Abstract
The history of Emergency Medicine (EM) in Missouri reflects the larger history of EM as a burgeoning specialty throughout the United States, but with some important and unique contributions that may not be generally appreciated. We discuss historical events and important leaders of EM, but there are many we could not mention. Much of the information comes from personal interviews with the physicians who “were in the room where it happened.”.
We hope the article will illuminate the progress made in caring for critical illness and injury through the development of a new specialty focused on that goal. We recognize there are many emergency physicians not mentioned that have played a large role in maintaining and growing the academic programs, improving the delivery of care through administrative and legislative actions, and navigating the specialty through enormously challenging times.
Introduction
Emergency Medicine became a reality about 60 years ago, recently enough to still be in living memory of many of its pioneers. During the 1960s and early 1970s, there was a cascade of events, discoveries, and innovations that led to recognizing a need for and feasibility of a specialty designed to treat life-threatening illness and injury (Figure 1). By the late 1960s the groundwork for treating several life-threatening conditions, including cardiac arrest, had been established. Now physicians knowledgeable and skilled in these life-saving procedures were needed to implement these changes. Recognizing the unique challenges facing practitioners dedicated to diagnosing and managing the full spectrum of medical and surgical emergencies, eight physicians formed the American College of Emergency Physicians (ACEP) in 1968. In 1969 these founders held their first annual scientific assembly.1 In 1970, the first “emergency medicine” resident began training at the University of Cincinnati in a two-year curriculum granted by the American Medical Association under a Family Practice program.2 This was followed in 1971 by an Emergency Medicine (EM) program at the Medical College of Pennsylvania and the first academic department of Emergency Medicine at the University of Southern California. By 1975, there were 31 residencies in EM, including one in Kansas City, Missouri, and one in St. Louis.2
Figure 1.
Timeline of events, clinical innovations, educational and legislative activities leading to the development of Emergency Medicine
The 1970s saw the seeds of EM first sprout across Missouri. While beginning as a tale of two cities, the story quickly developed into a multi-regional effort to develop clinical, educational, and legislative opportunities that would improve emergency care throughout the state. We begin with emergency care in St. Louis public and private hospitals and academic medical centers in the 1960s.
The St. Louis Story
The history of EM in St. Louis is intricately connected to the public hospitals and academic medical centers. In the early 1960s, St. Louis had three public hospitals. St. Louis City Hospital, built in 1846 (renamed Max C. Starkloff in 1942) served the white population of St. Louis (Figure 2). Homer G. Phillips Hospital, opened in 1937 and served the African American population of St. Louis. St. Louis County Hospital opened in 1931, caring for indigent county residents.3 These hospitals, along with three adult and two pediatric hospitals associated with Washington University and Saint Louis University, were staffed by academic faculty and volunteer physicians in private practice. Attending physicians were not present in the emergency departments (ED).
Figure 2.
Physicians and administrators in front of City Hospital (Max Starkloff Hospital) circa 1946
Some private hospitals also provided emergency care and had various models of ED staffing. Most were staffed by one or more nurses who, after assessing the patient, would contact an on-call physician or the patient’s private physician for medical orders. As physicians became reluctant to take every week-end call, hospitals found an alternative. Tom Cooper, having recently graduated from medical school at Indiana University, started a physician staffing program in St. Louis. He recalls being hired in 1970 to cover hospitalized patients at the old DePaul Hospital, followed by an ED staffing contract in 1971.4
Initially, contracts provided week-end shift coverage, provided by “moonlighting” residents from one of the affiliated teaching hospitals. Residents were hired to staff 60-hour shifts at $10/hour. These shifts were particularly prevalent and popular in the more rural hospitals. Within a year or so residents were covering Monday through Thursday overnight shifts as well.4 It was not until 1973 or ’74 that St. Louis area hospitals began to have licensed physicians staffing the ED 24/7. These physicians were often not board-certified, consisting of residents and fellows. During this time-period, academic centers traditionally divided the ED into a medical and surgical side, staffed accordingly with residents from the primary specialties of Medicine and Surgery. Patients were triaged to one area or the other by a triage nurse. Junior assistant residents were often the sole provider of care. Theoretically, they had access to more senior physicians as back-up at the teaching hospitals, but this rarely included actual attending physicians apart from surgeons for operative intervention.
Two decades earlier, this ED staffing model had been described as the “weakest link” in the chain of trauma care.5 Allen Klippel, a Washington University surgeon, started a two-year EM residency program at St. Louis City Hospital in 1973 to help correct this weakest link in the chain of care. The program was terminated two years later. There would not be another allopathic EM residency in St. Louis for more than 20 years.
That is not to say that progress stood still. In the late 1970s, under the direction of Samuel Bonney, a general surgeon by training, Saint Louis University Hospital (SLUH) committed to 24/7 ED coverage by full-time, board-certified physicians who were academic faculty. None were EM trained. As was the case across America, extensive on-the-job training and continuing medical education were essential. In 1979, Larry Lewis who had completed a residency in Internal Medicine at Jewish Hospital, was hired by Bonney and helped build a core group of physicians with the requisite skills and knowledge needed for the job. Lewis became the co-director of the ED in 1985 along with Joseph Stothert, MD, of the Trauma Service. Following a five-year practice period, he and many of his colleagues sat for the board examination in EM, which had been approved by the American Board of Medical Specialties in 1979.
In 1989, with the support of the medical school and other SLUH emergency physicians, Lewis applied for an EM residency program. Unfortunately, the application was not approved. While the ED saw a wide mix of cases, many with high acuity, it was felt that a census of 25,000 patients per year was too low.6 Despite this setback, the 1980s saw attending physician coverage proliferate across EDs in St. Louis, either through small private hospital-based groups or larger contract management groups. Physicians board-certified in emergency medicine however, remained scarce.7 Spectrum Emergency Care, organized and run by Drs. Tom Cooper and Joe Gatewood, staffed several hospitals in the St. Louis area and throughout Missouri, including Barnes Hospital.
In the early 1990s the Barnes Hospital ED, which was affiliated with Washington University School of Medicine, was still functioning under a resident-run model of care, using contracted physicians to “supervise” the residents. In late 1993, John Atkinson, MD, the newly appointed chair of Internal Medicine at Washington University, asked Lewis to review the ED clinical model. Lewis confirmed what Atkinson already knew from two prior department surveys. Both understood that for the department to be successful, the culture would need to change. Atkinson asked Lewis to take charge of the department in 1994, agreeing to support the development of a residency program. A core group of emergency physicians came with Lewis from SLUH, including Drs. Brent Ruoff, Rosanne Naunheim, and John Fortney. Additional faculty were hired, including Drs. Doug Char and Dane Chapman, who would be the inaugural program director. In 1997, Washington University initiated a four-year residency in EM, primarily situated at Barnes-Jewish and St. Louis Children’s Hospital. Dr. Char took over as residency program director in 2001, growing the training program and adding several fellowships over his 15 years at the helm. In 2004 Ruoff became the Chief of EM, helping the program to flourish, both academically and geographically, hiring subspecialty faculty in anticipation of developing specialty fellowships, and providing staffing across multiple hospitals in the BJC system.8
In 2008, Saint Louis University Hospital, whose ED volume had grown significantly over the years, was approved for a three-year residency program in EM under the leadership of Laurie Byrne, MD, as Chief of Emergency Medicine and Vijai Chauhan, MD, as the inaugural Program Director.
The Kansas City Story
Unlike initial events in St. Louis, Kansas City had early success initiating and sustaining an EM residency program which has graduated nearly 400 residents to date and will celebrate its 50th anniversary in 2023. W. Kendall McNabney, MD, a general surgeon by training, established the program in Kansas City in 1973 (Figure 3). McNabney’s interest in EM began during his residency at Kansas City General Hospital (which became Truman Medical Center and is now University Health) and continued during his military experience in Vietnam and Cambodia. Following his return to General Hospital in 1970, he was named Director of the Trauma Service and the hospital’s first Director of Emergency Services.
Figure 3.
Dr. McNabney (second from left) watches as Joseph Waeckerle performs chest compressions. Truman Medical Center Emergency Medicine residency circa 1975.
At that time, General Hospital had very few full-time staff, relying mostly on volunteer staff to supervise the interns and residents on the floors. Physician staffing in the ED consisted of rotating interns during the weekday and one or more moonlighting residents at night and weekends. Following McNabney’s return from military service, this began to change. Staffing consisted of McNabney, an internist, and several part-time physician staff. All moonlighting ceased and all medicine, surgical, and Ob-Gyn residents were required to spend two months during their PG-1 year and one month during their PG-2 year in the ED. To enlarge the resident base, resident physicians were solicited from training programs outside of General Hospital for a one to three month experience working in the ED. Inquiries returned asking if this was for a residency program in EM. The answer at the time was “no,” but the seed had been planted.9
In 1972 General Hospital established a department of Emergency Health Services within the hospital bylaws, resulting in parity with the departments of Internal Medicine, Surgery, Radiology, Pathology and Obstetrics-Gynecology. Correspondingly, these departments were recognized within the University of Missouri-Kansas City School of Medicine’s new innovative six-year curriculum shortly before the new residency program was established. As a result, there was not the same degree of ownership or turf wars regarding the running of the ED that was encountered at other older traditional medical centers. By 1973, there were about a dozen EM programs in the United States, most less than one year old, but there was no roadmap for how to teach emergency medicine.
McNabney, recognizing the need for curriculum development, attended a 1973 University Association of Emergency Medicine (UA/EM) workshop in Hamilton, Ontario, which focused on establishing training programs in EM. That year he started the Kansas City EM program with four residents. At the time of his retirement in 1986, McNabney said, “More than anything, the Emergency Medicine Residency Program has been my proudest accomplishment during my career at TMC [Truman Medical Center]”.
William (Bill) Robinson, MD, an early graduate of the UMKC program, became Chair of EM following McNabney’s retirement and reflects that it was “a period of extraordinary evolution for emergency medicine and I felt lucky to have been a part of it.” The most important change was the emerging acceptance of emergency medicine as a valued specialty. The demand for EM-trained, board-certified physicians was significant in the private sector almost instantly, but it took longer to convince more traditional medical centers that EM could meaningfully contribute to the provision of clinical services, training resident physicians and students, and carrying out medical research.
While there are many UMKC contributions to the pioneering efforts of EM, Joseph Waeckerle, MD, one the first residents, merits recognition. He had a profound impact on generations of emergency physicians and the entire clinical and academic field of emergency medicine. Waeckerle became the founder of the Emergency Medicine Residents’ Association and was the first residency-trained president of UA/EM, later to become the Society for Academic Emergency Medicine (SAEM). He also served as Editor-in-Chief of Annals of Emergency Medicine from 1989–2002. For these contributions, Waeckerle received the James D. Mills Outstanding Contribution to Emergency Medicine Award from the American College of Emergency Physicians (ACEP) in 2002.
Springfield, Columbia, and Joplin
The evolution of EM in more rural areas paralleled that of the two larger cities. With private staff physicians increasingly reluctant to cover patients in the ED 24/7, there was a clear need for competent full-time ED coverage. To staff these hospitals, many primary care physicians, like Roger Willcox, MD, made the transition to EM.10
In the late 1970s, Willcox was working in Branson, Missouri, as a family physician. His general practice group covered the local ED which, like many rural hospitals, did not have dedicated physician staffing. After Willcox attended an ACEP Scientific Assembly in 1976, he was hooked. Given the energy and excitement of the new specialty he noted, “I could not have done anything else.” Willcox caught the eye of the physicians at Cox Hospital in Springfield for his care of survivors of a helicopter crash, and he was offered a job in their ED in 1977. Two years later, he became medical director of the ED across town, at St. John’s Hospital (now Mercy Hospital Springfield). At the time, Springfield was unique in that both hospitals were seeing upwards of 100 patients per day in the ED, with each hospital staffed by an independent group.9 By 1990, when Ted McMurry, MD, started at St. John’s Hospital, he notes that almost all the physicians were board-certified in EM, with half of them residency trained like himself.11
In 1980, Willcox returned to his hometown of Columbia to become the medical director at Boone Hospital Center. Like other hospitals, Boone was looking for dedicated full-time, preferably board-certified physicians. While Willcox successfully made the transition to EM, becoming board-certified in 1984, he acknowledged that a significant number of physicians did not and “over time were weeded out.”
The University of Missouri Hospital (now MU Health) also had several pioneers in EM. Frank Mitchell, MD, who trained in general and thoracic surgery, returned from military service in 1959 and recognized the need to upgrade civilian prehospital care to that of military standards. Over the next decade and a half, he would take the lead in Missouri to develop training programs for ambulance attendants to become emergency medical technicians and paramedics. He also led the effort to develop standards for trauma centers nationwide and recognized the need for full-time emergency physicians to staff the ED.12 In 1982 Mitchell hired Dean Nierling, MD, after a chance encounter enroute to a medical meeting. Nierling became medical director and took over the training of the EMTs and paramedics. He was well liked and respected, and was working towards an EM residency at MU Health, but unfortunately died before this could happen.13
William Womack, MD, a family physician in Chillicothe started his EM career in 1977 moonlighting 60-hour weekend shifts at Hedrick Medical Center (HMC). He was hired in 1982 to be their one and only full-time ED physician. In 1988 Mitchell met Womack while working with HMC to install a helicopter pad and recruited him to join the faculty at the University of Missouri, where he served as the ED medical director from 1994–2002 and recalls that a residency site review done in the early 1990s concluded the ED volume was too low to support an EM residency.14
As the ED census grew, there was a renewed effort to start a residency program at MU Health. In 2011 Marc Borenstein, MD, joined the faculty as chair of EM, with that goal. A three-year program was approved in 2013. Borenstein was the initial program director with Brian Bausano taking over in 2015.
Freeman Hospital in Joplin also has a residency program in EM, with its first residents starting in 2001. John Dougherty, DO who was Director of Medical Education at Freeman, was instrumental in the development of the program. In 2018, the three-year program became Accreditation Committee on Graduate Medical Education certified.15,16
The Role of Organized Medicine
Emergency Medicine in Missouri received significant benefit from organized medicine, but it also made significant contributions as well. The Missouri Chapter of the American College of Emergency Physicians (MOCEP) was formed in 1978. Charter members included Joe Waeckerle, MD, and Ralston R. Hannas, MD, a “founding father” of emergency medicine. Hannas was the co-organizer of the first EM Scientific Assembly, chairman of the committee that formed the American Board of Emergency Medicine and helped start the EM residency program at Northwestern.17 Over the years, many Missouri emergency physicians, too many to list, have played key roles on national committees and effected real change in emergency medical care.
By the mid-1980s, MOCEP brought together academic, urban and rural emergency physicians from around the state to be included on the board of directors. In 1987, the statewide Combined Clinical Conference had its first educational meeting, bringing together EMTs, paramedics, emergency nurses and emergency physicians.18 The enthusiasm and collegiality for the new specialty was infectious. During its early years, to its benefit, MOCEP contracted with Missouri State Medical Association (MSMA) to provide an executive director, office space, and guidance. Over the years, MOCEP has found its place in the House of Medicine, working with MSMA on critical legislative issues and statewide initiatives to improve patient care.
The New Millennium
Missouri now has five EM residency programs, graduating 47 board-eligible emergency medicine physicians every year. With the nationwide growth in programs, the new millennium has seen a shift in staffing to residency trained physicians. More EM residents are interested in post-graduate specialized training, spurring the development of several fellowship programs (Table 1). The past few decades have led to a revolution in time-dependent therapies for life-threatening conditions such as myocardial infarction, stroke, trauma, and sepsis. Emergency Medicine has been as responsible as any specialty in pushing the envelope to rapidly diagnose and treat these conditions.19,20 A general belief held by the early academic and practicing pioneers in EM, both in Missouri and elsewhere, was that clinical care must drive the other two legs of the “tripartite” academic mission. One cannot teach students and residents how to best care for patients unless it is demonstrated to them, and medical research without clinical bedside implementation has minimal impact on patient care. Consequently, EM has been a leader in advancing clinical care through research and implementation21–23 and has stood as the safety net for all, something starkly illustrated during the COVID-19 global pandemic.24
Table 1.
Current Fellowships in Emergency Medicine Offered in Select Missouri Programs
Fellowship | Year started* |
---|---|
Pediatric EM* | 1992 |
EMS | 2005 |
Critical Care | 2009 |
Toxicology | 2011 |
Ultrasound | 2012 |
Medical Education/simulation* | 2012 |
Research | 2012 |
Administration* | 2016 |
These fellowships are offered at multiple EM residencies. Year started is for the initiation of the first program at any of the EM residencies in the state.
Another important characteristic among our earliest academic EM leaders was their leadership style. They considered the people working 24/7 under them as their most important constituents, rather than the upper echelons of hospital or medical school administration. They inherently recognized something codified by the Marriott organization; that ONLY by treating your workers in the best way can you ensure extraordinary services to your customers [patients].25
Emergency Medicine has come a long way in the last 50 years, and Missouri EM has been at the forefront of innovation in many areas.26–30 There continue to be new and recurring challenges facing the specialty, both nationally and locally.31,32 Many of us nearing the end of our careers might prefer the old challenges to the new ones, but EM is secure with amazing new leaders who are more than capable of taking the reins and navigating the evolving iterations of our specialty with a continued patient-centered focus.
Footnotes
Lawrence M. Lewis, MD, (above), is Professor, Emergency Medicine, at Washington University School of Medicine, St. Louis, Missouri. Mark T. Steele, MD, is Professor, Emergency Medicine, University Health Truman Medical Center, University Health Emergency Department and Trauma Center, Kansas City, Missouri. Michael Szewczyk, MD, specializes in Emergency, Occupational, and Internal Medicine at Boone Hospital in Columbia, Missouri.
Disclosure
None reported.
References
- 1.Suter RE. Emergency Medicine in the United States: a systemic review. World J Emerg Med. 2012;3:5–10. doi: 10.5847/wjem.j.1920-8642.2012.01.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Zink BJ. A Brief History of Emergency Medicine Residency Training in: Anyone, Anything, Anytime-A History of Emergency Medicine. Mosby. 2006 [Google Scholar]
- 3.Missouri Historical Society. https://mohistory.org/collections/item/P0966 .
- 4.Cooper Tom. Lewis personal communication. 2021;8:13. [Google Scholar]
- 5.Robert H. Kennedy “Oration on Trauma” American College of Surgeons’ Clinical Congress. Atlantic City, New Jersey: 1954. [Google Scholar]
- 6.St Louis University Hospital Emergency Medicine Residency Review Committee report. 1989 [Google Scholar]
- 7.Steele MT, Lewis LM, Schwab RA, Perez NM, Watson WA. Emergency medicine credentials in St. Louis and Kansas City: does the presence of an emergency medicine residency program have a geographic difference? Ann Emerg Med. 1996;28:27–30. doi: 10.1016/s0196-0644(96).70134-8. [DOI] [PubMed] [Google Scholar]
- 8.Char Douglas, Lewis Lawrence. Szewczyk Personal communication. Dec, 2021.
- 9.Kendall McNabney W. Department of Emergency Health Services, Truman Medical Center-University of Missouri-Kansas City School of Medicine. 1979 July 30; [Google Scholar]
- 10.Willcox Roger. Szewczyk personal communication. 2021;8:18. [Google Scholar]
- 11.McMurray Ted. Lewis personal communication. 2021;8:11. [Google Scholar]
- 12.Potter Erik. Battlefield Lessons: Trauma care in mid-Missouri owes a lot to American soldiers fighting overseas. Mizzou Magazine. May 21, 2013. https://mizzoumag.missouri.edu/2013/05/battlefield-lessons/index.html .
- 13.Nierling Carol. Szewczyk personal communication. 2021;8:16. [Google Scholar]
- 14.Womack William. Szewczyk personal communication. 12:20–2021. [Google Scholar]
- 15.Brenda Barger-Saunders, Szewczyk. personal communication; 12.21.21. [Google Scholar]
- 16.Linkedin. https://www.linkedin.com/in/john-dougherty-do-facofp-38274136/
- 17.Misssouri College of Emergency Physicians. Awards and Grants. https://mocep.org/grants-awards/
- 18.Missouri College of Emergency Physicians. The History of MOCEP. https://mocep.org/about/the-history-of-mocep/
- 19.Gorelick AR, Gorelick PB, Sloan EP. Emergency department evaluation and management of stroke: acute assessment, stroke teams, and care pathways. Neurologic Clinics. 2008;26:923–942. doi: 10.1016/j.ncl.2008.05.008. [DOI] [PubMed] [Google Scholar]
- 20.Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M for the early goal-directed therapy collaborative group. Early goal-directed therapy for the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368–1377. doi: 10.1056/NEJMoa010307. [DOI] [PubMed] [Google Scholar]
- 21.Hedges JR. The knowledge translation paradigm: historical, philosophical, and practice perspectives. Acad Emerg Med. 2007;14:924–27. doi: 10.1197/j.aem.2007.06.016924. [DOI] [PubMed] [Google Scholar]
- 22.Diner BM, Carpenter CR, O’Connell T, Pang P, Brown MD, Seupaul RA, Celentano JJ, Mayer D for the KT-CC Theme IIIa members. Graduate medical education and knowledge translation: role models, information pipeline, and practice change thresholds. Acad Emerg Med. 2007;14:1008–1014. doi: 10.1197/j.aem.2007.07.003. [DOI] [PubMed] [Google Scholar]
- 23.Neta G, Glasgow RE, Carpenter CR, Grimshaw JM, Rabin BA, Fernandez ME, Brownson RC. A framework for enhancing the value of research for dissemination and implementation. American Journal of Public Health. 2014;105:49–57. doi: 10.2105/AJPH.2014.302206. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Kline JA, Burton JH, Carpenter CR, Meisel ZF, Miner JR, Newgard CD, Quest T, Martin IBK, Holmes JF, Kaji AH, Bird SB, Coates WC, Lall MD, Mills AM, Ranney ML, Wolfe RE, Dorner SC. Unconditional care in academic emergency departments. Acad Emerg Med. 2020;27:527–28. doi: 10.1111/acem.14010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Vision and Mission of Marriott International Company. https://studycorgi.com/marriott-international-company-human-resources-management .
- 26.Ablordeppy EA, Drewry AM, Beyer AB, Theodoro DL, Fowler SA, Fuller BM, Carpenter CR. Diagnostic accuracy of central venous catheter placement by bedside ultrasound versus chest radiography in critically ill patients: a systematic review and meta-analysis. Crit Care Med. 2017;45:715–724. doi: 10.1097/CCM.0000000000002188.. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Fuller BM, Mohr NM, Drewry AM, Carpenter CR. Lower tidal volume at initiation of mechanical ventilation may reduce progression to acute respiratory distress syndrome: a systematic review. Crit Care. 2013 Jan 18;17(1R11) doi: 10.1186/cc11936. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Marks LR, Munigala S, Warren DK, Liang SY, Schwarz ES, Durkin MJ. Addiction Medicine consultations reduce readmission rates for patients with serious infections from opioid use disorder. Clinical Infectious Diseases. 2019;68:1935–1937. doi: 10.1093/cid/ciy924. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Lewis LM, Carpenter CR, Jotte R, Schwarz E. Healthcare provider wellness in the time of COVID and beyond. Missouri Medicine. 2021;118:13–17. [PMC free article] [PubMed] [Google Scholar]
- 30.Carpenter CR, Melady D, Krausz C, Wagner J, Froelke B, Cordia J, Lowery D, Ruoff BE, Byrne LE, Miller DK, Lewis LM. Improving emergency department care for aging Missourians: guidelines, accreditation, and collaboration. Missouri Medicine. 2017;114:447–452. [PMC free article] [PubMed] [Google Scholar]
- 31.McKenna P, Heslin SM, Vicellio P, Mallon WK, Hernandez C, Morley EJ. Emergency department and hospital crowding: causes, consequences, and cures. Clin Exp Emerg Med. 2019;6(3):189–195. doi: 10.15441/ceem.18.02232. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Lin M, Battaglioli M, Melamed M, Mott SE, Chung AS, Robinson DW. High prevalence of burnout among US emergency medicine residents: results from the 2017 national Emergency Medicine wellness survey. Ann Emerg Med. 2019;74:682–690. doi: 10.1016/j.annemergmed.2019.01.037. [DOI] [PubMed] [Google Scholar]