The current state of translational science and comparative effectiveness research (CER) faces inherent barriers to accuracy, which can compromise the integrity of the study. Design flaws such as information bias, inferential bias, selection bias, and reporting quality of trials require careful assessment in order to appropriately compare and contrast evidence in pursuit of the best evidence base (BEB). Here, we describe a novel research design, the Cluster Randomized Stepped Wedge Blinded Controlled Trials (CRSWBCT), which consists of a type of pragmatic trial that attempts to minimize these biases by implicating a system in which each unit of study acts as both the experimental group and control group. The CRSWBCT design has an inherent ability to enhance statistical stringency by minimizing risk of bias, and, in contrast to the traditional parallel, run-in, or cross -over trials, preserves ethical equipoise. In the CRSWBCT, all the clusters begin the study in the placebo-control, and roll-out into the experimental treatment group in a systematic, sequential fashion that retains the stringency of random double- blind protocol. CRSWBCT, while more complex in terms of power and statistical inference, has greater validity and is the preferred design with respect to ethical, logistical, and financial considerations over traditional simpler trials for the modern and contemporary pursuit of patient-centered outcomes research and individual patient data collection and analysis. In the context of CER, the adoption of CRSWBCT requires a revision of the CONSORT10 checklist (e.g., CONSORT10-R) to evaluate the evidence base obtained by the CRSWBCT design.

A cluster randomized controlled trial (CRCT) is a type of randomized controlled trial in which groups of subjects (as opposed to individual subjects) are randomized. In this paper, we discuss the fundamentals of CRCT, its statistical power, and the implications of this design in context of comparative effectiveness and patient-centered research. We propose that, whereas CRCT pertain more specifically to effectiveness-driven decisions in health care, better informed patient-centered clinical decisions about comparative efficacy for evidence-based dental practice result from traditional RCT’s.

Toward revitalizing the Nation’s primary medical care system, the Agency for Health Research & Quality (AHRQ) stated that new foundational measures must be crafted for achieving high-quality, accessible, efficient health care for all Americans. The efficiency of medical care is viewed along two dimensions: first, we must continue to pursue translational research; and second, we must translate research to optimize effectiveness in specific clinical settings. It is increasingly evident that the efficiency of both translational processes is critical to the revitalization of health care, and that it rests on the practical functionality of the nexus among three cardinal entities: the researcher, the clinician, and the patient. A novel model has evolved that encapsulates this notion, and that proposes the advanced pri-mary care “medical home”, more commonly referred to as the “patient-centered medical home” (PCMH). It is a promising model for transforming the organization and delivery of primary medical care, because it is not simply a place per se, but it is a function-ing unit that delivers medical care along the fundamental principles of being patient-centered, comprehensive, coordinated, and accessible. It is energized by translational research, and its principal aim and ultimate goal is translational effectiveness. The PCMH is a model that works well within the priorities set by the American Recovery and Reinvestment Act of 2009, and the Health Care Reform Act of 2010. However, while dentistry has a clearly defined place in both Acts, the PCMH is designed for medical and nursing care. A parallel model of the “patient-centered dental home” (PCDH) must be realized.

Several techniques exist for the surgical placement of dental implants. The aim of this study was to assess systematically, the efficacy of these protocols by the evidence-based perspective. Five best-case studies involving 607 early/immediately loaded implants and 300 conventionally loaded implants were identified by examining the available literature and rigorous inclusion/exclusion criteria. Overall analyses demonstrated a 98.4 percent success rate for the early/immediate procedure and a 95.3 percent for the conventional protocol. Success rates in the articles reviewed were based on implant survival over a follow-up period of between one to two years. A meta-analysis was generated to evaluate the presented evidence and to aid in decision-making. Despite its common implementation, this technique presents many caveats, among which publication bias is one of the most common. To investigate the possible presence of publication bias, a funnel plot analysis complemented several statistical tests. By means of the systematic investigation of dental implants, the authors' results confirm the presence of publication bias in implant dentistry literature, which strongly suggests that clinicians ought not base their decisions solely on the results presented by a few published studies. Rather, it is recommended that clinicians cautiously draw conclusions and seek studies that present accountable and clinically relevant results. Furthermore, it is suggested that clinicians attend seminars to learn of the effective advances in evidence-based dentistry, so as to develop the ability to easily detect inadequate literature due to attempted correlation with the most current research. It is also recommended that additional research is necessary to analyze which fields of research are more prone to bias, thus forewarning clinicians before formulating clinical conclusions.

As a model for Neuropsychiatric dysfunction in NeuroAIDS due to HIV-1 infection and drug abuse, we analyzed gene expression in human neurons treated with cocaine and HIV-1 proteins tat and envelope (env). One-way ANOVA showed statistically significant genes among the treatment groups (p < or = 0.0005). The identified genes were then subjected to a "stepwise" analysis using a repeated measures ANOVA to discover genes with parallel response group profiles across the treatment conditions. These groups were then analyzed using a repeated measures ANOVA to assess treatment main effects and gene-by-treatment interactions within groups. One-way ANOVA produced 35 genes that were significantly associated across all treatment conditions. Factorial analysis of each gene found statistically significant differences: 30--tat, 17--cocaine, 10--env, 6--tat/env, 6--coc/env, and 4--coc/tat. Analyses across genes found three sets of four genes, one set of three genes, and three sets of two genes with parallel profiles. Identified genes had functions included signaling, immune related, and transcription control. The genes were not stochastically arranged on the chromosomes, were in proximity to each other, and to other genes involved in neuropsychiatric diseases. We hypothesize that these genes fall in transcriptionally isolated groups and that abused drugs and HIV-1 proteins trigger transcription overload, coerced expression that may result in damage to the chromosome's control and organization of chromatin transcription machinery.

Co-use of illicit drugs, in particular cocaine and alcohol, is common among HIV-1(+) men and women of different ethnic groups. We compared cohorts of alcohol and cocaine co-users HIV-1(+) African American women and in cohorts of drug-free, or methamphetamine users HIV-1(+) men. We monitored clinical cellular immune parameters at repeated regular intervals. We found that significant inverse correlations between (CD8+)CD38+ cells and subpopulations of CD4+ cells distinguished by the expression of CD45RA in HIV-1(+) alcohol and cocaine co- users but not in drug-free HIV-1(+) patients. Following stratification for CD4+ cell number, we found the (CD4+)CD45RA+ subpopulation to be significantly higher (p < 0.05) in the drug user compared to drug-free HIV-1(+). Drug abuse may alter the change from the (CD4+)CD45RA+ to the (CD4+)CD45RA- phenotype selectively, which recovers in HIV-1+ methamphetamine abusers during treatment from baseline to 4-weeks, as manifested by improved IL-2 production in vitro. of TH1 and TH2 cytokines during progression to AIDS.