcoholic drinks per week, and previous use of psychiatric medications were more likely to report persistent symptoms. Divorced, widowed, or separated subjects, asthmatic subjects, and those having initial dermal symptoms were more likely to miss work or school for more than 2 days. Of patients evaluated at a health care facility, subjects with preexisting hypertension were more likely to receive medical treatment or have objective medical findings, whereas those with inhalation exposures and those decontaminated at the scene were less likely to be treated or have abnormalities. In our study, both incident and individual factors were predictive of adverse health effects, and these findings should be considered in planning the care of patients involved in hazardous materials incidents.

Hazardous materials events: evaluation of transport to health care facility and evacuation decisions.

The study objective was to analyze hazardous materials event and victim factors associated with transportation of victims to a health care facility, and evacuation or shelter-in-place of nearby populations. A retrospective review was conducted on hazardous materials events in Washington State from 1993 to 1997. Bivariate and multiple logistic regression were used to identify risk factors for transportation, evacuation, and shelter-in-place. Over five years, 2,654 victims from 457 events were reported, with 1,859 (70%) transported to a health care facility. Evacuation occurred in 279 (61%) events and shelter-in-place in 14 (3%) events. After excluding 14 deaths, regression analysis indicated that victims with trauma (OR 5.87, 95% CI 1.41-24.5), thermal burns (6.90, 1.15-41.3), dizziness/other CNS symptoms (1.59, 1.00-2.54), and headache (1.54, 1.01-2.35) were most likely to be transported. Chemical releases inside buildings (2.09, 1.06-4.10, compared with transportation events), and involving 3-5 victims (2.86, 1.54-5.31, compared to 1 victim) or > or =6 victims (8.74, 4.01-19.0), were most likely to involve evacuation or shelter-in-place. Events involving sulfuric acid (0.15, 0.05-0.49) and sodium hydroxide (0.19, 0.04-0.94) were least likely to involve evacuation or shelter-in-place. Prehospital decisions to transport victims to a health care facility and evacuate or shelter-in-place nearby populations are associated with event and victim factors. Further research is needed to determine if these factors also predict need for medical care or removal from exposure, and to develop evidence-based prehospital care protocols for hazardous materials exposure victims.

Serum hepatic biochemical activity in two populations of workers exposed to styrene.

OBJECTIVE: To determine whether hepatic biochemical changes, as measured by routinely available tests indicative of hepatocellular necrosis, cholestasis, or altered hepatic clearance of bilirubin, occur in association with low to moderate exposure to styrene commonly experienced in industrial production. METHODS: Two independent cross sectional studies were performed comparing serum hepatic transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), cholestatic enzymes (alkaline phosphatase (AP) and gamma glutamyl transpeptidase (GGT)), and bilirubin in (a) 47 workers of fibreglass reinforced plastics who were exposed to styrene and (b) 21 boat and tank fabricators, with separate referent groups of unexposed workers. Exposure to styrene was assessed in air by dosimetry, and in venous blood by headspace analysis. Hepatic biochemical variables were assessed across strata of exposure to styrene defined as 25 ppm in air, or 0.275 mg/l in blood, adjusting for age, sex, body mass index, and ethanol consumption. RESULTS: A consistent and significant linear trend for increasing direct bilirubin and direct/total bilirubin ratio was found in association with increasing exposure to styrene, by both air and blood monitoring, in both studies. Mean direct bilirubin concentrations increased from 0.05-0.08 mg% in referents to 0.12-0.19 in workers exposed above 25 ppm, with a significant exposure-response trend (p<0.005). Significantly increased direct/total bilirubin ratios, ranging from 0.22 to 0.35 were associated with exposure to styrene (p<0.001), indicating diminished hepatic clearance of conjugated bilirubin. Also, a significant linear association between the hepatic transaminases ALT and AST and exposure to styrene was found in pooled regression analyses, with an increase in AP of about 10 IU/ml in workers exposed above 25 ppm air or 0.275 mg/l blood styrene in pooled analyses from both studies. CONCLUSIONS: The consistent finding of increased direct bilirubin and AP concentrations in these two independent studies provides evidence for diminished hepatic clearance of conjugated bilirubin with associated cholestasis in workers exposed to styrene. The finding of a significant linear association between hepatic transaminase concentrations and exposure to styrene in pooled analyses is consistent with mild hepatic injury and associated metabolic dysfunction.

Use of a questionnaire to improve occupational and environmental history taking in primary care physicians.

New patient charts were reviewed before and after the introduction of a self-administered questionnaire, designed to elicit occupational and environmental (OE) information from patients. The Occupational Health Risk Assessment questionnaire (OHRA) was expected to prompt primary care physicians to make further inquiries into OE health issues. Chart reviews determined the amount and type of information detailed in the primary care physicians' notes. Twenty-three percent of completed OHRAs indicated a job-related health problem. Despite a high prevalence of self-reported work-related symptoms and exposures, the mean number of notations regarding OE exposures was less than one item per patient chart. A comparison of mean OE notations per chart before versus after introduction of the OHRA indicated a decline in notations after introduction of the OHRA (1.03 vs 0.72, P = 0.02). We detail the type of OE issues that patients presented to a primary care practice and the resulting information contained in primary care providers' notes. Suggestions are made to improve a self-administered patient questionnaire to better diagnose, prioritize, and formulate treatment plans related to OE issues.

Longitudinal decline in measured firefighter single-breath diffusing capacity of carbon monoxide values. A respiratory surveillance dilemma.

Seattle firefighters participate in a voluntary annual medical surveillance program including measurements of ventilatory capacity (FVC and FEV1) and single-breath diffusing capacity of carbon monoxide (DLCO). From 1989 to 1996, average % predicted DLCO (Crapo) for all participating firefighters declined from 94.4% (95% confidence interval [CI]: 93.4% to 95.5%) to 87.3% (95% CI: 86.2% to 88.3%), with no significant change in average FVC or FEV1. A random-effects regression model based on data from 812 firefighters with at least two annual sets of DLCO measurements showed the expected associations between DLCO and age, height, gender, race, ventilatory capacity, and smoking. In addition, two important temporal changes were observed, including, for an average firefighter, a large mean decline in DLCO of -1.02 ml/min/mm Hg associated with year of measurement, and a relatively smaller decline of -0.006 ml/min/mm Hg associated with number of fires fought. Although the stability of ventilatory capacity over time is reassuring, the marked temporal decline in diffusing capacity among this population of firefighters raises issues of concern. Interpretation of the observed decline poses a dilemma in terms of the reliability and efficacy of diffusing capacity as a screening tool, in whether DLCO is subject to unacceptable technical variability or whether it might provide more sensitive detection of early adverse respiratory effects of smoke inhalation.

Reproductive endocrine effects of acute exposure to toluene in men and women.

OBJECTIVES: Despite observation of adverse reproductive effects of toluene, including alterations of serum gonadotropins (luteinising hormone (LH) and follicle stimulating hormone (FSH)) in humans, little is known of the mechanism of toxicity. The hypothesis was tested that toluene acutely suppresses pulsatile gonadotropin secretion by measuring LH and FSH at frequent intervals during controlled exposure to toluene. METHODS: Women in the follicular and luteal phases of the menstrual cycle and men were randomised to inhale filtered air with or without 50 ppm toluene through a mouthpiece for 3 hours (19% of the OSHA permissible exposure limit). Blood was sampled by intravenous catheter at 20 minute intervals for 3 hours before, 3 hours during, and 3 hours after exposure. Plasma LH, FSH, and testosterone were measured. Pulse amplitude, pulse frequency, and mean concentrations of LH and FSH for each of the 3 hour periods before, during and after exposure to toluene versus sham exposure were calculated with the ULTRA pulse detection program and compared by analysis of variance (ANOVA) with repeated measures. RESULTS: In men mean concentrations of LH showed a significant interaction (p < 0.05) between exposure and sampling period, with a greater LH decline during exposure to toluene than sham exposure. However, there was no concomitant effect on testosterone concentrations. The LH pulse frequency of women in the luteal phase showed a trend towards a significant interaction between exposure and sampling period (p = 0.06), with a greater decline in pulse frequency during exposure to toluene than sham exposure. There were no other significant effects of exposure to toluene. CONCLUSIONS: Three hour exposure to 50 ppm toluene did not result in abnormal episodic LH or FSH secretion profiles, however, subtle effects on LH secretion in men and women in the luteal phase were found. The clinical relevance of these effects is unclear, indicating the need for further study of reproductive function in exposed workers.

Thyroid function in lead smelter workers: absence of subacute or cumulative effects with moderate lead burdens.

OBJECTIVE: To evaluate the effect of low to moderate occupational lead exposure on thyroid function we conducted a cross-sectional study of 151 male lead smelter workers. METHODS: Parameters of thyroid function were assessed in relation to both subacute and cumulative lead exposure over a 10-year employment period. Blood lead levels, obtained from plant surveillance records, were used to establish four ordinal levels of current and cumulative exposure (< 15, 15-24, 25-39, and > or =40 microg/dl). RESULTS: Mean values for the lowest as compared with the highest current exposure group were similar for thyroxine (T4: 6.8 versus 6.1 microg/dl), estimated free thyroxine (EFT4: 1.6 ng/dl in both groups), and thyroid-stimulating hormone (TSH: 1.8 versus 1.7 mIU/l); there was no evidence of a significant trend for diminished thyroid function associated with increasing current lead exposure. Similarly, no significant difference was observed for T4, EFT4, or TSH in relation to the 10-year cumulative exposure or for adjusted analyses controlling for potential confounders, including age and alcohol use. CONCLUSION: In contrast to studies observing thyroid dysfunction in the setting of high lead exposure and related clinical poisoning, our findings weigh against a significant physiologic effect on thyroid function at lower levels (< 60 microg/dl) of occupational lead exposure.

The validity of radiographic estimation of total lung capacity in patients with respiratory disease.

STUDY OBJECTIVE: To evaluate the validity of a state-of-the-art computerized planimetry technique for estimation of total lung capacity (TLC) from chest radiographs, when applied to patients with clinical lung disease receiving routine chest radiographs. DESIGN: Retrospective clinical survey. SETTING: An occupational medicine diagnostic clinic. PATIENTS: A convenience sample of 40 subjects with asbestos-related lung disease, 5 patients with nonasbestos-related restrictive defects, 15 subjects with occupational asthma, and 10 subjects with irritant tracheobronchitis. RESULTS: Estimation of TLC using state-of-the-art computerized algorithms demonstrated limited agreement with conventional measures of TLC when applied to patients with occupational lung disease receiving routine chest radiographs. The most pronounced differences occurred in patients with asbestos-related lung disease and restrictive defects, where the radiographic method of measurement significantly overestimated helium dilution TLC by 986 mL (r=0.73, p<0.001) and 1,135 mL (r=0.82, p<0.05), respectively. Good inspiratory effort was associated with significantly increased radiographic TLC relative to helium dilution TLC; however, radiographic features did not fully account for the observed differences between radiographic and helium dilution techniques. CONCLUSIONS: Our findings suggest that this planimetric technique should not be used as a substitute for conventional measures of TLC in clinic populations receiving routine radiographs. The large diagnostic group specific mean differences observed between radiographic and conventional measures of TLC also suggest that this method is of limited utility in clinical evaluation of occupational lung disease.

Lobe of origin and histologic type of lung cancer associated with asbestos exposure in the Carotene and Retinol Efficacy Trial (CARET).

Lower lobe origin and histologic diagnosis of adenocarcinoma have been described as useful parameters for attributing lung cancer to prior asbestos exposure. To assess whether these characteristics differed between asbestos-exposed individuals and smokers, we evaluated lobe of origin and histologic type of tumors in 78 asbestos-exposed and 214 nonexposed heavy smokers developing lung cancer during the Carotene and Retinol Efficacy Trial (CARET), a prospective cancer chemoprevention trial. Most tumors in both cohorts, regardless of radiographic fibrosis at baseline, originated in upper lobes, representing 67% in asbestos-exposed and 80% in smokers, respectively (adjusted OR for lower lobe = 1.41; 95% CI = 0.69-2.91). Adenocarcinoma represented 32% of lung tumors in the asbestos cohort, and 30% in the smoking cohort (adjusted OR = 0.78; 95% CI = 0.40-1.55), and was inversely associated with radiographic fibrosis (adjusted OR = 0.19; 95% CI = 0.06-0.62). We conclude that neither anatomic site nor histologic cell type of tumors distinguishes effectively between smoking and asbestos as causal factors in development of lung cancer.

The protective effect of beta-carotene and retinol on ventilatory function in an asbestos-exposed cohort.

The association between serum beta-carotene or retinol concentration and level of ventilatory function was investigated in a population of asbestos-exposed men with a high rate of current and former cigarette smoking. The study population consisted of 816 subjects enrolled in the pilot component of the Carotene and Retinol Efficacy Trial (CARET), a placebo-controlled trial of supplemental beta-carotene and retinyl palmitate for the chemoprevention of lung cancer. Data available for analysis included baseline questionnaire, spirometry, chest X-ray, food frequency questionnaire, and serum beta-carotene and retinol concentrations. Serum beta-carotene concentration was associated with FEV1 (p < 0.05) and FVC (p < 0.05), with an approximately 100-ml increase over predicted values associated with raising the serum concentration from the 25th to the 75th percentile of the distribution in the study population (absolute difference = 155 ng/ml), even after adjustment for the confounding effects of asbestos exposure and cigarette smoking. Raising the serum retinol concentration from the 25th to the 75th percentile (absolute difference = 211 ng/ml) was associated with an approximately 70 ml increase in FVC (p < 0.05) over the predicted value. These results provide support for the hypothesis that beta-carotene and retinol have a protective effect on loss of ventilatory function.

Hospital preparedness for hazardous materials incidents and treatment of contaminated patients.

Hospital-based facilities providing emergency care in the state of Washington were surveyed to determine their level of preparedness for hazardous materials incidents including the treatment of contaminated patients. Responses to a faxed questionnaire were received from 95 (94%) of the 101 emergency care facilities in Washington State. Only 42 (44%) of the facilities reported the ability to receive any chemically exposed patient. Of the 95 responding emergency care facilities, 39 (41%) had no designated decontamination facilities; 67 (70%) had protocols for handling chemical contamination and possible evacuation from hazardous materials spills, and 52 (55%) had protocols for handling medical facility contamination and possible evacuation from treating chemically contaminated patients. Twelve (13%) facilities had evacuated their emergency department or other part of the hospital for contamination incidents in the past 5 years. Despite the frequent occurrence of hazardous materials incidents, most emergency care facilities in Washington State are not fully prepared to handle contaminated patients and chemical spills. This may have important implications for the care of persons with exposure to hazardous materials and for implementing Joint Commission on Accreditation of Healthcare Organizations standards and federal Occupational Safety and Health Administration regulations.

Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial.

BACKGROUND: Evidence has accumulated from observational studies that people eating more fruits and vegetables, which are rich in beta-carotene (a violet to yellow plant pigment that acts as an antioxidant and can be converted to vitamin A by enzymes in the intestinal wall and liver) and retinol (an alcohol chemical form of vitamin A), and people having higher serum beta-carotene concentrations had lower rates of lung cancer. The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate (vitamin A) taken daily against placebo in 18314 men and women at high risk of developing lung cancer. The CARET intervention was stopped 21 months early because of clear evidence of no benefit and substantial evidence of possible harm; there were 28% more lung cancers and 17% more deaths in the active intervention group (active = the daily combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate). Promptly after the January 18, 1996, announcement that the CARET active intervention had been stopped, we published preliminary findings from CARET regarding cancer, heart disease, and total mortality. PURPOSE: We present for the first time results based on the pre-specified analytic method, details about risk factors for lung cancer, and analyses of subgroups and of factors that possibly influence response to the intervention. METHODS: CARET was a randomized, double-blinded, placebo-controlled chemoprevention trial, initiated with a pilot phase and then expanded 10-fold at six study centers. Cigarette smoking history and status and alcohol intake were assessed through participant self-report. Serum was collected from the participants at base line and periodically after randomization and was analyzed for beta-carotene concentration. An Endpoints Review Committee evaluated endpoint reports, including pathologic review of tissue specimens. The primary analysis is a stratified logrank test for intervention arm differences in lung cancer incidence, with weighting linearly to hypothesized full effect at 24 months after randomization. Relative risks (RRs) were estimated by use of Cox regression models; tests were performed for quantitative and qualitative interactions between the intervention and smoking status or alcohol intake. O'Brien-Fleming boundaries were used for stopping criteria at interim analyses. Statistical significance was set at the .05 alpha value, and all P values were derived from two-sided statistical tests. RESULTS: According to CARET's pre-specified analysis, there was an RR of 1.36 (95% confidence interval [CI] = 1.07-1.73; P = .01) for weighted lung cancer incidence for the active intervention group compared with the placebo group, and RR = 1.59 (95% CI = 1.13-2.23; P = .01) for weighted lung cancer mortality. All subgroups, except former smokers, had a point estimate of RR of 1.10 or greater for lung cancer. There are suggestions of associations of the excess lung cancer incidence with the highest quartile of alcohol intake (RR = 1.99; 95% CI = 1.28-3.09; test for heterogeneity of RR among quartiles of alcohol intake has P = .01, unadjusted for multiple comparisons) and with large-cell histology (RR = 1.89; 95% CI = 1.09-3.26; test for heterogeneity among histologic categories has P = .35), but not with base-line serum beta-carotene concentrations. CONCLUSIONS: CARET participants receiving the combination of beta-carotene and vitamin A had no chemopreventive benefit and had excess lung cancer incidence and mortality. The results are highly consistent with those found for beta-carotene in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study in 29133 male smokers in Finland.