The Translation Evidence Mechanism. The Compact between Researcher and Clinician.

Currently, best evidence is a concentrated effort by researchers. Researchers produce information and expect that clinicians will implement their advances in improving patient care. However, difficulties exist in maximizing cooperation and coordination between the producers, facilitators, and users (patients) of best evidence outcomes. The Translational Evidence Mechanism is introduced to overcome these difficulties by forming a compact between researcher, clinician and patient. With this compact, best evidence may become an integral part of private practice when uncertainties arise in patient health status, treatments, and therapies. The mechanism is composed of an organization, central database, and decision algorithm. Communication between the translational evidence organization, clinicians and patients is through the electronic chart. Through the chart, clinical inquiries are made, patient data from provider assessments and practice cost schedules are collected and encrypted (HIPAA standards), then inputted into the central database. Outputs are made within a timeframe suitable to private practice and patient flow. The output consists of a clinical practice guideline that responds to the clinical inquiry with decision, utility and cost data (based on the "average patient") for shared decision-making within informed consent. This shared decision-making allows for patients to "game" treatment scenarios using personal choice inputs. Accompanying the clinical practice guideline is a decision analysis that explains the optimized clinical decision. The resultant clinical decision is returned to the central database using the clinical practice guideline. The result is subsequently used to update current best evidence, indicate the need for new evidence, and analyze the changes made in best evidence implementation. When updates in knowledge occur, these are transmitted to the provider as alerts or flags through patient charts and other communication modalities

The Molecular Immunology of Mucositis: Implications for Evidence-Based Research in Alternative and Complementary Palliative Treatments

The terms ‘mucositis’ and ‘stomatitis’ are often used interchangeably. Mucositis, however, pertains to pharyngeal-esophago-gastrointestinal inflammation that manifests as red, burn-like sores or ulcerations throughout the mouth. Stomatitis is an inflammation of the oral tissues proper, which can present with or without sores, and is made worse by poor dental hygiene. Mucositis is observed in a variety of immunosuppressed patients, but is most often consequential to cancer therapy. It appears as early as the third day of intervention, and is usually established by Day 7 of treatment. Mucositis increases mortality and morbidity and contributes to rising health care costs. The precise immune components involved in the etiology of mucositis are unclear, but evidence-based research (EBR) data has shown that applications of granulocyte–macrophage-colony stimulating factor prevent the onset or the exacerbation of oropharyngeal mucositis. The molecular implications of this observation are discussed from the perspective of future developments of complementary and alternative treatments for this condition. It must be emphasized that this article is meant to be neither a review on mucositis and the various treatments for it, nor a discussion paper on its underlying molecular immunology. It is a statement of the implications of EBR for CAM-based interventions for mucositis. It explores and discusses the specific domain of molecular immunology in the context of mucositis and its direct implications for EBR research in CAM-based treatments for mucositis

Dissemination of evidence-based standards of care.

Standards of care pertain to crafting and implementing patient-centered treatment interventions. Standards of care must take into consideration the patient's gender, ethnicity, medical and dental history, insurance coverage (or socioeconomic level, if a private patient), and the timeliness of the targeted scientific evidence. This resolves into a process by which clinical decision-making about the optimal patient-centered treatment relies on the best available research evidence, and all other necessary inputs and factors to provide the best possible treatment. Standards of care must be evidence-based, and not merely based on the evidence - the dichotomy being critical in contemporary health services research and practice. Evidence-based standards of care must rest on the best available evidence that emerges from a concerted hypothesis-driven process of research synthesis and meta-analysis. Health information technology needs to become an every-day reality in health services research and practice to ensure evidence-based standards of care. Current trends indicate that user-friendly methodologies, for the dissemination of evidence-based standards of care, must be developed, tested and distributed. They should include approaches for the quantification and analysis of the textual content of systematic reviews and of their summaries in the form of critical reviews and lay-language summaries

Salivary biomarkers in psychobiological medicine.

The value of salivary biomarkers for diagnostic and prognostic assessments has become increasingly well established in medicine, pharmacology, and dentistry. Certain salivary components mirror the neuro-endocrine status of the organism. Other saliva products are protein in nature, and can serve to reflect immune surveillance processes. The autonomic nervous system regulates the process of salivation, and the concentration of yet other salivary components, such as alpha-amylase, which provide a reliable outcome measure of the sympathetic response. Here, we discuss molecular technologies that have permitted giant steps in the utilization of salivary samples and micro-fluidics for the benefit of diagnostic medicine and dentistry, and their putative role in springing forward research in psychobiology

Biomarkers for early detection of high risk cancers: From gliomas to nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NpC) is a malignant disease associated with Epstein-Barr virus infection, and often diagnosed at an advanced stage. This significantly curtails patient survival. We hypothesize that a panel of biomarkers can be assembled to assess NpC incidence, early detection, and tumor progression during therapeutic intervention. Our thesis rests on a model of successfully predicting high-risk gliomas by means of a carefully crafted panel of molecular mitotic biomarkers (i.e., securin, survivin and MCM2). The strategy we propose holds strong promise for prevention and cure of NpC. The approach we propose seeks to identify certain biomarkers from viral materials, patient tissues and assessment of related diseases, whose signatures, taken together, will be endowed with some degree of congruency, or sense of a coordinated language (i.e., “votes”). Biomarker “voting” will then permit to outline a broad coordinated molecular map for the molecular and epigenetic characterization of each individual patient's NpC tumor. We will draw on the process of contrasting biomarkers in health and disease, which rests on the auto-proteomic concept particularly relevant in high-risk cancer individuals, such as is the case for NpC. In brief we defend, current advances in human proteome profiling proffers the possibility of having individual baseline proteomic profiles using local body fluids (e.g., saliva, nasal secretions, sputum) or systemic fluids (e.g., plasma, serum, cerebrospinal fluid) to unravel a personalized molecular map for high-risk NpC individuals. Regular check-up will monitor for new or impending manifestations of NpC, and provide a secure assessment of incidence and early detection

Epigenetic regulation of osteogenesis: human embryonic palatal mesenchymal cells.

Mesenchymal stem cells (MSCs) provide an appropriate model to study epigenetic changes during osteogenesis and bone regeneration due to their differentiation potential. Since there are no unique markers for MSCs, methods of identification are limited. The complex morphology of human embryonic palatal mesenchyme stem cell (HEPM) requires analysis of fractal dimensions to provide an objective quantification of self-similarity, a statistical transformation of cellular shape and border complexity. We propose the hypothesis of a study to compare and contrast sequential steps of osteogenic differentiation in HEPMs both phenotypically using immunocytochemistry, and morphometrically using fractal analysis from undifferentiated passage 1 (P1) to passage 7 (P7) cells. The proof-of-concept is provided by results we present here that identify and compare the modulation of expression of certain epigenetic biomarkers (alkaline phosphatase, ALP; stromal interaction molecule-1, STRO-1; runt-related transcription factor-2, RUNX2), which are established markers of osteogenesis in bone marrow studies, of osteoblastic/skeletal morphogenesis, and of osteoblast maturation. We show that Osteoinductive medium (OIM) modulates the rate of differentiation of HEPM into Run-2+ cells, the most differentiated subpopulation, followed by ALP+ and STRO-1+ cells. Taken together, our phenotypical and morphometric data demonstrate the feasibility of using HEPM to assess osteogenic differentiation from an early undifferentiated to a differentiated stage. This research model may lay the foundation for future studies aimed at characterizing the epigenetic characteristics of osteoimmunological disorders and dysfunctions (e.g., osteoarthritis, temporomandibular joint disorders), so that proteomic profiling can aid the diagnosis and monitor the prognosis of these and other osteoimmunopathologies

Transforming scientific evidence into better consumer choices

Translational research using evidence-based and comparative effectiveness research continues to evolve, becoming a useful tool in improving informed consent and decision-making in the clinical setting. While in development, emerging technologies, including cellular and molecular biology, are leading to establishing evidence-based dental practices. One emerging technology, which conjoins bench proteomic findings to clinical decision-making for treatment intervention, is the Translational Evidence Mechanism. This mechanism was developed to be a foundation for a compact between researcher, translational researcher, clinician, and patient. The output of such a mechanism is the clinical practice guideline (CPG), an interactive tool for dentists and patients to game evidence in reaching optimum clinical decisions that correspond to individual patient preferences and values. As such, the clinical practice guideline requires the vesting of decision, utility, and cost best evidence. Evidence-based research provides decision data, a first attempt at supporting decision-making by providing best outcome data. Since then comparative effectiveness research has emerged, using systematic review analysis to compare similar treatments or procedures in maximizing the choice of the most effective cost/benefit option within the context of best evidence. With innovation in the clinical practice guideline for optimizing efficacy and comparative effectiveness research, evidence-based practices will shape a new approach to health-based systems that adhere to shared decision-making between bench scientists, healthcare providers and patients

Transitioning Toward Evidence-Based Research in the Health Sciences for the XXI Century

This article discusses some of the misconceptions of evidence-based research in the health sciences. It proposes that since not all treatments in medicine and dentistry can be evidence-based, clinical applications of the evidence-based process should become a specialty. The case is particularly evident in dentistry. Therefore dentistry is taken in this article as a model for discussion. We propose that to approach dentistry from the viewpoint of the patient-oriented evidence that matters (POEM) is perfectly acceptable so far as we also engage in the process of research evaluation and appraisal in dentistry (READ). We distinguish between dentistry based on the evidence, and evidence-based dentistry. We argue that when invoking an evidence-based approach to dentistry or medicine, it is not sufficient to establish the ‘levels of evidence’, but rather that all evidence-based clinical intervention must undergo the stringent process of evidence-based research so that clinical practice guidelines be revised based on the best available evidence

LCK, survivin and PI-3K in the molecular biomarker profiling of oral lichen planus and oral squamous cell carcinoma.

T cell signaling is critical in oral lichen planus (OLP) based on the pathogenesis of this chronic inflammatory autoimmune mucocutaneous lesion. Lck plays a key role in T cell signaling; ultimately this signaling affects other targets such as PI-3K. Excessive activity in PI-3K inhibits apoptosis and promotes uncontrolled cell growth. Molecular biomarker profiling in OLP, Chronic Interface Mucosities (CIM), Epithelial Dysplasia (EpD) and Oral Squamous Cell Carcinoma (SCCA) with application of the principle of biomarker voting may represent a new frontier in the diagnosis, assessment and the arguable debate of OLP transformation to cancer. The presence of Lck, PI-3K and Survivin, a cancer specific anti-apoptotic protein was assessed, using immunohistochemistry and tissue micro-array on patient samples, in OLP, SCCA, CIM and EpD. Lck expression was very high in 78.6 % of OLP patients compared to 3.7% in SCCA; PI-3K was high in 63% of SCCA, 100% of EpD, and 35.7% OLP cases. Survivin was high in 64.3% of OLP cases, 96.3% of SCCA, and 100% of EpD. CIM cases may be slightly different molecularly to OLP. Taken together, our data suggest that biomarker protein voting can be effectively used to isolate high-risk OLP cases. Specifically, we show data with four remarkable cases demonstrating that molecular factors are predictive of histopathology. We conclude that it is safer to treat OLP as premalignant lesions, to adopt aggressive treatment measure in histopathologic described well and moderately differentiated SCCA, and to monitor progress of these diseases molecularly using individualized auto-proteomic approach. The use of Lck inhibitors in OLP management needs to be investigated in the future