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Biomedical subjects

R Simon

Publications and source records attributed to R Simon.

At least 523 records · Page 29Linked to original sources
PubMedDate not supplied

A non-parametric graphical representation of the relationship between survival and the occurrence of an event: application to responder versus non-responder bias.

Reports of cancer clinical trials often attempt to evaluate whether tumour response is associated with prolonged survival. Proper analysis requires accounting for the time-dependent nature of response status. We review a valid and relatively simple method of significance testing for this problem, and develop a corresponding non-parametric method for displaying the association between survival and occurrence of response. The new method applies to many other clinical problems involving representation and the association between survival and the occurrence of an event. We illustrate the method with data from two clinical trials.

Humans↗
PubMedDate not supplied

The role of overviews in cancer therapeutics.

The implications of pooling based overviews for the design and conduct of cancer clinical trials are discussed. Because the results of overviews may be highly publicized and disruptive to ongoing trials, the timing of overviews should be carefully considered. Pooling based overviews can be valuable supplements to major clinical trials if the trials are themselves quite similar in design and quality. Such overviews may be essential for addressing subset questions based on results from such trials. Pooling based overviews are not, however, satisfactory alternatives to major clinical trials. Pooled results of many small dissimilar studies may be misleading with regard to the efficacy of treatments contributing to the average. For toxic cancer treatments, the assumption that unexpected qualitative interactions are unlikely does not provide a satisfactory justification for pooling results of trials that are dissimilar in design or quality of conduct.

Antineoplastic Agents↗
PubMedDate not supplied

New designs for the selection of treatments to be tested in randomized clinical trials.

The most important aspect of phase III randomized clinical trials is the selection of the experimental treatments to be tested. Often this decision is based on uncontrolled phase II trials. Substantial statistical attention has been focused on the design of phase III trials and for simple phase II trials, which determine whether a new drug has any anti-disease activity. Much less statistical effort has been devoted to the design and analysis of phase II trials for screening active experimental treatments to determine whether they are sufficiently active, relative to standard treatments, to warrant the conduct of a large randomized phase III trial. This problem is particularly acute in the development of drug combinations where many regimens are possible. We review several designs for such screening trials which we have developed.

Bayes Theorem↗
PubMedDate not supplied

A multiple decision procedure in clinical trials.

In some multiple treatment arm clinical trials there is an order of preference for the treatments based on secondary considerations like toxicity or cost. In this paper, we consider the case where two or more treatments could have equal prior preference. This formulation includes the problem of comparing several equally preferred experimental treatments to one control, or the comparison of a combination with its components. Our decision procedures will guarantee a high selection probability for the correct treatment(s) when that selection is appropriate. We establish sample size requirements for our decision procedures which can be applied to clinical trials with normal, binomial, or right censored exponential endpoints.

Carcinoma, Squamous Cell↗
PubMedDate not supplied

Some practical aspects of the interim monitoring of clinical trials.

The decision to stop accrual early to a clinical trial is often difficult and multifaceted. Interim monitoring boundaries have been found useful in U.S. oncology trials for such decisions for reasons described here. This paper also discusses rationale that lead to more conservative approaches to early stopping decisions than are currently employed. A recent initiative of the National Cancer Institute to achieve the objectives of independent data monitoring committees in the phase III clinical trials which it sponsors is also described.

Bias↗
PubMedDate not supplied

Excision of the rectum with colonic J pouch-anal anastomosis for adenocarcinoma of the low and mid rectum.

The results of rectal excision with colonic pouch-anal anastomosis are reviewed from a series of 162 patients covering 7 years. All patients have been operated upon in the same institution and consecutively. The follow-up is now sufficient to allow an accurate evaluation of the outcome of the patients. The main goal of this study was to provide a detailed report of the functional results. Continence was satisfactory in 96% of the patients, with either a perfect continence or minor troubles that would not have been detectable other than by a rigorous questioning. The mean number of bowel movements was 2 per 24 hours. Fragmentation of the defecation and urgency were absent. Twenty-five per cent of the patients had to elicit the evacuation of the reservoir with a suppository or an enema. Improvement of function yielded by a reservoir over straight colo-anal and low colo-rectal anastomoses are significant and, as suggested by manometric studies, are directly related to the restoration of a reservoir function.

Adult↗
PubMedDate not supplied

Viscous lidocaine as a posthemorrhoidectomy analgesic.

During hemorrhoidectomy, a standard 16-gauge plastic catheter was sutured to the operative site so that analgesic doses of viscous lidocaine solution could be delivered to the site for the first 36 hours postoperatively. Although 14 patients had urinary retention that necessitated catheterization, no complication was attributed to the analgesic method. Of 227 patients, 92 per cent were treated with this method plus orally administered nonnarcotic analgesics. Viscous lidocaine injected into the anus is concluded to provide safe, convenient analgesia following hemorrhoidectomy. Toxic reactions to lidocaine were not a problem because the doses were small, and the drug was used only intermittently over a period of 36 hours.

Administration, Topical↗
PubMedDate not supplied

Doppler ultrasound of the subclavian artery as an aid to quantification of aortic insufficiency.

Aortic insufficiency (AI) induces backflow of blood in the arterial system that is most pronounced in the major arteries close to the heart. Assuming that the intensity of the arterial backflow of blood may reflect the severity of AI, the systolic and diastolic flow profiles of the subclavian artery were studied in 40 patients with and 10 patients without AI that was angiographically proved by use of continuous wave Doppler ultrasound (8 MHz transducer, supraclavicular approach). Patients with angiographically determined severe AI (n = 17) had significantly higher diastolic regurgitant flow velocities (V-max) than patients with only mild (n = 9) or moderate (n = 14) degrees of AI (Severe AI = 35.0 +/- 12.0 cm/sec, moderate AI = 16.8 +/- 3.9 cm/sec, mild AI = 7.4 +/- 2.6 cm/sec; p < 0.01) and also showed significantly higher values with regard to the time velocity integral of the regurgitant jet (severe AI = 13.8 +/- 5.6 cm; moderate AI = 5.7 +/- 2.4 cm, mild AI = 1.4 +/- 0.9 cm; p < 0.01). After classification by jacknife discrimination analysis, the Doppler ultrasound grading was compared with a corresponding three-point scale (mild, moderate, severe) from aortic root angiography. A correct estimation of the severity of AI was possible in 44 of 50 patients (88%; overestimation in one, underestimation in five) and in 41 of 50 patients (83%; overestimation in one, underestimation in eight) with regard to V-max and the time velocity integral of the regurgitant jet, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve Insufficiency↗
PubMedDate not supplied

Teamwork in emergency medical services.

Emergency medical care is delivered by highly trained and motivated individuals working in groups. In some cases, these groups function as teams, but their teamwork has been poorly studied and rarely is the result of focused training. Medical outcome traditionally is described using patient parameters and often is related to the economics of care delivery. Errors in medical care typically are blamed on individuals and occasionally on system problems. Teams and teamwork, although a major part of the medical delivery system, usually are not included in training, outcome measures, or rigorous quality improvement efforts. This article outlines issues involved in the analysis of medical errors as they relate to measures of individual and team performance and introduces concepts related to emergency care teamwork and team training. Through analogy with aviation analysis of errors and corrective training medical care similarly is being analyzed and error-reduction efforts studied and implemented. The potential benefit of teamwork training for EMS personnel, including air medical crews, is discussed.

Air Ambulances↗
PubMedDate not supplied

Use of genomic signatures in therapeutics development in oncology and other diseases.

Pharmacogenomics is the science of determining how the benefits and adverse effects of a drug vary among a target population of patients based on genomic features of the patient's germ line and diseased tissue. By identifying those patients who are most likely to respond while eliminating serious adverse effects, the therapeutic index of a drug can be substantially increased. This may facilitate demonstrating the effectiveness of the drug and may avoid subsequent problems due to serious adverse events. Our objective here is to provide clinical trial designs and analysis strategies for the utilization of genomic signatures as classifiers for patient stratification or patient selection in therapeutics development. We review methods for the development of genomic signature classifiers of treatment outcome in high-dimensional settings, where the number of variables available for prediction far exceeds the number of cases. The split-sample and cross-validation methods for obtaining estimates of prediction accuracy in developmental studies are described. We present clinical trial designs for utilizing genomic signature classifiers in therapeutics development. The purpose of the classifier is to facilitate the identification of groups of patients with a high probability of benefiting from it and avoiding serious adverse events. We distinguish exploratory analysis during the development of the genomic classifier from prospective planning and rigorous testing of therapeutic hypotheses in studies that utilize the genomic classifier in therapeutics development. We discuss a variety of clinical trial designs including those utilizing specimen collection and assay prospectively for newly accrued patients and those involving a prospectively planned analysis of archived specimens from a previously conducted clinical trial. Our discussion of the development and use of classifiers of efficacy is mostly focused on applications in oncology using classifiers based on biomarkers measured in tumors. Some of the same considerations apply, however, to development of efficacy and safety classifiers in nononcologic diseases based on single-nucleotide germline polymorphisms.

Biomarkers↗
PubMedDate not supplied

Isolation of a Kell-reactive protein from red cell membranes.

A red cell membrane protein which exhibits Kell blood group antigen activity has been identified with a purified anti-Kell bound to a Protein-A agarose column and eluting with lithium diiodosalicylate (LIS). Although anti-Kell as well as the Kell-reactive membrane protein were eluted from the column, the eluate was capable of reducing the titer of added anti-Kell from 64 to 4. In addition, the eluate was shown to possess Kell reactivity by binding I125 Protein A after incubation with anti-Kell. Electrophoresis (SDS gel polyacrylamide 5-20% gradient) showed a band at approximately 90,000 daltons when solubilized membranes from Kell-positive red cells were used but not when membranes from dithiothreitol- and papain-treated Kell-positive red cells or Kell-negative red cells were used. A band isolated with unreduced conditions was capable of neutralizing anti-Kell.

Anion Exchange Protein 1, Erythrocyte↗