Radiation dose and leukemia risk in patients treated for cancer of the cervix.

To quantify the risk of radiation-induced leukemia and provide further information on the nature of the relationship between dose and response, a case-control study was undertaken in a cohort of over 150,000 women with invasive cancer of the uterine cervix. The cases either were reported to one of 17 population-based cancer registries or were treated in any of 16 oncologic clinics in Canada, Europe, and the United States. Four controls were individually matched to each of 195 cases of leukemia on the basis of age and calendar year when diagnosed with cervical cancer and survival time. Leukemia diagnoses were verified by one hematologist. Radiation dose to active bone marrow was estimated by medical physicists on the basis of the original radiotherapy records of study subjects. The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not increased [relative risk (RR) = 1.03; n = 52]. However, for all other forms of leukemia taken together (n = 143), a twofold risk was evident (RR = 2.0; 90% confidence interval = 1.0-4.2). Risk increased with increasing radiation dose until average doses of about 400 rad (4 Gy) were reached and then decreased at higher doses. This pattern is consistent with experimental data for which the down-turn in risk at high doses has been interpreted as due to killing of potentially leukemic cells. The dose-response information was modeled with various RR functions, accounting for the nonhomogeneous distribution of radiation dose during radiotherapy. The local radiation doses to each of 14 bone marrow compartments for each patient were incorporated in the models, and the corresponding risks were summed. A good fit to the observed data was obtained with a linear-exponential function, which included a positive linear induction term and a negative exponential term. The estimate of the excess RR per rad was 0.9%, and the estimated RR at 100 rad (1 Gy) was 1.7. The model proposed in this study of risk proportional to mass exposed and of risk to an individual given by the sum of incremental risks to anatomic sites appears to be applicable to a wide range of dose distributions. Furthermore, the pattern of leukemia incidence associated with different levels of radiation dose is consistent with a model postulating increasing risk with increasing exposure, modified at high doses by increased frequency of cell death, which reduces risk.

Severe soft-tissue injury following intravenous infusion of phenytoin. Patient and drug administration risk factors.

From April 8, 1982, through June 1984, 11 patients in a single hospital experienced 17 episodes of limb edema and discoloration after the intravenous (IV) administration of phenytoin sodium (Dilantin). One patient required a below-the-elbow amputation; all other patients recovered. No single drug lot was implicated. A case-control study was performed using three controls for each case; controls received IV infusions of phenytoin and were hospitalized close in time to the case patients. Compared with controls, patients with reactions were more often female and elderly and had underlying cardiovascular disease. Affected patients also received phenytoin through an IV catheter smaller than 20 gauge (50% vs 6%), at a rate greater than 25 mg/min (63% vs 19%), and in two or more IV infusions of phenytoin given "IV push" at the same site (81% vs 24%). High-risk patients require careful monitoring and stricter guidelines for the IV administration of phenytoin.

Cancer mortality following cardiac catheterization: a preliminary follow-up study on 4,891 irradiated children.

A retrospective cohort study was conducted on the risk of radiation-induced cancer mortality following cardiac catheterization. The study included 4,891 children with congenital heart disease who were assessed by cardiac catheterization during 1946 to 1968 at The Hospital for Sick Children, Toronto. The cohort was matched against the Ontario cancer death file from 1950 to 1975. The average period of follow-up was 13 years and more than 66,000 person-years have been accrued from the cohort. No deaths from breast cancer or thyroid cancer were identified. Five cancer deaths were observed and compared with 4.8 expected deaths based on Ontario cancer death rates. The five cancer deaths resulted from three leukemias, one Wilms' tumor, and one unspecified nervous system tumor. The preliminary findings did not demonstrate a significant leukemia risk arising from diagnostic cardiac catheterizations. Continued follow-up of this cohort is required to evaluate the risk of breast and thyroid cancers which can occur more than 20 years following radiation exposure.

Fatal farm injuries among young children.

Death certificate data concerning farm-related injury deaths among children 0 to 9 years of age in Wisconsin and Illinois for the period of 1979 to 1985 were reviewed. Average annual farm-related injury death rates were 3.2 per 100,000 rural children in Wisconsin (62 deaths) and 1.5 per 100,000 in Illinois (32 deaths). Rates were three times higher among boys than girls. The occurrence of two harvest-related peaks and the absence of fatality in children less than 1 year of age suggest that presence of children on the farm when supervision is diminished is a key factor in farm-related fatalities. Moving machinery (tractors, wagons, and trucks) was the source of injury in approximately 55% of all deaths. Drowning accounted for 15% of all farm-related deaths. Two fatalities related to gravity box wagons could have easily been prevented with simple safety devices. These findings suggest a need for developing environmental interventions in farms. This will require the allocation of more resources to farm safety programs and a revision of current farm safety legislation.

Assessment of reproductive disorders and birth defects in communities near hazardous chemical sites. I. Birth defects and developmental disorders.

Members of the workgroup on birth defects and developmental disorders discussed methods to assess structural anomalies, genetic changes and mutations, fetal and infant mortality, functional deficits, and impaired fetal and neonatal growth. Tier 1 assessments for all five adverse reproductive outcomes consist of questionnaires and reviews of medical records rather than laboratory testing of biologic specimens. The work-group members noted a role for neurodevelopmental testing and for limited genetic studies, such as karyotyping in Tier 2 assessments. Emerging methodologies to identify chromosomal aberrations, DNA adducts, and repair inhibition were reserved for Tier 3.

An evaluation of the Vermont worksite smoking law.

In view of the fact that the impact of statewide smoking laws on private worksite policies and the smoking behavior of employees has not been evaluated, two cross-sectional surveys were performed in Vermont to measure compliance with such a law: a random-digit telephone survey of employees and a subsequent mail survey of their employers. Employers were not aware that one of their employees had been surveyed. Roughly half (56 percent) of the employees and 66.5 percent of their employers described policies that are in compliance. Among all employers who described policies in compliance with the law, 68.1 percent of their employees also described compliant policies. Among all employees who described non-compliant policies, 48.8 percent had employers who described compliant policies. Overall, employees and employers agreed on how their policies stood with respect to compliance in 67.6 percent of cases. The prevalence and amount of smoking at work declined after the institution of the law but so did the prevalence and amount of smoking at home. Changes toward more restrictive policies were associated with reductions in cigarette consumption at work, but not with quitting. The study suggests that a large fraction of worksite smoking policies may not comply with a statewide worksite smoking law. The proportion of companies complying with such a law may be overestimated if information on compliance is obtained only from employers.

Interobserver and intraobserver variability in lung scan reading in suspected pulmonary embolism.

The interobserver and intraobserver variability in lung scan reading and interpretation was tested using a consecutive series of 96 lung scans done for patients clinically suspected to have pulmonary embolism. Lung scans were also done on 37 reference patients who were matched to a suspect case and consented to the procedure. Two experienced readers blindly read all films twice. Intraobserver agreement was low, especially for lung scans showing minor defects. Kappa, a measure of agreement beyond chance, was consistently less than .500. Interobserver agreement was lower. Only 4.3% of the suspect cases had lobar defects on the lung scan. The distribution of abnormalities in suspect and reference cases was similar. The results indicate that the reproducibility of lung scan readings is probably to low to be clinically useful, for readings involving defects that are segmental or smaller. The reproducibility for lobar defects could not be determined adequately because of their low frequency in this study.

Cancer mortality among immigrant populations in Ontario, 1969 through 1973.

Ontario is home to a sizeable, recently established immigrant population whose cancer mortality has until now remained unexamined. The province's six largest immigrant groups (British, Italian, German, Dutch, Polish and Soviet) were investigated to compare their cancer mortality experience with that prevailing in Ontario and in their countries of birth for the period 1969 through 1973. Standardized mortality ratios (SMRs) were computed from data from Statistics Canada and the World Health Organization (for 1971) for five sites of cancer. The rates of death from stomach cancer were significantly higher for the immigrant groups (except the Germans) than for the Canadian-born (SMRs 158.6 to 256.1) and were significantly lower for the immigrants (except the Dutch) than for the populations of their countries of birth (SMRs 26.5 to 72.9). The rates of death from colorectal cancer and cancer of the breast tended to be lower among the immigrants. Most male immigrants had high rates of death from lung cancer relative to the Canadian-born, whereas their female counterparts had relatively low rates. For most of the immigrant groups the rates of death from prostate cancer closely resembled those prevailing in the country of birth. Displacement of cancer mortality experience towards that in Ontario was most evident for Polish immigrants. It may have been too soon to see trends among the more recent immigrants (Italian, German and Dutch), who, for the most part, had not yet reached the age of highest cancer risk. Ontario should provide a valuable resource for further studies of lifestyle and environmental determinants of cancer.

PIP: Cancer mortality among the six largest immigrant groups in Ontario, Canada (British, Italian, German, Dutch, Polish, and Soviet), is investigated and compared with cancer mortality for the population of Ontario as a whole and with cancer mortality in the immigrants' countries of birth. Standardized mortality ratios for five major cancer sites are calculated for 1971 using official Canadian data and data from the World Health Organization. (summary in FRE)

Hospital costs and mortality attributed to nosocomial bacteremias.

Hospital patients with nosocomial bacteremia and matched hospital control patients without this infection were used to determine the excess hospital costs and mortality attributed to nosocomial bacteremias. Mortality was 14 times greater in patients with nosocomial bacteremia than in matched members of the control group with the same primary diagnoses. An itemized cost analysis, based on 81 case-control pairs, showed an average excess of approximately $3,600 in direct hospital costs for patients who had nosocomial bacteremias. It is estimated that only 24% of the total excess costs to these hospital patients are preventable. Patients with nosocomial bacteremia had an average hospitalization period that was 14 days longer than the average hospital stay for members of the control group.

Harmonizing human health studies in the Great Lakes.

Epidemiological studies of exposed human populations can provide valuable evidence of human health effects. Information has been sparse on human health effects associated with consumption of contaminated Great Lakes fish. As part of its Great Lakes Human Health Effects Research Program, the Agency for Toxic Substances and Disease Registry (ATSDR) has funded ten projects. Of these studies, eight are epidemiologic investigations of human exposure and potential health effects from consumption of contaminated fish. To strengthen and to enhance the findings and comparability across the health studies, ATSDR has initiated several activities. These activities include harmonizing questionnaires, analytical protocols, human health end points, and contaminants tested. Also included is the establishment of a quality assurance and quality control (QA/QC) program and tissue bank. These activities will allow ATSDR to enhance exposure assessment in the Great Lakes basin. In addition, these research activities allow ATSDR to evaluate and to interpret data across all the projects, including a basin-wide health risk analysis on exposure, levels of contaminants or body burden, and the potential for human health effects from exposure to Great Lakes contaminants.

Second primary cancer following treatment for cervical cancer.

A follow-up study of 7535 women in Ontario was carried out to assess the occurrence of second primary cancers following the treatment of invasive carcinoma of the cervix between 1960 and 1975. The study was part of a larger international investigation of late radiation effects in patients with cervical cancer. Data were collected on the date and the type of treatment for cervical cancer and on the occurrence of second primary cancers diagnosed before 1980. Observed and expected numbers of second primary cancers, the latter determined according to Ontario incidence rates, were compared for individual sites and for all sites combined. There were significantly more primary cancers of the lung than expected (64 v. 15.52) but significantly fewer second primary cancers of the breast (56 v. 105.01) and colon (27 v. 43.31). Overall, there were significantly fewer (p less than 0.05) observed second primary cancers than expected (280 v. 394). Although the median follow-up period was less than 10 years there was no marked evidence of an excess of radiation-induced second primary cancers.

Utilization of the preemployment health examination in a university staff health service.

This study assessed the utilization of a mandatory preemployment health examination (PEHE) for 507 new full-time university staff in 1976. A random sample of 126 new employees was interviewed by telephone. Of the 108(86%) who completed the interview, 80 (74%) had been examined by the staff health service. Notification to take the exam, a reminder, and the employee's perception of its importance were highly associated (p less than 0.0001) with compliance. Only 30% of the food handlers and maintenance personnel ahd their PEHE before employment started; the proportion was similar for all new employees (29%). Therefore, although this staff health service was moderately successful in getting most new employees to have a PEHE, if the value of the examination is to be enhances, more attention must be paid to notifying and reminding all prospective employees. Special consideration is needed to ensure that those in potentially high-risk jobs are examined prior to employment. The role of the university administration in improving compliance is emphasized.

A descriptive study of nosocomial bacteremias at The Johns Hopkins Hospital, 1968--1974.

Patient, infection and pathogen characteristics are analyzed for 935 cases of nosocomial bacteremia at The Johns Hopkins Hospital, 1968--1974. The overall nosocomial bacteremia attack rate was 4.1 cases per 1,000 hospital patients. Rougly 6% of all hospital deaths were among patients with nosocomial bacteremias. The case-fatality rate for the seven years was 37.1% compared with an overall hospital mortality rate of 2.7 deaths per 100 hospital patients. The mortality rate for the entire hospital and the case-fatality rate declined significantly (P less than 0.1) over the seven-year study period. There was a significant increase (P less than .01) in Gram-positive nosocomial bacteremias over the seven-year period. During the period, Bacteroides species and Escherichia coli bacteremias increased significantly (P less than .01) while Candida species and Klebsiella species bacteremias had significant decreases (P less than .01). The nosocomial bacteremia attack rate was high for infacts under one year of age, excluding newborns. The attack rates were low for young adults but increased markedly with age in adults older than 40. The cardiac surgery service had the highest nosocomial bacteremia attack rate of 12.4 cases per 1,000 patients. Hospital patients with infective diseases, neoplasms, digestive diseases, diseases of early infancy or circulatory diseases had a much greater risk of acquiring nosocomial bacteremias. Of the 935 cases, 9.5% had multiple episodes of bacteremia.

Type A botulism from sauteed onions. Clinical and epidemiologic observations.

Twenty-eight persons were hospitalized in Illinois with neurologic signs and symptoms compatible with botulism in October 1983. Twelve patients required ventilatory support, and 20 patients were treated with trivalent ABE antitoxin; one patient died while still in the hospital six months after onset of illness. Type A toxin and/or type A Clostridium botulinum were subsequently identified in specimens from 18 patients. Case-control studies implicated sauteed onions made from fresh raw onions and served on a patty-melt sandwich in a local restaurant as the vehicle of transmission. Although the original sauteed onions were not available for toxin testing, type A toxin was detected in washings from a wrapper in which a patty-melt sandwich was taken home by one of the ill persons. Also, type A C botulinum was cultured from five of 75 raw onions taken from the restaurant. This outbreak implicated an unusual vehicle for botulinal toxin that was initially not suspected and demonstrates the importance of considering all theoretically possible food items as potential vehicles for toxin until epidemiologic and laboratory data have been collected and analyzed.

Exogenous estrogens and endometrial cancer: a case-control study and assessment of potential biases.

Eighty-eight cases with newly diagnosed carcinoma of the endometrium and 177 age-matched neighborhood controls were interviewed to test the hypothesis that exogenous estrogens lead to an increased risk of endometrial cancer. Forth-five per cent of the cases and 22% of the controls reported a history of estrogen use which yielded an odds ratio of 2.9 (confidence interval (Cl) 1.7-5.1). Women with five or more years of estrogen use had an odds ratio of 8.6 (Cl 3.2-23.0). Approximately 80% of the estrogen users had used conjugated equine estrogens. For these women the odds ratio was 4.0 (Cl 1.9-8.4) for daily dosages of more than 1 mg of estrogen. Several sources of bias which might affect the estrogen association were investigated. These included comparability of cases and controls, selection procedures, difference between estrogen users and nonusers, exclusion of controls who had hysterectomy, source of estrogen information, and differential recall. The concept or medical surveillance was evaluated by access to medical care and prior history of dilatation and curettage. The strong association between exogenous estrogen use and endometrial cancer remained after consideration for the effects of these biases.

Medical costs and lost productivity from health conditions at volatile organic compound-contaminated superfund sites.

This paper estimates the health costs at Superfund sites for conditions associated with volatile organic compounds (VOCs) in drinking water. Health conditions were identified from published literature and registry information as occurring at excess rates in VOC-exposed populations. These health conditions were: (1) some categories of birth defects, (2) urinary tract disorders, (3) diabetes, (4) eczema and skin conditions, (5) anemia, (6) speech and hearing impairments in children under 10 years of age, and (7) stroke. Excess rates were used to estimate the excess number of cases occurring among the total population living within one-half mile of 258 Superfund sites. These sites had evidence of completed human exposure pathways for VOCs in drinking water. For each type of medical condition, an individual's expected medical costs, long-term care costs, and lost work time due to illness or premature mortality were estimated. Costs were calculated to be approximately $330 million per year, in the absence of any remediation or public health intervention programs. The results indicate the general magnitude of the economic burden associated with a limited number of contaminants at a portion of all Superfund sites, thus suggesting that the burden would be greater than that estimated in this study if all contaminants at all Superfund sites could be taken into account.

Nosocomial Pseudomonas pickettii colonization associated with a contaminated respiratory therapy solution in a special care nursery.

Pseudomonas pickettii caused respiratory tract colonization in five infants in the special care nursery of a Chicago hospital. All organisms had the same antimicrobial susceptibilities. Endotracheal suctioning with saline from 5-ml unit-dose vials was identified by epidemiologic investigation as a risk factor for colonization. The vials of saline were contaminated with a strain of P. pickettii having the same antimicrobial susceptibility pattern as the isolates from patients. As part of an investigation of the manufacturing plant where the saline solution was produced, P. pickettii was recovered from deionized water used to make the product and from several sites in the processing line. Bypassing of a 180 degrees F (ca. 82 degrees C) water-holding tank appeared to be temporally related to product contamination. The ability of P. pickettii to survive and grow in this solution has been demonstrated in the laboratory. This outbreak demonstrates that, despite pertinent Food and Drug Administration regulations and company programs for identifying such contamination, intrinsically contaminated solutions can occasionally reach the bedside of the patient.