Trends in the utilization of androgen-deprivation therapy for patients with prostate carcinoma suggest an effect on mortality.

BACKGROUND: After a surge in the incidence of prostate carcinoma in the early 1990s, diminishing rates of mortality became apparent in 1993. This decrease in mortality is unlikely to be explained entirely by treatment with curative intent alone following screen-detected cases, because the time frame between detection and mortality remains relatively brief. METHODS: This study used incidence and initial treatment data from the Detroit area SEER registry between 1973 and 1998 in addition to mortality data covering the Metropolitan Detroit area obtained from the Michigan Department of Community Health. Data for Caucasian and African-American men were analyzed. The use of androgen-deprivation therapy, which evolved during the study period, was evaluated in conjunction with mortality and incidence trend data for consideration of etiologic contributions. RESULTS: The incidence of prostate carcinoma, as noted previously in national data, increased sharply in 1988, peaking in 1992 in Southeast Michigan, whereas mortality rates began to decrease in approximately 1993, with a sustained decrease to the latest recorded data in 1998. These trends were identical in Caucasians and African Americans. A sharp increase in the use of androgen-deprivation therapy began in 1990. This use of androgen-deprivation therapy is high and sustained for patients with early-stage disease, increases for several years, and then diminishes for patients with regional disease. The use also diminished through the 1990s for patients with late-stage disease, paralleling the decrease in the incidence rate for late-stage disease. CONCLUSIONS: The pattern of androgen-deprivation therapy usage was consistent with that for hormonal monotherapy and adjuvant and neoadjuvant therapy. These findings suggest that androgen-deprivation therapy may contribute, along with advances in diagnostic techniques and curative therapy with radiation or surgery, toward decreasing prostate carcinoma mortality rates in Southeast Michigan.

Bacterial/viral filtration: let the breather beware!

Most clinicians believe that any device that is marketed as a "bacterial/viral filter" must necessarily be capable of capturing any individual bacteria or viruses that might be suspended within inhaled or exhaled gases. We were surprised to discover that this is, by no means, a justifiable assumption. This article describes testing methods that manufacturers employ to generate the often-misleading efficiency specifications that are claimed for some of these devices. We discuss articles that have documented the presence of airborne pathogens in the effluent of a ventilator circuit, and characterize the attributes that a competent filter must exhibit if it is to succeed in protecting patients and caregivers from incidental exposure to bacteria, viruses, aerosolized drugs, and endotoxins. This article continues with a discussion of the numbers of particles that are commonly produced with commercially available pneumatic nebulizers, the comparative performance characteristics of filters and heat/moisture exchanging filters (HMEFs), and the success or failure of various brands of HMEFs to comply with the guidelines recently developed by the Centers for Disease Control and Prevention for the management of patients who are harboring active tuberculosis. The presentation concludes with a description of the standards that apply to any filter that classifies as a high-efficiency particulate aerosol (HEPA) device, and demonstrates that the performance of filters/HMEFs in common clinical use can range from approximately 1/50th to > 30-fold the efficiency of a HEPA-grade device. Those who frequent the bedside of patients receiving ventilation might unwittingly be placing themselves at considerable risk of exposure to infectious microaerosols, but methods are available to dramatically decrease those risks.

Managing up in times of financial crisis.

The use of managing up in an institution's time of financial crisis is described. The goals of crisis management include survival, maintaining quality and service, learning issues and impacts, supporting the team, and preparing for the aftermath as the crisis subsides. Survival calls for a commitment by leaders to remain focused, and to maintain and support the management team. Pharmacy directors must be able to adapt to chaos and to the limited information disseminated by senior leadership. Identifying the underlying cause of the crisis, which may not be directly related to the measures taken to resolve it, is also critical to survival. Among the keys to maintaining quality and service are keeping the staff focused on patient care and maintaining credibility by sharing all information that is available. Pharmacy directors need to maintain the confidence of their staff members and to encourage them to do the best they can with the resources available. Taking the initiative to acquire appropriate data, to translate that data into relevant information, and to seek benchmarks for comparison is also important. Once the crisis has passed, attention must be given to updating and maintaining databases, supporting the staff, and improving morale. Scenario planning can help identify measures that might be taken if another crisis should develop. Using principles of managing up can prepare pharmacy directors for optimal response to an institutional financial crisis.

Expanding the linear dynamic range in quantitative high performance liquid chromatography/tandem mass spectrometry by the use of multiple product ions.

A strategy for expanding the linear working range in bioanalysis using quantitative high performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) is presented. The strategy involves monitoring multiple product ions. Herein we demonstrate the strategy on a rat plasma assay for a proprietary experimental drug where the linear range is expanded from 2 to 4 orders of magnitude. A primary sensitive ion was monitored to obtain a high sensitivity range calibration curve (0.400 to 100 ng/mL) while a less sensitive secondary ion was monitored to obtain a low sensitivity range calibration curve (90.0 to 4000 ng/mL). Each calibration curve gave acceptable linearity (r >0.990). Quality control samples at low, mid and high levels within each calibration curve demonstrated acceptable precision and accuracy (within 20% for all levels). The technique was successfully applied to rat pre-clinical sample analysis.

Impact of breast carcinoma on African-American women: the Detroit experience.

BACKGROUND: National and regional population-based data have demonstrated substantially worse outcome in African-American patients with breast carcinoma when compared with white patients, as well as a younger age distribution among African-American patients with breast carcinoma. The extent to which various socioeconomic, environmental, lifestyle, and genetic factors interact to account for this ethnicity-related disparity in survival is poorly understood. Greater than one-half of the inner-city population of Detroit, Michigan is African American, and greater metropolitan Detroit has been one of the contributing registries for the Surveillance, Epidemiology, and End Results (SEER) program since its inception in 1973. The impact of breast carcinoma on African Americans in the Detroit area is therefore well documented and provides significant insight into the history, epidemiology, and biology of this major public health care problem. METHODS: A review of the medical literature published over the past 20 years regarding African-American patients with breast carcinoma was performed. The pertinent findings were summarized in the context of advances made in breast carcinoma screening, treatment, and risk reduction during that period. RESULTS: The large African-American population of Detroit is a major factor contributing to the excessive breast carcinoma mortality rate reported for this city, which is one of the highest in the United States. Improvements in early detection of breast carcinoma by using screening mammography have been apparent in the earlier stage distributions of breast carcinoma observed in both white and African-American patients; however, progress has lagged substantially for the latter group. Detroit SEER registry data also have shown a younger age distribution of African-American patients with breast carcinoma and higher rates of estrogen receptor negative tumors. Finally, preliminary data from health maintenance organizations have suggested improved breast carcinoma outcome for African Americans who possess greater socioeconomic benefits, but disparities in disease stage at presentation persist. CONCLUSIONS: The diverse Detroit community is ideally suited for breast carcinoma screening programs and clinical investigations that seek to address and overcome ethnicity-related survival disparities and barriers to health care. Findings from these studies can be correlated with results from similar projects in other geographic areas.

Predictive modeling techniques in prostate cancer.

A number of new predictive modeling techniques have emerged in the past several years. These methods can be used independently or in combination with traditional modeling techniques to produce useful tools for the management of prostate cancer. Investigators should be aware of these techniques and avail themselves of their potentially useful properties. This review outlines selected predictive methods that can be used to develop models that may be useful to patients and clinicians for prostate cancer management.

Genetic adaptive neural network to predict biochemical failure after radical prostatectomy: a multi-institutional study.

BACKGROUND AND PURPOSE: Despite many new procedures, radical prostatectomy remains one of the commonest methods of treating clinically localized prostate cancer. Both from the physician's and the patient's point of view, it is important to have objective estimation of the likelihood of recurrence, which forms the foundation for treatment selection for an individual patient. Currently, it is difficult to predict the probability of biochemical recurrence (rising serum prostate specific antigen [PSA] concentration) in an individual patient, and approximately 30% of the patients do experience recurrence. Tools predicting the recurrence will be of immense practical utility in the treatment selection and planning follow up. We have utilized preoperative parameters through a computer based genetic adaptive neural network model to predict recurrence in such patients, which can help primary care physicians and urologists in making management recommendations. PATIENTS AND METHODS: Fourteen hundred patients who underwent radical prostatectomy at participating institutions form the subjects of this study. Demographic data such as age, race, preoperative PSA, systemic biopsy based staging and Gleason scores were used to construct a neural network model. This model simulated the functioning of a trained human mind and learned from the database. Once trained, it was used to predict the outcomes in new patients. RESULTS: The patients in this comprehensive database were representative of the average prostate cancer patients as seen in USA. Their mean age was 68.4 years, the mean PSA concentration before surgery was 11.6 ng/mL, and 67% patients had a Gleason sum of 5 to 7. The mean length of follow-up was 41.5 months. Eighty percent of the cancers were clinical stage T2 and 5% T3. In our series, 64% of patients had pathologically organ-confined cancer, 33% positive margins, and 14% had seminal vesicle invasion. Lymph node positive patients were not included in this series. Progression as judged by serum PSA was noted in 30.6%. With entry of a few routinely used parameters, the model could correctly predict recurrence in 76% of the patients in the validation set. The area under the curve was 0.831. The sensitivity was 85%, the specificity 74%, the positive predictive value 77%, and the negative predictive value of 83%. CONCLUSION: It was possible to predict PSA recurrence with a high accuracy (76%). Physicians desiring objective treatment counseling can use this model, and significant cost savings are anticipated because of appropriate treatment selection and patient-specific follow-up protocols. This technology can be extended to other treatments such as watchful waiting, external-beam radiation, and brachytherapy.

Consistency of occupational exposure history from pattern and model makers.

This study investigates the consistency of occupational histories reported by the same men in 1985 and again in 1988. Detroit-area pattern and model makers participating in a colorectal cancer screening program that was offered at 3-year intervals completed a career length occupational exposure questionnaire at each screening. Analysis of the data from the 243 men who participated in both screening programs provided the opportunity to examine the consistency with which these workers reported the extent of their exposure to 13 substances commonly found in their work environment. Workers were asked to provide a work history, and for each different pattern or model maker job they had held, to estimate the percentage of time they were exposed to the 13 substances. The data indicated that over the 3-year study period, pattern and model makers were highly consistent in reporting whether or not they were exposed to the 13 substances. In addition, their first estimates of the percentage of time they were exposed to each substance were within 10% of their second estimates more than 70% of the time. This concordance was somewhat diminished after excluding those who reported no exposure. These findings suggest that skilled tradesman can provide occupational exposure information that is likely to be useful for physicians in considering an occupational cause for a presenting health concern.

The Henry Ford Health System.

The Henry Ford Health System is a large, vertically integrated health care delivery system, with its core service delivery team comprised of a 1000-person salaried medical group. Oncology services are coordinated through its Cancer Center, which organizes regional distribution of oncology services for residents of southeast Michigan. Oncology services are delivered through five regionally distributed sites, affording a vast majority of cancer services to be provided for patients a short distance from their homes. The System owns the largest health maintenance organization in Michigan (Health Alliance Plan) and its organizational structure affords the opportunity of offering purchasers specific oncology service contracting opportunities. Advantages of providing comprehensive oncology services through an integrated health system include: 1) standardized cancer care guidelines, 2) medical information exchange through an electronic medical record, 3) interdisciplinary cancer care provided by salaried physicians, minimizing potentially conflicting financial issues in treatment decisions, 4) state-of-the-art care afforded through availability of involvement in a large number of National Institutes of Health-sponsored clinical trials, 5) high standards of credentialing for oncology physicians, and 6) integrative managed care perspectives and continuous attention to cost and quality of care issues.

Lung cancer in young patients: analysis of a Surveillance, Epidemiology, and End Results database.

PURPOSE: A large community-based cancer registry was analyzed to determine if the clinicopathologic characteristics and/or survival rates of lung cancer patients under 50 years of age at diagnosis differ from those of patients 50 years of age or greater at diagnosis. PATIENTS AND METHODS: Data regarding demographics, stage, histology, initial therapy, and survival were obtained on all patients with primary bronchogenic carcinoma registered in the metropolitan Detroit Surveillance, Epidemiology and End Results (SEER) registry from 1973 to 1992. RESULTS: Of 31,266 patients, 9.0% were under 50 years of age at diagnosis. Females (40.1% v 31.2%; P < .001) and blacks (28.7% v 21.9%, P < .001) were overrepresented in the younger group compared with the older group. Younger patients had a significantly higher incidence of adenocarcinoma and were less likely to present with local-stage disease (18.6% v 25.2%; P < .001). Younger patients were significantly more likely to undergo surgery and/or combined-modality therapy. Relative survival at 5 years was significantly better in the younger group (16.1% v 13.4%; P < .001), mainly because of better survival in patients with local-stage disease (48.7% v 35.4%; P < .001). In a multivariate analysis, advanced-stage, nonsurgical initial therapy, age 50 years or greater at diagnosis, and male gender were independent negative prognostic factors. CONCLUSION: The overrepresentation of females and blacks in the group of younger patients with lung cancer suggests an increased susceptibility to lung carcinogens in these populations. Overall, this study suggests that lung cancer is not a more aggressive disease in younger patients and that all patients with lung cancer should be managed along the same therapeutic guidelines.

Incidence of colorectal adenocarcinoma by anatomic subsite. An epidemiologic study of time trends and racial differences in the Detroit, Michigan area.

BACKGROUND: Colorectal adenocarcinoma may represent more than one disease process. Numerous epidemiologic studies suggest that rates of occurrence of colorectal adenocarcinoma at particular anatomic subsites (e.g., right colon, left colon, and rectum) may be associated with distinctive geographic, demographic, and risk factor profiles. This study explored time trends over a 22-year period of the incidence of adenocarcinoma of the colon and rectum at various subsites among patients of different race, gender, and stage of disease. METHODS: Data on the incidence of colorectal adenocarcinoma were obtained from a population-based cancer registry in the Detroit, Michigan area funded by the National Cancer Institute. Age-adjusted incidence rates were analyzed by year of diagnosis. Relative survival rates were also obtained for different race and gender categories, along with disease stage at diagnosis. RESULTS: A major rise was revealed in the incidence of adenocarcinoma in the right colon among African American men and women between the mid-1970s and the early 1980s. The rise was greatest among African American men and accounts for increases in late stage disease among them. Corresponding decreases in survival among African American men were noted. CONCLUSIONS: These findings indicated widely differing disease patterns based on anatomic subsite and patient demography and also indicated a need for targeted efforts at early detection of adenocarcinoma of the right colon among African Americans.

Family medicine in Japan.

Two networks of medical care have grown up in Japan: 1 network based in hospitals and 1 based in private clinics. Most physicians in clinics practice general medicine, although only a small proportion of them are trained in primary care. Postgraduate medical education is oriented toward the training of specialists. Owing to the impending retirement of the cohort of clinic-based physicians who have dominated medical politics in Japan, the system is expected to change substantially in the next decade. Among the reformers is a small group of physicians who are attempting to introduce family practice.

Neurobehavioral and health-related deficits in solvent-exposed painters.

The health status of 133 solvent-exposed painters was evaluated using the Neurobehavioral Evaluation System (NES) and blood test results from a physical exam. The comparison group consisted of 51 sheetmetal workers, minimally exposed to solvents. Degree of solvent exposure was calculated using three different indices derived from questionnaire responses. Multivariate analyses, adjusted for age, alcohol consumption, and smoking, indicated that painters performed less well on the symbol digit learning and vocabulary tasks. Evidence was also found for a dose-effect relationship, particularly when several features of the work environment were considered in estimating exposure. Degree of solvent exposure predicted levels of serum lead, BUN, and SGOT. These findings indicate that questionnaire-based measures of solvent exposure can be useful predictors of neurobehavioral and health-related deficits. Verbal ability, often used by researchers as a measure of premorbid functioning, may be adversely affected by solvent exposure.

Environmental medicine content in medical school curricula.

BACKGROUND: The Institute of Medicine has recommended basic clinical competence in environmental medicine (EM) for all physicians. However, the amount and content of instruction in EM currently offered in U.S. medical schools is unknown. METHOD: This cross-sectional study was based on responses to a questionnaire regarding the EM curriculum content of U.S. medical schools, mailed in June 1994 with the Association of American Medical Colleges curriculum survey. RESULTS: Of the 126 schools, 119 (94%) responded. Of these, 29 (24%) reported no required EM content in the curriculum. Schools with EM content averaged seven hours of instruction. Eighty-one schools (68%) had faculty with environmental and occupational medicine expertise, primarily within the departments of medicine, preventive medicine, and family medicine. CONCLUSION: There is a need for increased instruction in EM in medical school curricula for students to acquire the knowledge and skills to prevent, diagnose, and treat health problems with an environmental exposure component. For those schools without EM content in the curriculum, the necessary expertise to develop EM curriculum may be available in current faculty.

Medication use review process and information systems utilized for oncology chemotherapy quality improvement.

Fatal chemotherapy overdoses at prestigious institutions have prompted extensive reviews of policies and procedures in medical centers throughout the country. Improving medication use systems for chemotherapy requires a comprehensive multidisciplinary approach. A process to develop a medical center policy on chemotherapy based on the medication use model adopted by the Joint Commission on Accreditation of Healthcare Organizations will be discussed. This will include the prescribing, preparing, dispensing, administering, and monitoring process as well as quality improvement systems. Pharmacy information systems enhancements that safeguard patients are also discussed including maximum dose checks and specific dosing algorithms for bone marrow transplant patients.

Increasing incidence of adenocarcinomas and carcinoid tumors of the small intestine in adults.

Malignant neoplasms of the small intestine are relatively rare and have received little study. We report on trends in the age-adjusted, sex-, and race-specific incidence rates of adenocarcinomas and carcinoid tumors of the small intestine in the United States from 1973 through 1991. Data were derived from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. There were statistically significant increases in the incidence rates of both adenocarcinomas and carcinoid tumors during the time frame of the study. Rates increased most dramatically in black males, with 2- and 4-fold increases in adenocarcinomas and carcinoid tumors, respectively. The only rates that remained relatively unchanged were those of adenocarcinoma among white females. It remains to be determined if changing environmental factors are important causes of these observed trends. If environmental factors are involved in the etiology of small intestine cancers, analytic studies conducted while the disease is increasing in incidence may provide useful insights.

Prostate-specific antigen in a community screening program.

BACKGROUND: This study was designed to determine who participates in community-based prostate-specific antigen (PSA) screening programs and what serum PSA levels can be expected. METHODS: A descriptive analysis of men who participated in an annual community health screening program was used to compare men who chose PSA screening with those who did not. The relationship of demographic variables to PSA level was evaluated by multivariate regression analysis. Data were available on 5548 men, 6% of whom were black. RESULTS: The population of PSA screening participants included proportionately more middle-aged white men with higher median income, as compared with men who did not participate. Those who did not participate in the screening were more likely to be either very old or very young. PSA levels increased with age, and the percentage of men with elevated PSA levels increased with age. One tenth (9.6%) of all participants had PSAs between 4 ng/mL and 10 ng/mL, and 1.9% had levels greater than 10 ng/mL. Within 1 year of the screening, 1.7% of the screened participants had a diagnosis of prostate cancer. The mean PSA in this group was 15.9 ng/mL. CONCLUSIONS: These data confirm the need for age-specific PSA reference ranges. It is likely that the same reference range can be used for all racial ethnic populations.

Effect of age and race on the survival of men with prostate cancer in the Metropolitan Detroit tricounty area, 1973 to 1987.

OBJECTIVES: Reports have demonstrated that African Americans diagnosed with prostate cancer have a poor survival compared with whites. We examined the impact of age, race, and stage of disease on survival for men diagnosed with prostate cancer. METHODS: A retrospective analysis was made of men diagnosed with prostate cancer utilizing the Surveillance, Epidemiology, and End Results Program (SEER) database. A total of 12,907 men (9339 white, 3568 black) diagnosed from January 1, 1973 through December 31, 1987 were included in the study. For each stage of disease, survival experience was examined using Kaplan-Meier and life table methods, followed by analysis using Cox's proportional hazard model. RESULTS: African-American men have a poorer survival than whites for all stages of prostate cancer when the cancer is diagnosed at younger ages. These differences in survival were not demonstrated for men diagnosed with prostate cancer after age 70. CONCLUSIONS: Age and race should be taken into account when assessing the survival of patients with prostate cancer.