Letters COMMENTS
AND
Annals of Internal Medicine RESPONSES
Disclosures: Authors have disclosed no conflicts of interest. Forms can
be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms .do?msNum⫽L14-0174.
Aggregate Cost of Mammography Screening in the United States TO THE EDITOR: O’Donoghue and colleagues (1) have conserva-
tively estimated the aggregate cost of screening mammography in the United States under several scenarios. Screening advocates will argue that the number of lives extended under an aggressive annual screening scenario differs from that under the U.S. Preventive Services Task Force (USPSTF) guidelines. Although the authors cite a costeffectiveness ratio of annual screening compared with biennial screening of more than $340 000 per quality-adjusted life-year, the real ratio—including indirect costs and overdiagnosis—is probably double or triple that estimate (2). Furthermore, Hubbard and associates (3) have shown that annual screening in the United States has not reduced the proportion of cases of advanced cancer compared with biennial screening. Bleyer and Welch (4) have shown that the incidence of advanced breast cancer in the United States has only marginally decreased since screening mammography was introduced, with probably one half of screen-detected cases classified as overdiagnosis of pseudodisease (4). Screening cannot be beneficial (a reduction in mortality or mastectomy rates) if the incidence of advanced cancer does not decrease. Instead of promoting screening participation by claiming that the status quo “[falls] short of national goals,” the authors should acknowledge that the $8 billion consumed annually by screening mammography might be better spent on something else—that is, the opportunity cost of the resources. If physicians believe in promoting informed choice (insight) about cancer screening given the substantial personal harm from overdiagnosis of healthy women and false-positive recalls and biopsy results, then targeted participation rates (uptake) become irrelevant. As an alternative to a participation rate of 85%, the authors should model lower uptake to account for the current lack of insight about the tradeoff of harms to benefit and the uncertainty of the magnitude of these harms among women who have screening mammography. Screening advocates, including the American Cancer Society and some professional groups who benefit from screening (such as breast imaging radiologists, oncologists, and breast surgeons), will probably continue to support the status quo or an aggressive annual screening schedule instead of the USPSTF recommendations (5). This marketing of mammography no doubt increases screening participation and makes sense from a business perspective. The authors conservatively estimate that the breast imaging community receives $4.4 billion in additional revenue from the status quo each year. One person’s cost is another person’s income. The authors have quantified the financial conflict of interest among those most stridently defending aggressive annual screening mammography: an extra $2.3 billion in revenue beyond the status quo. Financial considerations best explain the organized resistance to the implementation of the reasonable USPSTF recommendations. John D. Keen, MD, MBA John H. Stroger, Jr. Hospital of Cook County Chicago, Illinois
References 1. O’Donoghue C, Eklund M, Ozanne EM, Esserman LJ. Aggregate cost of mammography screening in the United States: comparison of current practice and advocated guidelines. Ann Intern Med. 2014;160:145-53. [PMID: 24658691] doi: 10.7326/M13-1217 2. Keen JD. Analysis of health benefits and cost-effectiveness of mammography for breast cancer [Letter]. Ann Intern Med. 2011;155:566. [PMID: 22007057] doi: 10.7326/0003-4819-155-8-201110180-00028 3. Hubbard RA, Kerlikowske K, Flowers CI, Yankaskas BC, Zhu W, Miglioretti DL. Cumulative probability of false-positive recall or biopsy recommendation after 10 years of screening mammography: a cohort study. Ann Intern Med. 2011;155:481-92. [PMID: 22007042] doi:10.7326/0003-4819-155-8-201110180-00004 4. Bleyer A, Welch HG. Effect of three decades of screening mammography on breastcancer incidence. N Engl J Med. 2012;367:1998-2005. [PMID: 23171096] doi: 10.1056/NEJMoa1206809 5. Keen JD. The ACR/SBI breast cancer screening guidelines are wrong. Medscape Radiology. 2 March 2012. Accessed at www.medscape.com/viewarticle/759429 on 6 February 2014.
TO THE EDITOR: O’Donoghue and colleagues (1) compare the monetary costs to insurers of several mammography screening strategies. They conclude that the added cost of more aggressive screening is not justified because they imply that clinical outcomes with these strategies are similar. However, the outcome differences are substantial, which meaningfully affects the cost analysis. The results of the Cancer Intervention and Surveillance Modeling Network (CISNET) models, which the authors reference, show large outcome differences for life-years gained and mortality reduction with the annual mammography screening strategy (women aged 40 to 84 years) compared with the biennial strategy (women aged 50 to 74 years) (2, 3). Data from these models show that life-years gained increase by 72% with the annual strategy (189 per 1000 women) compared with the biennial strategy (110 per 1000 women). Mortality reduction nearly doubles from 23% to 40% (2). Life-years gained for women aged 40 to 49 years increase by 42% with annual screening compared with biennial screening. The CISNET models for digital mammography show that, among women aged 40 to 49 years, life-years gained increase from 36 per 1000 women with biennial screening to 51 per 1000 women with annual screening (3). Finally, the life-years gained per decade with annual screening of women in their 40s (51 per 1000 women) exceed those with biennial screening of women aged 50 to 74 years (44 per 1000 women) (3). Screening involves costs and harms. So does not screening, and this study does not estimate these factors. The financial cost of medical treatment for a woman with metastatic breast cancer is $250 000 (4). The financial cost due to lost productivity secondary to death of a woman in her 40s is $1.4 million (5). Hence, the financial cost of 1 excessive death from breast cancer due to not screening is large. The aggregate costs of these 2 factors, when attributed to excessive deaths from not screening based on results from the CISNET models, approach or exceed the authors’ estimates of mammography screening costs. Medical insurers do not insure the high financial costs of lost productivity, which are shifted to patients and their families. Insurers’ financial interests may not necessarily align with patient interests.
304 © 2014 American College of Physicians
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Letters Mark A. Helvie, MD University of Michigan Comprehensive Cancer Center, University of Michigan Health System Ann Arbor, Michigan Disclosures: Disclosures can be viewed at www.acponline.org/authors /icmje/ConflictOfInterestForms.do?msNum⫽L14-0175. References 1. O’Donoghue C, Eklund M, Ozanne EM, Esserman LJ. Aggregate cost of mammography screening in the United States: comparison of current practice and advocated guidelines. Ann Intern Med. 2014;160:145-53. [PMID: 24658691] doi: 10.7326/M13-1217 2. Mandelblatt JS, Cronin KA, Bailey S, Berry DA, de Koning HJ, Draisma G, et al; Breast Cancer Working Group of the Cancer Intervention and Surveillance Modeling Network. Effects of mammography screening under different screening schedules: model estimates of potential benefits and harms. Ann Intern Med. 2009;151:738-47. [PMID: 19920274] doi:10.7326/0003-4819-151-10-200911170-00010 3. van Ravesteyn NT, Miglioretti DL, Stout NK, Lee SJ, Schechter CB, Buist DS, et al. Tipping the balance of benefits and harms to favor screening mammography starting at age 40 years: a comparative modeling study of risk. Ann Intern Med. 2012;156:609-17. [PMID: 22547470] doi:10.7326/0003-4819-156-9-20120501000002 4. Montero AJ, Eapen S, Gorin B, Adler P. The economic burden of metastatic breast cancer: a U.S. managed care perspective. Breast Cancer Res Treat. 2012;134:815-22. [PMID: 22684273] doi:10.1007/s10549-012-2097-2 5. Bradley CJ, Yabroff KR, Dahman B, Feuer EJ, Mariotto A, Brown ML. Productivity costs of cancer mortality in the United States: 2000-2020. J Natl Cancer Inst. 2008;100:1763-70. [PMID: 19066273] doi:10.1093/jnci/djn384
of this disease that can develop (ranging from slow-growing to aggressive) vary, the opportunity is available to use scientific advances in calculating inherited risk, quantitative density, cancer biology, and imaging techniques to learn how to tailor screening accordingly. Today, we individualize patient care on the basis of tumor biology. It is time to design screening trials to enable us to harness new knowledge to shed more light on and acquire the data that will teach us how best to screen in the modern era. The Athena Breast Health Network is planning such a personalized screening trial. Dr. Keen’s letter and our analysis of the aggregate cost of mammography suggest that the opportunity cost of annual screening is high; the money to study new approaches is already in the system. Martin Eklund, PhD University of California, San Francisco San Francisco, California Cristina O’Donoghue, MD, MPH University of Illinois at Chicago Chicago, Illinois Laura J. Esserman, MD, MBA University of California, San Francisco San Francisco, California Disclosures: Authors have disclosed no conflicts of interest. Forms can
be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms .do?msNum⫽M13-1217.
IN RESPONSE: We agree with Dr. Keen that the estimates we present
References
are conservative. This approach is by design, in order to provide a lower bound of the probable cost implications of different screening strategies. Dr. Helvie expressed concern that the USPSTF strategy would lead to loss of life on the basis of the CISNET models, the very analyses on which the USPSTF based its guidelines for biennial screening (1). In fact, the CISNET models show that, over the same age range, the mortality reduction and life-years gained from annual screening are virtually nonexistent. The evidence of benefit of annual over biennial screening is marginal (2) to none (3). Outside of the United States, the same data have led to adoption of policies for biennial screening starting at age 49 years. Despite annual screening, breast cancer mortality is not lower in the United States than in similar countries (4). Dr. Helvie is also concerned that eliminating or reducing screening will increase the incidence of metastatic disease. However, screening has not reduced the rate of primary presentation of metastatic disease and aggressive annual screening has not decreased the incidence of stage II and III cancer as much as we would have hoped (5). Some population subgroups probably benefit from annual screening (2), but certainly not everyone (3). The debate over mammography’s risks, who benefits most, and who will not benefit is long-standing. More arguing over studies started decades ago will not improve our current approach or change polarized beliefs. The opportunity before us today is to stop screening as if everyone has the same risk for— or is even at risk for the same kind of— breast cancer. Not all women will benefit from the same screening strategy. Given that women’s risk for breast cancer and the types
1. Mandelblatt JS, Cronin KA, Bailey S, Berry DA, de Koning HJ, Draisma G, et al; Breast Cancer Working Group of the Cancer Intervention and Surveillance Modeling Network. Effects of mammography screening under different screening schedules: model estimates of potential benefits and harms. Ann Intern Med. 2009;151:738-47. [PMID: 19920274] doi:10.7326/0003-4819-151-10-200911170-00010 2. Kerlikowske K, Zhu W, Hubbard RA, Geller B, Dittus K, Braithwaite D, et al; Breast Cancer Surveillance Consortium. Outcomes of screening mammography by frequency, breast density, and postmenopausal hormone therapy. JAMA Intern Med. 2013;173:807-16. [PMID: 23552817] doi:10.1001/jamainternmed.2013.307 3. Miller AB, Wall C, Baines CJ, Sun P, To T, Narod SA. Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. BMJ. 2014;348:g366. [PMID: 24519768] doi: 10.1136/bmj.g366 4. Bleyer A. US breast cancer mortality is consistent with European data [Letter]. BMJ. 2011;343:d5630. [PMID: 21896600] doi:10.1136/bmj.d5630 5. Esserman L, Shieh Y, Thompson I. Rethinking screening for breast cancer and prostate cancer. JAMA. 2009;302:1685-92. [PMID: 19843904] doi:10.1001/ jama.2009.1498
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Prescription Drug Abuse TO THE EDITOR: Many persons who receive narcotics to treat chronic pain take them responsibly. Some don’t. Kirschner and colleagues’ (1) position paper deals with the irresponsible ones and raises questions. The authors support random urine drug testing. What should be done with the results? Results of urine testing that are negative for prescribed narcotics might indicate that a prescription was diverted from its intended use. They might also indicate that a patient took 19 August 2014 Annals of Internal Medicine Volume 161 • Number 4 305
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Letters more than the prescribed amount of a narcotic near the beginning of a prescription to try to improve pain control and ran out of the drug before the next prescription was due to be filled. Thus, results might be unexpectedly negative for dishonorable or honorable reasons. Should the presence of cocaine or cannabis metabolites lead to the withdrawal of narcotic treatment for chronic pain? Well, does evidence show that the patient or society benefits from withholding therapy for pain because of positive results for cocaine or cannabis on urine testing? And, if it is argued that some societal benefit accrues from punishing a patient with pain who has positive results, is that benefit limited only to patients with pain? Should we not also test the urine of patients with heart or lung failure or sniffles and withhold their therapy if results of urine testing are positive for controlled drugs that weren’t prescribed? Coffin and Banta-Green (2) argue that we should prescribe less pain medication, specifically for “less appropriate indications,” such as low back pain. Less appropriate? By whose judgment? And what criteria? They also suggest that “clinicians should rely on functional status, rather than on reported pain, as the metric of success for management of chronic, nonmalignant pain” and note that “[l]ong-term opioids . . . may not improve and may in fact worsen functional status.” They also may improve functional status. And shouldn’t patients, rather than clinicians, be empowered to choose their own metric of success? Pain moderation today versus only the possibility of a future adverse effect on functional status? Finally, Coffin and Banta-Green advocate for increased use of buprenorphine. Eight milligrams of Suboxone (Reckitt Benckiser Pharmaceuticals) costs our pharmacy approximately $2.00 per pill. Butrans (Purdue Pharma), the sustained-release transdermal formulation of buprenorphine, 20 mcg/h, costs our pharmacy approximately $100 for each patch, which equals 1 week’s worth of medication. Generic Lortab 10/500 (UCB) or 10 mg of methadone costs approximately $0.08 per pill wholesale. J. Walden Retan, MD The Pain Clinic, Cooper Green/Mercy Health Services Birmingham, Alabama Disclosures: Authors have disclosed no conflicts of interest. Forms can
be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms .do?msNum⫽L14-0178.
References 1. Kirschner N, Ginsburg J, Sulmasy LS; Health and Public Policy Committee of the American College of Physicians. Prescription drug abuse: executive summary of a policy position paper from the American College of Physicians. Ann Intern Med. 2014;160:198. [PMID: 24323199] doi:10.7326/M13-2209 2. Coffin P, Banta-Green C. The dueling obligations of opioid stewardship [Editorial]. Ann Intern Med. 2014;160:207. [PMID: 24322334] doi:10.7326/M13-2781
TO THE EDITOR: It is disappointing that Kirschner and colleagues’
(1) position paper on prescription drug abuse focuses almost exclusively on the supply end of the problem while ignoring demand— specifically, demand by those who are today dependent on prescription painkillers. In fact, the word “dependence” appears in only 1 paragraph of this lengthy paper and within a section subtitled “Drug Enforcement Administration.”
Surely physicians, more than any other segment of society, should be keenly aware that drug dependence is a chronic medical condition that in most cases requires treatment. Without treatment, successful efforts to curtail supply actually exacerbate the dangers to the patient and society. As availability of prescription painkillers decreases and price increases, many who are dependent will turn to misuse of heroin; precisely such a change has been widely reported in the past few years. The explanation for the distressing and unexpected failure of the American College of Physicians to emphasize first and foremost the need for treatment seems to lie in its focus on “abuse” rather than on medical and social consequences. Drug abuse is not a clinical diagnosis! I respectfully urge that, in addition to providing guidance on appropriate prescribing of potentially harmful medications, the College advocate strenuously for ready access to treatment of dependence for those who want it, need it, and may well die without it. Robert Newman, MD, MPH Beth Israel Medical Center New York, New York Disclosures: Authors have disclosed no conflicts of interest. Forms can
be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms .do?msNum⫽L14-0179. Reference 1. Kirschner N, Ginsburg J, Sulmasy LS; Health and Public Policy Committee of the American College of Physicians. Prescription drug abuse: executive summary of a policy position paper from the American College of Physicians. Ann Intern Med. 2014;160:198. [PMID: 24323199] doi:10.7326/M13-2209
IN RESPONSE: Dr. Retan asserts that the College supports random urine drug testing for patients at substantial risk for prescription drug abuse and then questions the appropriateness of this position. In actuality, the College does not take this position. Position statement 8 recognizes only that third parties (for example, public and private payers and law enforcement officials) may require such testing in patients identified as being at substantial risk and makes recommendations for when such testing is mandated. These recommendations are that physicians should not do such tests without patient consent and that “neither the patient nor the physician should bear the financial cost of random drug testing mandated by a third-party authority.” Furthermore, commentary on the policy states that participating physicians should be aware of the limitations of the monitoring procedure used and how various factors can affect the validity of the findings. Dr. Newman states that the position paper focuses on the “supply end of the problem” and does not give sufficient attention to drug dependence. He urges the College to “advocate strenuously for ready access to treatment of dependence for those who want it, need it, and may well die without it.” Frankly, this critique surprised us. The first position statement declares that the College “supports appropriate and effective efforts to reduce all substance abuse . . . [including] educational, prevention, diagnostic, and treatment efforts [italics added].” The accompanying text further indicates the College’s position that treatment and prevention are essential to eradicating drug abuse in our society. It also reflects that the College has a history of advocating for treatment guidelines to provide the best-
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Letters quality treatment for all who need it, recognizing that addiction is a chronic condition that must be treated continuously throughout the life of the drug-dependent patient, and calling for adequate funding to ensure that treatment is available.
opioids for chronic nonmalignant pain may not improve and may in fact worsen functional status.” They reference a Cochrane review (2) that simply says that evidence (specifically controlled trials comparing opioids with placebo or other drugs) is insufficient to comment on the efficacy and safety of opioids for low back pain. Coffin and Banta-Green have extended this statement to include all nonmalignant pain and have used the words “may not” and “may” to imply lack of effect of opioids and possible adverse effects. Association, let alone causation, between opioids and positive or negative effects is not evident. Such lack of evidence should not be used to dissuade (or promote) the use of any drug but only to call for badly needed research—preferably a definitive, randomized, placebocontrolled trial of long-term opioids for chronic, nonmalignant pain.
about unintended adverse consequences at population and individual levels. In 2012, an estimated 4.8 million persons had used prescription pain relievers for nonmedical purposes in the past month and 1.9 million persons began using these agents for such purposes. Most of these medications came from prescriptions from single physicians, with as few as 2% obtained by the practice commonly known as “doctor shopping” and 0.2% purchased online (1). Localities across the country have documented vast increases in mortality associated with prescription opioid overdose, followed by increasing rates of death from heroin overdose. One study found that 39% of heroin users were initially dependent on prescription opioids; these persons were on average 8 years younger than heroin users who were not initially dependent on prescription opioids, representing a new generation of heroin users (2). A systematic review of opioid treatment for chronic back pain found no evidence of a benefit to long-term therapy and high rates of aberrant medicationtaking behaviors (3). Opioids are now generally discouraged for many other types of chronic pain, such as headache (4) and fibromyalgia (5). To be clear, this fact does not imply that opioids are never useful in these or other chronic pain syndromes but rather that they are rarely a first-line agent and carry risks that we did not recognize 10 to 20 years ago. Many providers already feel forced to restrict their use of opioids by legislation, regulators, payers, and clinic systems. Many of these restrictions may carry real risks for our patients who are already dependent on opioids, including undertreatment of pain that may respond to opioids and harms related to illicit opioid use. Randomized studies of long-term opioid use are extremely challenging to do, and results would take years—time that policymakers are unlikely to grant in the setting of a perceived national emergency. If we do not step up as leaders by recognizing that a problem exists and pursuing innovative yet humane practice reform now, we and our patients may pay a steep price.
William M. Tierney, MD Regenstrief Institute Indianapolis, Indiana
Phillip Coffin, MD, MIA San Francisco Department of Public Health San Francisco, California
Disclosures: Authors have disclosed no conflicts of interest. Forms can
be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms .do?msNum⫽L14-0152.
Caleb Banta-Green, PhD University of Washington Seattle, Washington
References
Disclosures: Authors have disclosed no conflicts of interest. Forms can
1. Coffin P, Banta-Green C. The dueling obligations of opioid stewardship [Editorial]. Ann Intern Med. 2014;160:207. [PMID: 24322334] doi:10.7326/M13-2781 2. Chaparro LE, Furlan AD, Deshpande A, Mailis-Gagnon A, Atlas S, Turk DC. Opioids compared to placebo or other treatments for chronic low-back pain. Cochrane Database Syst Rev. 2013;8:CD004959. [PMID: 23983011] doi:10.1002/14651858 .CD004959.pub4
be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms .do?msNum⫽M13-2781.
Neil Kirschner, PhD American College of Physicians Philadelphia, Pennsylvania Thomas G. Tape, MD University of Nebraska Medical Center Omaha, Nebraska Disclosures: Authors have disclosed no conflicts of interest. Forms can
be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms .do?msNum⫽L14-0180.
The Dueling Obligations of Opioid Stewardship TO THE EDITOR: Coffin and Banta-Green (1) state, “Long-term
IN RESPONSE: We agree that data are insufficient to support or
refute the potential benefits of long-term opioid use for chronic, nonmalignant pain. However, evidence of harm is not lacking. We will refrain from repeating the findings of the referenced American College of Physicians policy statement. Instead, we will emphasize the growing literature that has questioned the potential benefits of long-term opioid therapy in this context and raised serious concerns www.annals.org
References 1. Substance Abuse and Mental Health Services Administration. Results from the 2012 National Survey on Drug Use and Health: summary of national findings. NSDUH Series H-41, HHS publication no. (SMA) 11-4658. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2013. 2. Peavy KM, Banta-Green CJ, Kingston S, Hanrahan M, Merrill JO, Coffin PO. “Hooked on” prescription-type opiates prior to using heroin: results from a survey of syringe exchange clients. J Psychoactive Drugs. 2012;44:259-65. [PMID: 23061326] 3. Martell BA, O’Connor PG, Kerns RD, Becker WC, Morales KH, Kosten TR, et al. Systematic review: opioid treatment for chronic back pain: prevalence, efficacy, and association with addiction. Ann Intern Med. 2007;146:116-27. [PMID: 17227935] 19 August 2014 Annals of Internal Medicine Volume 161 • Number 4 307
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Letters 4. Levin M. Opioids in headache. Headache. 2014;54:12-21. [PMID: 24127913] doi:10.1111/head.12266 5. Skaer TL. Fibromyalgia: disease synopsis, medication cost effectiveness and economic burden. Pharmacoeconomics. 2014;32:457-66. [PMID: 24504852] doi: 10.1007/s40273-014-0137-y
Reference 1. Mollan KR, Smurzynski M, Eron JJ, Daar ES, Campbell TB, Sax PE, et al. Association between efavirenz as initial therapy for HIV-1 infection and increased risk for suicidal ideation or attempted or completed suicide: an analysis of trial data. Ann Intern Med. 2014;161:1-10. [PMID: 24979445] doi:10.7326/M14-0293
Correction: Osteoarthritis
CORRECTIONS
Correction: Association Between Efavirenz as Initial Therapy for HIV-1 Infection and Increased Risk for Suicide In a recent article by Mollan and colleagues (1), 2 search terms were incorrect: “suicide” should not have been included, and the spelling of “behavior” should have been “behaviour.” This has been fixed in the online version.
In a recent In the Clinic (1), the last sentence on page ITC4-1 should read as follows: “Bony prominence is also a common finding, particularly at the finger joints, where enlargement of the distal and proximal interphalangeal joints produces the characteristic eponymous Heberden and Bouchard nodes, respectively.” This has been fixed in the online version. Reference 1. Gelber AC. In the Clinic: osteoarthritis. Ann Intern Med. 2014;161:ITC1-1-16. [PMID: 24979462] doi:10.7326/0003-4819-161-1-201407010-01001
ACP JOURNALWISE Personalized Literature Updating Service Available exclusively to ACP Members, ACP JournalWise is an e-mail notification service that provides the literature alerts you want when you want them. The alerts can be customized to meet your needs. Alerts are based on your preferred areas of speciality and on clinical impact. Benefits of ACP JournalWise: ● Research alerts: Receive notifications of the latest research in clinical areas you pick, filtered for quality and revelance ● Tables of contents: Browse the most recent tables of contents you select from over 150 medical journals ● Folder sharing: Share article titles and abstracts with your colleagues and follow those that others are reading ● Flexible format: Access it all on your desktop, tablet, or smartphone Sign up today at journalwise.acponline.org.
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AND
Annals of Internal Medicine RESPONSES
Disclosures: Authors have disclosed no conflicts of interest. Forms can
be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms .do?msNum⫽L14-0174.
Aggregate Cost of Mammography Screening in the United States TO THE EDITOR: O’Donoghue and colleagues (1) have conserva-
tively estimated the aggregate cost of screening mammography in the United States under several scenarios. Screening advocates will argue that the number of lives extended under an aggressive annual screening scenario differs from that under the U.S. Preventive Services Task Force (USPSTF) guidelines. Although the authors cite a costeffectiveness ratio of annual screening compared with biennial screening of more than $340 000 per quality-adjusted life-year, the real ratio—including indirect costs and overdiagnosis—is probably double or triple that estimate (2). Furthermore, Hubbard and associates (3) have shown that annual screening in the United States has not reduced the proportion of cases of advanced cancer compared with biennial screening. Bleyer and Welch (4) have shown that the incidence of advanced breast cancer in the United States has only marginally decreased since screening mammography was introduced, with probably one half of screen-detected cases classified as overdiagnosis of pseudodisease (4). Screening cannot be beneficial (a reduction in mortality or mastectomy rates) if the incidence of advanced cancer does not decrease. Instead of promoting screening participation by claiming that the status quo “[falls] short of national goals,” the authors should acknowledge that the $8 billion consumed annually by screening mammography might be better spent on something else—that is, the opportunity cost of the resources. If physicians believe in promoting informed choice (insight) about cancer screening given the substantial personal harm from overdiagnosis of healthy women and false-positive recalls and biopsy results, then targeted participation rates (uptake) become irrelevant. As an alternative to a participation rate of 85%, the authors should model lower uptake to account for the current lack of insight about the tradeoff of harms to benefit and the uncertainty of the magnitude of these harms among women who have screening mammography. Screening advocates, including the American Cancer Society and some professional groups who benefit from screening (such as breast imaging radiologists, oncologists, and breast surgeons), will probably continue to support the status quo or an aggressive annual screening schedule instead of the USPSTF recommendations (5). This marketing of mammography no doubt increases screening participation and makes sense from a business perspective. The authors conservatively estimate that the breast imaging community receives $4.4 billion in additional revenue from the status quo each year. One person’s cost is another person’s income. The authors have quantified the financial conflict of interest among those most stridently defending aggressive annual screening mammography: an extra $2.3 billion in revenue beyond the status quo. Financial considerations best explain the organized resistance to the implementation of the reasonable USPSTF recommendations. John D. Keen, MD, MBA John H. Stroger, Jr. Hospital of Cook County Chicago, Illinois
References 1. O’Donoghue C, Eklund M, Ozanne EM, Esserman LJ. Aggregate cost of mammography screening in the United States: comparison of current practice and advocated guidelines. Ann Intern Med. 2014;160:145-53. [PMID: 24658691] doi: 10.7326/M13-1217 2. Keen JD. Analysis of health benefits and cost-effectiveness of mammography for breast cancer [Letter]. Ann Intern Med. 2011;155:566. [PMID: 22007057] doi: 10.7326/0003-4819-155-8-201110180-00028 3. Hubbard RA, Kerlikowske K, Flowers CI, Yankaskas BC, Zhu W, Miglioretti DL. Cumulative probability of false-positive recall or biopsy recommendation after 10 years of screening mammography: a cohort study. Ann Intern Med. 2011;155:481-92. [PMID: 22007042] doi:10.7326/0003-4819-155-8-201110180-00004 4. Bleyer A, Welch HG. Effect of three decades of screening mammography on breastcancer incidence. N Engl J Med. 2012;367:1998-2005. [PMID: 23171096] doi: 10.1056/NEJMoa1206809 5. Keen JD. The ACR/SBI breast cancer screening guidelines are wrong. Medscape Radiology. 2 March 2012. Accessed at www.medscape.com/viewarticle/759429 on 6 February 2014.
TO THE EDITOR: O’Donoghue and colleagues (1) compare the monetary costs to insurers of several mammography screening strategies. They conclude that the added cost of more aggressive screening is not justified because they imply that clinical outcomes with these strategies are similar. However, the outcome differences are substantial, which meaningfully affects the cost analysis. The results of the Cancer Intervention and Surveillance Modeling Network (CISNET) models, which the authors reference, show large outcome differences for life-years gained and mortality reduction with the annual mammography screening strategy (women aged 40 to 84 years) compared with the biennial strategy (women aged 50 to 74 years) (2, 3). Data from these models show that life-years gained increase by 72% with the annual strategy (189 per 1000 women) compared with the biennial strategy (110 per 1000 women). Mortality reduction nearly doubles from 23% to 40% (2). Life-years gained for women aged 40 to 49 years increase by 42% with annual screening compared with biennial screening. The CISNET models for digital mammography show that, among women aged 40 to 49 years, life-years gained increase from 36 per 1000 women with biennial screening to 51 per 1000 women with annual screening (3). Finally, the life-years gained per decade with annual screening of women in their 40s (51 per 1000 women) exceed those with biennial screening of women aged 50 to 74 years (44 per 1000 women) (3). Screening involves costs and harms. So does not screening, and this study does not estimate these factors. The financial cost of medical treatment for a woman with metastatic breast cancer is $250 000 (4). The financial cost due to lost productivity secondary to death of a woman in her 40s is $1.4 million (5). Hence, the financial cost of 1 excessive death from breast cancer due to not screening is large. The aggregate costs of these 2 factors, when attributed to excessive deaths from not screening based on results from the CISNET models, approach or exceed the authors’ estimates of mammography screening costs. Medical insurers do not insure the high financial costs of lost productivity, which are shifted to patients and their families. Insurers’ financial interests may not necessarily align with patient interests.
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Letters Mark A. Helvie, MD University of Michigan Comprehensive Cancer Center, University of Michigan Health System Ann Arbor, Michigan Disclosures: Disclosures can be viewed at www.acponline.org/authors /icmje/ConflictOfInterestForms.do?msNum⫽L14-0175. References 1. O’Donoghue C, Eklund M, Ozanne EM, Esserman LJ. Aggregate cost of mammography screening in the United States: comparison of current practice and advocated guidelines. Ann Intern Med. 2014;160:145-53. [PMID: 24658691] doi: 10.7326/M13-1217 2. Mandelblatt JS, Cronin KA, Bailey S, Berry DA, de Koning HJ, Draisma G, et al; Breast Cancer Working Group of the Cancer Intervention and Surveillance Modeling Network. Effects of mammography screening under different screening schedules: model estimates of potential benefits and harms. Ann Intern Med. 2009;151:738-47. [PMID: 19920274] doi:10.7326/0003-4819-151-10-200911170-00010 3. van Ravesteyn NT, Miglioretti DL, Stout NK, Lee SJ, Schechter CB, Buist DS, et al. Tipping the balance of benefits and harms to favor screening mammography starting at age 40 years: a comparative modeling study of risk. Ann Intern Med. 2012;156:609-17. [PMID: 22547470] doi:10.7326/0003-4819-156-9-20120501000002 4. Montero AJ, Eapen S, Gorin B, Adler P. The economic burden of metastatic breast cancer: a U.S. managed care perspective. Breast Cancer Res Treat. 2012;134:815-22. [PMID: 22684273] doi:10.1007/s10549-012-2097-2 5. Bradley CJ, Yabroff KR, Dahman B, Feuer EJ, Mariotto A, Brown ML. Productivity costs of cancer mortality in the United States: 2000-2020. J Natl Cancer Inst. 2008;100:1763-70. [PMID: 19066273] doi:10.1093/jnci/djn384
of this disease that can develop (ranging from slow-growing to aggressive) vary, the opportunity is available to use scientific advances in calculating inherited risk, quantitative density, cancer biology, and imaging techniques to learn how to tailor screening accordingly. Today, we individualize patient care on the basis of tumor biology. It is time to design screening trials to enable us to harness new knowledge to shed more light on and acquire the data that will teach us how best to screen in the modern era. The Athena Breast Health Network is planning such a personalized screening trial. Dr. Keen’s letter and our analysis of the aggregate cost of mammography suggest that the opportunity cost of annual screening is high; the money to study new approaches is already in the system. Martin Eklund, PhD University of California, San Francisco San Francisco, California Cristina O’Donoghue, MD, MPH University of Illinois at Chicago Chicago, Illinois Laura J. Esserman, MD, MBA University of California, San Francisco San Francisco, California Disclosures: Authors have disclosed no conflicts of interest. Forms can
be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms .do?msNum⫽M13-1217.
IN RESPONSE: We agree with Dr. Keen that the estimates we present
References
are conservative. This approach is by design, in order to provide a lower bound of the probable cost implications of different screening strategies. Dr. Helvie expressed concern that the USPSTF strategy would lead to loss of life on the basis of the CISNET models, the very analyses on which the USPSTF based its guidelines for biennial screening (1). In fact, the CISNET models show that, over the same age range, the mortality reduction and life-years gained from annual screening are virtually nonexistent. The evidence of benefit of annual over biennial screening is marginal (2) to none (3). Outside of the United States, the same data have led to adoption of policies for biennial screening starting at age 49 years. Despite annual screening, breast cancer mortality is not lower in the United States than in similar countries (4). Dr. Helvie is also concerned that eliminating or reducing screening will increase the incidence of metastatic disease. However, screening has not reduced the rate of primary presentation of metastatic disease and aggressive annual screening has not decreased the incidence of stage II and III cancer as much as we would have hoped (5). Some population subgroups probably benefit from annual screening (2), but certainly not everyone (3). The debate over mammography’s risks, who benefits most, and who will not benefit is long-standing. More arguing over studies started decades ago will not improve our current approach or change polarized beliefs. The opportunity before us today is to stop screening as if everyone has the same risk for— or is even at risk for the same kind of— breast cancer. Not all women will benefit from the same screening strategy. Given that women’s risk for breast cancer and the types
1. Mandelblatt JS, Cronin KA, Bailey S, Berry DA, de Koning HJ, Draisma G, et al; Breast Cancer Working Group of the Cancer Intervention and Surveillance Modeling Network. Effects of mammography screening under different screening schedules: model estimates of potential benefits and harms. Ann Intern Med. 2009;151:738-47. [PMID: 19920274] doi:10.7326/0003-4819-151-10-200911170-00010 2. Kerlikowske K, Zhu W, Hubbard RA, Geller B, Dittus K, Braithwaite D, et al; Breast Cancer Surveillance Consortium. Outcomes of screening mammography by frequency, breast density, and postmenopausal hormone therapy. JAMA Intern Med. 2013;173:807-16. [PMID: 23552817] doi:10.1001/jamainternmed.2013.307 3. Miller AB, Wall C, Baines CJ, Sun P, To T, Narod SA. Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. BMJ. 2014;348:g366. [PMID: 24519768] doi: 10.1136/bmj.g366 4. Bleyer A. US breast cancer mortality is consistent with European data [Letter]. BMJ. 2011;343:d5630. [PMID: 21896600] doi:10.1136/bmj.d5630 5. Esserman L, Shieh Y, Thompson I. Rethinking screening for breast cancer and prostate cancer. JAMA. 2009;302:1685-92. [PMID: 19843904] doi:10.1001/ jama.2009.1498
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Prescription Drug Abuse TO THE EDITOR: Many persons who receive narcotics to treat chronic pain take them responsibly. Some don’t. Kirschner and colleagues’ (1) position paper deals with the irresponsible ones and raises questions. The authors support random urine drug testing. What should be done with the results? Results of urine testing that are negative for prescribed narcotics might indicate that a prescription was diverted from its intended use. They might also indicate that a patient took 19 August 2014 Annals of Internal Medicine Volume 161 • Number 4 305
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Letters more than the prescribed amount of a narcotic near the beginning of a prescription to try to improve pain control and ran out of the drug before the next prescription was due to be filled. Thus, results might be unexpectedly negative for dishonorable or honorable reasons. Should the presence of cocaine or cannabis metabolites lead to the withdrawal of narcotic treatment for chronic pain? Well, does evidence show that the patient or society benefits from withholding therapy for pain because of positive results for cocaine or cannabis on urine testing? And, if it is argued that some societal benefit accrues from punishing a patient with pain who has positive results, is that benefit limited only to patients with pain? Should we not also test the urine of patients with heart or lung failure or sniffles and withhold their therapy if results of urine testing are positive for controlled drugs that weren’t prescribed? Coffin and Banta-Green (2) argue that we should prescribe less pain medication, specifically for “less appropriate indications,” such as low back pain. Less appropriate? By whose judgment? And what criteria? They also suggest that “clinicians should rely on functional status, rather than on reported pain, as the metric of success for management of chronic, nonmalignant pain” and note that “[l]ong-term opioids . . . may not improve and may in fact worsen functional status.” They also may improve functional status. And shouldn’t patients, rather than clinicians, be empowered to choose their own metric of success? Pain moderation today versus only the possibility of a future adverse effect on functional status? Finally, Coffin and Banta-Green advocate for increased use of buprenorphine. Eight milligrams of Suboxone (Reckitt Benckiser Pharmaceuticals) costs our pharmacy approximately $2.00 per pill. Butrans (Purdue Pharma), the sustained-release transdermal formulation of buprenorphine, 20 mcg/h, costs our pharmacy approximately $100 for each patch, which equals 1 week’s worth of medication. Generic Lortab 10/500 (UCB) or 10 mg of methadone costs approximately $0.08 per pill wholesale. J. Walden Retan, MD The Pain Clinic, Cooper Green/Mercy Health Services Birmingham, Alabama Disclosures: Authors have disclosed no conflicts of interest. Forms can
be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms .do?msNum⫽L14-0178.
References 1. Kirschner N, Ginsburg J, Sulmasy LS; Health and Public Policy Committee of the American College of Physicians. Prescription drug abuse: executive summary of a policy position paper from the American College of Physicians. Ann Intern Med. 2014;160:198. [PMID: 24323199] doi:10.7326/M13-2209 2. Coffin P, Banta-Green C. The dueling obligations of opioid stewardship [Editorial]. Ann Intern Med. 2014;160:207. [PMID: 24322334] doi:10.7326/M13-2781
TO THE EDITOR: It is disappointing that Kirschner and colleagues’
(1) position paper on prescription drug abuse focuses almost exclusively on the supply end of the problem while ignoring demand— specifically, demand by those who are today dependent on prescription painkillers. In fact, the word “dependence” appears in only 1 paragraph of this lengthy paper and within a section subtitled “Drug Enforcement Administration.”
Surely physicians, more than any other segment of society, should be keenly aware that drug dependence is a chronic medical condition that in most cases requires treatment. Without treatment, successful efforts to curtail supply actually exacerbate the dangers to the patient and society. As availability of prescription painkillers decreases and price increases, many who are dependent will turn to misuse of heroin; precisely such a change has been widely reported in the past few years. The explanation for the distressing and unexpected failure of the American College of Physicians to emphasize first and foremost the need for treatment seems to lie in its focus on “abuse” rather than on medical and social consequences. Drug abuse is not a clinical diagnosis! I respectfully urge that, in addition to providing guidance on appropriate prescribing of potentially harmful medications, the College advocate strenuously for ready access to treatment of dependence for those who want it, need it, and may well die without it. Robert Newman, MD, MPH Beth Israel Medical Center New York, New York Disclosures: Authors have disclosed no conflicts of interest. Forms can
be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms .do?msNum⫽L14-0179. Reference 1. Kirschner N, Ginsburg J, Sulmasy LS; Health and Public Policy Committee of the American College of Physicians. Prescription drug abuse: executive summary of a policy position paper from the American College of Physicians. Ann Intern Med. 2014;160:198. [PMID: 24323199] doi:10.7326/M13-2209
IN RESPONSE: Dr. Retan asserts that the College supports random urine drug testing for patients at substantial risk for prescription drug abuse and then questions the appropriateness of this position. In actuality, the College does not take this position. Position statement 8 recognizes only that third parties (for example, public and private payers and law enforcement officials) may require such testing in patients identified as being at substantial risk and makes recommendations for when such testing is mandated. These recommendations are that physicians should not do such tests without patient consent and that “neither the patient nor the physician should bear the financial cost of random drug testing mandated by a third-party authority.” Furthermore, commentary on the policy states that participating physicians should be aware of the limitations of the monitoring procedure used and how various factors can affect the validity of the findings. Dr. Newman states that the position paper focuses on the “supply end of the problem” and does not give sufficient attention to drug dependence. He urges the College to “advocate strenuously for ready access to treatment of dependence for those who want it, need it, and may well die without it.” Frankly, this critique surprised us. The first position statement declares that the College “supports appropriate and effective efforts to reduce all substance abuse . . . [including] educational, prevention, diagnostic, and treatment efforts [italics added].” The accompanying text further indicates the College’s position that treatment and prevention are essential to eradicating drug abuse in our society. It also reflects that the College has a history of advocating for treatment guidelines to provide the best-
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Letters quality treatment for all who need it, recognizing that addiction is a chronic condition that must be treated continuously throughout the life of the drug-dependent patient, and calling for adequate funding to ensure that treatment is available.
opioids for chronic nonmalignant pain may not improve and may in fact worsen functional status.” They reference a Cochrane review (2) that simply says that evidence (specifically controlled trials comparing opioids with placebo or other drugs) is insufficient to comment on the efficacy and safety of opioids for low back pain. Coffin and Banta-Green have extended this statement to include all nonmalignant pain and have used the words “may not” and “may” to imply lack of effect of opioids and possible adverse effects. Association, let alone causation, between opioids and positive or negative effects is not evident. Such lack of evidence should not be used to dissuade (or promote) the use of any drug but only to call for badly needed research—preferably a definitive, randomized, placebocontrolled trial of long-term opioids for chronic, nonmalignant pain.
about unintended adverse consequences at population and individual levels. In 2012, an estimated 4.8 million persons had used prescription pain relievers for nonmedical purposes in the past month and 1.9 million persons began using these agents for such purposes. Most of these medications came from prescriptions from single physicians, with as few as 2% obtained by the practice commonly known as “doctor shopping” and 0.2% purchased online (1). Localities across the country have documented vast increases in mortality associated with prescription opioid overdose, followed by increasing rates of death from heroin overdose. One study found that 39% of heroin users were initially dependent on prescription opioids; these persons were on average 8 years younger than heroin users who were not initially dependent on prescription opioids, representing a new generation of heroin users (2). A systematic review of opioid treatment for chronic back pain found no evidence of a benefit to long-term therapy and high rates of aberrant medicationtaking behaviors (3). Opioids are now generally discouraged for many other types of chronic pain, such as headache (4) and fibromyalgia (5). To be clear, this fact does not imply that opioids are never useful in these or other chronic pain syndromes but rather that they are rarely a first-line agent and carry risks that we did not recognize 10 to 20 years ago. Many providers already feel forced to restrict their use of opioids by legislation, regulators, payers, and clinic systems. Many of these restrictions may carry real risks for our patients who are already dependent on opioids, including undertreatment of pain that may respond to opioids and harms related to illicit opioid use. Randomized studies of long-term opioid use are extremely challenging to do, and results would take years—time that policymakers are unlikely to grant in the setting of a perceived national emergency. If we do not step up as leaders by recognizing that a problem exists and pursuing innovative yet humane practice reform now, we and our patients may pay a steep price.
William M. Tierney, MD Regenstrief Institute Indianapolis, Indiana
Phillip Coffin, MD, MIA San Francisco Department of Public Health San Francisco, California
Disclosures: Authors have disclosed no conflicts of interest. Forms can
be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms .do?msNum⫽L14-0152.
Caleb Banta-Green, PhD University of Washington Seattle, Washington
References
Disclosures: Authors have disclosed no conflicts of interest. Forms can
1. Coffin P, Banta-Green C. The dueling obligations of opioid stewardship [Editorial]. Ann Intern Med. 2014;160:207. [PMID: 24322334] doi:10.7326/M13-2781 2. Chaparro LE, Furlan AD, Deshpande A, Mailis-Gagnon A, Atlas S, Turk DC. Opioids compared to placebo or other treatments for chronic low-back pain. Cochrane Database Syst Rev. 2013;8:CD004959. [PMID: 23983011] doi:10.1002/14651858 .CD004959.pub4
be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms .do?msNum⫽M13-2781.
Neil Kirschner, PhD American College of Physicians Philadelphia, Pennsylvania Thomas G. Tape, MD University of Nebraska Medical Center Omaha, Nebraska Disclosures: Authors have disclosed no conflicts of interest. Forms can
be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms .do?msNum⫽L14-0180.
The Dueling Obligations of Opioid Stewardship TO THE EDITOR: Coffin and Banta-Green (1) state, “Long-term
IN RESPONSE: We agree that data are insufficient to support or
refute the potential benefits of long-term opioid use for chronic, nonmalignant pain. However, evidence of harm is not lacking. We will refrain from repeating the findings of the referenced American College of Physicians policy statement. Instead, we will emphasize the growing literature that has questioned the potential benefits of long-term opioid therapy in this context and raised serious concerns www.annals.org
References 1. Substance Abuse and Mental Health Services Administration. Results from the 2012 National Survey on Drug Use and Health: summary of national findings. NSDUH Series H-41, HHS publication no. (SMA) 11-4658. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2013. 2. Peavy KM, Banta-Green CJ, Kingston S, Hanrahan M, Merrill JO, Coffin PO. “Hooked on” prescription-type opiates prior to using heroin: results from a survey of syringe exchange clients. J Psychoactive Drugs. 2012;44:259-65. [PMID: 23061326] 3. Martell BA, O’Connor PG, Kerns RD, Becker WC, Morales KH, Kosten TR, et al. Systematic review: opioid treatment for chronic back pain: prevalence, efficacy, and association with addiction. Ann Intern Med. 2007;146:116-27. [PMID: 17227935] 19 August 2014 Annals of Internal Medicine Volume 161 • Number 4 307
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Letters 4. Levin M. Opioids in headache. Headache. 2014;54:12-21. [PMID: 24127913] doi:10.1111/head.12266 5. Skaer TL. Fibromyalgia: disease synopsis, medication cost effectiveness and economic burden. Pharmacoeconomics. 2014;32:457-66. [PMID: 24504852] doi: 10.1007/s40273-014-0137-y
Reference 1. Mollan KR, Smurzynski M, Eron JJ, Daar ES, Campbell TB, Sax PE, et al. Association between efavirenz as initial therapy for HIV-1 infection and increased risk for suicidal ideation or attempted or completed suicide: an analysis of trial data. Ann Intern Med. 2014;161:1-10. [PMID: 24979445] doi:10.7326/M14-0293
Correction: Osteoarthritis
CORRECTIONS
Correction: Association Between Efavirenz as Initial Therapy for HIV-1 Infection and Increased Risk for Suicide In a recent article by Mollan and colleagues (1), 2 search terms were incorrect: “suicide” should not have been included, and the spelling of “behavior” should have been “behaviour.” This has been fixed in the online version.
In a recent In the Clinic (1), the last sentence on page ITC4-1 should read as follows: “Bony prominence is also a common finding, particularly at the finger joints, where enlargement of the distal and proximal interphalangeal joints produces the characteristic eponymous Heberden and Bouchard nodes, respectively.” This has been fixed in the online version. Reference 1. Gelber AC. In the Clinic: osteoarthritis. Ann Intern Med. 2014;161:ITC1-1-16. [PMID: 24979462] doi:10.7326/0003-4819-161-1-201407010-01001
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