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Biomedical subjects

D A Berry

Publications and source records attributed to D A Berry.

At least 19 recordsLinked to original sources
PubMed1992

Endoscopic release of the carpal tunnel: a randomized prospective multicenter study.

A 10-center randomized prospective multicenter study of endoscopic release of the carpal tunnel was carried out. Surgery was performed with a new device for transecting the transverse carpal ligament while control hands were treated with conventional open surgery. There were 122 patients in the study; 25 had carpal tunnel surgery on both hands and 97 had surgery on one hand. Of the surgical procedures, 65 were in the control group and 82 were in the device group. The endoscopic device was coupled to a fiberoptic light and a video camera. A trigger-activated blade was used to incise the transverse carpal ligament. After surgery, the best predictors of return to work and to activities of daily living were strength and tenderness variables. For patients in the device group with one affected hand, the median time for return to work was 21 1/2 days less than that for the control group. Two patients treated with the endoscopic device required reoperation by open surgical decompression; only one of these had incomplete release with the device. Two patients in the device group experienced transient ulnar neurapraxia.

Activities of Daily Living↗
PubMed1991

Experimental design for drug development: a Bayesian approach.

The Bayesian approach to inference and decision making provides an integrated way of addressing the various aspects of drug development, from the early preclinical study of compounds through the clinical and postmarketing phases. In particular, it provides a natural, convenient way for choosing among experimental designs. An essential aspect of the process of evaluating design strategies is the ability to calculate predictive probabilities of potential results. I describe a Bayesian approach to experimental design and illustrate it by considering a particular type of clinical trial. Also, I compare Bayesian and classical statistical attitudes toward design.

Bayes Theorem↗
PubMed1990

A comparison of antiarrhythmic drugs for the suppression of ventricular ectopic depolarizations: a meta-analysis.

This article reports the results of a meta-analysis of the effectiveness of antiarrhythmic drugs for the suppression of ventricular ectopic depolarizations. We analyzed 97 published articles that referred to a total of 27 drugs and contained data from 2989 patient-treatment trials; our goal was to determine the number of patients responding to therapy, defined as greater than or equal to 80% suppression of ventricular ectopic depolarizations. By means of logistic regression we tested the effect of 10 clinical and experimental variables on the likelihood of response to therapy. The likelihood of a drug response was significantly affected by the following six variables: increased by the use of dose titration (t = 3.59, p less than 0.0001), increased by the use of a higher daily dose (t = 3.21, p less than 0.0001), decreased by older age (t-2.67, p = 0.004), decreased by the use of blinding (t = -2.28, p = 0.011), increased by treating more male patients (t = 1.72, p = 0.043), and decreased by the presence of cardiovascular disease (t = -1.52, p = 0.064). Incorporating these six variables into our logistic regression model, we adjusted the response rate in each published study and calculated the mean response and standard error for each drug. Of the drugs tested in at least 100 patients, the most effective were amiodarone (estimated response rate 90%), encainide (80%), flecainide (79%), and propafenone (74%). Class IC drugs were significantly more effective than class IB and II drugs (p less than 0.05). With the exception of lorcainide and moricizine, class IC drugs were also more effective than class IA drugs (p less than 0.05). Amiodarone was significantly more effective than all drugs except encainide and flecainide (p less than 0.05). We found no significant differences among the response rates to class IA, IB, and II drugs. Whereas several patient and study characteristics affect the likelihood of response to antiarrhythmic drugs, class IC drugs and amiodarone are significantly more effective than other drugs in suppressing ventricular ectopic depolarizations.

Anti-Arrhythmia Agents↗
PubMed1989

Variability of different methods for measurement of ECG intervals and ECG interval temporal variation.

We found significant variation within each computer and cardiologist method for measurement of the ECG waveform intervals. Comparison between methods revealed that the HP system had a smaller variability than the MAC or the cardiologist, and that the MAC had a smaller variability than the cardiologist. No variability was found when a cardiologist used different paper trace speeds. Using HP measurements, we found a significant difference in ECG intervals over time, which was greater than the variability found within the method at baseline. The delineation of variability within and between ECG interval measurement methods may allow more reliable application of ECG interval changes in the therapeutic medical management of patients and prevention of side effects from drugs that affect ECG intervals. Computerized ECG waveform analysis is a widely available technology whose full role in therapeutic medical management may not be appreciated.

Adult↗
PubMed1989

The pharmacodynamic and pharmacokinetic interaction between single doses of flecainide acetate and verapamil: effects on cardiac function and drug clearance.

Flecainide and verapamil are antiarrhythmic agents that may be used in combination. We have examined their pharmacodynamic interaction by M-mode echocardiography and electrocardiography in eight normal male volunteers (24 +/- 1.8 years of age). Flecainide decreased the left ventricular ejection fraction (LVEF) (-4.4 +/- 1.2%, p less than 0.008), but verapamil did not. Neither drug affected cardiac output or vascular resistance. Both drugs increased the PR interval (12 +/- 4 msec, p less than 0.01 for flecainide; 12 +/- 5, p less than 0.04 for verapamil). Flecainide, but not verapamil, increased the QTc interval (23 +/- 8 msec, p less than 0.02). Both drugs also increased the systolic time interval ratio (PEPc/LVETc) (0.074 +/- 0.012, p less than 0.0004 for flecainide; 0.029 +/- 0.008, p less than 0.007 for verapamil). The combination of flecainide and verapamil had additive effects on myocardial contractility and on atrioventricular conduction. Verapamil slightly decreased the plasma clearance of flecainide (7.78 +/- 0.60 ml/kg/min for flecainide alone, 7.34 +/- 0.48 ml/kg/min for flecainide and verapamil together, p less than 0.05). On the other hand, flecainide had no effect on the plasma clearance of verapamil, which suggests that there was little interaction between the two drugs on their pharmacokinetic parameters.

Administration, Oral↗
PubMed1989

Monitoring accumulating data in a clinical trial.

A clinical trial is monitored for efficacy or safety; the variable of interest is death or a similarly serious event. The probability that one therapy has a greater mortality rate than the other is calculated ad libitum during the trial. Adjustments are made for differing patients' prognoses and for survival times.

Biometry↗
PubMed1988

One-sided sequential stopping boundaries for clinical trials: a decision-theoretic approach.

We address one-sided stopping rules for clinical trials, or more generally, drug development programs, from a decision-theoretic point of view. If efficacy results are sufficiently negative then the trial will be stopped. But regardless of how positive the efficacy results are, the trial will continue in order to demonstrate safety. We show how sequential decisions should be made by a pharmaceutical company attempting to maximize its expected profits.

Bayes Theorem↗
PubMed1987

Interim analyses in clinical research.

Interim analyses are those that occur before the scheduled completion of a clinical study. The motivation for such analyses may be to see whether conclusive evidence is available concerning the aims of the study, or it may be simple curiosity. Statisticians disagree about the impact that interim analyses have on inferences that can be drawn from the study. The significance testing view insists that conclusions from a study with interim analyses are different than from one without--even though the data are identical. In the Bayesian view there is no penalty for interim analyses: study results can even be monitored continually without changing the conclusions. Both views are explained and recommendations for designing and analyzing studies with interim analyses are made.

Bayes Theorem↗
PubMed1987

Logarithmic transformations in ANOVA.

A method is presented for choosing an additive constant c when transforming data x to y = log(x + c). The method preserves Type I error probability and power in ANOVA under the assumption that the x + c for some c are log-normally distributed. The method has advantages similar to those of rank transformations--namely, it is easy to use and is resistant to extreme observations. Since the special case c----infinity corresponds in ANOVA to y = x, the method is a useful generalization of least squares.

Analysis of Variance↗
PubMed1986

Synthesis of 8-amino-3-deazaguanine via imidazole precursors. Antitumor activity and inhibition of purine nucleoside phosphorylase.

8-Amino-3-deazaguanine (15), an analogue of both 3-deazaguanine (1) and 8-aminoguanine (6), an antitumor agent and a purine nucleoside phosphorylase (PNP) inhibitor, respectively, was synthesized from the ammonolysis of an imidazole precursor, methyl 2-(benzoylamino)-5-(cyanomethyl)-1H-imidazole-4-carboxylate (13). The requisite imidazole, methyl 2-(benzoylamino)-4-(methoxycarbonyl)-1H-imidazole-5-acetate (11), was prepared from the monoheterocyclic rearrangement of dimethyl 3-[(5-phenyl-1,2,4-oxadiazol-3-yl)amino]-2-pentenedioate (10) by NaH/DMF. Ammonolysis and subsequent dehydration of 11 provided the penultimate imidazole intermediate 13. Its deprotected (NaOMe/100 degrees C) product, methyl 2-amino-5-(cyanomethyl)-1H-imidazole-4-carboxylate (14), was also converted to 15. 8-Amino-3-deazaguanine, as its methanesulfonic acid (mesylate 7), exhibited an inhibition constant (IC50) of 9.9 microM against isolated mammalian PNP. It was a very weak inhibitor of T and B cell growth and did not enhance 2'-deoxyguanosine toxicity in the same cells. 8-Amino-3-deazaguanine mesylate was not significantly active in L1210 cells in vitro or L1210 leukemic mice. Thus, the amino group introduced in the 8-position of 3-deazaguanine enhances its PNP activity but diminishes its antitumor activity.

Animals↗
PubMed1986

The effects of single-dose atenolol, labetalol, and propranolol on cardiac and vascular function.

The pharmacodynamic effects of single oral doses of atenolol (100 mg), labetalol (300 mg), and propranolol (80 mg) were compared with those of placebo in a randomized, double-blind, Latin square design in 12 patients with hypertension. Atenolol and propranolol both significantly reduced cardiac output (-0.55 vs. -0.31 L/min) and heart rate (-8.0 vs. -6.6 bpm), whereas labetalol had no effect on either parameter (-0.08 L/min; + 1.0 bpm). Labetalol significantly reduced vascular resistance (-339 dynes X cm/sec5), but atenolol and propranolol did not (147 vs. 62 dynes X cm/sec5). Only labetalol significantly reduced the systolic (-15.3 mm Hg), diastolic (-11.5 mm Hg), and mean blood pressures (-12.8 mm Hg). Atenolol significantly reduced only diastolic blood pressure (-5.20 mm Hg), whereas propranolol failed to lower these parameters significantly. These data indicate that the hemodynamic profile of labetalol differs from that of selective and nonselective beta-blockers. Labetalol lowered blood pressure primarily by reducing vascular resistance, whereas reductions in heart rate and cardiac output were the predominant effects of atenolol and propranolol.

Aged↗
PubMed1985

Biochemical and antitumor activity of tiazofurin and its selenium analog (2-beta-D-ribofuranosyl-4-selenazolecarboxamide).

2-beta-D-Ribofuranosyl-4-selenazolecarboxamide (selenazofurin, CI-935), the selenium analog of tiazofurin (CI-909), was 3- to 10-fold more cytotoxic to murine or human tumor cells in vitro than tiazofurin and was also more active against P388 mouse leukemia in vivo. In vitro cytotoxicity could be reversed by guanosine or guanine but not by other purine nucleosides or bases. Three human tumor cell lines selected for selenazofurin or tiazofurin resistance showed cross resistance between selenazofurin and tiazofurin. Treatment with tiazofurin, selenazofurin, or mycophenolic acid decreased guanylate pools and caused an accumulation of IMP in WIL2 human lymphoma cells. The decrease in guanylate pools was accompanied by inhibition of RNA and DNA synthesis. The NAD analogs of tiazofurin and selenazofurin were inhibitors of L1210 IMP dehydrogenase (IMP:NAD oxidoreductase, EC 1.2.1.14), and both showed uncompetitive inhibition with respect to NAD having Kii values of 5.7 X 10(-8)M and 3.3 X 10(-8)M respectively.

Animals↗
PubMedDate not supplied

Optimal designs for clinical trials with dichotomous responses.

We consider two-stage designs for clinical trials that involve two treatments with dichotomous responses. The first is the information-gathering stage; the treatment chosen as the better from first stage and prior data is used exclusively in the second stage. Determination of treatment allocation in the first stage results from weighing the anticipated gain in information with effective treatment; the objective is to maximize the expected number of successes in the entire trial. This is in contrast to randomized controlled trials with the restricted objective of obtaining information concerning treatment differences. We allow the length of the first stage to be arbitrary and fixed in advance, or optimized as a function of prior information and the 'patient horizon'. We can regard this patient horizon as either the number of patients in the trial or the number who have the condition under treatment. We consider two forms of prior information: both success probabilities known but the better of the two treatments is unknown, and one success probability known whereas the other has an arbitrary distribution. In many instances of the latter case the optimal first stage size is of the order of the square root of the patient horizon.

Clinical Trials as Topic↗