Letters
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should: • Include no more than 400 words of text, three authors, and five references • Type with double-spacing • Send three copies of the letter and a transfer-of copyright form (see Table of Contents for location) signed by all authors • Provide a self addressed envelope if they want to be notified that the letter was received Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned. A Proposed Trial of Amiodarone for Atrial Fibrillation To the Editors: For several years, we have used low-dose amiodarone (< 200 mg/d) in the treatment of patients with supraventricular arrhythmias and have seen only minimal side effects (1). Use of low-dose amiodarone has also been advocated for the treatment of congestive heart failure in patients with severely impaired left ventricular function. We use the drug to prevent sudden death in patients with complex ventricular dysrhythmias with severely impaired left ventricular function (2). We agree with Middlekauff and colleagues that the time has come for a large-scale, long-term study in these patient groups. They indicated that hyperthyroidism necessitated cessation of amiodarone; however, by using high-dose methimazole and by following the results of thyroid function studies frequently, we have found that patients can continue to receive the drug. Patients can then be weaned to a low dose of methimazole or tapered off it. One complication not mentioned by Middlekauff and colleagues is hypercholesterolemia secondary to amiodarone, which can be treated effectively with lovastatin or similar drugs that inhibit cholesterol synthesis (3). Larry E. Alves, MD St. Louis University School of Medicine St. Louis, MO Edward P. Rose, MD Southern Illinois University Belleville, IL References 1. Middlekauff HR, Wiener I, Saxon LA, Stevenson WG. Low-dose amiodarone for atrial fibrillation. Time for a prospective study? Ann Intern Med. 1992;116:1017-20. 2. Alves LE, Rose EP. Low dose amiodarone in congestive heart failure. J Am Coll Cardiol. 1992;17:1672-3. 3. Albert SG, Alves LE, Rose EP. Effects of amiodarone on serum lipoprotein levels. Am J Cardiol. 1991;68:259-61. To the Editors: Amiodarone appears to be the most effective antiarrhythmic agent for atrial and ventricular arrhythmias. The relatively high incidence of atrial fibrillation and the low 972
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success of long-term, standard antiarrhythmic treatment makes a trial of amiodarone attractive. However, one must re-examine indications for antiarrhythmic treatment of chronic atrial fibrillation. Preventing stroke has been one reason to attempt to maintain normal sinus rhythm. However, recent data from controlled trials of lowdose warfarin have shown the safety and efficacy of this approach in patients with chronic atrial fibrillation (1, 2). If rate control cannot be achieved with well-tolerated doses of atrioventricular blocking agents, catheter ablation and permanent pacing can be used as an effective alternative; these techniques have been successful in more than 90% of patients. Treatment may be indicated in patients who are uncomfortable with the palpitation associated with atrial fibrillation and in the small group of patients who are dependent on atrioventricular synchrony for adequate hemodynamics. Yet, antiarrhythmic therapy for atrial fibrillation may actually worsen survival (3). Although amiodarone has a low incidence of proarrhythmia, this might not be the case in long-term studies of untreated patients with relatively good survival. In our study of 427 patients treated for recurrent, sustained ventricular tachycardia or ventricular fibrillation (4), the incidence of new pulmonary toxicity continued to be 5% per year in years 3, 4, and 5 of follow-up, despite average daily amiodarone doses of only 250 to 350 mg/d, similar to those proposed by Middlekauff. Between years 3 and 5, an additional 11% of patients with sustained ventricular tachycardia and ventricular fibrillation had to discontinue amiodarone because of side effects. Skin discoloration rarely appears before 2 years of therapy but may affect more than 50% of patients by 5 years. Although such side effects may be acceptable to patients with histories of cardiac arrest, they are unlikely to be acceptable to patients with atrial fibrillation. One of the lessons of the Cardiac Arrhythmia Suppression Trial (CAST) is that therapy of benign arrhythmias is ill advised (5). Although amiodarone is valuable in treating lifethreatening arrhythmias, we cannot assume that it would be as attractive for a less serious arrhythmia such as atrial fibrillation. John M. Herre, MD 150 Kingsley Lane Norfolk, VA 23505 References 1. The Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N Engl J Med. 1990; 323:1505-11. 2. Stroke Prevention in Atrial Fibrillation Study Group Investigators. Preliminary report of the stroke prevention in atrial fibrillation study. N Engl J Med. 1990;322:863-8. 3. Coplon SE, Antman EM, Berlin JA, Hewitt P, Chalmers TC. Efficacy and safety of quinidine therapy for maintenance of sinus rhythm after cardioversion. Circulation. 1990;82:1106-16. 4. Herre JM, Sauve MJ, Malone P, Griffin JC, Helmy I, Langberg JJ, et al. Long-term results of amiodarone therapy in patients with recurrent sustained ventricular tachycardia or ventricular fibrillation. J Am Coll Cardiol. 1989;13:442-9. 5. CAST Investigators. Preliminary report: effect of encainiade and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989;321:406-12. In response: We were encouraged that Drs. Alves and Rose were able to continue to use amiodarone in their patients despite the associated hyperthyroidism. We have had similar
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favorable experience; however, it has been far too limited to permit a recommendation. Although we were aware of their article reporting the association between amiodarone and hypercholesterolemia, we await further information about the best approach to this problem. In reference to Dr. Herre's letter, we make several comments. First, the indication for therapy in most patients with atrial fibrillation is the relief of symptoms such as palpitations, angina, or syncope. The use of warfarin, although clearly important, will not improve symptoms. In terms of safety, the doses of amiodarone for atrial fibrillation (< 200 mg/d) are much lower than those used for ventricular arrhythmias. In retrospective studies of low-dose amiodarone, the incidence of toxicity, including pulmonary toxicity, is extremely low (1). Finally, the purpose of the proposed study is the scientific investigation of all these concerns, including efficacy, patient acceptance, and toxicity of low-dose amiodarone for atrial fibrillation, in a prospective, randomized, double-blind, placebo-controlled trial.
eral blood mononuclear cells to mitogens such as phytohemagglutinin, an effect which is not reversed by exogenous interleukin-2 (3). Clinical immunosuppression is not ordinarily a feature of persistent measles virus infection, although subtle lymphocyte dysfunction has been noted (4). In the case of our patient, the extent of immunosuppression was life-threatening, although it is not certain whether the immunosuppression was related to the measles virus infection. Fatal bacterial infections as a result of measles virus-induced immunosuppression have been reported in primates (5), but the degree of measles-induced immunosuppression in humans does not generally predispose them to the opportunistic infections seen in AIDS. Although alternative etiologic agents are currently being evaluated in other cases of idiopathic CD4 T-lymphocytopenia, measles may have led to a transient immunosuppression and may have been responsible for the development of opportunistic infections such as candidiasis and P. carinii pneumonia in this HIV-seronegative homosexual man.
Holly R. Middlekauff, MD Isaac Wiener, MD William G. Stevenson, MD UCLA School of Medicine Los Angeles, CA
Ramon A. Torres, MD Michael R. Barr, BS St. Vincent's Hospital and Medical Center 153 West 11th Street New York, NY 10011
Reference 1. Middlekauff HR, Wiener I, Saxon LA, Stevenson WG. Low-dose amiodarone for atrial fibrillation: Time for a prospective study? Ann Intern Med. 1992;116:1017-20.
AIDS-associated Illness and HIV Negativity To the Editors: In light of recent cases of idiopathic CD4 T-lymphocytopenia (1), we report a case of an acquired immunodeficiency syndrome (AIDS)-associated illness in a human immunodeficiency virus (HlV)-seronegative man with disseminated measles infection. In April 1991, a 25-year-old homosexual man presented with 1-week history of a morbilliform skin eruption accompanied by fever, nonproductive cough, dyspnea, and lethargy. The patient had emigrated from Venezuela and had never received measles immunization. Five months before the onset of illness, he had tested negative for HIV-1 antibodies by enzyme immunoassay (EIA). Physical examination was remarkable for a temperature of 40 °C, oral candidiasis, conjunctivitis, and a diffuse erythematous maculopapular rash involving his face and trunk. No Koplik spots were noted. Laboratory examination showed hypoxemia (room air Po 2 , 56 mm Hg with an alveolar-arterial gradient of 46), lymphopenia (total lymphocyte count, 0.63 x 109/L), thrombocytopenia (platelet count, 96 x 109/L), and an elevated lactate dehydrogenase level (6.0 /ukat/L). Immunologic phenotyping was not done. Chest radiographs showed bilateral interstitial reticulonodular infiltrates. Bronchoscopy showed edematous, friable and erythematous bronchial mucosa, and bronchoalveolar lavage showed cysts and trophozoites of Pneumocystis carinii. He received 3 weeks of therapy with trimethoprim-sulfamethoxazole, which resulted in total resolution of symptoms. The rash resolved after 2 weeks without sequelae. During the following 10 months, three HIV-1 antibody tests by EIA were negative, as were an EIA for HIV-2, an HIV-1 p24 antigen assay, and a polymerase chain reaction (PCR) test for HIV-1. Four months later, his CD4+ lymphocyte count was 660/mm3, skin testing for anergy was positive to three antigens, and measles antibodies were present (measles index, 12.71 by enzyme immunoassay, Diamedix Corporation, Miami, Florida). Several non-HIV disorders are associated with CD4+ T-cell deficiency and dysfunction. The principal illnesses characterized by virus-induced immunodeficiency are measles and AIDS. Both viruses show an affinity for the immune system. The immunologic dysfunction due to measles virus infection develops quickly and is ordinarily short-lived in patients without pre-existing T-lymphocyte dysfunction (2). Measles virus infection also suppresses the proliferative response of periph-
References 1. Centers for Disease Control. Unexplained CD4+ T-lymphocyte depletion in persons without evident HIV infection—United States. MMWR. 1992;41:541-5. 2. Burnet FM. Measles as an index of immunological frequency. Lancet. 1968;2:610-3. 3. McChesney MB, Oldstone MB. Virus-induced immunosuppression: infections with measles virus and human immunodeficiency virus. Adv Immunol. 335-80. 4. ter Meulen V, Carter MJ. Measles Virus Persistency and Disease. Prog Med Virol. 1984;30:44-61. 5. McChesney MB, Fujinami RS, Lerche NW, Marx PA, Oldstone MB. Virus-induced immunosuppression: infection of peripheral blood mononuclear cells and suppression of immunoglobulin synthesis during natural measles virus infection of rhesus monkeys. J Infect Dis. 1989;159:757-60.
Internal Medicine Curriculum Reform To the Editors: The supplement, Internal Medicine Curriculum Reform (1), addresses the need to change the training of general internists and to attract the best and the brightest back to the most efficient, cost-effective way to manage adult health problems. However, there was too little discussion regarding the income of generalists compared with procedure-oriented subspecialists in internal medicine. Altruism may lead bright young people into medicine and may sustain them for a time in practice; however, as family needs and quality of life issues intrude, the gross discrepancies between incomes of procedure-oriented physicians and cognitive specialists become too obvious. To survive, internists' compensation must rise appreciably or procedure-oriented physicians' income must fall. We also suggest that a fourth year be added to the training of generalists and that emphasis be placed on the cost effectiveness of all medical procedures (including their risks and benefits) and that medical ethics, including quality-of-life issues, be emphasized to ensure that the patient's interests are kept foremost. With this background, these physicians could better interact with hospital administrators, insurance company representatives, and bureaucrats in advocating better care. Controlling the cost of medical care is not just a responsibility of politicians but should also be a concern of every physician. We have been in practice long enough to see the patient get lost in the swirl of subspecialty care without a true "conductor of the orchestra." This new breed of internist could help apply the brakes to the runaway American health care system. Jason E. McClellan, MD C. Patrick Laughlin, MD Riverside Hospital Newport News, VA 23601
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References 1. Inui TS, Nolan JP; eds. Internal medicine curriculum reform. Ann Intern Med. 1992;116:1041-115. 2. Petersdorf RG. Primary care applicants—they get no respect. N Engl J Med. 1992;326:408-9. 3. Karpf M, Levey GS. Training primary care physicians. Ann Intern Med. 1992;116:514-5. 4. Sulmasy DP. Physicians, cost control, and ethics. Ann Intern Med. 1992;116:920-6. 5. Davies NE, Felder LH. Applying brakes to the runaway American health care system. JAMA. 1990;263:73-6.
To the Editors: The burgeoning of knowledge and technology in each procedure-oriented subspecialty is not likely to abate. Even dramatic rearrangement of the resource-based, relative value scale may not sufficiently reward nonprocedureoriented cognition (1). One possible way to help develop the general internists is to train them in 1) endoscopic procedures such as diagnostic bronchoscopy, colonoscopy, or esophagogastroduodenoscopy; 2) cardiac or esophageal ultrasound, Doppler, Holter, or pacemaker technology; or 3) routine hemodialysis. These procedures are currently lucrative and are also within the lowest class of malpractice risk for the general internist. Most of these procedures can be done both in outpatient or hospital environments. By choosing one or more of these special techniques, they could become generalists with special competence. As Alfred North Whitehead said, "There can be no adequate technical education which is not liberal and no liberal education which is not technical." Gerald N. Olsen, MD University of South Carolina Columbia, SC 29208 Reference 1. Prashker MJ, Meenan RF. Subspecialty training: is it financially worthwhile? Ann Intern Med. 1991;115:715-9.
To the Editors: After completing their residency in internal medicine, as many as 70% of residents go on to receive further training in a subspecialty. I suggest that the subspecialty programs require at least 2 years of general internal medicine practice before subspecialty training. This requirement would increase the number of general internists by approximately 10 000, and fewer internists would pursue subspecialty training after being in practice for 2 years. Phasing in this policy over a period of 5 years would result in only minimal disruption of the fellowship programs. Subspecialists might also maintain their interest in general internal medicine and be more patient-oriented rather than diseaseoriented. Because of the higher income earned during practice, it should be possible for more of these physicians to pay off the loans incurred during college and medical school earlier than they would if they were to enter subspecialty training directly, thus removing some of the financial pressure on them to enter these subspecialties. Mahendr S. Kochar, MD The Medical College of Wisconsin Milwaukee, WI 53226 Reference 1. Inui TS, Nolan JP; eds. Internal medicine curriculum reform. Ann Intern Med. 1992;116:1041-115.
To the Editors: The supplement on curricular reform in internal medicine appropriately called for a shift back to the care of the whole patient. The accuracy of diagnoses and the establishment of therapeutic physician-patient relationships depend on effective medical interviewing skills. Patient satisfaction, compliance, perception of physician competence, health outcomes, and malpractice suits are strongly related to physicians' interpersonal skills (1). In addition, psychosocial problems are very common in ambulatory practice, and approximately 55% of all mental health care in the United States is provided by primary care physicians (2). 974
However, many residents are deficient in these areas (3, 4). There are also clear needs for faculty development to ensure effective teaching of interpersonal skills and psychosocial aspects of care as well as for adoption and expansion of core curricula (5, 6). With improved training, internal medicine residents will be more prepared to care for "the whole patient" and will be more satisfied with their practices. Dennis H. Novack, MD Rhode Island Hospital Providence, RI 02903 Mack Lipkin, Jr., MD New York University School of Medicine New York, NY References 1. Simpson M. Doctor-patient communication: the Toronto consensus statement. Br Med J. 1991;303:1385-7. 2. Regier DA, Goldberg ID, Taube CA. The de facto US mental health services system: a public health perspective. Arch Gen Psychiatry. 1978;35:685-93. 3. Beckman HB, Frankel RM. The effect of physician behavior on the collection of data. Ann Intern Med. 1984;101:692-6. 4. Piatt FW, McMath JC. Clinical hypocompetence: the interview. Ann Intern Med. 1979;91:898-902. 5. Lipkin M Jr, Quill TE, Napodano RJ. The medical interview: a core curriculum for residencies in internal medicine. Ann Intern Med. 1984;100:277-84. 6. Williamson PR, et al. The medical interview and psychosocial aspects of medicine: block curricula for residents. J Gen Intern Med. 1992;7:235-42.
To the Editors: Curricular innovations reflect continuing efforts to make internal medicine a more attractive career choice at a time when applications for internal medicine positions are down and when program alumni register continuing discontent with their preparation for the "real world" of medical practice (1). As program managers and teachers in Veterans Affairs (VA) teaching hospitals, we would like to share our own perspective. Twenty years ago, Feinstein (2) lamented the "decline of supervision" in U.S. training programs, emphasizing that no system of medical record-keeping could substitute for on-thescene supervision. Kosecoff's 1986 study (3) of top-rated U.S. residency programs showed that supervision was often inadequate and that quality assurance standards were unsatisfactorily met in many programs. Recognition by the educational establishment of the need for medical curricular reform is certainly welcome. Nevertheless, our medical schools and their affiliated hospitals (often VA medical centers) cannot precipitously accomplish a 50% increase in ambulatory care exposure. It will take cooperation, commitment, and strategic planning to accomplish the requisite program reorganization and faculty development objectives (4). Because VA facilities are major training sites, we recommend inclusion of VA decision-makers in the dialogue on internal medicine curriculum reform. In 1903, Osier observed, "[When] some historian traces the development of the profession . . . he will pass judgment—yes, severe judgment—on the absence of the sense of responsibility in medical education" (5). We believe that by developing clinical environments where the emphasis is on excellent clinical supervision, practical instruction, and superior medical care, medical educators can best serve their patients, their trainees, and the public. Thomas A. Parrino, MD Providence Veterans Affairs Medical Center Providence, RI 02908 Russell D. Tyler, MD David K. Lee, MD National Association of Veterans Affairs Physician Ambulatory Managers References 1. Dale DC. Alumni surveys for evaluation of innovations in medical education. J Gen Intern Med. 1991;6:587.
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2. Feinstein AR. The problems of the "problem-oriented record." Ann Intern Med. 1973;78:751-62. 3. Kosecoff J, Fink A, Brook RH, Davies AR, et al. General medical care and the education of internists in university hospitals. Ann Intern Med. 1985;102:250-7. 4. Lee D, Nugent G. Costs associated with ambulatory care and education. Acad Med. 1989;64:S44-50. 5. Nardone DA, Webb DW. Administration in ambulatory care. Acad Med. 1989;64:S28-34.
complexity of the problems associated with reforming the residency curriculum for internal medicine. Further substantive input by practicing and academic internists will be critical in moving this process of reform along.
To the Editors: I enjoyed your recent symposium on internal medicine curriculum reform but am moved to ask, when was the last time you took off your white coats, grabbed your black bags, and made a house call? You talk about what is wrong with the discipline of internal medicine and what can be done to fix it. Internists are rewarded like their surgical colleagues; you are not going to attract students unless you can show the beauty of practice. There is nothing more wonderful than a doctor at the bedside in a sick patient's home. Devoid of much technology, it is just the physician, his skills, and the patient. That is the substance of America's current hunger—a return to old time values and to old time doctoring. We cannot expect our medical youth to pursue the higher road for the greater good if the teachers themselves have lost touch with the quintessence of medical care. You senior clinicians should take a break from the medical center fracas and grab a couple of those impressionable residents and students and take them on a house call. Warning—you may have to pass some exotic places on the way. (In my neck of the woods, the towns have names like Warsaw, Callao, Hague, and Jamaica). The trip will do all of you some good—it will take you back to medicine's roots.
To the Editors: As a rheumatologist, I recently evaluated a patient with osteogenesis imperfecta, who had come for a second opinion. His enlarged bossed skull, blue sclera, and severely underdeveloped lower extremities were disturbingly distracting, even to a physician accustomed to dealing with physical deformities and who had seen such patients before. As I take a history, I usually scan the patient's visible joints, looking for signs of inflammation or deformity. With this patient, however, it was not until I was near the end of the physical examination when I felt his warm, swollen elbows, wrists, and metacarpals and noticed he had frank synovitis. When I questioned him about symptoms, he described morning stiffness, pain, and swelling of these joints for the past 7 years. He had been seeing an excellent rheumatologist during this period. When asked if he had told the rheumatologist about his joint symptoms, he replied, "Yes, but when normal people see someone with a handicap, a stop sign goes up, and they don't see beyond the handicap." After my initial feelings of embarrassment, I proceeded to aspirate his right elbow and obtained cloudy fluid with a white cell count of 16 x 109/L, negative for crystals. A rheumatoid factor was positive at 1:160, and radiographs showed diffuse joint space narrowing. These findings confirmed that he had rheumatoid arthritis in addition to his osteogenesis imperfecta. As physicians, putting up stop signs may be an adaptive response to the magnitude of data that we have to process daily. It is sometimes easier to categorize patients and to assign them common symptoms and problems even before we talk to them and examine them. My eyes saw his swollen joints, my fingers felt the warmth, yet I almost did not realize that he had arthritis because I had trouble blocking out his primary deformity. For those of us without physical disabilities, it is almost impossible to imagine the obstacles that the handicapped must have, including those sometimes imposed by their own physicians.
Jeffrey A. Margolis, MD Box 612 Tappahannock, VA 22560 In response: Drs. McClellan and Langlen highlight the role of income as a disincentive to careers in general medicine and suggest that a fourth year of training be added to the residency for generalists. Although more emphasis would be on cost effectiveness of medical procedures, it is difficult to see how this extra year would address the problem of the income differential with proceduralists. Dr. Olsen suggests using a fourth year of general residency to train internists in the "currently lucrative" procedures of the specialists. Although an attractive concept, it would seem to be more practical in geographic areas where specialization is less well developed. Dr. Kochar suggests that 2 years of required practice in general medicine before training in a subspecialty might both increase the number of generalists and decrease the number of subspecialists. One could argue that 2 years of practice in a primary care specialty might be mandated for further training in any of the nongeneralist disciplines, including the surgical specialties. Drs. Novack and Lipkin have correctly emphasized the need in training programs for the further development of interpersonal skills and increased competency in the psychosocial aspects of care. We agree that simply switching instructional sites to the ambulatory setting will be inadequate unless new models for training generalists are adopted. The difficulty in a precipitous movement of residents from the inpatient to outpatient setting is pointed out by Drs. Parrino, Tyler and Lee. Given the importance of VA Medical Centers in residency training, we agree that representatives from these centers should be involved in the dialogue on internal medicine curriculum reform. Dr. Margolis points out that showing the beauties of practicing general medicine is one of the few feasible ways of attracting students until such time as internists are rewarded like their surgical colleagues. He chides the academic community for failing to provide the role models of physicians still willing to make house calls. This is consistent with the emphasis in the Supplement on the increased use of community physician offices as sites of training. The Supplement Editors appreciate the thoughtful comments of the correspondents and agree with their emphasis on the
—The Editors Handicapping the Handicapped
Michael J. Maricic, MD University of Arizona Health Science Center Tucson, AZ 85724 Correction: Spectrum Bias in Evaluation of Diagnostic Tests In the article by Lachs and colleagues (1), Table 1 (column 1) gives incorrect percents for patients in the high-probability subgroup. Because of a programming error, four patients with missing previous probabilities of urinary tract infection were mistakenly classified as being in the high-probability subgroup. Thus, the percents should be based on a denominator of 103. The values for sensitivity and specificity and their associated CIs in Table 3 are all based on n = 103 and remain correct. Reference 1. Lachs MA, Nachamkin I, Edelstein PH, Goldman J, Feinstein AR, Schwartz JS. Spectrum bias in the evaluation of diagnostic tests: lessons from the rapid dipstick test for urinary tract infection. Ann Intern Med. 1992;117:135-40.
Correction: Review of Facing
A book review (1) incorrectly noted the author of the book and did not include the cost of the book's hardcover edition. The sole author is Sandra L. Bertman, and the hardcover price is $45.00. Reference 1. Abrams FR. Review of Facing Death: Images, Insights, and Interventions. Ann Intern Med. 1992;116:880.
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The Editors welcome submissions for possible publication in the Letters section. Authors of letters should: • Include no more than 400 words of text, three authors, and five references • Type with double-spacing • Send three copies of the letter and a transfer-of copyright form (see Table of Contents for location) signed by all authors • Provide a self addressed envelope if they want to be notified that the letter was received Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned. A Proposed Trial of Amiodarone for Atrial Fibrillation To the Editors: For several years, we have used low-dose amiodarone (< 200 mg/d) in the treatment of patients with supraventricular arrhythmias and have seen only minimal side effects (1). Use of low-dose amiodarone has also been advocated for the treatment of congestive heart failure in patients with severely impaired left ventricular function. We use the drug to prevent sudden death in patients with complex ventricular dysrhythmias with severely impaired left ventricular function (2). We agree with Middlekauff and colleagues that the time has come for a large-scale, long-term study in these patient groups. They indicated that hyperthyroidism necessitated cessation of amiodarone; however, by using high-dose methimazole and by following the results of thyroid function studies frequently, we have found that patients can continue to receive the drug. Patients can then be weaned to a low dose of methimazole or tapered off it. One complication not mentioned by Middlekauff and colleagues is hypercholesterolemia secondary to amiodarone, which can be treated effectively with lovastatin or similar drugs that inhibit cholesterol synthesis (3). Larry E. Alves, MD St. Louis University School of Medicine St. Louis, MO Edward P. Rose, MD Southern Illinois University Belleville, IL References 1. Middlekauff HR, Wiener I, Saxon LA, Stevenson WG. Low-dose amiodarone for atrial fibrillation. Time for a prospective study? Ann Intern Med. 1992;116:1017-20. 2. Alves LE, Rose EP. Low dose amiodarone in congestive heart failure. J Am Coll Cardiol. 1992;17:1672-3. 3. Albert SG, Alves LE, Rose EP. Effects of amiodarone on serum lipoprotein levels. Am J Cardiol. 1991;68:259-61. To the Editors: Amiodarone appears to be the most effective antiarrhythmic agent for atrial and ventricular arrhythmias. The relatively high incidence of atrial fibrillation and the low 972
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success of long-term, standard antiarrhythmic treatment makes a trial of amiodarone attractive. However, one must re-examine indications for antiarrhythmic treatment of chronic atrial fibrillation. Preventing stroke has been one reason to attempt to maintain normal sinus rhythm. However, recent data from controlled trials of lowdose warfarin have shown the safety and efficacy of this approach in patients with chronic atrial fibrillation (1, 2). If rate control cannot be achieved with well-tolerated doses of atrioventricular blocking agents, catheter ablation and permanent pacing can be used as an effective alternative; these techniques have been successful in more than 90% of patients. Treatment may be indicated in patients who are uncomfortable with the palpitation associated with atrial fibrillation and in the small group of patients who are dependent on atrioventricular synchrony for adequate hemodynamics. Yet, antiarrhythmic therapy for atrial fibrillation may actually worsen survival (3). Although amiodarone has a low incidence of proarrhythmia, this might not be the case in long-term studies of untreated patients with relatively good survival. In our study of 427 patients treated for recurrent, sustained ventricular tachycardia or ventricular fibrillation (4), the incidence of new pulmonary toxicity continued to be 5% per year in years 3, 4, and 5 of follow-up, despite average daily amiodarone doses of only 250 to 350 mg/d, similar to those proposed by Middlekauff. Between years 3 and 5, an additional 11% of patients with sustained ventricular tachycardia and ventricular fibrillation had to discontinue amiodarone because of side effects. Skin discoloration rarely appears before 2 years of therapy but may affect more than 50% of patients by 5 years. Although such side effects may be acceptable to patients with histories of cardiac arrest, they are unlikely to be acceptable to patients with atrial fibrillation. One of the lessons of the Cardiac Arrhythmia Suppression Trial (CAST) is that therapy of benign arrhythmias is ill advised (5). Although amiodarone is valuable in treating lifethreatening arrhythmias, we cannot assume that it would be as attractive for a less serious arrhythmia such as atrial fibrillation. John M. Herre, MD 150 Kingsley Lane Norfolk, VA 23505 References 1. The Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N Engl J Med. 1990; 323:1505-11. 2. Stroke Prevention in Atrial Fibrillation Study Group Investigators. Preliminary report of the stroke prevention in atrial fibrillation study. N Engl J Med. 1990;322:863-8. 3. Coplon SE, Antman EM, Berlin JA, Hewitt P, Chalmers TC. Efficacy and safety of quinidine therapy for maintenance of sinus rhythm after cardioversion. Circulation. 1990;82:1106-16. 4. Herre JM, Sauve MJ, Malone P, Griffin JC, Helmy I, Langberg JJ, et al. Long-term results of amiodarone therapy in patients with recurrent sustained ventricular tachycardia or ventricular fibrillation. J Am Coll Cardiol. 1989;13:442-9. 5. CAST Investigators. Preliminary report: effect of encainiade and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989;321:406-12. In response: We were encouraged that Drs. Alves and Rose were able to continue to use amiodarone in their patients despite the associated hyperthyroidism. We have had similar
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favorable experience; however, it has been far too limited to permit a recommendation. Although we were aware of their article reporting the association between amiodarone and hypercholesterolemia, we await further information about the best approach to this problem. In reference to Dr. Herre's letter, we make several comments. First, the indication for therapy in most patients with atrial fibrillation is the relief of symptoms such as palpitations, angina, or syncope. The use of warfarin, although clearly important, will not improve symptoms. In terms of safety, the doses of amiodarone for atrial fibrillation (< 200 mg/d) are much lower than those used for ventricular arrhythmias. In retrospective studies of low-dose amiodarone, the incidence of toxicity, including pulmonary toxicity, is extremely low (1). Finally, the purpose of the proposed study is the scientific investigation of all these concerns, including efficacy, patient acceptance, and toxicity of low-dose amiodarone for atrial fibrillation, in a prospective, randomized, double-blind, placebo-controlled trial.
eral blood mononuclear cells to mitogens such as phytohemagglutinin, an effect which is not reversed by exogenous interleukin-2 (3). Clinical immunosuppression is not ordinarily a feature of persistent measles virus infection, although subtle lymphocyte dysfunction has been noted (4). In the case of our patient, the extent of immunosuppression was life-threatening, although it is not certain whether the immunosuppression was related to the measles virus infection. Fatal bacterial infections as a result of measles virus-induced immunosuppression have been reported in primates (5), but the degree of measles-induced immunosuppression in humans does not generally predispose them to the opportunistic infections seen in AIDS. Although alternative etiologic agents are currently being evaluated in other cases of idiopathic CD4 T-lymphocytopenia, measles may have led to a transient immunosuppression and may have been responsible for the development of opportunistic infections such as candidiasis and P. carinii pneumonia in this HIV-seronegative homosexual man.
Holly R. Middlekauff, MD Isaac Wiener, MD William G. Stevenson, MD UCLA School of Medicine Los Angeles, CA
Ramon A. Torres, MD Michael R. Barr, BS St. Vincent's Hospital and Medical Center 153 West 11th Street New York, NY 10011
Reference 1. Middlekauff HR, Wiener I, Saxon LA, Stevenson WG. Low-dose amiodarone for atrial fibrillation: Time for a prospective study? Ann Intern Med. 1992;116:1017-20.
AIDS-associated Illness and HIV Negativity To the Editors: In light of recent cases of idiopathic CD4 T-lymphocytopenia (1), we report a case of an acquired immunodeficiency syndrome (AIDS)-associated illness in a human immunodeficiency virus (HlV)-seronegative man with disseminated measles infection. In April 1991, a 25-year-old homosexual man presented with 1-week history of a morbilliform skin eruption accompanied by fever, nonproductive cough, dyspnea, and lethargy. The patient had emigrated from Venezuela and had never received measles immunization. Five months before the onset of illness, he had tested negative for HIV-1 antibodies by enzyme immunoassay (EIA). Physical examination was remarkable for a temperature of 40 °C, oral candidiasis, conjunctivitis, and a diffuse erythematous maculopapular rash involving his face and trunk. No Koplik spots were noted. Laboratory examination showed hypoxemia (room air Po 2 , 56 mm Hg with an alveolar-arterial gradient of 46), lymphopenia (total lymphocyte count, 0.63 x 109/L), thrombocytopenia (platelet count, 96 x 109/L), and an elevated lactate dehydrogenase level (6.0 /ukat/L). Immunologic phenotyping was not done. Chest radiographs showed bilateral interstitial reticulonodular infiltrates. Bronchoscopy showed edematous, friable and erythematous bronchial mucosa, and bronchoalveolar lavage showed cysts and trophozoites of Pneumocystis carinii. He received 3 weeks of therapy with trimethoprim-sulfamethoxazole, which resulted in total resolution of symptoms. The rash resolved after 2 weeks without sequelae. During the following 10 months, three HIV-1 antibody tests by EIA were negative, as were an EIA for HIV-2, an HIV-1 p24 antigen assay, and a polymerase chain reaction (PCR) test for HIV-1. Four months later, his CD4+ lymphocyte count was 660/mm3, skin testing for anergy was positive to three antigens, and measles antibodies were present (measles index, 12.71 by enzyme immunoassay, Diamedix Corporation, Miami, Florida). Several non-HIV disorders are associated with CD4+ T-cell deficiency and dysfunction. The principal illnesses characterized by virus-induced immunodeficiency are measles and AIDS. Both viruses show an affinity for the immune system. The immunologic dysfunction due to measles virus infection develops quickly and is ordinarily short-lived in patients without pre-existing T-lymphocyte dysfunction (2). Measles virus infection also suppresses the proliferative response of periph-
References 1. Centers for Disease Control. Unexplained CD4+ T-lymphocyte depletion in persons without evident HIV infection—United States. MMWR. 1992;41:541-5. 2. Burnet FM. Measles as an index of immunological frequency. Lancet. 1968;2:610-3. 3. McChesney MB, Oldstone MB. Virus-induced immunosuppression: infections with measles virus and human immunodeficiency virus. Adv Immunol. 335-80. 4. ter Meulen V, Carter MJ. Measles Virus Persistency and Disease. Prog Med Virol. 1984;30:44-61. 5. McChesney MB, Fujinami RS, Lerche NW, Marx PA, Oldstone MB. Virus-induced immunosuppression: infection of peripheral blood mononuclear cells and suppression of immunoglobulin synthesis during natural measles virus infection of rhesus monkeys. J Infect Dis. 1989;159:757-60.
Internal Medicine Curriculum Reform To the Editors: The supplement, Internal Medicine Curriculum Reform (1), addresses the need to change the training of general internists and to attract the best and the brightest back to the most efficient, cost-effective way to manage adult health problems. However, there was too little discussion regarding the income of generalists compared with procedure-oriented subspecialists in internal medicine. Altruism may lead bright young people into medicine and may sustain them for a time in practice; however, as family needs and quality of life issues intrude, the gross discrepancies between incomes of procedure-oriented physicians and cognitive specialists become too obvious. To survive, internists' compensation must rise appreciably or procedure-oriented physicians' income must fall. We also suggest that a fourth year be added to the training of generalists and that emphasis be placed on the cost effectiveness of all medical procedures (including their risks and benefits) and that medical ethics, including quality-of-life issues, be emphasized to ensure that the patient's interests are kept foremost. With this background, these physicians could better interact with hospital administrators, insurance company representatives, and bureaucrats in advocating better care. Controlling the cost of medical care is not just a responsibility of politicians but should also be a concern of every physician. We have been in practice long enough to see the patient get lost in the swirl of subspecialty care without a true "conductor of the orchestra." This new breed of internist could help apply the brakes to the runaway American health care system. Jason E. McClellan, MD C. Patrick Laughlin, MD Riverside Hospital Newport News, VA 23601
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References 1. Inui TS, Nolan JP; eds. Internal medicine curriculum reform. Ann Intern Med. 1992;116:1041-115. 2. Petersdorf RG. Primary care applicants—they get no respect. N Engl J Med. 1992;326:408-9. 3. Karpf M, Levey GS. Training primary care physicians. Ann Intern Med. 1992;116:514-5. 4. Sulmasy DP. Physicians, cost control, and ethics. Ann Intern Med. 1992;116:920-6. 5. Davies NE, Felder LH. Applying brakes to the runaway American health care system. JAMA. 1990;263:73-6.
To the Editors: The burgeoning of knowledge and technology in each procedure-oriented subspecialty is not likely to abate. Even dramatic rearrangement of the resource-based, relative value scale may not sufficiently reward nonprocedureoriented cognition (1). One possible way to help develop the general internists is to train them in 1) endoscopic procedures such as diagnostic bronchoscopy, colonoscopy, or esophagogastroduodenoscopy; 2) cardiac or esophageal ultrasound, Doppler, Holter, or pacemaker technology; or 3) routine hemodialysis. These procedures are currently lucrative and are also within the lowest class of malpractice risk for the general internist. Most of these procedures can be done both in outpatient or hospital environments. By choosing one or more of these special techniques, they could become generalists with special competence. As Alfred North Whitehead said, "There can be no adequate technical education which is not liberal and no liberal education which is not technical." Gerald N. Olsen, MD University of South Carolina Columbia, SC 29208 Reference 1. Prashker MJ, Meenan RF. Subspecialty training: is it financially worthwhile? Ann Intern Med. 1991;115:715-9.
To the Editors: After completing their residency in internal medicine, as many as 70% of residents go on to receive further training in a subspecialty. I suggest that the subspecialty programs require at least 2 years of general internal medicine practice before subspecialty training. This requirement would increase the number of general internists by approximately 10 000, and fewer internists would pursue subspecialty training after being in practice for 2 years. Phasing in this policy over a period of 5 years would result in only minimal disruption of the fellowship programs. Subspecialists might also maintain their interest in general internal medicine and be more patient-oriented rather than diseaseoriented. Because of the higher income earned during practice, it should be possible for more of these physicians to pay off the loans incurred during college and medical school earlier than they would if they were to enter subspecialty training directly, thus removing some of the financial pressure on them to enter these subspecialties. Mahendr S. Kochar, MD The Medical College of Wisconsin Milwaukee, WI 53226 Reference 1. Inui TS, Nolan JP; eds. Internal medicine curriculum reform. Ann Intern Med. 1992;116:1041-115.
To the Editors: The supplement on curricular reform in internal medicine appropriately called for a shift back to the care of the whole patient. The accuracy of diagnoses and the establishment of therapeutic physician-patient relationships depend on effective medical interviewing skills. Patient satisfaction, compliance, perception of physician competence, health outcomes, and malpractice suits are strongly related to physicians' interpersonal skills (1). In addition, psychosocial problems are very common in ambulatory practice, and approximately 55% of all mental health care in the United States is provided by primary care physicians (2). 974
However, many residents are deficient in these areas (3, 4). There are also clear needs for faculty development to ensure effective teaching of interpersonal skills and psychosocial aspects of care as well as for adoption and expansion of core curricula (5, 6). With improved training, internal medicine residents will be more prepared to care for "the whole patient" and will be more satisfied with their practices. Dennis H. Novack, MD Rhode Island Hospital Providence, RI 02903 Mack Lipkin, Jr., MD New York University School of Medicine New York, NY References 1. Simpson M. Doctor-patient communication: the Toronto consensus statement. Br Med J. 1991;303:1385-7. 2. Regier DA, Goldberg ID, Taube CA. The de facto US mental health services system: a public health perspective. Arch Gen Psychiatry. 1978;35:685-93. 3. Beckman HB, Frankel RM. The effect of physician behavior on the collection of data. Ann Intern Med. 1984;101:692-6. 4. Piatt FW, McMath JC. Clinical hypocompetence: the interview. Ann Intern Med. 1979;91:898-902. 5. Lipkin M Jr, Quill TE, Napodano RJ. The medical interview: a core curriculum for residencies in internal medicine. Ann Intern Med. 1984;100:277-84. 6. Williamson PR, et al. The medical interview and psychosocial aspects of medicine: block curricula for residents. J Gen Intern Med. 1992;7:235-42.
To the Editors: Curricular innovations reflect continuing efforts to make internal medicine a more attractive career choice at a time when applications for internal medicine positions are down and when program alumni register continuing discontent with their preparation for the "real world" of medical practice (1). As program managers and teachers in Veterans Affairs (VA) teaching hospitals, we would like to share our own perspective. Twenty years ago, Feinstein (2) lamented the "decline of supervision" in U.S. training programs, emphasizing that no system of medical record-keeping could substitute for on-thescene supervision. Kosecoff's 1986 study (3) of top-rated U.S. residency programs showed that supervision was often inadequate and that quality assurance standards were unsatisfactorily met in many programs. Recognition by the educational establishment of the need for medical curricular reform is certainly welcome. Nevertheless, our medical schools and their affiliated hospitals (often VA medical centers) cannot precipitously accomplish a 50% increase in ambulatory care exposure. It will take cooperation, commitment, and strategic planning to accomplish the requisite program reorganization and faculty development objectives (4). Because VA facilities are major training sites, we recommend inclusion of VA decision-makers in the dialogue on internal medicine curriculum reform. In 1903, Osier observed, "[When] some historian traces the development of the profession . . . he will pass judgment—yes, severe judgment—on the absence of the sense of responsibility in medical education" (5). We believe that by developing clinical environments where the emphasis is on excellent clinical supervision, practical instruction, and superior medical care, medical educators can best serve their patients, their trainees, and the public. Thomas A. Parrino, MD Providence Veterans Affairs Medical Center Providence, RI 02908 Russell D. Tyler, MD David K. Lee, MD National Association of Veterans Affairs Physician Ambulatory Managers References 1. Dale DC. Alumni surveys for evaluation of innovations in medical education. J Gen Intern Med. 1991;6:587.
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2. Feinstein AR. The problems of the "problem-oriented record." Ann Intern Med. 1973;78:751-62. 3. Kosecoff J, Fink A, Brook RH, Davies AR, et al. General medical care and the education of internists in university hospitals. Ann Intern Med. 1985;102:250-7. 4. Lee D, Nugent G. Costs associated with ambulatory care and education. Acad Med. 1989;64:S44-50. 5. Nardone DA, Webb DW. Administration in ambulatory care. Acad Med. 1989;64:S28-34.
complexity of the problems associated with reforming the residency curriculum for internal medicine. Further substantive input by practicing and academic internists will be critical in moving this process of reform along.
To the Editors: I enjoyed your recent symposium on internal medicine curriculum reform but am moved to ask, when was the last time you took off your white coats, grabbed your black bags, and made a house call? You talk about what is wrong with the discipline of internal medicine and what can be done to fix it. Internists are rewarded like their surgical colleagues; you are not going to attract students unless you can show the beauty of practice. There is nothing more wonderful than a doctor at the bedside in a sick patient's home. Devoid of much technology, it is just the physician, his skills, and the patient. That is the substance of America's current hunger—a return to old time values and to old time doctoring. We cannot expect our medical youth to pursue the higher road for the greater good if the teachers themselves have lost touch with the quintessence of medical care. You senior clinicians should take a break from the medical center fracas and grab a couple of those impressionable residents and students and take them on a house call. Warning—you may have to pass some exotic places on the way. (In my neck of the woods, the towns have names like Warsaw, Callao, Hague, and Jamaica). The trip will do all of you some good—it will take you back to medicine's roots.
To the Editors: As a rheumatologist, I recently evaluated a patient with osteogenesis imperfecta, who had come for a second opinion. His enlarged bossed skull, blue sclera, and severely underdeveloped lower extremities were disturbingly distracting, even to a physician accustomed to dealing with physical deformities and who had seen such patients before. As I take a history, I usually scan the patient's visible joints, looking for signs of inflammation or deformity. With this patient, however, it was not until I was near the end of the physical examination when I felt his warm, swollen elbows, wrists, and metacarpals and noticed he had frank synovitis. When I questioned him about symptoms, he described morning stiffness, pain, and swelling of these joints for the past 7 years. He had been seeing an excellent rheumatologist during this period. When asked if he had told the rheumatologist about his joint symptoms, he replied, "Yes, but when normal people see someone with a handicap, a stop sign goes up, and they don't see beyond the handicap." After my initial feelings of embarrassment, I proceeded to aspirate his right elbow and obtained cloudy fluid with a white cell count of 16 x 109/L, negative for crystals. A rheumatoid factor was positive at 1:160, and radiographs showed diffuse joint space narrowing. These findings confirmed that he had rheumatoid arthritis in addition to his osteogenesis imperfecta. As physicians, putting up stop signs may be an adaptive response to the magnitude of data that we have to process daily. It is sometimes easier to categorize patients and to assign them common symptoms and problems even before we talk to them and examine them. My eyes saw his swollen joints, my fingers felt the warmth, yet I almost did not realize that he had arthritis because I had trouble blocking out his primary deformity. For those of us without physical disabilities, it is almost impossible to imagine the obstacles that the handicapped must have, including those sometimes imposed by their own physicians.
Jeffrey A. Margolis, MD Box 612 Tappahannock, VA 22560 In response: Drs. McClellan and Langlen highlight the role of income as a disincentive to careers in general medicine and suggest that a fourth year of training be added to the residency for generalists. Although more emphasis would be on cost effectiveness of medical procedures, it is difficult to see how this extra year would address the problem of the income differential with proceduralists. Dr. Olsen suggests using a fourth year of general residency to train internists in the "currently lucrative" procedures of the specialists. Although an attractive concept, it would seem to be more practical in geographic areas where specialization is less well developed. Dr. Kochar suggests that 2 years of required practice in general medicine before training in a subspecialty might both increase the number of generalists and decrease the number of subspecialists. One could argue that 2 years of practice in a primary care specialty might be mandated for further training in any of the nongeneralist disciplines, including the surgical specialties. Drs. Novack and Lipkin have correctly emphasized the need in training programs for the further development of interpersonal skills and increased competency in the psychosocial aspects of care. We agree that simply switching instructional sites to the ambulatory setting will be inadequate unless new models for training generalists are adopted. The difficulty in a precipitous movement of residents from the inpatient to outpatient setting is pointed out by Drs. Parrino, Tyler and Lee. Given the importance of VA Medical Centers in residency training, we agree that representatives from these centers should be involved in the dialogue on internal medicine curriculum reform. Dr. Margolis points out that showing the beauties of practicing general medicine is one of the few feasible ways of attracting students until such time as internists are rewarded like their surgical colleagues. He chides the academic community for failing to provide the role models of physicians still willing to make house calls. This is consistent with the emphasis in the Supplement on the increased use of community physician offices as sites of training. The Supplement Editors appreciate the thoughtful comments of the correspondents and agree with their emphasis on the
—The Editors Handicapping the Handicapped
Michael J. Maricic, MD University of Arizona Health Science Center Tucson, AZ 85724 Correction: Spectrum Bias in Evaluation of Diagnostic Tests In the article by Lachs and colleagues (1), Table 1 (column 1) gives incorrect percents for patients in the high-probability subgroup. Because of a programming error, four patients with missing previous probabilities of urinary tract infection were mistakenly classified as being in the high-probability subgroup. Thus, the percents should be based on a denominator of 103. The values for sensitivity and specificity and their associated CIs in Table 3 are all based on n = 103 and remain correct. Reference 1. Lachs MA, Nachamkin I, Edelstein PH, Goldman J, Feinstein AR, Schwartz JS. Spectrum bias in the evaluation of diagnostic tests: lessons from the rapid dipstick test for urinary tract infection. Ann Intern Med. 1992;117:135-40.
Correction: Review of Facing
A book review (1) incorrectly noted the author of the book and did not include the cost of the book's hardcover edition. The sole author is Sandra L. Bertman, and the hardcover price is $45.00. Reference 1. Abrams FR. Review of Facing Death: Images, Insights, and Interventions. Ann Intern Med. 1992;116:880.
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