| Specific Aim
The specific aim of this training program is to provide post-doctoral fellows (Trainees) with research training in the basic sciences relevant to unsolved problems in the treatment of various cardiopulmonary insufficiency states. The primary goal is to train clinicians to redefine clinical problems in terms of essential biological questions that can be answered through laboratory investigation. In general, however, such questions are so complex that even sophisticated approaches using immunology, molecular biology, cell biology, or biochemistry alone cannot resolve them. Time-dependent factors, organ-specific changes, and organ-organ interactions necessitate the integration of these powerful basic science molecular- and cellular-based tools with large-animal acute physiological models and clinical outcome-based studies. Significant strides forward in our understanding of the processes of cardiovascular insufficiency, multiple organ dysfunction and their response to specific therapies will require more than detailed physiological monitoring of precise animal models with specific therapies or identification of a specific regulator gene in cultured cells. Despite efforts to understand the time course and host response to cardiopulmonary insufficiency, and to improve knowledge of the molecular basis for many aspects of diseases, we still have little tangible evidence of benefit in terms of the quality or length of patients' lives. A basic science approach alone is insufficient to address the complexity that continues upward through macroscopic interactions. Integration of various levels of investigation is essential for the efficient and rational development of effective treatment strategies for the critically ill.
Critical care medicine, as a sub-specialty of anesthesiology, internal medicine, pediatrics, and surgery, is uniquely positioned to integrate disparate areas of investigation into a single theme. This proposal is focused on the effects of cardiopulmonary and associated renal insufficiency states, such as those that occur during trauma, hemorrhage, myocardial ischemia, and sepsis, on the cardiopulmonary response and remote organ system function of the host. This theme is developed from the basic concepts of gene activation, intra-cellular and cell surface protein modulation, cell-cell interactions, cytokine-induced inflammation, myocyte and endothelial cell function, myocardial and vascular regulatory function, cardiopulmonary interactions, and finally long-term functional outcome studies.
Trainees receive formal instruction through general didactic and an individualized program of coursework and laboratory investigation. The general didactic training program comprises a core lecture series in critical care medicine given daily at noon throughout the year for first year trainees which reviews all aspects of medicine and basic science relevant to critical care medicine. These lectures are given by faculty throughout the University and is considered one of the strengths of this program. This is supplemented by bedside teaching on the pathophysiology of critical illness in a practical fashion aimed to solidify the bridge between theory and application while highlighting gaps in medical knowledge to be addressed in the remained of the training program. Most of the basic science training is carried out by a Principal Trainer plus a group of associated research team members (Trainer Group). All trainers are engaged in NIH and American Heart Association funded investigations related to various aspects of this complex response. Additional Co-Trainers are chosen according to the Trainee's needs from among the affiliated faculty within the University, to complement the strengths of the Principal Trainer and the Trainer Group. This individualized training allows the Trainee to focus on specific questions within the broad context of critical care. Trainees are systematically exposed to all aspects of this research training program and related areas of interest through the twice weekly research conferences, Thursday afternoon Trainee meetings, formal course work, and associated research conferences and grand rounds given in the University Medical Center. Since the primary goal of this training program is to create a durable bridge between clinical practice and basic science investigation, continued and integrated clinical activities (participation in direct patient care, clinical and patient-care conferences) are maintained during the basic science years of the program. The clinical experience incorporated into this Training Program, however, stresses more integration of pathophysiology at the bedside, with clinical responsibilities shared with a senior critical care attending physician who is also a member of the Executive Training Committee. Care is taken to individualize the Trainee's clinical and basic science experience so as to complement their research studies, prior strengths, and future plans. This integration is overseen by the Executive Training Committee, composed of experts in post-graduate medical education. The overall structure of the Training Program reflects a balance between core curriculum and related educational opportunities and individualized advanced training. We strive to maintain a balance between a unified training program in which all trainees interact and a diversified program which addresses the multidisciplinary issues of critical care medicine through specific projects in which individualization and specialization in selected areas of interest are fostered.
Need for a Research Training Program [top]
Although critical care medicine is a relatively new discipline, it has rapidly grown into a major part of many clinical training programs. Most critical care physicians carry additional subspecialty training in other areas of medicine. These additional perspectives both broaden the scope and weaken the focus of critical care medicine. The advent of improved and more complex patient monitoring, support techniques, and therapies has made it clear that a single group of clinicians is needed to oversee the global care of critically ill patients, with consultation from others with specific expertise. This is the primary goal of critical care medicine. Several recent studies have documented the increased efficacy of resource utilization and decreased patient mortality when intensive care units are staffed with full-time critical care medicine physicians (Reynolds NH, Haupt MT, Thill-Baharozian MC, et al. Impact of critical care physician staffing on patients with septic shock in a university hospital medical intensive care unit. JAMA 1988; 260:3446; Pollack MM, Katz RW, Ruttimann UE, et al. Improving the outcome and efficiency of intensive care: The impact of an intensivist. Crit Care Med 1988;16:11; Brown JJ, Sullivan G. Effect on ICU mortality of a full-time critical care specialist. Chest 1989;96:127). The current barrier to effective clinical application of basic science research in critically ill patients, even when fully trained intensivists are in place, rests at the basic laboratory level. To the extent that clinicians trained in critical care can become facile in these technologies, the transmission of information from the basic laboratory to the bedside will increase in both efficiency and effectiveness, because the flow of information will be bi-directional. Fellowship training programs may be in place for other primary specialties of anesthesiology, medicine and surgery, but none focuses specifically on the multi-disciplinary aspects of critical care medicine and cardiovascular instability, or the need for a multi-disciplinary approach to basic science investigation in these fields. Our Training Program's approach of core curriculum and individualized training in the setting of multi-disciplinary clinical practice will allow for trainees to broaden their understanding of science and clinical practice while honing their skills in specific areas of research. Rationale [top]
Critical care-related health care expenses reflect the largest single item in the health care budget. An updated estimate of ICU costs based on general and ICU bed occupancy rates (Russell LB. Intensive Care. In: Technology in Hospitals: Medical Advances and Their Diffusion . Washington, DC: The Brookings Institute, 1979.) for 1990 identified $47 billion, with 28% of total hospital costs for acute care. Despite the wondrous advances made in medical technology, molecular biology, and related cellular biology in the last 20 years, there has been little improvement in survival from critical illness associated with shock and subsequent organ-system dysfunction. One reason for this apparent lack of benefit is the failure of research to define not only the molecular and cellular mechanisms of disease, but also the tissue and remote organ interactions as they relate to long-term outcome. The organ-systems common to all these states are the cardiovascular and respiratory systems, which through the vascular endothelium and smooth muscles, airways, heart and formed circulating blood elements, regulate oxygen and nutrient delivery to the tissues, deliver inflammatory and anti-inflammatory compounds, and clear waste products. Cardiopulmonary status is a primary determinant of survival in stress states and is the primary focus for monitoring of therapeutic efforts. These issues are underscored in the recent NHLBI Task Force Summary on Research in Cardiopulmonary Dysfunction (Lenfant C. NHLBI Task Force Summary on Research in Cardiopulmonary Dysfunction in Critical Care Medicine. Am J Respir Crit Care Med 1995;151:243-248.), which emphasizes that future studies of the sort outlined in this proposal be undertaken. Thus, although excellent clinical training of intensivist represents an effective method of optimizing present day practice guidelines, as described above, research training in these areas is also required to improve cost-effective health care delivery and patient outcomes. We believe traditional basic science programs are inadequate to resolve this important problem. The usual argument made by clinicians is that Ph.D. training in the biological sciences, based on an apprenticeship in a narrowly focused area plus formal didactic training, makes fine scientists but does not equip them to analyze human pathophysiology. Furthermore, training clinicians to be scientists may take them out of the clinical environment and produce a research focus and perspective indistinguishable from that of a Ph.D. Critical care physicians who commonly confront pathophysiology at the bedside have the opposite problem. They understand the broader issues of patient care, organ-system interactions, and long-term outcome but lack the scientific perspective necessary to address these issues at a basic level and the sophistication to define the clinical problem as a scientific question. Additional training of Ph.D.s or non-clinical physician/scientists is unlikely to durably close this gap. We believe that the optimal way to address this important problem is to train clinicians simultaneously in human pathophysiology and basic science in an environment that integrates clinical, methodological, and scientific skills.
Our research-training environment includes a Principal Trainer who is a senior basic scientist and may also be a physician. Affiliated faculty in the training program customized to the individual needs of each Trainee include scientists and clinicians with mutual interests plus a diversity of other interests that complement the expertise of the Principal Trainer. The Principal Trainer is personally responsible for each individual Trainee's training program. Associated faculty, referred to as the Training Group, oversee the educational content of fellow training, and monitor each Trainee's progress toward agreed-upon educational and scientific goals as articulated in the Trainee's educational contract. The overall training program, as well as the progress of each Trainee, is monitored biannually by the Executive Training Committee, which will include all senior Trainers.
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