Computerized prescribing alerts and group academic detailing to reduce the use of potentially inappropriate medications in older people

OBJECTIVES: To examine the effect of replacing drug-specific computerized prescribing alerts with age-specific alerts on rates of dispensing potentially inappropriate medications in older people and to determine whether group academic detailing enhances the effectiveness of these alerts. DESIGN: Cluster-randomized trial of group academic detailing and interrupted time-series analysis. SETTING: Fifteen clinics of a staff-model health maintenance organization. PARTICIPANTS: Seven practices (113 clinicians, 24,119 patients) were randomly assigned to receive age-specific prescribing alerts plus the academic detailing intervention; eight practices (126 clinicians, 26,805 patients) received alerts alone. Prior implementation of drug-specific alerts established a downward trend in use of target medications that served as the baseline trend for the present study. INTERVENTION: The computerized age-specific alerts occurred at the time of prescribing a targeted potentially inappropriate medication (e.g., tertiary tricyclic amine antidepressants, long-acting benzodiazepines, propoxyphene) and suggested an alternative medication. Clinicians at seven sites were randomized to group academic detailing, an interactive educational program delivering evidence-based information. MEASUREMENTS: Number of target medications dispensed per 10,000 patients per quarter, 2 years before and 1.5 years after the replacement of drug-specific with age-specific alerts. RESULTS: Age-specific alerts resulted in a continuation of the effects of the drug-specific alerts without measurable additional effect (P=.75 for level change), but the age-specific alerts led to fewer false-positive alerts for clinicians. Group academic detailing did not enhance the effect of the alerts. CONCLUSION: Age-specific alerts sustained the effectiveness of drug-specific alerts to reduce potentially inappropriate prescribing in older people and resulted in a considerably decreased burden of the alerts.     

To add or not to add a new treatment arm to a multiarm study: A decision-theoretic framework

Multiarm clinical trials, which compare several experimental treatments against control, are frequently recommended due to their efficiency gain. In practise, all potential treatments may not be ready to be tested in a phase II/III trial at the same time. It has become appealing to allow new treatment arms to be added into on-going clinical trials using a “platform” trial approach. To the best of our knowledge, many aspects of when to add arms to an existing trial have not been explored in the literature. Most works on adding arm(s) assume that a new arm is opened whenever a new treatment becomes available. This strategy may prolong the overall duration of a study or cause reduction in marginal power for each hypothesis if the adaptation is not well accommodated. Within a two-stage trial setting, we propose a decision-theoretic framework to investigate when to add or not to add a new treatment arm based on the observed stage one treatment responses. To account for different prospect of multiarm studies, we define utility in two different ways; one for a trial that aims to maximise the number of rejected hypotheses; the other for a trial that would declare a success when at least one hypothesis is rejected from the study. Our framework shows that it is not always optimal to add a new treatment arm to an existing trial. We illustrate a case study by considering a completed trial on knee osteoarthritis.     

基于CNFET的三值逐次逼近ADC设计

模数转换器(Analog-to-Digital Converter,ADC)是片上集成系统的关键部件,通过对逐次逼近逻辑电路和三值逻辑原理的研究,提出了一种基于碳纳米场效应晶体管(Carbon Nanotube Field Effect Transistor,CNFET)的三值逐次逼近ADC设计方案。该方案首先控制三值电容阵列的底板电压,逐次逼近其模拟量值,产生由高位到低位的二值信号,然后由编码器将二值转换为三值信号,完成整个转换过程,最后实验证明了所设计的电路逻辑功能正确,并具有明显的高速、低功耗特性。     

高校学术期刊数字化平台全面应用与建设策略的思考

本研究旨在探讨高校科技期刊如何在了解自身需求的基础上,去认识、利用、开发数字化平台,从而更有效的促进期刊内容快速的传播、推进期刊编辑部的办公流程、获取与分享期刊信息与资源,从而整体提高高校学术期刊的学术水平和出版质量。     

Use of three‐dimensional power doppler sonography in the diagnosis of uterine arteriovenous malformation and follow‐up after uterine artery embolization: Case report and brief review of literature

Arteriovenous malformations (AVM) of the uterus can cause life‐threatening hemorrhage. Unexplained, heavy vaginal bleeding in a reproductive age woman should raise suspicion for an AVM. Here a 37‐year‐old woman had increasingly severe vaginal bleeding for 15 days. Serum β‐hCG was elevated. Two‐dimensional transvaginal ultrasound suggested retained products of conception. Before dilation and curettage (D&C), color Doppler and three‐dimensional (3D) power Doppler demonstrated findings indicative of uterine AVM. A bilateral uterine artery embolization was performed without complications. Three months after uterine artery embolization, 3D power Doppler ultrasonography found complete resolution of the AVM. This case illustrates the importance of assessing both gray‐scale and 3D power Doppler, and the ability of postprocedure Doppler to assess resolution. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 43:327–334, 2015     

Bayesian probability of success for clinical trials using historical data

Developing sophisticated statistical methods for go/no‐go decisions is crucial for clinical trials, as planning phase III or phase IV trials is costly and time consuming. In this paper, we develop a novel Bayesian methodology for determining the probability of success of a treatment regimen on the basis of the current data of a given trial. We introduce a new criterion for calculating the probability of success that allows for inclusion of covariates as well as allowing for historical data based on the treatment regimen, and patient characteristics. A new class of prior distributions and covariate distributions is developed to achieve this goal. The methodology is quite general and can be used with univariate or multivariate continuous or discrete data, and it generalizes Chuang‐Stein's work. This methodology will be invaluable for informing the scientist on the likelihood of success of the compound, while including the information of covariates for patient characteristics in the trial population for planning future pre‐market or post‐market trials. Copyright © 2014 John Wiley & Sons, Ltd.     

A power series beta Weibull regression model for predicting breast carcinoma

The postmastectomy survival rates are often based on previous outcomes of large numbers of women who had a disease, but they do not accurately predict what will happen in any particular patient's case. Pathologic explanatory variables such as disease multifocality, tumor size, tumor grade, lymphovascular invasion, and enhanced lymph node staining are prognostically significant to predict these survival rates. We propose a new cure rate survival regression model for predicting breast carcinoma survival in women who underwent mastectomy. We assume that the unknown number of competing causes that can influence the survival time is given by a power series distribution and that the time of the tumor cells left active after the mastectomy for metastasizing follows the beta Weibull distribution. The new compounding regression model includes as special cases several well‐known cure rate models discussed in the literature. The model parameters are estimated by maximum likelihood. Further, for different parameter settings, sample sizes, and censoring percentages, some simulations are performed. We derive the appropriate matrices for assessing local influences on the parameter estimates under different perturbation schemes and present some ways to assess local influences. The potentiality of the new regression model to predict accurately breast carcinoma mortality is illustrated by means of real data. Copyright © 2015 John Wiley & Sons, Ltd.     

On generalized fixed sequence procedures for controlling the FWER

Testing a sequence of pre‐ordered hypotheses to decide which of these can be rejected or accepted while controlling the familywise error rate (FWER) is of importance in many scientific studies such as clinical trials. In this paper, we first introduce a generalized fixed sequence procedure whose critical values are defined by using a function of the numbers of rejections and acceptances, and which allows follow‐up hypotheses to be tested even if some earlier hypotheses are not rejected. We then construct the least favorable configuration for this generalized fixed sequence procedure and present a sufficient condition for the FWER control under arbitrary dependence. Based on the condition, we develop three new generalized fixed sequence procedures controlling the FWER under arbitrary dependence. We also prove that each generalized fixed sequence procedure can be described as a specific closed testing procedure. Through simulation studies and a clinical trial example, we compare the power performance of these proposed procedures with those of the existing FWER controlling procedures. Finally, when the pairwise joint distributions of the true null p‐values are known, we further improve these procedures by incorporating pairwise correlation information while maintaining the control of the FWER. Copyright © 2015 John Wiley & Sons, Ltd.