UPDATE Update in General Internal Medicine: Evidence Published in 2014 Reena H. Hemrajani, MD, and Stephanie A. Call, MD, MSPH
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ur goal was to select articles published in 2014 that are likely to help clinicians provide high-value care for ambulatory patients. To that end, we identified articles in ACP JournalWise that were “highest rated” or “most read.” We also searched MEDLINE by using 10 search topics rated highly by a panel of practicing generalists. We selected one article out of several that compared novel oral anticoagulants with warfarin in the management of atrial fibrillation. We also chose an article that evaluated the role of prolonged cardiac monitoring to detect atrial fibrillation in patients with cryptogenic stroke. In addition, we selected an article that examined how to use venous ultrasonography and D-dimer levels to decide how long to continue anticoagulation for venous thromboembolism. We found that 2014 was a big year for guidelines and reviews, and we chose articles that summarize guidelines about 4 conditions pertinent to generalist practice: obstructive sleep apnea, adult immunization, lung cancer, and hypertension. In addition, we highlight an update to a Cochrane review on the use of antibiotics in acute bronchitis. Finally, we discuss a systematic review that elucidates the value of confirmatory ambulatory blood pressure monitoring in patients with elevated blood pressure in the office.
Findings: Investigators compared dabigatran versus warfarin by using incident rates from the RE-LY study for benefits and harms, costs from Medicare payment schedules, and published estimates of quality of life in a model that estimated incremental costs per qualityadjusted life-year gained during a lifetime. Compared with patients receiving warfarin, those receiving dabigatran had fewer ischemic strokes and intracranial hemorrhages but more extracranial hemorrhages and acute myocardial infarctions. The incremental cost per quality-adjusted life-year for dabigatran versus warfarin was less than $100 000, the commonly accepted willingness-to-pay threshold. This finding was true for people who were younger than 75 years of age, 75 years of age or older, and all ages; it persisted in sensitivity analyses. In all 3 age groups, dabigatran cost less than warfarin for total events and long-term follow-up. Cautions: Because costs were based on Medicare expenditures, this study did not consider costs borne by patients and caregivers, unreimbursed provider costs, and other societal costs. Although the study used results of a high-quality clinical trial, it required assumptions that increased the uncertainty of its findings. Implications: In a comparison of dabigatran with warfarin, the tradeoffs between benefit, harm, and cost favor dabigatran for patients in all age groups. This information on groups of patients may be useful when clinicians make decisions about individual patients.
Atrial Fibrillation In Patients With Atrial Fibrillation of All Ages, Dabigatran Is Cost-Effective Compared With Warfarin Clemens A, Peng S, Brand S, et al. Efficacy and costeffectiveness of dabigatran etexilate versus warfarin in atrial fibrillation in different age subgroups. Am J Cardiol. 2014; 114:849-55. [PMID: 25103918] doi:10.1016/j.amjcard.2014 .06.015
Patients With Cryptogenic Stroke May Benefit From Prolonged Monitoring to Detect Atrial Fibrillation Gladstone DJ, Spring M, Dorian P, et al; EMBRACE Investigators and Coordinators. Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med. 2014;370:2467-77. [PMID: 24963566] doi:10.1056/NEJMoa1311376
Background: Atrial fibrillation is a known risk factor for stroke and was treated with warfarin until the availability of the novel oral anticoagulants. In the Randomized Evaluation of Long-Term Anticoagulation therapY (RELY) trial, dabigatran, a direct thrombin inhibitor, demonstrated efficacy and safety compared with warfarin (1). However, a follow-up analysis found that patients older than 75 years of age had higher rates of extracranial hemorrhage (2). Because this high-risk subgroup is most likely to benefit from anticoagulation given the high rate of embolic stroke, a cost-effectiveness study was conducted to estimate the tradeoff between dabigatran's benefits and harms in different age groups.
Background: Cryptogenic stroke accounts for 25% of ischemic strokes (3), and the role of prolonged cardiac monitoring to identify atrial fibrillation in these patients remains unclear (4). Identifying atrial fibrillation would allow secondary prevention, which decreases recurrent stroke by 64% when anticoagulation is used and by 22% when antiplatelet therapy is used (5). Findings: This randomized, controlled trial assessed whether prolonged cardiac monitoring in patients with cryptogenic stroke would increase detection of atrial fibrillation and lead to greater rates of anticoagulation. The investigators randomly assigned patients (older than 55 years in whom ischemic stroke or transient ischemic attack of cryptogenic cause was diagnosed after a standard work-up) (6, 7) to the intervention group (30day, event-triggered monitoring with a loop recorder)
Ann Intern Med. 2015;162:W80-W85. doi:10.7326/M15-0274 For author affiliations, see end of text. This article was published online first at www.annals.org on 30 April 2015.
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or the control group (an additional 24 hours of Holter monitoring). Of the 280 patients in the intervention group, 16.1% had at least one 30-second episode of atrial fibrillation detected compared with 3.2% of the 277 patients in the control group. The cumulative number of patients with new atrial fibrillation increased each week, with 7 patients detected in the fourth week of monitoring. Eight patients needed long-term monitoring to identify 1 patient with a new episode of atrial fibrillation. At 90 days, 18.6% of patients in the intervention group and 11.1% in the control group received anticoagulation (P < 0.010). Cautions: The study did not assess the effect of anticoagulation on stroke reduction, mortality, and adverse events. The authors used a conservative threshold of 30 seconds to define the duration of atrial fibrillation with an increased risk for stroke, in accordance with existing guidelines (8). Study patients presented in an ambulatory setting within 90 days of their stroke; these results may not be generalizable to other types of patients. Implications: This study supports the use of prolonged cardiac monitoring to detect atrial fibrillation in patients with cryptogenic stroke who are older than age 55 years. Future studies should assess whether anticoagulation improves outcomes in these patients.
eighty-two patients with a positive result were advised to restart anticoagulation, and 528 patients with all negative results remained off anticoagulation. Venous thromboembolism recurred in 1.1% of D-dimer–positive patients who resumed vitamin K antagonist therapy, 13.8% of D-dimer–positive patients who declined to resume therapy, and 3.7% of D-dimer–negative patients who stayed off anticoagulation. The hazard ratio for recurrent VTE in patients with positive D-dimer results who declined therapy versus those with positive D-dimer results who resumed therapy was 2.92 (95% CI, 1.87 to 9.72). Cautions: Study patients were not randomly assigned to different treatments. Threshold values for D-dimer were not defined by using objective criteria. The timing of D-dimer screening is potentially burdensome to patients and providers. The study did not include newer oral anticoagulants. Implications: Ultrasonography and D-dimer levels may help clinicians in their discussion of the risks and benefits of shorter versus longer anticoagulation with their patients who have idiopathic VTE or VTE with weak risk factors.
Guidelines and Guideline Updates Venous Thromboembolism Combination of D-Dimer and Ultrasonography May Be Useful in Discontinuing Anticoagulation in Patients With Venous Thromboembolism Palareti G, Cosmi B, Legnani C, et al; DULCIS (D-dimer and ULtrasonography in Combination Italian Study) Investigators. D-dimer to guide the duration of anticoagulation in patients with venous thromboembolism: a management study. Blood. 2014;124:196-203. [PMID: 24879813] doi:10.1182/blood -2014-01-548065
Background: Guidelines recommend more than 3 months of anticoagulation to prevent recurrence after unprovoked venous thromboembolism (VTE) in patients with a low to moderate risk for bleeding (9), but the optimal duration of anticoagulation is uncertain (10, 11). Previous studies have suggested that D-dimer testing (12) and follow-up ultrasonography (13) may help. Findings: This multicenter prospective cohort trial sought to assess whether D-dimer testing and ultrasonography would identify patients who could safely discontinue anticoagulation after 3 months. Study patients had idiopathic VTE or VTE associated with “weak risk factors” and had completed at least 3 months of therapy with warfarin or another vitamin K antagonist when they entered the study. Patients who had no evidence of residual thrombosis on ultrasonography and had a negative result on D-dimer testing (according to predefined thresholds determined by age and sex) were advised to stop anticoagulation. Those who stopped had repeated D-dimer measurement at approximately 2, 4, 8, and 12 weeks. Four hundred
Polysomnography Should Be Ordered for Patients With Excessive Daytime Sleepiness Qaseem A, Dallas P, Owens DK, et al; Clinical Guidelines Committee of the American College of Physicians. Diagnosis of obstructive sleep apnea in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2014;161:210-20. [PMID: 25089864] doi:10.7326/M12-3187
Background: Obstructive sleep apnea disrupts sleep and results in fatigue, impaired concentration, and decreased quality of life. It is associated with poor outcomes in many common medical conditions (14). The importance of diagnosing obstructive sleep apnea has gained considerable attention but is challenging because evaluation is complex, often not easily available, and expensive. This guideline reviews existing practices and controversies in diagnosing obstructive sleep apnea. Findings: The guideline was based on evidence from an updated review by the Agency for Healthcare Research and Quality in 2010. The evidence and recommendations were rated by using the American College of Physicians' (ACP's) guideline grading system (15). Summary of recommendations: 1. The ACP recommends a sleep study for patients with unexplained daytime sleepiness (weak recommendation, low-quality evidence). 2. The ACP recommends polysomnography for diagnostic testing. Portable sleep monitors are recommended only in patients without comorbid conditions and when polysomnography is not available (weak recommendation, moderate-quality evidence).
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UPDATE 3. Areas for which evidence was limited or inconclusive included preoperative screening for obstructive sleep apnea, phased testing for the diagnosis of obstructive sleep apnea, and alternative assessment in patients with comorbid conditions.
Immunization Standards for Adults Are Updated Bridges CB, Coyne-Beasley T; Advisory Committee on Immunization Practices. Advisory committee on immunization practices recommended immunization schedule for adults aged 19 years or older: United States, 2014. Ann Intern Med. 2014; 160:190-7. [PMID: 24658695] doi:10.7326/M13-2826
Background: The Advisory Committee on Immunization Practices annually reviews and updates the Adult Immunization schedule. This process enables physicians to keep up with new data and recommendations on vaccines and provides schedules, tables, and other information for educating physicians, office staff, and patients. Summary of changes to recommendations: 1. Over the past 2 years, 2 additional vaccines have been added to the vaccine schedule: pneumococcal 13-valent conjugate (PCV13) and Haemophilus influenza type B (Hib). A. The PCV13 vaccine should be given to adults age 19 years or older with immunocompromising conditions, functional or anatomical asplenia, cerebrospinal leaks, or cochlear implants who have not previously received PCV13. Patients who have never received pneumococcal polysaccharide vaccine (PPSV23) should receive a dose of PPSV23 at least 8 weeks after administration of PCV13. Patients receiving PPSV23 should receive PCV13 1 year or more after administration PPSV23. B. The Hib vaccine should be given to persons who have functional or anatomical asplenia or sickle cell disease if they have not previously received this vaccine. Recipients of a hematopoietic stem cell transplant should be vaccinated with a 3-dose regimen 6 to 12 months after transplantation. 2. The newly licensed recombinant influenza vaccine for patients age 18 to 49 years can be an alternative for individuals with hives-only reaction to eggs and can be given to individuals with severe reactions to egg protein. 3. Language was clarified regarding the timing for administering human papillomavirus vaccine; the dosing of the tetanus, diphtheria, and pertussis vaccine; and the number of doses required in meningococcal vaccination.
U.S. Preventive Services Task Force Recommends Annual Screening for Lung Cancer With Low-Dose Computed Tomography in High-Risk Populations Moyer VA; U.S. Preventive Services Task Force. Screening for lung cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;160:330-8. [PMID: 24378917] doi:10.7326/M13-2771
Update in General Internal Medicine
Background: Lung cancer is the leading cause of cancer-related death in the United States (16). Clearly identified risk factors, such as age and smoking, allow a physician to identify a high-risk population for screening. Despite the existence of potential screening tests, such as chest radiography, sputum cytology, and computed tomography, until recently there was no consensus that any screening test helped reduce mortality or improve quality of life. This U.S. Preventive Services Task Force (USPSTF) statement provides specific guidelines for screening in high-risk populations and serves as a basis for insurance coverage by the Centers for Medicare & Medicaid Services and private payers. Findings: The recommendation statement is based on evidence from a systematic review commissioned by USPSTF to assess the efficacy of low-dose computed tomography, chest radiography, and sputum cytology evaluation for lung cancer screening in asymptomatic average-risk and high-risk populations. Additional information was provided from modeling studies by the Cancer Intervention and Surveillance Modeling Network. The evidence and recommendations were rated by using the USPSTF's grading system. The published statement summarizes the review, which is primarily focused on the National Lung Screening Trial. That study showed a 16% reduction in lung cancer mortality (17). Combined data from the fair- and good-quality trials in the review led to a relative risk for death from lung cancer after screening of 0.81 (CI, 0.72 to 0.91). An annual screening strategy had the greatest benefit. In the largest single study, 96% of positive test results were falsely positive. Summary of recommendations: 1. Screen for lung cancer annually with low-dose computed tomography in asymptomatic adults age 55 to 80 years who have a 30 –pack-year smoking history and are currently smoking or had quit in the previous 15 years. (B recommendation) 2. Additional considerations include the following: A. Little potential benefit for those with serious comorbid conditions B. Lack of benefit for those unwilling to have surgery C. Importance of smoking cessation as adjunct therapy D. Importance of shared decision making, given the potential harms from screening E. Importance of standardizing screening and follow-up protocols
Panel Convened as the Eighth Joint National Committee Publishes Guidelines on Managing High Blood Pressure in Adults James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311: 507-20. [PMID: 24352797] doi:10.1001/jama.2013.284427
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Background: Effective diagnosis and treatment of hypertension reduce overall mortality and the incidence of myocardial infarction, stroke, heart failure, and renal failure. This long-awaited new set of guidelines takes a different approach than prior Joint National Committee (JNC) guidelines (18) by following recommendations in the recent Institute of Medicine report, “Clinical Practice Guidelines We Can Trust” (19). The JNC guideline answers 3 questions for adults with hypertension: 1) Does initiating hypertensive pharmacologic therapy at specific blood pressure (BP) thresholds improve health outcomes? 2) Does antihypertensive pharmacologic therapy to a specified BP goal improve health outcomes? 3) Do various antihypertensive drugs or drug classes differ in comparative benefits and harms on specific health outcomes? Findings: An external method team conducted an independent evidence review of original publications that included only randomized clinical trials. The article used the quality rating system for evidence and the grading system for strength of recommendation developed by the National Heart, Lung, and Blood Institute guideline panels. The panel emphasized that “recommendations are not a substitute for clinical judgment.” Summary of selected recommendations: 1. In the general population older than 60 years, initiate pharmacologic treatment to decrease BP at a systolic blood pressure (SBP) greater than 150 mm Hg and a diastolic blood pressure (DBP) greater than 90 mm Hg, and treat to a goal SBP less than 150 mm Hg and a goal DBP less than 90 mm Hg. (Strong recommendation, grade A) 2. In the general population younger than 60 years of age, initiate pharmacologic treatment to decrease BP at a DBP greater than 90 mm Hg and treat to a goal DBP less than 90 mm Hg. (For ages 30 to 59 years: strong recommendation, grade A; for ages 18 to 29, expert opinion, grade E) 3. In the general population younger than age 60 years and in those 18 years or older with diabetes or chronic kidney disease, treat to a goal SBP less than 140 mm Hg and a goal DBP less than 90 mm Hg. (Expert opinion, grade E) 4. In the general nonblack population, including patients with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic, calciumchannel blocker, angiotensin-converting enzyme inhibitor, or angiotensin-receptor blocker. Angiotensinconverting enzyme inhibitors and angiotensin-receptor blockers were not recommended for initial treatment in the general black population. (Moderate recommendation, grade B; for black patients with diabetes: weak recommendation, grade C) 5. In the population older than age 18 years with chronic kidney disease, initial (or add-on) antihypertensive treatment should include an angiotensinconverting enzyme inhibitor or angiotensin-receptor blocker to improve kidney outcomes. (Moderate recommendation, grade B)
Acute Bronchitis Antibiotic Therapy for Acute Bronchitis Provides Minimal Clinical Benefit and Significantly Increases Adverse Effects Smith SM, Fahey T, Smucny J, et al. Antibiotics for acute bronchitis. Cochrane Database Syst Rev. 2014;3:CD000245. [PMID: 24585130] doi:10.1002/14651858.CD000245.pub3
Background: Despite existing guidelines to the contrary, clinicians prescribe antibiotics to as many as 70% of adults with acute bronchitis (20). Prescribing decisions should incorporate information about the benefit from using antibiotics, the cost of using antibiotics, the morbidity from antibiotic adverse effects, and the harms from increased development of organisms resistant to antibiotics. Findings: The authors included 17 randomized, controlled trials in their analyses. Antibiotic-treated patients were less likely to have a cough at a follow-up visit (relative risk, 0.64; CI, 0.49 to 0.85; number needed to treat for benefit, 22). These patients also had reductions in the mean number of days feeling ill (mean difference, 0.64 day; CI, ⫺1.16 to ⫺0.13 day) and the mean number of days with impaired activity (mean difference, ⫺0.49 day; CI, ⫺0.94 to ⫺0.04 day). There were no differences in the frequency of a productive cough, the number of days of productive cough, or the amount of patient-reported improvement. Antibiotic-treated patients were more likely to report adverse effects thought to be related to their antibiotics (relative risk, 1.20; CI, 1.05 to 1.36; number needed to treat for harm, 5), and the most common effects were gastrointestinal symptoms. Cautions: Results varied from study to study. Overall results may not reflect results for all subgroups and individuals. Few studies included older or frail people, limiting the generalizability of the findings. Data on cost and antibiotic resistance were not available for study. Implications: Information about antibiotic-related numbers needed to treat for benefit and harm should be useful to clinicians and their patients when decisions have to be made about the management of acute bronchitis.
Ambulatory BP Monitoring for Hypertension Screening Ambulatory BP Monitoring Predicts Cardiovascular Outcomes and Aids in Screening for Hypertension Piper MA, Evans CV, Burda BU, et al. Diagnostic and predictive accuracy of blood pressure screening methods with consideration of rescreening intervals: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2015; 162:192-204. [PMID: 25531400] doi:10.7326/M14-1539].
Background: Current guidelines do not address the diagnostic accuracy of office BP measurement or the
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UPDATE roles of ambulatory BP monitoring and home BP monitoring (21, 22). Findings: This systematic review found that sensitivities of office BP measurements varied widely, but specificities were consistently greater than 90% for both manual and automated measurements. Repeated BP measurements during the same office visit had limited value, and false elevations of BP occurred after caffeine ingestion. Ambulatory BP monitoring consistently predicted cardiovascular outcomes independently of officebased BP measurement whether the monitoring was done at night, during the day, or for 24 hours. Limited data suggest that home BP monitoring is similar to ambulatory BP monitoring. Information from 24 studies found wide variability in the percentage of patients (35% to 95%) whose elevated office BP was confirmed with ambulatory testing. People in high-risk groups and people with high normal BP had greater probabilities of elevated BP on remeasurement. Cautions: The study did not examine differences among ambulatory BP monitoring devices and among home BP monitoring devices. Implications: An isolated office BP measurement that indicates hypertension may need to be confirmed with ambulatory BP monitoring. People with elevated BP in the office but not elsewhere have cardiovascular outcomes that are similar to those of normotensive people. From Virginia Commonwealth University, Richmond, Virginia. Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje /ConflictOfInterestForms.do?msNum=M15-0274. Requests for Single Reprints: Stephanie A. Call, MD, MSPH, PO Box 980509, 1200 East Broad Street, Richmond, VA 23298; e-mail, [email protected]. Current Author Addresses: Drs. Hemrajani and Call: PO Box 980509, 1200 East Broad Street, Richmond, VA 23298. Author Contributions: Analysis and interpretation of the data:
R.H. Hemrajani. Drafting of the article: R.H. Hemrajani, S.A. Call. Critical revision of the article for important intellectual content: R.H. Hemrajani, S.A. Call. Final approval of the article: R.H. Hemrajani, S.A. Call. Administrative, technical, or logistic support: S.A. Call. Collection and assembly of data: R.H. Hemrajani, S.A. Call.
References 1. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139-51. [PMID: 19717844] doi:10.1056/NEJMoa 0905561 2. Eikelboom JW, Wallentin L, Connolly SJ, Ezekowitz M, Healey JS, Oldgren J, et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anti-
Update in General Internal Medicine
coagulant therapy (RE-LY) trial. Circulation. 2011;123:2363-72. [PMID: 21576658] doi:10.1161/CIRCULATIONAHA.110.004747 3. Hart RG, Diener HC, Coutts SB, Easton JD, Granger CB, O’Donnell MJ, et al; Cryptogenic Stroke/ESUS International Working Group. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol. 2014;13:429-38. [PMID: 24646875] doi: 10.1016/S1474-4422(13)70310-7 4. Flint AC, Banki NM, Ren X, Rao VA, Go AS. Detection of paroxysmal atrial fibrillation by 30-day event monitoring in cryptogenic ischemic stroke: the Stroke and Monitoring for PAF in Real Time (SMART) Registry. Stroke. 2012;43:2788-90. [PMID: 22871679] 5. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146:857-67. [PMID: 17577005] 6. Aho K, Harmsen P, Hatano S, Marquardsen J, Smirnov VE, Strasser T. Cerebrovascular disease in the community: results of a WHO collaborative study. Bull World Health Organ. 1980;58:113-30. [PMID: 6966542] 7. Goldstein LB, Jones MR, Matchar DB, Edwards LJ, Hoff J, Chilukuri V, et al. Improving the reliability of stroke subgroup classification using the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. Stroke. 2001;32:1091-8. [PMID: 11340215] 8. Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, et al; European Heart Rhythm Association. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010;31:2369-429. [PMID: 20802247] doi:10.1093/eurheartj /ehq278 9. Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, et al; American College of Chest Physicians. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141: e419S-94S. [PMID: 22315268] doi:10.1378/chest.11-2301 10. Prandoni P, Noventa F, Ghirarduzzi A, Pengo V, Bernardi E, Pesavento R, et al. The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica. 2007;92:199-205. [PMID: 17296569] 11. Boutitie F, Pinede L, Schulman S, Agnelli G, Raskob G, Julian J, et al. Influence of preceding length of anticoagulant treatment and initial presentation of venous thromboembolism on risk of recurrence after stopping treatment: analysis of individual participants' data from seven trials. BMJ. 2011;342:d3036. [PMID: 21610040] doi: 10.1136/bmj.d3036 12. Cosmi B, Legnani C, Tosetto A, Pengo V, Ghirarduzzi A, Testa S, et al; PROLONG Investigators (on behalf of Italian Federation of Anticoagulation Clinics). Usefulness of repeated D-dimer testing after stopping anticoagulation for a first episode of unprovoked venous thromboembolism: the PROLONG II prospective study. Blood. 2010; 115:481-8. [PMID: 19965693] doi:10.1182/blood-2009-08-237354 13. Prandoni P, Prins MH, Lensing AW, Ghirarduzzi A, Ageno W, Imberti D, et al; AESOPUS Investigators. Residual thrombosis on ultrasonography to guide the duration of anticoagulation in patients with deep venous thrombosis: a randomized trial. Ann Intern Med. 2009;150:577-85. [PMID: 19414836] 14. Punjabi NM. The epidemiology of adult obstructive sleep apnea. Proc Am Thorac Soc. 2008;5:136-43. [PMID: 18250205] doi: 10.1513/pats.200709-155MG 15. Qaseem A, Snow V, Owens DK, Shekelle P; Clinical Guidelines Committee of the American College of Physicians. The development of clinical practice guidelines and guidance statements of the American College of Physicians: summary of methods. Ann Intern Med. 2010;153:194-9. [PMID: 20679562] doi:10.7326/0003-4819 -153-3-201008030-00010 16. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9-29. [PMID: 24399786] doi:10.3322/caac .21208
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17. Pinsky PF, Church TR, Izmirlian G, Kramer BS. The National Lung Screening Trial: results stratified by demographics, smoking history, and lung cancer histology. Cancer. 2013;119:3976-83. [PMID: 24037918] doi:10.1002/cncr.28326 18. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289: 2560-72. [PMID: 12748199] 19. Institute of Medicine. Clinical Practice Guidelines We Can Trust. Washington, DC: National Academies Press; 2011. 20. Gonzales R, Anderer T, McCulloch CE, Maselli JH, Bloom FJ Jr, Graf TR, et al. A cluster randomized trial of decision support strategies for reducing antibiotic use in acute bronchitis. JAMA Intern
Med. 2013;173:267-73. [PMID: 23319069] doi:10.1001/jamain ternmed.2013.1589 21. James PA, Oparil S, Carter BL, Cushman WC, DennisonHimmelfarb C, Handler J, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311:507-20. [PMID: 24352797] doi:10.1001 /jama.2013.284427 22. Go AS, Bauman MA, Coleman King SM, Fonarow GC, Lawrence W, Williams KA, et al; American Heart Association. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention. Hypertension. 2014;63:878-85. [PMID: 24243703] doi:10.1161/HYP.00000000 00000003
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O
ur goal was to select articles published in 2014 that are likely to help clinicians provide high-value care for ambulatory patients. To that end, we identified articles in ACP JournalWise that were “highest rated” or “most read.” We also searched MEDLINE by using 10 search topics rated highly by a panel of practicing generalists. We selected one article out of several that compared novel oral anticoagulants with warfarin in the management of atrial fibrillation. We also chose an article that evaluated the role of prolonged cardiac monitoring to detect atrial fibrillation in patients with cryptogenic stroke. In addition, we selected an article that examined how to use venous ultrasonography and D-dimer levels to decide how long to continue anticoagulation for venous thromboembolism. We found that 2014 was a big year for guidelines and reviews, and we chose articles that summarize guidelines about 4 conditions pertinent to generalist practice: obstructive sleep apnea, adult immunization, lung cancer, and hypertension. In addition, we highlight an update to a Cochrane review on the use of antibiotics in acute bronchitis. Finally, we discuss a systematic review that elucidates the value of confirmatory ambulatory blood pressure monitoring in patients with elevated blood pressure in the office.
Findings: Investigators compared dabigatran versus warfarin by using incident rates from the RE-LY study for benefits and harms, costs from Medicare payment schedules, and published estimates of quality of life in a model that estimated incremental costs per qualityadjusted life-year gained during a lifetime. Compared with patients receiving warfarin, those receiving dabigatran had fewer ischemic strokes and intracranial hemorrhages but more extracranial hemorrhages and acute myocardial infarctions. The incremental cost per quality-adjusted life-year for dabigatran versus warfarin was less than $100 000, the commonly accepted willingness-to-pay threshold. This finding was true for people who were younger than 75 years of age, 75 years of age or older, and all ages; it persisted in sensitivity analyses. In all 3 age groups, dabigatran cost less than warfarin for total events and long-term follow-up. Cautions: Because costs were based on Medicare expenditures, this study did not consider costs borne by patients and caregivers, unreimbursed provider costs, and other societal costs. Although the study used results of a high-quality clinical trial, it required assumptions that increased the uncertainty of its findings. Implications: In a comparison of dabigatran with warfarin, the tradeoffs between benefit, harm, and cost favor dabigatran for patients in all age groups. This information on groups of patients may be useful when clinicians make decisions about individual patients.
Atrial Fibrillation In Patients With Atrial Fibrillation of All Ages, Dabigatran Is Cost-Effective Compared With Warfarin Clemens A, Peng S, Brand S, et al. Efficacy and costeffectiveness of dabigatran etexilate versus warfarin in atrial fibrillation in different age subgroups. Am J Cardiol. 2014; 114:849-55. [PMID: 25103918] doi:10.1016/j.amjcard.2014 .06.015
Patients With Cryptogenic Stroke May Benefit From Prolonged Monitoring to Detect Atrial Fibrillation Gladstone DJ, Spring M, Dorian P, et al; EMBRACE Investigators and Coordinators. Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med. 2014;370:2467-77. [PMID: 24963566] doi:10.1056/NEJMoa1311376
Background: Atrial fibrillation is a known risk factor for stroke and was treated with warfarin until the availability of the novel oral anticoagulants. In the Randomized Evaluation of Long-Term Anticoagulation therapY (RELY) trial, dabigatran, a direct thrombin inhibitor, demonstrated efficacy and safety compared with warfarin (1). However, a follow-up analysis found that patients older than 75 years of age had higher rates of extracranial hemorrhage (2). Because this high-risk subgroup is most likely to benefit from anticoagulation given the high rate of embolic stroke, a cost-effectiveness study was conducted to estimate the tradeoff between dabigatran's benefits and harms in different age groups.
Background: Cryptogenic stroke accounts for 25% of ischemic strokes (3), and the role of prolonged cardiac monitoring to identify atrial fibrillation in these patients remains unclear (4). Identifying atrial fibrillation would allow secondary prevention, which decreases recurrent stroke by 64% when anticoagulation is used and by 22% when antiplatelet therapy is used (5). Findings: This randomized, controlled trial assessed whether prolonged cardiac monitoring in patients with cryptogenic stroke would increase detection of atrial fibrillation and lead to greater rates of anticoagulation. The investigators randomly assigned patients (older than 55 years in whom ischemic stroke or transient ischemic attack of cryptogenic cause was diagnosed after a standard work-up) (6, 7) to the intervention group (30day, event-triggered monitoring with a loop recorder)
Ann Intern Med. 2015;162:W80-W85. doi:10.7326/M15-0274 For author affiliations, see end of text. This article was published online first at www.annals.org on 30 April 2015.
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or the control group (an additional 24 hours of Holter monitoring). Of the 280 patients in the intervention group, 16.1% had at least one 30-second episode of atrial fibrillation detected compared with 3.2% of the 277 patients in the control group. The cumulative number of patients with new atrial fibrillation increased each week, with 7 patients detected in the fourth week of monitoring. Eight patients needed long-term monitoring to identify 1 patient with a new episode of atrial fibrillation. At 90 days, 18.6% of patients in the intervention group and 11.1% in the control group received anticoagulation (P < 0.010). Cautions: The study did not assess the effect of anticoagulation on stroke reduction, mortality, and adverse events. The authors used a conservative threshold of 30 seconds to define the duration of atrial fibrillation with an increased risk for stroke, in accordance with existing guidelines (8). Study patients presented in an ambulatory setting within 90 days of their stroke; these results may not be generalizable to other types of patients. Implications: This study supports the use of prolonged cardiac monitoring to detect atrial fibrillation in patients with cryptogenic stroke who are older than age 55 years. Future studies should assess whether anticoagulation improves outcomes in these patients.
eighty-two patients with a positive result were advised to restart anticoagulation, and 528 patients with all negative results remained off anticoagulation. Venous thromboembolism recurred in 1.1% of D-dimer–positive patients who resumed vitamin K antagonist therapy, 13.8% of D-dimer–positive patients who declined to resume therapy, and 3.7% of D-dimer–negative patients who stayed off anticoagulation. The hazard ratio for recurrent VTE in patients with positive D-dimer results who declined therapy versus those with positive D-dimer results who resumed therapy was 2.92 (95% CI, 1.87 to 9.72). Cautions: Study patients were not randomly assigned to different treatments. Threshold values for D-dimer were not defined by using objective criteria. The timing of D-dimer screening is potentially burdensome to patients and providers. The study did not include newer oral anticoagulants. Implications: Ultrasonography and D-dimer levels may help clinicians in their discussion of the risks and benefits of shorter versus longer anticoagulation with their patients who have idiopathic VTE or VTE with weak risk factors.
Guidelines and Guideline Updates Venous Thromboembolism Combination of D-Dimer and Ultrasonography May Be Useful in Discontinuing Anticoagulation in Patients With Venous Thromboembolism Palareti G, Cosmi B, Legnani C, et al; DULCIS (D-dimer and ULtrasonography in Combination Italian Study) Investigators. D-dimer to guide the duration of anticoagulation in patients with venous thromboembolism: a management study. Blood. 2014;124:196-203. [PMID: 24879813] doi:10.1182/blood -2014-01-548065
Background: Guidelines recommend more than 3 months of anticoagulation to prevent recurrence after unprovoked venous thromboembolism (VTE) in patients with a low to moderate risk for bleeding (9), but the optimal duration of anticoagulation is uncertain (10, 11). Previous studies have suggested that D-dimer testing (12) and follow-up ultrasonography (13) may help. Findings: This multicenter prospective cohort trial sought to assess whether D-dimer testing and ultrasonography would identify patients who could safely discontinue anticoagulation after 3 months. Study patients had idiopathic VTE or VTE associated with “weak risk factors” and had completed at least 3 months of therapy with warfarin or another vitamin K antagonist when they entered the study. Patients who had no evidence of residual thrombosis on ultrasonography and had a negative result on D-dimer testing (according to predefined thresholds determined by age and sex) were advised to stop anticoagulation. Those who stopped had repeated D-dimer measurement at approximately 2, 4, 8, and 12 weeks. Four hundred
Polysomnography Should Be Ordered for Patients With Excessive Daytime Sleepiness Qaseem A, Dallas P, Owens DK, et al; Clinical Guidelines Committee of the American College of Physicians. Diagnosis of obstructive sleep apnea in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2014;161:210-20. [PMID: 25089864] doi:10.7326/M12-3187
Background: Obstructive sleep apnea disrupts sleep and results in fatigue, impaired concentration, and decreased quality of life. It is associated with poor outcomes in many common medical conditions (14). The importance of diagnosing obstructive sleep apnea has gained considerable attention but is challenging because evaluation is complex, often not easily available, and expensive. This guideline reviews existing practices and controversies in diagnosing obstructive sleep apnea. Findings: The guideline was based on evidence from an updated review by the Agency for Healthcare Research and Quality in 2010. The evidence and recommendations were rated by using the American College of Physicians' (ACP's) guideline grading system (15). Summary of recommendations: 1. The ACP recommends a sleep study for patients with unexplained daytime sleepiness (weak recommendation, low-quality evidence). 2. The ACP recommends polysomnography for diagnostic testing. Portable sleep monitors are recommended only in patients without comorbid conditions and when polysomnography is not available (weak recommendation, moderate-quality evidence).
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UPDATE 3. Areas for which evidence was limited or inconclusive included preoperative screening for obstructive sleep apnea, phased testing for the diagnosis of obstructive sleep apnea, and alternative assessment in patients with comorbid conditions.
Immunization Standards for Adults Are Updated Bridges CB, Coyne-Beasley T; Advisory Committee on Immunization Practices. Advisory committee on immunization practices recommended immunization schedule for adults aged 19 years or older: United States, 2014. Ann Intern Med. 2014; 160:190-7. [PMID: 24658695] doi:10.7326/M13-2826
Background: The Advisory Committee on Immunization Practices annually reviews and updates the Adult Immunization schedule. This process enables physicians to keep up with new data and recommendations on vaccines and provides schedules, tables, and other information for educating physicians, office staff, and patients. Summary of changes to recommendations: 1. Over the past 2 years, 2 additional vaccines have been added to the vaccine schedule: pneumococcal 13-valent conjugate (PCV13) and Haemophilus influenza type B (Hib). A. The PCV13 vaccine should be given to adults age 19 years or older with immunocompromising conditions, functional or anatomical asplenia, cerebrospinal leaks, or cochlear implants who have not previously received PCV13. Patients who have never received pneumococcal polysaccharide vaccine (PPSV23) should receive a dose of PPSV23 at least 8 weeks after administration of PCV13. Patients receiving PPSV23 should receive PCV13 1 year or more after administration PPSV23. B. The Hib vaccine should be given to persons who have functional or anatomical asplenia or sickle cell disease if they have not previously received this vaccine. Recipients of a hematopoietic stem cell transplant should be vaccinated with a 3-dose regimen 6 to 12 months after transplantation. 2. The newly licensed recombinant influenza vaccine for patients age 18 to 49 years can be an alternative for individuals with hives-only reaction to eggs and can be given to individuals with severe reactions to egg protein. 3. Language was clarified regarding the timing for administering human papillomavirus vaccine; the dosing of the tetanus, diphtheria, and pertussis vaccine; and the number of doses required in meningococcal vaccination.
U.S. Preventive Services Task Force Recommends Annual Screening for Lung Cancer With Low-Dose Computed Tomography in High-Risk Populations Moyer VA; U.S. Preventive Services Task Force. Screening for lung cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;160:330-8. [PMID: 24378917] doi:10.7326/M13-2771
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Background: Lung cancer is the leading cause of cancer-related death in the United States (16). Clearly identified risk factors, such as age and smoking, allow a physician to identify a high-risk population for screening. Despite the existence of potential screening tests, such as chest radiography, sputum cytology, and computed tomography, until recently there was no consensus that any screening test helped reduce mortality or improve quality of life. This U.S. Preventive Services Task Force (USPSTF) statement provides specific guidelines for screening in high-risk populations and serves as a basis for insurance coverage by the Centers for Medicare & Medicaid Services and private payers. Findings: The recommendation statement is based on evidence from a systematic review commissioned by USPSTF to assess the efficacy of low-dose computed tomography, chest radiography, and sputum cytology evaluation for lung cancer screening in asymptomatic average-risk and high-risk populations. Additional information was provided from modeling studies by the Cancer Intervention and Surveillance Modeling Network. The evidence and recommendations were rated by using the USPSTF's grading system. The published statement summarizes the review, which is primarily focused on the National Lung Screening Trial. That study showed a 16% reduction in lung cancer mortality (17). Combined data from the fair- and good-quality trials in the review led to a relative risk for death from lung cancer after screening of 0.81 (CI, 0.72 to 0.91). An annual screening strategy had the greatest benefit. In the largest single study, 96% of positive test results were falsely positive. Summary of recommendations: 1. Screen for lung cancer annually with low-dose computed tomography in asymptomatic adults age 55 to 80 years who have a 30 –pack-year smoking history and are currently smoking or had quit in the previous 15 years. (B recommendation) 2. Additional considerations include the following: A. Little potential benefit for those with serious comorbid conditions B. Lack of benefit for those unwilling to have surgery C. Importance of smoking cessation as adjunct therapy D. Importance of shared decision making, given the potential harms from screening E. Importance of standardizing screening and follow-up protocols
Panel Convened as the Eighth Joint National Committee Publishes Guidelines on Managing High Blood Pressure in Adults James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311: 507-20. [PMID: 24352797] doi:10.1001/jama.2013.284427
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Background: Effective diagnosis and treatment of hypertension reduce overall mortality and the incidence of myocardial infarction, stroke, heart failure, and renal failure. This long-awaited new set of guidelines takes a different approach than prior Joint National Committee (JNC) guidelines (18) by following recommendations in the recent Institute of Medicine report, “Clinical Practice Guidelines We Can Trust” (19). The JNC guideline answers 3 questions for adults with hypertension: 1) Does initiating hypertensive pharmacologic therapy at specific blood pressure (BP) thresholds improve health outcomes? 2) Does antihypertensive pharmacologic therapy to a specified BP goal improve health outcomes? 3) Do various antihypertensive drugs or drug classes differ in comparative benefits and harms on specific health outcomes? Findings: An external method team conducted an independent evidence review of original publications that included only randomized clinical trials. The article used the quality rating system for evidence and the grading system for strength of recommendation developed by the National Heart, Lung, and Blood Institute guideline panels. The panel emphasized that “recommendations are not a substitute for clinical judgment.” Summary of selected recommendations: 1. In the general population older than 60 years, initiate pharmacologic treatment to decrease BP at a systolic blood pressure (SBP) greater than 150 mm Hg and a diastolic blood pressure (DBP) greater than 90 mm Hg, and treat to a goal SBP less than 150 mm Hg and a goal DBP less than 90 mm Hg. (Strong recommendation, grade A) 2. In the general population younger than 60 years of age, initiate pharmacologic treatment to decrease BP at a DBP greater than 90 mm Hg and treat to a goal DBP less than 90 mm Hg. (For ages 30 to 59 years: strong recommendation, grade A; for ages 18 to 29, expert opinion, grade E) 3. In the general population younger than age 60 years and in those 18 years or older with diabetes or chronic kidney disease, treat to a goal SBP less than 140 mm Hg and a goal DBP less than 90 mm Hg. (Expert opinion, grade E) 4. In the general nonblack population, including patients with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic, calciumchannel blocker, angiotensin-converting enzyme inhibitor, or angiotensin-receptor blocker. Angiotensinconverting enzyme inhibitors and angiotensin-receptor blockers were not recommended for initial treatment in the general black population. (Moderate recommendation, grade B; for black patients with diabetes: weak recommendation, grade C) 5. In the population older than age 18 years with chronic kidney disease, initial (or add-on) antihypertensive treatment should include an angiotensinconverting enzyme inhibitor or angiotensin-receptor blocker to improve kidney outcomes. (Moderate recommendation, grade B)
Acute Bronchitis Antibiotic Therapy for Acute Bronchitis Provides Minimal Clinical Benefit and Significantly Increases Adverse Effects Smith SM, Fahey T, Smucny J, et al. Antibiotics for acute bronchitis. Cochrane Database Syst Rev. 2014;3:CD000245. [PMID: 24585130] doi:10.1002/14651858.CD000245.pub3
Background: Despite existing guidelines to the contrary, clinicians prescribe antibiotics to as many as 70% of adults with acute bronchitis (20). Prescribing decisions should incorporate information about the benefit from using antibiotics, the cost of using antibiotics, the morbidity from antibiotic adverse effects, and the harms from increased development of organisms resistant to antibiotics. Findings: The authors included 17 randomized, controlled trials in their analyses. Antibiotic-treated patients were less likely to have a cough at a follow-up visit (relative risk, 0.64; CI, 0.49 to 0.85; number needed to treat for benefit, 22). These patients also had reductions in the mean number of days feeling ill (mean difference, 0.64 day; CI, ⫺1.16 to ⫺0.13 day) and the mean number of days with impaired activity (mean difference, ⫺0.49 day; CI, ⫺0.94 to ⫺0.04 day). There were no differences in the frequency of a productive cough, the number of days of productive cough, or the amount of patient-reported improvement. Antibiotic-treated patients were more likely to report adverse effects thought to be related to their antibiotics (relative risk, 1.20; CI, 1.05 to 1.36; number needed to treat for harm, 5), and the most common effects were gastrointestinal symptoms. Cautions: Results varied from study to study. Overall results may not reflect results for all subgroups and individuals. Few studies included older or frail people, limiting the generalizability of the findings. Data on cost and antibiotic resistance were not available for study. Implications: Information about antibiotic-related numbers needed to treat for benefit and harm should be useful to clinicians and their patients when decisions have to be made about the management of acute bronchitis.
Ambulatory BP Monitoring for Hypertension Screening Ambulatory BP Monitoring Predicts Cardiovascular Outcomes and Aids in Screening for Hypertension Piper MA, Evans CV, Burda BU, et al. Diagnostic and predictive accuracy of blood pressure screening methods with consideration of rescreening intervals: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2015; 162:192-204. [PMID: 25531400] doi:10.7326/M14-1539].
Background: Current guidelines do not address the diagnostic accuracy of office BP measurement or the
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UPDATE roles of ambulatory BP monitoring and home BP monitoring (21, 22). Findings: This systematic review found that sensitivities of office BP measurements varied widely, but specificities were consistently greater than 90% for both manual and automated measurements. Repeated BP measurements during the same office visit had limited value, and false elevations of BP occurred after caffeine ingestion. Ambulatory BP monitoring consistently predicted cardiovascular outcomes independently of officebased BP measurement whether the monitoring was done at night, during the day, or for 24 hours. Limited data suggest that home BP monitoring is similar to ambulatory BP monitoring. Information from 24 studies found wide variability in the percentage of patients (35% to 95%) whose elevated office BP was confirmed with ambulatory testing. People in high-risk groups and people with high normal BP had greater probabilities of elevated BP on remeasurement. Cautions: The study did not examine differences among ambulatory BP monitoring devices and among home BP monitoring devices. Implications: An isolated office BP measurement that indicates hypertension may need to be confirmed with ambulatory BP monitoring. People with elevated BP in the office but not elsewhere have cardiovascular outcomes that are similar to those of normotensive people. From Virginia Commonwealth University, Richmond, Virginia. Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje /ConflictOfInterestForms.do?msNum=M15-0274. Requests for Single Reprints: Stephanie A. Call, MD, MSPH, PO Box 980509, 1200 East Broad Street, Richmond, VA 23298; e-mail, [email protected]. Current Author Addresses: Drs. Hemrajani and Call: PO Box 980509, 1200 East Broad Street, Richmond, VA 23298. Author Contributions: Analysis and interpretation of the data:
R.H. Hemrajani. Drafting of the article: R.H. Hemrajani, S.A. Call. Critical revision of the article for important intellectual content: R.H. Hemrajani, S.A. Call. Final approval of the article: R.H. Hemrajani, S.A. Call. Administrative, technical, or logistic support: S.A. Call. Collection and assembly of data: R.H. Hemrajani, S.A. Call.
References 1. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139-51. [PMID: 19717844] doi:10.1056/NEJMoa 0905561 2. Eikelboom JW, Wallentin L, Connolly SJ, Ezekowitz M, Healey JS, Oldgren J, et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anti-
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