Future studies are necessary to further explore these associations. Collaboration between basic science and clinical investigators is essential with team-based research as a model. A dose-response effect may be observed between the causal agent and the outcome, and there should also be biologic plausibility for the association, with a specific cause-and-effect relationship. They determined that chronic ethanol ingestion in rats renders the lung susceptible to endotoxin-mediated edematous injury (figure 9) [13]. Observed associations may actually be (either completely or in part) due to one or more other factors that had been unrecognized. The Meaning of Translational Research and Why It Matters.
The application of findings derived in basic science to the development of new understanding of disease mechanisms, diagnoses, and therapeutics in humans is known as translational research [1]. In 2000, we reported that individuals with a positive history of chronic alcohol abuse have decreased concentrations of GSH in the epithelial lining fluid of the lung, similar to what was observed in the animal model (figure 10) [14]. Unfortunately, not all risk factors for clinically relevant outcomes fit into a nice package, as no factor is purely genetic, acquired, or related to the acute illness.
The relative risk of death from a variety of causes was increased in the adopted children whose biological parents had died at an early age, thus suggesting a potential genetic etiology of the increased risk of premature death.
Get free access to newly published articles. Work by Nuckton and colleagues highlights an example of a component of acute illness correlating with outcome [9].
As an example, glutathione replacement therapy may only work for ARDS patients with pre-existing glutathione deficiency, such as in a patient with a history of chronic alcohol abuse. document.write(new Date().getFullYear())
However heterogeneity may be problematic when evaluating specific therapies for ICU patients.
Performance of successful translational research is highly dependent on an investigator's environment, as evidenced by the examples cited in this monograph.
By Ellen L. Burnham, MD and Marc Moss, MD. The magnitude of the effect of body position on the development of VAP was stratified based on the presence or absence of enteral feeding. By 2012, the NIH expects to fund 60 such centers with a budget of $500
The next step in examining a hypothesis is to determine how significant an association may be using Bradford-Hill criteria. Biological plausibility for hypotheses in these types of epidemiological studies arises from critical reading of a publication or careful data examination. sign up for alerts, and more, to access your subscriptions, sign up for alerts, and more, to download free article PDFs, sign up for alerts, customize your interests, and more, to make a comment, download free article PDFs, sign up for alerts and more, Archives of Neurology & Psychiatry (1919-1959), JAMAevidence: The Rational Clinical Examination, JAMAevidence: Users' Guides to Medical Literature, FDA Approval and Regulation of Pharmaceuticals, 1983-2018, Global Burden of Skin Diseases, 1990-2017, Health Care Spending in the US and Other High-Income Countries, Life Expectancy and Mortality Rates in the United States, 1959-2017, Medical Marketing in the United States, 1997-2016, Practices to Foster Physician Presence and Connection With Patients in the Clinical Encounter, US Burden of Cardiovascular Disease, 1990-2016, Waste in the US Health Care System: Estimated Costs and Potential for Savings, Register for email alerts with links to free full-text articles. These investigators examined the first part of this proposed mechanism in the animal model, reporting that ethanol-fed rats have significantly decreased glutathione concentrations in lung tissue, lung lavage fluid, and alveolar type II cells. American Thoracic Society, all rights reserved. More generally speaking, it is the movement of ideas from the basic science laboratory to the clinical arena. An example from the recent literature is the relationship between body position (the primary exposure) and the incidence of ventilator-associated pneumonia (the outcome variable) [12]. Customize your JAMA Network experience by selecting one or more topics from the list below. Translational research – a term often used interchangeably with translational medicine or translational science or bench to bedside – is an effort to build on basic scientific research to create new therapies, medical procedures, or diagnostics. Translational research seeks to produce more meaningful, applicable results that directly benefit human health. Our website uses cookies to enhance your experience.
Terms of Use| Another model for translational research is bi-directional, where ideas flow from the bedside to the bench and back again. Additionally, there has been increased funding and visibility of general clinical research centers. The authors reported a decreased frequency of ventilator-associated pneumonia in a semi-recumbent patient position (8%) than in a supine position (34%); however, the presence of enteral feedings was demonstrated to be an effect modifier. Once a clinically important association has been identified, translation to the basic science laboratory is often necessary to determine the actual causal pathway or mechanism. For example, whether or not a consultant intensivist supervises patient care in the ICU has an impact on both ICU and overall hospital mortality [10]. Our confounding variable of concern is smoking. Although the association of patient positioning and the development of ventilator-associated pneumonia were still evident in patients not receiving enteral nutrition, it is much greater in those who are (figure 8).
Author Affiliation: Departments of Family Medicine and Epidemiology and Community Health, Virginia Commonwealth University, Richmond.
© 2020 American Medical Association. By some accounts, translational research has become a centerpiece of the European Commission's €6 Initially, studies are necessary to determine whether findings in animal models actually apply to true human disease states.
For example, if regular physical activity is being examined in relationship to cardiovascular disease, one might not include HDL levels in the multivariable analysis because the effect of exercise on HDL levels may be the mechanism by which physical activity limits the cardiovascular disease, thus masking the effects of a sedentary life style on cardiovascular disease. The stronger an association, the more likely it is to be causal, and associations that are consistently reported in the literature are more likely to be causal.
Founded in 1905 to combat TB, the ATS has grown to tackle asthma, COPD, lung cancer, sepsis, acute respiratory distress, and sleep apnea, among other diseases. Examples include activated protein C for severely septic patients, or a low tidal volume ventilation strategy for ARDS patients. As illustrated in figure 6, an exposure is identified that is believed to be associated with a specific outcome.
All Rights Reserved, 2008;299(2):211-213. doi:10.1001/jama.2007.26, Challenges in Clinical Electrocardiography, Clinical Implications of Basic Neuroscience, Health Care Economics, Insurance, Payment, Scientific Discovery and the Future of Medicine, United States Preventive Services Task Force. In summary, heterogeneity in the incidence of ARDS due to chronic alcohol abuse was initially observed in a clinical sample of patients with ARDS. This was consistent with our clinical epidemiological studies. The National Institutes of Health (NIH) has made translational research a priority, forming centers of translational research at its institutes and launching the Clinical and Translational Science Award (CTSA) program in 2006. Moss and colleagues have reported that a prior history of alcohol abuse, an acquired risk factor, is associated with an increased incidence and severity of ARDS [8]. Additionally, patient-oriented research applications in NIH study sections receive poorer priority scores and funding rates when compared to basic science research applications, especially when these applications are assigned to study sections unfamiliar with reviewing clinical science [2]. In this study ARDS mortality increased in a "dose-dependent" fashion with the dead-space fraction.
Patient heterogeneity may account for some of the disappointing results of clinical trials for ICU patients, as some therapies may only benefit a specific sub-group of ICU patients. Accessibility Statement. © 1998 - Glutathione deficiency was proposed as a mechanism to account for these findings through its effects on surfactant secretion, apoptosis, and alveolar epithelial fluid transport, leading to increased susceptibility for ARDS. With the development of diverse new technologies, remarkable advances have occurred in the understanding of the molecular and genetic bases of disease.
Similarly, anti-TNF antibodies may only be benefit septic patients who are TNF hypersecretors based on genetic polymorphisms, and might be harmful for those septic patients who are TNF hyposecretors. By continuing to use our site, or clicking "Continue," you are agreeing to our, 2020 American Medical Association. Obviously, many more cases of lung cancer are present in the smoking individuals compared to the non-smokers. Some investigators have recommended new definitions of ICU syndromes based on biochemical criteria of inflammation, rather than clinical parameters to direct therapies at specific inflammatory components. Epidemiological studies can also be analytical, where determinants of variability in a disease are sought. Both the children's biological and adoptive parents were identified. They are often purely descriptive and useful in public health issues or resource allocation. The American Thoracic Society improves global health by advancing research, patient care, and public health in pulmonary disease, critical illness, and sleep disorders.
Potential confounding variables can be identified by careful examination of the literature. AMERICAN THORACIC SOCIETY 25 Broadway New York, NY 10004 United States of America Phone: +1 (212) 315-8600 Fax: +1 (212) 315-6498 Email: atsinfo@thoracic.org. but it seems important to almost everyone. Although the number of investigators performing patient-oriented translational research is small, these individuals are vital to the future of medicine. Over 70 such federally-funded facilities currently exist across the US that provide inpatient and outpatient facilities and several core laboratory facilities. Training of future translational scientists will require a broad-based curriculum that includes molecular biology and genetic techniques, epidemiology and biostatistics, and clinical trial design and implementation . With large samples (databases), some factors such as race, gender, and age should be examined as potential confounding variables. million per year.1
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