The peer-review process--and an acknowledgement of our peerless reviewers.
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Biomedical subjects
Publications and source records attributed to A R Feinstein.
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The 'epidemiological necropsy' is a newly proposed research strategy in which the size and composition of the epidemiological reservoir of undetected disease is estimated from the relative frequency of necropsy surprise patients, in whom the disease was not suspected during life. The current study was done to help validate a basic premise of the strategy. We examined the surprise necropsy discovery of two upper gastrointestinal malignancies: oesophageal cancer, for which an undetected reservoir would not be expected because the cancer has little room to grow, and gastric cancer, for which a sizeable reservoir might be anticipated. In a review of 15,812 necropsies during 1953-1982 at Yale-New Haven Hospital, 70 cases of oesophageal cancer were identified postmortem. Except for five surprise cases, located at the gastro-oesophageal junction where there is room to grow, no oesophageal cancer reservoir was found during the 30-year period. In the same secular period, however, a distinctive set of reservoir cases was found among 162 necropsy instances of gastric cancer. About two-thirds of these gastric cancers had been previously diagnosed during life, but the remainder consisted of either necropsy surprise cases or patients with wrong primary cancer diagnoses during life. The secular rates of occurrence remained stable and similar in both sexes for surprise gastric cancer cases during the three 10-year periods from 1953-1982, but no wrong primary diagnoses occurred during 1978-1982, after the introduction of improved methods of premortem diagnosis. The results help validate the cancer reservoir theory for malignancies that have room to grow, and confirm the concept that the 'epidemiological necropsy' can reflect qualitative and quantitative changes in cancer reservoirs.
In previous research, we have demonstrated the value of using necropsy "surprise" lung cancer cases, in those in whom lung cancer was not suspected during life, to estimate the size and composition of the "reservoir" of undetected lung cancer in the general population. The current research was done to determine the characteristics and consequences of secular changes over time in the composition of the lung cancer "reservoir." The results suggest that further advances in diagnostic technology will enhance detection during life of the large "reservoir" of resectable lung cancer, particularly in women. With the increased detection of these reservoir cases during life, the statistical occurrence rates for lung cancer will seem to increase, but survival rates will seem to improve because more of the detected cases will be resectable.
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Many substances used in daily life, such as coffee, alcohol, and pharmaceutical treatment for hypertension, have been accused of "menace" in causing cancer or other major diseases. Although some of the accusations have subsequently been refuted or withdrawn, they have usually been based on statistical associations in epidemiologic studies that could not be done with the customary experimental methods of science. With these epidemiologic methods, however, the fundamental scientific standards used to specify hypotheses and groups, get high-quality data, analyze attributable actions, and avoid detection bias may also be omitted. Despite peer-review approval, the current methods need substantial improvement to produce trustworthy scientific evidence.
To understand why the dexamethasone suppression test (DST) for the diagnosis of depression became widely accepted and later rejected, we reviewed the sequence of publications in the DST literature. To evaluate the events, we developed and applied concepts of a five-phase process that can be used to assess the clinical utility of diagnostic marker tests. The review showed that when the DST was introduced into the clinical arena, the initial and final two phases of testing (I, IV, and V) had not been adequately conducted. When these phases of testing were suitably checked many years later, the Phase I studies (exploring basic mechanics of test procedures) showed that dexamethasone had variable bioavailability and that the cortisol assay procedure was unreliable. The Phase IV and V studies (examining test results in groups with suitably broad spectrums of cases and controls) showed that the test did not differentiate depression from most pertinent comorbid conditions. Beyond application to the specific problems of the DST, the proposed five phases of development and evaluation for diagnostic marker tests can be used to plan suitable research and avoid similar problems in the future.
A system of scientific classification should have a suitable basic axis of organization, standardized names, clearly specified operational criteria, and multiaxial arrangements for citing important attributes beyond those included in the basic axis. During the past century, the main nosologic system for identifying human ailments has been the International Classification of Diseases (ICD), which has a well-organized and well-accepted nomenclature, but which lacks operational criteria and an appropriate multiaxial pattern. Two new systems of classification during the past two decades are intended for other purposes and would not be satisfactory as nosologic substitutes. The Problem-Oriented Record (POR) does not have a standardized nomenclature or criteria; and the Diagnosis-Related Group (DRG) approach was organized mainly for fiscal goals. As the basic taxonomy used for classifying human ailments, the ICD needs substantial improvement to fulfill its scientific role in statistics for the occurrence and treatment of disease.
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The statistical standardization of rates produces a single summary value that converts crude rates of occurrence into "standardized" rates that are adjusted for differences in the composition of compared populations. Although the process is well described in the epidemiologic literature and is regularly applied in comparisons of large populations, many investigators are not familiar with three important hazards that are magnified for the smaller groups studied in clinical epidemiologic research. This report contains a new "symmetrical" outline of the direct and indirect standardization processes, and an illustration of three pragmatic hazards: (1) Because the direct standardizing factor uses the observed stratum-specific rates, and because any stratum-specific rates that depend on small denominators may be misleading or unstable, the indirect method is preferred when the observed strata have small denominators. (2) Both the direct and indirect standardizing methods are highly vulnerable both to the choice of reference population and to the boundaries chosen when strata are demarcated or consolidated. The standardized rates can be altered dramatically according to differences in the stratum proportions of the reference population, or to distinctions produced when standardizing strata are consolidated. (3) If the stratum-specific rates and stratum proportions have different patterns of variation across the strata of the compared groups, the use of a single summary value--no matter what method of standardization is applied--may obscure cogent patterns of variation and significant differences in the stratum-specific rates. These hazards can be overcome if the studied group and the reference population are carefully compared for inconsistent variations in the stratum-specific rates and proportions before any standardizing procedure is applied. In many instances, the best approach may be to compare the unaltered stratum-specific rates, without standardization.
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