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 Unpublished letters cannot be returned. Cyclophosphamide in Progressive Membranous Glomerulopathy: Pro and Con To the Editors: Although the report by Falk and associates (1) provides new data regarding the prognosis and therapy of membranous glomerulopathy, several aspects of this study limit its general applicability to the treatment of patients with progressive forms of this disease. A convincingly negative clinical trial should have a power of 80% or greater. Table 1 is based on the comparison of two survival distributions (2) using data provided in the paper. For this purpose the median renal survival in the study's steroid only treated group was taken as either 30 or 36 months from randomization. This assumption is conservative based on the observed 60% renal survival at 24 months (1). With 13 patients in each treatment arm, this study had the power to detect the differences in median survival between the treatment groups shown in Table 1.
Table 1. Survival and Power of Tests among Patients with Membranous Glomerulopathy Treated with Steroids Alone or with Steroids plus Cyclophosphamide Subset Median Survival in Median Survival in Power* Steroid-Only Group Steroid-plus-Cyclophosphamide Group mo % 1 2 3 4 5 6
30 30 30 36 36 36
48 60 92 54 72 108
11 17 29 9 15 25
* Statistical power to detect differences in median survival at P < 0.05.
If the median survival in the steroid-only group was longer than 36 months, then the statistical power of this study would be even lower. Thus, the study's negative findings do not 696
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exclude the possibility of a clinically important difference between the two treatment regimens. The inclusion criteria for progressive membranous glomerulopathy were likely to have identified patients without advancing disease; patients with persistent proteinuria or a sustained serum creatinine greater than 2.0 mg/dL may not have had a progressively declining glomerular filtration rate (3, 4). Their inclusion would likely bias the results toward no difference. Additionally, the use of the reciprocal of serum creatinine to monitor renal function may have led to a substantial under- or overestimation of the progression of renal disease (5), further complicating the interpretation of the study's results. Finally, no outcome data are provided to show that the 10 eligible patients excluded from the trial had outcomes similar to study participants. Harold I. Feldman, MD, MS Michael P. Madaio, MD University of Pennsylvania School of Medicine Philadelphia, PA 19104 References 1. Falk RJ, Hogan SL, Muller KE, Jennette JC, the Glomerular Disease Collaborative Network. Treatment of progressive membranous glomerulopathy: A randomized trial comparing cyclophosphamide and corticosteroids with corticosteroids alone. Ann Intern Med. 1992; 116: 438-45. 2. Schoenfeld DA, Richter JR. Nomograms for calculating the number of patients needed for a clinical trial with survival as an endpoint. Biometrics. 1982;38:163-70. 3. Ponticelli C, Zucchelli P, Imbasciati E, Cagnoli L, Pozzi C, et al. Controlled trial of methylprednisolone and chlorambucil in idiopathic membranous nephropathy. N Engl J Med. 1984;310:946-50. 4. Collaborative Study of the Adult Idiopathic Nephrotic Syndrome. A controlled study of short-term prednisone treatment in adjuts with membranous nephropathy. N Engl J Med. 1979;301:1301-6. 5. Walser M, Drew HH, LaFrance ND. Reciprocal creatinine slopes often give erroneous estimates of progression of chronic renal failure. Kidney Int. 1989;36:S81-5.
To the Editors: As a nephrologist in training I read with interest the article by Falk and coworkers (1) on the aggressive treatment of membranous nephropathy with intravenous cyclophosphamide and high dose corticosteroids. Their conclusion that combination therapy does not improve renal function in patients with progressive membranous nephropathy deserves comment. Most other trials have initiated cytotoxic therapy in combination with high-dose corticosteroids at a much earlier stage. Rather than 24.2 ± 39.1 months (2-4), the mean latent period before initiating therapy was 8.4 to 16 months, and all trials cited found improvement or stabilization of renal function with combination therapy. None was randomized, and all used oral cytotoxic agents for a longer duration. Second, having already failed short-term, high-dose treatment with corticosteroids, the study patients may have had a particularly poor prognosis. Last, the study was not designed to test the hypothesis whether combination therapy slows the rate of decline of renal function. Until there are better randomized trials of combination therapy, because high-dose corticosteroids do not alter the outcome of membranous nephropathy (5), we will elect to use a
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combination of oral cytotoxic therapy combined with corticosteroids in those with relentlessly progressive renal failure. Rajiv Agarwal MD University of Texas Southwestern Medical Center at Dallas Dallas, TX 75235-8856 References 1. Falk RJ, Hogan SL, Muller KE, Jennette C, the Glomerular Disease Collaborative Network. Treatment of progressive membranous nephropathy: a randomized trail comparing cyclophosphamide and corticosteroids with corticosteroids alone. Ann Intern Med. 1992;116: 438-45. 2. Jindal K, West M, Bear R, Goldstein M. Long term benefits of therapy with cyclophosphamide and prednisone in patients with membranous glomerulonephritis and impaired renal function. Am J Kidney Dis. 1992;19:61-7. 3. Bruns FJ, Adler S, Fraley DS, Segel JP. Sustained remission of membranous glomerulonephritis after cyclophosphamide and prednisone. Ann Intern Med. 1991;114:725-30. 4. Mathieson PW, Turner AN, Maidment CG, Evans DJ, Rees AJ. Prednisolone and chlorambucil treatment in idiopathic membranous nephropathy with deteriorating renal function. Lancet. 1988;2:869-72. 5. Cameron JS, Healy M, Adu D. The medical research council trial of short term, high-dose alternate day prednisone in idiopathic membranous nephropathy with a nephrotic syndrome in adults. Q J Med. 1990;74:133-45.
In response: Our study examined the role of intravenous cyclophosphamide in the treatment of progressive membranous glomerulopathy (1). We compared an aggressive form of therapy using pulse methylprednisolone, oral corticosteroids, and six monthly injections of intravenous cyclophosphamide with a regimen of corticosteroids alone given as alternate-day prednisone for 8 weeks. Doctors Feldman and Madaio raise several important issues. The statistical power of our study based on survival analysis is limited, a fact that is not surprising because we did not base power or sample size on survival as an end point. We stopped the study when we had sufficient power to state that aggressive therapy with corticosteroids and intravenous cyclophosphamide therapy had no significant effect on improving renal function or preventing end-stage disease and before we had long-term survival data because of the toxicity of cyclophosphamide. Instead, we were interested in improving renal function or preventing end-stage disease. In our study, the power to detect a substantial improvement in renal function, defined as doubling the reciprocal of the serum creatinine, was 0.92 at the significance level of 0.05. The power to detect the development of end-stage renal disease was 0.88 at the significance level of 0.01. The power calculations reported in our paper were conducted before the completion of the trial to determine the stopping rule. Using the observed sample sizes and variance estimates yields power estimates somewhat higher than those we reported. Patients were included in our study because of progressive renal insufficiency or "persistent proteinuria with morbid complications." Because the patients in this latter group developed renal insufficiency during treatment, we analyzed both randomized groups together. We acknowledge that the serum creatinine values are not the most accurate measurement of progression of chronic renal failure, particularly for small changes over short periods. However, either large differences in progression of chronic renal failure or clear improvement in one group over 2 years could have been detected using the reciprocal creatinine values. Reciprocal creatinine levels were used to provide values that were approximately Gaussian in distribution, thus allowing the use of normal-theory statistical models that can have substantial power in studies with small sample sizes. Slopes of creatinine values plotted against time were not used to evaluate differences between the two therapy groups because of known limitations in this method (3, 4). Instead, all values were used in a repeated-measures analysis, thereby taking into account variation within each patient as well as variation between treatment groups. The collection of clearances of iothalamate or of inulin was not feasible in the setting of this study.
Outcome data were provided for 5 of the 10 eligible but excluded patients who were given oral cyclophosphamide. As noted, the results of this form of therapy were disappointing. The other five patients received in a nonrandomized fashion intravenous cyclophosphamide (two patients), chlorambucil (one patient), corticosteroids alone (one patient), and supportive care (one patient). The renal function outcome of these 5 patients was similar to that of the 26 patients entered into the randomized trial. Dr. Agarwal notes that other uncontrolled trials have used therapeutic interventions at a point earlier than that used in our study. Our large registry database provided us with the opportunity to identify patients with progressive membranous nephropathy. Patients were entered in our randomized, prospective, controlled trial when they met strict entry criteria. It is certainly possible, however, that earlier therapy in patients who later proceed to renal insufficiency may be of benefit. This issue was not the subject of our study. We are unaware of any conclusive data that support the notion that failure to "respond" to oral corticosteroids represents an independent risk factor for poor prognosis. Although we agree that randomized trials are needed, we disagree that we must use "a combination of oral cytotoxic therapy combined with corticosteroids." This form of therapy has not been subject to randomized, prospective study and remains an experimental approach using a mutagenic drug with significant side effects. The use of this drug may result in severe side effects including life-threatening infections, gonadal dysfunction and failure, hemorrhagic cystitis, and malignancy. In a recent study of Wegener granulomatosis from the National Institutes of Health, Hoffman and colleagues (2) noted a 2.4% overall increase in cancer risk, and a 33-fold increased risk for transitional-cell carcinomas of the bladder. The first rule is "first, do no harm." Ronald J. Falk, MD Susan L. Hogan J. Charles Jennette, MD University of North Carolina School of Medicine Chapel Hill, NC 27599 References 1. Falk RJ, Hogan SL, Muller KE, Jennette JC, the Glomerular Disease Collaborative Network. Treatment of progressive membranous glomerulopathy: a randomized trial comparing cyclophosphamide and corticosteroids with corticosteroids alone. Ann Intern Med. 1992; 116: 438-45. 2. Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD, et al. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med. 1992;116:488-98. 3. Walser M, Drew HH, LaFrance NC. Reciprocal creatinine slopes often give erroneous estimates of progression of chronic renal failure. Kidney Int. 1989;35(S27):S81-85. 4. Modification of Diet in Renal Disease (MDRD) Study Group. Assessing the progression of renal disease in clinical studies: effects of duration of follow-up and regression to the mean. J Am Soc Nephrol. 1991;1:187-94.
Exercise and Osteoarthritis To the Editors: Dr. Charlson and her colleagues have made an important contribution toward understanding the rational use of exercise for osteoarthritis (1). However, their statement that "sessions included light stretching and strengthening exercises" merits some elaboration. Stretching and strengthening have many descriptors in addition to light (for example, isometric, maximal contraction, passive, and so forth) (2). Furthermore, various types of stretching and strengthening may be effective in arthritis treatment (3, 4) independent of ambulation. Perhaps the authors could elaborate on the nature of the light stretching and strengthening in their study and their relevance to its outcome. Robert D. Bunning, MD Richard S. Materson, MD National Rehabilitation Hospital Washington, DC 20010
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References 1. Kovar PA, Allegrante JP, Mackenzie CR, Peterson MG, Gutin B, Charlson M. Supervised fitness walking in patients with osteoarthritis of the knee. Annals of Internal Medicine. 1992;116:529-34. 2. Bunning RD, Materson RS. A rational program of exercise for patients with osteoarthritis. Semin Arthritis Rheum. 1991;21(Suppl 2): 33-43. 3. Fisher NM, Pendergast DR, Gresham GE, Calkins F. Muscle rehabilitation: Its effect on muscular and functional performance of patients with knee osteoarthritis. Arch Phys Med Rehabil. 1991;72:367-74. 4. Leivseth G, Tortstensson J, Reikeras O. Effect of passive muscle stretching in osteoarthritis of the hip. Clin Sci. 1988;76:113-7.
In response: Patients in one intervention protocol were encouraged to do light stretching and strengthening isotonic exercises as described by Daniels and Worthingham (1). Patients in the intervention arm of the trial were taught to stretch the affected extremities through pain-free ranges of motion during each exercise session prior to walking. All patients were taught how to use gravity as a resistance to strengthen muscles in both upper and lower extremities (especially quadriceps and knee extensors). Those patients who did not experience pain were also given a Thera-Band (The Hygenic Corporation, Akron, Ohio). This rubberized material provides varying levels of resistance and was used by patients to introduce progressive levels of resistance throughout the range of motion. Although we did not measure strength, we agree that both the stretching and especially the strengthening exercises, combined with walking, are likely to have contributed significantly to the improvements in patient outcomes we observed. By gaining additional flexibility and stability through these exercises, patients were probably able to decrease stress on the affected joints, thereby enhancing functional mobility. Evidence supporting the importance of the relation between muscle strength and functional status has been growing. For example, Fiatarone and colleagues (2) have suggested that muscle weakness in the frail elderly may be an important risk factor in falls, fracture, and functional dependency, and they have shown that high-intensity strength training can enable frail elderly up to 96 years of age to regain muscle strength, size, and functional mobility. The comments of Bunning and Materson attest to the importance of strength training. John P. Allegrante, PhD Pamela A. Kovar, EdD C. Ronald Mackenzie, MD Cornell Arthritis and Musculoskeletal Disease Center New York, NY 10021 References 1. Daniels L, Worthingham CA. Therapeutic Exercise for Body Alignment and Function. 2nd edition. Philadelphia: W.B. Saunders; 1977. 2. Fiatarone MA, Marks EC, Ryan ND, Meredith CN, Lipsitz LA, Evans WJ. High-intensity strength training in nonagenarians: effects on skeletal muscle. JAMA. 1990;263:3029-34.
Typhlitis and HIV To the Editors: The recent paper by Till and colleagues describes six patients with human immunodeficiency virus type 1 (HIV-1) infection who had clinical and radiographic findings consistent with typhlitis (1). However, in none of these cases, nor in two previously reported cases (2), was cecal inflammation confirmed at surgery or at autopsy. We recently treated an HIV-1-infected patient with typhlitis confirmed at laparotomy, associated with Clostridium septicum infection. A 34-year-old woman with advanced acquired immunodeficiency syndrome (AIDS) developed acute vomiting, diarrhea, and periumbilical pain which subsequently localized to the right lower quadrant. Her past history was significant for multiple opportunistic infections including disseminated Mycobacterium avium-intracellulare and cytomegalovirus retinitis. Physical examination showed an acutely ill, cachectic female with board-like abdominal rigidity, rebound tenderness, and absent bowel sounds. The white blood count was 3300/mm3 with 33% segmented neutrophils and 51% bands. Radiographs 698
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of the abdomen showed no evidence of free air. A computed tomographic scan showed multiple, fluid-filled large and small bowel loops without evidence of abscess. Laparoscopy showed fibrinopurulent exudates without an obvious etiology. Subsequent exploratory laparotomy showed the proximal colon at the hepatic flexure to be indurated and covered with a fibrinous exudate. No perforation or luminal obstruction was evident. The abdomen was irrigated with saline and closed. Postoperatively, cefoxitin and amikacin were administered. A culture of peritoneal exudate obtained at the time of surgery grew only Clostridium septicum. Cefoxitin was withdrawn, and a regimen of imipenem plus cilastatin was begun. Postoperatively, the patient improved rapidly. Clostridium difficile toxin was subsequently detected in a diarrheal stool specimen, and oral vancomycin was given. The remainder of her hospital course was uneventful. Her wound healed well and she was discharged home on the eighth postoperative day. Clostridium septicum has been the most common organism associated with typhlitis in patients with other predisposing conditions (3), and its isolation in our patient with surgically confirmed disease of the proximal colon suggests that this syndrome in HIV-1-infected patients may represent a similar pathologic process. Connie Jumper, MD J. John Weems, Jr., MD Ludwig A. Lettau, MD, MPH Greenville Hospital System Greenville, SC 29605 References 1. Till M, Lee N, Soper WD, Murphy RL. Typhlitis in patients with HIV-1 infection. Ann Intern Med. 1992;116:998-1000. 2. Cutrona AF, Blinkhorn RJ, Crass J, Spagnuolo PJ. Probable neutropenic enterocolitis in patients with AIDS. Rev Infect Dis. 1991; 13: 828-31. 3. Clostridium septicum and neutropenic enterocolitis [Editorial]. Lancet. 1987;2:608.
Calculating Body Mass Index To the Editors: The 1985 National Institutes of Health (NIH) Consensus Development Panel on Health Implications of Obesity recommended that physicians adopt the body mass index (BMI) (body weight in kilograms divided by square of height in meters) in evaluating patients (1). The 1992 NIH Technology Assessment Conference Panel on Methods for Voluntary Weight Loss and Control noted its importance as " a widely used means to define overweight" (2). Nomograms and tables for determining BMI have long been available, as has the Portland Health Institute Body Mass Index Graph (3). More than 1000 free copies have been mailed after receipt of selfaddressed, stamped envelopes. Physicians and other health professionals have found the Portland Health Institute Body Mass Index Graph useful in patient counseling and education. To meet the occasional need for an even simpler, more rapid means of determining BMIs from weight (in pounds) and height (in inches) for other purposes, as when reviewing medical records, fitness test data, or research reports, the following equation permits the easy determination of BMI with the aid of a hand calculator.
BMI =
kg (m) x (m) lb 4- 2.2 lb/kg
~ (in x 0.0254 m/in) x (in x 0.0254 m/in) lb " (in) x (in) x (0.0254 x 0.0254 x 2.2) = lb ^ in H- in + (0.0254 x 0.0254 x 2.2) BMI = lb -s- in +- in + (0.0014192)
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Herman M. Frankel, MD Jean C. Staeheli Portland Health Institute, Inc. Portland, OR 97219-4028 References 1. National Institutes of Health Consensus Development Panel. Health implications of obesity: National Institutes of Health Consensus Development Conference statement. Ann Intern Med. 1985;103:147-51; Ann Intern Med. 1985;103(Suppl 6, Part 2): 1073-7. 2. Technology Assessment Conference Panel. Methods for voluntary weight loss and control: Technology Assessment Conference statement. Ann Intern Med. 1992;116:942-9. 3. Frankel HM. Determination of body mass index. JAMA. 1986;255: 1292. Striking " F M G " from Our Vocabulary To the Editors: Varki (1) appropriately emphasizes the importance of individual performance as the standard for judging individual capability as opposed to professional pedigree. I received pedestrian to downright poor teaching in a standard U.S. medical school (and have published an essay so stating in its alumni publication) but, I trust, have been able to surmount that obstacle. Like U.S. graduates, foreign graduates attend medical schools of varying quality and must be considered individually. That so many have performed well has been a major factor in keeping many U.S. housestaffs afloat, for which we should be grateful. David H. Spodick, MD, DSc Saint Vincent Hospital University of Massachusetts Medical School Worcester, MA 01604 Reference 1. Varki A. Of pride, prejudice, and discrimination. Why generalizations can be unfair to the individual. Ann Intern Med. 1992; 116: 762-4. To the Editors: Dr. Varki (1) addressed sensitive issues directly and expressed the salient points clearly. The sentence, "In categorizing the [foreign medical graduate] " F M G , " the only possible outcome is the risk for prejudice and discrimination," is so appropriate and accurate, that it should appear in bold letters. Every program director should keep this in mind before deciding on an applicant for a position. The prejudice that this categorization promotes is further exemplified by the way in which a teaching program is graded based on the number of FMGs. Program directors are under constant pressure to avoid FMGs to maintain "their grade." Meanwhile, the FMG is caught in a situation in which he or she is forced to accept training programs that are undesirable, locking him or her in a no-win situation. Future academic appointments are denied to this individual based on this "less desirable" training. This unfortunate outcome can be avoided if candidates are selected based on individual knowledge, skill, and merit. It is time we abandon the FMG label. Arcot A. Dwarakanathan, Rush Medical College Chicago, IL 60612
graphically. At the very least, a blinded rater should be able to identify correctly, on the basis of quality of care, the location of a physician's medical school, more often than by chance. Ideally, a prospective study of FMG and USMG physicians entering residency together should include a 15-year follow-up period to determine their quality of care. For the analysis to be meaningful, such variables as recency of medical education, quality and location of residency training, elective and moonlighting opportunities, postresidency career opportunities, and the nature of the hospitals and populations with which they work should be controlled for. My hypothesis is that there would be more within-group variation than between-group variation. Just as good schools have graduated bad doctors and vice versa, group means may be misleading. It seems likely that individual differences in ability, skill, and motivation explain far more of the variance in quality of care than does the location of schools. Generalizations from spurious findings are not only unethical but are also unscientific. Until we can find a better reason to split, we should probably be content to lump. Mary Ganguli MD, MPH University of Pittsburgh Pittsburgh, PA 15261 Reference 1. Varki, A. Of pride, prejudice, and discrimination. Why generalizations can be unfair to the individual. Ann Intern Med. 1992; 116: 762-4. To the Editors: Varki clarifies common flaws in evaluating individual members of the heterogenous group of foreign or international medical graduates (IMGs) (1). To support his contention that the lower average score of IMGs cannot be extrapolated to infer the abilities of an individual IMG, we present data from our residency program experience. Our faculty has been impressed by the motivation, fund of knowledge, scholarly activity, and overall clinical performance of most IMGs. At our institution, 37 carefully selected IMGs completing training in internal medicine between 1987 and 1991 took the Certifying Examination of the American Board of Internal Medicine. They represented 16.8% of our 220 residents who took the examination during this period. Of these 37 IMGs, 35 (94.6%) passed. More impressively, among 34 IMGs for whom the specific overall score is known, 9 (26.5%) ranked in the top 10% nationally; 14 (41.2%), in the top quartile; and 27 (79.4%), in the top half. Both the subjective evaluations of performance and the scores clearly show that selected IMGs can excel. Andre L. Weigert, MD Edward C. Lynch, MD Baylor College of Medicine Houston, TX 77030 Reference 1. Varki A. Of pride, prejudice, and discrimination. Why generalizations can be unfair to the individual. Ann Intern Med. 1992; 116: 762-4.
MD
Reference 1. Varki A. Of pride, prejudice, and discrimination. Why generalizations can be unfair to the individual. Ann Intern Med. 1992; 116: 762-4. To the Editors: As Dr. Varki (1) points out, in science we often seek to understand information by categorizing it. Categories divide individuals into groups with shared characteristics, but to be meaningful, they should have predictive value. For example, in making a diagnosis we make a statement about prognosis. From this heuristic point of view, the burden is on the splitters to prove that FMGs and United States medical graduates (USMGs) differ "clinically," rather than simply demo-
In response: Discussing the sensitive and difficult issue of discrimination in a public forum can be a two-edged sword. On one hand, it can serve to shed light on a serious matter, thus encouraging rational behaviour. On the other hand, it could serve to fan the flames and aggravate, rather than improve, the situation. The intent of this perspective (1) was to suggest that the " F M G " or " I M G " issue should become a nonissue. Thus, the very best response one could have hoped for would have been none at all. However, that is wishful thinking. Fortunately, the responses printed here (and the many letters received directly) are uniformly supportive of my position; it is possible that those opposed have chosen not to speak out in public. Dr. Spodick correctly points out that the same principles could be applied to discrimination based upon site of medical training within the U.S. Dr. Dwarakanathan suggests that the phrase " . . . in categorizing the " F M G " the only possible outcome is the risk for discrimination and prejudice" should be
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strongly emphasized as the primary message. It is worth considering if this phrase would ring equally true if one substituted "black," "Hispanic" or " w o m a n " for " F M G . " Professor Ganguli correctly points out that the onus is upon the "splitters" to prove that categorizing physicians by their original medical training is justifiable. Actually, one hopes the "splitters" will give up this unscientific and inflammatory activity altogether. In this regard, the supportive response of Drs. Weigert and Lynch falls into the trap of presenting extremely well-meaning condescension. To the bigot, their data could actually mean that "carefully selected I M G s " can be quite good, ergo, most of them are not. Because all the residents in the Baylor program are probably "carefully selected," why classify a subgroup of them for separate "scientific" study? Also, why assume that none of these individuals is an American? It is my own fervent hope that I will never again see the term " F M G " or " I M G " in print in a public forum. However, such issues are difficult ones, open to varied opinions and interpretations. Ultimately, individuals must come to peace with their own intellectual honesty in such matters, as Tagore (2) did: Where the mind is without fear and the head is held high; Where knowledge is free; Where the world has not been broken up into fragments by narrow domestic walls; Where words come out from the depths of truth; Where tireless striving stretches its arms towards perfection; Where the clear stream of reason has not lost its way into the dreary desert sand of dead habit, . . . Into that heaven of freedom . . . let my country awake. Ajit Varki, MD UCSD School of Medicine La Jolla, CA 92093 References 1. Varki A. Of pride, prejudice, and discrimination. Why generalizations can be unfair to the individual. Ann Intern Med. 1992; 116: 762-4. 2. Tagore R. (Nobel Laureate 1913) from Gitanjali xxxv; 1910.
Randomized Clinical Trials and Patient Preferences To the Editors: Levine and colleagues (1), presented a useful tool for eliciting patient preference for adjuvant chemotherapy that gives a statistical perspective on the risks and benefits. However, they did not discuss another major and important method of dealing with the uncertainty of the situation in node-negative breast cancer: participation in randomized clinical trials. Not enough patients are being enrolled in clinical trials, making it difficult to answer important clinical questions such as those concerning risks and benefits in different subpopulations (2, 3). By participating in a clinical trial, the patient gets information about the current state of knowledge and may directly help her daughter, who will not face the same uncertainty, when results from properly conducted clinical trials become available.
References 1. Levine MN, Amiram G, Markham B, MacFarlane D. A bedside decision instrument to elicit a patient's preference concerning adjuvant chemotherapy for breast cancer. Ann Intern Med. 1992; 117: 53-8. 2. Benson AB ID, Pregler JP, Bean JA, Rademaker AW, Eshler B, Anderson K. Oncologists' reluctance to accrue patients onto clinical trials: An Illinois Cancer Center study. J Clin Oncol. 1991;9:2067-75. 3. Editorial on Clinical Trial Participation. J Clin Oncol. 1991;9:1927-30. 15 October 1992 • Annals of Internal Medicine
To the Editors: Howard Spiro gives a touching description of the human concern of one person for another and its importance in medicine (1). I think, however, that he mistakes medical student enthusiasm for empathy and misplaces its locus in our feelings instead of in our intellect. Do medical students come full of empathy only to lose it as they become physicians, as Dr. Spiro suggests? Surely not. They come imbued with romantic illusions and often real humanity but are seldom skilled at empathy. Placing empathy within the zone of feelings confuses empathy with sympathy, the vicarious experiencing of another's emotions. I prefer to consider empathy to be an intellectual understanding of those feelings. Key steps to effective empathy are 1) recognition that we are in the presence of a strong feeling; 2) a pause to imagine how the patient might be feeling to say what he has said or act as he has acted; 3) a clear statement of our perception of the patient's feeling or predicament; 4) legitimization of that feeling; 5) respect for the patient's efforts to deal with his predicament; and 6) offers of support and partnership. All of these are learnable and teachable (2-5). Frederic W. Piatt, MD 1901 East 20th Avenue Denver, CO 80205 References 1. Spiro H. What is empathy and can it be taught? Ann Intern Med. 1992;116:843-6. 2. Piatt FW, McMath JC. Clinical hypocompetence: the interview. Ann Intern Med. 1979;91:898-902. 3. Suchman AL, Mathews DA. What makes the physician-patient relationship therapeutic? Exploring the connexional dimension of medical care. Ann Intern Med. 1988;108:125-30. 4. Cohen-Cole SA. The Medical Interview: The Three Function Approach. St. Louis: Mosby Year Book; 1991:22. 5. Smith RC, Hoppe RB. The patient's story; integrating the patientand physician-centered approaches to interviewing. Ann Intern Med. 1991;115:470-7. To the Editors: It is rare that an eminent physician like Dr. Spiro discusses such a "soft" subject in a general medical journal (1). Two comments are worth adding. First, empathy requires time; not time spent learning it but time spent with the patient. If a physician is too busy seeing too many patients or for other reasons, then no amount of innate or learned empathy will ever find its way to a needy patient. Therefore, in this sense empathy relates to the type of professional life we choose to lead. Second, I agree with his comments on the loss of "spontaneous collegiality" among members of our profession. In the old days, some hospitals had coffee rooms where attending physicians and housestaff could meet informally, trade stories, follow up on consultations, and socialize. Resurrecting this custom would return its cost a thousandfold. Edward J. Volpintesta, MD 155 Greenwood Avenue Bethel, CT 06801 Reference 1. Spiro H. What is empathy and can it be taught? Ann Intern Med. 1992;116:843-6.
Aroop Mangaliky MD James Neidhart, MD University of New Mexico Cancer Center Albuquerque, NM 87131
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To the Editors: I found the questions raised by Dr. Spiro (1) on the importance of empathy in medical education interesting. At the University of Missouri-Kansas City School of Medicine (2) we admit the majority of our students directly from high school to take advantage of their youthful energy, passion, and empathy and to begin their medical education before their attitudes are shaped by a competitive premedical education. Students interact with patients from the first week of school throughout a curriculum that integrates clinical medicine, basic science, and the humanities 11 months a year for 6 years.
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This approach to medical education, with its emphasis on the human condition, allows students to maintain their naturally acquired empathy, compassion, sensitivity, and honesty. These attitudes are encouraged and fostered by full-time faculty members (docents) from the Department of Medicine who supervise, teach, and serve as role models for groups of 12 students on inpatient medicine rotations and weekly ambulatory care clinics through the last 4 years. As a graduate of this program and now as a faculty member at this school, I can attest to its advantages. After 21 years, we have trained over 1200 physicians in the science and technology of medicine, while retaining their empathy for the individual patient. The early admission aspect of our program will only work with a select group of students and not in all schools. Early exposure of students to continuity of care in an outpatient clinic supervised by appropriate physician role models throughout medical school can and should be tried in other schools. We cannot teach empathy. This "almost magical" emotion is acquired and lost through life experiences. However, by recognizing the importance of the intangible qualities of a humanistic physician, we can enhance and promote these essential qualities. Gary A. Salzman, MD University of Missouri-Kansas City School of Medicine Kansas City, Missouri 64108 References 1. Spiro H. What is empathy and can it be taught? Ann Intern Med. 1992;116:843-6. 2. Dimond EG. The UMKC medical education experiment: an alternative pathway to physicianhood. JAMA. 1988;260:956-8.
To the Editors: The report by Spiro (1) was an insightful dissection of empathy and how it seems to melt away during the course of medical education. However, at the risk of sounding sacrilegious, I ask if empathy is really necessary for the highly trained scientific physician of the 1990's? We all know that too much emotional involvement (?empathy) may interfere with making good sound scientific judgments; I raise the question of how empathy enters into our modern sophisticated technologic treatment of patients. Is empathy simply a remnant of the days past when the physician did not have the modern tools of treatment? Kevin B. Lake, MD 50 Alessandro Place, Suite 330 Pasadena, CA 91105 Reference 1. Spiro H. What is empathy and can it be taught? Ann Intern Med. 1992;116:843-6.
To the Editors: Spiro's moving description of empathy (1) contains several sections where it appears that empathy and equanimity are conflicting attributes. Equanimity is equated with detachment, whose advocacy he links with Osier. Ironically, in the same issue of Annals, Osier is praised for his astute ability to make deductions from inconspicuous features (2). Osier did indeed promote "Aequanimitas" which he equates with imperturbability, the "coolness and presence of mind under all circumstances, calmness amid storm, clearness of judgment in moments of grave peril, immobility, impassiveness, or, to use an old and expressive word, phlegm" (3). He noted that a physician "who betrays indecision and worry . . .
loses rapidly the confidence of his patients." Many if not most life-threatening conditions were incurable in Osier's time. When caring for a young, healthy-appearing patient infected with HIV, it would be frightening if my attitude contributed to his fears. Indeed, what Osier advocates is "a judicious measure of obtuseness . . . without . . . 'hardening the human heart by which we live.' " Empathy and equanamity are not conflicting but complementary attributes which physicians should develop. Stephen J. Seligman, MD State University of New York Brooklyn, NY 11203 References 1. Spiro H. What is empathy and can it be taught? Ann Intern Med. 1992;116:843-6. 2. Belkin BM, Neelon FA. The art of observation: William Osier and the method of Zadig. Ann Intern Med. 1992;116:863-6. 3. Osier W. Aequanimitas. With other addresses to medical students, nurses and practitioners of medicine. Philadelphia: The Blakiston Company; 1944.
In response: What Dr. Piatt offers is eminently professional and helpful, but it is not empathy. He is at liberty to redefine empathy as an intellectual rather than an emotional sensation, but then he is not really talking about what most others mean by empathy. Dr. Volpintesta hits the proverbial nail on its head—more time should be spent with patients. But doctors are "too busy," so I ask, how do we know there are "too many" doctors. Too many for what? for a good living? Let's train more, so they can have time to talk. What Dr. Saltzman describes going on in Kansas City is right on target; medical students discussing patients and the human condition with older physicians. Most patients, possibly 80%, that doctors see in their offices require understanding and not technology. For Dr. Lake's specialty, critical care medicine, I would choose technical skill over empathy, to be sure. Still I would want a physician who could put himself or herself in my place. Dr. Seligman and I read Aequanimitas in the same way. I agree that a doctor empathic with an HIV-infected patient would not want to contribute to very real fear. He or she might well sit by the patient's side, however, and share their sorrow. As I wrote, it is not an "either/or" situation. Both empathy and equanimity have a place, but equanimity needs to be moved to the side as empathy is refurbished. I hope that the article, to which I have had many private responses, will help to begin to do just that. Howard M. Spiro, MD Yale University School of Medicine New Haven, CT 06510 Making It Easier To the Editors: Hurrah for "Making it Easier"! Your policy of clarifying generic drug names, abbreviations, and SI unit conversions at the beginnings of articles represents a long overdue acknowledgment that readers need help dealing with these issues. This new feature will improve both communication and education. Hunter Heath III, MD University of Utah School of Medicine Salt Lake City, UT 84132
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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. Cyclophosphamide in Progressive Membranous Glomerulopathy: Pro and Con To the Editors: Although the report by Falk and associates (1) provides new data regarding the prognosis and therapy of membranous glomerulopathy, several aspects of this study limit its general applicability to the treatment of patients with progressive forms of this disease. A convincingly negative clinical trial should have a power of 80% or greater. Table 1 is based on the comparison of two survival distributions (2) using data provided in the paper. For this purpose the median renal survival in the study's steroid only treated group was taken as either 30 or 36 months from randomization. This assumption is conservative based on the observed 60% renal survival at 24 months (1). With 13 patients in each treatment arm, this study had the power to detect the differences in median survival between the treatment groups shown in Table 1.
Table 1. Survival and Power of Tests among Patients with Membranous Glomerulopathy Treated with Steroids Alone or with Steroids plus Cyclophosphamide Subset Median Survival in Median Survival in Power* Steroid-Only Group Steroid-plus-Cyclophosphamide Group mo % 1 2 3 4 5 6
30 30 30 36 36 36
48 60 92 54 72 108
11 17 29 9 15 25
* Statistical power to detect differences in median survival at P < 0.05.
If the median survival in the steroid-only group was longer than 36 months, then the statistical power of this study would be even lower. Thus, the study's negative findings do not 696
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exclude the possibility of a clinically important difference between the two treatment regimens. The inclusion criteria for progressive membranous glomerulopathy were likely to have identified patients without advancing disease; patients with persistent proteinuria or a sustained serum creatinine greater than 2.0 mg/dL may not have had a progressively declining glomerular filtration rate (3, 4). Their inclusion would likely bias the results toward no difference. Additionally, the use of the reciprocal of serum creatinine to monitor renal function may have led to a substantial under- or overestimation of the progression of renal disease (5), further complicating the interpretation of the study's results. Finally, no outcome data are provided to show that the 10 eligible patients excluded from the trial had outcomes similar to study participants. Harold I. Feldman, MD, MS Michael P. Madaio, MD University of Pennsylvania School of Medicine Philadelphia, PA 19104 References 1. Falk RJ, Hogan SL, Muller KE, Jennette JC, the Glomerular Disease Collaborative Network. Treatment of progressive membranous glomerulopathy: A randomized trial comparing cyclophosphamide and corticosteroids with corticosteroids alone. Ann Intern Med. 1992; 116: 438-45. 2. Schoenfeld DA, Richter JR. Nomograms for calculating the number of patients needed for a clinical trial with survival as an endpoint. Biometrics. 1982;38:163-70. 3. Ponticelli C, Zucchelli P, Imbasciati E, Cagnoli L, Pozzi C, et al. Controlled trial of methylprednisolone and chlorambucil in idiopathic membranous nephropathy. N Engl J Med. 1984;310:946-50. 4. Collaborative Study of the Adult Idiopathic Nephrotic Syndrome. A controlled study of short-term prednisone treatment in adjuts with membranous nephropathy. N Engl J Med. 1979;301:1301-6. 5. Walser M, Drew HH, LaFrance ND. Reciprocal creatinine slopes often give erroneous estimates of progression of chronic renal failure. Kidney Int. 1989;36:S81-5.
To the Editors: As a nephrologist in training I read with interest the article by Falk and coworkers (1) on the aggressive treatment of membranous nephropathy with intravenous cyclophosphamide and high dose corticosteroids. Their conclusion that combination therapy does not improve renal function in patients with progressive membranous nephropathy deserves comment. Most other trials have initiated cytotoxic therapy in combination with high-dose corticosteroids at a much earlier stage. Rather than 24.2 ± 39.1 months (2-4), the mean latent period before initiating therapy was 8.4 to 16 months, and all trials cited found improvement or stabilization of renal function with combination therapy. None was randomized, and all used oral cytotoxic agents for a longer duration. Second, having already failed short-term, high-dose treatment with corticosteroids, the study patients may have had a particularly poor prognosis. Last, the study was not designed to test the hypothesis whether combination therapy slows the rate of decline of renal function. Until there are better randomized trials of combination therapy, because high-dose corticosteroids do not alter the outcome of membranous nephropathy (5), we will elect to use a
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combination of oral cytotoxic therapy combined with corticosteroids in those with relentlessly progressive renal failure. Rajiv Agarwal MD University of Texas Southwestern Medical Center at Dallas Dallas, TX 75235-8856 References 1. Falk RJ, Hogan SL, Muller KE, Jennette C, the Glomerular Disease Collaborative Network. Treatment of progressive membranous nephropathy: a randomized trail comparing cyclophosphamide and corticosteroids with corticosteroids alone. Ann Intern Med. 1992;116: 438-45. 2. Jindal K, West M, Bear R, Goldstein M. Long term benefits of therapy with cyclophosphamide and prednisone in patients with membranous glomerulonephritis and impaired renal function. Am J Kidney Dis. 1992;19:61-7. 3. Bruns FJ, Adler S, Fraley DS, Segel JP. Sustained remission of membranous glomerulonephritis after cyclophosphamide and prednisone. Ann Intern Med. 1991;114:725-30. 4. Mathieson PW, Turner AN, Maidment CG, Evans DJ, Rees AJ. Prednisolone and chlorambucil treatment in idiopathic membranous nephropathy with deteriorating renal function. Lancet. 1988;2:869-72. 5. Cameron JS, Healy M, Adu D. The medical research council trial of short term, high-dose alternate day prednisone in idiopathic membranous nephropathy with a nephrotic syndrome in adults. Q J Med. 1990;74:133-45.
In response: Our study examined the role of intravenous cyclophosphamide in the treatment of progressive membranous glomerulopathy (1). We compared an aggressive form of therapy using pulse methylprednisolone, oral corticosteroids, and six monthly injections of intravenous cyclophosphamide with a regimen of corticosteroids alone given as alternate-day prednisone for 8 weeks. Doctors Feldman and Madaio raise several important issues. The statistical power of our study based on survival analysis is limited, a fact that is not surprising because we did not base power or sample size on survival as an end point. We stopped the study when we had sufficient power to state that aggressive therapy with corticosteroids and intravenous cyclophosphamide therapy had no significant effect on improving renal function or preventing end-stage disease and before we had long-term survival data because of the toxicity of cyclophosphamide. Instead, we were interested in improving renal function or preventing end-stage disease. In our study, the power to detect a substantial improvement in renal function, defined as doubling the reciprocal of the serum creatinine, was 0.92 at the significance level of 0.05. The power to detect the development of end-stage renal disease was 0.88 at the significance level of 0.01. The power calculations reported in our paper were conducted before the completion of the trial to determine the stopping rule. Using the observed sample sizes and variance estimates yields power estimates somewhat higher than those we reported. Patients were included in our study because of progressive renal insufficiency or "persistent proteinuria with morbid complications." Because the patients in this latter group developed renal insufficiency during treatment, we analyzed both randomized groups together. We acknowledge that the serum creatinine values are not the most accurate measurement of progression of chronic renal failure, particularly for small changes over short periods. However, either large differences in progression of chronic renal failure or clear improvement in one group over 2 years could have been detected using the reciprocal creatinine values. Reciprocal creatinine levels were used to provide values that were approximately Gaussian in distribution, thus allowing the use of normal-theory statistical models that can have substantial power in studies with small sample sizes. Slopes of creatinine values plotted against time were not used to evaluate differences between the two therapy groups because of known limitations in this method (3, 4). Instead, all values were used in a repeated-measures analysis, thereby taking into account variation within each patient as well as variation between treatment groups. The collection of clearances of iothalamate or of inulin was not feasible in the setting of this study.
Outcome data were provided for 5 of the 10 eligible but excluded patients who were given oral cyclophosphamide. As noted, the results of this form of therapy were disappointing. The other five patients received in a nonrandomized fashion intravenous cyclophosphamide (two patients), chlorambucil (one patient), corticosteroids alone (one patient), and supportive care (one patient). The renal function outcome of these 5 patients was similar to that of the 26 patients entered into the randomized trial. Dr. Agarwal notes that other uncontrolled trials have used therapeutic interventions at a point earlier than that used in our study. Our large registry database provided us with the opportunity to identify patients with progressive membranous nephropathy. Patients were entered in our randomized, prospective, controlled trial when they met strict entry criteria. It is certainly possible, however, that earlier therapy in patients who later proceed to renal insufficiency may be of benefit. This issue was not the subject of our study. We are unaware of any conclusive data that support the notion that failure to "respond" to oral corticosteroids represents an independent risk factor for poor prognosis. Although we agree that randomized trials are needed, we disagree that we must use "a combination of oral cytotoxic therapy combined with corticosteroids." This form of therapy has not been subject to randomized, prospective study and remains an experimental approach using a mutagenic drug with significant side effects. The use of this drug may result in severe side effects including life-threatening infections, gonadal dysfunction and failure, hemorrhagic cystitis, and malignancy. In a recent study of Wegener granulomatosis from the National Institutes of Health, Hoffman and colleagues (2) noted a 2.4% overall increase in cancer risk, and a 33-fold increased risk for transitional-cell carcinomas of the bladder. The first rule is "first, do no harm." Ronald J. Falk, MD Susan L. Hogan J. Charles Jennette, MD University of North Carolina School of Medicine Chapel Hill, NC 27599 References 1. Falk RJ, Hogan SL, Muller KE, Jennette JC, the Glomerular Disease Collaborative Network. Treatment of progressive membranous glomerulopathy: a randomized trial comparing cyclophosphamide and corticosteroids with corticosteroids alone. Ann Intern Med. 1992; 116: 438-45. 2. Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD, et al. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med. 1992;116:488-98. 3. Walser M, Drew HH, LaFrance NC. Reciprocal creatinine slopes often give erroneous estimates of progression of chronic renal failure. Kidney Int. 1989;35(S27):S81-85. 4. Modification of Diet in Renal Disease (MDRD) Study Group. Assessing the progression of renal disease in clinical studies: effects of duration of follow-up and regression to the mean. J Am Soc Nephrol. 1991;1:187-94.
Exercise and Osteoarthritis To the Editors: Dr. Charlson and her colleagues have made an important contribution toward understanding the rational use of exercise for osteoarthritis (1). However, their statement that "sessions included light stretching and strengthening exercises" merits some elaboration. Stretching and strengthening have many descriptors in addition to light (for example, isometric, maximal contraction, passive, and so forth) (2). Furthermore, various types of stretching and strengthening may be effective in arthritis treatment (3, 4) independent of ambulation. Perhaps the authors could elaborate on the nature of the light stretching and strengthening in their study and their relevance to its outcome. Robert D. Bunning, MD Richard S. Materson, MD National Rehabilitation Hospital Washington, DC 20010
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References 1. Kovar PA, Allegrante JP, Mackenzie CR, Peterson MG, Gutin B, Charlson M. Supervised fitness walking in patients with osteoarthritis of the knee. Annals of Internal Medicine. 1992;116:529-34. 2. Bunning RD, Materson RS. A rational program of exercise for patients with osteoarthritis. Semin Arthritis Rheum. 1991;21(Suppl 2): 33-43. 3. Fisher NM, Pendergast DR, Gresham GE, Calkins F. Muscle rehabilitation: Its effect on muscular and functional performance of patients with knee osteoarthritis. Arch Phys Med Rehabil. 1991;72:367-74. 4. Leivseth G, Tortstensson J, Reikeras O. Effect of passive muscle stretching in osteoarthritis of the hip. Clin Sci. 1988;76:113-7.
In response: Patients in one intervention protocol were encouraged to do light stretching and strengthening isotonic exercises as described by Daniels and Worthingham (1). Patients in the intervention arm of the trial were taught to stretch the affected extremities through pain-free ranges of motion during each exercise session prior to walking. All patients were taught how to use gravity as a resistance to strengthen muscles in both upper and lower extremities (especially quadriceps and knee extensors). Those patients who did not experience pain were also given a Thera-Band (The Hygenic Corporation, Akron, Ohio). This rubberized material provides varying levels of resistance and was used by patients to introduce progressive levels of resistance throughout the range of motion. Although we did not measure strength, we agree that both the stretching and especially the strengthening exercises, combined with walking, are likely to have contributed significantly to the improvements in patient outcomes we observed. By gaining additional flexibility and stability through these exercises, patients were probably able to decrease stress on the affected joints, thereby enhancing functional mobility. Evidence supporting the importance of the relation between muscle strength and functional status has been growing. For example, Fiatarone and colleagues (2) have suggested that muscle weakness in the frail elderly may be an important risk factor in falls, fracture, and functional dependency, and they have shown that high-intensity strength training can enable frail elderly up to 96 years of age to regain muscle strength, size, and functional mobility. The comments of Bunning and Materson attest to the importance of strength training. John P. Allegrante, PhD Pamela A. Kovar, EdD C. Ronald Mackenzie, MD Cornell Arthritis and Musculoskeletal Disease Center New York, NY 10021 References 1. Daniels L, Worthingham CA. Therapeutic Exercise for Body Alignment and Function. 2nd edition. Philadelphia: W.B. Saunders; 1977. 2. Fiatarone MA, Marks EC, Ryan ND, Meredith CN, Lipsitz LA, Evans WJ. High-intensity strength training in nonagenarians: effects on skeletal muscle. JAMA. 1990;263:3029-34.
Typhlitis and HIV To the Editors: The recent paper by Till and colleagues describes six patients with human immunodeficiency virus type 1 (HIV-1) infection who had clinical and radiographic findings consistent with typhlitis (1). However, in none of these cases, nor in two previously reported cases (2), was cecal inflammation confirmed at surgery or at autopsy. We recently treated an HIV-1-infected patient with typhlitis confirmed at laparotomy, associated with Clostridium septicum infection. A 34-year-old woman with advanced acquired immunodeficiency syndrome (AIDS) developed acute vomiting, diarrhea, and periumbilical pain which subsequently localized to the right lower quadrant. Her past history was significant for multiple opportunistic infections including disseminated Mycobacterium avium-intracellulare and cytomegalovirus retinitis. Physical examination showed an acutely ill, cachectic female with board-like abdominal rigidity, rebound tenderness, and absent bowel sounds. The white blood count was 3300/mm3 with 33% segmented neutrophils and 51% bands. Radiographs 698
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of the abdomen showed no evidence of free air. A computed tomographic scan showed multiple, fluid-filled large and small bowel loops without evidence of abscess. Laparoscopy showed fibrinopurulent exudates without an obvious etiology. Subsequent exploratory laparotomy showed the proximal colon at the hepatic flexure to be indurated and covered with a fibrinous exudate. No perforation or luminal obstruction was evident. The abdomen was irrigated with saline and closed. Postoperatively, cefoxitin and amikacin were administered. A culture of peritoneal exudate obtained at the time of surgery grew only Clostridium septicum. Cefoxitin was withdrawn, and a regimen of imipenem plus cilastatin was begun. Postoperatively, the patient improved rapidly. Clostridium difficile toxin was subsequently detected in a diarrheal stool specimen, and oral vancomycin was given. The remainder of her hospital course was uneventful. Her wound healed well and she was discharged home on the eighth postoperative day. Clostridium septicum has been the most common organism associated with typhlitis in patients with other predisposing conditions (3), and its isolation in our patient with surgically confirmed disease of the proximal colon suggests that this syndrome in HIV-1-infected patients may represent a similar pathologic process. Connie Jumper, MD J. John Weems, Jr., MD Ludwig A. Lettau, MD, MPH Greenville Hospital System Greenville, SC 29605 References 1. Till M, Lee N, Soper WD, Murphy RL. Typhlitis in patients with HIV-1 infection. Ann Intern Med. 1992;116:998-1000. 2. Cutrona AF, Blinkhorn RJ, Crass J, Spagnuolo PJ. Probable neutropenic enterocolitis in patients with AIDS. Rev Infect Dis. 1991; 13: 828-31. 3. Clostridium septicum and neutropenic enterocolitis [Editorial]. Lancet. 1987;2:608.
Calculating Body Mass Index To the Editors: The 1985 National Institutes of Health (NIH) Consensus Development Panel on Health Implications of Obesity recommended that physicians adopt the body mass index (BMI) (body weight in kilograms divided by square of height in meters) in evaluating patients (1). The 1992 NIH Technology Assessment Conference Panel on Methods for Voluntary Weight Loss and Control noted its importance as " a widely used means to define overweight" (2). Nomograms and tables for determining BMI have long been available, as has the Portland Health Institute Body Mass Index Graph (3). More than 1000 free copies have been mailed after receipt of selfaddressed, stamped envelopes. Physicians and other health professionals have found the Portland Health Institute Body Mass Index Graph useful in patient counseling and education. To meet the occasional need for an even simpler, more rapid means of determining BMIs from weight (in pounds) and height (in inches) for other purposes, as when reviewing medical records, fitness test data, or research reports, the following equation permits the easy determination of BMI with the aid of a hand calculator.
BMI =
kg (m) x (m) lb 4- 2.2 lb/kg
~ (in x 0.0254 m/in) x (in x 0.0254 m/in) lb " (in) x (in) x (0.0254 x 0.0254 x 2.2) = lb ^ in H- in + (0.0254 x 0.0254 x 2.2) BMI = lb -s- in +- in + (0.0014192)
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Herman M. Frankel, MD Jean C. Staeheli Portland Health Institute, Inc. Portland, OR 97219-4028 References 1. National Institutes of Health Consensus Development Panel. Health implications of obesity: National Institutes of Health Consensus Development Conference statement. Ann Intern Med. 1985;103:147-51; Ann Intern Med. 1985;103(Suppl 6, Part 2): 1073-7. 2. Technology Assessment Conference Panel. Methods for voluntary weight loss and control: Technology Assessment Conference statement. Ann Intern Med. 1992;116:942-9. 3. Frankel HM. Determination of body mass index. JAMA. 1986;255: 1292. Striking " F M G " from Our Vocabulary To the Editors: Varki (1) appropriately emphasizes the importance of individual performance as the standard for judging individual capability as opposed to professional pedigree. I received pedestrian to downright poor teaching in a standard U.S. medical school (and have published an essay so stating in its alumni publication) but, I trust, have been able to surmount that obstacle. Like U.S. graduates, foreign graduates attend medical schools of varying quality and must be considered individually. That so many have performed well has been a major factor in keeping many U.S. housestaffs afloat, for which we should be grateful. David H. Spodick, MD, DSc Saint Vincent Hospital University of Massachusetts Medical School Worcester, MA 01604 Reference 1. Varki A. Of pride, prejudice, and discrimination. Why generalizations can be unfair to the individual. Ann Intern Med. 1992; 116: 762-4. To the Editors: Dr. Varki (1) addressed sensitive issues directly and expressed the salient points clearly. The sentence, "In categorizing the [foreign medical graduate] " F M G , " the only possible outcome is the risk for prejudice and discrimination," is so appropriate and accurate, that it should appear in bold letters. Every program director should keep this in mind before deciding on an applicant for a position. The prejudice that this categorization promotes is further exemplified by the way in which a teaching program is graded based on the number of FMGs. Program directors are under constant pressure to avoid FMGs to maintain "their grade." Meanwhile, the FMG is caught in a situation in which he or she is forced to accept training programs that are undesirable, locking him or her in a no-win situation. Future academic appointments are denied to this individual based on this "less desirable" training. This unfortunate outcome can be avoided if candidates are selected based on individual knowledge, skill, and merit. It is time we abandon the FMG label. Arcot A. Dwarakanathan, Rush Medical College Chicago, IL 60612
graphically. At the very least, a blinded rater should be able to identify correctly, on the basis of quality of care, the location of a physician's medical school, more often than by chance. Ideally, a prospective study of FMG and USMG physicians entering residency together should include a 15-year follow-up period to determine their quality of care. For the analysis to be meaningful, such variables as recency of medical education, quality and location of residency training, elective and moonlighting opportunities, postresidency career opportunities, and the nature of the hospitals and populations with which they work should be controlled for. My hypothesis is that there would be more within-group variation than between-group variation. Just as good schools have graduated bad doctors and vice versa, group means may be misleading. It seems likely that individual differences in ability, skill, and motivation explain far more of the variance in quality of care than does the location of schools. Generalizations from spurious findings are not only unethical but are also unscientific. Until we can find a better reason to split, we should probably be content to lump. Mary Ganguli MD, MPH University of Pittsburgh Pittsburgh, PA 15261 Reference 1. Varki, A. Of pride, prejudice, and discrimination. Why generalizations can be unfair to the individual. Ann Intern Med. 1992; 116: 762-4. To the Editors: Varki clarifies common flaws in evaluating individual members of the heterogenous group of foreign or international medical graduates (IMGs) (1). To support his contention that the lower average score of IMGs cannot be extrapolated to infer the abilities of an individual IMG, we present data from our residency program experience. Our faculty has been impressed by the motivation, fund of knowledge, scholarly activity, and overall clinical performance of most IMGs. At our institution, 37 carefully selected IMGs completing training in internal medicine between 1987 and 1991 took the Certifying Examination of the American Board of Internal Medicine. They represented 16.8% of our 220 residents who took the examination during this period. Of these 37 IMGs, 35 (94.6%) passed. More impressively, among 34 IMGs for whom the specific overall score is known, 9 (26.5%) ranked in the top 10% nationally; 14 (41.2%), in the top quartile; and 27 (79.4%), in the top half. Both the subjective evaluations of performance and the scores clearly show that selected IMGs can excel. Andre L. Weigert, MD Edward C. Lynch, MD Baylor College of Medicine Houston, TX 77030 Reference 1. Varki A. Of pride, prejudice, and discrimination. Why generalizations can be unfair to the individual. Ann Intern Med. 1992; 116: 762-4.
MD
Reference 1. Varki A. Of pride, prejudice, and discrimination. Why generalizations can be unfair to the individual. Ann Intern Med. 1992; 116: 762-4. To the Editors: As Dr. Varki (1) points out, in science we often seek to understand information by categorizing it. Categories divide individuals into groups with shared characteristics, but to be meaningful, they should have predictive value. For example, in making a diagnosis we make a statement about prognosis. From this heuristic point of view, the burden is on the splitters to prove that FMGs and United States medical graduates (USMGs) differ "clinically," rather than simply demo-
In response: Discussing the sensitive and difficult issue of discrimination in a public forum can be a two-edged sword. On one hand, it can serve to shed light on a serious matter, thus encouraging rational behaviour. On the other hand, it could serve to fan the flames and aggravate, rather than improve, the situation. The intent of this perspective (1) was to suggest that the " F M G " or " I M G " issue should become a nonissue. Thus, the very best response one could have hoped for would have been none at all. However, that is wishful thinking. Fortunately, the responses printed here (and the many letters received directly) are uniformly supportive of my position; it is possible that those opposed have chosen not to speak out in public. Dr. Spodick correctly points out that the same principles could be applied to discrimination based upon site of medical training within the U.S. Dr. Dwarakanathan suggests that the phrase " . . . in categorizing the " F M G " the only possible outcome is the risk for discrimination and prejudice" should be
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strongly emphasized as the primary message. It is worth considering if this phrase would ring equally true if one substituted "black," "Hispanic" or " w o m a n " for " F M G . " Professor Ganguli correctly points out that the onus is upon the "splitters" to prove that categorizing physicians by their original medical training is justifiable. Actually, one hopes the "splitters" will give up this unscientific and inflammatory activity altogether. In this regard, the supportive response of Drs. Weigert and Lynch falls into the trap of presenting extremely well-meaning condescension. To the bigot, their data could actually mean that "carefully selected I M G s " can be quite good, ergo, most of them are not. Because all the residents in the Baylor program are probably "carefully selected," why classify a subgroup of them for separate "scientific" study? Also, why assume that none of these individuals is an American? It is my own fervent hope that I will never again see the term " F M G " or " I M G " in print in a public forum. However, such issues are difficult ones, open to varied opinions and interpretations. Ultimately, individuals must come to peace with their own intellectual honesty in such matters, as Tagore (2) did: Where the mind is without fear and the head is held high; Where knowledge is free; Where the world has not been broken up into fragments by narrow domestic walls; Where words come out from the depths of truth; Where tireless striving stretches its arms towards perfection; Where the clear stream of reason has not lost its way into the dreary desert sand of dead habit, . . . Into that heaven of freedom . . . let my country awake. Ajit Varki, MD UCSD School of Medicine La Jolla, CA 92093 References 1. Varki A. Of pride, prejudice, and discrimination. Why generalizations can be unfair to the individual. Ann Intern Med. 1992; 116: 762-4. 2. Tagore R. (Nobel Laureate 1913) from Gitanjali xxxv; 1910.
Randomized Clinical Trials and Patient Preferences To the Editors: Levine and colleagues (1), presented a useful tool for eliciting patient preference for adjuvant chemotherapy that gives a statistical perspective on the risks and benefits. However, they did not discuss another major and important method of dealing with the uncertainty of the situation in node-negative breast cancer: participation in randomized clinical trials. Not enough patients are being enrolled in clinical trials, making it difficult to answer important clinical questions such as those concerning risks and benefits in different subpopulations (2, 3). By participating in a clinical trial, the patient gets information about the current state of knowledge and may directly help her daughter, who will not face the same uncertainty, when results from properly conducted clinical trials become available.
References 1. Levine MN, Amiram G, Markham B, MacFarlane D. A bedside decision instrument to elicit a patient's preference concerning adjuvant chemotherapy for breast cancer. Ann Intern Med. 1992; 117: 53-8. 2. Benson AB ID, Pregler JP, Bean JA, Rademaker AW, Eshler B, Anderson K. Oncologists' reluctance to accrue patients onto clinical trials: An Illinois Cancer Center study. J Clin Oncol. 1991;9:2067-75. 3. Editorial on Clinical Trial Participation. J Clin Oncol. 1991;9:1927-30. 15 October 1992 • Annals of Internal Medicine
To the Editors: Howard Spiro gives a touching description of the human concern of one person for another and its importance in medicine (1). I think, however, that he mistakes medical student enthusiasm for empathy and misplaces its locus in our feelings instead of in our intellect. Do medical students come full of empathy only to lose it as they become physicians, as Dr. Spiro suggests? Surely not. They come imbued with romantic illusions and often real humanity but are seldom skilled at empathy. Placing empathy within the zone of feelings confuses empathy with sympathy, the vicarious experiencing of another's emotions. I prefer to consider empathy to be an intellectual understanding of those feelings. Key steps to effective empathy are 1) recognition that we are in the presence of a strong feeling; 2) a pause to imagine how the patient might be feeling to say what he has said or act as he has acted; 3) a clear statement of our perception of the patient's feeling or predicament; 4) legitimization of that feeling; 5) respect for the patient's efforts to deal with his predicament; and 6) offers of support and partnership. All of these are learnable and teachable (2-5). Frederic W. Piatt, MD 1901 East 20th Avenue Denver, CO 80205 References 1. Spiro H. What is empathy and can it be taught? Ann Intern Med. 1992;116:843-6. 2. Piatt FW, McMath JC. Clinical hypocompetence: the interview. Ann Intern Med. 1979;91:898-902. 3. Suchman AL, Mathews DA. What makes the physician-patient relationship therapeutic? Exploring the connexional dimension of medical care. Ann Intern Med. 1988;108:125-30. 4. Cohen-Cole SA. The Medical Interview: The Three Function Approach. St. Louis: Mosby Year Book; 1991:22. 5. Smith RC, Hoppe RB. The patient's story; integrating the patientand physician-centered approaches to interviewing. Ann Intern Med. 1991;115:470-7. To the Editors: It is rare that an eminent physician like Dr. Spiro discusses such a "soft" subject in a general medical journal (1). Two comments are worth adding. First, empathy requires time; not time spent learning it but time spent with the patient. If a physician is too busy seeing too many patients or for other reasons, then no amount of innate or learned empathy will ever find its way to a needy patient. Therefore, in this sense empathy relates to the type of professional life we choose to lead. Second, I agree with his comments on the loss of "spontaneous collegiality" among members of our profession. In the old days, some hospitals had coffee rooms where attending physicians and housestaff could meet informally, trade stories, follow up on consultations, and socialize. Resurrecting this custom would return its cost a thousandfold. Edward J. Volpintesta, MD 155 Greenwood Avenue Bethel, CT 06801 Reference 1. Spiro H. What is empathy and can it be taught? Ann Intern Med. 1992;116:843-6.
Aroop Mangaliky MD James Neidhart, MD University of New Mexico Cancer Center Albuquerque, NM 87131
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Empathy: Can It Be Taught?
To the Editors: I found the questions raised by Dr. Spiro (1) on the importance of empathy in medical education interesting. At the University of Missouri-Kansas City School of Medicine (2) we admit the majority of our students directly from high school to take advantage of their youthful energy, passion, and empathy and to begin their medical education before their attitudes are shaped by a competitive premedical education. Students interact with patients from the first week of school throughout a curriculum that integrates clinical medicine, basic science, and the humanities 11 months a year for 6 years.
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This approach to medical education, with its emphasis on the human condition, allows students to maintain their naturally acquired empathy, compassion, sensitivity, and honesty. These attitudes are encouraged and fostered by full-time faculty members (docents) from the Department of Medicine who supervise, teach, and serve as role models for groups of 12 students on inpatient medicine rotations and weekly ambulatory care clinics through the last 4 years. As a graduate of this program and now as a faculty member at this school, I can attest to its advantages. After 21 years, we have trained over 1200 physicians in the science and technology of medicine, while retaining their empathy for the individual patient. The early admission aspect of our program will only work with a select group of students and not in all schools. Early exposure of students to continuity of care in an outpatient clinic supervised by appropriate physician role models throughout medical school can and should be tried in other schools. We cannot teach empathy. This "almost magical" emotion is acquired and lost through life experiences. However, by recognizing the importance of the intangible qualities of a humanistic physician, we can enhance and promote these essential qualities. Gary A. Salzman, MD University of Missouri-Kansas City School of Medicine Kansas City, Missouri 64108 References 1. Spiro H. What is empathy and can it be taught? Ann Intern Med. 1992;116:843-6. 2. Dimond EG. The UMKC medical education experiment: an alternative pathway to physicianhood. JAMA. 1988;260:956-8.
To the Editors: The report by Spiro (1) was an insightful dissection of empathy and how it seems to melt away during the course of medical education. However, at the risk of sounding sacrilegious, I ask if empathy is really necessary for the highly trained scientific physician of the 1990's? We all know that too much emotional involvement (?empathy) may interfere with making good sound scientific judgments; I raise the question of how empathy enters into our modern sophisticated technologic treatment of patients. Is empathy simply a remnant of the days past when the physician did not have the modern tools of treatment? Kevin B. Lake, MD 50 Alessandro Place, Suite 330 Pasadena, CA 91105 Reference 1. Spiro H. What is empathy and can it be taught? Ann Intern Med. 1992;116:843-6.
To the Editors: Spiro's moving description of empathy (1) contains several sections where it appears that empathy and equanimity are conflicting attributes. Equanimity is equated with detachment, whose advocacy he links with Osier. Ironically, in the same issue of Annals, Osier is praised for his astute ability to make deductions from inconspicuous features (2). Osier did indeed promote "Aequanimitas" which he equates with imperturbability, the "coolness and presence of mind under all circumstances, calmness amid storm, clearness of judgment in moments of grave peril, immobility, impassiveness, or, to use an old and expressive word, phlegm" (3). He noted that a physician "who betrays indecision and worry . . .
loses rapidly the confidence of his patients." Many if not most life-threatening conditions were incurable in Osier's time. When caring for a young, healthy-appearing patient infected with HIV, it would be frightening if my attitude contributed to his fears. Indeed, what Osier advocates is "a judicious measure of obtuseness . . . without . . . 'hardening the human heart by which we live.' " Empathy and equanamity are not conflicting but complementary attributes which physicians should develop. Stephen J. Seligman, MD State University of New York Brooklyn, NY 11203 References 1. Spiro H. What is empathy and can it be taught? Ann Intern Med. 1992;116:843-6. 2. Belkin BM, Neelon FA. The art of observation: William Osier and the method of Zadig. Ann Intern Med. 1992;116:863-6. 3. Osier W. Aequanimitas. With other addresses to medical students, nurses and practitioners of medicine. Philadelphia: The Blakiston Company; 1944.
In response: What Dr. Piatt offers is eminently professional and helpful, but it is not empathy. He is at liberty to redefine empathy as an intellectual rather than an emotional sensation, but then he is not really talking about what most others mean by empathy. Dr. Volpintesta hits the proverbial nail on its head—more time should be spent with patients. But doctors are "too busy," so I ask, how do we know there are "too many" doctors. Too many for what? for a good living? Let's train more, so they can have time to talk. What Dr. Saltzman describes going on in Kansas City is right on target; medical students discussing patients and the human condition with older physicians. Most patients, possibly 80%, that doctors see in their offices require understanding and not technology. For Dr. Lake's specialty, critical care medicine, I would choose technical skill over empathy, to be sure. Still I would want a physician who could put himself or herself in my place. Dr. Seligman and I read Aequanimitas in the same way. I agree that a doctor empathic with an HIV-infected patient would not want to contribute to very real fear. He or she might well sit by the patient's side, however, and share their sorrow. As I wrote, it is not an "either/or" situation. Both empathy and equanimity have a place, but equanimity needs to be moved to the side as empathy is refurbished. I hope that the article, to which I have had many private responses, will help to begin to do just that. Howard M. Spiro, MD Yale University School of Medicine New Haven, CT 06510 Making It Easier To the Editors: Hurrah for "Making it Easier"! Your policy of clarifying generic drug names, abbreviations, and SI unit conversions at the beginnings of articles represents a long overdue acknowledgment that readers need help dealing with these issues. This new feature will improve both communication and education. Hunter Heath III, MD University of Utah School of Medicine Salt Lake City, UT 84132
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