How useful is linear regression analysis in detecting the existence of dose-response relationships in large-scale epidemiologic studies when only a fraction of the population is sensitive? The case of methylmercury.

The existence of a dose response in epidemiologic studies is generally determined from the linear regression slope after controlling for covariates. This approach assumes the entire population is equally sensitive to the toxicant and that response is a function only of dose and a random error function. However, sensitive subpopulations have been identified for a variety of toxicants possibly including methylmercury (MeHg). The study of MeHg exposure in the Seychelles Islands has failed to find significant effects (dose-response slope not significantly different from zero) while other studies have found such effects. Using data on the error function in developmental test scores and MeHg exposure distributions from that study, and assuming plausible dose-response relationships for sensitive subpopulations, we conducted Monte-Carlo simulations of the power of linear regression analysis to detect a dose-response relationship from the total sample (n=700), and to compare dose-response slopes in the total and sensitive populations. Linear regression did not reliably detect a dose-response relationship for most scenarios when sensitives were 5% of the total and for some scenarios when sensitives were 10% of the total. We also found that the dose-response slope for the total population underestimated the sensitive dose-response slope in all cases by about an order of magnitude. These findings may have important implications for detection and quantification of dose-response relationships from epidemiologic studies.

Cardiovascular stress responses and their relation to symptoms in Gulf War veterans with fatiguing illness.

OBJECTIVE: The objective of this study was to examine whether inappropriate cardiovascular responses to stressors may underlie symptoms in Gulf War veterans with chronic fatigue. METHODS: Psychophysiological stress testing was performed on 51 Gulf War veterans with chronic fatigue (using the 1994 case definition of the Centers for Disease Control and Prevention) and 42 healthy veterans. Hemodynamic responses to cold pressor, speech, and arithmetic stressors were evaluated using impedance cardiography. RESULTS: Veterans with chronic fatigue had diminished blood pressure responses during cognitive (speech and arithmetic) stress tests due to unusually small increases in total peripheral resistance. The cold pressor test, however, evoked similar blood pressure responses in the chronic fatigue and control groups. Low reactivity to cognitive stressors was associated with greater fatigue ratings among ill veterans, whereas an opposite relation was observed among healthy veterans. Self-reported neurocognitive decline was associated with low reactivity to the arithmetic task. CONCLUSIONS: These results suggest a physiological basis for some Gulf War veterans' reports of severe chronic fatigue. A greater deficit with responses processed through cerebral centers, as compared with a sensory stimulus (cold pressor), suggests a defect in cortical control of cardiovascular function. More research is needed to determine the specific mechanisms through which the dissociation between behavioral and cardiovascular activities identified in this study may be contributing to symptoms in Gulf War veterans.

Physical activity before and after exercise in women with chronic fatigue syndrome.

We measured physical activity after strenuous exercise in 20 women with chronic fatigue syndrome (CFS), compared to 20 sedentary healthy volunteers who exercised no more than once per week. Activity was measured for 2 weeks using a portable waist-worn vertical accelerometer. After the first week of activity monitoring, all participants returned for a maximal treadmill test, followed by continued activity monitoring for the second week. Five activity measures were derived from the data: (i) average activity; (ii) total activity; (iii) duration of waking day; (iv) duration; and (v) number of daily rests. A repeated measures ANCOVA was used to determine post-treadmill group differences accounting for pre-treadmill differences. There was a significant reduction in overall average activity after the treadmill test, with the greatest decrease on days 12 through 14. This reduction was accompanied by a significant increase in the duration of the waking day and number of daily rests. Thus, marked exertion does produce changes in activity, but later than self-report would suggest, and are apparently not so severe that CFS patients cannot compensate.

The effects of fatigue on neuropsychological performance in patients with chronic fatigue syndrome, multiple sclerosis, and depression.

The effects of fatigue on neuropsychological performance were examined in patients with fatiguing illnesses. Repeated testing with the Paced Auditory Serial Addition Test (PASAT; Gronwall, 1977) was employed over the course of a demanding neuropsychological testing session. It was hypothesized that if fatigue affects performance, one would expect to observe "blunting" of the PASAT practice effect. Fifteen of the study participants live with chronic fatigue syndrome (CFS), 15 with multiple sclerosis (MS), 14 with depression (DEP), and 15 are healthy, sedentary controls. Overall PASAT performance was significantly reduced for CFS and DEP participants compared to controls, whereas mean performance did not differ across the three fatiguing illness groups. Degree of improvement across trials (i.e., practice effect) for the groups did not differ from controls'. Neither subjective fatigue or DEP were significantly related to PASAT performance. These findings suggest that fatigue does not universally impair performance during neuropsychological assessment even in groups in which fatigue is a prominent symptom.

Estimation of fish consumption and methylmercury intake in the New Jersey population.

Despite scientific attention to the toxicology of methylmercury (MeHg), little is known about population-based exposure to this compound. In this study, fish consumption and MeHg intake were estimated based on a seven-day recall survey of fish consumption among 1000 randomly selected New Jersey residents. Survey data were reported on a per-meal basis, and the fish species/dishes consumed at each meal were identified. Portion sizes for each meal were reported or estimated. To correct a possible bias due to underrepresentation of infrequent consumers, several schemes for weighting fish consumption data were investigated. MeHg concentration for most fish species was estimated from the National Marine Fisheries Service database or from recent United States Food and Drug Administration data. Commercial fish accounted for about 95% of all consumption. Mean fish consumption is estimated for all New Jersey adult consumers at 50.2 g/day (90th percentile = 107.4 g/day) and for women 18-40 years old (childbearing age) at 41.0 g/day (90th percentile = 88.1 g/day). Mean MeHg intake is estimated for all New Jersey adult consumers at 7.5 micrograms/day (90th percentile = 1.79 micrograms/day) and for women 18-40 at 6.3 micrograms/day (90th percentile = 14.8 micrograms/day). When MeHg concentrations are adjusted to account for the possible overestimation of current concentrations by the 20-year-old National Marine Fisheries Service database, it is estimated that MeHg intakes may be about 70-80% of unadjusted estimates. Based on these analyses, it is estimated that 21-30% of New Jersey women 18-40 and 5-8% of all New Jersey adults exceed their respective U.S. Environmental Protection Agency Reference Doses for MeHg. Because of uncertainty associated with the Reference Doses, exceeding the U.S. Environmental Protection Agency guidelines does not necessarily correspond to adverse effects on consumers or their fetuses.

Prevalence of and potential risk factors for symptoms associated with insecticide use among animal groomers.

Pet groomers make numerous insecticide applications during the flea season, but few studies have examined their health complaints. The Pesticide Control Program of the New Jersey Department of Environmental Protection conducted a health and safety survey of this population. All licensed pet applicators in New Jersey were contacted, as were New Jersey veterinarians listed as pet-animal practitioners by the American Veterinary Medical Association. Approximately 36% of the respondents indicated that during the 1994 flea season, they had experience at least one of the 17 symptoms associated with insecticide application. Central nervous system symptoms (headache, dizziness, or confusion) and skin symptoms (skin rash or numbness/tingling) were reported most frequently. Logistic regression results suggest that applications per season, years as an applicator, certain hygiene variables, certain classes of products, and status of applicator (veterinary vs veterinary) are potentially important risk factors.

Chromium exposure assessment of outdoor workers in Hudson County, NJ.

A large quantity of chromate chemical production waste, containing hexavalent chromium, has been used as fill at over 150 sites in Hudson County, New Jersey. One site is in a state park, and several other sites are adjacent to the park. Blood and urinary chromium levels were compared between 17 employees at the Hudson County park and 35 employees from two other state parks. A limited number of soil and personal air samples were also taken. Urinary and RBC chromium levels between the two groups were similar, even after adjusting for potentially confounding variables. The air sampling results demonstrated slightly higher chromium levels at Hudson County, but these were still very low level in nature (mean = 0.18 micrograms/m3). These results call into question the utility of chromium biomonitoring under environmental exposure conditions.

Comparative plaque removal efficacy of three toothbrushes in two independent clinical studies.

Two independent studies were conducted to evaluate and compare the clinical performance of three toothbrushes on plaque removal. Both studies were carried out under the same protocol. A total of 73 adult male and female subjects who met the inclusion/exclusion criteria completed Study I and 78 different subjects completed Study II. Subjects were initially screened for dental plaque eligibility. After plaque was scored on the facial and lingual surfaces of all natural teeth using the Rustogi, et al. index, qualifying subjects were randomly assigned to one of three groups on the basis of initial plaque scores and number of teeth. Subjects were then dismissed and scheduled to return for Visit 1 a week later, having abstained from all oral hygiene procedures for a prior 24-hour period. At Visit 1, each group was evaluated for plaque before brushing with their assigned toothbrush for sixty seconds. They were again scored for plaque after brushing. Subjects were dismissed and instructed to resume their normal routine and return to the clinical site for two more weekly visits. At each visit, a different test toothbrush was assigned to each group in a cross-over design. Plaque evaluations and brushing procedures were performed as in Visit 1 of the study. In both studies, the Colgate Precision toothbrush was significantly more effective (p < 0.01) than both the Oral-B 40 and Reach Full-Head soft toothbrushes in reducing the whole mouth plaque scores, as well as plaque at the gumline and at interproximal areas. The Oral-B 40 and Reach toothbrushes were not significantly different from each other with regard to plaque removal.

Clinical studies regarding the plaque removal efficacy of manual toothbrushes.

Two independent cross-over design studies were performed to compare two toothbrushes for their ability to remove plaque. In Study I, the Colgate Precision toothbrush was compared to the Oral-B 40 toothbrush; in Study II, the Colgate Precision toothbrush was compared to the Reach Full-Head soft toothbrush. A total of 54 and 72 adult male and female subjects who met the inclusion/exclusion criteria completed Study I and Study II, respectively. In each study, subjects refrained from brushing for 24 hours, and were screened for dental plaque on the facial and lingual surfaces of all natural teeth, using the Rustogi, et al. index. Based on mean scores and number of teeth, qualifying subjects were randomly assigned to one of two groups. Subjects were then scheduled to return one week later, having again abstained from all oral hygiene procedures for a 24-hour period. At this visit, each subject was evaluated for plaque, then brushed with his/her assigned toothbrush for sixty seconds, and was again scored for plaque after brushing. Subjects were instructed to resume their normal routine and return to the clinical site one week later. At this visit, a different test toothbrush was assigned to each group in a cross-over design. Plaque evaluations and toothbrushing procedures were again performed. In both studies, the Colgate Precision toothbrush was significantly more effective (p < 0.01) than either the Oral-B 40 toothbrush or the Reach Full-Head soft toothbrush in reducing whole mouth plaque scores, plaque scores at the gumline, and plaque scores at interproximal areas.

Refinement of the Modified Navy Plaque Index to increase plaque scoring efficiency in gumline and interproximal tooth areas.

To improve the assessment of plaque present on teeth, a new index, based on the original Modified Navy Plaque Index, has been developed. The primary modifications to the original Modified Navy Plaque Index were: (1) extending areas F (distal) and D (mesial) into the region just below the interproximal contact point, and (2) extending areas C and A so as to increase the gumline (or marginal gingiva) region. The new index assesses the amount of plaque in the tooth area bounded by the tooth contact, the free gingival margin, and mesial or distal line angles. The use of this new index enables the examiner to evaluate and record both the gumline (or marginal areas) and interproximal areas of the tooth, thus giving these an anatomical areas an increased importance. A pilot clinical assessment study was conducted to utilize this new index in evaluating the plaque removal efficacy of five manual toothbrushes. The results from this pilot study indicated that, when the new plaque scoring index was used, significant differences between pre-toothbrushing and post-toothbrushing plaque scores (as well as among toothbrush groups) could be demonstrated. Further, these differences (plaque removal efficacy) were demonstrated on an interproximal (mesial and distal) basis and a gumline (or gingival margin) basis, as well as on a whole mouth basis.