Biomedical subjects
Publications and source records attributed to A I Neugut.
Creutzfeldt-Jakob disease was studied among Libyan-born Israelis, in whom the disease appears with unusual frequency. Interviews with relatives of deceased victims revealed statistically significant clustering within families. The results suggest either a common source of exposure or a genetic influence on susceptibility to the virus.
The in vitro effects of asbestos fibers on the growth and viability of CHO cells, an epithelioid cell line derived from Chinese hamster ovary, and on K-22 cells, an epithelial cell line derived from rat liver, have been studied. Relatively low concentrations of asbestos (10 micrograms/ml) were quite cytotoxic to both cell types. A sample of chrysotile asbestos was more toxic than samples of crocidolite or amosite. The toxic factor could not be extracted from the asbestos and toxicity occurred only if there was physical contact between the fibers and the cells. Although the phorbol ester class of tumor promoters induces the synthesis of plasminogen activator in various cell cultures, asbestos did not induce this protease in epithelioid or fibroblast cell cultures. The results obtained are compared to previous in vitro results obtained with fibroblast or macrophage cultures and are discussed in terms of their possible relevance to asbestos-induced fibrosis and tumorigenesis.
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An evaluation of treatment practices in 13 countries, not including the United States, has shown oral terbinafine to be more cost-effective (from a government payer perspective) than griseofulvin, itraconazole, and ketoconazole in the treatment of onychomycosis of toenails and fingernails. The purpose of this study was to evaluate the clinical and economic effects of oral griseofulvin, itraconazole, ketoconazole, and terbinafine in the treatment of onychomycosis from the perspective of a third-party payer in the United States. A previously constructed decision-analytic model evaluating the costs of onychomycosis in 13 countries outside the United States was updated to determine the costs of treating onychomycosis in the United States. Clinical management patterns were assessed to identify and quantify physician visits, laboratory tests, and adverse drug reaction treatment components for patients with toenail and fingernail onychomycosis. A random-effects model meta-analysis of treatment efficacy (mycologic cure) and New York Metropolitan Medicare charge data for physician fees were used in the treatment model. A sensitivity analysis assessing alternative dosing regimens and a rank order stability analysis investigating the effects of length of treatment, success rates, relapse rates, and drug acquisition costs on overall results were also conducted. Terbinafine had the lowest cost per mycologic cure after one treatment regimen for onychomycosis in both toenail and fingernail infections ($791.00 and $454.00, respectively). The costs of treating toenail and fingernail infections were comparatively higher for therapy with itraconazole ($1535.00 and $767.00, respectively), griseofulvin ($2385.00 and $837.00, respectively), and ketoconazole ($10,025.00 and $1512.00, respectively). As a primary treatment choice, terbinafine also had the lowest overall expected cost per patient for both toenail and fingernail infections ($977.00 and $550.00, respectively). Griseofulvin had expected costs ($1543.00 and $822.00, respectively) similar to itraconazole ($1588.00 and $894.00, respectively), whereas ketoconazole was the most expensive primary treatment choice ($2359.00 and $1287.00, respectively). This study demonstrates that terbinafine is an economical and cost-effective treatment for patients with dermatophytic onychomycosis, supporting European and Canadian studies. Except for the rank order of griseofulvin and itraconazole, sensitivity analyses show that these results are fairly stable.
PURPOSE: This study was conducted to obtain and compare the preferences assigned to cancer states and prevention measures by women who had breast cancer, were at high risk for breast cancer, or had neither condition. PATIENTS AND METHODS: We administered a time trade-off questionnaire to 21 breast cancer patients, 28 women with a personal history of multiple breast biopsies or a family history of breast cancer, and 135 women without these conditions (the reference group). We stratified the reference group into two groups aged 20 to 32 years and 33 to 50 years, respectively. RESULTS: All four groups assigned higher preference to breast cancer than to ovarian cancer. Both reference groups preferred using a tamoxifen-like drug to having mastectomy or oophorectomy for cancer prevention; the high-risk and breast cancer groups did not. None of the four groups had a preference between prophylactic mastectomy and breast cancer. All the groups were willing to subtract more years from their life expectancy to protect offspring from genetic risk than to protect themselves. Reference group members in the 33- to 50-year age range had lower mean ratings than the breast cancer group for almost all the health states, and breast cancer patients were less willing than other respondents to trade time for health. Most of these differences were not statistically significant. The high-risk group was similar to the older reference group in time trade-off ratings. DISCUSSION: The time trade-off-based preferences of healthy women may be used to predict the treatment preferences of women with BRCA1/2 mutations. Obtaining healthy women's ratings of treatment outcomes may help health care policy makers envision the consequences of the difficult choices that high-risk women face.
PURPOSE: Recent randomized controlled trials have shown that tamoxifen and raloxifene may prevent invasive breast cancer. This decision analysis study compares the outcomes of chemoprevention with tamoxifen, raloxifene, or oral contraceptives with the outcomes of prophylactic surgery among women with high-risk BRCA1/2 mutations. PATIENTS AND METHODS: We used a simulated cohort of 30-year-old women who tested positive for BRCA1/2 mutations and constructed a Markov model with Monte Carlo simulations, incorporating cumulative breast and ovarian cancer incidence rates from the literature and survival figures from SEER data. We assumed that prophylactic surgery reduces ovarian cancer risk by 45% and breast cancer risk by 90%, that tamoxifen reduces invasive breast cancer risk by 49%, and that raloxifene has similar efficacy and safety in premenopausal and postmenopausal women. We used data obtained from high-risk women by a time trade-off questionnaire to calculate quality-adjusted life-years. We based our cost estimates for hospital and ambulatory care on Health Care Financing Administration payments, the SEER-HCFA database, and the Pharmacy Fundamental Reference. RESULTS: In our model, a 30-year-old BRCA1/2+ woman could prolong survival by 0.9 years (95% probability interval, 0.4-1.2 years) by having bilateral oophorectomy, 3.4 years (2.7-3.7 years) by having bilateral mastectomy, and 4.3 years (3.6-4.6 years) by having both procedures instead of surveillance alone. Chemoprevention with tamoxifen and raloxifene increased survival by 1.6 years (1.0-2.1 years) and 2.2 years (1.3-2.8 years), respectively. Chemoprevention yielded more quality-adjusted life-years than did prophylactic surgery, even when treatment was delayed to age 40 or 50 years. All these procedures were cost-effective or cost-saving compared with surveillance alone. DISCUSSION: Our model suggests that although surgery may yield more substantial survival and cost benefits, quality of life issues may make chemoprevention a more attractive option for young women at high genetic risk.
PURPOSE: The recent Breast Cancer Prevention Trial has shown that tamoxifen may prevent invasive breast cancer. We used a Markov model to estimate the long-term effects of chemoprevention with tamoxifen on survival, quality-adjusted survival, and health care costs. METHODS: We used a hypothetical cohort of women with breast-cancer risk similar to that of participants in the Breast Cancer Prevention Trial, and a computer-based decision analysis (Markov model and 500 Monte Carlo simulations) to model the outcomes of interest. Survival calculations were from Surveillance, Epidemiology, and End-Results (SEER) data; preference ratings from a time trade-off questionnaire administered to a group of average-risk women; and cost estimates from the Group Health Cooperative of Puget Sound and the Health Care Financing Administration. We obtained utility measures for quality-adjustment by administering a time trade-off questionnaire to a group of community-based women. RESULTS: Use of tamoxifen prolonged the average survival of cohort members by 69 days (95% probability interval [PI] 27 to 117) for those who started use at age 35 years; 40 days (95% PI 16 to 67) for those who started use at age 50 years; and 27 days (95% PI 14 to 40) for those who started use at age 60 years. Tamoxifen extended quality-adjusted survival by 38 days (95% PI 0.1 to 82) at age 35, 25 days (95% PI 0 to 50) at age 50, and 22 days (95% PI 5 to 39) days at age 60. Chemoprevention with tamoxifen cost $46,619 (95% PI $27,928 to $98,796) per life year life saved for women who started at age 35; for women over age 50, it cost more than $50,000 per life year saved. DISCUSSION: Tamoxifen use may improve long-term survival and quality-adjusted survival among women who are at increased risk of breast cancer, but this benefit diminishes with age. Tamoxifen is cost-effective in comparison with other cancer treatment strategies for younger women only.
BACKGROUND: Since 1990, the recommended adjuvant therapy for patients with surgically resected node-positive colon cancer has been 5-fluorouracil (5-FU), usually in combination with leucovorin or levamisole. The purpose of this study is to assess the distribution of adjuvant 5-FU treatment in the elderly. METHODS: The Surveillance, Epidemiology and End Results-Medicare database provides population-based information on cancer patients, representing approximately 14% of the United States population, along with health care utilization data from Medicare claims files. We studied patients with node-positive colon cancer diagnosed between 1992 and 1996 who survived at least 120 days beyond diagnosis (N = 4998). RESULTS: About 50% of elderly patients received 5-FU within 4 months of diagnosis. The proportion of patients treated with 5-FU increased by about 10% from 1992 to 1996. In a multiple logistic regression model, 5-FU treatment was less likely to be given to older patients (compared with those aged 65-69 years, the odds ratio (OR) [95% CI] was 0.82 [0.67-1.00] for ages 70 to 74 years, 0.47 [0.39-0.57] for ages 75 to 79, 0.17 [0.13-0.20] for ages 80 to 84, and 0.04 [0.03-0.05] for ages 85 to 88 years. Non-Hispanic black patients were less likely to be treated than non-Hispanic white patients (OR 0.46 [0.36-0.59]); patients with more than three positive lymph nodes were more likely to be treated than those with three or less, and those with comorbid conditions were less likely to be treated than those without such conditions. CONCLUSIONS: Despite its proven efficacy in reducing colon cancer mortality, 5-FU-based chemotherapy is not widely used among apparently eligible patients over age 65. Efforts are needed to ensure that elderly and non-Hispanic black patients receive appropriate treatment.
Data from the Surveillance, Epidemiology, and End Results (SEER) Program were used to compare the histological distribution of second lung cancer following an initial cancer of the lung, head and neck, and breast to primary lung carcinoma occurring as a first cancer. Following initial head and neck cancer or initial squamous cell carcinoma of the lung, the proportion of second primary lung cancer which was of squamous cell histology rose dramatically, while the proportion of pulmonary adenocarcinomas rose following initial adenocarcinoma of the lung. The histological distribution of lung cancer following an initial breast cancer in women was similar to the distribution of de novo lung cancer in women. These results persisted as the time interval between diagnosis of the two primaries was increased from 12 to 48 months. We conclude that the histology of a second primary lung cancer following an initial cancer of the lung or head and neck tends to repeat the histology of the initial cancer (field effect), and this observation is not likely to be due to misdiagnosis of a recurrence of the initial cancer.
Population-based data on more than 1 million patients registered in the Surveillance, Epidemiology, and End-Results Program of the National Cancer Institute, 1973 to 1984, were analyzed to determine the survival of patients with de novo acute nonlymphocytic leukemia (ANLL) and following a first primary tumor treated (with chemotherapy and/or radiation therapy) or untreated. Cases that occurred within 12 months of the first malignant neoplasm were excluded. Survival was estimated using Cox proportional-hazards modeling, with age, sex, and specific type of ANLL as covariates. The 6271 patients with de novo ANLL had an estimated 12-month survival of 30%, while the 107 patients with treatment-related ANLL (radiation therapy, 60; chemotherapy, 29; both, 18) had an estimated 12-month survival of 10%. This is not due to lingering effects of the first tumor since ANLL following solid tumors not treated with chemotherapy or radiation therapy (118 cases) has similar survival (estimated 12-month survival, 36%) as de novo ANLL. We conclude that ANLL that occurs after chemotherapy or radiation therapy is biologically more aggressive and/or resistant to therapy than spontaneous ANLL. This provides a rationale for current studies on treatment-induced cellular changes and on more aggressive therapy for these patients.
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In the Multiple Primary Tumor Registry of the Northern Israel Cancer Center we found 247 patients with breast cancer who developed a second primary tumor. The major sites of the second tumor were mainly the other breast (42%), colon (14%), ovary (8%), and endometrium (7%). Only 24% of the second tumors were diagnosed in asymptomatic patients on a routine follow-up examination; 60% of these patients had contralateral breast cancer and 8% had colon cancer. More patients in this group had localized disease as compared to those diagnosed following appearance of symptoms. The time interval between the first symptoms suggesting malignancy and the diagnosis was longer than 6 weeks in 7%, as compared to 24% in patients diagnosed with a single cancer. In 69 patients (30%), delay was found between the first medical consultation and diagnosis. The agents responsible for the delay were the specialist (32%), the system and normal tests (54%), and the patients (8%). In the diagnosis of a single tumor, the physician and the patient shared a similar percentage of responsibility (29% and 33%). Educational efforts aimed mainly at physicians and patients regarding the early detection of second primary tumors are advocated. Methods that have been proven to detect cancer early, such as mammography, stool for occult blood, and sigmoidoscopy, should be utilized in asymptomatic patients with single tumors in the same way as in the healthy population.
Although the small intestine contains 75% of the mucosal surface of the gastrointestinal tract, it is the site of only 2% as many malignancies as the large bowel. The association of Crohn's disease with small intestine adenocarcinoma is well known, but the analytic epidemiology of small intestine malignancies has not received much attention. We reviewed the medical records of 19 patients with adenocarcinoma and 17 with malignant carcinoids identified from the Columbia-Presbyterian Medical Center Tumor Registry in the years 1980-1987. These were compared with 52 controls with nonmalignant conditions from the same time period. Three adenocarcinoma patients but no carcinoid patients or controls had previous Crohn's disease (P < 0.004). Three adenocarcinomas and three carcinoids, but no controls, had previous cholecystectomy (P < 0.004). Previous peptic ulcer disease was recorded for two patients with adenocarcinoma and three with carcinoid but no controls (P < 0.02, P < 0.0002). The age and sex adjusted odds ratio for cigarette smoking was 4.6 (95% confidence interval, 1.0-20.7) for adenocarcinomas and 4.2 (0.8-22.4) for carcinoids. The adjusted odds ratio for alcohol consumption was 4.0 (1.0-15.9) for adenocarcinomas and 3.1 (0.7-13.9) for carcinoids. Further studies are warranted to confirm these associations and to identify potential protective factors in the small intestine.
Malignant tumors of the small bowel are rare and little is known about their etiology, although adenocarcinomas share certain epidemiological features with colorectal cancer. This study investigated what cancers, if any, occurred as second neoplasms following adenocarcinomas, malignant carcinoid tumors, lymphomas, and sarcomas of the small bowel. For all 2581 cases of small bowel malignancy registered in one of the Surveillance, Epidemiology, and End-Results program areas, 1973-1988, the relative risk of a second malignancy was determined. The risk of colorectal cancer was increased following adenocarcinoma of the small bowel, and the risk of adenocarcinoma of the small bowel was increased following colorectal cancer in both males and females. This study also found an association between small bowel sarcomas and malignant melanoma in males, consistent with earlier studies, and an association between prostate cancer and malignant carcinoid tumors of the small bowel, a new observation. We conclude that adenocarcinomas of the small bowel may share risk factors with colorectal cancer.
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