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REDUNDANT PUBLICATION: A REMINDER NOBODY is well served by the practice of reporting the same study in two journals, publishing a review of the same subject nearly simultaneously in two journals, or splitting a study into two or more parts and submitting each to separate journals. A recent mini-epidemic of attempts to publish redundantly in the Journal has alerted us to the need to remind authors and investigators of policies that seem to be breached increasingly often now. We have not called attention to this issue for several years, and a new generation of authors may have overlooked previous commentaries.1,2 Our guidelines regarding redundant publication are published each week on the Information for Authors page. In a practice followed by many journals, we ask authors to send us copies of any manuscripts closely related to the manuscript they want us to consider for publication. This allows us to decide whether there is excessive overlap between two manuscripts or whether the results of a single study are inappropriately divided into two or more papers. In the trade, the latter practice is sometimes referred to as “salami slicing.” The reasons for preventing redundant publication are not arbitrary. As earlier editorials have pointed out, multiple reports of the same observations can overemphasize the importance of the findings, overburden busy reviewers, fill the medical literature with inconsequential material, and distort the academic reward system.1,2 The results of huge clinical trials or epidemiologic studies with multiple and unrelated end points, such as the GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) trial of thrombolytic therapy after acute myocardial infarction, the Framingham Heart Study, or the Physicians’ Health Study, could not be reported as a single study. It often takes years to collect and analyze such data, and it is legitimate to describe important outcomes of such studies separately. On the other hand, reports of studies involving several dozen patients should not be split into overlapping manuscripts. Because the line between appropriate and inappropriate practice is not always clear, it might be helpful to provide several concrete examples. First, some examples of overlapping publications: Two years ago we accepted a paper on bone lesions in patients with chronic renal failure. We asked a distinguished nephrologist to write an editorial to accompany the paper. While preparing the editorial, the nephrologist came across a study published in a specialty journal several months earlier. It was written by the same authors, described the same patients, and reported virtually the same end points. The authors had not told us they had published similar data elsewhere. Although we were well along in the production process, we pulled the paper. This example of fragmenting the results of a single study and reporting them in several papers is not unique. Several months ago, for example, we received a manuscript describing a controlled intervention in a birthing center. The authors sent the re-

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sults on the mothers to us, and the results on the infants to another journal. The two outcomes would have more appropriately been reported together. We also received a manuscript on a molecular marker as a prognostic tool for a type of cancer; another journal was sent the results of a second marker from the same pathological specimens. Combining the two sets of data clearly would have added meaning to the findings. After we published a recent study describing diagnostic tests on 101 consecutive patients with suspected traumatic rupture of the thoracic aorta,3 we learned that the report was remarkably similar to two papers that had been published in the surgical literature.4,5 One, published only two months earlier, described 160 patients.5 The other, published two years earlier, described 69 patients.4 All three papers were from the same institution; three persons were listed as authors on all three papers, and two others were listed as authors on two of the papers. Before we accepted the paper for publication, we were not informed about the report on 160 patients, although it had already been accepted for publication elsewhere. The paper published two years earlier was also not brought to our attention by the authors, although we were aware of it because it was listed in the bibliography. No information was given in any of the papers about which patients were being reported on two or more times. In fact, as the letter from Drs. Smith and Kearney in the Correspondence section of this issue of the Journal indicates,6 some patients in fact were reported on in all three papers, providing a misleading impression of the number of patients studied and the value of the tests. It is surprising that these practices still occur, despite growing attention and nearly universal disapproval. Most of the time the redundant publication is quickly exposed by readers. In addition, an investigator’s peers often recognize a succession of “least publishable units.” The motivation for publishing two or more papers when one would do is not always clear. In some instances authors have argued that they were interested in getting the information to different audiences. In others, they have claimed that they perceived the overlap to be far less substantial than did the editors. Finally, there is reason to suspect that the academic incentive system fosters a desire by authors to lengthen their bibliographies. Ways of counteracting this distorted incentive have been proposed7 but have not been universally implemented. We are not eager to act as prior-publication police, and we do not regularly search the literature to determine whether an author has committed one of the several forms of redundant publication. But we have rewritten the relevant portion of our Information for Authors as follows: “Authors should submit to the Editor copies of any published papers or other manuscripts in preparation or submitted elsewhere that are related to the manuscript to be considered by the Journal” (we formerly asked for “copies of any related manuscripts”). We will continue to rely on the honesty and judgment of authors in informing us of any work of

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theirs that is related to a manuscript they are submitting to the Journal. When preparing a manuscript, authors might heed the advice offered previously.2 In deciding whether reports are redundant, authors should ask themselves whether a single paper would be more cohesive and more informative than two. When there is any doubt, authors should submit with their manuscripts any other papers possibly representing duplication or fragmentation of results, whether published, submitted for publication, or already accepted for publication. JEROME P. KASSIRER, M.D. MARCIA ANGELL, M.D.

TIME TO HIT HIV, EARLY AND HARD EARLY treatment of asymptomatic human immunodeficiency virus type 1 (HIV-1) infection remains controversial. In the AIDS Clinical Trials Group 019 study, zidovudine was shown in 1990 to slow the clinical progression to AIDS in infected but asymptomatic subjects.1 However, a follow-up of those subjects found no evidence of longer survival with the use of zidovudine.2 Furthermore, the Concorde study found that there was not only no survival benefit from early treatment with zidovudine, but also no effect on the overall progression of disease.3 Now, in this issue of the Journal, Volberding et al. report the further results of the AIDS Clinical Trials Group study, which show that immediate zidovudine therapy, as compared with deferred treatment, in asymptomatic persons with CD4 lymphocyte counts of 500 or more cells per cubic millimeter does not prolong the disease-free period or confer a survival benefit.4 At the same time, Kinloch-de Loës et al. show that the use of zidovudine earlier, during primary HIV-1 infection and six months thereafter, results in a detectable improvement in the clinical course as well as an increase in the CD4 cell count.5 The seemingly contradictory nature of these new findings, although attributable in part to differences in study design and study subjects, can be explained in the light of recent observations on the pathogenesis of HIV-1. Three sets of recent scientific findings and therapeutic developments converge to favor an aggressive interventional strategy early in the course of HIV-1 infection. First, over the past several years, it has been shown that newly infected persons generally harbor a relatively homogeneous population of HIV-1, in contrast to the diverse swarm of viruses found in persons with chronic infection.6-8 This monoclonality or oligoclonality of the virus around the time of seroconversion is believed to result from a “bottleneck” effect exerted by as yet undefined selective forces during the transmission of HIV-1. A relatively homogeneous viral population is less likely to contain preexisting variants with drug resistance and is thus more likely to respond to therapy. These theoretical considerations support the early treatment of HIV-1, as is the case with any treatable infectious disease.

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REFERENCES 1. Relman AS. Publish or perish — or both. N Engl J Med 1977;297:724-5. 2. Angell M, Relman AS. Redundant publication. N Engl J Med 1989;320:12124. 3. Smith MD, Cassidy JM, Souther S, et al. Transesophageal echocardiography in the diagnosis of traumatic rupture of the aorta. N Engl J Med 1995;332: 356-62. 4. Kearney PA, Smith DW, Johnson SB, Barker DE, Smith MD, Sapin PM. Use of transesophageal echocardiography in the evaluation of traumatic aortic injury. J Trauma 1993;34:696-703. 5. Buckmaster MJ, Kearney PA, Johnson SB, Smith MD, Sapin PM. Further experience with transesophageal echocardiography in the evaluation of thoracic aortic injury. J Trauma 1994;37:989-95. 6. Smith MD, Kearney PA. Notice of redundant publication: transesophageal echocardiography in the diagnosis of traumatic rupture of the aorta. N Engl J Med 1995;333:458. 7. Angell M. Publish or perish: a proposal. Ann Intern Med 1986;104:261-2.

Second, the recent demonstration of the highly dynamic nature of HIV-1 replication in vivo has important implications for early therapeutic intervention.9-11 In infected persons this replication is continuous, with very rapid kinetics. Half the virus in plasma is cleared and replenished every two days or less, and overall rates of virion production average nearly 1 billion particles per day. Over a typical course of HIV-1 infection lasting about 10 years, thousands of replication cycles occur, resulting in a total production of close to 10 trillion virions. Given this relentless, high-level viral replication in conjunction with the known mutation rate of HIV-1 reverse transcriptase of approximately 1 in 1000 to 1 in 10,000 per base,12 it is expected that viral variants will be generated rapidly. (Therapeutically, the generation of viral diversity in HIV-1 infection may be likened to the development of metastasis in cancer.) Simple calculations suggest that after a few years of infection, every viable mutation at every position in the 10-kb genome will occur; certain combinations of double mutations may also emerge. Therefore, monotherapy as we know it is doomed to fail, especially in the case of antiviral agents to which HIV-1 can become resistant with a substitution of a single base. In the long run, effective treatment must instead force the virus to mutate simultaneously at multiple positions in one viral genome. This is best achieved by using a combination of multiple, potent antiretroviral agents. From our understanding of viral dynamics9,10 and levels of plasma viremia during different stages of HIV-1 infection,13-17 it can be estimated that the number of virions produced during the typical one-month duration of primary infection approximates the number produced in several subsequent years of asymptomatic infection. Consequently, the effect of zidovudine therapy during the seroconversion period is expected to be greater than the effect of similar treatment for a year during the asymptomatic period. This concept provides a potential explanation for the apparent discrepancy between the results of Volberding et al.4 and those of Kinloch-de Loës et al.5 Moreover, a recent study demonstrates that the plateau concentration of plasma viral RNA after primary HIV-1 infection is predictive of the long-term clinical outcome.18 Treatment at the time of seroconversion may lower the initial viral

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plateau (“set point”) and thereby improve the subsequent clinical course. Although these theoretical considerations argue strongly for early aggressive treatment, we have been limited to date by the lack of sufficiently potent drugs. When used individually, the currently available nucleoside inhibitors of reverse transcriptase — zidovudine, didanosine, zalcitabine, and stavudine — are relatively weak antiretroviral agents that at best lower the viral load by 0.7 log.14,19 It could be argued that such imperfect therapy does not adequately test the concept of early treatment. As a crude analogy, although no one disputes the merit of early diagnosis and treatment of breast cancer, it is doubtful that a therapy that decreased the tumor burden by only 80 percent would be clinically beneficial, regardless of the timing of its administration. It is therefore most encouraging that substantial progress is being made in developing more potent antiretroviral agents and regimens. Novel inhibitors of HIV-1 protease, such as ritonavir (formerly known as ABT-538)20 and MK-639,21 lower plasma viremia by about 2.0 log.9,10 Certain non-nucleoside blockers of reverse transcriptase, such as nevirapine, have an inhibitory effect of 1.0 to 1.5 log,9 whereas the regimen of zidovudine plus lamivudine has shown an activity of about 1.7 log in vivo.19 These advances suggest that we may now have a number of better weapons with which to fight HIV-1. Collectively, these drugs provide the third rationale for early intervention. Given the measurable benefit of zidovudine treatment in primary infection observed by Kinloch-de Loës et al.,5 imagine what might be achieved if HIV-1 replication were reduced by 3.0 log or more. When safe and effective treatment regimens are defined, the time will be right to test the concept of ablative treatment in HIV-1 infection. To stack the deck in favor of success, we should exert maximal antiviral pressure (using the optimal regimen) on the virus when it is most homogeneous — during the initial phase of infection. We should bear in mind the lessons learned from the treatment of tuberculosis and childhood leukemia, in which monotherapy resulted in transient responses that were quickly followed by relapses. It was aggressive combination chemotherapy at the outset that led to cures. Optimistically, we can hope that such an approach will become possible in patients infected with HIV-1. Aaron Diamond AIDS Research Center New York University School of Medicine New York, NY 10016

DAVID D. HO, M.D.

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REFERENCES 1. Volberding PA, Lagakos SW, Koch MA, et al. Zidovudine in asymptomatic human immunodeficiency virus infection — a controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter. N Engl J Med 1990;322:941-9. 2. Volberding PA, Lagakos SW, Grimes JM, et al. The duration of zidovudine benefit in persons with asymptomatic HIV infection: prolonged evaluation of protocol 019 of the AIDS Clinical Trials Group. JAMA 1994;272:437-42. 3. Concorde Coordinating Committee. Concorde: MRC/ANRS randomised double-blind controlled trial of immediate and deferred zidovudine in symptom-free HIV infection. Lancet 1994;343:871-81. 4. Volberding PA, Lagakos SW, Grimes JM, et al. A comparison of immediate with deferred zidovudine therapy for asymptomatic HIV-infected adults with CD4 cell counts of 500 or more per cubic millimeter. N Engl J Med 1995; 333:401-7. 5. Kinloch-de Loës S, Hirschel BJ, Hoen B, et al. A controlled trial of zidovudine in primary human immunodeficiency virus infection. N Engl J Med 1995;333:408-13. 6. Zhu T, Mo H, Wang N, et al. Genotypic and phenotypic characterization of HIV-1 in patients with primary infection. Science 1993;261:1179-81. 7. Zhang LQ, MacKenzie P, Cleland A, Holmes EC, Leigh Brown AJ, Simmonds P. Selection for specific sequences in the external envelope protein of human immunodeficiency virus type 1 upon primary infection. J Virol 1993; 67:3345-56. 8. Wolinsky SM, Wike CM, Korber BT, et al. Selective transmission of human immunodeficiency virus type-1 variants from mother to infants. Science 1992;255:1134-7. 9. Wei X, Ghosh SK, Taylor ME, et al. Viral dynamics in human immunodeficiency virus type 1 infection. Nature 1995;373:117-22. 10. Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 1995;373:123-6. 11. Coffin JM. HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science 1995;267:483-9. 12. Preston BD, Poiesz BJ, Loeb LA. Fidelity of HIV-1 reverse transcriptase. Science 1988;242:1168-71. 13. Piatak M Jr, Saag MS, Yang LC, et al. High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR. Science 1993;259: 1749-54. 14. Cao Y, Ho DD, Todd J, et al. Clinical evaluation of branched DNA signal amplification for quantifying HIV type 1 in human plasma. AIDS Res Hum Retroviruses 1995;11:353-61. 15. Daar ES, Moudgil T, Meyer RD, Ho DD. Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection. N Engl J Med 1991;324:961-4. 16. Clark SJ, Saag MS, Decker WD, et al. High titers of cytopathic virus in plasma of patients with symptomatic primary HIV-1 infection. N Engl J Med 1991;324:954-60. 17. Ho DD, Moudgil T, Alam M. Quantitation of human immunodeficiency virus type 1 in the blood of infected persons. N Engl J Med 1989;321:1621-5. 18. Mellors JW, Kingsley LA, Rinaldo CR Jr, et al. Quantitation of HIV-1 RNA in plasma predicts outcome after seroconversion. Ann Intern Med 1995;122: 573-9. 19. Eron J, Benoit S, Jemsek J, Quinn J, Fallon MA, Rubin M. A randomized double-blind multicenter comparative trial of lamivudine (3TC) monotherapy vs. zidovudine (ZDV) monotherapy vs. 3TC  ZDV combination in naive patients with CD4 cell counts of 200-500/mm3. In: Program and abstracts of the Second National Conference on Human Retroviruses and Related Infections, Washington, D.C., February 1, 1995. Washington, D.C.: American Society for Microbiology, 1995:173. abstract. 20. Kempf DJ, Marsh KC, Denissen JF, et al. ABT-538 is a potent inhibitor of human immunodeficiency virus protease and has high oral bioavailability in humans. Proc Natl Acad Sci U S A 1995;92:2484-8. 21. Vacca JP, Dorsey BD, Schleif WA, et al. L-735,524: an orally bioavailable human immunodeficiency virus type 1 protease inhibitor. Proc Natl Acad Sci U S A 1994;91:4096-100.

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TICK-BORNE DISEASES — A GROWING RISK TEN tick-borne diseases are now recognized in the United States. Three of these have been discovered in the past three decades: Lyme disease in the 1970s, human ehrlichiosis (caused by Ehrlichia chaffeensis) in the 1980s, and a new human ehrlichial infection, human granulocytic ehrlichiosis, in the 1990s.1 Tick-borne diseases have challenged researchers and physicians since studies in the early 1900s established the wood tick (Dermacentor andersoni) as a vector of Rocky Mountain spotted fever. This disease, although uncommon, was widely feared because of its case fatality rate of 70 percent. Deaths decreased dramatically after the introduction of antibiotics, but Rocky Mountain spotted fever continued to attract the attention of public health professionals because of unexplained changes in its epidemiologic features. There was a shift toward the more highly populated south central, southern, and eastern regions of the United States, where the disease is transmitted by the dog tick, D. variabilis, and in the late 1970s the number of reported cases increased to more than 1000 per year. Although the number of cases decreased again in the 1980s, new foci of infection are still being identified, and this lethal disease remains a source of public health concern.2,3 Lyme disease is now the most commonly reported vector-borne disease in the United States.4 In 1994, more than 13,000 cases were reported to the Centers for Disease Control and Prevention (CDC) by 43 states, an increase of nearly 60 percent over the number of cases reported in 1993 and a 26-fold increase from the 491 reported by 11 states in 1982. The risk of acquiring Lyme disease is highly focal, with 89 percent of cases reported from the eight states with the highest incidence (Connecticut, Rhode Island, New York, New Jersey, Delaware, Pennsylvania, Wisconsin, and Maryland). Infections with Borrelia burgdorferi result from exposure to nymphal and adult stages of tick vectors in the genus ixodes. These infections are often undetected, and even when diagnosed, they are underreported. Ixodes ticks also transmit babesiosis and possibly human granulocytic ehrlichiosis. Exposure to Amblyomma americanum, the Lone Star tick, is commonly reported by patients with rashes resembling erythema migrans in the southern United States. Uncultivatable spirochetes have been identified in the midguts of about 2 percent of these ticks by a number of investigators, and a species of borrelia distinct from previously known members of the genus has recently been identified in A. americanum by the polymerase chain reaction (PCR).5 The initial recognition of human ehrlichiosis was based on the finding of inclusions in mononuclear cells in a peripheral-blood smear from a patient bitten by ticks in Arkansas. The inclusions resembled those found in canine ehrlichiosis, a tick-borne infection, and serologic testing with E. canis confirmed the diagnosis. Although the inclusions proved to be an unusual finding, early serologic and epidemiologic studies revealed sporadic cases of the disease in south central, southern,

Aug. 17, 1995

and eastern states in a distribution similar to that of A. americanum ticks. The disease was usually acquired in recreational settings or near homes and was more common among older persons.6,7 One study found an incidence of 5.3 per 100,000 among patients in a community hospital,8 and active surveillance revealed clusters in military units.9 However, passive national surveillance detected only about 50 cases per year (0.02 per 100,000 population).7 Isolation of E. chaffeensis led to somewhat more sensitive serologic tests and to the development of primers for PCR.10 Most recently, human granulocytic ehrlichiosis has been recognized in areas of the northern United States where Lyme disease and babesiosis are endemic; transmission by I. scapularis or D. variabilis is suspected.1 Although the disease is clinically similar to infection with E. chaffeensis, inclusions were found in neutrophils in all cases of human granulocytic ehrlichiosis in the initial series.1 These inclusions and the results of PCR tests suggest that the causal agent is closely related to a different tick-borne ehrlichia infecting animals (E. equi or E. phagocytophila).1 The report by Standaert et al. in this issue of the Journal11 expands our knowledge and challenges assumptions about human ehrlichiosis. As part of their investigation of 4 patients who had infections caused by E. chaffeensis in a Tennessee community of 3000 people, retrospective and prospective studies in medical facilities identified a total of 11 cases. Two of the 11 patients had no evidence of seroconversion, possibly because they were treated very early in the illness, and the diagnosis was established by detecting E. chaffeensis in acute-phase blood samples by PCR. The incidence of symptomatic infection (330 per 100,000) was nearly 100 times greater than in other community-based studies. A serologic survey found evidence of past infection in 39 of 311 community members (12.5 percent), but only 3 of the 39 (8 percent) reported a recent acute illness. Several investigations of isolated cases of ehrlichiosis have identified previously unrecognized foci of symptomatic and asymptomatic infections. In studies of military personnel, 0.5 to 11.2 percent had seroconversion for ehrlichia, spotted-fever–group rickettsia, or both, after field maneuvers lasting a few weeks to three months, but only one third of the seropositive patients reported associated illnesses.9 Standaert et al. extended this observation to an older civilian population exposed in a recreational setting. According to their data on seroprevalence, a relatively large proportion of the community had been infected, but only a small proportion had recently had symptoms. Persons who avoided tick-infested areas and regularly used a tick repellent were less likely than others to have antibodies to E. chaffeensis. The fact that antibodies to E. chaffeensis were found in asymptomatic persons in these studies9,11 suggests that infection may be even more common than previously suspected. Standaert et al. demonstrated the value of PCR in establishing the diagnosis of ehrlichiosis, and others

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have suggested that biopsies of skin lesions in patients with Rocky Mountain spotted fever should be used for early diagnosis. However, the prompt treatment of seriously ill patients in whom Rocky Mountain spotted fever or human ehrlichiosis is suspected is essential1,2,7 and cannot await the preparation and transport of specimens to facilities where rapid diagnostic tests are available. Epidemiologic and clinical information usually provides the physician with sufficient information to initiate treatment. The disease typically appears in spring and summer, and there is generally a history of a tick bite or exposure to ticks. In serious infections, fever and headache are almost universal.1-3,7 In ehrlichiosis, leukopenia, thrombocytopenia, and abnormalities of liver function are also common during the first week of illness. Older patients, for whom the index of suspicion is often low, and those who lack some of the typical features of the disease are at greatest risk for complications and death, in part because they are often treated late in the course of illness.1-3 Recent data suggest that doxycycline should be considered the treatment of choice for patients with ehrlichiosis or Rocky Mountain spotted fever. Doxycycline and amoxicillin are drugs of choice for treating early, uncomplicated Lyme disease; amoxicillin is not effective in treating ehrlichiosis or Rocky Mountain spotted fever. Although infection with E. chaffeensis appears to respond to both tetracyclines and chloramphenicol, in vitro sensitivity testing has shown E. chaffeensis to be resistant to the latter agent.12 Chloramphenicol has been considered an acceptable alternative in Rocky Mountain spotted fever, but in uncontrolled studies case fatality rates were lower with tetracyclines than with chloramphenicol.2 In Rocky Mountain spotted fever and both types of human ehrlichiosis, the disease usually responds to tetracyclines in 24 to 48 hours, quickly enough for the response to be helpful in supporting the presumptive diagnosis.1,7 Perhaps because the risk of tick-borne infections is geographically determined, the reporting of tick-borne illnesses to public health authorities is especially impor-

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tant. The public can be informed about the avoidance of tick-infested areas, the use of tick repellents, and other measures that have now been shown to decrease the risk of infection with tick-borne agents.4,9,11 When ehrlichiosis and other tick-borne diseases are recognized in areas where they were previously unknown, a search for unrecognized cases will increase public awareness and remind physicians about the importance of promptly treating patients in whom acute febrile illnesses develop after exposure to ticks. Centers for Disease Control and Prevention Atlanta, GA 30333 Centers for Disease Control and Prevention Fort Collins, CO 80522

DANIEL B. FISHBEIN, M.D. DAVID T. DENNIS, M.D., M.P.H. REFERENCES

1. Bakken JS, Dumler JS, Chen SM, Eckman MR, Van Etta LL, Walker DH. Human granulocytic ehrlichiosis in the upper Midwest United States: a new species emerging? JAMA 1994;272:212-8. 2. Dalton MJ, Clarke MJ, Holman RC, et al. National surveillance for Rocky Mountain spotted fever, 1981-1992: epidemiologic summary and evaluation of risk factors for fatal outcome. Am J Trop Med Hyg 1995;52:40513. 3. Kirkland KB, Wilkinson WE, Sexton DJ. Therapeutic delay and mortality in cases of Rocky Mountain spotted fever. Clin Infect Dis 1995;20:1118-21. 4. Lyme disease — United States, 1994. MMWR 1995;44:459-62. 5. Barbour AG. New Borrelia species. Presented at the National Institutes of Health, Centers for Disease Control and Prevention Workshop on Emerging Diseases, Galveston, Tex., May 8–9, 1995. abstract. 6. Eng TR, Harkess JR, Fishbein DB, et al. Epidemiologic, clinical, and laboratory findings of human ehrlichiosis in the United States, 1988. JAMA 1990;264:2251-8. 7. Fishbein DB, Dawson JE, Robinson LE. Human ehrlichiosis in the United States, 1985 to 1990. Ann Intern Med 1994;120:736-43. 8. Fishbein DB, Kemp A, Dawson JE, Greene NR, Redus MA, Fields DH. Human ehrlichiosis: prospective active surveillance in febrile hospitalized patients. J Infect Dis 1989;160:803-9. 9. Yevich SJ, Sánchez JL, DeFraites RF, et al. Seroepidemiology of infections due to spotted fever group rickettsiae and Ehrlichia species in military personnel exposed in areas of the United States where such infections are endemic. J Infect Dis 1995;171:1266-73. 10. Dawson JE, Anderson BE, Fishbein DB, et al. Isolation and characterization of an Ehrlichia sp. from a patient diagnosed with human ehrlichiosis. J Clin Microbiol 1991;29:2741-5. 11. Standaert SM, Dawson JE, Schaffner W, et al. Ehrlichiosis in a golf-oriented retirement community. N Engl J Med 1995;333:420-5. 12. Brouqui P, Raoult D. In vitro antibiotic susceptibility of the newly recognized agent of ehrlichiosis in humans, Ehrlichia chaffeensis. Antimicrob Agents Chemother 1992;36:2799-803.

The Journal’s E-Mail Addresses: For letters to the Editor: [email protected] For information about submitting material for Images in Clinical Medicine: [email protected] For information about the status of a submitted manuscript: [email protected]

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SOUNDING BOARD CORRECTING THE OVERSUPPLY OF SPECIALISTS BY LIMITING RESIDENCIES FOR GRADUATES OF FOREIGN MEDICAL SCHOOLS IT is estimated that there will be an excess of approximately 165,000 specialist physicians in the United States in the year 2000.1,2 Consistent with these projections are anecdotal reports that physicians completing residency training in some specialties are having difficulty finding suitable professional opportunities and that the growth of managed care is adversely affecting established specialty practices in some regions. There is no consensus on how to address the problem of an oversupply of physicians. At issue are conflicting views on the appropriate roles of government and the market in restricting the supply of specialist physicians. Analysts who see the current size and specialty mix of the physician work force as irrefutable evidence that the market has failed to correct the problem are convinced that the government must begin to regulate both the number of new physicians and their specialty choices. Other analysts, primarily members of the medical profession, are adamantly opposed to any form of government regulation of medical education. They believe that market forces will ultimately correct the oversupply of physicians. I believe there is a role for both the government and the market in restricting the supply of specialist physicians in the United States. I propose here the respective roles of government and the market in decreasing the number of physicians who enter practice and altering the specialty mix. SUPPLY OF PHYSICIANS AND SPECIALTY MIX The primary factors that determine the future size and specialty mix of the physician work force are the number of medical school graduates who enter residency programs each year and their specialty choices. This relation persists even though residents may ultimately choose subspecialties or switch specialties. The majority of residents are graduates of allopathic and osteopathic medical schools in the United States. The number of such graduates who enter residencies (approximately 17,500 in 1994) has remained relatively constant for more than a decade. In contrast, there has been a marked increase in recent years in the number of graduates of foreign medical schools who enter residencies in the United States. In 1994, approximately 6750 graduates of foreign medical schools entered residency programs, or almost 40 percent of the number of graduates of U.S. medical schools who entered residencies.3 Seventeen percent of these graduates of foreign medical schools were U.S. citizens. Graduates of U.S. and foreign medical schools do not generally compete for the same residency positions. The majority of graduates of U.S. medical schools comDETERMINANTS

OF THE

THE

Aug. 17, 1995

pete for positions in residency programs participating in the National Resident Matching Program. In contrast, the majority of graduates of foreign medical schools fill residency positions either not offered in the matching program or offered in the program but not filled by U.S. graduates.4 Approximately 75 percent of the graduates of foreign medical schools who train in the United States ultimately establish practices here.5 If their number continues to increase, the specialty choices made by graduates of U.S. medical schools will have a diminishing influence on the specialty mix of the physician work force. What would happen if medical students in the United States learned that opportunities to practice in certain specialties were soon going to decline dramatically? The number of students applying for residency training in those specialties would almost certainly decline as well. (An example is the downward trend in the number of U.S. students applying to anesthesiology programs.) Would the residency programs in those specialties respond by reducing the number of training positions? Would some programs even close? Hardly. Experience has shown that graduates of foreign medical schools would simply fill the extra positions. If U.S. students altered their specialty choices in response to market forces, the result would be a shift in the proportional representation of graduates of U.S. and foreign medical schools. There would be no change in the supply of future physicians or in the specialty mix. THE ROLE OF GOVERNMENT The number of entry-level positions filled in the graduate-medical-education system can be restricted by market forces only if those forces are powerful enough either to compel the institutions that sponsor residency programs to reduce or eliminate programs voluntarily or to dissuade a large number of graduates of foreign medical schools from entering U.S. residency programs. There is no reason to believe that program directors, department heads, and others whose individual decisions determine the number of entry-level positions will voluntarily reduce that number.6 Similarly, graduates of foreign medical schools who hope to practice in the United States are not likely to choose to forgo residency training because of concern about the availability of practice opportunities in the specialties with unfilled residency positions. It is therefore unrealistic to believe that market forces alone can substantially decrease the number of entry-level positions in residency programs each year. To control the supply of physicians, the Council on Graduate Medical Education and the Physician Payment Review Commission recommended that the federal government limit the number of entry-level residency positions to 110 percent of the number of U.S. medical school graduates.7,8 This recommendation was embraced by the Clinton administration and included in the work-force provisions of its original plan for health care reform. Although the proposal for regulating residency positions was widely endorsed by medical

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Vol. 333

No. 7

SOUNDING BOARD

educators and health policy analysts, it is unrealistic to expect serious consideration of this approach now. I suggest that the federal government control the supply of physicians not by regulating the number of residency positions but by limiting the number of graduates of foreign medical schools who enter residency programs each year. In my view, it is not reasonable at this point to consider limiting access to residency training for graduates of U.S. medical schools. Because of the substantial public investment required to educate medical students and the extraordinary debt they accumulate, it would be unreasonable to prevent graduates of U.S. medical schools from acquiring the additional education required for licensure. Current immigration law cannot be used to limit access to residency training by graduates of foreign medical schools, because the majority of such graduates who enter residency programs in the United States are U.S. citizens or have permanent-resident status in this country.5 In recent years, only approximately one third of all graduates of foreign medical schools in U.S. residency programs have been exchange visitors. I believe that the federal government, guided by an appropriate advisory group (such as the Council on Graduate Medical Education), should determine how many graduates of foreign medical schools will be allowed to enter residencies in the United States. The responsibility of selecting the specific candidates to fill the allocated positions should be delegated to a professional group. Those selected would be granted “residency-training cards,” which would allow them to enter any residency program to which they were accepted. The Educational Commission on Foreign Medical Graduates (sponsored by the American Board of Medical Specialties, the American Hospital Association, the American Medical Association, the Association of American Medical Colleges, the Association for Hospital Medical Education, the National Medical Association, and the Federation of State Medical Boards) is the most logical choice for the group that selects the candidates for residency-training cards. The commission currently certifies graduates of foreign medical schools who are eligible to enter U.S. residencies. Because the commission administers standardized examinations for this purpose, it should not be difficult to develop criteria to determine who should receive training cards. Although performance on standardized examinations should be the primary criterion, an effort should also be made to maintain a balance between applicants who are obligated to return to their native countries (i.e., applicants with J-1 visas) and those who are not. This approach will ensure that the United States continues to provide residency training to physicians who will use the knowledge and skills they acquire in their own countries. In my view, no preference should be given to U.S. citizens who are graduates of foreign medical schools, most of whom failed to gain entry to medical schools in the United States. Although the policy will be controversial, the performance of this group on the examinations administered by the Educational Com-

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mission on Foreign Medical Graduates and on specialty-board examinations is not as good as that of other graduates of foreign medical schools. Only graduates with training cards would be allowed to enter U.S. residency programs. If the proposed policy of limiting entry-level positions to 110 percent of the number of U.S. graduates had been in place in 1994, only about 1750 graduates of foreign medical schools would have entered U.S. residencies, or slightly more than a quarter of the 6750 who actually began residency training that year. To ensure compliance with this policy, the Medicare program would have to be changed so that any hospital that accepted residents without training cards would not receive direct and indirect medical-education payments. Medicare funds are a crucial source of support for hospital residencies; the potential loss of these funds would provide a compelling reason for hospitals to comply with the policy. Limiting the number of graduates of foreign medical schools in residency programs may seriously affect the continued provision of patient care by some hospitals, primarily those that provide care to underserved populations. According to accreditation standards, residency programs cannot be justified on the basis of hospital service needs. Research is needed to determine how many institutions depend on graduates of foreign medical schools to provide care to the poor and how many of those institutions would be adversely affected by the new policy. The problem could be addressed in part by making federal funds available to hospitals with a demonstrated need for assistance; the funds would be used to hire nurse practitioners, physician’s assistants, or staff physicians to replace residents.9 Such a mechanism was included in the Clinton administration’s proposal for health care reform. During a transitional period, selected hospitals could be granted temporary waivers that would allow them to continue to accept residents without training cards. This approach was used in the late 1970s, when limits were placed on the number of foreign medical graduates with J-1 visas who were allowed to enter residencies. THE ROLE OF THE MARKET If the federal government limits the number of graduates of foreign medical schools entering residency programs so that the total number of entering residents is approximately equal to the number of graduates of U.S. medical schools, the specialty mix of the work force will ultimately reflect the specialty choices of students in U.S. medical schools. There is no reason to believe that these students will choose specialties without regard to market forces. Their choices in recent years have reflected the market — that is, the availability of many high-income opportunities in procedurally oriented specialties — quite accurately. Now that the market appears to favor generalists, there is evidence that career choices are beginning to shift.10 Indeed, this year the number of students in U.S. medical schools who chose residency programs in family practice through the National Resident Matching Program

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THE NEW ENGLAND JOURNAL OF MEDICINE

was the highest in the history of the specialty. The number of students who chose residency training in internal medicine or pediatrics also increased, as compared with the number in 1994. These trends suggest that market forces, rather than government regulation, should be allowed to determine the specialty choices of graduates of U.S. medical schools. The success of this proposal depends on two factors. First, medical students must be provided with up-todate, accurate information about practice opportunities for each specialty in each region of the country. The choices students make can reflect the market only if they are well informed. Such information has not been as important in the past, because there have been plenty of practice opportunities available in most, if not all, specialties. To meet this need, both the directors and the recent graduates of residency programs could be surveyed regularly to obtain information, based on their personal experiences, about the influence of market forces on professional opportunities. In fact, the American Medical Association, with support from the Robert Wood Johnson Foundation, is currently conducting surveys of this kind. A national network of group-practice physicians or administrators could also be established to collect information on professional opportunities. Second, the effect of the market on students’ choices must not be distorted by federal regulation of the specialty mix of residency positions (as opposed to the number of positions filled), despite the recent proposal for such regulation.11 Medical students who have reliable market information must be free, within reasonable limits, to choose their specialties. The extremely large number of entry-level positions now available in the system is an advantage in this respect. CONCLUSIONS The problem of the oversupply of specialist physicians will not be solved if the parties involved in the current policy debate continue to frame the solution as a choice between government regulation and market forces. My proposal requires both sides to cast off some strongly held views. Those who believe in the effectiveness of market forces must acknowledge that the market will not restrict the flow of graduates of foreign

Aug. 17, 1995

medical schools into U.S. residency programs. Those who believe the federal government should solve the problem must relinquish the notion that the government can decide the appropriate specialty mix for the physician work force. The effects of a continued stalemate are clear: the United States will invest substantial sums of money to educate physicians who are not needed, and some of the young men and women who pursue careers in medicine may find few professional opportunities when they finish their education. Since neither of these outcomes is acceptable, there are compelling reasons to agree on a strategy that incorporates federal regulation and market forces to correct the oversupply of specialist physicians. Association of American Medical Colleges Washington, DC 20037

MICHAEL E. WHITCOMB, M.D.

Dr. Whitcomb was formerly the director of the Graduate Medical Education Division, American Medical Association, and is currently senior vice-president for medical education, Association of American Medical Colleges. The opinions and views expressed in this article are those of the author and do not necessarily represent the policies or positions of either the American Medical Association or the Association of American Medical Colleges.

REFERENCES 1. Summary report of the Graduate Medical Education National Advisory Committee. Vol. 1. Washington, D.C.: Department of Health and Human Services, 1980. 2. Weiner JP. Forecasting the effects of health reform on US physician workforce requirement: evidence from HMO staffing patterns. JAMA 1994;272: 222-30. 3. Medical education research and information database. Chicago: American Medical Association, 1994. 4. Report from the NRMP: results of the National Resident Matching Program for 1994. Acad Med 1994;69:508-10. 5. Mullan F, Politzer RM, Davis CH. Medical migration and the physician workforce: international medical graduates and American medicine. JAMA 1995;273:1521-7. 6. Whitcomb ME, Caswell J. The market structure of residency training. N Engl J Med 1986;314:710-2. 7. Council on Graduate Medical Education. Third report: improving access to health care through physician workforce reform: directions for the 21st century. Washington, D.C.: Department of Health and Human Services, 1992. 8. Annual report to Congress. Washington, D.C.: Physician Payment Review Commission, 1993. 9. Stoddard JJ, Kindig DA, Libby D. Graduate medical education reform: service provision transition costs. JAMA 1994;272:53-8. 10. Altman DF. Medical student career choice: will the market provide the solution to our health care workforce needs? Am J Med 1994;97:407-9. 11. Mullan F, Politzer RM, Gamliel S, Rivo ML. Balance and limits: modeling graduate medical education reform based on recommendations of the Council on Graduate Medical Education. Milbank Q 1994;72:385-98.

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