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Biomedical subjects

A R Feinstein

Publications and source records attributed to A R Feinstein.

At least 163 records · Page 9Linked to original sources
PubMed1986

Diethylstilbestrol and clear cell vaginal carcinoma. Reappraisal of the epidemiologic evidence.

The association between DES and the development of clear cell vaginal carcinoma may have several alternative explanations rather than a cause- and-effect relation. One important possibility is that susceptibility bias, arising from reasons for use of the drug in a problem pregnancy, is a prime source of the observed effect in the case-control studies. Rather than being a cause of clear cell vaginal carcinoma, exposure to DES would serve as a prognostic "marker" to identify women born of problem pregnancies that increased their risk for development of the disease. Since medical advances in prenatal and perinatal care allowed these problem pregnancies to be carried to the term delivery of a viable child, DES may have been associated with an increased occurrence of clear cell vaginal carcinoma--without causing the disease. Another alternative hypothesis is needed to account for the high rates of reported previous exposure to DES in the case subjects of the two case-control studies. These rates may have been elevated by some form of interviewer bias or recall bias. The relatively high incidence of clear cell vaginal carcinoma that would be expected from the results of these case-control studies has not been observed in cohort studies. No instances of clear cell vaginal carcinoma have thus far been found in suitably assembled cohorts of women exposed to DES in utero. The history of science contains abundant examples of fervently held beliefs about cause- and-effect relations that were later found to be erroneous. The existing evidence of a DES/vaginal cancer relation is currently too weak for the causal role of DES to be regarded as established. To get better evidence, the problems of biased comparison and biased data can be addressed in at least three ways. The first is to carry out an appropriately objective new case-control study, with suitably chosen control subjects; the second is to study the issue of susceptibility bias by getting additional information about the occurrence of problem pregnancies in the mothers of patients with clear cell vaginal carcinoma who were not exposed to DES; the third is to review past tissue specimens from previously diagnosed genital adenocarcinomas, searching for clear cell cancers that may have been unrecognized. Until the suspected biases are addressed and either confirmed or refuted, the relation between DES and clear cell vaginal carcinoma remains a statistical association that is unaccompanied by the quality of evidence required for scientific conclusions.

Adenocarcinoma↗
PubMed1986

Effect of restraints on diagnostic approaches to abdominal pain and weight loss.

To examine the effects of restraint on the diagnostic process, 25 physicians were urged to be as economical as possible when requesting diagnostic tests for case report simulations of nine patients who had previously been hospitalized with abdominal pain and weight loss. The results of the tests correctly changed the physicians' initial diagnoses, increased their diagnostic confidence, and led to appropriate management decisions. When restrained, individual physicians needed only 3.0 (1.7 to 4.1) diagnostic procedures per patient to reach management decisions, whereas 6.1 (3.0 to 11) diagnostic procedures had actually been performed. Diagnostic approaches were so diverse, however, that the number of procedures collectively requested by randomly assembled "teams" consisting of four to five "economical" physicians equaled the number of procedures actually performed. Moreover, 20 percent of the procedures requested by "economical" physicians were invasive compared with only 7 percent of those actually performed. These findings suggest that, without uniform diagnostic approaches, "team" management may increase testing despite restraint by individual physicians. Moreover, quests for economy may increase invasive diagnostic testing.

Abdomen↗
PubMed1986

A new clinical-anatomic staging system for evaluating prognosis and treatment of prostatic cancer.

Because the existing systems of staging for prostatic cancer depend exclusively on the extent of anatomic spread, the stages do not demarcate distinctive patterns of survival, particularly in patients with extremely good or poor prognoses. In this research, we demonstrate that the evaluation of prognosis and therapy can be improved if anatomic staging is augmented by various features of the patients' clinical severity. In 280 patients with prostatic cancer, we first created rating scales for severity of three distinct clinical variables: symptoms referable to cancer; host factors unrelated to cancer; and overall level of function. In univariate analysis each of these clinical variables substantially affected 5-year survival for patients with similar anatomic stages, but in multivariate analysis, only the first two (symptoms and host factors) remained impressive. Retaining the anatomic stages and adding the two most important clinical variables, we then created a composite new staging system, containing four clinical-anatomic (C-A) categories. The new C-A categories were statistically more distinctive than conventional anatomic stages, and demarcated patients with more extreme high (91%) and low (8%) 5-year survival rates. In addition to the increased prognostic precision, the new C-A staging system demonstrated an important distinction in treatment. Although radical radiotherapy seemed superior to palliative therapy within conventional anatomic stages, the survival differences disappeared within the C-A stages.

Adult↗
PubMed1986

An analysis of Berkson's bias in case-control studies.

The bias described by Berkson arises as a mathematical phenomenon, caused by the probabilistic union of different rates of hospitalization for people with different medical phenomena. When the concept is extended to case-control studies, these rates will occur as hd for people with the target disease, he for people with the control condition, and hc for the separate effect of exposure to the suspected etiologic agent. An algebraic analysis of patterns of hospitalization and case-control selection demonstrates that Berkson's bias will be avoided if both cases and controls are chosen from the community or if he = 0. When the cases are chosen from hospitalized patients, the odds ratio will be biased if, as in the usual clinical situation, he not equal to 0. The odds ratio will be falsely elevated if the control groups are chosen from a community population rather than from hospitalized patients, and falsely lowered if the controls are hospitalized patients who do not have the target disease. If the control groups are chosen from patients hospitalized with specific comparison conditions, the odds ratio will be falsely elevated or lowered, depending on the relative magnitudes of hd and hc. In Berkson's mathematical model, the probabilistic calculations depend on the assumption that each of the exposed or diseased clinical conditions has an independent additive effect on hospitalization rates. In reality, however, the concurrence of two or more conditions of disease and exposure may synergistically affect the examining physician's nosocomial decisions and may thereby substantially change the hospitalization rates from what is expected mathematically. In creating hospitalization bias in case-control studies, these selective clinical decisions about referral to hospital may be more cogent than the probabilistic distinctions described by Berkson.

Biometry↗
PubMed1986

Rates of sensitivity reactions to aspirin: problems in interpreting the data.

This work was done to determine the reasons for variation in the reported rates--ranging from less than 1% to greater than 50%--of sensitivity to aspirin and cross-reactivity to acetaminophen and ibuprofen. In 47 studies that reported rates of sensitivity and in 23 reports that contained series of sensitive patients, we examined the research setting, source of patients, clinical attributes of the study group, admission process, and selection, operational definition, and method of determining sensitivity reactions. In five studies with reasonably well-specified methods, the reported sensitivity rates to aspirin were lowest (0.3% to 0.9%) for patients without allergic tendencies, higher in asthmatics, and highest if patients had nasal polyps or severe atopy. Although not determined in any of these studies, the rate of sensitivity in a general (nonclinical) population would doubtlessly be substantially lower than the rate of three per 1000 reported for nonallergic patients. The admixture of different clinical groups, varying definitions, and ascertainment of a sensitivity reaction seem to be responsible for the variations in the reported rates of sensitivity and cross-reactivity.

Acetaminophen↗
PubMed1986

Further specification and evaluation of a new clinical index for dyspnea.

When breathlessness is described in conventional clinical indexes-such as the Pneumoconiosis Research Unit score or the Medical Research Council index-the ratings depend only on the magnitude of the most taxing task that the patient can perform. No attention is given to the patient's effort in performing tasks or to the functional impairment produced by dyspnea in everyday activities. To improve the effectiveness and scope of the assessment, the patient's magnitude of effort and task, as well as functional impairment, were combined in a recently developed new index of dyspnea. In the current research, this new index has been further improved and tested. The ratings have been cited with more precise criteria, and the results of the Modified Dyspnea Index created by the new criteria have been compared with results of the conventional Pneumoconiosis Research Unit score, and with physiologic measurements of pulmonary function. For 32 patients with stable chronic obstructive pulmonary disease (COPD), the Modified Dyspnea Index had a moderate correlation with the Pneumoconiosis Research Unit score (Spearman rho = -0.62) and with the FEV1 (Pearson r = 0.71) and FVC (Pearson r = 0.69). Among patients with the same Pneumoconiosis Research Unit score, however, the Modified Dyspnea Index scores showed a substantial gradient. Ratings with both the previous and the modified new dyspnea indexes correlated most strongly with respiratory muscle strength, supporting the idea that dyspnea is mediated by alteration of respiratory muscle function.(ABSTRACT TRUNCATED AT 250 WORDS)

Dyspnea↗
PubMed1986

Clinical features of lung cancers discovered as a postmortem "surprise".

Despite improved modern diagnostic techniques, many patients with primary lung cancer escape detection of their disease during life. In a review of postmortem records at a university hospital, 28 percent of 153 primary lung cancers found at necropsy had not been diagnosed while the patient was alive. The male/female ratio was 1.3 in this undetected group, compared with 2.3 in the detected group. The main clinical features that seemed to lead to nondiagnosis were a terminal clinical state in patients who were too sick for further diagnostic searches, the absence of suggestive primary symptoms, a chest x-ray film interpreted as not showing primary lung cancer, and the absence of cigarette smoking. Among the patients with lung cancer at necropsy, the proportion of nonsmokers was higher in the previously undiagnosed group than in the group with antemortem diagnoses, even when patients were stratified for primary symptoms. The findings suggest the need for diagnostic alertness to the possibility that curable lung cancer can occur in patients who have a positive chest-film lesion but who are nonsmokers and who lack typical symptoms.

Adult↗
PubMed1986

Scientific and clinical problems in indexes of functional disability.

Indexes of functional disability are being used increasingly to rate the status of patients studied in clinical research or treated in clinical practice. To determine why so many indexes have been developed and to evaluate their scientific quality, we reviewed the construction and other attributes of 43 indexes that offer ratings for activities of daily living. The six most prominent problems, and some proposed solutions, are as follows: Ratings for the magnitude of performed tasks will be misleading unless the patient's effort or collaboration is suitably considered. Each patient's preferences should be sought to determine which types of disability are the most important goals of therapy. Special transition indexes should be developed if subtle or overt changes are not discerned from the repeated use of single-state indexes. Hierarchical scale arrangements can avoid the loss of descriptive power that occurs when multiple variables are aggregated merely as summations. Documentary evidence can be required to demonstrate the anticipated achievements of an index. New indexes can be constructed if the high statistical "reliability" and "validity" of established indexes are not accompanied by satisfactory clinical "sensibility."

Activities of Daily Living↗
PubMed1986

Necropsy evidence of detection bias in the diagnosis of lung cancer.

The correct diagnosis had not been made during life in 26% of 153 patients with lung cancer found in necropsies performed between 1971 and 1982. The likelihood of a correct antemortem diagnosis showed distinctive gradients in relation to the patients' history and amount of cigarette smoking, symptomatic manifestations, and anatomic extensiveness of the cancers. However, cigarette smoking still exerted a diagnostic effect in patients with similar symptoms and similar degrees of anatomic spread. Furthermore, if a lesion was present, chest films were more likely to be radiologically interpreted as a cancer in smokers. The results suggest that smokers receive preferential consideration regarding the diagnosis of lung cancer. This detection bias can have adverse scientific consequences in depriving nonsmokers of suitable therapy, in leading to falsely high estimates of the true magnitude of the smoking/lung cancer association, and in distracting etiologic attention from other agents that may cause lung cancer.

Adult↗
PubMed1985

The Will Rogers phenomenon. Stage migration and new diagnostic techniques as a source of misleading statistics for survival in cancer.

We found that a cohort of patients with lung cancer first treated in 1977 had higher six-month survival rates for the total group and for subgroups in each of the three main TNM stages (tumor, nodes, and metastases) than a cohort treated between 1953 and 1964 at the same institutions. The more recent cohort, however, had undergone many new diagnostic imaging procedures. According to the "old" diagnostic data for both cohorts, the recent cohort had a prognostically favorable "zero-time shift." In addition, by demonstrating metastases that had formerly been silent and unidentified, the new technological data resulted in a stage migration. Many patients who previously would have been classified in a "good" stage were assigned to a "bad" stage. Because the prognosis of those who migrated, although worse than that for other members of the good-stage group, was better than that for other members of the bad-stage group, survival rates rose in each group without any change in individual outcomes. When classified according to symptom stages that would be unaltered by changes in diagnostic techniques, the two cohorts had similar survival rates.

Female↗