Projections of lung cancer mortality in the United States: 1985-2025.

Lung cancer has been the leading cause of cancer death in the United States for the larger part of this century. Increases in smoking prevalence from the 1900s through the 1950s have resulted in more than 100,000 deaths annually. Because of the changes during the last three decades in smoking prevalence, the decreasing tar content of cigarettes, and the increasing popularity of low-tar cigarettes, trends in lung cancer are difficult to predict. This article presents an analysis of smoking and lung cancer data using an age-period-cohort model for projecting lung cancer mortality through the year 2025. The projections are based on the initial parameterization of the model and on prevention objectives related to smoking behavior established by the National Cancer Institute. It is concluded that the recent trends in lung cancer are unlikely to be affected by changes in cigarette composition and consumption in the near term, but increasing the effectiveness of anti-smoking campaigns can have a considerable effect on lung cancer rates in the more distant future.

The use of gene tests to detect hereditary predisposition to cancer: economic considerations.

Several mutations recently have been shown to be associated with hereditary nonpolyposis colon cancer (HNPCC) in families displaying unusually strong predisposition to colorectal cancer. Laboratory tests to detect such gene mutations soon will be commercially available, raising the possibility for population-wide screening. The purpose of this study was to explore the economic implications of conducting a population-wide screening for HNPCC compared with restricted screening among members of the families at high risk. An exploratory analysis was performed to determine which factors are most important in determining the cost-effectiveness of such a testing program. The base-case analysis focuses on current uncertainty about the population prevalence of the HNPCC genotype and phenotype. The uncertainty with regard to parameters related to the cost-effectiveness of screening and preventive interventions for HNPCC were explored, using additional sensitivity analyses. Cost-effectiveness is achieved for population-wide screening only when assumptions most favorable to that outcome are made regarding the HNPCC prevalence, the cost and effectiveness of screening, and preventive intervention. Information on the population prevalence of HNPCC genotypes and the penetrance of these genotypes is essential for making policy decisions. Additional information is needed regarding the determinants of the cost of genetic testing and counseling, the efficacy of preventive regimens for individuals at high risk, and the accuracy and cost of alternative methods of identifying families at risk.

Representativeness of the surveillance, epidemiology, and end results program data: recent trends in cancer mortality rates.

BACKGROUND: Mortality, incidence, and survival rates are the primary measures used by the National Cancer Institute (NCI) to monitor cancer in the United States. The Surveillance, Epidemiology, and End Results (SEER) data system collects data on all cancers diagnosed among residents in geographically defined populations, which comprise about 10% of the U.S. population. This data system is the major component of the NCI system for tracking these rates. Thus, it is important to assess the degree to which SEER data are representative of the entire U.S. population. PURPOSE: National data on mortality, but not on incidence or survival, are available from the National Center for Health Statistics. These data provide a census against which mortality data from the subset of the SEER regions may be compared. METHODS: Multivariate regression analyses of age-adjusted mortality rates from 1975 to 1988, computed for the SEER areas and for the entire United States, were performed for race- and sex-specific data from 15 cancer sites. Representativeness was evaluated by testing for differences in trends and levels between the data from the U.S. population and those from the SEER Program. RESULTS: Data from the SEER regions reflected the correct direction of trend for all sites, although some race-, sex-, and site-specific differences existed for the magnitude of the trends and levels of mortality when compared with data from the U.S. population. CONCLUSIONS: The demonstration that data from the SEER population do occasionally yield mortality rates that differ from those for the entire U.S. population suggests that data from the SEER coverage population are, in some cases, not representative of the greater U.S. population. IMPLICATIONS: This issue is of particular relevance to the interpretation of incidence measures, computed from the SEER data, for which there is no national database. Future efforts should be directed at a better understanding of how the SEER population differs from the U.S. population so that SEER rates can be adjusted to be more nationally representative.

Factors associated with surgical and radiation therapy for early stage breast cancer in older women.

BACKGROUND: In addition to demographic and health care-related characteristics, the age and physiologic status of women at the time of breast cancer diagnosis have been reported to influence receipt of standard treatments. Previous studies of the influence of age and comorbidity have not examined whether other patient-, region-, or health care-related characteristics altered the association of age and comorbidity with type of treatment received. PURPOSE: This study examined factors associated with receipt of breast-conserving surgery and radiation therapy, both of which are recommended treatments for breast cancer, among a cohort of 18,704 women aged 65 years or more who had breast cancer diagnosed during the period from 1985 through 1989. METHODS: A data file linking Medicare claims records to data from the Surveillance, Epidemiology, and End Results (SEER) Program of the U.S. National Cancer Institute was utilized. Logistic regression analysis was used to examine associations between patient, region, and hospital characteristics and the receipt of specific treatments. The likelihood test was used to assess the significance of observed associations (expressed as odds ratios [ORs]). Because of multiple comparisons, only those ORs with two-sided P values <.01 were considered statistically significant. RESULTS: The frequency of breast-conserving surgery was highest (54%) among women aged 80 years or more, who had two or more comorbid conditions and stage I disease. However, in general, the receipt of radiation therapy among women undergoing breast-conserving surgery declined markedly with age, irrespective of comorbidity status and disease stage. Between the ages of 65-69 years and 80 years or older, radiation therapy declined from 77% to 24% among women with no comorbid conditions and from 50% to 12% among women with two or more comorbid conditions. In regression models that included hospital, region, and patient characteristics as variables, age and comorbidity remained independently associated with the receipt of radiation therapy (OR = 0.12 and 95% confidence interval [CI] = 0.10-0.14 for women aged 80 years or more compared with women 65-69 years of age and OR of 0.33 [95% CI = 0.24-0.46] for women with two or more comorbid conditions versus no comorbid conditions). CONCLUSIONS: After adjustment for multiple clinical and nonclinical factors influencing treatment, chronologic age remains an important independent factor associated with the receipt of radiation therapy after breast-conserving surgery among women aged 65 years or more who were diagnosed with early stage breast cancer. IMPLICATIONS: Future studies should determine whether these differences in treatment patterns among older women result in increased morbidity (e.g., from recurrence), shortened disease-free or overall survival, or decreased quality of life.

Recent trends in U.S. breast cancer incidence, survival, and mortality rates.

BACKGROUND: Clinical trials have demonstrated that use of mammographic screening and advances in therapy can improve prognosis for women with breast cancer. PURPOSE: We determined the trends in breast cancer mortality rates, as well as incidence and survival rates by extent of disease at diagnosis, for white women in the United States and considered whether these trends are consistent with widespread use of such beneficial medical interventions. METHODS: We examined mortality data from the National Center for Health Statistics and incidence and survival data by extent of disease from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute, all stratified by patient age, using statistical-regression techniques to determine changes in the slope of trends over time. RESULTS: The age-adjusted breast cancer mortality rate for U.S. white females dropped 6.8% from 1989 through 1993. A significant decrease in the slope of the mortality trend of approximately 2% per year was observed in every decade of age from 40 to 79 years of age. Trends in incidence rates were also similar among these age groups: localized disease rates increased rapidly from 1982 through 1987 and stabilized or increased more slowly thereafter; regional disease rates decreased after 1987; and distant disease rates have remained level over the past 20 years. Three-year relative survival rates increased steadily and significantly for both localized and regional disease from 1980 through 1989 in all ages, with no evidence of an increase in slope in the late 1980s. IMPLICATIONS: The decrease in the diagnosis of regional disease in the late 1980s in women over the age of 40 years likely reflects the increased use of mammography earlier in the 1980s. The increase in survival rates, particularly for regional disease, likely reflects improvements in systemic adjuvant therapy. Statistical modeling indicates that the recent drop in breast cancer mortality is too rapid to be explained only by the increased use of mammography; likewise, there has been no equivalent dramatic increase in survival rates that would implicate therapy alone. Thus, indications are that both are involved in the recent rapid decline in breast cancer mortality rates in the United States.

Cigarette smoking among U.S. adults by state and region: estimates from the current population survey.

BACKGROUND: Cigarette smoking is responsible for at least one third of all cancer deaths annually in the United States. Few sources exist in the peer-reviewed literature documenting state and regional differences in smoking behavior, despite the fact that cancer prevention and control efforts are increasingly being implemented below the national level. PURPOSE: Our goals were to determine smoking prevalence rates among men and women, by region, and for each of the 50 states and the District of Columbia from census survey data collected in 1992 and 1993 and to compare these rates with rates determined in 1985. METHODS: Every month, the U.S. Bureau of the Census collects labor force statistics on more than 100000 individuals on its Current Population Survey (CPS). For the September 1992, January 1993, and May 1993 CPS, the National Cancer Institute sponsored a 40-item Tobacco Use Supplement. The definition of a current smoker changed slightly between 1985 and 1992-1993. For the 1985 CPS, individuals were considered current smokers if they had smoked 100 cigarettes in their lifetime and were smoking at the time of interview; for the 1992-1993 CPS, current smokers included anyone who had smoked 100 cigarettes and was currently smoking every day or just on some days. We calculated current smoking rates (every day and some days combined) based on more than a quarter million adults (n = 266988) interviewed in 1992-1993. RESULTS: Substantial geographic variation exists in rates of current cigarette use among adults within the United States. In general, adults in the southern United States have higher rates of smoking and adults in the western states have lower rates of smoking and adults in the rest of the country, although differences in smoking behavior between men and women and among various racial and ethnic populations strongly influence these patterns. Only two states, Kentucky and West Virginia, exhibited adult smoking rates (men and women combined) of 30% or higher in 1992-1993; in contrast, in 1985, such rates were reported from 20 states. The only states in which the prevalence was below 20% in 1992-1993 were Utah (17.1%) and California (19.5%). Rates approaching 20% were reported from New Jersey (20.7%), Massachusetts (21.5%), and Nebraska, New York, and Hawaii (22.0% each) in 1992-1993. Rhode Island experienced the greatest relative decline in smoking prevalence from 1985 to 1992-1993, with a calculated relative change of -30.7% (based on a change in rate from 33.5% to 23.2%), followed by Delaware (-25.9%) the District of Columbia and New Jersey (-23.9% each), Connecticut (-23.2%), California (-22.9%), Alaska (-22.8%), Georgia (-22.6%), Massachusetts (-22.1%), and New York (-22.0%). CONCLUSIONS: Smoking rates are not uniform in the United States but vary considerably from state to state, even within the same region of the country. The CPS is the only mechanism currently capable of simultaneously monitoring smoking trends nationally, regionally, and on a state-by-state basis.

Genetic Variation and Geographic Differentiation in Mitochondrial DNA of the Horseshoe Crab, LIMULUS POLYPHEMUS.

Restriction site variation in mitochondrial DNA (mtDNA) of the horseshoe crab (Limulus polyphemus) was surveyed in populations ranging from New Hampshire to the Gulf Coast of Florida. MtDNA clonal diversity was moderately high, particularly in southern samples, and a major genetic "break" (nucleotide sequence divergence approximately 2%) distinguished all sampled individuals which were north vs. south of a region in northeastern Florida. The area of genotypic divergence in Limulus corresponds to a long-recognized zoogeographic boundary between warm-temperate and tropical marine faunas, and it suggests that selection pressures and/or gene flow barriers associated with water mass differences may also influence the evolution of species widely distributed across such transition zones. On the other hand, a comparison of the mtDNA divergence patterns in Limulus with computer models involving stochastic lineage extinction in species with limited gene flow demonstrates that deterministic explanations need not necessarily be invoked to account for the observations. Experiments to distinguish stochastic from deterministic possibilities are suggested. Overall, the pattern and magnitude of mtDNA differentiation in horseshoe crabs is very similar to that typically reported for freshwater and terrestrial species assayed over a comparable geographic range. Results demonstrate for the first time that, geographically, at least some continuously distributed marine organisms can show considerable mtDNA genetic differentiation.

Psychiatric disorders in primary care. Results of a follow-up study.

Despite extensive documentation of high rates of psychiatric morbidity among primary care patients, there have been, to our knowledge, no US studies following up these patients over time. We analyzed data based on two administrations of the Schedule for Affective Disorders and Schizophrenia-Life-time version (SADS-L) six months apart to 166 attenders at a primary care clinic in Marshfield, Wis. In the short span between interviews, 35% of the study group exhibited at least one Research Diagnostic Criteria disorder, and almost two thirds of these individuals had significant changes in diagnostic status based on SADS-L data. Diagnosis of these transient and episodic cases by the primary care physicians was under 10%, demonstrating the need for careful evaluation of the psychiatric status of primary care patients.

Screening for mental disorder among primary care patients. Usefulness of the General Health Questionnaire.

The General Health Questionnaire (GHQ) and a structured psychiatric interview (lifetime version of the Schedule for Affective Disorders and Schizophrenia) were administered to a sample of primary care patients in the United States. Responses to the GHQ tended to form factors that have substantive interpretations, such as depression, anxiety, sleep problems, and social functioning. However, there seems to be little gain in using subscale scores to help identify persons with different types of psychiatric disorders.

The design of the Epidemiologic Catchment Area surveys. The control and measurement of error.

Several methods are used to minimize and measure error in the NIMH Epidemiologic Catchment Area program. Sampling methods involve the inclusion of group quarters such as prisons, nursing homes, and mental hospitals in the sample frame and the use of probability sampling throughout. Interviewing, methods include use of identical diagnostic interview protocols, centralized training of interview supervisors, standard instructions to interviewers, and reinterview of a subsample by clinicians. In the area of completion, the methods include a 75% to 80% respondent completion rate, a 95% or greater completion rate for individual questions, use of informant interviews where necessary, and statistical adjustments to correct for low completion rates in some subgroups. Analytic methods include use of a computerized diagnostic algorithm, common estimation formulas on identically formatted data files, and estimation of exact variances that take account of the multistage sample design.

Utilization of health and mental health services. Three Epidemiologic Catchment Area sites.

Utilization of health and mental health services by non-institutionalized persons aged 18 years and older is examined based on interviews with probability samples of 3,000 to 3,500 persons in each of three sites of the National Institute of Mental Health Epidemiologic Catchment Area (ECA) program: New Haven, Conn, Baltimore, and St Louis. In all three ECAs, 6% to 7% of the adults made a visit during the prior six months for mental health reasons; proportions were considerably higher among persons with recent DSM-III disorders covered by the Diagnostic Interview Schedule (DIS) or severe cognitive impairment. Between 24% and 38% of all ambulatory visits by persons with DIS disorders were to mental health specialists. In seeking mental health services, men were more likely to turn to the specialty sector than to the generalist; women used both sectors about equally. The aged infrequently received care from mental health specialists. Visits for mental health reasons varied considerably depending on specific types of DIS disorder.

High users of outpatient mental health services, I: Definition and characteristics.

Mental health coverage generally limits benefits for high use, which is assumed to be discretionary. The authors present data from the National Medical Care Utilization and Expenditure Survey. Of the individuals who made mental health outpatient visits in 1980, 9.4% made 25 or more visits and accounted for 50% of mental health visits and expenditures. These high users were compared with low users and with high users of other health care. One-third of the mental health high users were highly disabled and had multiple medical disorders. The authors point out the heterogeneity of this population and suggest that psychiatric benefits be differentiated according to patients' needs and services offered.

Medical device tracking: results of a case study of the implantable cardioverter defibrillator.

Case reports were received of a fatal tachycardia caused by a malfunction of an implantable cardioverter defibrillator (ICD), a device that is subject to the tracking regulations of the Food and Drug Administration's Center for Devices and Radiological Health. The case reports led to a decision to notify 5,604 patients of the need for reprogramming of their ICDs to prevent the tachycordia. In the first 60 days, a total of 98.7% of the patients were successfully located and their devices reprogrammed. Multiple logistic regression analysis was conducted to examine an extensive array of factors that might have been related to the time to reprogramming. Patient-specific factors such as age, sex, and ejection fraction did not serve as a barrier to reprogramming in the first week (p = NS). Patients whose regular physician had >5 patients with the ICD subject to the recall were significantly more likely to have their ICDs reprogrammed in the first week (odds ratio [OR] 2.11, 95% confidence interval [CI] 1.85 to 2.43, p<0.001). Patients who changed physicians were significantly less likely to undergo reprogramming in the first week (OR 0.73, 95% CI 0.63 to 0.86, p<0.001). The experience of the recall of this tracked device is highly encouraging because it demonstrates that most tracked device recipients can be successfully located and receive medical intervention. Although tracking devices is a manufacturer's responsibility, the clinical community plays a critical role in its success. This report highlights the importance of understanding that role among physicians.

The impact of breakthrough clinical trials on survival in population based tumor registries.

Three statistical models are developed to study the impact that two breakthrough clinical trials (MOPP for Hodgkin's disease and PVB for disseminated testicular cancer) had on survival in the Connecticut tumor registry and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry program. A segmented regression model is used in conjunction with the Cox semi-parametric proportional hazards model, as well as the parametric Weibull and exponential cure models. These models allow us to determine approximately when survival first began to improve dramatically, indicating that improved treatments had become available, and how long it took for survival to level off again indicating that the full population survival impact had been realized. In addition, the degree to which the parametric models fit allows us to determine if the survival improvements occur within a parametric family. Results of the modelling indicate that dissemination took approximately 11 years in Hodgkin's disease while only 3 years in disseminated testicular cancer. In both disease sites survival first broke with prior trends between the time that the breakthrough trial started and its publication, indicating that earlier moderately successful 'precursor' trials with combination chemotherapy may have initiated the improved population survival trends. Reasons for the difference in dissemination time in the two cancer sites are examined in order to understand what factors may be responsible for the speed of dissemination and effective utilization of new therapies.

Temporal variation in nucleolar organizer region expression in bone marrow cells of individuals with leukemia.

Silver staining was used to study nucleolar organizer region (NOR) expression in bone marrow cells obtained at two or, in one case, three time points from each of six leukemia patients. Using three measures of silver positivity, we observed that NOR expression was influenced by both metaphase stage and time. Silver positivity decreased significantly from one metaphase stage to the next, from prometaphase through late metaphase. When this variable was controlled for, significant changes in NOR activity were documented in comparisons between disease stages in the patients examined. However, patterns of NOR expression were not consistently associated with disease stage. These results indicate that in previous reports both the metaphase stage effect and the temporally changing nature of NOR activity have, as unrecognized variables, influenced observations of heterogeneity in NOR expression.

Estimating the probability and level of ambulatory mental health services use.

Analysis of the National Medical Care Utilization and Expenditure Survey for persons with positive out-of-pocket expenses for one or more ambulatory mental health visits indicates that demand for such visits is responsive to price, and considerably more so than demand for health visits. Income, education, and insurance coverage interact in predicting demand, and price elasticity varies across income groups.

Mental health training of primary care residents: a review of recent literature (1974-1981).

As the mental health role of primary care physicians has been formally recognized in recent years, educational efforts have also been directed toward the development of mental health attitudes, knowledge, and skills. To assess gains in the latter area, recent literature (1974-81) on mental health training for primary care residents was reviewed. Although shifts from the pre-1975 literature in the training objectives, content, teaching methods and setting were observed, further needs were noted. These include more systematic instruction in the diagnosis and management of mental disorder, evaluation of such training and more extensive collaboration among primary care, psychiatric, and behavioral science disciplines in the teaching of mental health content to primary care physicians.

Study design in the evaluation of breast cancer imaging technologies.

RATIONALE AND OBJECTIVES: Bringing a new imaging technology to market is a complex process. Beyond conceptualization and proof of concept, obtaining U.S. Food and Drug Administration (FDA) approval for clinical use depends on the documented experimental establishment of safety and efficacy. In turn, safety and efficacy are evaluated in the context of the intended use of the technology. The purpose of this study was to examine a conceptual framework for technology development and evaluation, focusing on new breast imaging technologies as a highly visible and current case in point. MATERIALS AND METHODS: The FDA views technology development in terms of a preclinical and four clinical phases of assessment. With a concept of research and development as a learning model, this phased-assessment concept of regulatory review against intended use was integrated with a five-level version of a hierarchy-of-efficacy framework for evaluating imaging technologies. Study design and analysis issues are presented in this context, as are approaches to supporting expanded clinical indications and new intended uses after a new technology is marketed. CONCLUSION: Breast imaging technologies may be intended for use as replacements for standard-of-care technologies, as adjuncts, or as complementary technologies. Study designs must be appropriate to establish claims of superiority or equivalence to the standard for the intended use. Screening technologies are ultimately judged on their demonstrated effectiveness in decreasing cause-specific mortality through early detection, but they may be brought to market for other uses on the basis of lesser standards of efficacy (eg, sensitivity, specificity, positive and negative predictive value, and stage of disease detected).

Epidemiology and health service resource allocation policy for alcohol, drug abuse, and mental disorders.

Data from the NIMH Epidemiologic Catchment Area (ECA) Study in Baltimore, Md., are used to illustrate the association between alcohol, drug abuse, and mental disorder diagnoses with health service use. A probability sample of 3,481 adult (age 18 and over) residents of a geographically defined Baltimore City population of 175,000 was found to have a 23.4 per 100 population, 6-month prevalence of 13 specific alcohol, drug, and mental disorders. Of this population, 7.1 percent sought outpatient mental health treatment from both general medical physicians and mental health specialists in a 6-month period. The presence of a mental disorder diagnosis increased the average number of visits to all health providers from 1.91 to 4.06 during the same 6-month period. Although the presence of a mental disorder diagnosis clearly increased the probability of using both general medical and mental health services, only 15.6 percent of the persons with a mental disorder sought any mental health treatment during this 6-month timeframe--leaving 84 percent of those with mental disorders not seeking any outpatient treatment during the same period. The addition of a measure of high symptomatology (a score of 4 or more on the General Health Questionnaire) increased the percentage of persons with mental disorder using services to 30.5 percent. When a measure of disability was added to the diagnosis and the high symptom level score, 54.7 percent of the population could be predicted to use some mental health service. These data demonstrate the necessity of having additional patient assessment measures with a diagnosis to predict probable service use. However, even in the most comprehensive multidimensional model, more research is required to explore the phenomena of presumed unmet need--the 45 percent of those with a diagnosis, disability, and high symptoms who do not use services. Hence, epidemiologists who wish to participate in setting policy for resource allocation must join with their colleagues in economics, sociology, and health services research to identify all factors in addition to disease states that either predispose population groups to use services or represent additional resource allocation needs.

Cancer awareness among African Americans: a survey assessing race, social status, and occupation.

Knowledge of cancer prevention and control was defined in terms of prevention, etiology, treatment, symptoms, cancer rates, screening, and detection examinations. A survey of 86 African Americans and 68 white Americans in Alameda County, California was completed in 1985. An index comprised of 69 knowledge items was assessed. A multivariate analysis of race, education, socioeconomic status, and occupation confirmed that these characteristics were independent predictors of knowledge. Blue collar work status was the most important predictor of low knowledge levels. African Americans were less knowledgeable than white Americans with regard to diet in preventing cancer and treatment modalities for cancer, and were most likely to perceive surgery as contributing to metastases. Low education and income status predicted low levels of knowledge. An important consideration in changing knowledge levels is the need to translate technical information about treatment and metastases in ways that are effective in reaching target populations at risk for low levels of knowledge. Cancer prevention and control programs need to develop materials and strategies that are responsive to communities whose members are predominantly African Americans or blue collar workers, or have low levels of education and income.