Generalizing the standardized hazard ratio to multivariate proportional hazards regression,with an application to clinical~genomic studies

The standardized hazard ratio for univariate proportional hazards regression is generalized as a scalar to multivariate proportional hazards regression. Estimators of the standardized log hazard ratio are developed, with corrections for bias and for regression to the mean in high-dimensional analyses. Tests of point and interval null hypotheses and confidence intervals are constructed. Cohort sampling study designs, commonly used in prospective–retrospective clinical genomic studies, are accommodated.     

Utilizing Bayesian predictive power in clinical trial design

The Bayesian paradigm provides an ideal platform to update uncertainties and carry them over into the future in the presence of data. Bayesian predictive power (BPP) reflects our belief in the eventual success of a clinical trial to meet its goals. In this paper we derive mathematical expressions for the most common types of outcomes, to make the BPP accessible to practitioners, facilitate fast computations in adaptive trial design simulations that use interim futility monitoring, and propose an organized BPP-based phase II-to-phase III design framework.     

Development of predictive signatures for treatment selection in precision medicine with survival outcomes

For survival endpoints in subgroup selection, a score conversion model is often used to convert the set of biomarkers for each patient into a univariate score and using the median of the univariate scores to divide the patients into biomarker‐positive and biomarker‐negative subgroups. However, this may lead to bias in patient subgroup identification regarding the 2 issues: (1) treatment is equally effective for all patients and/or there is no subgroup difference; (2) the median value of the univariate scores as a cutoff may be inappropriate if the sizes of the 2 subgroups are differ substantially. We utilize a univariate composite score method to convert the set of patient's candidate biomarkers to a univariate response score. We propose applying the likelihood ratio test (LRT) to assess homogeneity of the sampled patients to address the first issue. In the context of identification of the subgroup of responders in adaptive design to demonstrate improvement of treatment efficacy (adaptive power), we suggest that subgroup selection is carried out if the LRT is significant. For the second issue, we utilize a likelihood‐based change‐point algorithm to find an optimal cutoff. Our simulation study shows that type I error generally is controlled, while the overall adaptive power to detect treatment effects sacrifices approximately 4.5% for the simulation designs considered by performing the LRT; furthermore, the change‐point algorithm outperforms the median cutoff considerably when the subgroup sizes differ substantially.     

Response‐adaptive designs for binary responses: How to offer patient benefit while being robust to time trends?

Response‐adaptive randomisation (RAR) can considerably improve the chances of a successful treatment outcome for patients in a clinical trial by skewing the allocation probability towards better performing treatments as data accumulates. There is considerable interest in using RAR designs in drug development for rare diseases, where traditional designs are not either feasible or ethically questionable. In this paper, we discuss and address a major criticism levelled at RAR: namely, type I error inflation due to an unknown time trend over the course of the trial. The most common cause of this phenomenon is changes in the characteristics of recruited patients—referred to as patient drift. This is a realistic concern for clinical trials in rare diseases due to their lengthly accrual rate. We compute the type I error inflation as a function of the time trend magnitude to determine in which contexts the problem is most exacerbated. We then assess the ability of different correction methods to preserve type I error in these contexts and their performance in terms of other operating characteristics, including patient benefit and power. We make recommendations as to which correction methods are most suitable in the rare disease context for several RAR rules, differentiating between the 2‐armed and the multi‐armed case. We further propose a RAR design for multi‐armed clinical trials, which is computationally efficient and robust to several time trends considered.     

The case of vegetovascular dystonia: inventing the most common Soviet disease

ABSTRACT

The paper considers the case of vegetovascular dystonia, one of the most typical and common “Soviet” diseases. This syndrome emerged in Soviet medicine after World War II, and very quickly become a popular diagnosis among physicians. The author describes how the construct of vegetovascular dystonia was formed and developed, what changes it underwent, and what affected those changes. The concept and history of vegetovascular dystonia can provide an understanding of Soviet medicine and health science in general.     

Enacting reflective and deliberative practices in action research

ABSTRACT

We consider action research as a form of deliberative policy analysis. This analysis explores a “reconstruction clinic” in which stakeholders and public officials engaged memories, hopes and obligations as they sought to resolve controversies over details of policy implementation. We ask how institutional design shaped participants’ reflective and deliberative progress. Reflection in action can prompt not only changes in cognitive frames, but new behavioural capacities for action. Deliberative practices can shape new relationships between parties through the work of apology, recognition, appreciation, and emergent collaboration.     

Integrating self-care into clinical practice with trauma clients

ABSTRACT

Self-care is recognized as an important aspect of social work practice. Beginning in educational settings, developing social workers are encouraged to learn about and practice self-care. However, self-care is typically promoted through strategies and approaches outside of the practice context. Social workers are oftentimes encouraged to use individualized self-care plans, which often feature a variety of relaxation and secondary techniques; focus on self-awareness and self-reflection; and have proper use of supervision. Although these strategies are invaluable, they do little to directly benefit the social worker during direct practice or while in session with a client which is a time period when clinicians are particularly vulnerable to distress or burnout. The importance of real-time self-care strategies is particularly critical for clinicians, especially those who engage in trauma work, given the sensitivity of topics that clients may have endured or benefit from assistance in processing. Further, little information has been published on the use of self-care techniques during a session with a client or in a clinical context. The purpose of the present paper is to discuss self-care strategies that can be useful both outside of and within a clinical setting and present a model of such strategies that focus on integrating self-care in clinical practice particularly for those engaging in trauma work. The paper will conclude by discussing the relevancy of the developed model in practice.     

Adaptive designs for single‐arm phase II trials in oncology

Clinical phase II trials in oncology are conducted to determine whether the activity of a new anticancer treatment is promising enough to merit further investigation. Two‐stage designs are commonly used for this situation to allow for early termination. Designs proposed in the literature so far have the common drawback that the sample sizes for the two stages have to be specified in the protocol and have to be adhered to strictly during the course of the trial. As a consequence, designs that allow a higher extent of flexibility are desirable. In this article, we propose a new adaptive method that allows an arbitrary modification of the sample size of the second stage using the results of the interim analysis or external information while controlling the type I error rate. If the sample size is not changed during the trial, the proposed design shows very similar characteristics to the optimal two‐stage design proposed by Chang et al. (Biometrics 1987; 43:865–874). However, the new design allows the use of mid‐course information for the planning of the second stage, thus meeting practical requirements when performing clinical phase II trials in oncology. Copyright © 2012 John Wiley & Sons, Ltd.     

Cognitive-Behavioral Therapy for Bipolar Disorder: Implications for Clinical Social Workers

ABSTRACT

The purposes of this review article are to orient clinical social workers to cognitive-behavioral theory, intervention, and research on bipolar disorder (BD); identify pros and cons of applying cognitive-behavioral therapy (CBT) to social work clients with BD; and identify specific implications for clinical social work practice. Of the 545 articles that were obtained via the systematic review, 18 studies were identified as being potentially eligible for inclusion, and 9 of those studies ultimately satisfied the inclusion criteria. The results of each study were summarized via identifying statistically significant (p< .05) differences that existed between experimental cohorts who received CBT (plus pharmacotherapy) and control cohorts who received treatment as usual. Outcomes showed CBT cohorts as having significant improvement over their respective control groups. The review's implications for clinical social workers and the need for future research are discussed.     

东晋南朝医学知识的新发展:以医家、病者为中心的研究

本文以医家、病者为中心,结合医籍的相关叙述,来探讨东晋南朝医学知识的新发展。文中分析指出,此时期医家与病者多数都是出自社会地位较高的士大夫阶层。作为病者,他们世代内部通婚,过度优逸,嗜好饮酒,易受精神刺激,早婚多妾侍,多种因素导致了体貌柔弱,不堪劳作。显现于医学典籍,则是许多医方以体质偏虚之人为预设目标。而又作为医家的他们,传习家学,博通医术,或由信仰之故,兼修岐黄,这促使医界病源学理盛行以及佛道知识常被引入医书。综合诸历史迹象,作者认为东晋南朝医学知识有显著的贵胜特点。