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Update in Endocrinology To the Editor: This letter is written to clarify several statements

in the article "Update in Endocrinology" (1). First, the article stated that neutropenia may occur in up to 20% of patients receiving troglitazone. It seems that this statement is based on data from Kumar and coworkers (2). The actual report refer­enced states " . . .there was a decrease in the neutrophil count (to less than 0.9 times the lower limit of normal) in 9-20% of patients receiving troglitazone, with the highest incidences at the highest doses, although similar decreases were seen in 9% of patients on placebo." The data from the U.S. studies (n = 2510 patients), as cited in the Food and Drug Administration (FDA)-approved labeling for troglitazone, indicated that "small de­creases in hemoglobin, hematocrit and neutrophil counts (within the normal range) were more common in troglitazone-treated patients than placebo patients and may be related to increased plasma volume seen with troglitazone treatment" (3). Troglita­zone does not appear to lead to true "neutropenia."

Second, the article also erroneously stated that "at least 35 cases of liver failure have occurred among the 600 000 patients receiving troglitazone." The exact wording in the FDA paper of 3 November 1997 from which this statement is drawn is different (4): "As of October 21, 1997, 35 post-marketing reports of liver injury of various degrees have been received. These reports range from mildly elevated blood levels of the liver transaminase en­zymes to liver failure leading to one liver transplant and one death." The inference that all 35 of these reported cases involved liver failure is therefore incorrect. On 1 December 1997, the warning about liver dysfunction was further strengthened, and recommendations for liver function test monitoring were issued.

The final point regards the current approved indications for troglitazone. The article states that "the Food and Drug Admin­istration has approved the drug [troglitazone] for use in patients with type 2 diabetes receiving insulin whose hemoglobin A l c

levels continue to be greater than 0.085." This was, in fact, the initial indicated use for troglitazone, granted in late January 1997. However, on 4 August 1997, the FDA approved troglita­zone as an adjunct to diet and exercise and as a combination agent for concomitant use with either sulfonylurea or insulin in patients with type 2 diabetes (3). The wording about the recom­mended hemoglobin A l c level (>0.085) to define the patient population that was appropriate was also dropped with the new indications. This has important implications for the treatment algorithm included in the update. The statement is also made that use with insulin "is currently the major role of troglitazone." In fact, troglitazone has been and continues to be prescribed for all of its indications, including as initial therapy and in combi­

nation with other oral agents, as well as in combination with insulin. I believe these clarifications will update the information presented in the article and give the readers the most current facts.

Randall W. Whitcomb, MD Parke-Davis Pharmaceutical Research Ann Arbor, MI 48105

References 1. Schlechte JA, Kreisberg R. Update in endocrinology. Ann Intern Med.

1998;128:378-85. 2. Kumar S, Boulton AJ, Beck-Nielsen H, Berthezene F, Muggeo M,

Persson B, et al. Troglitazone, an insulin action enhancer, improves metabolic control in NIDDM patients. Troglitazone Study Group. Dia-betologia. 1996;39:701-9.

3. Prescribing Information for Rezulin (Troglitazone). Morris Plains, NJ: Parke-Davis Pharmaceuticals; December 1997.

4. FDA Talk Paper. Rezulin Labeling Changes. 3 November 1997.

Guidelines for Glycemic Control in Type 2 Diabetes

To the Editor: Vijan and colleagues (1) used a Markov decision model to estimate the benefit of glycemic control with respect to the end points of blindness and end-stage renal disease in per­sons with type 2 diabetes without preexisting microvascular com­plications. They found that the benefit of glycemic control de­creased with increasing age at diabetes onset.

The decrease in absolute risk resulting from decreased dura­tion of diabetes permits risk stratification in determining a pa­tient's target hemoglobin A l c level, an approach used to design the Veterans Health Administration (VHA) Guidelines for Man­agement of Diabetes Mellitus. Developed in collaboration with members of the Executive Committee of the National Diabetes Education Program, the VHA guidelines are available on the Internet (http://www.va.gov/health/diabetes/default.htm) and are to be used in all VHA facilities.

Participants in the guideline development concluded that a synthesis of the evidence, including key controlled trials (2), epidemiologic studies (3), and computer modeling (1, 4), sup­ported the use of life expectancy and clinical microvascular dis­ease as major determinants in setting a target value for glycemic control in an individual patient. Clinicians should still assess other factors, such as psychosocial issues and patient preferences, when negotiating a target with their patients.

The VHA guidelines suggest that patients who are likely to live only a few years might have a target hemoglobin A l c level of about 0.09, whereas younger patients, especially those with mi­crovascular changes, may benefit from a target value of 0.07. Many, perhaps most, patients will have a target of about 0.08.

With risk stratification and flexible individual assessment, the VHA guidelines consider both the likelihood of an absolute reduction in microvascular outcomes and the likelihood of safely achieving a given level of glycemic control in a particular patient. We believe that this approach provides the evidence that prac­titioners and patients need to make informed choices and strengthens clinicians' role in caring for their patients.

Leonard Pogach, MD Veterans Affairs New Jersey Health Care System East Orange, NJ 07019

Clark T Sawin, MD Boston Veterans Affairs Medical Center Boston, MA 02130

References 1. Vijan S, Hofer TP, Hayward RA. Estimated benefits of glycemic control

in microvascular complications in type 2 diabetes. Ann Intern Med. 1997;127:788-95.

2. The relationship of glycemic exposure (HbAlc) to the risk of develop-

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ment and progression of retinopathy in the Diabetes Control and Complications Trial. Diabetes. 1995;44:968-83.

3. Klein R, Klein BE, Moss SE. Relation of glycemic control to diabetic microvascular complications in diabetes mellitus. Ann Intern Med. 1996;124(1 Pt 2):90-6.

4. Eastman RC, Javitt JC, Herman WH, Dasbach EJ, Copley-Merriman C, Maier W, et al. Model of complications of NIDDM. II. Analysis of the health benefits and cost-effectiveness of treating NIDDM with the goal of normoglycemia. Diabetes Care. 1997;20:735-44.

In response: The VHA guideline group has done an excellent job of reviewing the available evidence and condensing it into a flexible practice guideline that is usable by clinicians and re­searchers. Adoption and dissemination of the guideline have been mandated by the VHA; plans are being made to monitor patients with diabetes and provide clinicians with feedback on their care.

Although the guideline states that patient preferences should be considered when goals are being set for glycemic control, it also provides numeric goals (for example, "patients who are likely to live a few years might have a target hemoglobin A l c

level of about 0.09" and "Many, perhaps most, patients will have a target of about 0.08"). We would caution against letting these "treatment goals" metamorphose into "quality standards." Our experience with an ongoing study suggests that for many patients, treatment characteristics, rather than outcomes, may be the dom­inant factor in preference for therapy across the ranges of ben­efits predicted by our Markov model. To the extent that specific glycemic goals become quality standards, patient autonomy may be jeopardized by concerns over provider and institutional ac­countability.

Our primary purpose was to provide information for both patients and providers regarding outcomes and treatment char­acteristics before decisions about therapy are made. This is par­ticularly important in diabetes, for which the treatments not only affect long-term outcomes but are also likely to affect patients' quality of life and can accrue substantial short-term costs. For example, in our preliminary work, patients with diabetes report that insulin therapy, which is often required to achieve glycemic goals set forth in guidelines, is perceived as extremely onerous compared with diet and oral hypoglycemic agents. Unfortunately, patients are not routinely presented with quantifiable information about treatments and outcomes, and the best means of providing such information to patients remains uncertain. We hope that ongoing research will contribute to our understanding of the effect of patient preferences on outcomes research and guideline development.

Sandeep Vijan, MD, MS Timothy P. Hofer, MD, MS Rodney A. Hayward, MD Veterans Affairs Center for Practice Management and

Outcomes Research Ann Arbor, MI 48113-0170

Cost-Effectiveness of Echocardiography after Stroke

To the Editor: McNamara and colleagues (1) reported on the cost-effectiveness of transesophageal echocardiography (TEE) and the cost advantages over transthoracic echocardiography (TTE) in patients with stroke in normal sinus rhythm. As clinical echocardiographers, we are not as willing to dismiss the role of TTE. In contrast to the 2% to 3% incidence of complications with TEE (2), TTE is not associated with significant adverse reactions. Furthermore, many patients often have a readily iden­tifiable cause apparent on TTE (for example, left ventricular dysfunction, left ventricular thrombus, mitral stenosis), and evi­dence suggests (3) that newer-generation TTE systems can detect left atrial thrombus with high sensitivity.

In patients with sinus rhythm, absence of clinical heart disease, or normal TTE findings, the incidence of left atrial thrombus is low. In the nine studies selected by McNamara and colleagues that provided this subgroup information (their references 8-14, 17, and 21), only 6 of 736 patients (0.8%) had left atrial throm­bus detected by TEE. Of 824 consecutive patients with stroke, peripheral embolism, or transient ischemic attack referred for

Figure. Algorithm for use of transthoracic echocardiography {TTE) and transesophageal echocardiography {TEE). *TEE only in select cases.

TEE at the Cleveland Clinic (4), 236 (29%) had sinus rhythm and normal TTE findings; none of these 236 had left atrial thrombus on TEE. Although TEE may be able to identify other associated abnormalities, such as patent foramen ovale or atrial septal aneurysm, more readily than TTE can, the subsequent effect on patient management remains unproven.

We suggest that TTE still be used as the first-line approach, with TEE to follow in a selective fashion (Figure). Cost-effec­tiveness issues require additional formal analysis.

lames W. Tarn, MD, FRCP(C) Normand Lazarow, MD, PhD, FRCP(C) Kevin Wolfe, MD, FRCP(C) University of Manitoba Winnepeg, Manitoba R3A 1R9, Canada

References 1. McNamara RL, Lima JA, Whelton PK, Powe NR. Echocardiographic

identification of cardiovascular sources of emboli to guide clinical man­agement of stroke: a cost-effectiveness analysis. Ann Intern Med. 1997; 127:773-87.

2. Tarn JW, Burwash IG, Ascah KJ, Baird MG, Chan KL. Feasibility and complications of single-plane and biplane versus multiplane transesoph­ageal imaging: a review of 2947 consecutive studies. Can J Cardiol. 1997;13:81-4.

3. Omran H, Jung W, Wirtz P, Schimpf R, Illien S, Luderitz B. Assess­ment of left atrial appendage function and detection of thrombi: a prospective study comparing transthoracic and transesophageal echo­cardiography. Circulation. 1997;96:1-134.

4. Leung DY, Black IW, Cranney GB, Walsh WF, Grimm RA, Stewart WJ, et al. Selection of patients for transesophageal echocardiography after stroke and systemic embolic events. Role of transthoracic echocardiog­raphy. Stroke. 1995;26:1820-4.

To the Editor: McNamara and colleagues (1) showed that TEE is more cost-effective than TTE in ischemic stroke. They also concluded that all patients with new-onset stroke should have TEE. I do not think that their study supports the latter conclu­sion. In calculating costs for TEE, the authors included only the cost of the test. It is most likely that if all patients with new-onset stroke were to receive TEE, the average length of hospital stay for strokes would be increased.

The authors also estimate an 8% rate of cardiac thrombus and a 33% reduction in the rate of recurrent stroke if these patients were treated with anticoagulation. Thus, for 1000 patients with new ischemic stroke, 1000 TEE studies would be performed and 80 patients with cardiac thrombus would be detected. By treating these 80 patients for 1 year with warfarin, 10 recurrent strokes would be prevented at a cost of one cerebral hemorrhage and two cases of gastrointestinal bleeding. It does not seem reason-

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able to do a procedure involving conscious sedation on 1000 patients to potentially benefit 9 of them.

James R. Korb, MD Los Angeles, CA 90034

Reference 1. McNamara RL, Lima JA, Whelton PK, Powe NR. Echocardiographic

identification of cardiovascular sources of emboli to guide clinical man­agement of stroke: a cost-effectiveness analysis. Ann Intern Med. 1997; 127:775-87.

In response: Tarn and colleagues disagree with our recommen­dations and present the clinical algorithm used at their institu­tion. The main difference between their proposed algorithm and our formal analysis lies in their recommendation for using TTE to select patients for TEE, a strategy that they admit has not been formally validated. We believe that clinical history plays a larger role in selecting patients who may benefit from TEE. In our analysis, the cost-effectiveness ratio for the strategy that includes TEE only for patients with a "cardiac history" was indeed lowest compared with no imaging and no treatment. Because the conditions constituting a cardiac history can range from restrictive (myocardial infarction) to broad (hypertension), the value of clinical history is difficult to quantify by using the evidence currently in the literature. Nonetheless, in the studies that reported on cardiac history, findings on TTE rarely changed management, confirming the results of Sansoy and colleagues (1).

More than half of the 1.8% incidence of complications for TEE in the study that Tarn and colleagues cite (2) involved "minor adverse events" or "superficial thrombophlebitis"; only one patient died. This retrospective study did not have a control group, making attribution of clinical events difficult.

Dr. Korb postulates that the average length of stay for strokes would be increased if all patients with new-onset stroke were to have TEE. This may be true in some patients. However, there is no stipulation that TEE must be performed on an inpatient basis. In addition, bypassing the use of TTE before TEE may actually decrease length of stay. We also believe that cost-effectiveness analysis is a more comprehensive approach than the simpler analysis of the number needed to test. Decision analysis quanti­fies the tradeoffs by using explicitly stated values of probabilities, costs, and utilities of various outcomes. The threshold that soci­ety, a clinician, or a patient is willing to "pay" for better out­comes is left open to debate. Our analysis suggests that the strokes prevented may be "worth" the cost of TEE. In addition, we made the conservative assumption in our analysis that the only reason to perform echocardiography was to identify a thrombus. It remains to be seen whether treating other potential sources of intrathoracic emboli will reduce recurrent strokes.

Robert L. McNamara, MD, MHS Joao AC. Lima, MD Neil R. Powe, MD, MPH, MBA Johns Hopkins University Baltimore, MD 21205

References 1. Sansoy V, Abbott RD, Jayaweera AR, Kaul S. Low yield of transtho­

racic echocardiography for cardiac source of embolism. Am J Cardiol. 1995;75:166-9.

2. Tam JW, Burwash IG, Ascah KJ, Baird MG, Chan KL. Feasibility and complications of single-plane and biplane versus multiplane transesoph­ageal imaging: a review of 2947 consecutive studies. Can J Cardiol. 1997;13:81-4.

Intracoronary Stenting for Postpartum Coronary Artery Dissection

To the Editor: Spontaneous coronary artery dissection is a rare and often fatal cause of ischemic heart disease occurring pre­dominantly in young or middle-aged, otherwise healthy patients. The cause of and the optimal management approach for this challenging condition are still being debated (1-4). To our knowledge, about 200 cases of spontaneous coronary artery dis­section have been reported in the world literature. Sixty-eight percent of the reported cases occurred in women, and 30% of

Figure. Angiogram before intervention shows extensive dissection {arrows) in proximal left anterior descending coronary artery.

these patients were peripartum or puerperal. We describe the second case of postpartum coronary dissection successfully treated by intracoronary stenting; the first case was recently reported elsewhere (2).

A 31-year-old woman was admitted with a diagnosis of acute anterior myocardial infarction 4 days after an uncomplicated spontaneous vaginal delivery. She was a heavy smoker. Because her symptoms had started more than 18 hours before admission, thrombolytic therapy was avoided. The patient was given aspirin and intravenous nitroglycerin, metoprolol, and heparin. When she was discharged 6 days later, she was asymptomatic. However, she later developed recurrent, atypical angina pectoris, and car­diac catheterization was done. Coronary angiography revealed a longitudinal dissection of the proximal left anterior descending artery (Figure). Subsequently, an intracoronary stent was success­fully implanted, and the patient's condition stabilized. The pa­tient was discharged and continued to receive aspirin and ticlo-pidine. At a follow-up visit 5 months after stenting, the patient remained asymptomatic.

Physicians must maintain a high index of suspicion for isch­emic heart disease when evaluating peripartum or puerperal women with acute chest pain. Confirmation of acute myocardial infarction in this setting should prompt a diligent search for a possible coronary dissection. In the absence of severe left ven­tricular impairment, symptomatic patients with single-vessel dis­section not involving the left main coronary artery could benefit from primary coronary stenting to decrease the chance of sudden death, reinfarction, and arrhythmia.

Miguel Carrascosa Porras, MD Miguel Ares Ares, MD Hospital of Laredo 39770 Laredo, Cantabria, Spain

Javier Zucco Gill, MD Marques Valdecilla University Hospital 39008 Santander, Cantabria, Spain

References 1. Jorgensen MB, Aharonian V, Mansukhani P, Mahrer PR. Spontaneous

coronary dissection: a cluster of cases with this rare finding. Am Heart J. 1994;127:1382-7.

2. Klutstein MW, Tzivoni D, Bitran D, Mendzelevski B, Ilan M, Almagor Y. Treatment of spontaneous coronary artery dissection: report of three cases. Cathet Cardiovasc Diagn. 1997;40:372-6.

3. Borczuk AC, Hoeven KH, Factor SM. Review and hypothesis: the eosinophil and peripartum heart disease (myocarditis and coronary artery dissection)—coincidence or pathogenetic significance? Cardio­vasc Res. 1997;33:527-32.

4. Basso C, Morgagni GL, Thiene G. Spontaneous coronary artery dissec­tion: a neglected cause of acute myocardial ischaemia and sudden death. Heart. 1996;75:451-4.

Erythrocyte Sedimentation Rate and C-Reactive Protein in the Diagnosis of Polymyalgia Rheumatica

To the Editor: An erythrocyte sedimentation rate (ESR) of at least 40 mm/h has been included in the diagnostic criteria of

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polymyalgia rheumatica (1). However, some studies have re­ported a percentage of patients with polymyalgia rheumatica who have an ESR at diagnosis that oscillates between 10% to 20% of normal (2-4). C-reactive protein, a direct measure of acute phase response, could be a more sensitive marker of disease activity than ESR in patients with polymyalgia rheumatica. As a result, it could be useful for diagnosis and evaluation of relapse and recurrence.

We determined ESR (by the Westergren method) and C-reactive protein levels (by nephelometry; normal value < 0.5 mg/ dL) in 177 consecutive patients with polymyalgia rheumatica who were clinically assessed at diagnosis, monthly for the first 6 months, and then every 3 months during the follow-up period. The median duration of follow-up was 37 months (range, 5 to 70 months). At diagnosis and during follow-up, all patients were also evaluated for the 1987 modified American Rheumatism Association criteria for rheumatoid arthritis (5).

Ten of 177 patients (5.6%) had normal (<30 mm/h) ESRs at diagnosis (median, 22 mm/h [range, 14 to 30 mm/h]). Fifteen of 177 patients (8.5%) had ESRs less than 40 mm/h at diagnosis (median, 27 mm/h [range, 14 to 39 mm/h]). Only 2 of 177 patients (1.1%) had normal C-reactive protein values at diagnosis (0.5 and 0.3 mg/dL, respectively). One of these patients also had a normal ESR (18 mm/h), and the other had an elevated ESR (49 mm/h).

Compared with patients who had high ESRs, patients who had normal ESRs were more frequently male (32% compared with 70%; P = 0.03) and had systemic signs and symptoms less fre­quently (62% compared with 70%; P = 0.002). C-reactive protein levels were lower in patients with normal ESRs (1.9 ± 1.4 mg/dL compared with 6.8 ± 5.2 mg/dL; P = 0.005). However, 9 of 10 patients with a normal ESR at diagnosis had increased C-reactive protein levels (median, 1.4 mg/dL [range, 0.7 to 4.7 mg/dL]).

Our prospective follow-up study suggests that the frequency of polymyalgia rheumatica with normal ESR at diagnosis is lower than that reported in previous retrospective studies (2-4). The C-reactive protein level is more sensitive than ESR in the assess­ment of disease activity at diagnosis of polymyalgia rheumatica and could substitute for ESR in the diagnostic criteria for the condition.

Fabrizio Cantini, MD Ospedale di Prato Prato, Italy

Carlo Salvarani, MD Aziendo Ospedaliera Arcispedale S. Maria Nuovo Reggio Emilia, Italy

Ignazio Olivieri, MD Ospedale S. Orsola-Malpighi Bologna, Italy

References

1. Salvarani C, Macchioni PL, Boiardi L. Polymyalgia rheumatica. Lancet. 1997;350:43-7.

2. Ellis ME, Ralsto S. The ESR in the diagnosis and management of the polymyalgia rheumatica/giant cell arteritis syndrome. Ann Rheum Dis. 1983;42:168-70.

3. Helfgott SM, Kieval RI. Polymyalgia rheumatica in patients with a normal erythrocyte sedimentation rate. Arthritis Rheum. 1996;39:304-7.

4. Gonzalez Gay MA, Rodriguez-Valverde V, Blanco R, Fernandez-Sueiro JL, Armona J, Figueroa M, et al. Polymyalgia rheumatica without significantly increased erythrocyte sedimentation rate. Arch Intern Med. 1997;157:317-20.

5. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31: 315-24.

Cardiac Arrest and Myocardial Infarction Immediately after Sumatriptan Injection

To the Editor: Sumatriptan is a selective 5-hydroxytryptamine agonist efficacious in the treatment of migraine headache. Al­though chest discomfort associated with use of this product is

common, cardiovascular complications are rare. We describe a woman who had cardiac arrest and a right ventricular myocardial infarction immediately after subcutaneous injection of sumatriptan.

A 48-year-old surgically postmenopausal woman with a history of type 2 diabetes mellitus and tobacco abuse presented to our ambulatory care clinic with a migraine headache. She was given 6 mg of sumatriptan subcutaneously and within 10 minutes had chest tightness and nausea that persisted despite administration of meperidine and promethazine. Shortly thereafter, she col­lapsed and was found pulseless and apneic; the initial cardiac rhythm was polymorphic ventricular tachycardia. She was resus­citated after prolonged cardiopulmonary resuscitation and multiple direct-current countershocks; the initial postresuscitation electrocar­diogram showed diffuse ST-segment elevation. Subsequent elec­trocardiograms obtained minutes later showed inferior and right precordial ST-segment elevation. Emergent coronary angiography showed left dominant circulation, moderate left coronary disease, and a proximally occluded nondominant right coronary artery. Because of the small caliber of the vessel, intervention was not attempted. Over the next several days, the patient required large volumes of normal saline and early inotropic support to maintain cardiac output, but she gradually stabilized. The creatine phos-phokinase level peaked at 2881 U/L (MB fraction, 41) with a troponin I level of 31.9 ng/mL. The patient was discharged approximately 1 week later with mild cognitive defects and new decreased visual acuity attributed to ischemic optic neuropathy.

Although sumatriptan exerts its therapeutic effect through ce­rebral vasoconstriction, studies have also documented vasocon­striction in the coronary, pulmonary, and systemic vasculature after subcutaneous injection (1). Despite the generalized vaso­constrictive nature of this agent, few reports have associated sumatriptan with myocardial infarction. In two cases, no enzy­matic evidence of myocardial necrosis was reported (2, 3), and coronary angiography revealed either normal coronary arteries (2) or minimal luminal irregularities (3). In a third report, a 47-year-old man presented with an inferior myocardial infarction temporally associated with sumatriptan use; angiography was not performed (4). In a fourth case, a 35-year-old woman with severe coronary artery disease and history of cocaine abuse had cardiac arrest shortly after use of subcutaneous sumatriptan with subse­quent evidence of myocardial necrosis (5).

In contrast to previous associations, our patient developed symptoms immediately after sumatriptan injection, acute myocar­dial infarction was documented by both ST-segment elevation and enzymatic evidence of myocardial necrosis, and acute coro­nary angiography showed coronary occlusion in the distribution of electrocardiographic changes.

In light of this report and others (2-5) and the previously documented coronary vasoconstrictive properties of this medica­tion (1), sumatriptan is contraindicated in patients with coronary artery disease or vasospastic angina. Physicians should carefully question patients about risk factors for coronary artery disease before prescribing this drug.

Michael L. Main, MD Karthik Ramaswamy, MD Thomas C. Andrews, MD University of Texas Southwestern Medical Center at Dallas Dallas, TX 75235

References

1. Maclntyre PD, Bhargava B, Hogg KJ, Gemmill JD, Hillis WS. Effect of subcutaneous sumatriptan, a selective 5HT1 agonist on the systemic, pulmonary, and coronary circulation. Circulation. 1993;87:401-5.

2. Mueller L, Gallagher M, Ciervo CA. Vasospasm-induced myocardial infarction with sumatriptan. Headache. 1996;36:329-31.

3. O'Conner P, Gladstone P. Oral sumatriptan-associated transmural myo­cardial infarction. Neurology. 1995;45:2274-6.

4. Kelly KM. Cardiac arrest following use of sumatriptan. Neurology. 1995;45:1211-3.

5. Ottervanger JP, Paalman HJ, Boxma GL, Strieker BH. Transmural myocardial infarction with sumatriptan. Lancet. 1993;341:861-2.

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Large-Database Research: Complement to Randomized Trials?

To the Editor: We are disappointed by the emphasis that the articles on database research in the supplement published on 15 October 1997 place on sophisticated new mathematical models to control for confounding factors and by the classic commonplace that clinical database studies are "attractive alternatives to ran­domized trials" (1). Using large databases to compare therapies remains controversial (2). By design, databases record observa­tions made in clinical practice. Because treatment decisions are not randomly allocated, any observed therapeutic effect may be due to unrecognized factors affecting the treatment allocation rather than the treatment itself.

It is surprising that a supplement focused on the future of databases did not mention new research methods, such as cross-design synthesis (3), directed toward the generation of results with an acceptable balance between internal and external validity. Specifically, cross-design synthesis proposes the assessment, ad­justment, and combination of treatment effects obtained with randomized studies and database analyses.

Our group has recently proposed the simultaneous use of both experimental and observational methods to assess the effective­ness of drugs (4). Because randomization is essential to minimize comparison bias, we suggested the possibility of including ran­domization modules in new computer-based patient records. To our knowledge, this is the first time that the use of randomiza­tion with large databases has been proposed in the medical literature. These "randomized database studies" could be con­ducted when there is an interest in evaluating the actual effec­tiveness of several different options with demonstrated "equiva­lent" efficacy in previous research. Ideally, new computer-based clinical records should automatically suggest that patients are candidates for inclusion in a specific study. The progressive im­plantation of clinical practice guidelines and the new computer support systems for prescribing might contribute to better iden­tification of the best diagnostic and therapeutic options in every clinical situation. This research strategy could be used to com­plete with "medicine-based evidence" the circle that started with evidence-based medicine.

Jose A. Sacristan, MD Javier Soto, MD, PhD Ines Galende, MD Spanish Group for the Study of Methodology

in Clinical Research 28230 Las Rozas, Madrid, Spain

References

1. Hornberger J, Wrone E. When to base clinical policies on observational versus randomized trial data. Ann Intern Med. 1997;127:(8 pt 2)697-703.

2. Byar DP. Problems with using observational databases to compare treatments. Stat Med. 1991;10:663-6.

3. Cross design synthesis: a new strategy for studying medical outcomes? [Editorial] Lancet. 1992;340:944-6.

4. Sacristan JA, Soto J, Galende I. Assessment of effectiveness through the application of randomisation using databases: medicine-based evi­dence? Med Clin. (Bare) [In press.]

In response: The question of how to generalize data from randomized trials for use in real-world decisions is timely and important. Many decision makers desire credible information about the clinical and economic effects of new interventions. In response to this, Section 114 of the recently passed Food and Drug Administration Modernization Act of 1997 regulates the dissemination of pharmacoeconomic information that is "compe­tent and reliable" (1).

Representatives of the Food and Drug Administration, public interest groups, the legislative committee that drafted the bill, managed care organizations, the pharmaceutical industry, and academia recently convened in Washington, D.C., at a special briefing of the act sponsored by the International Society of Pharmacoeconomic and Outcomes Research (ISPOR). The sen­timent of many speakers was that randomized trials, although providing the greatest assurance of internal validity, fall short of

providing the data needed for economic analyses to be useful in the real world.

Sacristan and colleagues comment on one key limitation of randomized trials: the challenge of generalizing results from a highly selected trial population to the broader base of patients cared for in managed care plans. They offer a "randomized databases" solution that warrants critical appraisal. But there are other concerns, raised at the ISPOR briefing, about basing eco­nomic inferences on only the results of randomized trials. First, the variability in economic end points—both costs and quality of life—is often greater than the variability in clinical end points. The sample size of trials may be insufficient to detect significant differences in economic end points. By contrast, Bayesian ap­proaches permit estimation of sample sizes that are economically sensible, considering the costs of data collection and the value of new economic information (2). Second, the medical resources actually used in trials are often driven by the research protocol in response to regulatory concerns, which can limit the generaliz-ability of the findings when applied to real-world situations. Third, the costs of conducting long-term trials can be substantial, so that the only practical alternative is to measure in the trial the effect of a new intervention on a surrogate end point, which then may be linked to other observational data to estimate the poten­tial long-term consequences (3). The ever-increasing emphasis on health maintenance instead of disease treatment further under­scores the need for methods with which to estimate potential long-term consequences. Most technology must be adopted be­fore all long-term consequences can be established with certainty.

Controversy remains about how best to overcome the limita­tions of randomized trials. Different constituencies, despite their varied agendas, have expressed concern that existing methods of randomized trials do not provide the quality and timeliness of evidence that they and the public need for making real-world decisions. It is encouraging, however, that these groups are striv­ing to work together to develop competent and reliable stan­dards, perhaps considering new solutions, for estimating the clin­ical and economic consequences of new therapies.

John Hornberger, MD, MS Roche Global Pharmacoeconomic Research Palo Alto, CA 94304

Louis Garrison, PhD Stanford University School of Medicine Stanford, CA

References 1. U.S. Congress. Food and Drug Administration Modernization Act of

1997. Washington, DC: US Gov Pr Office; 1997. 2. Hornberger J. Cost-benefit of a cardiovascular disease-prevention trial:

folate as an example. Am J Publ Health. [In press.] 3. Mark DB, Hlatky MA, Califf RM, Naylor CD, Lee KL, Armstrong PW,

et al. Cost effectiveness of thrombolytic therapy with tissue plasminogen activator as compared with streptokinase for acute myocardial infarc­tion. N Engl J Med. 1995;332:1418-24.

The Language of Case Histories

To the Editor: I read with interest Dr. Donnelly's essay on the problematic language practices in case presentations and reports in teaching hospitals (1). Dr. Donnelly suggests that during group discussions, patients should be presented as "Mr. John Jones" rather than "37-year-old male." I do not know whether he is talking about a fictitious name, but real names are routinely withheld to preserve a patient's privacy.

Another phenomenon is worth mentioning; we like to call it group countertransference. The presentation given in the morning report or during hospital rounds goes something like this: "This is a patient who signed out AMA [against medical advice] twice and failed two clinic appointments" or "this is a frequent flier who is here every week with an asthmatic attack." When speak­ing these words, the presenter usually wears a sarcastic grin. Beyond that, the patient is treated as the biggest sinner on the planet. Nobody tries to explore the possibility that the patient might have missed the appointments because he recently lost his

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son or because his wife had had a heart attack. No one goes an extra few yards to find out whether a frequent flier visits the hospital so frequently because we are not managing her asthma properly. All of this is the direct result of problematic language practices, and it can have painful consequences for the patient.

Keshav Chander, MD The Chicago Medical School North Chicago, IL 60064

Reference

1. Donnelly WJ. The language of medical case histories. Ann Intern Med. 1998;128:1045-8.

To the Editor: Dr. Donnelly's well-referenced critique of ques­tionable language practices commonly encountered in case his­tories at teaching hospitals (1) is an important call to arms for educators in internal medicine. Although none of the seven language maladies represents abject failure in and of itself, the total tends to dehumanize or minimize the patient and all too often ignores the patient's understanding of his or her condition.

Two points, however, require further emphasis. First, charac­terizing a patient as "a 55-year-old self-employed architect who lives with his architect wife in their Westchester home" rather than simply as "a 55-year-old man" not only emphasizes the patient as a person but indicates that the physician was thorough and interested to know the patient's employment and occupa­tional history, marital relationship, family status, and place of residence. This information is crucial not only in helping under­stand the patient and his illness but in giving the caregiver an opportunity to connect with the patient. The lack of this under­standing leaves the caregiver little such opportunity; as a result, the patient is described purely in terms of symptoms, physical findings, and medical diagnoses. Second, the power of narrative in medical case histories relates to our fundamental roles as storytellers. When a case history is described in a narrative from the patient's viewpoint, it becomes a story. Suddenly, the large amount of detail necessary to provide a thorough medical eval­uation becomes woven into a tapestry that often provides a clear image of the pertinent issues at hand.

Our teachers of medicine need to take heed of Dr. Donnelly's seven language maladies. As Donnelly himself points out, none represents the deadliest of sins, although the total may limit a physician's ability to connect with the patient and provide effec­tive care.

Gregory C. Kane, MD Jefferson Medical College Philadelphia, PA 19107

Reference 1. Donnelly WJ. The language of medical case histories. Ann Intern Med.

1997;127:1045-8.

To the Editor: Dr. Donnelly has catalogued seven language maladies in the clinical case history (1). We agree with his list and would like to suggest two additions:

1. Using jargon and cliches. In addition to biomedical lan­guage, case histories often include stock phrases that are unin-formative and depersonalizing. Examples include such terms as "social admission" or "nursing home admission." Particularly troublesome is the use of age-inappropriate terms, such as as­cribing a diagnosis of "failure to thrive" to an elderly person. The remedy for this malady is simple: Such terms have no place in the case history.

2. Blaming the patient for deficiencies in the case history. Too often, histories begin with the phrase "the patient is a poor historian." Sometimes, the presenter should more accurately ad­mit that "I took a poor history." Other histories may be difficult to elicit because patients are confused or aphasic or speak a different language than the interviewer's. However, the use of frankly insulting language to describe these situations is unbe­coming to the physician and demeaning to the patient. A better option is for physicians to say, "I was unable to take a complete history because the patient was confused" or even " . . .because time was limited." Physicians can better recognize the context of a patient's illness by acknowledging their own limitations.

Dr. Donnelly's arguments can be extended to examine the power relationship between patients and physicians. To patients, oral case histories are often the translation of their intimate experience into an impersonal and incomprehensible code. The danger in "taking" a history is that physicians may also take control of telling the patient's story. Many patients grant this permission willingly, but we believe that physicians should have as much respect for this part of the patient encounter as they do for the physical examination.

Ahmed M. Bayoumi, MD, MSc Dena Bravata, MD Stanford University School of Medicine Palo Alto Veterans Affairs Health Care System Palo Alto, CA 94304

Reference 1. Donnelly WJ. The language of medical case histories. Ann Intern Med.

1997;127:1045-8.

To the Editor: I agree with most aspects of Dr. Donnelly's essay on questionable language of medical case histories (1). Dr. Donnelly wonders why the seven practices (or maladies) continue despite extensive criticism. He cites two main reasons: that sick­ness is considered a matter of disordered biology and, accord­ingly, that physicians adopt the viewpoint and methods of natural scientists. Thus, he states that a conventional, biomedically ori­ented history of present illness just reflects the facts and that more attention should be paid to the patient's personal experi­ence. In discussing the remedies to correct the language mala­dies, he suggests that a two-perspective history of present illness be incorporated—the biomedical perspective (disease) and the patient's perspective (illness). Both perspectives should appear in the medical case history as two separate narratives, from admission to discharge and in subsequent outpatient clinic visits.

Although such practices are probably used worldwide, they do not necessarily reflect what physicians do. In fact, large amounts of the patient's experience of illness are treated in off-the-record physician-patient talks. Thus, the problem is that the patient's perspective may not be transcribed but rather just discussed. In my opinion, an important reason that this sort of information is not recorded in the case histories is that, especially in a hospital setting, physicians simply do not have the time to do it. Most clinicians just get to the point; for that reason, we write "a 55-year-old patient" instead of "Mr. John Jones, a 55-year-old self-employed architect who lives with his architect wife. . . ." Although the patient has his or her own ideas, feelings, and fears, he or she is in the hospital because a physiologic function is failing. Thus, when time is precious, the case history may describe the patient's illness primarily in terms of disordered biology because that is the main reason for hospitalization.

To save time, I suggest that such otherwise important infor­mation be tape-recorded. A two-perspective history of the present illness can be easily acquired in this manner: the hard history (biomedical perspective) and the soft history (patient's perspective). For example, the hard history entry would state, "sixth hospital day: do not resuscitate according to patient's decision"; the soft history would state, "sixth hospital day: today Mr. Jones has been told of his diagnosis and prognosis; he prefers only supportive measures at the end-of-life days." The soft history could be periodically updated as needed according to psychological events or changes. It could also be used in out­patient visits; for example, the cassette could be played back just before the patient comes to the office to remind the physician of the patient's perspective of illness, and an update could be re­corded just after the patient's visit. In any case, each medical case hard history cassette would have to be accompanied by a corresponding patient's perspective cassette.

The more tools that can be used, the more prepared we will be to deal with patients' illnesses and perspectives.

Xavier Bosch, MD, PhD Hospital Casa Maternitat 08028 Barcelona, Spain

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Reference 1. Donnelly WJ. The language of medical case histories. Ann Intern Med.

1997;127:1045-8.

To the Editor: I read with interest and pleasure Dr. Donnelly's essay (1), and I agree with most of its sentiments. My complaint about language in case history presentation is more specific. I am a graduate of an Irish medical school who has been in the United States for the past 3 and a half years. Since coming here, I have found the use of the term "status post" in referring to aspects of the patient's history (recent or remote) to be appalling, both linguistically and humanely. "The patient had bypass surgery" is much gentler to my ear than "the patient is status post CABG." More important, I think that this ugly phrase is mechanistic and even degrading. Am I alone? Could I even dare suggest that we become status post "status post" and drop this abomination from our medical histories and case presentations?

Norman Delanty, MD Hospital of the University of Pennsylvania Philadelphia, PA 19104

Reference

1. Donnelly WJ. The language of medical case histories. Ann Intern Med. 1997;127:1045-8.

To the Editor: It has been nearly 30 years since Weed intro­duced the problem-oriented medical record (1). His system rev­olutionized the manner in which patient care was described in the medical record. It later resulted in the development of the progress note formatted by the acronym SOAP (S = subjective, O = objective, A = assessment, and P = plan). These terms have evolved and have often led to the misunderstanding of clinical information as either subjective or objective (2). Subjective in­formation has come to be viewed as "existing only in the mind," whereas objective information is seen to reflect "actual existence or reality" (3). The net effect is to minimize the patient's world while exaggerating the reality of the physician's (2). Dr. Donnelly previously suggested that we confront this issue and replace SOAP with HOAP (H = history, O = observation, A = assess­ment, and P = plan) (2). His "hope" was to legitimize what the patient reported as true by replacing "subjective" with "history." Furthermore, he noted that replacing "objective" with "observa­tion" is both more accurate and less presumptuous (2).

It was refreshing to read about this issue again in Donnelly's essay "The Language of Medical Case Histories" (4). Certainly, a more patient-centered medical record enhances the importance of the patient's perspective to our medical record keeping. With computers and the Internet, our patients have more access to medical information and can enrich our medical record.

I suggest we also add the final letter E, for "education," to Donnelly's acronym—HOAPE. Educating our patients shifts the emphasis from our patients' compliance to their participation in their health care. It invites our patients to take ownership of their health. It reminds the health care provider that education is an important component of the total care of the patient. Cer­tainly, it better expresses our "hope" (and not soap) that our patients will be restored to health.

Barry J. Wu, MD Hospital of St. Raphael New Haven, CT 06511

References

1. Weed LL. Medical records that guide and teach. N Engl J Med. 1968; 278:652-7.

2. Donnelly WJ, Brauner DJ. Why SOAP is bad for the medical record. Arch Intern Med. 1992;152:481-4.

3. American Heritage Dictionary. 2d College Edition. Boston: Houghton Mifflin; 1985. 1997;127:1045-8.

4. Donnelly WJ. The language of medical case histories. Ann Intern Med. 1997;127:1045-8.

To the Editor: In "The Language of Medical Case Histories," Dr. Donnelly advances the correct premise that the very descrip-tives we use determine the interpretation and valuation we apply to that which is being described (1).

The term "denies" does put a burden of proof on the patient.

"Subjective" is sterile and does imply a certain "second-class" quality in comparison to the unassailable "objective" of the phy­sician's input. HOAP may be viewed as a somewhat more useful (dare I say hopeful) formulation. As a believer in taking parallel "illness behavior" and "biomedical model" approaches to the understanding and management of patient, I thought that HOAP did not go far enough.

"History" is too limited because it seems to deal only with "chief complaint"; it does not encourage either the use of the patient's voice or an expansion of input to deal with life-issues. "Observations" is certainly an improvement on "Objective." "As­sessment" implies decision making that may not be appropriate. "Plan" is very action-oriented; perhaps a term is needed that adds reflection to action.

As a lover of acronyms, I would like to offer an alternative to SOAP/HOAP: AXIS.

"A" is for anamnesis: the recollections of the patient, not limited to the "chief complaint." By focusing on the memory and recollections of the patient, we emphasize the use of the patient's own words and do not devalue or circumvent the impressions expressed (2).

"X" is for examinations: the physical and laboratory examina­tions, whose results are open to interpretation and thus not necessarily objective.

"I" is for integration: the process whereby the care provider coordinates the patient's perception of his or her illness ("illness behavior"), the possible underlying disease process (as repre­sented in physical examination and laboratory testing results—the "biomedical model"), and other data into an interim understand­ing. Integration is meant to emphasize the two parallel views: illness and disease, experience and organ pathology.

"S" is for strategies, not explicitly limited to plans. This can be used to focus trainees on various issues, including, but not lim­ited to, means of gaining insights into the patient's understanding of his or her illness (for example, "illness meaning," "catastroph-izing" [3]); need for advanced directives; do-not-resuscitate sta­tus; social support systems and possible need for placement; and the diagnostic tests and therapies to be used.

AXIS emphasizes the biopsychosocial approach (4), focusing on a nonjudgmental hearing of the patient's recall and the pa­tient's experience of the illness. For this reason, SOAP/HOAP might best be modified, perhaps to demonstrate that patient evaluation does in fact revolve about a somewhat different axis than was defined nearly 30 years ago (5).

Leonard H. Sigal, MD University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School New Brunswick, NJ 08903

Reference 1. Donnelly WJ. The language of medical case histories. Ann Intern Med.

1997;127:1045-8. 2. Barbour A. Caring for Patients: A Critique of the Medical Model.

Stanford, CA: Stanford Univ Pr; 1995. 3. Sigal LH. Illness behavior and the biomedical model. Bull Rheum Dis.

1997;46:1-4. 4. Engel G. The need for a new medical model: a challenge for biomed-

icine. Science. 1977;196:129-36. 5. Weed LL. Medical Records, Medical Education, and Patient Care: The

Problem-Oriented Medical Record as a Basic Tool. Cleveland, OH: Press of Case Western University; 1969.

In response: I thank the correspondents for their supportive comments, examples of additional language maladies in case histories, and suggestions.

Dr. Chander's example of pejorative doctor talk in the morn­ing report illustrates some of the misunderstanding, frustration, and anger resulting from the collision of two different cultures, one predominantly Anglo and the other Hispanic. This type of cultural conflict was recently explored by Fadiman (1).

Dr. Kane reminds us that stories are the indispensable way that human beings make sense of their everyday experience of themselves and the world. The stories of our patients tell us what sickness, disability, and medical care mean to them.

Drs. Bayoumi and Bravata justly condemn the popular practice of calling the patient a "poor historian." This poisonous misno-

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mer also harms the speaker and the audience by obscuring the actual historian's role and the historical character of the entire history. Antidotes might include a reading of Toulmin's insightful essay about historical knowledge in medicine (2). Furthermore, I agree that translating the patient's story of his or her experience of sickness into a history that relates the sickness solely in biomedical terms is a dismissive, authoritarian act that casts the physician as a powerful, all-knowing expert and the patient as a weak and ignorant nobody.

Although Dr. Bosch worries that physicians do not have time to transcribe the patient's perspective, he provides some exam­ples of progress notes that convey the patient's voice both briefly and adequately. However, his labeling of the patient's perspective as "soft history" would perpetuate the mischief engendered by calling the patient's account "subjective."

Dr. Delanty rightly faults the careless use of "status post CABG" to describe the patient. Correctly punctuated, the words "status: post" modify instead the disorder for which surgery was performed: coronary arteriosclerotic heart disease; status: post coronary-aorta bypass graft.

Dr. Wu suggests adding the letter "E" for education to HOAP (history, observations, assessment, and plans). However, the P in HOAP stands for, as it did in SOAP, plans for 1) diagnosis, 2) treatment, and 3) patient education.

Dr. Sigal's observations remind us that problem-oriented for­mulas such as SOAP and HOAP are necessarily reductive, best at dealing with such matters as a symptom, an abnormal physical finding, or a disease. To convey patients' views of their personal situation, it is often better, as I suggested in my article, to write a progress note captioned simply as "history" or, better yet, as "patient perspective."

William J. Donnelly, MD Edward Hines, Jr. Veterans Affairs Hospital Hines, IL 60141

Reference 1. Fadiman A. The Spirit Catches You and You Fall Down: A Hmong

Child, Her American Doctors, and the Collision of Two Cultures. New York: Farrar, Straus & Giroux; 1997.

2. Toulmin S. Knowledge and art in the practice of medicine. In: Delkeskamp-Hayes C, Cutter MA, eds. Science, Technology, and the Art of Medicine: European-American Dialogues. Dordrecht, the Neth­erlands: Kluwer; 1993:231-49.

Correction: Cost-Effectiveness of Screening Mammography

Table 5 of a recent article on the cost-effectiveness of screen­ing mammography in women 40 to 49 years of age (1) contained an error. The table title should read "Efficacy Required To Achieve Various Levels of Cost-Effectiveness for Women 40 to 49 Years of Age," not " . . .Women 40 to 59 Years of Age." In addition, the Conclusion section of the abstract should have read "The cost-effectiveness ratio of screening mammography in women 40 to 49 years of age is almost five times that in older women."

Reference 1. Salzmann P, Kerlikowske K, Phillips K. Cost-effectiveness of extending

screening mammography guidelines to include women 40 to 49 years of age. Ann Intern Med. 1997;127:955-65.

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