Biomedical subjects
A R Feinstein
Publications and source records attributed to A R Feinstein.
Spectrum bias in the evaluation of diagnostic tests: lessons from the rapid dipstick test for urinary tract infection.
OBJECTIVE: To determine if the leukocyte esterase and bacterial nitrite rapid dipstick test for urinary tract infection (UTI) is susceptible to spectrum bias (when a diagnostic test has different sensitivities or specificities in patients with different clinical manifestations of the disease for which the test is intended). DESIGN: Cross-sectional study. PATIENTS: A total of 366 consecutive adult patients in whom clinicians performed urinalysis to diagnose or exclude UTI. SETTING: An urban emergency department and walk-in clinic. MEASUREMENTS: After the patient encounter, but before dipstick test or culture was done, clinicians recorded the signs and symptoms that were the basis for suspecting UTI and for performing a urinalysis and an estimate of the probability of UTI based on the clinical evaluation. For all patients who received urinalysis, dipstick tests and culture were done in the clinical microbiology laboratory by medical technologists blinded to clinical evaluation. Sensitivity for the dipstick was calculated using a positive result in either leukocyte esterase or bacterial nitrite, or both, as the criterion for a positive dipstick, and greater than 10(5) CFU/mL for a positive culture. RESULTS: In the 107 patients with a high (greater than 50%) prior probability of UTI, who had many characteristic UTI symptoms, the sensitivity of the test was excellent (0.92; 95% CI, 0.82 to 0.98). In the 259 patients with a low (less than or equal to 50%) prior probability of UTI, the sensitivity of the test was poor (0.56; CI, 0.03 to 0.79). CONCLUSIONS: The leukocyte esterase and bacterial nitrite dipstick test for UTI is susceptible to spectrum bias, which may be responsible for differences in the test's sensitivity reported in previous studies. As a more general principle, diagnostic tests may have different sensitivities or specificities in different parts of the clinical spectrum of the disease they purport to identify or exclude, but studies evaluating such tests rarely report sensitivity and specificity in subgroups defined by clinical symptoms. When diagnostic tests are evaluated, information about symptoms in the patients recruited for study should be included, and analyses should be done within appropriate clinical subgroups so that clinicians may decide if reported sensitivities and specificities are applicable to their patients.
Problems of comorbidity in mortality after prostatectomy.
OBJECTIVE: In recent studies of patients with benign prostatic hyperplasia (BPH), men undergoing transurethral resection of the prostate (TURP) had higher long-term mortality than men undergoing open prostatectomy. We tested the hypothesis that the higher mortality for patients undergoing TURP could have occurred if these patients were older and sicker at the time of surgery than patients undergoing open prostatectomy. DESIGN AND SETTING: Retrospective cohort study at Yale-New Haven (Conn) Hospital. PATIENTS: Two hundred fifty-two men who underwent TURP or open prostatectomy from 1979 through 1981 for the treatment of BPH. MAIN OUTCOME MEASURES: Five-year mortality adjusted for age and severity of comorbid illness at the time of surgery. RESULTS: The crude 5-year mortality rates were 17.5% (22 of 126 patients) for the TURP group and 13.5% (17 of 126 patients) for the open group. At the time of surgery, however, patients in the TURP group were sicker and older than patients in the open group. As the detail and quality of the assessment of comorbidity increased, the adjusted risk of TURP decreased. Improved classifications of comorbidity in three different forms of statistical analysis did not show an effect of type of prostatectomy on long-term mortality (Mantel-Haenszel relative risk, 1.03; 95% confidence interval, 0.57 to 1.87). CONCLUSIONS: These results suggest that TURP does not increase long-term mortality after surgery for the treatment of BPH. Inadequate accounting for severity of illness may also affect other statistical "adjustments" used in research concerned with patient outcomes.
Invidious comparisons and unmet clinical challenges.
Explore the source record for details and available documents.
The role of diagnostic inconsistency in changing rates of occurrence for coronary heart disease.
The ante-mortem (in vivo) and post-mortem diagnoses of coronary heart disease (CHD) were compared in necropsies at a university hospital for 1965, 1975, and 1985. The secular trends showed gradually rising proportions in both true positive and false negative ante-mortem diagnoses. Both types of change in diagnostic error would progressively lower the counted numbers of CHD in official vital statistics. With suitable statistical corrections, the occurrence rates of CHD in Connecticut became much higher and showed less dramatic trends in secular decline. The results indicate that major improvements in accuracy are needed before vital statistics data are accepted at face value and analyzed for biologic explanations of the changing numbers.
A bibliography of publications on observer variability (final installment).
Explore the source record for details and available documents.
A comparative contrast of clinimetric and psychometric methods for constructing indexes and rating scales.
Explore the source record for details and available documents.
Oxygen as a cause of blindness in premature infants: "autopsy" of a decade of errors in clinical epidemiologic research.
Several intellectual "autopsies" have recently reviewed errors in clinical epidemiologic studies of causation, such as the original claim that amyl nitrite "poppers" caused AIDS. The current autopsy was done to determine why it took more than a decade--1942 to 1954--to end an iatrogenic epidemic in which high-dose oxygen therapy led to retrolental fibroplasia (RLF) in premature infants, blinding about 10,000 of them. The autopsy revealed a museum of diverse intellectual pathology. When first noted, RLF was regarded as neither a new disease nor a postnatal effect. In early investigations, the ophthalmologists did not establish explicit criteria for diagnosis and confused RLF with malformations previously seen in full-term infants. Because the patients were not referred until months after birth, the ophthalmologists assumed that the lesion, which resembled an embryologic structure, must have occurred prenatally. Other events suggesting a prenatal cause for RLF were its strong statistical associations with fetal anomalies, multiple gestations, and maternal infections. Although these events were also associated with prematurity, it was ignored when the RLF cases were compared with controls who were mainly full-term infants. The postnatal timing of RLF was eventually recognized when investigators did cohort studies in premature infants and found that RLF could develop in eyes that were normal at birth. As the search for a cause turned to events occurring after birth, statistical associations were produced for agents such as light, vitamins, iron, vitamin E deficiency, and hypoadrenalism. Each study had its own methodologic flaws: controls were missing for light; co-maneuvers were ignored for vitamins and iron; objective diagnosis was not used for vitamin E deficiency; and the research on hypoadrenalism contained biases in susceptibility and detection as well as problems of a competing outcome event. When the role of oxygen administration was first considered, the statistical association with RLF was stronger for vitamin- and iron-therapy than for oxygen. In addition, many investigators were dissuaded by contradictory evidence from institutions in which RLF was either absent despite high-dose oxygen or persistent despite reduced dosage. The contradictory evidence was later regarded as erroneous because of unsatisfactory delivery systems for the oxygen or failure to check the actual oxygen concentrations. An alternative explanatory hypothesis, rejecting the role of high-dose and long-duration oxygen, was the idea that RLF was due to "relative hypoxia", produced by overly rapid weaning from oxygen therapy rather than the duration of oxygen treatment itself.(ABSTRACT TRUNCATED AT 400 WORDS)
Benefits and obstacles for development of health status assessment measures in clinical settings.
Health status measures offer scientific, humanistic, and economic benefits for clinical medicine. The main problem is the many intellectual and pragmatic obstacles that block successful development of these measures. The inventory of such problems includes the following: definition of health; medical components of health status; who makes the choice about what to include and emphasize; attributes to be rated by patients or clinicians; indexes to be created from those attributes (including mega-variable indexes, global indexes, and oligo-category indexes); different measurements of the same entity; and clinimetric problems in nonclinimetric models. Several solutions to these multiple, complex difficulties can be offered: 1) ensure that a specific purpose, focus, and setting are clearly identified for every health status index; 2) recognize that an off-the-shelf index with high statistical scores for so-called reliability and validity may not be pertinent for a given current situation in which it is to be used; 3) avoid indexes involving combinations of excessive numbers of variables; 4) let patients choose the most significant foci and components of the indexes; 5) seek greater communication and understanding among multidisciplinary collaborators, who may have many differences in the ethos and goals with which they approach the construction of health status indexes; and 6) recognize that the construction of suitable health status indexes is an outstanding challenge in basic scientific inquiry, and, in this spirit, support major alterations in the current ideology for conceptualization and funding of what is basic science in clinical medicine.
Improving the reliability of orthopaedic measurements.
Explore the source record for details and available documents.
Response to initial therapy and new onset as predictors of prognosis in patients hospitalized with congestive heart failure.
Clinical predictors of in-hospital fatality were assessed in 191 persons admitted to the Yale-New Haven Hospital Intensive Care Unit with a diagnosis of congestive heart failure. In the 17 (8.9%) patients who died, the most important individual predictors among the presenting clinical features were absence of dyspnea, presence of anterior chest pain or jugulovenous distension, and cardiac severity due to ischemia, valvular disease, or arrhythmia. Two important predictors, largely neglected in previous literature, were a prior history of congestive heart failure and a poor clinical response after 24 h of therapy. Multivariable analysis led to the identification of 6 features (age greater than 70 y, prior history of congestive heart failure, jugulovenous distension, chest pain, cardiac severity, and poor early response to therapy) that could be combined into a simple clinical predictive index. The new index identified 5 prognostic groups with fatality rates of 0, 3.5, 7.4, 19.2, and 85.7 percent. An advantage of the clinical index is the identification of a subgroup of patients, with low risk for fatality, who may not need prolonged treatment in an intensive care unit.
In-vivo and post-mortem gallstones: support for validity of the "epidemiologic necropsy" screening technique.
This research was done to evaluate the "epidemiologic necropsy" procedure as a "screening" technique for disease that has been clinically unsuspected or inactive during life. The post-mortem occurrence rates of gallstones in necropsies at Yale-New Haven Hospital were compared and found reasonably similar to the analogous rates of gallstones detected in-vivo via ultrasonographic screening of large general populations. Because the authors could not find an appropriate in-vivo screening study done in the United States, they used data mainly from screening studies in Copenhagen, Denmark, and Rome and Sirmione, Italy. Two additional ultrasonographic screening studies have been done in Norway and in populations of Hispanic Americans. Previous disparities between post-mortem and in-vivo screening results probably arose because of failure to stratify for age and sex, to remove patients with cholecystectomy from the analysis, or to account for small-size stones that would be detected at necropsy but not with ultrasonography. The current results help confirm the value of the epidemiologic necropsy procedure in estimating the size of the substantial reservoir of undetected disease that does not appear in the customary tabulations of "vital statistics."
Construction, consent, and condemnation in research on peer review.
Explore the source record for details and available documents.
Scientific paradigms and ethical problems in epidemiologic research.
In previous eras of medical history, when major changes were proposed in customary scientific paradigms, the perceived threats to the status quo led to profound intellectual discomforts. Rational discussion of the proposed changes was sometimes replaced by passionate accusations about ethical behavior. A similar situation may arise in epidemiology today, as fundamental problems are noted in paradigmatic scientific methods, and as the available epidemiologic evidence is used not only in public policy controversies, but particularly in adversarial legal conflicts. When the basic scientific quality of epidemiologic evidence and methods is questioned, defenders of the status quo may respond by castigating the dissenters as fools or heretics, or by insinuating that they have been bribed with consultation honoraria. Since progress in any scientific field requires that problems be suitably recognized and solved, the current disputes about epidemiologic methods should be debated as issues in science, not as transgressions in ethics.
The qualification period.
For randomized trials that do not require prompt onset of therapy, a pre-admission preparation, called the qualification period, can deal with certain customary difficulties in design, analysis, and ethics. For the patients' baseline state, the qualification period can be used to "wash out" effects of previous treatment, to verify admission criteria, and to identify or stratify suitable prognostic indicators. For treatment, the qualification period can be used to test and adjust therapeutic dosages, to exclude placebo responders, and to confirm early responsiveness to long-term active therapy. For intention-to-treat analyses, the qualification period can allow special stratifications for patients who are therapeutically difficult to regulate or who comply imperfectly. By offering the cited improvements as well as a brief "pilot exposure" for each patient, the qualification period can also enhance the "informed consent" and general ethics of a trial.
Reprise and lyrics for another chorus.
Explore the source record for details and available documents.
A methodological appraisal of research on prognosis after transient ischemic attacks.
We analyzed existing research on the prognosis of patients who have had a transient ischemic attack to identify studies that adhere to basic methodological principles and to identify underinvestigated questions. Studies were eligible for analysis if they were published in peer-reviewed journals after 1950, written in English, and included at least 50 patients with transient ischemia. Studies that included patients with stroke were included only if they reported outcome rates separately for the subgroup of patients with transient ischemia. All eligible studies were extracted by one investigator who recorded adherence to six key methodological principles. Among 60 eligible studies, 54 were observational cohort studies and six were randomized trials. Adherence to the six methodological principles was as follows: eight studies included an adequate description of diagnostic criteria and of procedures used to assure adherence to the criteria, 54 used appropriate end points, two assembled inception cohorts, 10 included an adequate description of end point surveillance, 22 adequately reported and analyzed censored patients, and 10 included a multivariate analysis for predictive variables. No study adhered to all six principles, but two adhered to the three most important ones (appropriate end points, inception cohort, and adequate reporting and analysis of censored patients). Aspects of prognosis after transient ischemia that have not been completely investigated include the severity of subsequent strokes and methods for estimating the outcome risk for individual patients. We conclude that only a few published investigations on prognosis after transient ischemia are methodologically complete. This finding helps explain why it is difficult to interpret many studies. Further research is needed and should target underinvestigated topics.
Measurement of lower limb alignment using long radiographs.
Long radiographs are used to measure lower limb axial alignment, to assess the progression of deformity, and to plan corrective surgery. The purpose of this study was to test the belief that jigs are necessary in order to control limb position for radiography. Above-knee amputated limbs were fixed in different positions of rotation and of knee flexion and radiographed to study the effect on the apparent alignment of the limb. If the limb was rotated no more than 10 degrees from the neutral the effect on apparent axial alignment was minimal and radiographic measurement was reliable. This suggests that standardised positioning jigs are not needed in routine clinical practice.