LETTERS COMMENTS AND RESPONSES
Genetic and Environmental Risk Assessment and Colorectal Cancer Screening TO THE EDITOR: Weinberg and colleagues' article (1) high-
lights the complexities of using genetic polymorphisms and their associated cancer risk to encourage lifestyle modifications. The study attempts to consider risks, benefits, and potential barriers to personalized medicine and associated patient and provider uptake. The authors discuss their rationale for using trained nurses in lieu of genetic counselors, stating that the number of genetic counselors seems inadequate to meet health service needs even in high-risk settings, citing a reference from 1990 (2) that does not reflect current data. Currently, there are more than 4000 certified genetic counselors in the United States, all of whom are trained to provide a cancer genetics consult and approximately 30% of whom report cancer genetics as their primary specialty (3). The certified genetic counselor workforce has increased by 75% since 2006. Annual growth in the profession is trending upward of 7% to 10%; this finding partially reflects the increase in the number and capacity of training programs as we prepare for future needs. Recently, genetic counselors were cited in the “Top 10 Fastest-Growing Careers” (4). According to the U.S. Bureau of Labor Statistics, the genetic counseling profession is predicted to increase 41% by the end of 2022, a rate much faster than that of other health care professions (5, 6). Access to certified genetic counselors is excellent. Approximately one half of respondents to the National Society of Genetic Counselors' 2014 Professional Status Survey report availability for a new patient consultation within 1 week (3). Alternative genetic service methods, including video or telephone genetic counseling, increase access to patients in underserved areas. A directory of genetic counselors is available at www.nsgc.org. The authors state that “a lack of familiarity with genomics on the part of patients (and providers) has been cited as a concern limiting the effect of genetic testing.” This “lack of familiarity” and the mounting complexity of genetic and genomic testing highlight the importance of collaboration between genetics and genomics and medical specialties. The National Society of Genetic Counselors welcomes opportunities to partner with health care organizations to provide genetics and genomics education. Genetic counselors are essential members of the health care team and work with our physician partners to provide counseling, enhance overall patient care, accelerate educational opportunities for clinicians, and facilitate appropriate utilization of genetic services and testing to ensure sound medical management and decision making. The National Society of Genetic Counselors suggests that health care organizations and providers unfamiliar with genetic services work with genetic counselors to ensure delivery of high-quality genetic services to patients.
Annals of Internal Medicine Sara M. Pirzadeh-Miller, MS University of Texas Southwestern Medical Center Dallas, Texas Victoria M. Raymond, MS University of Michigan Ann Arbor, Michigan Sara Knapke, MS Cincinnati Children's Hospital Cincinnati, Ohio Disclosures: Disclosures can be viewed at www.acponline.org /authors/icmje/ConflictOfInterestForms.do?msNum=L15-0019. References 1. Weinberg DS, Myers RE, Keenan E, Ruth K, Sifri R, Ziring B, et al. Genetic and environmental risk assessment and colorectal cancer screening in an averagerisk population: a randomized trial. Ann Intern Med. 2014;161:537-45. [PMID: 25329201] doi:10.7326/M14-0765 2. Wilfond BS, Fost N. The cystic fibrosis gene: medical and social implications for heterozygote detection. JAMA. 1990;263:2777-83. [PMID: 11653890] 3. National Society of Genetic Counselors. NSGC Professional Status Survey 2014. Chicago: National Society of Genetic Counselors; 2014. 4. AllHealthcare. 10 best healthcare jobs with a master's degree: genetic counselor. 2014. Accessed at http://allhealthcare.monster.com/careers/articles /3125-10-best-healthcare-jobs-with-a-masters-degree?page=11 on 19 November 2014. 5. Weintraub A. Study a hot concentration today for a future health care job. U.S. News & World Report. 19 March 2014. Accessed at www.usnews .com/education/best-graduate-schools/articles/2014/03/19/study-a-hot -concentration-today-for-a-future-health-care-job on 19 November 2014. 6. Dorfman M. Six-figure jobs: genetic counselors earn up to $250K. AOL Jobs. 10 November 2014. Accessed at http://jobs.aol.com/articles/2014/11/10/six -figure-jobs-genetic-counselors-earn-up-to-250k on 9 November 2014.
TO THE EDITOR: Although Weinberg and colleagues' study
(1) is interesting and well-done, the negative results are not surprising. Among several possibilities for these results are the time frame for estimating risk for colorectal cancer (CRC), the magnitude of the risk, the 6-month interval for assessing screening uptake, and whether the genetic and environmental risk assessment had meaning to study participants. With regard to the time frame for CRC risk, it seems that study participants were told about their lifetime risk for this condition. Knowing about lifetime CRC risk may motivate persons or patients less—particularly in the short term (6 months or perhaps 1 year)—than would knowing about a current or near-term risk. In general, persons want to know what they need to do now or in the near term in response to learning about “risk.” Because CRC prevalence is so low and advanced precancerous polyps have become the target lesion of screening, telling persons about their current risk for advanced neoplasia (that is, the combination of CRC and advanced polyps) could result in screening uptake sooner and to a greater degree or extent than telling them their lifetime CRC risk (a future risk). The perception of a low magnitude of risk may be another reason for inaction in the short term. Average lifetime risk for CRC is approximately 5% (or 1 in 20). Even if the genetic and environmental risk assessment suggests a doubling of lifetime risk, that risk is still just 10%, which many would
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LETTERS interpret as having a 90% chance of not getting CRC. This interpretation supports inertia to avoid screening, especially in the short term. In contrast, telling persons that they have a 20% to 25% (1 in 4 or 1 in 5) chance of having an advanced, precancerous polyp present “now” (because of several phenotypic features) may be a greater motivator to get screened in the short term. Given a future risk for CRC—whether elevated or not—allowing just 6 months to assess screening uptake likely contributed to the negative results. Finally, whether persons understand and accept the results of genetic and environmental risk assessment may be questioned. Persons can probably comprehend and relate better to older age, male sex, cigarette smoking, a family history of CRC, overweight status, and other phenotypic features as risk factors than they can to polymorphic variants of methylenetetrahydrofolate reductase and low serum folate levels as increasing their risk for CRC and, thus, as motivators toward CRC screening. Thomas F. Imperiale, MD Indiana University Medical Center, Regenstrief Institute, and Roudebush Veterans Affairs Medical Center Indianapolis, Indiana Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOf InterestForms.do?msNum=L15-0020.
protocol at our institutions (4). Nursing staff has favored this delirium screening tool because of its short administration time and ease of use. The ability to quickly train nurses to use it has also been viewed as an advantage. However, the NuDESC is not perfect and problems with accuracy of assessment by nurses despite high accuracy by investigators have been reported (5). In our experience, for a delirium screening test to accepted by nurses, it must be quick and accurate and perceived as valuable. The difference between 1 minute and 3 minutes can become quite important when applied to multiple patients cared for during each shift. If the delirium assessment tool does not have workflow efficiency, then sustainability of its use is jeopardized. The Nu-DESC should be considered for broader clinical use in hospitals and should certainly be considered in any future comparative research trials. Rex Wilford, DO, RPh Sue Fosnight, RPh, CGP, BCPS Summa Health System Akron, Ohio Kyle Allen, DO Riverside Health System Newport News, Virginia Disclosures: Authors have disclosed no conflicts of interest. Forms
Reference 1. Weinberg DS, Myers RE, Keenan E, Ruth K, Sifri R, Ziring B, et al. Genetic and environmental risk assessment and colorectal cancer screening in an averagerisk population: a randomized trial. Ann Intern Med. 2014;161:537-45. [PMID: 25329201] doi:10.7326/M14-0765
3D-CAM TO THE EDITOR: We read Marcantonio and colleagues' article
(1) with great interest. The early recognition of delirium across all hospital settings is an important factor in patient safety and care. Nurses caring for patients have the best opportunity to recognize a disorder that fluctuates over time, such as this condition. The ultimate goal of having a brief and accurate tool to aid nurses in the early detection of delirium without adding excess burden to ever-increasing nurse charting time is important. Marcantonio and colleagues did, indeed, show that the 3D-CAM (3D-Confusion Assessment Method) decreases the time to complete delirium assessment to 3 minutes while maintaining high sensitivity and specificity. In the Discussion section, the authors comment, “We currently have no brief instrument that is well-suited for widespread use across clinical settings.” We argue that the Nursing Delirium Screening Scale (Nu-DESC) is such an instrument. This tool is an observational, 5-item delirium screening scale that can be completed in approximately 1 minute (2). When studied in medical (2), surgical (3), and intensive care units, the Nu-DESC took less time and had clinically similar sensitivity and specificity to other instruments, such as the CAM, and showed efficacy in identification of hypoactive delirium. The Nu-DESC has been successfully implemented hospital-wide among medical–surgical patients as a major part of a delirium www.annals.org
can be viewed at www.acponline.org/authors/icmje/ConflictOf InterestForms.do?msNum=L15-0018.
References 1. Marcantonio ER, Ngo LH, O’Connor M, Jones RN, Crane PK, Metzger ED, et al. 3D-CAM: derivation and validation of a 3-minute diagnostic interview for CAM-defined delirium: a cross-sectional diagnostic test study. Ann Intern Med. 2014;161:554-61. [PMID: 25329203] doi:10.7326/M14-0865 2. Gaudreau JD, Gagnon P, Harel F, Tremblay A, Roy MA. Fast, systematic, and continuous delirium assessment in hospitalized patients: the nursing delirium screening scale. J Pain Symptom Manage. 2005;29:368-75. [PMID: 15857740] 3. Radtke FM, Franck M, Schust S, Boehme L, Pascher A, Bail HJ, et al. A comparison of three scores to screen for delirium on the surgical ward. World J Surg. 2010;34:487-94. [PMID: 20066416] doi:10.1007/s00268-009-0376-9 4. Allen KR, Fosnight SM, Wilford R, Benedict LM, Sabo A, Holder C, et al. Implementation of a system-wide quality improvement project to prevent delirium in hospitalized patients. J Clin Outcomes Manag. 2011;18:253-8. 5. Solberg LM, Plummer CE, May KN, Mion LC. A quality improvement program to increase nurses' detection of delirium on an acute medical unit. Geriatr Nurs. 2013;34:75-9. [PMID: 23614146]
IN RESPONSE: Dr. Wilford and colleagues describe their experience with the Nu-DESC (1), a brief delirium screening instrument that assesses 5 features: disorientation, inappropriate behavior, inappropriate communication, illusions/hallucinations, and psychomotor retardation. Each feature is rated 0, 1, or 2, and a total score of 2 or higher out of 10 is considered a positive screen for delirium. Of note, Nu-DESC scoring is based on routine nursing observations and requires no formal interviewing or cognitive testing. Therefore, it can be completed very quickly—in 1 minute or less. In the references that Dr. Wilford and colleagues provide, this tool has excellent test characteristics relative to a reference standard. However, Annals of Internal Medicine • Vol. 162 No. 7 • 7 April 2015 527
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LETTERS other publications report worse performance; for example, a recent study of surgical patients reported sensitivities between 29% and 32% (2), indicating that 7 of 10 cases of delirium were missed. The key to delirium assessment is the quality of data that go into determining the presence or absence of core diagnostic features of delirium. In modern hospital care, physicians and nurses do not routinely interact with patients in ways that reliably elicit delirium features. For example, when the CAM algorithm was completed by nurses solely on the basis of observations from routine care, its sensitivity was 30% relative to a reference standard (3). Information provided by structured testing is essential, particularly for patients with hypoactive delirium. The 3D-CAM incorporates patient symptom probes (such as “Have you felt confused today?”) and cognitive testing (such as stating the days of the week backward) in addition to observational items. Structured testing enhances sensitivity so that cases will not be missed, ensures that all key features of delirium are assessed, and enhances reliability by collecting a uniform set of data. It also provides an objective measure of cognitive function that facilitates assessment of change in future days. Defining a brief yet informative set of cognitive items is a key contribution of the 3D-CAM. The 3D-CAM, when administered in full, can be completed in 3 minutes. Using skip patterns or up-front screening items may shorten the 3D-CAM further while retaining excellent performance. Our group is actively developing and testing methods to enhance the feasibility of delirium identification in clinical practice. For the time being, we urge clinicians to incorporate structured testing, such as the items in the 3DCAM, into their routine assessment of delirium.
should be used to avoid a recurrence of nephrolithiasis. If hypercalciuria is present, thiazide diuretics obviously should be used. However, use of thiazides in the presence of uricosuria may be counterproductive. Allopurinol should be used with uricosuria, but allopurinol and citrates also may be successfully used in the absence of hypercalciuria or uricosuria. Obese patients with type 2 diabetes frequently have acidic urine due to hyperinsulinemia, inducing a decrease in ammonia production in the proximal tubule and sodium clearance. The resulting lower urine pH can cause uric acid to “come out” of solution and crystallize (2). Although most calculi in obese participants with type 2 diabetes are composed of calcium oxylate, the proportion of uric acid stones is higher than in control participants (35.8% vs. 11.3%) (3). Normal uric acid excretion is less than 800 mg/d, but uric acid can crystallize at levels as low as 200 mg/day in the presence of acidic urine. In this situation, the most effective therapies to prevent stone formation are allopurinol to reduce uricosuria and citrates to neutralize the acidic urine. In the absence of an analysis of a previous stone or hypercalciuria, a low urine pH should suggest that therapy with allopurinol, a citrate, or both will decrease the formation of calculi (4).
Edward R. Marcantonio, MD, SM Beth Israel Deaconess Medical Center Boston, Massachusetts
1. Qaseem A, Dallas P, Forciea MA, Starkey M, Denberg TD; Clinical Guidelines Committee of the American College of Physicians. Dietary and pharmacologic management to prevent recurrent nephrolithiasis in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2014;161:659-67. [PMID: 25364887] doi:10.7326/M13-2908 2. Sakhaee K, Adams-Huet B, Moe OW, Pak CY. Pathophysiologic basis for normouricosuric uric acid nephrolithiasis. Kidney Int. 2002;62:971-9. [PMID: 12164880] 3. Daudon M, Traxer O, Conort P, Lacour B, Jungers P. Type 2 diabetes increases the risk for uric acid stones. J Am Soc Nephrol. 2006;17:2026-33. [PMID: 16775030] 4. Bell DS. Beware the low urine pH—the major cause of the increased prevalence of nephrolithiasis in the patient with type 2 diabetes. Diabetes Obes Metab. 2012;14:299-303. [PMID: 21992452] doi:10.1111/j.1463-1326 .2011.01519.x
David S.H. Bell, MD Southside Endocrinology Mountain Brook, Alabama Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOf InterestForms.do?msNum=L15-0050. References
Sharon K. Inouye, MD MPH Hebrew SeniorLife Boston, Massachusetts Disclosures: Disclosures can be viewed at www.acponline.org /authors/icmje/ConflictOfInterestForms.do?msNum=M14-0865. References 1. Gaudreau JD, Gagnon P, Harel F, Tremblay A, Roy MA. Fast, systematic, and continuous delirium assessment in hospitalized patients: the nursing delirium screening scale. J Pain Symptom Manage. 2005;29:368-75. [PMID: 15857740] 2. Neufeld KJ, Leoutsakos JS, Sieber FE, Joshi D, Wanamaker BL, Rios-Robles J, et al. Evaluation of two delirium screening tools for detecting post-operative delirium in the elderly. Br J Anaesth. 2013;111:612-8. [PMID: 23657522] doi: 10.1093/bja/aet167 3. Inouye SK, Foreman MD, Mion LC, Katz KH, Cooney LM Jr. Nurses' recognition of delirium and its symptoms: comparison of nurse and researcher ratings. Arch Intern Med. 2001;161:2467-73. [PMID: 11700159]
Prevention of Recurrent Nephrolithiasis in Adults TO THE EDITOR: Qaseem and colleagues (1) did not indicate under what circumstances citrates, thiazides, or allopurinol
TO THE EDITOR: Qaseem and colleagues' (1) recommenda-
tion to drink at least 2 L of fluid per day and use thiazide diuretics, citrate, or allopurinol when fluids alone are insufficient mirror a recent guideline released by the American Urological Association. However, several features of the American College of Physicians' recommendations disagree with those of the American Urological Association. For example, Qaseem and colleagues do not recommend baseline evaluation of stone composition or 24-hour urine analysis for stone risk factors. Kidney stone analysis by infrared spectroscopy is relatively inexpensive; very precise; and, in our opinion, essential to properly diagnose the form of kidney stone disease. A thi-
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LETTERS azide diuretic would not be helpful for a patient with uric acid kidney stones or someone with cystinuria, both of which can be determined by stone analysis alone. Furthermore, 24-hour urine analysis can help to guide logical therapeutic choices and specific dietary advice for an individual patient. For example, pharmacotherapy may not help persons in whom a very low urine volume is the only major risk factor and those with enteric hyperoxaluria need specific therapy geared toward dietary measures to reduce oxalate loads. In these cases, allopurinol or thiazide would probably not have any benefit. Although rare, certain genetic conditions associated with stone disease, such as primary hyperoxaluria, can be diagnosed by extreme abnormalities noted on 24-hour urine studies. Early intervention in such conditions can slow disease progression. Urine studies would be diagnostic and extremely helpful for management of patients in only a few situations and show potential flaws in the minimalistic approach recommended by Qaseem and colleagues. Like many disorders, kidney stone disease is complicated with a variable phenotype. The guideline does little to acknowledge or highlight these issues. Current studies indicate that fewer than 10% of persons with kidney stone disease have a full metabolic workup to prevent further stone formation (2). The approach implied by Qaseem and colleagues' guideline will do little to increase the rate of appropriate metabolic evaluations or help to abate the increasing incidence of stone disease in the United States (3). In contrast, the American Urological Association guideline seems to be more balanced and, in general, contain more useful advice for a physician faced with a patient who has recurrent kidney stones. Amy E. Krambeck, MD John C. Lieske, MD Mayo Clinic O’Brien Urology Research Center Rochester, Minnesota Disclosures: Disclosures can be viewed at www.acponline.org /authors/icmje/ConflictOfInterestForms.do?msNum=L15-0049. References 1. Qaseem A, Dallas P, Forciea MA, Starkey M, Denberg TD; Clinical Guidelines Committee of the American College of Physicians. Dietary and pharmacologic management to prevent recurrent nephrolithiasis in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2014;161:659-67. [PMID: 25364887] doi:10.7326/M13-2908 2. Milose JC, Kaufman SR, Hollenbeck BK, Wolf JS Jr, Hollingsworth JM. Prevalence of 24-hour urine collection in high risk stone formers. J Urol. 2014;191: 376-80. [PMID: 24018242] doi:10.1016/j.juro.2013.08.080 3. Scales CD Jr, Smith AC, Hanley JM, Saigal CS; Urologic Diseases in America Project. Prevalence of kidney stones in the United States. Eur Urol. 2012;62: 160-5. [PMID: 22498635] doi:10.1016/j.eururo.2012.03.052
or controls for recurrent stone outcomes. In addition, no randomized, controlled trials compared risk for stone recurrence according to follow-up biochemistry measures or changes from pretreatment biochemistry values. A post hoc analysis of 1 randomized, controlled trial described in the evidence review on which this guideline was based (1) suggested that the benefit of allopurinol treatment was limited to patients with baseline hyperuricemia or hyperuricosuria. However, this finding was the only available evidence from a randomized, controlled trial linking stone biochemistry to recurrent stone outcomes, it was only for 1 drug, and the analysis was done post hoc. As we point out in the guideline, we are aware that many physicians do select medications on the basis of stone type (for example, allopurinol for uric acid stones) and we do not discourage that practice. Drs. Krambeck and Lieske also suggest that the American College of Physicians should have recommended biochemical testing to determine stone type and suggest that such testing is inexpensive and recommended by other organizations. However, as stated previously, the American College of Physicians cannot make an evidence-based recommendation in light of what the studies currently show. Further, just because a test or intervention is inexpensive does not mean that we should do it without evidence, because costs do add up. Amir Qaseem, MD, PhD American College of Physicians Philadelphia, Pennsylvania Howard A. Fink, MD, MPH Minneapolis Veterans Affairs Medical Center Minneapolis, Minnesota Thomas D. Denberg, MD, PhD Carilion Clinic Roanoke, Virginia Disclosures: Disclosures can be viewed at www.acponline.org /authors/icmje/ConflictOfInterestForms.do?msNum=M13-2908. Reference 1. Fink HA, Wilt TJ, Eidman KE, Garimella PS, MacDonald R, Rutks IR, et al. Medical management to prevent recurrent nephrolithiasis in adults: a systematic review for an American College of Physicians Clinical Guideline. Ann Intern Med. 2013;158:535-43. [PMID: 23546565] doi:10.7326/0003-4819-158-7 -201304020-00005
Models in the Development of Clinical Practice Guidelines
IN RESPONSE: Dr. Bell raises an important issue and suggests
TO THE EDITOR: Habbema and colleagues (1) have presented
that the American College of Physicians should offer guidance on what drugs to use under specific circumstances. We acknowledge in the guideline that biochemistry suggests a link between the mode of action of the various drugs and stone type. However, results were mixed about whether baseline biochemistry measures predicted treatment effectiveness for reducing the risk for stone recurrence or for the efficacy of dietary or pharmacologic treatments compared with placebo
a particularly interesting article about the position of models in clinical practice guidelines. Indeed, models can bridge the gap between direct evidence provided from randomized, controlled trials (RCTs) or observational studies and questions raised in daily practice. To estimate the degree that models are used in the development of current guidelines, we evaluated the list of the 100 most cited guidelines of the National Guideline Clearinghouse (www.guideline.gov) that we had
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LETTERS identified for a previous study. The number of citations was extracted from the Thomson Reuters Web of Science (formerly ISI Web of Science). The search of the most cited guidelines was done to select those most influential in clinical practice and research development. Using the results of that search, we did a secondary analysis with a major outcome being the degree of incorporation of mathematical models in guideline justification. Surprisingly, we found that 54% of these guidelines use conclusions derived from modeling studies to support their recommendations. This observed magnitude of models in the development of practice guidelines and their expected growing use in the future raises a need for an objective (to the extent possible) assessment of their merits in terms of internal validity and reproducibility. Habbema and colleagues mention reasonable criteria for the assessment of the credibility of models. However, so far, consensus statements have mostly focused on the quality of presentation and reporting, such as the recently published Consolidated Health Economic Evaluation Reporting Standards checklist for cost-effectiveness studies (2), whereas statements for the assessment of the internal validity of the reporting outcomes, similar to the Cochrane Collaboration tool for RCTs (3) or the Newcastle–Ottawa Scale for observational studies (4), are currently lacking. Furthermore, given that the model on which a guideline is based should be calibrated to every meaningful measurement that is published, there might be a need for a systematic and predefined verification and update of included models at fixed intervals separate from the overall assessment of the guideline. In summary, more than 50% of the examined guidelines of the National Guideline Clearinghouse included results derived from mathematical models to support their recommendations. Admittedly, models can be of substantial help in guiding daily clinical practice about questions that cannot be answered directly by conventional RCTs or observational studies. However, an objective assessment of their internal validity should be established. Otherwise, we risk undermining the high-quality data provided by RCTs. Ioannis M. Zacharioudakis, MD Fainareti N. Zervou, MD Eleftherios Mylonakis, MD, PhD Warren Alpert Medical School of Brown University Providence, Rhode Island Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterest Forms.do?msNum=L15-0055.
References 1. Habbema JD, Wilt TJ, Etzioni R, Nelson HD, Schechter CB, Lawrence WF, et al. Models in the development of clinical practice guidelines. Ann Intern Med. 2014;161:812-8. [PMID: 25437409] doi:10.7326/M14-0845 2. Husereau D, Drummond M, Petrou S, Carswell C, Moher D, Greenberg D, et al; CHEERS Task Force. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. BMJ. 2013;346:f1049. [PMID: 23529982] doi:10.1136/bmj.f1049 3. Higgins JP, Altman DG, Gøtzsche PC, Ju¨ni P, Moher D, Oxman AD, et al; Cochrane Bias Methods Group. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. [PMID: 22008217] doi:10.1136/bmj.d5928
4. Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2014. Accessed at www.ohri.ca/programs/clinical _epidemiology/oxford.asp on 10 December 2014.
IN RESPONSE: We welcome Dr. Zacharioudakis and col-
leagues' comment about the effect of internal validity on model quality and the corresponding guideline. Internal validity, or calibration, refers to successful fitting of the model to the results of primary studies (1). Models with high internal validity are necessary to reliably inform guideline developers. Zacharioudakis and colleagues' statements reaffirm our remark that consensus standards for model quality have not been established. We believe that their suggestion that models should be calibrated to “every meaningful measurement that is published” is not realistic. Given the enormous amount of published meaningful measurements, judgments on data relevance and quality will be required. We believe that calibration should be targeted to the most relevant high-quality data from randomized and observational studies. For example, if a U.S. screening guideline is under consideration, then calibration to U.S. population data might be preferred and could yield different estimates of key model parameters (2). Transparency in how data are selected and incorporated is required; so is identifying plausible alternative calibration targets that can be used for external validation purposes. Zacharioudakis and colleagues suggest using fixed time intervals for updating models. We agree that updating models is important but believe that updates should be based on the emergence of important new data rather than fixed time intervals. For example, after the publication of the results of sigmoidoscopy screening trials, guideline groups and modelers discussed the need for recalibrating colorectal cancer models. These data were too important to delay recalibration. On the other hand, if no crucial new data are published during the preset time interval, waiting can save time and resources without losing guideline relevance. Because many guideline groups do update recommendations on a timederived basis, this practice may alternatively be a pragmatic opportunity to assess the need of a model update. We are encouraged to learn that more than one half of the most cited guidelines incorporated modeling studies. However, of greater importance is determining whether “model use” correlates with our recommended favorable condition for model involvement; namely, that strong primary evidence existed to inform the model but that critical gaps remained between the evidence and the questions that the guideline developers addressed. This circumstance will provide guideline users with increased confidence when implementing model-based guideline recommendations. Irrespective, better internal—and external—model validity will enhance the quality of model results; resulting guidelines; and, ultimately, population health. J. Dik F. Habbema, PhD Erasmus MC University Medical Center Rotterdam, the Netherlands
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LETTERS Timothy J. Wilt, MD, MPH University of Minnesota School of Medicine Minneapolis, Minnesota Ruth Etzioni, PhD Fred Hutchinson Cancer Research Center Seattle, Washington Disclosures: Disclosures can be viewed at www.acponline.org /authors/icmje/ConflictOfInterestForms.do?msNum=M14-0845. References 1. Kopec JA, Fine`s P, Manuel DG, Buckeridge DL, Flanagan WM, Oderkirk J, et al. Validation of population-based disease simulation models: a review of concepts and methods. BMC Public Health. 2010;10:710. [PMID: 21087466] doi:10.1186/1471-2458-10-710 2. Wever EM, Draisma G, Heijnsdijk EA, Roobol MJ, Boer R, Otto SJ, et al. Prostate-specific antigen screening in the United States vs in the European Randomized Study of Screening for Prostate Cancer-Rotterdam. J Natl Cancer Inst. 2010;102:352-5. [PMID: 20142584] doi:10.1093/jnci/djp533
Chikungunya TO THE EDITOR: Hamer and Chen's article (1) failed to men-
tion and address the incidence of chikungunya virus in Puerto Rico, although the Centers for Diseases Control and Prevention eloquently did so in the Morbidity and Mortality Weekly Report (2). The first locally acquired, laboratory-confirmed case of chikungunya virus was detected in Puerto Rico in early May 2014, and 10 201 suspected cases (282 per 100 000 residents) had been reported by 12 August 2014. Certainly, there have been and will be implications locally in terms of public health. However, because of the known shunt between Puerto Rico and the mainland United States, U.S. physicians should become more aware of chikungunya virus when advising someone who will be traveling to Puerto Rico or treating an ill patient who has come from there. William Rodriguez-Cintron, MD Veterans Affairs Caribbean Healthcare System San Juan, Puerto Rico Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterest Forms.do?msNum=L15-0052. References 1. Hamer DH, Chen LH. Chikungunya: establishing a new home in the Western hemisphere. Ann Intern Med. 2014;161:827-8. [PMID: 25244354] doi: 10.7326/M14-1958 2. Sharp TM, Roth NM, Torres J, Ryff KR, Pe´rez Rodrı´guez NM, Mercado C, et al; Centers for Disease Control and Prevention (CDC). Chikungunya cases identified through passive surveillance and household investigations—Puerto Rico, May 5-August 12, 2014. MMWR Morb Mortal Wkly Rep. 2014;63:1121-8. [PMID: 25474032]
TO THE EDITOR: We read Hamer and Chen's article (1) with great interest. However, chronic chikungunya arthritis can persist for months after infection (2, 3). Among 47 travelers returning from the Indian Ocean islands, including Comoros, Mayotte, Mauritius, the Seychelles, and Re´union Island, folwww.annals.org
lowed for 14 months, late (developing after the 10th day) arthropathy— defined by the presence of at least 1 of the following symptoms: symmetric oligo- or polyarthritis accompanied by morning stiffness, nonspecific edema or tenosynovitis, or worsening of mechanical pain in a preexisting injured joint or bone—was identified in 38 persons (2). In another series of 21 cases of newly diagnosed chikungunya virus with a mean follow-up of 2 years, all patients fulfilled the American College of Rheumatology's criteria for rheumatoid arthritis, with symptoms starting from the onset of viral infection to rheumatoid arthritis diagnosis (3). Our department recently treated a patient with confirmed chikungunya virus who returned to Canada and presented with inflammatory polyarthritis after travelling to the Dominican Republic and Jamaica. The patient still had joint pain, 1 of the initial symptoms, after 3 months. We pursued work-up for a connective tissue disease. Initial antinuclear antibody titers were 1:80 in a speckled pattern persisting to 1:160 a month later, and initial anti– double-stranded DNA levels were 38.7 IU/mL; however, results of repeated measurement of anti– double-stranded DNA titers were normal by Farr assay. Rheumatoid factor and anticyclic citrullinated peptide antibodies were not present. Whether the virus can trigger an autoimmune event remains unknown. The mainstay treatment in the acute phase is analgesics or nonsteroidal anti-inflammatory drugs, as Hamer and Chen describe, and allowing some time before considering starting immunosuppressive therapy. However, reports are limited about resolution of symptoms by treating the chronic arthritic phase with hydroxychloroquine, methotrexate, or steroids (3, 4). Research is ongoing on the mechanism of ␣ virus–related arthritis. Some data suggest that the presence of chikungunya in synovial macrophages triggers release of proinflammatory mediators (interleukin-10 and interferon-␣), leading to activation of matrix metalloprotease, induction of apoptosis, and fibroblast hyperplasia. These findings obviously suggest some similarities between the mechanism of chikungunya arthritis and rheumatoid arthritis (5). In conclusion, consider work-up for a connective tissue disease and follow-up in patients with chikungunya virus with prolonged arthralgia, arthritis, or both. Tariq Al-Araimi, MD University of Toronto Toronto, Ontario, Canada Shikha Mittoo, MD, MHS Mount Sinai Hospital and University of Toronto Toronto, Ontario, Canada Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOf InterestForms.do?msNum=L15-0053. References 1. Hamer DH, Chen LH. Chikungunya: establishing a new home in the Western hemisphere. Ann Intern Med. 2014;161:827-8. [PMID: 25244354] doi: 10.7326/M14-1958 2. Simon F, Parola P, Grandadam M, Fourcade S, Oliver M, Brouqui P, et al. Chikungunya infection: an emerging rheumatism among travelers returned from Indian Ocean islands. Report of 47 cases. Medicine (Baltimore). 2007;86: 123-37. [PMID: 17505252] Annals of Internal Medicine • Vol. 162 No. 7 • 7 April 2015 531
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LETTERS 3. Bouquillard E, Combe B. A report of 21 cases of rheumatoid arthritis following Chikungunya fever. A mean follow-up of two years. Joint Bone Spine. 2009;76:654-7. [PMID: 19945329] doi:10.1016/j.jbspin.2009.08.005 4. Chopra A, Anuradha V, Lagoo-Joshi V, Kunjir V, Salvi S, Saluja M. Chikungunya virus aches and pains: an emerging challenge. Arthritis Rheum. 2008;58: 2921-2. [PMID: 18759351] doi:10.1002/art.23753 5. Jaffar-Bandjee MC, Das T, Hoarau JJ, Krejbich Trotot P, Denizot M, Ribera A, et al. Chikungunya virus takes centre stage in virally induced arthritis: possible cellular and molecular mechanisms to pathogenesis. Microbes Infect. 2009;11: 1206-18. [PMID: 19835977] doi:10.1016/j.micinf.2009.10.001
IN RESPONSE: We agree with Dr. Rodriguez-Cintron about the importance of chikungunya virus infections in Puerto Rico. Because of the large numbers of islands and countries affected by this widespread outbreak, our article on chikungunya virus in the Americas was unable to include a comprehensive list of all locations with autochthonous transmission (1); however, the Pan American Health Organization regularly provides updated case numbers and incidence rates for each island and country (2). As of 20 February 2015, Puerto Rico has reported 24 714 suspected and 4302 confirmed cases, with an incidence rate of 787 cases per 100 000 persons. According to the Pan American Health Organization, the chikungunya virus outbreaks in the Dominican Republic and the French part of Saint Martin are even more dramatic, with more than 500 000 suspected cases in the former and an incidence rate of 17 016 cases per 100 000 persons in the latter (2). Because of the high volume of travel between the United States and all infected areas, it is imperative that we raise the awareness of clinicians practicing in the contiguous United States about chikungunya virus in the Americas—all Caribbean islands and most countries in Central and South America. We appreciate Drs. Al-Araimi and Mittoo's comments about the similarity in presentation between chikungunya arthritis and rheumatoid arthritis and their recommendation that work-up is warranted for connective tissue disease in patients diagnosed with chikungunya virus who have persistent or recurrent arthritis. After the chikungunya virus epidemic in La Re´union in 2005, a cohort study of 147 patients with chikungunya virus found that 57% reported rheumatic symptoms at 15 months (nearly two thirds with persistent symptoms and one third with recurrent or relapsing symptoms) (3). These findings are similar to those of the patient that Drs. Al-Araimi and Mittoo describe. As Drs. Al-Araimi and Mittoo note, whether chikungunya virus triggers an autoimmune process is not yet known; however, some immunologic findings suggest inflammatory mechanisms (4). In patients with chikungunya virus who are later diagnosed with rheumatoid arthritis, the usefulness of therapy with disease-modifying antirheumatic drugs—such as methotrexate, tumor necrosis factor blockers, hydroxychloroquine, and corticosteroids— has not yet been established (5). Finally, because patients with persistent or relapsing arthralgia or arthritis may present to rheumatologists and primary care providers for evaluation, specialists should remain vigilant about assessing for chikungunya virus. Longitudinal natural history studies and randomized, controlled trials of inter-
ventions for patients with this condition who have persistent arthritis are critically needed. Davidson H. Hamer, MD Center for Global Health and Development, Boston University School of Public Health Boston, Massachusetts Lin H. Chen, MD Mount Auburn Hospital Cambridge, Massachusetts Disclosures: Disclosures can be viewed at www.acponline.org /authors/icmje/ConflictOfInterestForms.do?msNum=M14-1958. References 1. Hamer DH, Chen LH. Chikungunya: establishing a new home in the Western hemisphere. Ann Intern Med. 2014;161:827-8. [PMID: 25244354] doi: 10.7326/M14-1958 2. Pan American Health Organization; World Health Organization. Chikungunya. 2015. Accessed at www.paho.org/hq/index.php?Itemid=40931 on 25 February 2015. 3. Sissoko D, Malvy D, Ezzedine K, Renault P, Moscetti F, Ledrans M, et al. Post-epidemic Chikungunya disease on Reunion Island: course of rheumatic manifestations and associated factors over a 15-month period. PLoS Negl Trop Dis. 2009;3:e389. [PMID: 19274071] doi:10.1371/journal.pntd.0000389 4. Roques P, Gras G. Chikungunya fever: focus on peripheral markers of pathogenesis [Editorial]. J Infect Dis. 2011;203:141-3. [PMID: 21288810] doi: 10.1093/infdis/jiq026 5. Simon F, Javelle E, Oliver M, Leparc-Goffart I, Marimoutou C. Chikungunya virus infection. Curr Infect Dis Rep. 2011;13:218-28. [PMID: 21465340] doi: 10.1007/s11908-011-0180-1
CORRECTION Correction: Inviting Patients to Read Their Doctors' Notes A recent article (1) included an error in the number of patients from Geisinger Health System (GHS) who viewed 1 or more available notes. A total of 4795 patients at GHS viewed 1 or more available notes, not 5437 as originally reported. Therefore, 82% (not 92%) of GHS patients opened at least 1 note, 59% (not 87%) opened all of their notes, and 82% (not 90%) of patients at all 3 sites opened at least 1 note. A total of 11 155 (not 11 797) of 13 564 patients with visit notes available opened at least 1 note, and 5219 (not 5391) patients opened at least 1 note and completed a postintervention survey. This led to corrections in the Abstract, Results, and Discussion and Appendix Figure 2 and Appendix Table 1. These corrections do not materially affect the conclusions. This has been changed in the online version. Reference 1. Delbanco T, Walker J, Bell SK, Darer JD, Elmore JG, Farag N, et al. Inviting patients to read their doctors' notes: a quasi-experimental study and a look ahead. Ann Intern Med. 2012;157:461-70. [PMID: 23027317] doi:10.7326/ 0003-4819-157-7-201210020-00002
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Genetic and Environmental Risk Assessment and Colorectal Cancer Screening TO THE EDITOR: Weinberg and colleagues' article (1) high-
lights the complexities of using genetic polymorphisms and their associated cancer risk to encourage lifestyle modifications. The study attempts to consider risks, benefits, and potential barriers to personalized medicine and associated patient and provider uptake. The authors discuss their rationale for using trained nurses in lieu of genetic counselors, stating that the number of genetic counselors seems inadequate to meet health service needs even in high-risk settings, citing a reference from 1990 (2) that does not reflect current data. Currently, there are more than 4000 certified genetic counselors in the United States, all of whom are trained to provide a cancer genetics consult and approximately 30% of whom report cancer genetics as their primary specialty (3). The certified genetic counselor workforce has increased by 75% since 2006. Annual growth in the profession is trending upward of 7% to 10%; this finding partially reflects the increase in the number and capacity of training programs as we prepare for future needs. Recently, genetic counselors were cited in the “Top 10 Fastest-Growing Careers” (4). According to the U.S. Bureau of Labor Statistics, the genetic counseling profession is predicted to increase 41% by the end of 2022, a rate much faster than that of other health care professions (5, 6). Access to certified genetic counselors is excellent. Approximately one half of respondents to the National Society of Genetic Counselors' 2014 Professional Status Survey report availability for a new patient consultation within 1 week (3). Alternative genetic service methods, including video or telephone genetic counseling, increase access to patients in underserved areas. A directory of genetic counselors is available at www.nsgc.org. The authors state that “a lack of familiarity with genomics on the part of patients (and providers) has been cited as a concern limiting the effect of genetic testing.” This “lack of familiarity” and the mounting complexity of genetic and genomic testing highlight the importance of collaboration between genetics and genomics and medical specialties. The National Society of Genetic Counselors welcomes opportunities to partner with health care organizations to provide genetics and genomics education. Genetic counselors are essential members of the health care team and work with our physician partners to provide counseling, enhance overall patient care, accelerate educational opportunities for clinicians, and facilitate appropriate utilization of genetic services and testing to ensure sound medical management and decision making. The National Society of Genetic Counselors suggests that health care organizations and providers unfamiliar with genetic services work with genetic counselors to ensure delivery of high-quality genetic services to patients.
Annals of Internal Medicine Sara M. Pirzadeh-Miller, MS University of Texas Southwestern Medical Center Dallas, Texas Victoria M. Raymond, MS University of Michigan Ann Arbor, Michigan Sara Knapke, MS Cincinnati Children's Hospital Cincinnati, Ohio Disclosures: Disclosures can be viewed at www.acponline.org /authors/icmje/ConflictOfInterestForms.do?msNum=L15-0019. References 1. Weinberg DS, Myers RE, Keenan E, Ruth K, Sifri R, Ziring B, et al. Genetic and environmental risk assessment and colorectal cancer screening in an averagerisk population: a randomized trial. Ann Intern Med. 2014;161:537-45. [PMID: 25329201] doi:10.7326/M14-0765 2. Wilfond BS, Fost N. The cystic fibrosis gene: medical and social implications for heterozygote detection. JAMA. 1990;263:2777-83. [PMID: 11653890] 3. National Society of Genetic Counselors. NSGC Professional Status Survey 2014. Chicago: National Society of Genetic Counselors; 2014. 4. AllHealthcare. 10 best healthcare jobs with a master's degree: genetic counselor. 2014. Accessed at http://allhealthcare.monster.com/careers/articles /3125-10-best-healthcare-jobs-with-a-masters-degree?page=11 on 19 November 2014. 5. Weintraub A. Study a hot concentration today for a future health care job. U.S. News & World Report. 19 March 2014. Accessed at www.usnews .com/education/best-graduate-schools/articles/2014/03/19/study-a-hot -concentration-today-for-a-future-health-care-job on 19 November 2014. 6. Dorfman M. Six-figure jobs: genetic counselors earn up to $250K. AOL Jobs. 10 November 2014. Accessed at http://jobs.aol.com/articles/2014/11/10/six -figure-jobs-genetic-counselors-earn-up-to-250k on 9 November 2014.
TO THE EDITOR: Although Weinberg and colleagues' study
(1) is interesting and well-done, the negative results are not surprising. Among several possibilities for these results are the time frame for estimating risk for colorectal cancer (CRC), the magnitude of the risk, the 6-month interval for assessing screening uptake, and whether the genetic and environmental risk assessment had meaning to study participants. With regard to the time frame for CRC risk, it seems that study participants were told about their lifetime risk for this condition. Knowing about lifetime CRC risk may motivate persons or patients less—particularly in the short term (6 months or perhaps 1 year)—than would knowing about a current or near-term risk. In general, persons want to know what they need to do now or in the near term in response to learning about “risk.” Because CRC prevalence is so low and advanced precancerous polyps have become the target lesion of screening, telling persons about their current risk for advanced neoplasia (that is, the combination of CRC and advanced polyps) could result in screening uptake sooner and to a greater degree or extent than telling them their lifetime CRC risk (a future risk). The perception of a low magnitude of risk may be another reason for inaction in the short term. Average lifetime risk for CRC is approximately 5% (or 1 in 20). Even if the genetic and environmental risk assessment suggests a doubling of lifetime risk, that risk is still just 10%, which many would
526 © 2015 American College of Physicians
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LETTERS interpret as having a 90% chance of not getting CRC. This interpretation supports inertia to avoid screening, especially in the short term. In contrast, telling persons that they have a 20% to 25% (1 in 4 or 1 in 5) chance of having an advanced, precancerous polyp present “now” (because of several phenotypic features) may be a greater motivator to get screened in the short term. Given a future risk for CRC—whether elevated or not—allowing just 6 months to assess screening uptake likely contributed to the negative results. Finally, whether persons understand and accept the results of genetic and environmental risk assessment may be questioned. Persons can probably comprehend and relate better to older age, male sex, cigarette smoking, a family history of CRC, overweight status, and other phenotypic features as risk factors than they can to polymorphic variants of methylenetetrahydrofolate reductase and low serum folate levels as increasing their risk for CRC and, thus, as motivators toward CRC screening. Thomas F. Imperiale, MD Indiana University Medical Center, Regenstrief Institute, and Roudebush Veterans Affairs Medical Center Indianapolis, Indiana Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOf InterestForms.do?msNum=L15-0020.
protocol at our institutions (4). Nursing staff has favored this delirium screening tool because of its short administration time and ease of use. The ability to quickly train nurses to use it has also been viewed as an advantage. However, the NuDESC is not perfect and problems with accuracy of assessment by nurses despite high accuracy by investigators have been reported (5). In our experience, for a delirium screening test to accepted by nurses, it must be quick and accurate and perceived as valuable. The difference between 1 minute and 3 minutes can become quite important when applied to multiple patients cared for during each shift. If the delirium assessment tool does not have workflow efficiency, then sustainability of its use is jeopardized. The Nu-DESC should be considered for broader clinical use in hospitals and should certainly be considered in any future comparative research trials. Rex Wilford, DO, RPh Sue Fosnight, RPh, CGP, BCPS Summa Health System Akron, Ohio Kyle Allen, DO Riverside Health System Newport News, Virginia Disclosures: Authors have disclosed no conflicts of interest. Forms
Reference 1. Weinberg DS, Myers RE, Keenan E, Ruth K, Sifri R, Ziring B, et al. Genetic and environmental risk assessment and colorectal cancer screening in an averagerisk population: a randomized trial. Ann Intern Med. 2014;161:537-45. [PMID: 25329201] doi:10.7326/M14-0765
3D-CAM TO THE EDITOR: We read Marcantonio and colleagues' article
(1) with great interest. The early recognition of delirium across all hospital settings is an important factor in patient safety and care. Nurses caring for patients have the best opportunity to recognize a disorder that fluctuates over time, such as this condition. The ultimate goal of having a brief and accurate tool to aid nurses in the early detection of delirium without adding excess burden to ever-increasing nurse charting time is important. Marcantonio and colleagues did, indeed, show that the 3D-CAM (3D-Confusion Assessment Method) decreases the time to complete delirium assessment to 3 minutes while maintaining high sensitivity and specificity. In the Discussion section, the authors comment, “We currently have no brief instrument that is well-suited for widespread use across clinical settings.” We argue that the Nursing Delirium Screening Scale (Nu-DESC) is such an instrument. This tool is an observational, 5-item delirium screening scale that can be completed in approximately 1 minute (2). When studied in medical (2), surgical (3), and intensive care units, the Nu-DESC took less time and had clinically similar sensitivity and specificity to other instruments, such as the CAM, and showed efficacy in identification of hypoactive delirium. The Nu-DESC has been successfully implemented hospital-wide among medical–surgical patients as a major part of a delirium www.annals.org
can be viewed at www.acponline.org/authors/icmje/ConflictOf InterestForms.do?msNum=L15-0018.
References 1. Marcantonio ER, Ngo LH, O’Connor M, Jones RN, Crane PK, Metzger ED, et al. 3D-CAM: derivation and validation of a 3-minute diagnostic interview for CAM-defined delirium: a cross-sectional diagnostic test study. Ann Intern Med. 2014;161:554-61. [PMID: 25329203] doi:10.7326/M14-0865 2. Gaudreau JD, Gagnon P, Harel F, Tremblay A, Roy MA. Fast, systematic, and continuous delirium assessment in hospitalized patients: the nursing delirium screening scale. J Pain Symptom Manage. 2005;29:368-75. [PMID: 15857740] 3. Radtke FM, Franck M, Schust S, Boehme L, Pascher A, Bail HJ, et al. A comparison of three scores to screen for delirium on the surgical ward. World J Surg. 2010;34:487-94. [PMID: 20066416] doi:10.1007/s00268-009-0376-9 4. Allen KR, Fosnight SM, Wilford R, Benedict LM, Sabo A, Holder C, et al. Implementation of a system-wide quality improvement project to prevent delirium in hospitalized patients. J Clin Outcomes Manag. 2011;18:253-8. 5. Solberg LM, Plummer CE, May KN, Mion LC. A quality improvement program to increase nurses' detection of delirium on an acute medical unit. Geriatr Nurs. 2013;34:75-9. [PMID: 23614146]
IN RESPONSE: Dr. Wilford and colleagues describe their experience with the Nu-DESC (1), a brief delirium screening instrument that assesses 5 features: disorientation, inappropriate behavior, inappropriate communication, illusions/hallucinations, and psychomotor retardation. Each feature is rated 0, 1, or 2, and a total score of 2 or higher out of 10 is considered a positive screen for delirium. Of note, Nu-DESC scoring is based on routine nursing observations and requires no formal interviewing or cognitive testing. Therefore, it can be completed very quickly—in 1 minute or less. In the references that Dr. Wilford and colleagues provide, this tool has excellent test characteristics relative to a reference standard. However, Annals of Internal Medicine • Vol. 162 No. 7 • 7 April 2015 527
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LETTERS other publications report worse performance; for example, a recent study of surgical patients reported sensitivities between 29% and 32% (2), indicating that 7 of 10 cases of delirium were missed. The key to delirium assessment is the quality of data that go into determining the presence or absence of core diagnostic features of delirium. In modern hospital care, physicians and nurses do not routinely interact with patients in ways that reliably elicit delirium features. For example, when the CAM algorithm was completed by nurses solely on the basis of observations from routine care, its sensitivity was 30% relative to a reference standard (3). Information provided by structured testing is essential, particularly for patients with hypoactive delirium. The 3D-CAM incorporates patient symptom probes (such as “Have you felt confused today?”) and cognitive testing (such as stating the days of the week backward) in addition to observational items. Structured testing enhances sensitivity so that cases will not be missed, ensures that all key features of delirium are assessed, and enhances reliability by collecting a uniform set of data. It also provides an objective measure of cognitive function that facilitates assessment of change in future days. Defining a brief yet informative set of cognitive items is a key contribution of the 3D-CAM. The 3D-CAM, when administered in full, can be completed in 3 minutes. Using skip patterns or up-front screening items may shorten the 3D-CAM further while retaining excellent performance. Our group is actively developing and testing methods to enhance the feasibility of delirium identification in clinical practice. For the time being, we urge clinicians to incorporate structured testing, such as the items in the 3DCAM, into their routine assessment of delirium.
should be used to avoid a recurrence of nephrolithiasis. If hypercalciuria is present, thiazide diuretics obviously should be used. However, use of thiazides in the presence of uricosuria may be counterproductive. Allopurinol should be used with uricosuria, but allopurinol and citrates also may be successfully used in the absence of hypercalciuria or uricosuria. Obese patients with type 2 diabetes frequently have acidic urine due to hyperinsulinemia, inducing a decrease in ammonia production in the proximal tubule and sodium clearance. The resulting lower urine pH can cause uric acid to “come out” of solution and crystallize (2). Although most calculi in obese participants with type 2 diabetes are composed of calcium oxylate, the proportion of uric acid stones is higher than in control participants (35.8% vs. 11.3%) (3). Normal uric acid excretion is less than 800 mg/d, but uric acid can crystallize at levels as low as 200 mg/day in the presence of acidic urine. In this situation, the most effective therapies to prevent stone formation are allopurinol to reduce uricosuria and citrates to neutralize the acidic urine. In the absence of an analysis of a previous stone or hypercalciuria, a low urine pH should suggest that therapy with allopurinol, a citrate, or both will decrease the formation of calculi (4).
Edward R. Marcantonio, MD, SM Beth Israel Deaconess Medical Center Boston, Massachusetts
1. Qaseem A, Dallas P, Forciea MA, Starkey M, Denberg TD; Clinical Guidelines Committee of the American College of Physicians. Dietary and pharmacologic management to prevent recurrent nephrolithiasis in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2014;161:659-67. [PMID: 25364887] doi:10.7326/M13-2908 2. Sakhaee K, Adams-Huet B, Moe OW, Pak CY. Pathophysiologic basis for normouricosuric uric acid nephrolithiasis. Kidney Int. 2002;62:971-9. [PMID: 12164880] 3. Daudon M, Traxer O, Conort P, Lacour B, Jungers P. Type 2 diabetes increases the risk for uric acid stones. J Am Soc Nephrol. 2006;17:2026-33. [PMID: 16775030] 4. Bell DS. Beware the low urine pH—the major cause of the increased prevalence of nephrolithiasis in the patient with type 2 diabetes. Diabetes Obes Metab. 2012;14:299-303. [PMID: 21992452] doi:10.1111/j.1463-1326 .2011.01519.x
David S.H. Bell, MD Southside Endocrinology Mountain Brook, Alabama Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOf InterestForms.do?msNum=L15-0050. References
Sharon K. Inouye, MD MPH Hebrew SeniorLife Boston, Massachusetts Disclosures: Disclosures can be viewed at www.acponline.org /authors/icmje/ConflictOfInterestForms.do?msNum=M14-0865. References 1. Gaudreau JD, Gagnon P, Harel F, Tremblay A, Roy MA. Fast, systematic, and continuous delirium assessment in hospitalized patients: the nursing delirium screening scale. J Pain Symptom Manage. 2005;29:368-75. [PMID: 15857740] 2. Neufeld KJ, Leoutsakos JS, Sieber FE, Joshi D, Wanamaker BL, Rios-Robles J, et al. Evaluation of two delirium screening tools for detecting post-operative delirium in the elderly. Br J Anaesth. 2013;111:612-8. [PMID: 23657522] doi: 10.1093/bja/aet167 3. Inouye SK, Foreman MD, Mion LC, Katz KH, Cooney LM Jr. Nurses' recognition of delirium and its symptoms: comparison of nurse and researcher ratings. Arch Intern Med. 2001;161:2467-73. [PMID: 11700159]
Prevention of Recurrent Nephrolithiasis in Adults TO THE EDITOR: Qaseem and colleagues (1) did not indicate under what circumstances citrates, thiazides, or allopurinol
TO THE EDITOR: Qaseem and colleagues' (1) recommenda-
tion to drink at least 2 L of fluid per day and use thiazide diuretics, citrate, or allopurinol when fluids alone are insufficient mirror a recent guideline released by the American Urological Association. However, several features of the American College of Physicians' recommendations disagree with those of the American Urological Association. For example, Qaseem and colleagues do not recommend baseline evaluation of stone composition or 24-hour urine analysis for stone risk factors. Kidney stone analysis by infrared spectroscopy is relatively inexpensive; very precise; and, in our opinion, essential to properly diagnose the form of kidney stone disease. A thi-
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LETTERS azide diuretic would not be helpful for a patient with uric acid kidney stones or someone with cystinuria, both of which can be determined by stone analysis alone. Furthermore, 24-hour urine analysis can help to guide logical therapeutic choices and specific dietary advice for an individual patient. For example, pharmacotherapy may not help persons in whom a very low urine volume is the only major risk factor and those with enteric hyperoxaluria need specific therapy geared toward dietary measures to reduce oxalate loads. In these cases, allopurinol or thiazide would probably not have any benefit. Although rare, certain genetic conditions associated with stone disease, such as primary hyperoxaluria, can be diagnosed by extreme abnormalities noted on 24-hour urine studies. Early intervention in such conditions can slow disease progression. Urine studies would be diagnostic and extremely helpful for management of patients in only a few situations and show potential flaws in the minimalistic approach recommended by Qaseem and colleagues. Like many disorders, kidney stone disease is complicated with a variable phenotype. The guideline does little to acknowledge or highlight these issues. Current studies indicate that fewer than 10% of persons with kidney stone disease have a full metabolic workup to prevent further stone formation (2). The approach implied by Qaseem and colleagues' guideline will do little to increase the rate of appropriate metabolic evaluations or help to abate the increasing incidence of stone disease in the United States (3). In contrast, the American Urological Association guideline seems to be more balanced and, in general, contain more useful advice for a physician faced with a patient who has recurrent kidney stones. Amy E. Krambeck, MD John C. Lieske, MD Mayo Clinic O’Brien Urology Research Center Rochester, Minnesota Disclosures: Disclosures can be viewed at www.acponline.org /authors/icmje/ConflictOfInterestForms.do?msNum=L15-0049. References 1. Qaseem A, Dallas P, Forciea MA, Starkey M, Denberg TD; Clinical Guidelines Committee of the American College of Physicians. Dietary and pharmacologic management to prevent recurrent nephrolithiasis in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2014;161:659-67. [PMID: 25364887] doi:10.7326/M13-2908 2. Milose JC, Kaufman SR, Hollenbeck BK, Wolf JS Jr, Hollingsworth JM. Prevalence of 24-hour urine collection in high risk stone formers. J Urol. 2014;191: 376-80. [PMID: 24018242] doi:10.1016/j.juro.2013.08.080 3. Scales CD Jr, Smith AC, Hanley JM, Saigal CS; Urologic Diseases in America Project. Prevalence of kidney stones in the United States. Eur Urol. 2012;62: 160-5. [PMID: 22498635] doi:10.1016/j.eururo.2012.03.052
or controls for recurrent stone outcomes. In addition, no randomized, controlled trials compared risk for stone recurrence according to follow-up biochemistry measures or changes from pretreatment biochemistry values. A post hoc analysis of 1 randomized, controlled trial described in the evidence review on which this guideline was based (1) suggested that the benefit of allopurinol treatment was limited to patients with baseline hyperuricemia or hyperuricosuria. However, this finding was the only available evidence from a randomized, controlled trial linking stone biochemistry to recurrent stone outcomes, it was only for 1 drug, and the analysis was done post hoc. As we point out in the guideline, we are aware that many physicians do select medications on the basis of stone type (for example, allopurinol for uric acid stones) and we do not discourage that practice. Drs. Krambeck and Lieske also suggest that the American College of Physicians should have recommended biochemical testing to determine stone type and suggest that such testing is inexpensive and recommended by other organizations. However, as stated previously, the American College of Physicians cannot make an evidence-based recommendation in light of what the studies currently show. Further, just because a test or intervention is inexpensive does not mean that we should do it without evidence, because costs do add up. Amir Qaseem, MD, PhD American College of Physicians Philadelphia, Pennsylvania Howard A. Fink, MD, MPH Minneapolis Veterans Affairs Medical Center Minneapolis, Minnesota Thomas D. Denberg, MD, PhD Carilion Clinic Roanoke, Virginia Disclosures: Disclosures can be viewed at www.acponline.org /authors/icmje/ConflictOfInterestForms.do?msNum=M13-2908. Reference 1. Fink HA, Wilt TJ, Eidman KE, Garimella PS, MacDonald R, Rutks IR, et al. Medical management to prevent recurrent nephrolithiasis in adults: a systematic review for an American College of Physicians Clinical Guideline. Ann Intern Med. 2013;158:535-43. [PMID: 23546565] doi:10.7326/0003-4819-158-7 -201304020-00005
Models in the Development of Clinical Practice Guidelines
IN RESPONSE: Dr. Bell raises an important issue and suggests
TO THE EDITOR: Habbema and colleagues (1) have presented
that the American College of Physicians should offer guidance on what drugs to use under specific circumstances. We acknowledge in the guideline that biochemistry suggests a link between the mode of action of the various drugs and stone type. However, results were mixed about whether baseline biochemistry measures predicted treatment effectiveness for reducing the risk for stone recurrence or for the efficacy of dietary or pharmacologic treatments compared with placebo
a particularly interesting article about the position of models in clinical practice guidelines. Indeed, models can bridge the gap between direct evidence provided from randomized, controlled trials (RCTs) or observational studies and questions raised in daily practice. To estimate the degree that models are used in the development of current guidelines, we evaluated the list of the 100 most cited guidelines of the National Guideline Clearinghouse (www.guideline.gov) that we had
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LETTERS identified for a previous study. The number of citations was extracted from the Thomson Reuters Web of Science (formerly ISI Web of Science). The search of the most cited guidelines was done to select those most influential in clinical practice and research development. Using the results of that search, we did a secondary analysis with a major outcome being the degree of incorporation of mathematical models in guideline justification. Surprisingly, we found that 54% of these guidelines use conclusions derived from modeling studies to support their recommendations. This observed magnitude of models in the development of practice guidelines and their expected growing use in the future raises a need for an objective (to the extent possible) assessment of their merits in terms of internal validity and reproducibility. Habbema and colleagues mention reasonable criteria for the assessment of the credibility of models. However, so far, consensus statements have mostly focused on the quality of presentation and reporting, such as the recently published Consolidated Health Economic Evaluation Reporting Standards checklist for cost-effectiveness studies (2), whereas statements for the assessment of the internal validity of the reporting outcomes, similar to the Cochrane Collaboration tool for RCTs (3) or the Newcastle–Ottawa Scale for observational studies (4), are currently lacking. Furthermore, given that the model on which a guideline is based should be calibrated to every meaningful measurement that is published, there might be a need for a systematic and predefined verification and update of included models at fixed intervals separate from the overall assessment of the guideline. In summary, more than 50% of the examined guidelines of the National Guideline Clearinghouse included results derived from mathematical models to support their recommendations. Admittedly, models can be of substantial help in guiding daily clinical practice about questions that cannot be answered directly by conventional RCTs or observational studies. However, an objective assessment of their internal validity should be established. Otherwise, we risk undermining the high-quality data provided by RCTs. Ioannis M. Zacharioudakis, MD Fainareti N. Zervou, MD Eleftherios Mylonakis, MD, PhD Warren Alpert Medical School of Brown University Providence, Rhode Island Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterest Forms.do?msNum=L15-0055.
References 1. Habbema JD, Wilt TJ, Etzioni R, Nelson HD, Schechter CB, Lawrence WF, et al. Models in the development of clinical practice guidelines. Ann Intern Med. 2014;161:812-8. [PMID: 25437409] doi:10.7326/M14-0845 2. Husereau D, Drummond M, Petrou S, Carswell C, Moher D, Greenberg D, et al; CHEERS Task Force. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. BMJ. 2013;346:f1049. [PMID: 23529982] doi:10.1136/bmj.f1049 3. Higgins JP, Altman DG, Gøtzsche PC, Ju¨ni P, Moher D, Oxman AD, et al; Cochrane Bias Methods Group. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. [PMID: 22008217] doi:10.1136/bmj.d5928
4. Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2014. Accessed at www.ohri.ca/programs/clinical _epidemiology/oxford.asp on 10 December 2014.
IN RESPONSE: We welcome Dr. Zacharioudakis and col-
leagues' comment about the effect of internal validity on model quality and the corresponding guideline. Internal validity, or calibration, refers to successful fitting of the model to the results of primary studies (1). Models with high internal validity are necessary to reliably inform guideline developers. Zacharioudakis and colleagues' statements reaffirm our remark that consensus standards for model quality have not been established. We believe that their suggestion that models should be calibrated to “every meaningful measurement that is published” is not realistic. Given the enormous amount of published meaningful measurements, judgments on data relevance and quality will be required. We believe that calibration should be targeted to the most relevant high-quality data from randomized and observational studies. For example, if a U.S. screening guideline is under consideration, then calibration to U.S. population data might be preferred and could yield different estimates of key model parameters (2). Transparency in how data are selected and incorporated is required; so is identifying plausible alternative calibration targets that can be used for external validation purposes. Zacharioudakis and colleagues suggest using fixed time intervals for updating models. We agree that updating models is important but believe that updates should be based on the emergence of important new data rather than fixed time intervals. For example, after the publication of the results of sigmoidoscopy screening trials, guideline groups and modelers discussed the need for recalibrating colorectal cancer models. These data were too important to delay recalibration. On the other hand, if no crucial new data are published during the preset time interval, waiting can save time and resources without losing guideline relevance. Because many guideline groups do update recommendations on a timederived basis, this practice may alternatively be a pragmatic opportunity to assess the need of a model update. We are encouraged to learn that more than one half of the most cited guidelines incorporated modeling studies. However, of greater importance is determining whether “model use” correlates with our recommended favorable condition for model involvement; namely, that strong primary evidence existed to inform the model but that critical gaps remained between the evidence and the questions that the guideline developers addressed. This circumstance will provide guideline users with increased confidence when implementing model-based guideline recommendations. Irrespective, better internal—and external—model validity will enhance the quality of model results; resulting guidelines; and, ultimately, population health. J. Dik F. Habbema, PhD Erasmus MC University Medical Center Rotterdam, the Netherlands
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LETTERS Timothy J. Wilt, MD, MPH University of Minnesota School of Medicine Minneapolis, Minnesota Ruth Etzioni, PhD Fred Hutchinson Cancer Research Center Seattle, Washington Disclosures: Disclosures can be viewed at www.acponline.org /authors/icmje/ConflictOfInterestForms.do?msNum=M14-0845. References 1. Kopec JA, Fine`s P, Manuel DG, Buckeridge DL, Flanagan WM, Oderkirk J, et al. Validation of population-based disease simulation models: a review of concepts and methods. BMC Public Health. 2010;10:710. [PMID: 21087466] doi:10.1186/1471-2458-10-710 2. Wever EM, Draisma G, Heijnsdijk EA, Roobol MJ, Boer R, Otto SJ, et al. Prostate-specific antigen screening in the United States vs in the European Randomized Study of Screening for Prostate Cancer-Rotterdam. J Natl Cancer Inst. 2010;102:352-5. [PMID: 20142584] doi:10.1093/jnci/djp533
Chikungunya TO THE EDITOR: Hamer and Chen's article (1) failed to men-
tion and address the incidence of chikungunya virus in Puerto Rico, although the Centers for Diseases Control and Prevention eloquently did so in the Morbidity and Mortality Weekly Report (2). The first locally acquired, laboratory-confirmed case of chikungunya virus was detected in Puerto Rico in early May 2014, and 10 201 suspected cases (282 per 100 000 residents) had been reported by 12 August 2014. Certainly, there have been and will be implications locally in terms of public health. However, because of the known shunt between Puerto Rico and the mainland United States, U.S. physicians should become more aware of chikungunya virus when advising someone who will be traveling to Puerto Rico or treating an ill patient who has come from there. William Rodriguez-Cintron, MD Veterans Affairs Caribbean Healthcare System San Juan, Puerto Rico Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterest Forms.do?msNum=L15-0052. References 1. Hamer DH, Chen LH. Chikungunya: establishing a new home in the Western hemisphere. Ann Intern Med. 2014;161:827-8. [PMID: 25244354] doi: 10.7326/M14-1958 2. Sharp TM, Roth NM, Torres J, Ryff KR, Pe´rez Rodrı´guez NM, Mercado C, et al; Centers for Disease Control and Prevention (CDC). Chikungunya cases identified through passive surveillance and household investigations—Puerto Rico, May 5-August 12, 2014. MMWR Morb Mortal Wkly Rep. 2014;63:1121-8. [PMID: 25474032]
TO THE EDITOR: We read Hamer and Chen's article (1) with great interest. However, chronic chikungunya arthritis can persist for months after infection (2, 3). Among 47 travelers returning from the Indian Ocean islands, including Comoros, Mayotte, Mauritius, the Seychelles, and Re´union Island, folwww.annals.org
lowed for 14 months, late (developing after the 10th day) arthropathy— defined by the presence of at least 1 of the following symptoms: symmetric oligo- or polyarthritis accompanied by morning stiffness, nonspecific edema or tenosynovitis, or worsening of mechanical pain in a preexisting injured joint or bone—was identified in 38 persons (2). In another series of 21 cases of newly diagnosed chikungunya virus with a mean follow-up of 2 years, all patients fulfilled the American College of Rheumatology's criteria for rheumatoid arthritis, with symptoms starting from the onset of viral infection to rheumatoid arthritis diagnosis (3). Our department recently treated a patient with confirmed chikungunya virus who returned to Canada and presented with inflammatory polyarthritis after travelling to the Dominican Republic and Jamaica. The patient still had joint pain, 1 of the initial symptoms, after 3 months. We pursued work-up for a connective tissue disease. Initial antinuclear antibody titers were 1:80 in a speckled pattern persisting to 1:160 a month later, and initial anti– double-stranded DNA levels were 38.7 IU/mL; however, results of repeated measurement of anti– double-stranded DNA titers were normal by Farr assay. Rheumatoid factor and anticyclic citrullinated peptide antibodies were not present. Whether the virus can trigger an autoimmune event remains unknown. The mainstay treatment in the acute phase is analgesics or nonsteroidal anti-inflammatory drugs, as Hamer and Chen describe, and allowing some time before considering starting immunosuppressive therapy. However, reports are limited about resolution of symptoms by treating the chronic arthritic phase with hydroxychloroquine, methotrexate, or steroids (3, 4). Research is ongoing on the mechanism of ␣ virus–related arthritis. Some data suggest that the presence of chikungunya in synovial macrophages triggers release of proinflammatory mediators (interleukin-10 and interferon-␣), leading to activation of matrix metalloprotease, induction of apoptosis, and fibroblast hyperplasia. These findings obviously suggest some similarities between the mechanism of chikungunya arthritis and rheumatoid arthritis (5). In conclusion, consider work-up for a connective tissue disease and follow-up in patients with chikungunya virus with prolonged arthralgia, arthritis, or both. Tariq Al-Araimi, MD University of Toronto Toronto, Ontario, Canada Shikha Mittoo, MD, MHS Mount Sinai Hospital and University of Toronto Toronto, Ontario, Canada Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOf InterestForms.do?msNum=L15-0053. References 1. Hamer DH, Chen LH. Chikungunya: establishing a new home in the Western hemisphere. Ann Intern Med. 2014;161:827-8. [PMID: 25244354] doi: 10.7326/M14-1958 2. Simon F, Parola P, Grandadam M, Fourcade S, Oliver M, Brouqui P, et al. Chikungunya infection: an emerging rheumatism among travelers returned from Indian Ocean islands. Report of 47 cases. Medicine (Baltimore). 2007;86: 123-37. [PMID: 17505252] Annals of Internal Medicine • Vol. 162 No. 7 • 7 April 2015 531
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LETTERS 3. Bouquillard E, Combe B. A report of 21 cases of rheumatoid arthritis following Chikungunya fever. A mean follow-up of two years. Joint Bone Spine. 2009;76:654-7. [PMID: 19945329] doi:10.1016/j.jbspin.2009.08.005 4. Chopra A, Anuradha V, Lagoo-Joshi V, Kunjir V, Salvi S, Saluja M. Chikungunya virus aches and pains: an emerging challenge. Arthritis Rheum. 2008;58: 2921-2. [PMID: 18759351] doi:10.1002/art.23753 5. Jaffar-Bandjee MC, Das T, Hoarau JJ, Krejbich Trotot P, Denizot M, Ribera A, et al. Chikungunya virus takes centre stage in virally induced arthritis: possible cellular and molecular mechanisms to pathogenesis. Microbes Infect. 2009;11: 1206-18. [PMID: 19835977] doi:10.1016/j.micinf.2009.10.001
IN RESPONSE: We agree with Dr. Rodriguez-Cintron about the importance of chikungunya virus infections in Puerto Rico. Because of the large numbers of islands and countries affected by this widespread outbreak, our article on chikungunya virus in the Americas was unable to include a comprehensive list of all locations with autochthonous transmission (1); however, the Pan American Health Organization regularly provides updated case numbers and incidence rates for each island and country (2). As of 20 February 2015, Puerto Rico has reported 24 714 suspected and 4302 confirmed cases, with an incidence rate of 787 cases per 100 000 persons. According to the Pan American Health Organization, the chikungunya virus outbreaks in the Dominican Republic and the French part of Saint Martin are even more dramatic, with more than 500 000 suspected cases in the former and an incidence rate of 17 016 cases per 100 000 persons in the latter (2). Because of the high volume of travel between the United States and all infected areas, it is imperative that we raise the awareness of clinicians practicing in the contiguous United States about chikungunya virus in the Americas—all Caribbean islands and most countries in Central and South America. We appreciate Drs. Al-Araimi and Mittoo's comments about the similarity in presentation between chikungunya arthritis and rheumatoid arthritis and their recommendation that work-up is warranted for connective tissue disease in patients diagnosed with chikungunya virus who have persistent or recurrent arthritis. After the chikungunya virus epidemic in La Re´union in 2005, a cohort study of 147 patients with chikungunya virus found that 57% reported rheumatic symptoms at 15 months (nearly two thirds with persistent symptoms and one third with recurrent or relapsing symptoms) (3). These findings are similar to those of the patient that Drs. Al-Araimi and Mittoo describe. As Drs. Al-Araimi and Mittoo note, whether chikungunya virus triggers an autoimmune process is not yet known; however, some immunologic findings suggest inflammatory mechanisms (4). In patients with chikungunya virus who are later diagnosed with rheumatoid arthritis, the usefulness of therapy with disease-modifying antirheumatic drugs—such as methotrexate, tumor necrosis factor blockers, hydroxychloroquine, and corticosteroids— has not yet been established (5). Finally, because patients with persistent or relapsing arthralgia or arthritis may present to rheumatologists and primary care providers for evaluation, specialists should remain vigilant about assessing for chikungunya virus. Longitudinal natural history studies and randomized, controlled trials of inter-
ventions for patients with this condition who have persistent arthritis are critically needed. Davidson H. Hamer, MD Center for Global Health and Development, Boston University School of Public Health Boston, Massachusetts Lin H. Chen, MD Mount Auburn Hospital Cambridge, Massachusetts Disclosures: Disclosures can be viewed at www.acponline.org /authors/icmje/ConflictOfInterestForms.do?msNum=M14-1958. References 1. Hamer DH, Chen LH. Chikungunya: establishing a new home in the Western hemisphere. Ann Intern Med. 2014;161:827-8. [PMID: 25244354] doi: 10.7326/M14-1958 2. Pan American Health Organization; World Health Organization. Chikungunya. 2015. Accessed at www.paho.org/hq/index.php?Itemid=40931 on 25 February 2015. 3. Sissoko D, Malvy D, Ezzedine K, Renault P, Moscetti F, Ledrans M, et al. Post-epidemic Chikungunya disease on Reunion Island: course of rheumatic manifestations and associated factors over a 15-month period. PLoS Negl Trop Dis. 2009;3:e389. [PMID: 19274071] doi:10.1371/journal.pntd.0000389 4. Roques P, Gras G. Chikungunya fever: focus on peripheral markers of pathogenesis [Editorial]. J Infect Dis. 2011;203:141-3. [PMID: 21288810] doi: 10.1093/infdis/jiq026 5. Simon F, Javelle E, Oliver M, Leparc-Goffart I, Marimoutou C. Chikungunya virus infection. Curr Infect Dis Rep. 2011;13:218-28. [PMID: 21465340] doi: 10.1007/s11908-011-0180-1
CORRECTION Correction: Inviting Patients to Read Their Doctors' Notes A recent article (1) included an error in the number of patients from Geisinger Health System (GHS) who viewed 1 or more available notes. A total of 4795 patients at GHS viewed 1 or more available notes, not 5437 as originally reported. Therefore, 82% (not 92%) of GHS patients opened at least 1 note, 59% (not 87%) opened all of their notes, and 82% (not 90%) of patients at all 3 sites opened at least 1 note. A total of 11 155 (not 11 797) of 13 564 patients with visit notes available opened at least 1 note, and 5219 (not 5391) patients opened at least 1 note and completed a postintervention survey. This led to corrections in the Abstract, Results, and Discussion and Appendix Figure 2 and Appendix Table 1. These corrections do not materially affect the conclusions. This has been changed in the online version. Reference 1. Delbanco T, Walker J, Bell SK, Darer JD, Elmore JG, Farag N, et al. Inviting patients to read their doctors' notes: a quasi-experimental study and a look ahead. Ann Intern Med. 2012;157:461-70. [PMID: 23027317] doi:10.7326/ 0003-4819-157-7-201210020-00002
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