Letters Annals of Internal Medicine COMMENTS AND RESPONSES Graduate Medical Education and Patient Safety TO THE EDITOR: I read with interest the excellent Quality Grand Kobayashi M, Fussell SR, Xiao Y, Seagull FJ Work coordination, workflow, and workarounds in a medical context In: Proceedings of the CHI 2005 Conference on Human Factors in Computing Systems, Portland, Oregon, 2-7 April 2005 New York: Assoc for Computing Machinery Pr; 2005:1561-64 TO THE EDITOR: In their recent Quality Grand Rounds article, Rounds article on graduate medical education by Shojania and colleagues (1) Although I work at a small (100-bed), community-based, semirural, nonteaching hospital, I was struck by the similarity of the case to a recent root-cause analysis performed at my hospital These similarities include an unreported, unlooked-for imaging study; “anchoring bias” (2); lack of a structured sign-out system; lack of communication between the admitting and covering physicians; and time and workload pressures I was also struck that the authors’ case analysis did not consider the nursing involvement in the care The authors did not indicate whether the nurse was aware of why she was asked to insert a nasogastric tube or whether this issue was recognized as a contributing cause If the nurse or nurses involved had known the reason for the nasogastric tube, then the correct tube and, perhaps, the appropriate type of suction would have been used At a time when medicine is increasingly systems- and protocol-driven and nursing care is increasingly task-oriented, having a team approach that includes the nursing staff has become more important but harder to accomplish It is clear that a major barrier to a more collaborative approach is interruptions (3) and workarounds (4, 5) that interfere with nurses’ workflow Over a shift, these disruptions can add up to considerable time Getting back on task can take additional time and can lead to errors Addressing this issue could give nurses more time to be involved with the medical staff and become more aware of the medical issues involved We are working very hard to correct this situation so that nurses can better function as part of the team In this case, if the hole in the nursing staff ’s slice of the Swiss cheese was smaller, the outcome could have been much different I would like to thank the authors of this report and the editors of this series for putting patient safety on a more equal footing with the more traditional medical specialties Attention to these issues will not only improve patient care, but it will also make good care of patients more rewarding and enjoyable for everyone involved However, we can’t make progress unless we believe that there are solutions Shojania and colleagues (1) described a case in which problems in communication and supervision among and between residents and an attending physician led to the possibly preventable death of an 88-year-old woman with intestinal obstruction The authors suggested how one might minimize sign-out and handoff problems, reduce tension between service and supervision, and encourage trainees to call for help The case description noted that a fourth-year medical student offered to insert a nasogastric tube because she wanted to learn how to perform the procedure Miscommunication between the student and the supervising nurse resulted in the insertion of a feeding tube instead—just one in a sequence of errors that ultimately led to the death of the patient In their discussion of this portion of the case, the authors overlooked an opportunity to comment on approaches to “learning by doing” through the use of simulation Soon it will no longer be necessary for medical students to perform their first procedures on actual patients Simulation laboratories in medical schools will provide the opportunity for students, trainees, and faculty to achieve core competencies in invasive procedures without the risk for harm to patients Consensus statements have been developed about the use of such tools as simulation and virtual reality for teaching and evaluating these competencies (2) How the current and future use of these technologies will replace the apprenticeship model for developing procedural skills should be of interest to all medical educators (3) The case also highlighted the importance of knowing when to call for help In their discussion of this issue, however, the authors failed to suggest strategies to reduce the potential for patient harm when the resident does not call for help One such strategy is the development of a hospital rapid response system in which nurses are authorized to call for medical emergency teams when a patient’s condition is observed to be unexpectedly and seriously worse Although this approach was initially developed in nonteaching hospitals, it is equally relevant in teaching hospital settings Readers may be interested in the recently published findings of the first consensus conference on medical emergency teams (4) Matthew N Fine, MD Oroville Hospital Oroville, CA 95966 Paul F Griner, MD University of Rochester School of Medicine Rochester, NY 14642 Potential Financial Conflicts of Interest: None disclosed Potential Financial Conflicts of Interest: None disclosed References References Shojania KG, Fletcher KE, Saint S Graduate medical education and patient safety: a busy—and occasionally hazardous—intersection Ann Intern Med 2006;145:592-8 [PMID: 17043341] Redelmeier DA Improving patient care The cognitive psychology of missed diagnoses Ann Intern Med 2005;142:115-20 [PMID: 15657159] Brixey JJ, Robinson DJ, Tang Z, Johnson TR, Zhang J, Turley JP Interruptions in workflow for RNs in a level one trauma center AMIA Annu Symp Proc 2005: 86-90 [PMID: 16779007] Spear SJ, Schmidhofer M Ambiguity and workarounds as contributors to medical error Ann Intern Med 2005;142:627-30 [PMID: 15838069] Shojania KG, Fletcher KE, Saint S Graduate medical education and patient safety: a busy—and occasionally hazardous—intersection Ann Intern Med 2006;145:592-8 [PMID: 17043341] Vozenilek J, Huff JS, Reznek M, Gordon JA See one, one, teach one: advanced technology in medical education Acad Emerg Med 2004;11:1149-54 [PMID: 15528578] Gorman PJ, Meier AH, Rawn C, Krummel TM The future of medical education is no longer blood and guts, it is bits and bytes Am J Surg 2000;180:353-6 [PMID: 11137686] Devita MA, Bellomo R, Hillman K, Kellum J, Rotondi A, Teres D, et al Findings © 2007 American College of Physicians 685 Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/20135/ by a University of California San Diego User on 01/16/2017 Letters of the first consensus conference on medical emergency teams Crit Care Med 2006; 34:2463-78 [PMID: 16878033] TO THE EDITOR: In the case described in the recent Quality Grand Rounds article by Shojania and colleagues (1), the initial management of the patient reflects the treating clinician’s understandable expectation of a rapid recovery from “mild pancreatitis.” This expectation is wrong Pancreatitis in patients older than 65 years of age would have a statistical mortality rate of 20% (2) In patients older than 80 years, the mortality rate is probably higher—perhaps 40% (3) Usual prognostic criteria not seem to apply to elderly patients (3, 4) Nor does resolution of pancreatitis, which occurred in this case, guarantee a good outcome Age-adjusted mortality rates are 30 times higher in the first month after admission and times higher in the second month (2) Failure to appreciate that even “mild” disease in this particular patient had a very high mortality rate was probably the single biggest contributor to a potentially preventable death Admission to an acute care unit to help ensure closer monitoring and adherence to therapy was likely the fundamental oversight Stephen R Workman, MD, MSc Dalhousie University Halifax, B3H 4R2 Nova Scotia, Canada Dr Workman highlights our characterization of the treating clinicians’ impression of “mild pancreatitis” and their expectation of an uneventful recovery As part of our preparation of the case discussion, we reviewed the study cited by Dr Workman, which reported outcomes of pancreatitis stratified by age (3) Although it is not clear what proportion of patients who died had initially appeared clinically stable (as in the case we discussed), we agree that the possibility of adverse outcomes from pancreatitis should never be underestimated, especially in elderly persons Kaveh G Shojania, MD Ottawa Hospital and Ottawa Health Research Institute Ottawa, K1Y 4E9 Ontario, Canada Kathlyn E Fletcher, MD, MA Clement J Zablocki Veterans Affairs Medical Center and Medical College of Wisconsin Milwaukee, WI 53295 Sanjay Saint, MD, MPH Ann Arbor Veterans Affairs Medical Center and University of Michigan Medical School Ann Arbor, MI 48109 Potential Financial Conflicts of Interest: None disclosed Potential Financial Conflicts of Interest: None disclosed References References Shojania KG, Fletcher KE, Saint S Graduate medical education and patient safety: a busy—and occasionally hazardous—intersection Ann Intern Med 2006;145:592-8 [PMID: 17043341] Goldacre MJ, Roberts SE Hospital admission for acute pancreatitis in an English population, 1963-98: database study of incidence and mortality BMJ 2004;328: 1466-9 [PMID: 15205290] Paajanen H, Jaakkola M, Oksanen H, Nordback I Acute pancreatitis in patients over 80 years Eur J Surg 1996;162:471-5 [PMID: 8817224] Fan ST, Choi TK, Lai CS, Wong J Influence of age on the mortality from acute pancreatitis Br J Surg 1988;75:463-6 [PMID: 3390679] IN RESPONSE: We thank Dr Fine for his kind remarks about the Quality Grand Rounds series Our article highlighted the importance of clear communication and the ways in which failure to explain key aspects of the care plan contributed to several errors in the case We focused on physician trainees because of space limitations However, we agree that poor physician–nurse communication contributed to the mistaken insertion of a feeding tube instead of a nasogastric tube, and failings in this area are an important source of medical errors We agree with Dr Griner that the use of simulation promises to improve the acquisition of key procedural skills by trainees A rapid response team may also have helped in the case, but the physicians’ responses to the nurse’s pages were in fact quite timely and the nurse seemed satisfied by the physicians’ assessments In other words, even if a rapid response team had been available in the hospital at the time, there was no indication that the nurse would have called for it Moreover, despite widespread enthusiasm for rapid response teams, the only randomized, controlled trial to evaluate their efficacy showed no benefit (1) and other studies that have reported benefits suffer from important methodological limitations (2) Hillman K, Chen J, Cretikos M, Bellomo R, Brown D, Doig G, et al Introduction of the medical emergency team (MET) system: a cluster-randomised controlled trial Lancet 2005;365:2091-7 [PMID: 15964445] Winters BD, Pham J, Pronovost PJ Rapid response teams—walk, don’t run JAMA 2006;296:1645-7 [PMID: 17018807] Goldacre MJ, Roberts SE Hospital admission for acute pancreatitis in an English population, 1963-98: database study of incidence and mortality BMJ 2004;328: 1466-9 [PMID: 15205290] Blood Products for Spanish Influenza: A Future H5N1 Treatment? TO THE EDITOR: We would like to add to the discussion in Luke and colleagues’ meta-analysis (1) of historic literature about the possible beneficial effect of transfusion on the clinical outcome of patients with Spanish influenza We suggest that the effect might not be due to the specific neutralizing effects of anti-influenza antibodies in the blood product but rather to the transfusion of whole blood, including immunoglobulins (and thus the provision of plasma oncotic pressure) We recently reported on a previously healthy man with severe shock who required admission to the intensive care unit His condition was associated with an almost complete disappearance of circulating immunoglobulins (2) Immunoglobulin levels were 0.23 g/L (IgA), 0.12 g/L (IgM), and 1.0 g/L (IgG) at admission With supportive treatment, including administration of fresh frozen plasma, the condition of the patient improved rapidly In days, immunoglobulin levels returned to normal Only influenza A virus (H3N2) could be isolated, which suggested a causal relationship The acute onset and nearly fatal course resembled that of patients during the Spanish influenza pandemic We were able to retrieve a plasma sample from 686 May 2007 Annals of Internal Medicine Volume 146 • Number Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/20135/ by a University of California San Diego User on 01/16/2017 www.annals.org Letters the patient that had been obtained weeks before the acute onset of disease We found that predisease immunoglobulin levels were normal, as opposed to the almost total disappearance of immunoglobulins in the acute stage of the illness Therefore, keeping limitations of this single observation in mind, we suggest that the possible beneficial effect might be caused by the administration of protein, including immunoglobulins, that occurs in whole-blood transfusion Susan J Logtenberg, MD Henk J Bilo, MD, PhD Isala Clinics 8025 AB, Zwolle, the Netherlands Potential Financial Conflicts of Interest: None disclosed References Luke TC, Kilbane EM, Jackson JL, Hoffman SL Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med 2006;145:599-609 [PMID: 16940336] Logtenberg SJ, Pasma FH, Wolfhagen MJ, Dikkeschei LD, Bilo HJ Disappearance of immunoglobulins in acute phase of influenza A infection Lancet 2006;368:1546 [PMID: 17071289] IN RESPONSE: We agree with Drs Logtenberg and Bilo that the possible benefit of convalescent blood products, including plasma, for treating Spanish influenza pneumonia may not have been entirely due to the presence of neutralizing antibodies Plasma is a complex mixture of immunoglobulins, coagulation factors, cytokines, and other immunologically and physiologically active molecules It is sometimes used to treat patients with circulatory collapse—presumably because it expands volume while increasing oncotic pressure, as theorized by Drs Logtenberg and Bilo Furthermore, both adaptive and innate immune responses likely contribute to the control of influenza infections Products of the innate immune system in plasma may have contributed to controlling the infection in the patient in Drs Logtenberg and Bilo’s study and in the patients reported in our paper However, the therapeutic effect of passively delivered neutralizing antibodies cannot be dismissed Multiple strains of H3N2 influenza have circulated globally since the illness first arose in 1968, and many if not most plasma donors have been exposed to multiple wild-type H3N2 strains, seasonal influenza vaccines, or both The fresh frozen plasma units transfused into the patient in their report may have contained neutralizing H3 antibodies We believe that Drs Logtenberg and Bilo’s experience suggests that patients with serious seasonal H1 or H3 influenza infections may benefit from receiving transfusions with plasma with an unknown titer of neutralizing antibodies or preferably with plasma or purified immunoglobulin that is specifically selected for a high titer of H1 and H3 antibodies Thomas C Luke, MD, MTMH, MA Stephen L Hoffman, MD, DTMH Bureau of Medicine and Surgery, U.S Navy Washington, DC 20372-3000 Potential Financial Conflicts of Interest: None disclosed www.annals.org CLINICAL OBSERVATION Sirolimus Treatment for Pulmonary Lymphangioleiomyomatosis Background: Lymphangioleiomyomatosis (LAM) is a rare disease characterized by abnormal proliferation of smooth-muscle cells within the lung (1) that are responsible for the cystic destruction of lung parenchyma, leading to chronic respiratory failure (2) No effective treatment, except for lung transplantation, is available Abdominal tumors (renal angiomyolipomas, lymphangioleiomyomas, and enlarged lymph nodes) are frequently associated with lung involvement Recently, loss-of-function mutations in the tumor suppressor genes tuberous sclerosis and (TSC1 and TSC2, respectively) have been described in LAM (3) In vitro studies on LAM smooth-muscle cells have shown that mutation on the TSC1–TSC2 complex dysregulates the activation of ribosomal protein S6 kinase (S6K1), which leads to abnormal cell proliferation (4) Sirolimus (rapamycin), a specific S6K1 inhibitor, abolishes LAM cell abnormal proliferation in vitro (5) Objective: To determine whether sirolimus could provide clinical benefit for patients with LAM Case Report: A 34-year-old black female nonsmoker received a diagnosis of sporadic LAM in the setting of diffuse, round, thinwalled pulmonary cysts and chylothorax in the right lung that were associated with several large retroperitoneal and pelvic lymphangioleiomyomas and large uterine myomas At diagnosis, pulmonary function tests revealed reduced lung volumes and low diffusing capacity of the lung for carbon monoxide (DLCO), and arterial blood gas analysis showed profound hypoxemia Lung biopsy was not considered because of the severity of respiratory failure Sirolimus treatment, mg/d, was started in October 2005 The treatment was well tolerated, expect for a moderate elevation of serum cholesterol level General status improved, with a total weight gain of kg Arterial blood gases improved (PO2 increased from 54 to 65 mm Hg on room air), allowing weaning from oxygen support after months Exercise capacity, assessed by a 6-minute walking test, also greatly improved: The patient could walk 105 meters at diagnosis and 450 meters after months of treatment The FVC increased from 1820 mL (51% of predicted value) to 2700 mL (75% of predicted value), FEV1 increased from 900 mL (32% of predicted value) to 1470 mL (47% of predicted value), and DLCO did not change after treatment On computed tomography of the chest, right pleural effusion disappeared after months, but the number and size of pulmonary cysts did not change after months (Figure, A and B) On magnetic resonance imaging, abdominal and pelvic masses completely disappeared (Figure, C and D) Discussion and Conclusion: This case supports the hypothesis that given its antiproliferative effects on smooth-muscle cells, sirolimus could be a therapeutic option for lymphangioleiomyomatosis However, sirolimus seems to have more important effects on the reduction of abdominal masses than on the reduction of lung cysts Camille Taille´, MD, PhD Marie-Pierre Debray, MD Bruno Crestani, MD, PhD Hoˆpital Bichat–Claude Bernard and Hoˆpitaux de Paris Paris 75018, France May 2007 Annals of Internal Medicine Volume 146 • Number 687 Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/20135/ by a University of California San Diego User on 01/16/2017 Letters Figure Magnetic resonance imaging and computed tomography scans A Right chylothorax was observed at diagnosis B The chylothorax completely disappeared after months of sirolimus treatment C Axial fast spin-echo T2-weighted magnetic resonance imaging scan of the pelvis revealed large retroperitoneal and pelvic masses (arrows) at diagnosis D After months of treatment, no abdominal mass was observed (arrows) Magnetic resonance imaging was always done at the same hour to avoid diurnal variation of lymphangioleimomyoma size Potential Financial Conflicts of Interest: None disclosed CORRECTIONS References Finlay G The LAM cell: what is it, where does it come from, and why does it grow? [Editorial] Am J Physiol Lung Cell Mol Physiol 2004;286:L690-3 [PMID: 15003933] Sullivan EJ Lymphangioleiomyomatosis: a review Chest 1998;114:1689-703 [PMID: 9872207] Strizheva GD, Carsillo T, Kruger WD, Sullivan EJ, Ryu JH, Henske EP The spectrum of mutations in TSC1 and TSC2 in women with tuberous sclerosis and lymphangiomyomatosis Am J Respir Crit Care Med 2001;163:253-8 [PMID: 11208653] Goncharova EA, Goncharov DA, Eszterhas A, Hunter DS, Glassberg MK, Yeung RS, et al Tuberin regulates p70 S6 kinase activation and ribosomal protein S6 phosphorylation A role for the TSC2 tumor suppressor gene in pulmonary lymphangioleiomyomatosis (LAM) J Biol Chem 2002;277:30958-67 [PMID: 12045200] Goncharova EA, Goncharov DA, Spaits M, Noonan DJ, Talovskaya E, Eszterhas A, et al Abnormal growth of smooth muscle-like cells in lymphangioleiomyomatosis: role for tumor suppressor TSC2 Am J Respir Cell Mol Biol 2006;34:561-72 [PMID: 16424383] Correction: New Tests for the Diagnosis of Latent Tuberculosis Infection The recent meta-analysis on new tests for diagnosing latent tuberculosis infection (1) contained errors in some table headings Under the “Concordant Results” heading in Table and Table 5, the second heading should have stated “TST-Negative and IGRA-Negative.” Under the “Concordant Reactions” heading in Table 6, the second heading should have stated “T-SPOT.TB–-Negative and QFT-G– Negative.” These errors not affect the results reported in the tables Reference Menzies D, Pai M, Comstock G Meta-analysis: new tests for the diagnosis of latent tuberculosis infection: areas of uncertainty and recommendations for research Ann Intern Med 2007;146:340-54 [PMID: 17339619] 688 May 2007 Annals of Internal Medicine Volume 146 • Number Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/20135/ by a University of California San Diego User on 01/16/2017 www.annals.org ... Interest: None disclosed www.annals.org CLINICAL OBSERVATION Sirolimus Treatment for Pulmonary Lymphangioleiomyomatosis Background: Lymphangioleiomyomatosis (LAM) is a rare disease characterized... given its antiproliferative effects on smooth-muscle cells, sirolimus could be a therapeutic option for lymphangioleiomyomatosis However, sirolimus seems to have more important effects on the reduction... within the lung (1) that are responsible for the cystic destruction of lung parenchyma, leading to chronic respiratory failure (2) No effective treatment, except for lung transplantation, is available