LETTERS
Annals of Internal Medicine COMMENTS AND RESPONSES
References 1. Rochwerg B, Alhazzani W, Sindi A, Heels-Ansdell D, Thabane L, FoxRobichaud A, et al; Fluids in Sepsis and Septic Shock Group. Fluid resuscitation in sepsis: a systematic review and network meta-analysis. Ann Intern Med.
Albumin Administration in Patients With Sepsis
2014;161:347-55. [PMID: 25047428] doi:10.7326/M14-0178 2. Delaney AP, Dan A, McCaffrey J, Finfer S. The role of albumin as a resuscitation fluid for patients with sepsis: a systematic review and meta-analysis.
TO THE EDITOR: In their network meta-analysis (NMA),
Crit Care Med. 2011;39:386-91. [PMID: 21248514] doi:10.1097/CCM
Rochwerg and colleagues (1) concluded that albumin is superior to crystalloids and starches. However, their review did not include several studies that directly compare albumin with other fluids. Therefore, we did an updated meta-analysis based on a previous one (2). We excluded 6 studies by Dr. Joachim Boldt because of suspected lack of integrity and 3 studies that focused on the pediatric population. We also added 3 recently published studies (CRISTAL [Colloids Versus Crystalloids for the Resuscitation of the Critically Ill], EARSS [Early Albumin Resuscitation During Septic Shock], and ALBIOS [Albumin Italian Outcome Sepsis]). In total, we included 9 studies that compared albumin with crystalloids (odds ratio, 0.91 [95% CI, 0.77 to 1.06]), 7 studies that compared albumin with starches (odds ratio, 0.92 [CI, 0.48 to 1.76]), and 1 study that compared albumin with Gelofusine (B. Braun) (odds ratio, 1.00 [CI, 0.09 to 11.03]). After we excluded the SAFE (Saline Versus Albumin Fluid Evaluation) study, the pooled odds ratio was 0.99 (CI, 0.80 to 1.22), which also suggested that mortality did not differ between albumin and crystalloids. There was no heterogeneity between studies. In the ALBIOS study (3), we included only patients who received albumin within 6 hours of randomization. Our results suggest that albumin did not significantly affect the mortality rate compared with other fluids, which is inconsistent with Rochwerg and colleagues' conclusion (1). This finding is particularly important because the costeffectiveness of albumin mostly depends on its ability to decrease risk for death (4). Moreover, albumin can be 20 to 100 times more expensive than crystalloids, and the reported cost per case avoided based on the results of the EARSS study is $31 220 (4, 5). In addition, several problems about albumin remain unclear: Which concentration (4% to 5% vs. 20% to 25%) and what dose of albumin should be used, and when should physicians begin to administer albumin therapy? It would be better if Rochwerg and colleagues had described these issues in more detail. Publication bias also may be a factor in their review, because they did not include several studies in their meta-analysis. Given albumin's limited ability to decrease risk for death, its high cost, and several uncertainties, crystalloids should be the first choice for fluid resuscitation in patients with sepsis.
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Libing Jiang, MM Yuefeng Ma, MD, PhD Mao Zhang, MD, PhD Second Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou, China Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterest Forms.do?msNum=L14-0523.
3. Caironi P, Tognoni G, Masson S, Fumagalli R, Pesenti A, Romero M, et al; ALBIOS Study Investigators. Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med. 2014;370:1412-21. [PMID: 24635772] doi: 10.1056/NEJMoa1305727 4. Latour-Pe´rez J. New recommendations for the use of serum albumin in patients with severe sepsis and septic shock [Letter]. Crit Care Med. 2013;41: e289. [PMID: 24060790] doi:10.1097/CCM.0b013e31828ced28 5. Lyu PF, Murphy DJ. Economics of fluid therapy in critically ill patients. Curr Opin Crit Care. 2014;20:402-7. [PMID: 24979711] doi:10.1097/MCC .0000000000000117
IN RESPONSE: We thank Dr. Zhang and colleagues for their points about the administration of albumin for resuscitation in patients with sepsis. The methods of their meta-analysis differ from those of ours in several respects, and it is thus unsurprising that our results are discordant. We used an NMA framework that has the advantage of incorporating indirect evidence as opposed to only direct evidence as in a conventional meta-analysis. We excluded the ALBIOS (1) and EARSS (2) studies because albumin administration in these trials was independent of hemodynamic instability and the focus of our NMA was resuscitation fluid. We included the CRISTAL study (3) only in the pairwise meta-analysis of colloids versus crystalloids because patients were randomly assigned to receive any colloids or any crystalloids. Although the CRISTAL study presented results based on the specific fluid received, this factor was not a randomization characteristic; accordingly, we did not integrate these data in our NMA because of the potential for bias. Finally, we included the SAFE study (4), whereas Dr. Zhang and colleagues excluded it for unclear reasons. We agree that, for most patients with sepsis, the first choice of resuscitative fluid should be crystalloids. The results of our NMA suggest that a “balanced” crystalloid solution with a more physiologic chloride concentration may be preferred, but we believe that more research is needed to confirm or refute this finding (5). Although the CIs around the mortality estimate comparing albumin with any crystalloid (NMA odds ratio, 0.83 [95% credible interval, 0.65 to 1.04]) include the potential that albumin confers a mortality benefit, this factor must be balanced against important considerations of cost and transfusion risk. Our results show that albumin seems to be at worst similar to crystalloids with respect to mortality risk. When albumin is used for resuscitation, research is sparse to guide the choice of dose, concentration, or timing. Presently, we do not advocate that albumin be used as a first choice for resuscitation in sepsis. However, until further research becomes available suggesting otherwise, we believe that it is reasonable to include it as 1 potential resuscitative fluid. Meanwhile, in clinical practice, most patients will continue to receive a combination of fluids for resuscitation rather © 2015 American College of Physicians 319
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LETTERS than a single subtype, guided by physiologic variables and sometimes such factors as institutional policies, physician preferences, or fluids readily at hand. Bram Rochwerg, MD McMaster University Medical Centre Hamilton, Ontario, Canada Waleed Alhazzani, MD Roman Jaeschke, MD Deborah J. Cook, MD St. Joseph's Healthcare Hamilton, Ontario, Canada Disclosures: Disclosures can be viewed at www.acponline.org /authors/icmje/ConflictOfInterestForms.do?msNum=M14-0178. References 1. Caironi P, Tognoni G, Masson S, Fumagalli R, Pesenti A, Romero M, et al; ALBIOS Study Investigators. Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med. 2014;370:1412-21. [PMID: 24635772] doi: 10.1056/NEJMoa1305727 2. Charpentier J, Mira J-P. Efficacy and tolerance of hyperoncotic albumin administration in septic shock patients: the EARSS study. Intensive Care Med. 2011;37(Suppl 1):S115. 3. Annane D, Siami S, Jaber S, Martin C, Elatrous S, Decle`re AD, et al; CRISTAL Investigators. Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial. JAMA. 2013;310:1809-17. [PMID: 24108515] doi:10.1001 /jama.2013.280502 4. Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R; SAFE Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004;350:2247-56. [PMID: 15163774] 5. Rochwerg B, Wludarczyk A, Szczeklik W, Alhazzani W, Sindi A, Alshamsi F, et al; FISSH group. Fluid resuscitation in severe sepsis and septic shock: systematic description of fluids used in randomized trials. Pol Arch Med Wewn. 2013;123:603-8. [PMID: 24185099]
Rethinking the Use of Physicians as Hired Expert Lecturers TO THE EDITOR: Avorn's commentary (1) mentions Glaxo-
SmithKline's (GSK's) retreat from support of physician lecture programs. We find the drug company's actions lamentable, particularly at a time when the introduction of novel pharmaceuticals with complex mechanisms of action and clinicians' desire for education have never been greater. In 2014, the U.S. Food and Drug Administration (FDA) approved 41 new drugs, many of them completely novel. Commercially supported physician lectures answer an urgent need for high-quality information about new drugs from experienced peers. The content of these programs is rigorous and satisfies the FDA's stringent requirements for accuracy, objectivity, fair balance, and reliance on well-controlled studies. Commercial interests are fully disclosed, and layers of oversight—from corporate integrity agreements and adherence to the U.S. Department of Health and Human Services Office of Inspector General guidelines (2) and the Pharmaceutical Research and Manufacturers of America Code on Interactions with Healthcare Professionals (3)—protect prescribers and patients from unsupported claims that could lead to inappropriate use. 320 Annals of Internal Medicine • Vol. 162 No. 4 • 17 February 2015
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In contrast, non– commercially sponsored lecturers, including academicians and other key opinion leaders, typically are accountable only to themselves and their institutions. These speakers may lack legal compulsion to disclose conflicts of interest and be motivated by drug costs, politics, a desire for peer admiration, or fear of change. Little prevents them from advocating uses not proved to meet the FDA's standards of safety and efficacy. Absence of commercial sponsorship does not ensure freedom from bias, nor does commercial support necessarily compromise objectivity. Medical, legal, engineering, and accountancy journals, for example, have long enjoyed subsidy provided by their advertising pages while trusting their readership to discern information from promotion. In a recent independent survey of 500 clinicians, more than 90% responded that they found information provided by sponsored speakers to be timely, useful, and reliable; 94% agreed that these programs improved their care for patients (4). Clinicians also show that they value commercially sponsored speaker programs for the information provided, not “complimentary meals.” According to Manhattan Research, 71% of physicians participated in online medical conferences last year (5). High-quality medical education programs require substantial expertise, time, and other resources to produce. Further declines in commercial support for them would seriously compromise physician knowledge and, ultimately, patient care. We hope that other pharmaceutical manufacturers do not follow GSK's lead and that GSK rethinks this unfortunate decision. Marc B. Garnick, MD Harvard Medical School and Beth Israel Deaconess Medical Center Boston, Massachusetts Wendy Balter, MBA Phase Five Communications New York, New York Disclosures: Disclosures can be viewed at www.acponline.org /authors/icmje/ConflictOfInterestForms.do?msNum=L14-0570.
References 1. Avorn J. Rethinking the use of physicians as hired expert lecturers. Ann Intern Med. 2014;161:363-4. [PMID: 25178570] doi:10.7326/M14-0847 2. Office of Inspector General's compliance program guidance for pharmaceutical manufacturers. Fed Regist. 2003;68:23731-42. Accessed at https://oig .hhs.gov/authorities/docs/03/050503FRCPGPharmac.pdf on 3 September 2014. 3. Pharmaceutical Research and Manufacturers of America. Code on Interactions with Healthcare Professionals. Washington, DC: Pharmaceutical Research and Manufacturers of America; 2008. Accessed at www.phrma.org/sites /default/files/pdf/phrma_marketing_code_2008.pdf on 4 September 2014. 4. KRC Research. Survey of Physicians about Pharmaceutical and Biotech Research Company Activities and Information. (Commissioned by Pharmaceutical Research and Manufacturers of America.) Washington, DC: KRC Research; 2011.Accessedatwww.phrma.org/sites/default/files/pdf/krcsurveyofphysicians _1.pdf on 4 September 2014. 5. Manhattan Research. Trends and the Future: Physicians and Patients in a Connected World. New York: Manhattan Research; 2013. Accessed at www.annals.org
LETTERS ehealthcaresolutions.com/summit/presentations/mressi_2013.pptx on 5 Sep-
References
tember 2014.
1. Avorn J. Rethinking the use of physicians as hired expert lecturers. Ann Intern Med. 2014;161:363-4. [PMID: 25178570] doi:10.7326/M14-0847 2. Lea D, Spigset O, Slørdal L. Norwegian medical students' attitudes towards the pharmaceutical industry. Eur J Clin Pharmacol. 2010;66:727-33. [PMID: 20300742] doi:10.1007/s00228-010-0805-6 3. O’Brien MA, Rogers S, Jamtvedt G, Oxman AD, Odgaard-Jensen J, Kristoffersen DT, et al. Educational outreach visits: effects on professional practice and health care outcomes. Cochrane Database Syst Rev. 2007:CD000409. [PMID: 17943742] 4. Yousif MA, Eldalo AS, Abd Allah MA, Al-Sawat MA, Al-Wahaibi HM, Al-Osaimi AA, et al. Pharmacy education instruction: Preference and practices, Saudi students' perception. Saudi Pharm J. 2014;22:309-14. [PMID: 25161374] doi:10.1016/j.jsps.2013.06.005 5. Stojan JN, Schiller JH, Mullan P, Fitzgerald JT, Christner J, Ross PT, et al. Medical school handoff education improves postgraduate trainee performance and confidence. Med Teach. 2014:1-8. [PMID: 25155969]
TO THE EDITOR: GlaxoSmithKline is an internationally re-
nowned pharmaceutical agency, and we believe that their recent decision to discontinue hiring physicians as expert lecturers as described in Avorn's commentary (1) has significant consequences. The author presumes that physicians' desire to lecture is due to the monetary reward. However, a study of senior Norwegian medical students found that only 17.5% had a positive attitude toward the pharmaceutical industry, and most said that they would decline monetary gifts (2). This study shows that the new generation of physicians is less influenced by a drug company's monetary offers than previous generations. Therefore, GSK's plan to stop hiring physicians as expert lecturers could mean that future physicians who truly had a desire to educate could potentially miss out on opportunities to teach and share their knowledge. GlaxoSmithKline could combat this loss by assessing physicians' teaching content beforehand. Avorn mentions that “academic detailing” is an excellent alternative to educate physicians about evidence-based prescribing free of commercial influences (3). Implementing such methods opens new pathways for physicians to learn while being influenced not by drug companies but rather by the evidence behind drugs. However, evidence-based prescribing cannot replace the knowledge or skills taught by expert lecturers. One argument Avorn poses is that “physician performance of paid speaking engagement seems to be diminishing” (1). First, in the same way that fewer physicians are accepting paid speaking engagements, fewer teachers in medical and pharmacy schools are solely educators and more educators also work as practicing physicians. A study of pharmacy students in Saudi Arabia concluded that 53.7% preferred a direct type of lecturing and that their aid for revision was handouts made by the lecturers (4). Second, postgraduates who have had training and feedback from physicians in terms of their practical skills do better in Objective Structured Clinical Examinations (5). This finding shows that performance is not diminishing but that practicing physicians are used to being taught by colleagues and subsequently trust information provided by them. Because physicians will be the front-line prescribers, it is logical that they would educate their peers. It is a shame that GSK is no longer using such a good resource, because we believe that physicians provide pharmaceutical knowledge in a more clinically oriented way. Kaenat Mulla Adebusola Shonubi, iBSc Dev Katarey, BMBS, MSc St. George's University of London London, United Kingdom Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterest Forms.do?msNum=L14-0571. www.annals.org
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TO THE EDITOR: I read Avorn's commentary (1) with great
interest. As far I can remember, great ideas didn't come preprinted in journals or textbooks. They come from free minds speaking without restrictions about a subject or an issue while sipping a cup of coffee or sharing lunch or a drink. To suggest that respected, well-paid physicians would change their practicing behavior and put aside their patient care just for a meal is demeaning. It is not relevant who pays for a dinner and who sponsors it. What's more important is that it's an effort to get a few physicians to start talking about clinical care in the context of a new therapy that might help their patients. Thanks to the bureaucracy of a few, this opportunity is now lost. Abrar Khan, MD Banner Health Glendale, Arizona Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterest Forms.do?msNum=L14-0572.
Reference 1. Avorn J. Rethinking the use of physicians as hired expert lecturers. Ann Intern Med. 2014;161:363-4. [PMID: 25178570] doi:10.7326/M14-0847
IN RESPONSE: Dr. Garnick and Ms. Balter argue that we should be grateful that drug companies hire physicians to teach us about the many new drugs that are introduced annually. But the purpose of such talks, often arranged through a company's marketing department, is primarily to increase product sales rather than present a comprehensive view. It is unrealistic to expect these presentations to emphasize that a generic medication may be as effective as the sponsor's more expensive product or have a longer safety track record (1). Several major investigations and more than $15 billion in settlements have documented widespread violations of guidelines because companies promoted uses of their drugs that were poorly justified, dangerous, or both (2). The unpublished industry survey that Dr. Garnick and Ms. Balter cite found that 75% of physicians said that they receive information about prescribing choices through company-sponsored programs that do not offer continuing medical education credits and Annals of Internal Medicine • Vol. 162 No. 4 • 17 February 2015 321
LETTERS feature hired physician–speakers—not a statistic to be proud of (3). Of course, we academic physicians also have biases and conflicts, but claiming that the information provided by physicians who are not paid by the pharmaceutical industry is inherently less reliable than that provided by company spokespersons is simply implausible. A recent survey of 2336 medical students and residents found that those who relied more on company-sponsored information were significantly less likely to provide evidence-based answers to prescribing questions and significantly more likely to recommend brandname products than generic ones (4). Non–industrysupported sources of information are a better way to meet the profession's growing need to assimilate data on the comparative effectiveness of medications (5). Ms. Mulla and colleagues worry that a reduction in pharmaceutical payments to physicians will decrease physicians' involvement in teaching. Fortunately, clinicians' participation in educating our peers and students is a well-established tradition in medicine that will continue even if drug manufacturers don't pay us to do so. Dr. Khan is concerned that GSK's plan to withdraw funding for sponsored lectures will mean that physicians will no longer be able to meet to discuss new drugs that may benefit their patients. Of course we will; we'll just have to pay for our own food. As a nation, we have accepted the false economy that it is a bargain to accept “free” medical education from drugmakers about their products. Such bargains can only exacerbate our per capita drug spending, which is the highest in the world. With growing concern about providing safe, effective, and affordable drug regimens, now is a good time to rethink who should be defining our understanding of the medications that we prescribe. Jerry Avorn, MD Harvard Medical School and Brigham and Women's Hospital Boston, Massachusetts Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterest Forms.do?msNum=M14-0847. References 1. Avorn J. Healing the overwhelmed physician. The New York Times. 12 June 2013:A27. Accessed at www.nytimes.com/2013/06/12/opinion/healing-the -overwhelmed-physician.html?_r=0 on 12 January 2015. 2. List of largest pharmaceutical settlements. Wikipedia. 2014. Accessed at http://en.wikipedia.org/wiki/List_of_largest_pharmaceutical_settlements on 12 January 2015. 3. KRC Research. Survey of Physicians about Pharmaceutical and Biotech Research Company Activities and Information. (Commissioned by Pharmaceutical Research and Manufacturers of America.) Washington, DC: KRC Research; 2011:16. Accessed at www.phrma.org/sites/default/files/pdf/krcsurveyof physicians_1.pdf on 12 January 2015. 4. Austad KE, Avorn J, Franklin JM, Campbell EG, Kesselheim AS. Association of marketing interactions with medical trainees' knowledge about evidencebased prescribing: results from a national survey. JAMA Intern Med. 2014;174: 1283-90. [PMID: 24911123] doi:10.1001/jamainternmed.2014.2202 5. Fischer MA, Avorn J. Academic detailing can play a key role in assessing and implementing comparative effectiveness research findings. Health Aff (Millwood). 2012;31:2206-12. [PMID: 23048098] doi:10.1377/hlthaff.2012.0817 322 Annals of Internal Medicine • Vol. 162 No. 4 • 17 February 2015
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OBSERVATION Metabolic Acidosis in a Patient With Isopropyl Alcohol Intoxication: A Case Report Background: An elevated plasma osmolal gap is common in all forms of alcohol intoxication. Methyl alcohol and ethylene glycol are metabolized to compounds that produce metabolic acidosis. Isopropyl alcohol, however, is metabolized to acetone, which does not cause metabolic acidosis and cannot be metabolized to compounds that do (1). Therefore, the presence of metabolic acidosis is used to rule out isopropyl alcohol intoxication. This distinction is important because fomepizole is used to treat methyl alcohol and ethylene glycol intoxication but is contraindicated in isopropyl alcohol intoxication because it reduces the clearance of isopropyl alcohol and thus prolongs its effects (2). Objective: To describe a patient with isopropyl alcohol intoxication and metabolic acidosis. Case Report: A 45-year-old woman with a history of alcohol abuse came to the emergency department with confusion, agitation, and chest pain. She described drinking large amounts of alcohol during the previous 2 weeks but no alcohol during the past 2 days. An evaluation for the acute coronary syndrome was negative. She had a wide plasma osmolal gap (44 mmol/kg) and anion gap metabolic acidosis (15 mmol/L) with elevated serum -hydroxybutyric acid levels (3620 μmol/L), normal serum lactate levels, and negligible serum salicylate and ethyl alcohol levels. The urinary acetone level was elevated (at least 80 mg/dL, the highest level that our assay could measure). We diagnosed methyl alcohol or ethylene glycol intoxication, considering the history of alcohol abuse, wide osmolal gap, metabolic acidosis, and normal serum ethyl alcohol levels. We administered a loading dose of 15 mg/kg of fomepizole. Ten hours later—shortly before the next dose of fomepizole—the patient remained confused, which we interpreted as failure to respond. A screening test of the patient's blood for volatile chemicals found elevated levels of isopropyl alcohol (1.69 mmol/L) and acetone (38 mmol/L), with negligible levels of ethyl alcohol, methyl alcohol, and ethylene glycol. On further questioning, the patient described drinking rubbing alcohol and eating little food for several days. We discontinued fomepizole therapy and continued supportive therapy. She improved over 24 hours, developed alcohol withdrawal symptoms that responded to treatment, and returned to baseline mental and functional status after 3 days. Discussion: This patient had isopropyl alcohol intoxication. We believe that she also had alcoholic ketoacidosis, which occurs when persons who chronically abuse ethyl alcohol suddenly decrease their calorie intake (3). The unexpected metabolic acidosis prevented us from initially recognizing the possibility of isopropyl alcohol intoxication, although in retrospect the high levels of urinary acetone might have alerted us to this condition. Our experience shows that isopropyl alcohol intoxication combined with alcoholic ketoacidosis can be misdiagnosed as ethyl or methyl alcohol or ethylene glycol intoxication. This possibility is not widely appreciated in the medical literature; for example, it is not mentioned in UpToDate, a frequently www.annals.org
LETTERS used electronic textbook of medicine (4). It is important for clinicians to note that the laboratory findings of alcoholics who drink isopropyl alcohol and have reduced caloric intake are similar to those of alcoholics who consume ethyl or methyl alcohol or ethylene glycol. Therefore, we advise clinicians to consider isopropyl alcohol intoxication in patients who have a high osmolal gap with anion gap metabolic acidosis. Xiaomei Meng, MD, PhD Suman Paul, MBBS, PhD University of Toledo Medical Center Toledo, Ohio Douglas J. Federman, MD University of Toledo College of Medicine Toledo, Ohio Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterest Forms.do?msNum=L14-0336.
References 1. Slaughter RJ, Mason RW, Beasley DM, Vale JA, Schep LJ. Isopropanol poisoning. Clin Toxicol (Phila). 2014;52:470-8. [PMID: 24815348] doi:10.3109 /15563650.2014.914527 2. Pappas AA, Ackerman BH, Olsen KM, Taylor EH. Isopropanol ingestion: a report of six episodes with isopropanol and acetone serum concentration time data. J Toxicol Clin Toxicol. 1991;29:11-21. [PMID: 2005658] 3. Mihai B, Lacatusu C, Graur M. [Alcoholic ketoacidosis]. Rev Med Chir Soc Med Nat Iasi. 2008;112:321-6. [PMID: 19294998] 4. Sivilotti MLA. Isopropyl alcohol poisoning. UpToDate. 2013. Accessed at www.uptodate.com/contents/isopropyl-alcohol-poisoning?source=search _result&search=isopropyl&selectedTitle=1~31 on 7 August 2014.
CORRECTIONS Correction: Screening for Asymptomatic Carotid Artery Stenosis In a recent guideline (1), the first sentence under “Screening Tests” should read as follows: “Although screening with ultrasonography has few direct harms, all screening strategies, including those with or without confirmatory tests (that is, digital subtraction or magnetic resonance angiography), have imperfect sensitivity and specificity [italics added] and could lead to unnecessary surgery. . . . ” This has been corrected in the online version. Reference 1. LeFevre ML; U.S. Preventive Services Task Force. Screening for asymptomatic carotid artery stenosis: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;161:356-62.
Correction: In the Clinic: Hypertension A recent In the Clinic (1) contained errors. In the Guidelines for Blood Pressure Goalssidebar on page ITC6, the first recommendation is JNC 8, reference 4. In the third row of boxes in the Figure on ITC10, the first box should have a greater than/equal to sign and the second box should have a less than sign. The arrow to the next step is missing from the blood pressure goal boxes to the following step. The corrected figure appears below. On page ITC11, amlodipine is a dihydropyridine calciumchannel blocker as opposed to a nonhydropine calciumchannel blocker, as implied by the heading. This has been corrected in the online version. Reference 1. Weir M. In the Clinic: hypertension. Ann Intern Med. 2014;161:ITC1-16.
Figure. Algorithm for treatment of hypertension.
From reference 4. ACE = angiotensin-converting enzyme; ARB = angiotensin-receptor blocker; CCB = calcium-channel blocker; CKD = chronic kidney disease; DBP = diastolic blood pressure; SBP = systolic blood pressure. www.annals.org
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Annals of Internal Medicine • Vol. 162 No. 4 • 17 February 2015 323
Annals of Internal Medicine COMMENTS AND RESPONSES
References 1. Rochwerg B, Alhazzani W, Sindi A, Heels-Ansdell D, Thabane L, FoxRobichaud A, et al; Fluids in Sepsis and Septic Shock Group. Fluid resuscitation in sepsis: a systematic review and network meta-analysis. Ann Intern Med.
Albumin Administration in Patients With Sepsis
2014;161:347-55. [PMID: 25047428] doi:10.7326/M14-0178 2. Delaney AP, Dan A, McCaffrey J, Finfer S. The role of albumin as a resuscitation fluid for patients with sepsis: a systematic review and meta-analysis.
TO THE EDITOR: In their network meta-analysis (NMA),
Crit Care Med. 2011;39:386-91. [PMID: 21248514] doi:10.1097/CCM
Rochwerg and colleagues (1) concluded that albumin is superior to crystalloids and starches. However, their review did not include several studies that directly compare albumin with other fluids. Therefore, we did an updated meta-analysis based on a previous one (2). We excluded 6 studies by Dr. Joachim Boldt because of suspected lack of integrity and 3 studies that focused on the pediatric population. We also added 3 recently published studies (CRISTAL [Colloids Versus Crystalloids for the Resuscitation of the Critically Ill], EARSS [Early Albumin Resuscitation During Septic Shock], and ALBIOS [Albumin Italian Outcome Sepsis]). In total, we included 9 studies that compared albumin with crystalloids (odds ratio, 0.91 [95% CI, 0.77 to 1.06]), 7 studies that compared albumin with starches (odds ratio, 0.92 [CI, 0.48 to 1.76]), and 1 study that compared albumin with Gelofusine (B. Braun) (odds ratio, 1.00 [CI, 0.09 to 11.03]). After we excluded the SAFE (Saline Versus Albumin Fluid Evaluation) study, the pooled odds ratio was 0.99 (CI, 0.80 to 1.22), which also suggested that mortality did not differ between albumin and crystalloids. There was no heterogeneity between studies. In the ALBIOS study (3), we included only patients who received albumin within 6 hours of randomization. Our results suggest that albumin did not significantly affect the mortality rate compared with other fluids, which is inconsistent with Rochwerg and colleagues' conclusion (1). This finding is particularly important because the costeffectiveness of albumin mostly depends on its ability to decrease risk for death (4). Moreover, albumin can be 20 to 100 times more expensive than crystalloids, and the reported cost per case avoided based on the results of the EARSS study is $31 220 (4, 5). In addition, several problems about albumin remain unclear: Which concentration (4% to 5% vs. 20% to 25%) and what dose of albumin should be used, and when should physicians begin to administer albumin therapy? It would be better if Rochwerg and colleagues had described these issues in more detail. Publication bias also may be a factor in their review, because they did not include several studies in their meta-analysis. Given albumin's limited ability to decrease risk for death, its high cost, and several uncertainties, crystalloids should be the first choice for fluid resuscitation in patients with sepsis.
.0b013e3181ffe217
Libing Jiang, MM Yuefeng Ma, MD, PhD Mao Zhang, MD, PhD Second Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou, China Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterest Forms.do?msNum=L14-0523.
3. Caironi P, Tognoni G, Masson S, Fumagalli R, Pesenti A, Romero M, et al; ALBIOS Study Investigators. Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med. 2014;370:1412-21. [PMID: 24635772] doi: 10.1056/NEJMoa1305727 4. Latour-Pe´rez J. New recommendations for the use of serum albumin in patients with severe sepsis and septic shock [Letter]. Crit Care Med. 2013;41: e289. [PMID: 24060790] doi:10.1097/CCM.0b013e31828ced28 5. Lyu PF, Murphy DJ. Economics of fluid therapy in critically ill patients. Curr Opin Crit Care. 2014;20:402-7. [PMID: 24979711] doi:10.1097/MCC .0000000000000117
IN RESPONSE: We thank Dr. Zhang and colleagues for their points about the administration of albumin for resuscitation in patients with sepsis. The methods of their meta-analysis differ from those of ours in several respects, and it is thus unsurprising that our results are discordant. We used an NMA framework that has the advantage of incorporating indirect evidence as opposed to only direct evidence as in a conventional meta-analysis. We excluded the ALBIOS (1) and EARSS (2) studies because albumin administration in these trials was independent of hemodynamic instability and the focus of our NMA was resuscitation fluid. We included the CRISTAL study (3) only in the pairwise meta-analysis of colloids versus crystalloids because patients were randomly assigned to receive any colloids or any crystalloids. Although the CRISTAL study presented results based on the specific fluid received, this factor was not a randomization characteristic; accordingly, we did not integrate these data in our NMA because of the potential for bias. Finally, we included the SAFE study (4), whereas Dr. Zhang and colleagues excluded it for unclear reasons. We agree that, for most patients with sepsis, the first choice of resuscitative fluid should be crystalloids. The results of our NMA suggest that a “balanced” crystalloid solution with a more physiologic chloride concentration may be preferred, but we believe that more research is needed to confirm or refute this finding (5). Although the CIs around the mortality estimate comparing albumin with any crystalloid (NMA odds ratio, 0.83 [95% credible interval, 0.65 to 1.04]) include the potential that albumin confers a mortality benefit, this factor must be balanced against important considerations of cost and transfusion risk. Our results show that albumin seems to be at worst similar to crystalloids with respect to mortality risk. When albumin is used for resuscitation, research is sparse to guide the choice of dose, concentration, or timing. Presently, we do not advocate that albumin be used as a first choice for resuscitation in sepsis. However, until further research becomes available suggesting otherwise, we believe that it is reasonable to include it as 1 potential resuscitative fluid. Meanwhile, in clinical practice, most patients will continue to receive a combination of fluids for resuscitation rather © 2015 American College of Physicians 319
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LETTERS than a single subtype, guided by physiologic variables and sometimes such factors as institutional policies, physician preferences, or fluids readily at hand. Bram Rochwerg, MD McMaster University Medical Centre Hamilton, Ontario, Canada Waleed Alhazzani, MD Roman Jaeschke, MD Deborah J. Cook, MD St. Joseph's Healthcare Hamilton, Ontario, Canada Disclosures: Disclosures can be viewed at www.acponline.org /authors/icmje/ConflictOfInterestForms.do?msNum=M14-0178. References 1. Caironi P, Tognoni G, Masson S, Fumagalli R, Pesenti A, Romero M, et al; ALBIOS Study Investigators. Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med. 2014;370:1412-21. [PMID: 24635772] doi: 10.1056/NEJMoa1305727 2. Charpentier J, Mira J-P. Efficacy and tolerance of hyperoncotic albumin administration in septic shock patients: the EARSS study. Intensive Care Med. 2011;37(Suppl 1):S115. 3. Annane D, Siami S, Jaber S, Martin C, Elatrous S, Decle`re AD, et al; CRISTAL Investigators. Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial. JAMA. 2013;310:1809-17. [PMID: 24108515] doi:10.1001 /jama.2013.280502 4. Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R; SAFE Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004;350:2247-56. [PMID: 15163774] 5. Rochwerg B, Wludarczyk A, Szczeklik W, Alhazzani W, Sindi A, Alshamsi F, et al; FISSH group. Fluid resuscitation in severe sepsis and septic shock: systematic description of fluids used in randomized trials. Pol Arch Med Wewn. 2013;123:603-8. [PMID: 24185099]
Rethinking the Use of Physicians as Hired Expert Lecturers TO THE EDITOR: Avorn's commentary (1) mentions Glaxo-
SmithKline's (GSK's) retreat from support of physician lecture programs. We find the drug company's actions lamentable, particularly at a time when the introduction of novel pharmaceuticals with complex mechanisms of action and clinicians' desire for education have never been greater. In 2014, the U.S. Food and Drug Administration (FDA) approved 41 new drugs, many of them completely novel. Commercially supported physician lectures answer an urgent need for high-quality information about new drugs from experienced peers. The content of these programs is rigorous and satisfies the FDA's stringent requirements for accuracy, objectivity, fair balance, and reliance on well-controlled studies. Commercial interests are fully disclosed, and layers of oversight—from corporate integrity agreements and adherence to the U.S. Department of Health and Human Services Office of Inspector General guidelines (2) and the Pharmaceutical Research and Manufacturers of America Code on Interactions with Healthcare Professionals (3)—protect prescribers and patients from unsupported claims that could lead to inappropriate use. 320 Annals of Internal Medicine • Vol. 162 No. 4 • 17 February 2015
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In contrast, non– commercially sponsored lecturers, including academicians and other key opinion leaders, typically are accountable only to themselves and their institutions. These speakers may lack legal compulsion to disclose conflicts of interest and be motivated by drug costs, politics, a desire for peer admiration, or fear of change. Little prevents them from advocating uses not proved to meet the FDA's standards of safety and efficacy. Absence of commercial sponsorship does not ensure freedom from bias, nor does commercial support necessarily compromise objectivity. Medical, legal, engineering, and accountancy journals, for example, have long enjoyed subsidy provided by their advertising pages while trusting their readership to discern information from promotion. In a recent independent survey of 500 clinicians, more than 90% responded that they found information provided by sponsored speakers to be timely, useful, and reliable; 94% agreed that these programs improved their care for patients (4). Clinicians also show that they value commercially sponsored speaker programs for the information provided, not “complimentary meals.” According to Manhattan Research, 71% of physicians participated in online medical conferences last year (5). High-quality medical education programs require substantial expertise, time, and other resources to produce. Further declines in commercial support for them would seriously compromise physician knowledge and, ultimately, patient care. We hope that other pharmaceutical manufacturers do not follow GSK's lead and that GSK rethinks this unfortunate decision. Marc B. Garnick, MD Harvard Medical School and Beth Israel Deaconess Medical Center Boston, Massachusetts Wendy Balter, MBA Phase Five Communications New York, New York Disclosures: Disclosures can be viewed at www.acponline.org /authors/icmje/ConflictOfInterestForms.do?msNum=L14-0570.
References 1. Avorn J. Rethinking the use of physicians as hired expert lecturers. Ann Intern Med. 2014;161:363-4. [PMID: 25178570] doi:10.7326/M14-0847 2. Office of Inspector General's compliance program guidance for pharmaceutical manufacturers. Fed Regist. 2003;68:23731-42. Accessed at https://oig .hhs.gov/authorities/docs/03/050503FRCPGPharmac.pdf on 3 September 2014. 3. Pharmaceutical Research and Manufacturers of America. Code on Interactions with Healthcare Professionals. Washington, DC: Pharmaceutical Research and Manufacturers of America; 2008. Accessed at www.phrma.org/sites /default/files/pdf/phrma_marketing_code_2008.pdf on 4 September 2014. 4. KRC Research. Survey of Physicians about Pharmaceutical and Biotech Research Company Activities and Information. (Commissioned by Pharmaceutical Research and Manufacturers of America.) Washington, DC: KRC Research; 2011.Accessedatwww.phrma.org/sites/default/files/pdf/krcsurveyofphysicians _1.pdf on 4 September 2014. 5. Manhattan Research. Trends and the Future: Physicians and Patients in a Connected World. New York: Manhattan Research; 2013. Accessed at www.annals.org
LETTERS ehealthcaresolutions.com/summit/presentations/mressi_2013.pptx on 5 Sep-
References
tember 2014.
1. Avorn J. Rethinking the use of physicians as hired expert lecturers. Ann Intern Med. 2014;161:363-4. [PMID: 25178570] doi:10.7326/M14-0847 2. Lea D, Spigset O, Slørdal L. Norwegian medical students' attitudes towards the pharmaceutical industry. Eur J Clin Pharmacol. 2010;66:727-33. [PMID: 20300742] doi:10.1007/s00228-010-0805-6 3. O’Brien MA, Rogers S, Jamtvedt G, Oxman AD, Odgaard-Jensen J, Kristoffersen DT, et al. Educational outreach visits: effects on professional practice and health care outcomes. Cochrane Database Syst Rev. 2007:CD000409. [PMID: 17943742] 4. Yousif MA, Eldalo AS, Abd Allah MA, Al-Sawat MA, Al-Wahaibi HM, Al-Osaimi AA, et al. Pharmacy education instruction: Preference and practices, Saudi students' perception. Saudi Pharm J. 2014;22:309-14. [PMID: 25161374] doi:10.1016/j.jsps.2013.06.005 5. Stojan JN, Schiller JH, Mullan P, Fitzgerald JT, Christner J, Ross PT, et al. Medical school handoff education improves postgraduate trainee performance and confidence. Med Teach. 2014:1-8. [PMID: 25155969]
TO THE EDITOR: GlaxoSmithKline is an internationally re-
nowned pharmaceutical agency, and we believe that their recent decision to discontinue hiring physicians as expert lecturers as described in Avorn's commentary (1) has significant consequences. The author presumes that physicians' desire to lecture is due to the monetary reward. However, a study of senior Norwegian medical students found that only 17.5% had a positive attitude toward the pharmaceutical industry, and most said that they would decline monetary gifts (2). This study shows that the new generation of physicians is less influenced by a drug company's monetary offers than previous generations. Therefore, GSK's plan to stop hiring physicians as expert lecturers could mean that future physicians who truly had a desire to educate could potentially miss out on opportunities to teach and share their knowledge. GlaxoSmithKline could combat this loss by assessing physicians' teaching content beforehand. Avorn mentions that “academic detailing” is an excellent alternative to educate physicians about evidence-based prescribing free of commercial influences (3). Implementing such methods opens new pathways for physicians to learn while being influenced not by drug companies but rather by the evidence behind drugs. However, evidence-based prescribing cannot replace the knowledge or skills taught by expert lecturers. One argument Avorn poses is that “physician performance of paid speaking engagement seems to be diminishing” (1). First, in the same way that fewer physicians are accepting paid speaking engagements, fewer teachers in medical and pharmacy schools are solely educators and more educators also work as practicing physicians. A study of pharmacy students in Saudi Arabia concluded that 53.7% preferred a direct type of lecturing and that their aid for revision was handouts made by the lecturers (4). Second, postgraduates who have had training and feedback from physicians in terms of their practical skills do better in Objective Structured Clinical Examinations (5). This finding shows that performance is not diminishing but that practicing physicians are used to being taught by colleagues and subsequently trust information provided by them. Because physicians will be the front-line prescribers, it is logical that they would educate their peers. It is a shame that GSK is no longer using such a good resource, because we believe that physicians provide pharmaceutical knowledge in a more clinically oriented way. Kaenat Mulla Adebusola Shonubi, iBSc Dev Katarey, BMBS, MSc St. George's University of London London, United Kingdom Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterest Forms.do?msNum=L14-0571. www.annals.org
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TO THE EDITOR: I read Avorn's commentary (1) with great
interest. As far I can remember, great ideas didn't come preprinted in journals or textbooks. They come from free minds speaking without restrictions about a subject or an issue while sipping a cup of coffee or sharing lunch or a drink. To suggest that respected, well-paid physicians would change their practicing behavior and put aside their patient care just for a meal is demeaning. It is not relevant who pays for a dinner and who sponsors it. What's more important is that it's an effort to get a few physicians to start talking about clinical care in the context of a new therapy that might help their patients. Thanks to the bureaucracy of a few, this opportunity is now lost. Abrar Khan, MD Banner Health Glendale, Arizona Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterest Forms.do?msNum=L14-0572.
Reference 1. Avorn J. Rethinking the use of physicians as hired expert lecturers. Ann Intern Med. 2014;161:363-4. [PMID: 25178570] doi:10.7326/M14-0847
IN RESPONSE: Dr. Garnick and Ms. Balter argue that we should be grateful that drug companies hire physicians to teach us about the many new drugs that are introduced annually. But the purpose of such talks, often arranged through a company's marketing department, is primarily to increase product sales rather than present a comprehensive view. It is unrealistic to expect these presentations to emphasize that a generic medication may be as effective as the sponsor's more expensive product or have a longer safety track record (1). Several major investigations and more than $15 billion in settlements have documented widespread violations of guidelines because companies promoted uses of their drugs that were poorly justified, dangerous, or both (2). The unpublished industry survey that Dr. Garnick and Ms. Balter cite found that 75% of physicians said that they receive information about prescribing choices through company-sponsored programs that do not offer continuing medical education credits and Annals of Internal Medicine • Vol. 162 No. 4 • 17 February 2015 321
LETTERS feature hired physician–speakers—not a statistic to be proud of (3). Of course, we academic physicians also have biases and conflicts, but claiming that the information provided by physicians who are not paid by the pharmaceutical industry is inherently less reliable than that provided by company spokespersons is simply implausible. A recent survey of 2336 medical students and residents found that those who relied more on company-sponsored information were significantly less likely to provide evidence-based answers to prescribing questions and significantly more likely to recommend brandname products than generic ones (4). Non–industrysupported sources of information are a better way to meet the profession's growing need to assimilate data on the comparative effectiveness of medications (5). Ms. Mulla and colleagues worry that a reduction in pharmaceutical payments to physicians will decrease physicians' involvement in teaching. Fortunately, clinicians' participation in educating our peers and students is a well-established tradition in medicine that will continue even if drug manufacturers don't pay us to do so. Dr. Khan is concerned that GSK's plan to withdraw funding for sponsored lectures will mean that physicians will no longer be able to meet to discuss new drugs that may benefit their patients. Of course we will; we'll just have to pay for our own food. As a nation, we have accepted the false economy that it is a bargain to accept “free” medical education from drugmakers about their products. Such bargains can only exacerbate our per capita drug spending, which is the highest in the world. With growing concern about providing safe, effective, and affordable drug regimens, now is a good time to rethink who should be defining our understanding of the medications that we prescribe. Jerry Avorn, MD Harvard Medical School and Brigham and Women's Hospital Boston, Massachusetts Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterest Forms.do?msNum=M14-0847. References 1. Avorn J. Healing the overwhelmed physician. The New York Times. 12 June 2013:A27. Accessed at www.nytimes.com/2013/06/12/opinion/healing-the -overwhelmed-physician.html?_r=0 on 12 January 2015. 2. List of largest pharmaceutical settlements. Wikipedia. 2014. Accessed at http://en.wikipedia.org/wiki/List_of_largest_pharmaceutical_settlements on 12 January 2015. 3. KRC Research. Survey of Physicians about Pharmaceutical and Biotech Research Company Activities and Information. (Commissioned by Pharmaceutical Research and Manufacturers of America.) Washington, DC: KRC Research; 2011:16. Accessed at www.phrma.org/sites/default/files/pdf/krcsurveyof physicians_1.pdf on 12 January 2015. 4. Austad KE, Avorn J, Franklin JM, Campbell EG, Kesselheim AS. Association of marketing interactions with medical trainees' knowledge about evidencebased prescribing: results from a national survey. JAMA Intern Med. 2014;174: 1283-90. [PMID: 24911123] doi:10.1001/jamainternmed.2014.2202 5. Fischer MA, Avorn J. Academic detailing can play a key role in assessing and implementing comparative effectiveness research findings. Health Aff (Millwood). 2012;31:2206-12. [PMID: 23048098] doi:10.1377/hlthaff.2012.0817 322 Annals of Internal Medicine • Vol. 162 No. 4 • 17 February 2015
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OBSERVATION Metabolic Acidosis in a Patient With Isopropyl Alcohol Intoxication: A Case Report Background: An elevated plasma osmolal gap is common in all forms of alcohol intoxication. Methyl alcohol and ethylene glycol are metabolized to compounds that produce metabolic acidosis. Isopropyl alcohol, however, is metabolized to acetone, which does not cause metabolic acidosis and cannot be metabolized to compounds that do (1). Therefore, the presence of metabolic acidosis is used to rule out isopropyl alcohol intoxication. This distinction is important because fomepizole is used to treat methyl alcohol and ethylene glycol intoxication but is contraindicated in isopropyl alcohol intoxication because it reduces the clearance of isopropyl alcohol and thus prolongs its effects (2). Objective: To describe a patient with isopropyl alcohol intoxication and metabolic acidosis. Case Report: A 45-year-old woman with a history of alcohol abuse came to the emergency department with confusion, agitation, and chest pain. She described drinking large amounts of alcohol during the previous 2 weeks but no alcohol during the past 2 days. An evaluation for the acute coronary syndrome was negative. She had a wide plasma osmolal gap (44 mmol/kg) and anion gap metabolic acidosis (15 mmol/L) with elevated serum -hydroxybutyric acid levels (3620 μmol/L), normal serum lactate levels, and negligible serum salicylate and ethyl alcohol levels. The urinary acetone level was elevated (at least 80 mg/dL, the highest level that our assay could measure). We diagnosed methyl alcohol or ethylene glycol intoxication, considering the history of alcohol abuse, wide osmolal gap, metabolic acidosis, and normal serum ethyl alcohol levels. We administered a loading dose of 15 mg/kg of fomepizole. Ten hours later—shortly before the next dose of fomepizole—the patient remained confused, which we interpreted as failure to respond. A screening test of the patient's blood for volatile chemicals found elevated levels of isopropyl alcohol (1.69 mmol/L) and acetone (38 mmol/L), with negligible levels of ethyl alcohol, methyl alcohol, and ethylene glycol. On further questioning, the patient described drinking rubbing alcohol and eating little food for several days. We discontinued fomepizole therapy and continued supportive therapy. She improved over 24 hours, developed alcohol withdrawal symptoms that responded to treatment, and returned to baseline mental and functional status after 3 days. Discussion: This patient had isopropyl alcohol intoxication. We believe that she also had alcoholic ketoacidosis, which occurs when persons who chronically abuse ethyl alcohol suddenly decrease their calorie intake (3). The unexpected metabolic acidosis prevented us from initially recognizing the possibility of isopropyl alcohol intoxication, although in retrospect the high levels of urinary acetone might have alerted us to this condition. Our experience shows that isopropyl alcohol intoxication combined with alcoholic ketoacidosis can be misdiagnosed as ethyl or methyl alcohol or ethylene glycol intoxication. This possibility is not widely appreciated in the medical literature; for example, it is not mentioned in UpToDate, a frequently www.annals.org
LETTERS used electronic textbook of medicine (4). It is important for clinicians to note that the laboratory findings of alcoholics who drink isopropyl alcohol and have reduced caloric intake are similar to those of alcoholics who consume ethyl or methyl alcohol or ethylene glycol. Therefore, we advise clinicians to consider isopropyl alcohol intoxication in patients who have a high osmolal gap with anion gap metabolic acidosis. Xiaomei Meng, MD, PhD Suman Paul, MBBS, PhD University of Toledo Medical Center Toledo, Ohio Douglas J. Federman, MD University of Toledo College of Medicine Toledo, Ohio Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterest Forms.do?msNum=L14-0336.
References 1. Slaughter RJ, Mason RW, Beasley DM, Vale JA, Schep LJ. Isopropanol poisoning. Clin Toxicol (Phila). 2014;52:470-8. [PMID: 24815348] doi:10.3109 /15563650.2014.914527 2. Pappas AA, Ackerman BH, Olsen KM, Taylor EH. Isopropanol ingestion: a report of six episodes with isopropanol and acetone serum concentration time data. J Toxicol Clin Toxicol. 1991;29:11-21. [PMID: 2005658] 3. Mihai B, Lacatusu C, Graur M. [Alcoholic ketoacidosis]. Rev Med Chir Soc Med Nat Iasi. 2008;112:321-6. [PMID: 19294998] 4. Sivilotti MLA. Isopropyl alcohol poisoning. UpToDate. 2013. Accessed at www.uptodate.com/contents/isopropyl-alcohol-poisoning?source=search _result&search=isopropyl&selectedTitle=1~31 on 7 August 2014.
CORRECTIONS Correction: Screening for Asymptomatic Carotid Artery Stenosis In a recent guideline (1), the first sentence under “Screening Tests” should read as follows: “Although screening with ultrasonography has few direct harms, all screening strategies, including those with or without confirmatory tests (that is, digital subtraction or magnetic resonance angiography), have imperfect sensitivity and specificity [italics added] and could lead to unnecessary surgery. . . . ” This has been corrected in the online version. Reference 1. LeFevre ML; U.S. Preventive Services Task Force. Screening for asymptomatic carotid artery stenosis: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;161:356-62.
Correction: In the Clinic: Hypertension A recent In the Clinic (1) contained errors. In the Guidelines for Blood Pressure Goalssidebar on page ITC6, the first recommendation is JNC 8, reference 4. In the third row of boxes in the Figure on ITC10, the first box should have a greater than/equal to sign and the second box should have a less than sign. The arrow to the next step is missing from the blood pressure goal boxes to the following step. The corrected figure appears below. On page ITC11, amlodipine is a dihydropyridine calciumchannel blocker as opposed to a nonhydropine calciumchannel blocker, as implied by the heading. This has been corrected in the online version. Reference 1. Weir M. In the Clinic: hypertension. Ann Intern Med. 2014;161:ITC1-16.
Figure. Algorithm for treatment of hypertension.
From reference 4. ACE = angiotensin-converting enzyme; ARB = angiotensin-receptor blocker; CCB = calcium-channel blocker; CKD = chronic kidney disease; DBP = diastolic blood pressure; SBP = systolic blood pressure. www.annals.org
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