Academic Medical Center Research Research Articles

Developing a Clinical Research Infrastructure embedded in an Academic Medicine Center that Equitably Supports Future Clinician Scientists.

Clinical research in academic medical centers can be difficult to conduct and meet enrollment goals. Students underrepresented in medicine (URiM) are also underrepresented in academic leadership positions and as physician-scientists but are critical to help solve health disparities. Barriers in pursuing medicine as a career may be high for URiM students, therefore it is important to create pre-medicine opportunities accessible to all students interested in health care careers. We describe an undergraduate clinical research platform, the Academic Associate Program, embedded in the medical system that supports clinical research for academic physician scientists and provides students equitable access to experiences and mentoring opportunities. Students have the opportunity of completing a Pediatric Clinical Research Minor (PCRM) degree. This program satisfies many pre-medicine opportunities for undergraduate students, including those URiM, and allows access to physician mentors and unique educational experiences for graduate school or employment. Since 2009, 820 students participated in the AcA program (17.5% URiM) and 235 students (18% URiM) completed the PCRM. Of the 820 students, 126 (10% URiM) students matriculated to medical school, 128 (11%URiM) to graduate school, and 85 (16.5% URiM) gained employment in biomedical research fields. Students in our program supported 57 publications and were top-enrollers for several multi-centered studies. The AcA program is cost-effective and achieves a high level of success enrolling patients into clinical research. Additionally, the AcA program provides equitable access for students URiM to physician mentorship, pre-medical experiences, and an avenue to early immersion in academic medicine.

Consenting in the time of the COVID-19 pandemic

Consenting in the time of the COVID-19 pandemic

Differences in Cardiometabolic Comorbidities Between Black and White Persons Living With Multiple Sclerosis

ObjectiveTo determine differences in obesity, type 2 diabetes, and hypertension in Black patients compared with White patients with multiple sclerosis (MS). DesignCross-sectional database review. SettingLarge academic medical center research records database. ParticipantsA total of 3191 patient cases (N=3191; 77% female, 34% Black) identified by MS diagnosis within the medical record. InterventionsNot applicable. Main Outcome MeasuresDiagnosis codes for type 2 diabetes and hypertension. Body mass index (BMI), race, age, and sex were collected. Analysis of variance (continuous variables) and chi-square analyses (categorical variables) were conducted to determine differences in obesity, diabetes, and hypertension between race and sex. Logistic regression was conducted to determine odds ratios (ORs) of developing diabetes and hypertension based on race, sex, BMI, and age. ResultsBlack patients were more than twice as likely to be diagnosed as having diabetes (OR, 2.15 [95% CI, 1.70-2.72]; P<.0001) or hypertension (OR, 2.44 [95% CI, 2.05-2.91], P<.0001) compared with White patients. Sex did not present a greater likelihood of being diagnosed as having diabetes; however, men were 1.22 times more likely be diagnosed as having hypertension compared with women (95% CI, 1.01-1.49; P=.0439). Increased age and BMI were also significantly associated with likelihood of diagnosis of diabetes and hypertension (age: diabetes OR, 1.05 [95% CI, 1.04-1.06], P<.0001; hypertension OR, 1.06 [95% CI, 1.05-1.06], P<.0001; BMI: diabetes obese vs normal: OR, 2.11 [95% CI, 1.43-3.11], P=.0002; hypertension: obese vs normal: OR, 1.72 [95% CI, 1.39-2.13], P<.0001). ConclusionsBlack patients with MS are significantly more likely to have cardiometabolic conditions than White patients. These conditions have been associated with poorer health outcomes for people with MS and may have some effect on the differences in MS disease course reported in Black patients.

Pharmacists in Critical Care.

The beginnings of caring for critically ill patients date back to Florence Nightingale's work during the Crimean War in 1854, but the subspecialty of critical care medicine is relatively young. The first US multidisciplinary intensive care unit (ICU) was established in 1958, and the American Board of Medical Subspecialties first recognized the subspecialty of critical care medicine in 1986. Critical care pharmacy services began around the 1970s, growing in the intervening 40 years to become one of the largest practice areas for clinical pharmacists, with its own section in the SCCM, the largest international professional organization in the field. During the next decade, pharmacy services expanded to various ICU settings (both adult and pediatric), the operating room, and the emergency department. In these settings, pharmacists established clinical practices consisting of therapeutic drug monitoring, nutrition support, and participation in patient care rounds. Pharmacists also developed efficient and safe drug delivery systems with the evolution of critical care pharmacy satellites and other innovative programs. In the 1980s, critical care pharmacists designed specialized training programs and increased participation in critical care organizations. The number of critical care residencies and fellowships doubled between the early 1980s and the late 1990s. Standards for critical care residency were developed, and directories of residencies and fellowships were published. In 1989, the Clinical Pharmacy and Pharmacology Section was formed within the Society of Critical Care Medicine, the largest international, multidisciplinary, multispecialty critical care organization. This recognition acknowledged that pharmacists are necessary and valuable members of the physician-led multidisciplinary team. The Society of Critical Care Medicine Guidelines for Critical Care Services and Personnel deem that pharmacists are essential for the delivery of quality care to critically ill patients. These guidelines recommend that a pharmacist monitor drug regimen for dosing, adverse reactions, drug-drug interactions, and cost optimization for all hospitals providing critical care services. The guidelines also advocate that a specialized, decentralized pharmacist provide expertise in nutrition support, cardiorespiratory resuscitation, and clinical research in academic medical centers providing comprehensive critical care.

Author response: The state of clinical research in neurology.

Dr. Meador makes excellent points regarding our article addressing the state of clinical research in neurology.1 The results of the survey showed that some areas of clinical research had clearly worsened over the last 10 years, such as time spent on research or number of early career applicants to the NIH. These results are consistent with a recent report by Dr. Meador2 addressing the decline of clinical research in academic medical centers. However, survey respondents reported improvement in other areas, including adequate support by institutional grants and the availability of training opportunities.1 I agree that it will be important to monitor and address the drop in the pipeline of neurologists and neuroscientists focused on neuroscience research. I also agree that additional work is needed to distinguish changes within subgroups of researchers (such as between pharmaceutical-sponsored and investigator-initiated research), to clearly distinguish and to evaluate changes in funding mechanisms other than K or R awards over time, and to investigate individual pressures that decrease available time for research, such as the electronic medical record. Continued vigilance in these areas is critical to ensuring a robust network of clinical researchers in neuroscience that can bring the advances we need for our neurologic patients.

Association Between Early Life Adversity and Risk for Poor Emotional and Physical Health in Adolescence

Adverse childhood experiences (ACEs) have been associated with poor mental and physical health outcomes. However, the mechanism of this effect, critical to enhancing public health, remains poorly understood. To investigate the neurodevelopmental trajectory of the association between early ACEs and adolescent general and emotional health outcomes. A prospective longitudinal study that began when patients were aged 3 to 6 years who underwent neuroimaging later at ages 7 to 12 years and whose mental and physical health outcomes were observed at ages 9 to 15 years. Sequential mediation models were used to investigate associations between early ACEs and brain structure, emotion development, and health outcomes longitudinally. Children were recruited from an academic medical center research unit. Early life adversity. Early ACEs in children aged 3 to 7 years; volume of a subregion of the prefrontal cortex, the inferior frontal gyrus, in children aged 6 to 12 years; and emotional awareness, depression severity, and general health outcomes in children and adolescents aged 9 to 15 years. The mean (SD) age of 119 patients was 9.65 (1.31) years at the time of scan. The mean (SD) ACE score was 5.44 (3.46). The mean (SD) depression severity scores were 2.61 (1.78) at preschool, 1.77 (1.58) at time 2, and 2.16 (1.64) at time 3. The mean (SD) global physical health scores at time 2 and time 3 were 0.30 (0.38) and 0.33 (0.42), respectively. Sequential mediation in the association between high early ACEs and emotional and physical health outcomes were found. Smaller inferior frontal gyrus volumes and poor emotional awareness sequentially mediated the association between early ACEs and poor general health (model parameter estimate = 0.002; 95% CI, 0.0002-0.056) and higher depression severity (model parameter estimate = 0.007; 95% CI, 0.001-0.021) in adolescence. An increase from 0 to 3 early ACEs was associated with 15% and 25% increases in depression severity and physical health problems, respectively. Study findings highlight 1 putative neurodevelopmental mechanism by which the association between early ACEs and later poor mental and physical health outcomes may operate. This identified risk trajectory may be useful to target preventive interventions.

Improving email strategies to target stress and productivity in clinical practice.

Physician burnout is gaining increased attention in medicine and neurology and often relates to hours worked and insufficient time. One component of this is administrative burden, which relates to regulatory requirements and electronic health record tasks but may also involve increased time spent processing emails. Research in academic medical centers demonstrates that physicians face increasing inbox sizes related to mass distribution emails from various sources on top of emails required for patient care, research, and teaching. This commentary highlights the contribution of administrative tasks to physician burnout, research to date on email in medical contexts, and corporate strategies for reducing email burden that are applicable to neurology clinical practice. Increased productivity and decreased stress can be achieved by limiting the amount one accesses email, managing inbox size, and utilizing good email etiquette. Department and practice physician leaders have roles in decreasing email volume and modeling good practice.

Association of Biotin Ingestion With Performance of Hormone and Nonhormone Assays in Healthy Adults

Biotinylated antibodies and analogues, with their strong binding to streptavidin, are used in many clinical laboratory tests. Excess biotin in blood due to supplemental biotin ingestion may affect biotin-streptavidin binding, leading to potential clinical misinterpretation. However, the degree of interference remains undefined in healthy adults. To assess performance of specific biotinylated immunoassays after 7 days of ingesting 10 mg/d of biotin, a dose common in over-the-counter supplements for healthy adults. Nonrandomized crossover trial involving 6 healthy adults who were treated at an academic medical center research laboratory. Administration of 10 mg/d of biotin supplementation for 7 days. Analyte concentrations were compared with baseline (day 0) measures on the seventh day of biotin treatment and 7 days after treatment had stopped (day 14). The 11 analytes included 9 hormones (ie, thyroid-stimulating hormone, total thyroxine, total triiodothyronine, free thyroxine, free triiodothyronine, parathyroid hormone, prolactin, N-terminal pro-brain natriuretic peptide, 25-hydroxyvitamin D) and 2 nonhormones (prostate-specific antigen and ferritin). A total of 37 immunoassays for the 11 analytes were evaluated on 4 diagnostic systems, including 23 assays that incorporated biotin and streptavidin components and 14 assays that did not include biotin and streptavidin components and served as negative controls. Among the 2 women and 4 men (mean age, 38 years [range, 31-45 years]) who took 10 mg/d of biotin for 7 days, biotin ingestion-associated interference was found in 9 of the 23 (39%) biotinylated assays compared with none of the 14 nonbiotinylated assays (P = .007). Results from 5 of 8 biotinylated (63%) competitive immunoassays tested falsely high and results from 4 out of 15 (27%) biotinylated sandwich immunoassays tested falsely low. In this preliminary study of 6 healthy adult participants and 11 hormone and nonhormone analytes measured by 37 immunoassays, ingesting 10 mg/d of biotin for 1 week was associated with potentially clinically important assay interference in some but not all biotinylated assays studied. These findings should be considered for patients taking biotin supplements before ordering blood tests or when interpreting results. clinicaltrials.gov Identifier: NCT03034707.

Characterization of Neck Strength in Healthy Young Adults

BackgroundThe role of cervical muscle (neck) strength in traumatic brain and spine injury and chronic neck pain disorders is an area of active research. Characterization of the normal ranges of neck strength in healthy young adults is essential to designing future investigations of how strength may act as a modifier for risk and progression in head and neck disorders. ObjectiveTo develop a normative reference database of neck strength in a healthy young adult population, and to evaluate the relationship of neck strength to anthropometric measurements. DesignCross-sectional. SettingAn academic medical center research institution. ParticipantsA total of 157 healthy young adults (18-35 years of age) had their neck strength measured with fixed frame dynamometry (FFD) during 1 visit to establish a normative neck strength database. InterventionsNot applicable. Main Outcome MeasurementsPeak and average strength of the neck muscles were measured in extension, forward flexion, and right and left lateral flexion using FFD. The ranges of peak and average neck strength were characterized and correlated with anthropometric characteristics. ResultsIn all, 157 subjects (84 male, 73 female; average age 27 years) were included in the normative sample. Neck strength ranged from 38 to 383 Newtons in men and from 15 to 223 Newtons in women. Normative data are provided for each gender in all 4 directions. Weight, body mass index, neck circumference, and estimated neck muscle volume were modestly correlated with neck strength in multiple directions (correlation coefficients < .4). In a multivariate regression model, weight in women and neck volume in men were significant predictors of neck strength. ConclusionsNeck strength in healthy young adults exhibits a broad range, is significantly different in men from that in women, and correlates only modestly with anthropometric characteristics. Level of EvidenceNot applicable.

Decline of clinical research in academic medical centers.

Marked changes in US medical school funding began in the 1960s with progressively increasing revenues from clinical services. The growth of clinical revenues slowed in the mid-1990s, creating a funding crisis for US academic health care centers, who responded by having their faculty increase their clinical duties at the expense of research activities. Surveys document the resultant stresses on the academic clinician researcher. The NIH provides greater funding for basic and translational research than for clinical research, and the new Patient-Centered Outcomes Research Institute is inadequately funded to address the scope of needed clinical research. An increasing portion of clinical research is funded by industry, which leaves many important clinical issues unaddressed. There is an inadequate supply of skilled clinical researchers and a lack of external support for clinical research. The impact on the academic environment in university medical centers is especially severe on young faculty, who have a shrinking potential to achieve successful academic careers. National health care research funding policies should encourage the right balance of life-science investigations. Medical universities need to improve and highlight education on clinical research for students, residents, fellows, and young faculty. Medical universities also need to provide appropriate incentives for clinical research. Without training to ensure an adequate supply of skilled clinical researchers and a method to adequately fund clinical research, discoveries from basic and translational research cannot be clinically tested and affect patient care. Thus, many clinical problems will continue to be evaluated and treated with inadequate or even absent evidence-based knowledge.

Research in academic medical centers: two threats to sustainable support.

Reductions in federal support and clinical revenue jeopardize biomedical research and, in turn, clinical medicine.

Developing Future Clinician Scientists while Supporting a Research Infrastructure

Supporting clinical research is a national priority. Clinician scientists are rare and clinical trials in academic medical centers (AMC) often fail to meet enrollment goals. Undergraduate students interested in biomedical careers often lack opportunities to perform clinical research. Describe an innovative undergraduate course that supports clinical research in an AMC. The course, Clinical Research Methods and Practice, offers undergraduate students the opportunity to learn clinical research through didactic and practical experiences. The students in turn support clinician scientists' conduct of clinical studies in an AMC. Clinician scientists receive research support and participate in mentoring sessions for students. Over seven semesters, 128 students have assisted in 21 clinical studies located in outpatient and inpatient units of two hospitals. Students identified and screened eligible patients, collected clinical data, assisted in obtaining informed consent, and transported specimens. Many of the clinician scientists have met their enrollment goals and several have been top-enrollers in multicenter clinical trials as a result of student support. The Clinical Research Methods and Practice class addresses barriers to clinical research in AMC. This may be a model for institutions committed to mentoring students early in their career and to developing infrastructures for clinical research.

What Can Be Done to Protect the Translational Investigator?

The Association for Patient-Oriented Research (APOR) arose from concerns expressed beginning in the late 1970s about a growing shortage of investigators interested and well trained in conducting research on human subjects. Educational debt, difficulties in securing grant funding, and greater financial rewards in clinical practice continue to discourage young practitioners from pursuing careers in clinical research. Academic medical centers have seen their margins from clinical earnings decline and have asked potential clinician-investigators to contribute to the bottom line by seeing more patients. There was also an assumption, mostly unspoken, that basic research should be the focus of support and training, and that self-evident clinical and public health applications of basic research findings would be developed without much support from government or academic institutions. But the translation of basic research knowledge to the clinic and community has proven to be challenging and complex, and the rate by which the pharmaceutical industry has been developing significant new drugs is disappointing. An especially endangered species is the clinical investigator who asks questions at the bedside, and may then pursue answers initially in the laboratory and animal models before returning to the patient with a scientifically meaningful and ethical research protocol. This bidirectional aspect has been recognized as an essential and exciting aspect of patient-oriented research for many years, as exemplified by the comments of John Oates in 1982 (Figure 1). The career development of effective investigators who are comfortable both at the bedside and in the laboratory requires many years of mentoring and experience as well as stable research funding and institutional support. Integral role of patient-oriented clinical investigation both in the discovery of new knowledge and development of new therapies (from Oates JA. Presidential address: Clinical investigation: a pathway to discovery. Trans Assoc Am Physicians. 1982; 95: lxxviii-xc). Since the 1950s, the National Institutes of Health (NIH) has provided basic infrastructure for patient-oriented research in academic medical centers through the General Clinical Research Center (GCRC) program. GCRCs were also important for training patient-oriented investigators. In the 1990s, the NIH initiated K30 grants, which supported development of curricula for clinical research education, and individual K grants for trainees (NCRR K12), young investigators (K23, K08, etc.), and mentors (K24). The NIH Roadmap proposed by former NIH Director Elias Zerhouni, MD, emphasized clinical research and culminated in the Institutional Clinical and Translational Science Awards (ICTSAs). APOR supports the ICTSA program, which aims to expand support across the broad spectrum of translational research—from bench to bedside and the community—and for training at multiple levels. Unfortunately, this comprehensive program is being implemented at a time when NIH funding is limited. There are no progress reports yet on ICTSAs, but concerns have been expressed that at some institutions infrastructure for patient-oriented research has been downsized and that support has shifted to more basic research in the translational spectrum. If so, this will impede development of patient-oriented researchers. Current plans are for fewer ICTSAs than the number of previous GCRCs, which may mean that students and junior faculty at many academic health centers will have little exposure to hypothesis-driven, investigator-initiated clinical research. Clinical research at such institutions may be visible only as clinical trials sponsored by the pharma. While partnering with pharma is a key component of the NIH Roadmap, academic centers must also provide an environment favorable to patient-oriented research that investigators pursue based on hypotheses generated at the bedside. APOR will continue to promote patient-oriented research in a rapidly changing healthcare and clinical research environment. Because patient-oriented research represents a partnership between all practitioners and patients affected by disease, APOR welcomes all who are interested in CTS research to join in this effort. APOR is partnering with other organizations with complementary goals, such as the Society for Clinical and Translational Science (SCTS) and the Association for Clinical Research Training (ACRT), in planning an annual spring meeting that will benefit members of all these organizations. APOR and SCTS are also partners in supporting CTS. APOR will continue to provide further information about its activities in future issues of this journal, as well as in our newsletter (http://www.apor.org).

Longitudinal studies of inter-alpha inhibitor proteins in severely septic patients: A potential clinical marker and mediator of severe sepsis*

To determine the clinical relevance and prognostic significance of serial measurement of inter-alpha inhibitor proteins (IalphaIp) in severely septic patients. A laboratory-based study of serial plasma samples over the first 5 days of severe sepsis from a prospective clinical trial. Small business and academic medical center research laboratories. Two hundred sixty-six patients with severe sepsis from a multiple-center phase III clinical trial. None. Inter-alpha inhibitor proteins serve as endogenous serine protease inhibitors in human plasma. The levels of IalphaIp were markedly reduced to a mean value of 290+/-15 microg/mL at the onset of severe sepsis compared with normal plasma levels (617+/-197 microg/mL). Failure of IalphaIp levels to recover over the first 5 days of sepsis was associated with an unfavorable outcome (p<.001). IalphaIp levels were inversely correlated with interleukin-6 levels at study entry and over the first 5 days of management of severe sepsis. IalphaIp levels were significantly lower in women, with increased age, in the presence of multiple organ failure and in patients with intra-abdominal sources of sepsis. Inter-alpha inhibitor proteins are markedly reduced in severe sepsis, and failure of recovery of IalphaIp levels over the course of sepsis is associated with an unfavorable outcome.

Obstacles facing translational research in academic medical centers.

Over the last quarter of the 20th century, there has been a boom in biomedical research discoveries that, for the most part, has not been successfully exploited for improving medical therapy or diagnosis. This lack of success is surprising because there is a broad consensus within academic medical centers (AMCs) that a primary mission is to move scientific discoveries into meaningful clinical outcomes, and there are numerous opportunities for doing so. We illustrate the latter point with 10 clinical opportunities for translating scientific discoveries from our field of vascular biology and transplantation. We attribute the limited success of translation to various factors, chief of which is that translation is rarely straightforward and requires continuing research in both the clinic and the laboratory. Translational research is hindered by insufficient targeted resources, a shortage of qualified investigators, an academic culture that hinders collaboration between clinical and laboratory-based investigators, a traditional structure of the AMC that favors departmental efforts over interdisciplinary programs, an increasing regulatory burden, and a lack of specific mechanisms within the AMC for facilitating solutions to these problems. We offer several suggestions to reduce these impediments.

The role of institutional support in protecting human research subjects.

Institutional review boards (IRBs) and the federal "assurance" procedures play critical roles in the current research and regulatory environments for clinical research in academic medical centers and other institutions. The author focuses on what institutions can and ought to do to create an infrastructure that assures the protection of human subjects. Specifically, an institution should (1) create an ethics infrastructure in which both IRBs and the function of protecting human subjects are respected; (2) assure that adequate resources (space, staff, equipment) are available; (3) support IRB members with appropriate recognition and time, since their IRB workloads can be heavy; and (4) provide adequate and appropriate education for IRB administrators, members, and staff, and for investigators and research staff. Academic medical centers should also use their expertise in analyzing the current system and developing means of improving it. Nevertheless, providing adequate resources for proper research conduct will be challenging, given the current financial limitations within academic medical centers.

Using information technology to improve the quality and efficiency of clinical trial research in academic medical centers.

In the area of clinical trial research, academic medical centers (AMCs) need to create additional capacity and improve performance on vital indicators to attract more studies, as they are currently losing their share to stand-alone research sites. Through the utilization of information technology, AMCs will be in a better position to fend off the competitive threats to their clinical research dollars. Most AMCs are in an enviable position to leverage the value of information technology because of the existing people, processes, and technologies that probably already exist throughout the AMC. The challenge, then, is to deploy these resources in a different manner to support clinical trial research.

Clinical Research: Assessing the Future in a Changing Environment; Summary Report of Conference Sponsored by the American Medical Association Council on Scientific Affairs, Washington, DC, March 1996

Concerns about funding of clinical research underlie all other problems identified at the Council on Scientific Affairs conference. Future National Institutes of Health (NIH) budgets are likely to be constant at best, and the general public expects cost containment to be an ongoing goal; this is exacerbated by the impending Medicare Trust Fund crisis. Meanwhile, traditional financial support of clinical research in academic medical centers (AMCs) through cross-subsidization is imperiled by competitive pressures largely caused by managed care. Although managed care organizations (MCOs) are potentially rich sources of funding and other resources, and some not-for-profit companies are conducting some research, for-profit MCOs have not demonstrated an understanding of the importance of clinical research. Young physicians are being discouraged from careers as clinical researchers and established investigators are “dropping out” because of demands for clinical productivity and competition for research grants, loss of patients/research subjects to managed care, perceived lack of status and compensation, and overall uncertainty about continued financial support. Efforts to assist current and potential clinical investigators are discussed in this report. Loss of patients, denial of reimbursement, and competition with MCOs and contract research organizations (CROs) have placed AMCs under unprecedented pressure. However, research centers located in AMCs have allowed investigators to conduct clinical research by providing a “protected environment.” Furthermore, many AMCs are determined to continue conducting clinical research and are addressing related problems. Although the NIH will continue to be a major source of funding for clinical research, partnerships between various private and public entities provide important opportunities to maximize the productivity of all individuals and institutions involved. Potential partnerships include MCOs, AMCs, CROs, pharmaceutical companies and other industry, the Department of Defense, the Veterans Health Administration, practice-based physicians, and private foundations and patient support groups. “Partnerships in advocacy” for clinical research will be essential. Efforts to recruit for-profit MCOs to the clinical research endeavor identified in this report include (1) emphasizing issues of interest to them (eg, outcomes research); (2) stressing the significance of some research to the marketplace; (3) developing criteria to distinguish individual MCOs on the basis of their contribution to the public interest; (4) equating money spent on research with “R&D dollars” spent in nonmedical business enterprises; and (5) educating purchasers of health care (eg, corporate health plan directors) about clinical research. Conducting clinical research in all managed care settings requires leadership, the understanding and cooperation of physicians and support staff, wise use of limited resources (ie, funding only the best research projects), sound methodology, and above all, the perception that the research will ultimately improve patient care.

US neurologists: attitudes on the US health care system.

Because the American Academy of Neurology (AAN) exists to represent the views and needs of neurologists, a mailed survey to a randomly selected sample of 520 US-based, board-certified or board-eligible neurologist members was conducted in early 1995 to determine their attitudes in four key changing areas of the US health care system: (1) provision of neurologic care, (2) neurology workforce, (3) academic research, industry sponsorship, and pharmaceutical issues, and (4) health care delivery systems issues. Frequency distributions of degree of agreement and disagreement with 40 statements regarding issues in these four areas were tabulated for the entire group of 430 respondents (response rate = 83%). Associations between these attitudes and six demographic and practice variables (age, gender, board certification, practice type, degree of managed care, and geographical region) were evaluated in an exploratory analysis. The high response rate to the survey and the similarity in demographic and practice characteristics of respondents to the entire US-based, board-certified or -eligible AAN membership support that the attitudes that were measured are likely to be representative of US neurologists, excluding resident trainees. The survey results show that neurologists are deeply concerned that patients with chronic neurologic disorders are not receiving all the neurologic services they need. Respondent show uncertainty about whether there is a current oversupply of neurologists but generally agree that there are too many neurology residency positions. Neurologists support industry sponsorship of academic medical center research and new drug development. With respect to many of the current mechanisms for health care cost containment, respondents indicate they have little confidence that these strategies are in the best interests of patients or physicians. The survey results confirm that there is no consensus among US neurologists on how to improve today's health care delivery system, and the results suggest that certain attitudes are related to neurologists' demographic and practice characteristics. Since today's health care market is volatile, regular assessments of neurologists' attitudes will be needed to assure that their views are understood and clearly represented by the AAN.

Blockade of Platelet GPIIb/IIIa Receptors as an Antithrombotic Strategy

Moving from bench to bedside in the development of the monoclonal antibody 7E3, directed against the platelet GPIIb/IIIa receptor, from a basic science laboratory reagent to an antithrombotic drug was a long, incremental process. From the beginning, we hoped that this powerful new agent would allow us to define better the biochemistry of the GPIIb/IIIa receptor and its role in platelet physiology and pathology, and we dreamed that we might be able to use it to improve the therapy of patients with vascular disease. I first review the evolution of our understanding of platelet physiology since the 1960s and why the platelet GPIIb/IIIa receptor appeared to be a logical target for antithrombotic therapy. I then describe our studies with 7E3 to block the receptor in experimental animal models of thrombosis. The results of these studies encouraged us to try to develop 7E3 as a human therapeutic agent. The development was a monumental effort conducted by hundreds of people working for nearly a decade and culminated in the approval by the Food and Drug Administration of c7E3 Fab (abciximab [ReoPro]) in December 1994 as conjunctive therapy for use in patients undergoing high-risk coronary artery angioplasty and atherectomy. A detailed description of the developmental process is beyond the scope of this essay, so it is only briefly described. My experience in moving back and forth from the academic medical center research bench to the world of drug development has allowed me to reflect on the processes involved, and at the end of this essay, I share some of my thoughts and concerns. The choice of the GPIIb/IIIa receptor as a therapeutic target rests on an enormous amount of basic and clinical research by many investigators working in what might appear to be quite disparate fields, including platelet-fibrinogen interactions, the rare blood platelet …