Search PubMed⌕ Search

Biomedical subjects

C K Wells

Publications and source records attributed to C K Wells.

At least 37 records · Page 2Linked to original sources
PubMed1990

A comparison of multivariable mathematical methods for predicting survival--I. Introduction, rationale, and general strategy.

This paper and the two following papers (Parts I-III) report an investigation of performance variability for four multivariable methods: discriminant function analysis, and linear, logistic, and Cox regression. Each method was examined for its performance in using the same independent variables to develop predictive models for survival of a large cohort of patients with lung cancer. The cogent biologic attributes of the patients had previously been divided into five ordinal stages having a strong prognostic gradient. With stratified random sampling, we prepared seven "generating" sets of data in which the five biologic stages were arranged in proportional, uniform, symmetrical unimodal, decreasing exponential, increasing exponential, U-shaped, or bi-modal distributions. Each of the multivariable methods was applied to each of the seven generating distributions, and the results were tested in a separate "challenge" set, which had not been included in any of the generating sets. The research was intended not merely to compare the performance of the multivariable methods, but also to see how their performance would be affected by different statistical distributions of the same cogent biologic attributes. The results, which are presented in the second and third papers, were compared for selection of independent variables and coefficients, and for accuracy in fitting the generating sets and the challenge set.

Cohort Studies↗
PubMed1990

A comparison of multivariable mathematical methods for predicting survival--III. Accuracy of predictions in generating and challenge sets.

This paper concludes a study of "performance variability" when four methods of multivariable analysis--multiple linear regression, discriminant function analysis, multiple logistic regression, and two arrangements of Cox's proportional hazards regression--were applied to the same stratified random samples of "generating sets" containing seven different statistical distributions of cogent biologic attributes in a composite staging system for a large cohort of patients with lung cancer. Each model developed from the generating sets was also applied for predictions in a previously sequestered "challenge set". Across the different generating sets, the multivariable methods showed good agreement with one another in the stepwise choice of first two powerful predictor variables, but not in the sequence of subsequent choices or in the standardized coefficients assigned to the same collection of "forced" variables. In concordance of predictions for individual patients in the generating sets, the overall proportions of disagreement for pairs of methods ranged from 0 to 28%, and kappa values ranged from 0.49 to 1.00. The accuracy of individual predictions showed relatively similar results when the different methods were applied to the same generating set. Across the generating sets, the different methods showed similar total results but substantial variations in predictions for alive and dead patients. When the models from the generating sets were applied for predictions in the challenge set, the results showed an analogous pattern: similar accuracy within models for overall and live/dead predictions, but substantial variations in live/dead predictions across models derived from different generating sources. The results showed that the multivariable methods often had good agreement with one another in predictions for groups but not for individual persons; and that no single method was superior to the others or to the composite staging system. We conclude that multivariable analytic methods may be most effective and consistent if used to find the few most powerful predictor variables, omitting the many other variables that may be "statistically significant" but less cogent. The powerful predictors may sometimes be best constructed, before the analysis begins, as composite variables containing appropriate unions or ordinal arrangements of elemental candidate variables.

Cohort Studies↗
PubMed1990

A clinical-severity staging system for patients with lung cancer.

The prognostic staging of cancer in general, and lung cancer in particular, has customarily depended mainly on morphologic distinctions. The gross anatomic extensiveness of cancers is cited with TNM stages that describe the primary tumor (T), spread to regional lymph nodes (N), and metastatic dissemination (M) to distant sites. Microscopic characteristics are cited according to the cancer's cell type (e.g., adenocarcinoma, epidermoid carcinoma) and/or grade of differentiation (e.g., well differentiated, poorly differentiated, anaplastic). Although the clinical manifestations, functional effects, and associated co-morbidity of a cancer are universally recognized as having major prognostic importance, they have not been classified with a standard system of taxonomy. When considered at all, clinical phenomena have been cited with a surrogate index of "performance status" that ignores the underlying clinical dysfunctions while being greatly affected by non-clinical phenomena, such as the patient's psychic status, economic motivations, and system of social support. The current research was done to develop a standard system of taxonomy (or "staging") for the prognostic impact of clinical distinctions in patients with primary lung cancer. Appropriate data were obtained, computer-coded, and analyzed from medical records for the complete clinical course of an inception cohort of 1266 patients who were first treated at either the Yale-New Haven Hospital or the West Haven Veterans Administration Hospital during the interval January 1, 1953-December 31, 1964. The information under analysis included clinical phenomena as well as anatomic extensiveness (TNM stage), microscopic histology, the chronometric duration of the interval from the first symptom of lung cancer to zero time, the iatrotropic reason why the patient sought medical attention, the presence of anemia, the amount of customary cigarette use, and the conventional demographic data for age and gender. The main clinical phenomena were expressed in variables for symptom pattern severity, and co-morbidity. Symptom pattern referred to the existence of specific pulmonic symptoms (e.g., hemoptysis), systemic symptoms (e.g., complaint of weight loss), and metastatic symptoms that might be mediastinal (e.g., superior vena cava syndrome), regional (e.g., the Horner syndrome), or distantly metastatic (e.g., central nervous system). The symptom severity variable included the amount of weight loss, and the existence of severe dyspnea or particularly severe tumor effects (such as mental obtundation, rather than hemiparesis in patients with CNS metastasis). Prognostic co-morbidity was cited for coexisting diseases, such as recurrent myocardial infarctions, that might be more lethal than the lung cancer itself.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗
PubMed1989

A new prognostic staging system for the acquired immunodeficiency syndrome.

An improved prognostic staging system is needed for patients with the acquired immunodeficiency syndrome (AIDS). To construct such a system, we analyzed the course of 117 consecutive adults who received a diagnosis of AIDS at Yale-New Haven Hospital from 1981 through 1987. The staging system was developed from the data on the first 76 patients, confirmed in the remaining 41 patients, and then applied to the entire cohort. The staging system, which is based on physiologic deficits rather than demographic or diagnostic features, gives one point for each of the following: severe diarrhea or serum albumin level under 2.0 g per deciliter, any neurologic deficit, arterial oxygen tension of 50 mm Hg or less, hematocrit below 30 percent, lymphocyte count below 150 per microliter, white-cell count below 2500, and platelet count below 140,000. The total score determines the presence of Stages I (0 points), II (1 point), or III (2 to 7 points). The three stages had distinctive prognostic gradients in our cohort. For patients in Stages I, II, and III, the median survival times were 11.6, 5.1, and 2.1 months, respectively, with one-year survival rates of 50, 30, and 8 percent. When the staging system was tested with a proportional-hazards model, no other descriptive or laboratory variable added any additional predictive power. Although this new staging system requires further validation in other populations, we believe it will be useful in evaluating new therapies and improving the precision of prognosis in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1989

An analysis of gastric and oesophageal cancers found with 'epidemiological necropsy' during 1953-1982.

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.

Autopsy↗
PubMed1989

More lung cancer but better survival. Implications of secular trends in "necropsy surprise" rates.

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.

Autopsy↗
PubMed1988

The value and hazards of standardization in clinical epidemiologic research.

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.

Adult↗
PubMed1988

Detection bias in the diagnostic pursuit of lung cancer.

Autopsy studies have shown that lung cancer is often not detected during life and that a correct antemortem diagnosis is made preferentially in patients with pulmonary symptoms, in smokers, and in men. The current research was done as a case-control study to determine whether the autopsy suggestions of detection bias in diagnostic pursuit of lung cancer were confirmed by the way that sputum Papanicolaou smears (Pap smears) were ordered in an inpatient setting. The cases were 385 hospitalized patients in whom sputum Pap tests had been newly performed from October 1977 to September 1980. Each case was matched by age, admission date, and admission diagnosis to a control patient who had not received a Pap test. Excluded from the study were patients in whom sputum Pap tests were obligatory (e.g., those with manifestations of hemoptysis) or unnecessary (e.g., those with a previous diagnosis of lung cancer or multiple previous sputum Pap tests). Demographic data, amount and duration of cigarette smoking, and details of clinical manifestations were extracted from the patients' medical records by research assistants blind to the study hypothesis. Compared with controls, the cases had distinctive elevations in odds ratios for chronic cough, recent cough, male sex, and cigarette smoking, which also showed a distinctive dose-response relation. In multivariate analyses, all four of these "risk factors" for selective ordering of a sputum Pap smear remained independently highly significant. In the extreme category, men who smoked and coughed were 22 times more likely to have a sputum Pap test ordered than were nonsmoking women who did not cough. Clinically, the results suggest that women and nonsmokers may be deprived of appropriate diagnosis and therapy unless a diagnostic workup for lung cancer is guided mainly by radiographic findings and presenting manifestations. Statistically, detection bias has probably led to an excessively elevated magnitude for the cigarette smoking-lung cancer association and to a falsely low estimate of incidence rates in women.

Adult↗
PubMed1988

Evaluation of clinical methods for rating dyspnea.

To evaluate available clinical methods (self ratings and questionnaire) for rating dyspnea, we (1) compared scores from the recently developed baseline dyspnea index (BDI) with the Medical Research Council (MRC) scale and the oxygen-cost diagram (OCD) in 153 patients with various respiratory diseases who sought medical care for shortness of breath; and (2) evaluated the relationships between dyspnea scores and standard measures of physiologic lung function in the same patients. The dyspnea scores were all significantly correlated (r = 0.48 to 0.70; p less than 0.001). Agreement between two observers or with repeated use was satisfactory with all three clinical rating methods. The BDI showed the highest correlations with physiologic measurements. Dyspnea scores were most highly related to spirometric values (r = 0.78; p less than 0.001) for patients with asthma, maximal respiratory pressures (r = 0.34 and 0.35; p less than 0.001) for patients with chronic obstructive pulmonary disease, and PImax (r = 0.51; p = 0.01) and FVC (r = 0.44; p = 0.03) for those with interstitial lung disease. These results show that: (1) the BDI, MRC scale, and OCD provide significantly related measures of dyspnea; (2) the clinical ratings of dyspnea correlate significantly with physiologic parameters of lung function; and (3) breathlessness may be related to the pathophysiology of the specific respiratory disease. The clinical rating of dyspnea may provide quantitative information complementary to measurements of lung function.

Aged↗
PubMed1987

The 'epidemiologic necropsy'. Unexpected detections, demographic selections, and changing rates of lung cancer.

When rising rates of occurrence are reported for a particular disease, clinicians often cannot determine whether the disease has increased in actual occurrence or in the improved detection provided by better diagnostic technology and expanded access to medical care. The epidemiologic use of necropsy data, which might help answer these questions, has been inhibited by fears of bias in demographic and clinical selection of patients for necropsy. The demographic problem can be managed by suitable adjustment and standardization of the disease rates found at necropsy, and the clinical problem can be reduced or avoided by studying the rates with which the disease is found unexpectedly in necropsies performed for other, unrelated clinical reasons. The results, obtained in population groups "screened" via necropsy, can suggest the magnitude of the "undetected reservoir" that coexists and supplements the rates of reported occurrence for a disease. In a study of necropsies at Yale-New Haven (Conn) Hospital from 1972 to 1981, the necropsy detection rates for lung cancer were slightly higher for women than for men, and were substantially higher for both genders than the customarily reported rates in the general population. The results suggest that the reported rates may continue to rise in both genders until they become essentially equal at a size approximating that of the currently undetected reservoir. The "epidemiologic necropsy" offers a potentially valuable method to help distinguish the true occurrence rates of disease from the changes attributable to improved diagnostic detection with modern technology.

Adult↗
PubMed1987

Coding ordinal independent variables in multiple regression analyses.

The authors present a coding scheme for ordinal independent variables which may be used in various forms of regression analysis. The scheme is useful in dose-response analyses, when the objective is to identify contrasts in the dependent (or response) variable between successive levels of the independent variable, or to identify critical threshold values of the independent variables at which significant changes occur in the response. An example is given of evaluating the survival of lung cancer patients according to their stage of symptomatology. The authors discuss the interpretation of the regression coefficients when this coding scheme is used with linear regression, logistic regression, or in the proportional hazards regression model.

Humans↗
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↗