P Courtesy Dr. Jonathan Corren epithelial cell–derived thymic cytokine stro- subcutaneous tezepelumab, targets which the controlled of three dosing trial regimens of reported on aphase 2,randomized placebo- England Journal of Medicine, researchers Society. annualthe congress of European the Respiratory asthmatic according airways, to data presented at knownflammatory cytokine promoted to be in inhibition without lipid lowering lipid inhibition without The effects ofinflammation NEWS Frontline Medical News Frontline Medical BY NOGRADY BIANCA exacerbationsasthma in Tezepelumab reduces Writing 7issue Sept. inthe of New the monoclonal antibody that targets an in- despite treatment may from benefit anew atients asthma remains whose uncontrolled PAID U.S. Postage U.S. Permit No. 384 No. Permit Lebanon Jct. KY Lebanon Presorted Standard Presorted // 7 CHANGE SERVICE REQUESTED CHANGE SERVICE a first exacerbation,a first notedDr. Corren andcolleagues. It tooklongerforthosetreated withtezepelumabtohave each ARDS patient // each ARDS for Finding the optimalPEEP setting MEDICINE CARE CRITICAL

at 280 mg every 2 weeks, they were 2weeks,at they 66%lower 280mg every were 4weeks, they 71%lower;and210 mg every were 61%lower than group; placebo inthe at 2017;377:936-46). exacerbation with tezepelumab (NEngl JMed. with an overall 34%reduction risk of in the es of tezepelumab, compared with placebo, rates were significantly lower for three dos- all coids. medium ofglucocorti- doses to inhaled high treatment with long-acting beta-agonists and 584 patients with uncontrolled asthma, despite lymphopoietinmal involved (TSLP). The trial At 4weeks, exacerbation 70mg rates every The investigators found that exacerbation TIME TOFIRST EXACERBATION UPPED 10 CHEST PHYSICIAN 151 Fairchild Ave., Ave., 151 Fairchild Suite 2, NY 11803-1709 Plainview, Hurricane Harvey teamsprovideHospital care during RESPONSE DISASTER 2017 Online Registration ClosesOctober25 // continued // on page 4 chestmeeting.chestnet.org // 29 issue of CHEST (2017;152;486-93). statin use.” The study appears September inthe subtype of COPD patients that may from benefit suggest evidence, ed that there may aspecific be findings, inconjunction with previously report- measures of statin exposure,” wrote. they “Our mortality “persisteddecreased across several al, but association the statin and between use and his associates. Their study was observation- Universitythe of British Columbia, Vancouver, D.wrote Lynd, Larry PhD, aprofessor at at the to first exacerbation COPD inhigh-risk patients, (40 mg) didnot exacerbation affect rates or time (STATCOPE) daily inwhich simvastatin trial, tatin Prevention inthe of COPD Exacerbation rospective administrative database study. mortality, according to results the of alarge ret- mortality and a45%drop inrisk of pulmonary subsequent inthe 21% decrease risk of all-cause wastive associated pulmonary with a disease within ayear after diagnosis of chronic obstruc- FROM News Frontline Medical BYAMY KARON rates in COPD rates in lower death linkedStatins to COPD about affects 12%of adults aged 30 ofThe those recent the findings belie Simvas- CHEST MOST RECEIVEDA INSIDE HIGHLIGHT aspirin in stable CAD and PADand CAD stable aspirin in ofrivaroxabanThe benefits plus CARDIOVASCULAR MEDICINE n Receiving astatin prescription VOL. 12 TORVASTATIN // incoming CHEST • NEWS FROMNEWS CHEST An interview An interview NO. 10 President with the Page 59 • OCTOBER 2017 continued6 on page // 44 “The observed improvements Time to first exacerbation upped // continued from page 1 in disease control in patients (P was less than .001 in compari- in the placebo group, regardless volume in 1 second at week 52, who received tezepelumab sons between each group and the of a patient’s baseline eosinophil when compared with patients on highlight the potential placebo). count. Patients treated with teze- the placebo. The overall annualized exacer- pelumab had a longer time to first “The observed improvements pathogenic role of TSLP across bation rates by week 52 were 0.26 asthma exacerbation. They also in disease control in patients who different asthma phenotypes,” for the 70-mg group, 0.19 for the experienced a significantly higher received tezepelumab highlight the said Dr. Jonathan Corren. 210-mg group, and 0.22 for the change from baseline in their pre- potential pathogenic role of TSLP 280-mg group, compared with 0.67 bronchodilator forced expiratory across different asthma phenotypes,”

4 • OCTOBER 2017 • CHEST PHYSICIAN reported Jonathan Corren, MD, of type 2 inflammation.” Tezepelumab ‘most promising’ New England Journal of Medi- the University of California, Los An- The incidences of adverse events asthma biologic to date cine’s publication of this study geles, and his coauthors. “... Although and serious adverse events were Tezepelumab is the first biologic (2017;377:989-91). It appears to be TSLP is central to the regulation of similar across all groups in the that has a substantial positive effect the broadest and most promising type 2 immunity, many cell types that study. Three serious adverse events on two important markers of the biologic for the treatment of per- are activated by or respond to TSLP, – pneumonia and stroke in the inflammation of asthma – namely, sistent uncontrolled asthma to date, such as mast cells, basophils, natural same patient and one case of Guil- blood eosinophil counts and the said Dr. Bel, of the department of killer T cells, innate lymphoid cells, lain-Barré syndrome – in patients fraction of exhaled nitric oxide, respiratory medicine, Academic and neutrophils, may play a role in taking tezepelumab, were deemed noted Elisabeth H. Bel, MD, PhD, Medical Center, the University of inflammation in asthma beyond to be related to the treatment. in an editorial accompanying the Amsterdam. The observation that tezepelumab reduces the level of both inflammato- ry markers shows that it hits a more upstream target and that it blocks at least two relevant inflammatory Tezepelumab is the first biologic that has a substantial positive effect on two important markers of the inflammation of asthma, noted Elisabeth H. Bel, MD, PhD.

pathways in asthma, she noted. This is likely to be clinically relevant, since simultaneously increased exhaled ni- tric oxide levels and blood eosinophil counts are related to increased mor- bidity due to asthma. The study was supported by tezepelumab manufacturers Med- Immune (a member of the Astra- Zeneca group) and Amgen. Six of the seven authors are employees of MedImmune or Amgen. One author declared support and honoraria from several pharmaceutical compa- nies, one declared a related patent, and five also had stock options in either MedImmune or Amgen. Dr. Bel declared consultancies and grants from pharmaceutical companies including AstraZeneca.

VIEW ON THE NEWS Vera A. De Palo, MD, MBA, FCCP, comments: The impact of chronic respi- ratory disease on patients can be bur- densome. Therapies seek to reduce this disease’s impact on pa- tients’ lives. The disease burden takes a particularly heavy toll when the response to therapies is less than optimal. Quality of life and health pay the price. The authors of this phase 2 trial advance another possi- ble therapy which may hold promise for patients severely affected by persistent, treat- ment-resistant asthma.

CHESTPHYSICIAN.ORG • OCTOBER 2017 • 5 Most received atorvastatin // continued from page 1 NEWS FROM CHEST // 59 NETWORKS years and older worldwide and is COPD were prescribed a statin at Transbronchial cryobiopsy, associated with increased risk of least once during the subsequent updates to pediatric chronic progressive cardiovascular disease year. These patients had a signifi- and cardiovascular mortality. “Lo- cantly reduced risk of subsequent cough guidelines, and more // 63 calized chronic all-cause mortality CHEST PHYSICIAN inflammation of “Localized chronic in univariate and IS ONLINE the airways has multivariate anal- Vera A. De Palo, MD, MBA, inflammation of the CHEST Physician is available at FCCP, is Medical Editor in long been ob- yses, with hazard chestphysician.org. Chief of CHEST Physician. served in COPD airways has long been ratios of 0.79 (95% IN THIS ISSUE patients, but there observed in COPD confidence inter- is a growing un- vals, 0.68-0.91; P derstanding of patients, but there is a less than .002). systemic inflam- growing understanding Statins also showed mation in a subset a protective effect of systemic inflammation AMERICAN COLLEGE OF CHEST CHEST PHYSICIAN, the newspaper of the American of patients,” the against pulmonary PHYSICIANS (CHEST) College of Chest Physicians, provides cutting-edge researchers noted. in a subset of patients.” mortality, with EDITOR IN CHIEF reports from clinical meetings, FDA coverage, clinical Vera A. De Palo, MD, MBA, FCCP trial results, expert commentary, and reporting on For example, stud- univariate and mul- the business and politics of chest medicine. Each ies have linked chronic low-level tivariate hazard ratios of 0.52 (P DEPUTY EDITOR IN CHIEF issue also provides material exclusive to CHEST systemic inflammation or elevat- = .01) and 0.55 (P = .03), respec- David A. Schulman, MD, FCCP members. Content for CHEST PHYSICIAN is provided PRESIDENT by Frontline Medical Communications Inc. Content ed C-reactive protein levels with tively. Gerard A. Silvestri, MD, MS, FCCP for News From Chest is provided by the American College of Chest Physicians. increased risks of severe airway The protective effect of statins EXECUTIVE VICE PRESIDENT & CEO The statements and opinions expressed in CHEST obstruction, other pulmonary out- held up when the investigators Stephen J. Welch PHYSICIAN do not necessarily reflect those of the comes, and adverse cardiovascular narrowed the exposure period to MANAGER, EDITORIAL RESOURCES American College of Chest Physicians, or of its events. Such findings prompted 6 months after COPD diagnosis Pamela L. Goorsky officers, regents, members, and employees, or those experts to suggest that COPD and when they PUBS & DIGITAL CONTENT EDITOR of the Publisher. The American College of Chest Martha Zaborowski Physicians, its officers, regents, members, and progression results from systemic expanded it to employees, and Frontline Medical Communications SECTION EDITORS Inc. do not assume responsibility for damages, loss, inflammation, not a “spill over” of 18 months. Ex- Nitin Puri, MD, FCCP or claims of any kind arising from or related to the pulmonary inflammation, and that posure to statins Pulmonary Perspectives¨ information contained in this publication, including any claims related to products, drugs, or services statins might help slow or block for 80% of the Lee E. Morrow, MD, FCCP mentioned herein. Critical Care Commentary this process. Although STATCOPE 1-year window POSTMASTER: Send change did not support this idea, several after COPD Jeremy A. Weingarten, MD, FCCP of address (with old mailing prior observational studies did. In- diagnosis – a Sleep Strategies label) to CHEST PHYSICIAN, flammation-inhibiting therapy also proxy for statin EDITORIAL ADVISORY BOARD Subscription Service, 151 reduced cardiovascular events and adherence – also G. Hossein Almassi, MD, FCCP, Wisconsin Fairchild Ave., Suite 2, Plainview, NY 11803-1709. lung cancer in the recent CANTOS DR. LYND led to a reduced Jennifer Cox, MD, FCCP, Florida Scan this QR CHEST PHYSICIAN Code to visit Jacques-Pierre Fontaine, MD, FCCP, Florida trial, which this issue covers on risk of all-cause (ISSN 1558-6200) is chestnet.org/ page 7. mortality, but the 95% confidence Eric Gartman, MD, FCCP, Rhode Island published monthly for chestphysician Octavian C. Ioachimescu, MD, PhD, FCCP, the American College of To further explore the question, interval for the hazard ratio did not Georgia Chest Physicians by Frontline Medical the researchers analyzed linked reach statistical significance (0.71- Jason Lazar, MD, FCCP, New York Communications Inc., 7 Century Drive, health databases from nearly 40,000 1.01; P = .06). Susan Millard, MD, FCCP, Michigan Suite 302, Parsippany, NJ 07054-4609. Michael E. Nelson, MD, FCCP, Kansas Subscription price is $237.00 per year. patients aged 50 years and older The most common prescription Phone 973-206-3434, fax 973-206-9378. Daniel Ouellette, MD, FCCP, Michigan EDITORIAL OFFICES 2275 Research Blvd, who had received at least three was for atorvastatin (49%), usually Frank Podbielski, MD, FCCP, Massachusetts Suite 400, Rockville, MD 20850, 240-221- prescriptions for an anticholinergic for 90 days (23%), 100 days (20%), M. Patricia Rivera, MD, FCCP, North Carolina 2400, fax 240-221-2548 or a short-acting beta agonist in 12 or 30 days (15%), the research- Nirmal S. Sharma, MD, San Francisco, ADVERTISING OFFICES 7 Century Drive, months some time between 1998 ers said. While the “possibility of California Suite 302, Parsippany, NJ 07054-4609 Eleanor Summerhill, MD, FCCP, Rhode Island 973-206-3434, fax 973-206-9378 and 2007. The first prescription the ‘healthy user’ or the ‘healthy Krishna Sundar, MD, FCCP, Utah ©Copyright 2017, by the American was considered the date of COPD adherer’ cannot be ignored,” they College of Chest Physicians E-mail: [email protected] “diagnosis.” The average age of the adjusted for other prescriptions, patients was 71 years; 55% were fe- comorbidities, and income level, FRONTLINE MEDICAL COMMUNICATIONS male. which should have helped eliminate CHAIRMAN Stephen Stoneburn A total of 7,775 patients (19.6%) this effect, they added. However, PRESIDENT/CEO Alan J. Imhoff who met this definition of incident they lacked data on smoking and CFO Douglas E. Grose FRONTLINE MEDICAL PRESIDENT, DIGITAL Douglas E. Grose lung function assessments, both of COMMUNICATIONS CHIEF DIGITAL OFFICER Lee Schweizer which are “important confounders SOCIETY PARTNERS VICE PRESIDENT, DIGITAL PUBLISHING Amy Pfeiffer VIEW ON THE NEWS and contributors to mortality,” they VP/GROUP PUBLISHER; DIRECTOR, PRESIDENT, CUSTOM SOLUTIONS JoAnn Wahl Vera A. De Palo, MD, MBA, FCCP, acknowledged. FMC SOCIETY PARTNERS Mark Branca VICE PRESIDENT, CUSTOM PROGRAMS Carol Nathan EDITOR IN CHIEF Mary Jo M. Dales VICE PRESIDENT, CUSTOM SOLUTIONS Wendy comments: The interplay of Despite [its] limitations, the study EXECUTIVE EDITORS Denise Fulton, Raupers multiple chronic diseases con- results are intriguing and in line Kathy Scarbeck SENIOR VICE PRESIDENT, FINANCE Steven J. Resnick tributing to a patient’s medi- with findings from other retro- CREATIVE DIRECTOR Louise A. VICE PRESIDENT, HUMAN RESOURCES & FACILITY Koenig OPERATIONS Carolyn Caccavelli cal history is a complex one. spective cohorts, noted Or Kalch- VICE PRESIDENT, MARKETING & CUSTOMER ADVOCACY DIRECTOR, PRODUCTION/ Jim McDonough As the provider seeks to treat iem-Dekel, MD, and Robert M. MANUFACTURING Rebecca VICE PRESIDENT, OPERATIONS Jim Chicca the whole patient, improve- Reed, MD, in an editorial published Slebodnik VICE PRESIDENT, SALES Mike Guire ments in common endpoints in CHEST (2017;152:456-7. doi: DIRECTOR, BUSINESS DEVELOPMENT VICE PRESIDENT, SOCIETY PARTNERS Mark Branca may occur. The observations Angela Labrozzi, 973-206-8971, CIRCULATION DIRECTOR Jared Sonners 10.1016/j.chest.2017.04.156). cell 917-455-6071, alabrozzi@ CORPORATE DIRECTOR, RESEARCH & COMMUNICATIONS of the authors of this study How then can we reconcile the frontlinemedcom.com Lori Raskin are interesting. Further study apparent benefits observed in ret- CLASSIFIED SALES REPRESENTATIVE EDITORIAL DIRECTOR, CLINICAL Karen J. Clemments could help better understand rospective studies with the lack Drew Endy 215-657-2319, cell 267-481-0133 dendy@ In affiliation with Global Academy for Medical the effects of statins in COPD of clinical effect seen in prospec- frontlinemedcom.com Education, LLC patients. tive trials, particularly the in the SENIOR DIRECTOR OF CLASSIFIED SALES VICE PRESIDENT, MEDICAL EDUCATION & CONFERENCES Tim LaPella, 484-921-5001, Sylvia H. Reitman, MBA Continued on following page VICE PRESIDENT, EVENTS David J. Small, MBA [email protected]

6 • OCTOBER 2017 • CHEST PHYSICIAN NEWS CANTOS sings of new strategy for reducing CV events BY BRUCE JANCIN ous MI and a chronically high level with a median LDL cholesterol of 82 monoclonal antibody targeting IL-1B, Frontline Medical News of systemic inflammation as reflect- mg/dL when randomized to subcu- a key player in systemic inflamma- ed in a median baseline high-sensi- taneous canakinumab at 50, 150, or tion. The cytokine is activated by BARCELONA – Inhibiting the in- tivity C-reactive protein (CRP) level 300 mg or to placebo once every 3 the nucleotide-binding oligomeriza- terleukin-1 beta innate immunity of 4.1 mg/L. Ninety-one percent of months. tion domain-like receptor protein 3 pathway with canakinumab reduced participants were on statin therapy, Canakinumab is a fully human Continued on following page recurrent cardiovascular events and lung cancer in the groundbreaking phase 3 CANTOS trial, Paul M. Ridker, MD, reported at the annual congress of the European Society of Cardiology. “These data provide the first proof that inflammation inhibition in the absence of lipid lowering can im- prove atherogenic outcomes and potentially alter progression of some fatal cancers,” declared Dr. Ridker, director of the Center for Cardiovas- cular Disease Prevention at Brigham and Women’s Hospital, Boston, and professor of medicine at Harvard Medical School. “Just like we’ve learned that low- er LDL is better, I think we’re now learning that lower inflammation is better,” he said. CANTOS (Canakinumab Anti- inflammatory Thrombosis Out- come Study) was a randomized, double-blind, placebo-controlled trial involving 10,061 patients in 39 countries, all of whom had a previ-

Continued from previous page STATCOPE study? Could it be that both negative and positive studies are “correct”? Prospective studies have thus far not been ad- equately powered for mortality as an endpoint, said the editorialists, who are both at the pulmonary and critical care medicine division, University of Maryland, Baltimore. This most recent study reinforc- es the idea that statins may play a beneficial role in COPD, but it isn’t clear which patients to target for therapy. It is unlikely that the find- ings will reverse recent recommen- dations by the American College of Chest Physicians and Canadian Thoracic Society against the use of statins for the purpose of preven- tion of COPD exacerbations, but the suggestion of survival advan- tage related to statins certainly may breathe new life into an enthusiasm greatly tempered by STATCOPE, they said. Canadian Institutes of Health Research supported the study. One coinvestigator disclosed consulting relationships with Teva, Pfizer, and Novartis; the others had no conflicts of interest. Neither editorialist had conflicts of interest.

CHESTPHYSICIAN.ORG • OCTOBER 2017 • 7 NEWS Increase in sepsis incidence stable from 2009 to 2014 BY RICHARD FRANKI Unadjusted sepsis incidence, 2009-2014 sensitive than explicit sepsis codes Frontline Medical News on medical record review, with 5% comparable [positive predictive val- he trend for sepsis incidence ue]; EHR-based criteria had similar from 2009 to 2014, “calcu- sensitivity to implicit or explicit 4% Tlated relative to the observed Clinical criteria codes combined but higher [pos- 2014 rates,” was a stable increase itive predictive value],” they said. of 0.6% per year using the more 3% The estimates provided by Dr. Rhee accurate of two forms of analysis, and his associates lead to “a clearer investigators reported. Explicit codes understanding of trends in the in- The incidence of sepsis was an 2% cidence and mortality of sepsis in adjusted 5.9% among hospitalized the United States but also a better adults in 2014, with in-hospital 1% understanding of the challenges in mortality of 15%, according to a improving ICD coding to accurate- retrospective cohort study published ly document the global burden of 0 MEDICAL FRONTLINE NEWS online Sept. 13 in JAMA. 2009 2010 2011 2012 2013 2014 sepsis,” Kristina E. Rudd, MD, of the “Most studies [of sepsis incidence] University of Washington, Seattle, have used claims data, but increas- Notes: Based on data for adults admitted to 409 academic, community, and federal hospitals. and her associates said in an editorial ing clinical awareness, changes in Rates for 2009-2013 calculated relative to observed 2014 rates. (JAMA. 2017 Sep 13. doi: 10.1001/ diagnosis and coding practices, Source: JAMA 2017 Sep 13. doi: 10.1001/jama.2017.13836 jama.2017.13697). and variable definitions have led The Centers for Disease Control to uncertainty about the accuracy admitted to 409 U.S. academic, level of 2.0 mmol/L or greater. and Prevention, Agency for Health- of reported trends,” wrote Chanu community, and federal acute-care The explicit-codes approach pro- care Research and Quality, National Rhee, MD, of Harvard Medical hospitals in 2014. The claims- duced an increase of 10.3% per year Institutes of Health, Department School, Boston, and his associates based explicit-codes approach in sepsis incidence from 2009 to of Veterans Affairs, National Insti- (JAMA. 2017 Sep 13. doi: 10.1001/ used discharge diagnoses of severe 2014, compared with 0.6% per year tutes of Health Clinical Center, and jama.2017.13836). sepsis (995.92) or septic shock for the clinical-criteria approach, National Institute of Allergy and They used claims-based esti- (785.52), while the EHR-based, while in-hospital mortality declined Infectious Diseases funded the study. mates using ICD-9-CM codes and clinical-criteria method included by 7% a year using explicit codes Three authors received personal fees clinical data from electronic health blood cultures, antibiotics, and and 3.3% using clinical criteria, Dr. from private companies or served on records (EHRs) to analyze data concurrent organ dysfunction with Rhee and his associates reported. advisory boards or as consultants. for more than 2.9 million adults or without the criterion of a lactate “EHR-based criteria were more [email protected]

Continued from previous page that’s a progression-of-atherosclerosis inhalation of asbestos or other sil- (NLRP3) inflammasome, a part of the endpoint and also obviously a cost icates – these cause inflammation innate immune system. Canakinumab and financial endpoint,” he observed. which activates the NLRP3 inflam- is approved as Ilaris for treatment of A key finding in CANTOS was masome, but in the pulmonary several uncommon rheumatologic that patients with a reduction in system rather than the arteries,” diseases, including cryopryin-associ- CRP at or exceeding the median de- explained Dr. Ridker, who reported ated periodic syndrome and systemic crease just 3 months into the study – serving as a consultant to Novartis. juvenile idiopathic arthritis. that is, after a single injection – had An entry requirement in CAN- At a median follow-up of 3.7 a 27% reduction in major vascular TOS was that patients needed to years, the incidence of the prima- events during follow-up. Patients be free of known cancer. During ry composite efficacy endpoint with a lesser reduction in CRP at study follow-up, 129 patients were of nonfatal MI, nonfatal stroke, that point did not experience a sig- diagnosed with lung cancer. The or cardiovascular death was 4.5 nificant reduction in the primary risk was reduced in dose-dependent events per 100 person-years in the endpoint, compared with placebo. Dr. Paul M. Ridker fashion with canakinumab: by 39% control group, significantly higher “The clinician in me would say we relative to placebo in the 150-mg than the 3.86 and 3.9 events per probably ought to give a single dose You would imagine that, if this does group and by 67% in the 300-mg 100 person-years in patients on of the drug, see what happens, and become a treatment, physicians will group. Lung cancer mortality was canakinumab at 150 and 300 mg, if you get a large inflammation re- get much better at bringing patients reduced by 77% in the canakinumab respectively. duction we could perhaps consider in early when they have signs and 300-mg group. Since event rates were virtually treating that patient, but if you did symptoms of infection,” the cardiol- “I don’t think this is about onco- identical in the 150- and 300-mg not get a large reduction perhaps ogist continued. genesis per se. I think the tumors study arms, Dr. Ridker combined this is not a therapy for that patient. Patients on canakinumab showed are already there, but they don’t those two patient groups in his Why not avoid the toxicity in people significant reductions in incident progress because we’ve altered the analysis. They showed a 15% re- who aren’t going to respond?” Dr. rheumatoid arthritis, gout, and os- tumor’s inflammatory microenvi- duction in the risk of the primary Ridker said. teoarthritis. The drug had no kidney ronment,” he continued. efficacy endpoint, compared with Side effects related to canakinum- or liver adverse events. Simultaneous with Dr. Ridker’s placebo-treated controls, along ab consisted of mild leukopenia and Cancer was a prespecified sec- presentation in Barcelona, both with a 39% reduction from base- a small but statistically significant ondary outcome in CANTOS. The the atherosclerotic disease find- line in CRP. They also were 30% increase in fatal infections, which he investigators saw the trial as an op- ings (N Engl J Med. 2017 Aug 27. less likely to undergo percutane- called “not surprising.” portunity to test a longstanding hy- doi: 10.1056/NEJMoa1707914) ous coronary intervention or cor- “It’s in the same range as one gets pothesis that inhibiting IL-1B would and the cancer findings (Lancet. onary artery bypass graft during in treating rheumatoid arthritis with have a positive impact on lung can- 2017 Aug 27. doi: 10.1016/S0140- follow-up. a biologic drug, which rheumatol- cer in particular. 6736(17)32247-X) were published. “That’s quite important, because ogists are very comfortable doing. “Smoking, exposure to diesel fuel, [email protected]

8 • OCTOBER 2017 • CHEST PHYSICIAN

CRITICAL CARE MEDICINE Bedside imaging finds best PEEP settings

BY MICHELE G. SULLIVAN Marie Curie University, Paris. then lowered by 5-cm H2O decre- bution,” they concluded. “To achieve Frontline Medical News “Using EIT allowed monitoring ments with the potential of reaching that goal, EIT seems to be an inter- of the PEEP effect that prevented PEEP 0. esting bedside noninvasive tool to noninvasive bedside imaging excessive lung collapse or overdis- The EIT device, consisting of provide real-time monitoring of the technique can individually tension. ... The large variability of a silicone belt with 16 surface PEEP effect and ventilation distribu- A calibrate positive end-expira- EIT-based best compromise PEEP electrodes, was placed around tion on ECMO.” tory pressure settings in patients on settings … reinforces the notion of the thorax aligning with the sixth extracorporeal membrane oxygen- an individually tailored approach intercostal parasternal space and Positive PEEP trial, but ation (ECMO) for severe acute re- to mechanical ventilation. Because connected to a monitor. By mea- questions remain spiratory distress syndrome (ARDS), of the wide diversity of respirato- suring conductivity and impedi- This first study to examine EIT a study showed. ry-system mechanical properties tivity in the underlying tissues, in patients under extracorpore- The step-down PEEP (positive among patients, bedside tools for the device generates a low-reso- al membrane oxygenation shows end-expiratory pressure) trial could monitoring mechanical ventilation lution, two-dimensional image. important clinical potential, but not identify a single PEEP set- on ECMO are crucial to achieve The image was sufficient to show also raises important questions, ting that optimally balanced lung this goal.” lung distension and collapse as Claude Guerin, MD, wrote in an overdistension and lung collapse The 4-month study involved 15 the PEEP settings changed. Inves- accompanying editorial. (Am J Re- for all 15 patients. But, electrical patients (aged, 18-79 years) who tigators looked for the best com- spir Crit Care Med. doi: 10.1164/ impedance tomography (EIT) al- were in acute respiratory distress promise between overdistension rccm.201701-0167ed). lowed investigators to individually syndrome for a variety of reasons, and collapsed zones, which they The ability to titrate PEEP set- titrate PEEP settings for each pa- including influenza (7 patients), defined as the lowest pressure able tings to a patient’s individual needs tient, Guillaume Franchineau, MD, pneumonia (3), leukemia (2), and to limit EIT-assessed collapse to could substantially reduce the risk wrote (Am J Respir Crit Care Med. 1 case each of Pneumocystis, anti- no more than 15% with the least of lung derecruitment or damage 2017;196[4]:447-57. doi: 10.1164/ synthetase syndrome, and trauma. overdistension. by overdistension. rccm.201605-1055OC). All patients were receiving ECMO There was no one-size-fits-all The current study, however, has “We found that EIT could pro- with a constant driving pressure of PEEP setting, the authors found. limitations that must be addressed vide individual, noninvasive, 14 cm H2O. After verifying that the The setting that minimized both in the next phase of research, before real-time, radiation-free lung inspiratory flow was 0 at the end of overdistension and collapse was this technique can be adopted into imaging with reliable global and inspiration, PEEP was increased to PEEP 15 in seven patients, PEEP 10 clinical practice, noted Dr. Guerin, regional dynamic analyses of 20 cm H2O (PEEP 20) with a peak in six patients, and PEEP 5 in two a pulmonologist at the Hospital de the lungs on ECMO,” wrote Dr. inspiratory pressure of 34 cm H2O. patients. la Croix Rousse, Lyon, France. The Franchineau of the Pierre and PEEP 20 was held for 20 minutes and At each patient’s optimal PEEP 5-cm H20 PEEP steps may be too setting, the median tidal volume was large to detect relevant changes, he similar: 3.8 mL/kg ideal body weight said. for PEEP 15, 3.9 mL/kg ideal body In several other studies, PEEP weight for PEEP 10, and 4.3 mL/kg was reduced more gradually in 2- to ideal body weight for PEEP 5. 3-cm H2O increments. “Surprising- 2017 Respiratory system compliance ly, PEEP was reduced to 0 cm H2O was also similar among the groups, in this study, with this step main- at 20 mL/cm H2O, 18 mL/cm H2O, Continued on following page and 21 mL/cm H2O, respectively. However, arterial partial pressure of oxygen decreased as the PEEP set- VIEW ON THE NEWS ting decreased, dropping from 148 Daniel Ouellette, MD, FCCP, com- mm Hg to 128 mm Hg to 100 mm ments: We have learned that Hg, respectively. Conversely, arterial patients with partial pressure of CO2 increased ARDS should (32-41 mm Hg). be treated EIT also allowed clinicians to with mechani- pinpoint areas of distension or col- cal ventilation CHEST Annual Meeting is your connection to education opportunities that will help optimize lapse. As PEEP decreased, there was in a fashion your patient care. This year’s focus is on the entire team, and we’re busy preparing our sessions, steady ventilation loss in the medi- that mini- speakers, networking events, and foundation events to make sure each experience is centered al-dorsal and dorsal regions, which mizes driving around the complete care team, so you can optimize your patient care. shifted to the medial-ventral and pressure and

The CHEST Annual Meeting offers: ventral regions. optimizes n More than 400 general sessions “Most end-expiratory lung imped- PEEP. The use of electrical n Hands-on simulation sessions, virtual patient tours (VPTs), and GAMEs ances were located in medial-dorsal impedence tomography to n Full- and half-day postgraduate tracks to accommodate all schedules and medial-ventral regions, whereas noninvasively inform clinicians n Interdisciplinary programs designed around the entire care team, the dorsal region constantly contrib- about optimal PEEP in ARDS addressing clinical issues across the disciplines uted less than 10% of total end-expi- patients receiving extracorpo- n Original investigation presentations n New diagnostic and treatment solutions showcased in the exhibit hall ratory lung impedance,” the authors real membrane oxygenation is n Networking and social opportunities with experts in your field noted. therefore intriguing. Conclu- “The broad variability of EIT- sions are limited by the small size of this study. Further Online Registration Closes October 25 based best compromise PEEPs in these patients with severe ARDS work will be needed to learn chestmeeting.chestnet.org reinforces the need to provide ven- if these measurements will be tilation settings individually tailored generally applicable. to the regional ARDS-lesion distri-

10 • OCTOBER 2017 • CHEST PHYSICIAN CRITICAL CARE MEDICINE Doubts about pediatric CAP diagnostic practices

BY THOMAS R. COLLINS In one study, 128 cases of suspect- minutes of each other. Only 3 of the lower end of the 95% confiden- Frontline Medical News ed CAP in children aged 3 months 19 exam findings used to diagnose tial interval at a Fleiss’ kappa value to 18 years presenting to an ED CAP – wheezing, retractions, and of 0.4 or higher. ew studies raise doubts on the from July 2013 to May 2016 under- respiratory rate – had acceptable Eight exam findings – capillary reliability of physical exam went paired assessments within 20 levels of inter-rater reliability, with Continued on following page Nfindings in suspected pediatric community-acquired pneumonia cases and on the value of blood cul- tures in hospitalized pediatric CAP cases.

Continued from previous page tained for 20 minutes, raising the risk of derecruitment and further stretching once higher PEEP levels were resumed.” The investigators did not perform any recruitment maneuvers before proceeding with PEEP adjustment. This is contrary to what has been done in prior animal and human studies. The computation of driving pres- sure was done without taking total PEEP into account. “As total PEEP is frequently greater than PEEP in patients with [acute respiratory dis- tress syndrome], driving pressure can be overestimated with the com- mon computation.” The optimal PEEP that the investi- gators aimed for was determined ret- rospectively from an offline analysis of the data; this technique would not be suitable for bedside management. “When ‘optimal’ PEEP was defined from [EIT criteria], from a higher PaO2 [arterial partial pressure of ox- ygen] or from a higher compliance of the respiratory system during the decremental PEEP trial, these three criteria were observed together in only four patients with [acute respi- ratory distress syndrome].” The study was done only once and cannot comply with the need for regular PEEP-level assessments over time, as could be done with some other strategies. “Further studies should also con- sider taking into account the role of chest wall mechanics,” Dr. Guerin said. Nevertheless, he concluded, EIT- based PEEP titration for each individ- ual patient represents a prospective tool for assisting with the treatment of acute respiratory distress syndrome, and should be fully investigated in a large, prospective trial. Dr. Franchineau reported receiv- ing speakers fees from Mapquet. Dr. Sunovion Pharmaceuticals Inc. is a U.S. subsidiary of Sumitomo Dainippon Pharma Co., Ltd. UTIBRON and are trademarks of Novartis AG, used under license. Guerin had no relevant financial NEOHALER is a registered trademark of Novartis AG, used under license. disclosures. © 2017 Sunovion Pharmaceuticals Inc. All rights reserved. 07/17 UTB253-17 [email protected] On Twitter @alz_gal

CHESTPHYSICIAN.ORG • OCTOBER 2017 • 11 Continued from previous page search in Pneumonia Etiology and refill time, cough, rhonchi, head Diagnostic Innovations in Emergen- bobbing, behavior, grunting, general cy Medicine, or CARPE DIEM. appearance, and decreased breath “The reliability of these findings sounds – had poor to fair reliability, must be considered in the clinical with a kappa of 0-0.4, the investiga- management and research of chil- tors found. These results came from dren with CAP,” said lead author an ongoing prospective cohort study Todd Florin, MD, associate research of children with suspected CAP director in emergency medicine at

CDC/Amanda CDC/Amanda Mills called Catalyzing Ambulatory Re- Cincinnati Children’s Hospital Med-

12 • OCTOBER 2017 • CHEST PHYSICIAN ical Center and his associate. (Pedi- the pathogens that were found; it was pital and his associates (Pediatrics. and radiographic information is atrics. 2017;140[3]:e20170310) detected in only 2% of all children 2017;140[3]:e20171013). stored from six tertiary children’s In a retrospective cohort analysis, who had blood cultures taken. The analysis was drawn from a hospitals. researchers found that just 2.5% of Just 11 children – or 0.43% of cohort of 7,509 children hospitalized The investigators said that one 2,568 hospitalized children with CAP the children with a blood cul- from 2007 to 2011, with children challenge is that when blood cul- who had a blood culture performed ture performed – had growth of with complex chronic conditions tures are drawn early in the course actually grew a pathogen. And of the a pathogen that was not treatable excluded. Data for the analysis came of evaluation and treatment, the se- detected pathogens, 82% were sus- with penicillin, said lead author from the Pediatric Health Informa- verity of the child’s CAP might not ceptible to penicillin. Streptococcus Mark Neuman, MD, director of tion System Plus database, in which be apparent, which makes it difficult pneumoniae accounted for 78% of all research at Boston Children’s Hos- administrative, billing, laboratory, to know which children would ben- efit from a blood culture. The routine performance of blood cultures in these children may not be indicated,” Dr. Neuman and his associates said. “Researchers in future studies should seek to identify the clinical characteristics of children in whom obtaining blood cultures would lead to changes in clinical management, especially when iden- tifying those patients at risk for CAP caused by organisms not susceptible to guideline-recommended, nar- row-spectrum antibiotics.” Both studies were funded by the National Institutes of Health. For the physician exam study, additional funding was provided by individual grants from the Gerber Foundation, the National Center for Research Resources and the National Center for Advancing Translational Scienc- es, the National Institute for Allergy and Infectious Diseases and the National Institutes of Health, and a Trustee Award from Cincinnati Children’s Hospital Medical Center. For the blood cultures study, indi- vidual researchers received funding from the National Institute of Al- lergy and Infectious Diseases and the Agency for Healthcare Research and Quality. For the physician exam study, no financial disclosures were reported. For the blood cultures study, Anne Blaschke, MD, PhD, reported receiving research funding from and other financial relation- ships with BioFire Diagnostics.

VIEW ON THE NEWS Susan Millard, MD, FCCP, com- ments: This study is import- ant, because it included a large number of children. We have known for a long time that blood cultures are typically not helpful in older infants and children with CAP. The study also reminds me when educating residents and medical students that physical exam won’t necessarily dis- tinguish between bacterial vs viral pneumonias.

CHESTPHYSICIAN.ORG • OCTOBER 2017 • 13 CRITICAL CARE COMMENTARY Can we stop worrying about the age of blood?

BY CHRISTOPHER L. CARROLL, MD, MS, in circulation 24 hours after the transfusion. But Dr. Carroll is Professor FCCP some have suggested that these specifications of Pediatrics, University aren’t comprehensive enough, citing studies that of Connecticut, Division lood transfusions are common in critically have linked prolonged storage to the development of Critical Care, Con- ill patients; two in five adults admitted to an of “red blood storage lesion.” Red blood storage necticut Children’s Med- BICU receive at least one transfusion during lesion has been theorized to have a variety of ical Center, Hartford, their hospitalization (Corwin HL, et al. Crit Care effects, including altered immunologic response Connecticut. Med. 2004;32[1]:39). Recently, there has been and defective oxygen carrying capacity (Spinella growing concern about the potential dangers PC, et al. Transfusion. 2011;51[4]:894). But do involved with prolonged blood storage. Several these changes have clinical implications? provocative observational and retrospective stud- In a randomized study of 100 critically ill ies found that prolonged storage time (ie, the age adults supported by mechanical ventilation, 50 of the blood being transfused) negatively affects were randomized to receive “fresh” blood (me- clinical outcomes (Wang D, et al. Transfusion. dian storage age 4 days, interquartile range 3-5 The INFORM (Informing Fresh versus Old 2012;52[6]:1184). But now, some newly published days) and 50 were randomized to receive “stan- Red Cell Management) trial was a randomized trials on blood transfusion practice, including dard” blood (median storage age 26.5 days, study of patients hospitalized in six centers one published in late September 2017 (Cooper interquartile range 21-36 days) (Kor DJ, et al. in Canada, Australia, Israel, and the Unit- DJ, et al. N Engl J Med. Published online, Septem- Am J Respir Crit Care Med. 2012;185[8]:842). ed States (Heddle NM, et al. N Engl J Med. ber 27, 2017) seem to debunk much of this liter- The primary outcome was gas exchange, as 2016;375[2]:1937). A total of 24,736 patients ature. Was all of the concern about age of blood prolonged storage of red blood cells could po- received transfusions with either “fresh” blood overblown? tentially lead to an increased inflammatory re- (median storage age 11 days) or “standard” The appeal of “fresh” blood is intuitive. As sponse in patients. However, the authors found blood (median storage age 23 days). The prima- consumers, we’re conditioned that the fresher the no difference in gas exchange between the two ry outcome was in-hospital death, with a 90% better. Fresh food tastes best. Carbonated bev- groups, and there were no differences in im- power to detect a 15% lower relative risk. When erages go “flat” over time. The newest iPhone® munologic function or coagulation status. comparing the 8,215 patients who received device is superior to your old one. So, of course, The ABLE (Age of Blood Evaluation) trial was “fresh” blood and the 16,521 patients who re- it follows that fresh blood is also better for your a randomized, blinded trial of transfusion prac- ceived “standard” blood, the authors found no health than older blood. tices in critically ill patients (Lacroix J, et al. N difference in mortality between the two groups But, in order to have a viable transfusion service, Engl J Med. 2015;372:1410). In 64 centers in Can- (9.1% vs 8.8%; odds ratio 1.04; 95% CI 0.95 to blood has to be stored. Blood is a scarce resource, ada and Europe, 2,430 critically ill adults were 1.14). Furthermore, there were no differences and blood banks need to keep an adequate supply randomized to receive either “fresh” blood (mean in outcomes in the high-risk subgroups that in- on hand for expected clinical necessities, as well storage age 6.1 ± 4.9 days) or “standard” blood cluded patients with cancer, patients in the ICU, as for emergencies. Donors can’t be on standby, (mean storage age 22.0 ± 8.4 days). The primary and patients undergoing cardiovascular surgery. waiting in the hospital to provide immediate whole outcome was 90-day mortality, with a power of A meta-analysis examined 12 trials of patients blood transfusion. Also, blood needs to be tested 90% to detect a 5% change in mortality between who received “fresh” blood compared with those for infections and for potential interactions with the two groups. The investigators found no statis- who received “older” or “standard” blood (Alex- the patient, and whole blood must be broken down tically significant difference in 90-day mortality ander PE, et al. Blood. 2016;127[4]:400); 5,229 into individual components for transfusion. All of between the “fresh” and “standard” groups (37% patients were included in these trials, in which this requires time and storage. vs 35.3%; hazard ratio 1.1; 95% CI 0.9 – 1.2). Ad- “fresh” blood was defined as blood stored for According to the US FDA, blood can safely be ditionally, there were no differences in secondary 3 to 10 days and “older” blood was stored for stored for up to 42 days, requiring that there be outcomes, including multiorgan system dysfunc- longer durations. There was no difference in less than 1% hemolysis at the end of storage, and tion, duration of supportive care, or development mortality between the two groups (relative risk that more than 75% of the red blood cells remain of nosocomial infections. 1.04; 95% CI 0.94 - 1.14), and no difference in adverse events (relative risk 1.02; 95% CI 0.91 - 1.14). However, perhaps surprisingly, “fresh” blood was associated with an increased risk of nosocomial infections (relative risk 1.09; 95% CI 1.00 - 1.18). And finally, in the recently published TRANS- FUSE trial (Cooper DJ, et al. N Engl J Med. Published online, September 27, 2017), 4,994 critically ill adults were randomized by 59 cen- ters in five countries to receive transfusions stored for a short-term (median storage of 11 days) or long-term (median 21 days). Similar to the other three randomized trials, there was no difference in mortality between the two groups at both 90 and 180 days. So, can we stop worrying about the age of the blood that we are about to transfuse? Probably. Taken together, these studies suggest that differ- ences in the duration of red blood cell storage allowed within current US FDA standards aren’t clinically relevant, even in critically ill patients. At least, for now, the current practices for age of blood and duration of storage appear unrelated to

Tomasz Gierygowski/Thinkstock Tomasz adverse clinical outcomes.

14 • OCTOBER 2017 • CHEST PHYSICIAN CHPH_15.indd 1 9/25/2017 3:05:50 PM PEDIATRIC PULMONARY MEDICINE Thirdhand smoke shaping Transient tachypnea ups up as potential hazard

bronchiolitis risk BY BRUCE JANCIN known to be harmful develop- Frontline Medical News mentally are nicotine, tobacco- BY BRUCE JANCIN en pulmonary fluid transport may specific nitrosamines, lead, Frontline Medical News predispose to clinically significant DENVER – Thirdhand smoke – cadmium, and various reactive bronchiolitis during the first year of the persistent residue that collects molecules. The odiferous third- MADRID – A new Finnish study life,” said Dr. Helve, a pediatrician at on indoor surfaces where peo- hand smoke residue, composed of raises a provocative question: Is the National Institute for Health and ple have smoked – is “clearly” a tobacco-smoke toxins and known transient tachypnea of the newborn Welfare, Helsinki, and the Universi- potentially hazardous exposure, cancer-causing agents, adheres really transient? ty of Helsinki. John M. Rogers, PhD, said at the to house dust, furniture, carpets, Transient tachy- Data from Finland’s Of more than 1 annual meeting of the Teratology walls, window glass, and other pnea of the new- comprehensive national million term babies Society. surfaces. It’s difficult to remove. born (TTN) has born in Finland Everyone Unlike with sec- traditionally been health registries indicate that during 1996-2015, knows about the ondhand smoke, viewed as a benign, transient tachypnea of the 17,569 were diag- hazards of sec- The odiferous thirdhand ventilation won’t self-limited condi- nosed with TTN. ondhand smoke, smoke residue, composed do the job. tion involving 1-3 newborn in term babies is During the same which have led The main po- days of respiratory associated with significantly period, 40,338 to widespread of tobacco-smoke toxins tential health risk distress. But data increased risk of subsequent infants were hos- bans on smoking and known cancer-causing is to young chil- from Finland’s pitalized with a in public spaces. dren, who ingest comprehensive bronchiolitis during infancy. diagnosis of bron- Still, the Cen- agents, adheres to house thirdhand smoke national health chiolitis attributable ters for Disease dust, furniture, carpets, by the hand-to- registries indicate that TTN in term to respiratory syncytial virus infec- Control and Pre- walls, window glass, mouth route and babies is associated with signifi- tion. vention estimates skin contact. cantly increased risk of subsequent In a multivariate analysis adjusted that 58 million and other surfaces. Thirdhand bronchiolitis during infancy, Otto for birth year, gender, delivery meth- nonsmokers smoke is a much Helve, MD, reported at the annual od, gestational age, and parity, TTN in the United newer concept meeting of the European Society for was independently associated with a States are exposed to second- than secondhand smoke and has Paediatric Infectious Diseases. 1.2-fold increased risk of bronchiol- hand smoke on a regular basis. not yet actually been shown to “This association suggests similar itis during the first year of life. And where there is secondhand pose a significant health risk. The pathogenic mechanisms in tran- Dr. Helve reported having no smoke, there is typically exposure term “thirdhand smoke” is still sient tachypnea of the newborn and financial conflicts of interest regard- to thirdhand smoke as well. unfamiliar to many physicians and bronchiolitis. We suggest that an ing his study. “If you walk into a hotel room the general public. But that is likely intrinsic defect in sodium ion–driv- [email protected] you were told is a nonsmoking to change. room and you take one breath Thirdhand smoke has become and you know it’s not nonsmok- an area of intensive research in- VIEW ON THE NEWS ing, that’s thirdhand smoke. terest, with California leading the Susan Millard, MD, FCCP, comments: In the old days, Thirdhand smoke is all over the way. The Tobacco-Related Disease transient tachypnea of the newborn (TTN) was place where smokers have been,” Research Program, a state agen- a diagnosis that didn’t get much press. Now we explained Dr. Rogers, director of cy funded by a tax on the sale of know that children with primary ciliary dyskine- the toxicity assessment division tobacco products, has created a sia have an increased incidence of TTN at birth at the Environmental Protection research consortium on thirdhand and this registry reports a risk for future bron- Agency in Research Triangle smoke, with studies underway chiolitis. We clearly need to learn more about Park, N.C. investigating thirdhand smoke’s this neonatal respiratory disease! Tobacco smoke contains thou- precise chemical composition, sands of chemicals. Among those Continued on following page E-cigarettes most popular Prevalence of e-cigarette use among adults by age, 2016 25% among youngest adults Ever used an e-cigarette 20% Currently use e-cigarettes BY RICHARD FRANKI 4.5% were currently vaping ei- Frontline Medical News ther every day or on some days, 15% the CDC reported (MMWR. ver 15% of adults have used 2017;66[33]:892). 10% Oelectronic cigarettes at some For adults aged 25-44 years, ever time, and about 3% reported current use of e-cigarettes was 21.1% and use when they were surveyed in current use was 4.2%, with adults 5% 2016, according to the Centers for aged 45-64 years at 13.1% and 2.9% Disease Control and Prevention. and those aged 65 years and older 0 When those numbers are broken checking in at 4.5% ever use and 18-24 25-44 45-64 ≥65 down by age group, the youngest 1% current use, based on estimates Age group (years) adults are the most likely e-cig- derived from National Health Inter- arette users: 23.5% of those aged view Survey data. Note: Based on data from the National Health Interview Survey. 18-24 years had ever vaped and [email protected] Source: MMWR. 2017;66(33):892

16 • OCTOBER 2017 • CHEST PHYSICIAN Continued from previous page Also of concern is evidence cytotoxicity, genotoxicity, and true impact on public health (www.trdrp. of a striking socioeconomic org). disparity in smoking Concern regarding thirdhand prevalence: Low-education, smoke’s potential public health impact ramped up in response to a low-income Americans have study in which investigators at the far higher tobacco use rates. University of York (England) mea-

sured levels of various tobacco-spe- DIEGO_CERVO/THINKSTOCK cific nitrosamines, N-nitrosamines, and nicotine in house dust samples from the homes of smokers. The researchers estimated that years of early-life exposure to these com- pounds at the levels they detected could result in one excess case of cancer per 1,000 exposed individu- als (Environ Int. 2014 Oct;71:139- 47). In addition to his update on thirdhand smoke, Dr. Rogers also touched on other recent tobacco-re- lated developments, including a de- termination by the Food and Drug Administration that there has been no decline in tobacco use in the last 5 years in adolescents and young adults. While cigarette smoking by young people decreased, this was offset by a large increase in the use of electronic cigarettes and a smaller rise in the use of hookah tobacco. Indeed, e-cigarette use is now about double that of cigarettes among youth. Also of concern is evidence of a striking socioeconomic disparity in smoking prevalence: Low-education, low-income Americans have far higher tobacco use rates. “That’s pretty alarming,” he said. “I think a lot of people in this au- dience probably don’t see a lot of smoking these days, but it’s still arou n d .” Dr. Rogers drew attention to updated evidence reviews on the reproductive and developmental effects of smoking contained in the U.S. Surgeon General’s volu- minous 2014 report on the health consequences of smoking. The report concluded that there is now sufficient evidence to infer a caus- al relationship between maternal smoking in pregnancy, ectopic pregnancy, and orofacial clefts. The available evidence is “sug- gestive but not sufficient” to infer causality between maternal smok- ing in pregnancy and atrial septal defects, clubfoot, gastroschisis, and attention-deficit/hyperactivity disorder and other disruptive be- havior disorders. Dr. Rogers reported having no financial disclosures related to his presentation, which he noted did not necessarily reflect the views and policies of the EPA. [email protected]

CHESTPHYSICIAN.ORG • OCTOBER 2017 • 17 PEDIATRIC PULMONARY MEDICINE Respiratory infections linked to celiac disease BY LORI LAUBACH will develop celiac disease (CD) In a prospective cohort study, age, the researchers noted. In the Frontline Medical News from those who will not in those 373 newborns from families with first year when no child produced with a family history of CD, ac- at least one relative with CD were anti–tissue transglutaminase (an- he frequency of respiratory in- cording to Renata Auricchio, MD, recruited. The cumulative inci- ti-tTG) antibodies, respiratory Tfections in the first 2 years of University of Naples (Italy) Federi- dence of new cases of CD was 6% infections (upper and lower tract) life could distinguish children who co II, and her associates. at 3 years and 13.5% at 5 years of were more common among the

18 • OCTOBER 2017 • CHEST PHYSICIAN case patients than among the con- in the control group. from the stepwise discriminant cluded. “It is possible that the ex- trols (58% vs. 40%). During the In a multivariate analysis, the analysis suggested respiratory infec- posure to early infection stimulates second year, respiratory infections researchers found that only respira- tions in the first and second years of a genetically predisposed immune were again more frequent among tory infections in the second year of life significantly contributed to the profile, which contributes to the the case patients than among con- life were associated with a twofold index of discrimination between the switch from tolerance to intolerance trols (52% vs. 32%). And in the increase in the risk of developing case patients and the controls. to gluten, which is a common food third year of life when most of the CD (odds ratio, 2.25; P = .04). The “In this study, we report that early antigen.” case patients were diagnosed with second variable was respiratory infections significantly contribute Read the full study in Pediatrics CD, no clinical event was more infections in the first year of life, to the risk of developing CD,” Dr. (doi: 10.1542/peds.2016-4102). frequent in the case patients than which had a score of 1.58. Results Auricchio and her associates con- [email protected]

CHESTPHYSICIAN.ORG • OCTOBER 2017 • 19 PULMONARY MEDICINE Hospital-led interventions cut hospitalizations BY BIANCA NOGRADY significant reductions in monthly diatric asthma is challenging, and Kercsmar, MD, of Children’s Hos- Frontline Medical News asthma-related hospitalizations and around 40% of children and adoles- pital Medical Center in Cincinnati, emergency department visits, ac- cents hospitalized with the disease and her coauthors. ospital-driven interventions cording to a paper published online tend to be rehospitalized or revisit “Traditional care models do not Hdesigned to improve manage- Sept. 18 in JAMA Pediatrics. the emergency department within adequately address underlying risk ment of asthma in children achieved Long-term management of pe- 12 months, according to Carolyn M. factors, propagating disparities

20 • OCTOBER 2017 • CHEST PHYSICIAN and costly health care use,” they more than 36,000 children and ado- ing assessment of chronic asthma Over the 5-year study, research- wrote (JAMA Pediatrics. 2017, lescents with asthma, approximately control, severity, and triggers; a ers saw a 41.8% relative reduction Sep 18. doi: 10.1001/jamapediat- 13,000 of whom were Medicaid home health pathway of up to five in asthma-related hospitaliza- rics.2017.2600). insured. in-home nurse visits; and care coor- tions – from 8.1 to 4.7 per 10,000 This study, initiated by Cincinnati These included a program that dinators who applied interventions Medicaid patients per month. Children’s Hospital Medical Center, gave all patients a 30-day supply of such as a risk assessment, education, Asthma-related visits to the ED involved a range of interventions medications, an asthma action plan, medication home delivery, collab- decreased by 42.4%, from 21.5 to implemented with inpatients and and standardized inhaler training; oration with a Medicaid managed 12.4 per 10,000 Medicaid patients outpatients and through the com- an asthma-specific history and care practitioner, and improved ac- per month, and the percentage of munity setting, targeting the region’s physical examination form prompt- cess to community resources. Continued on following page

CHESTPHYSICIAN.ORG • OCTOBER 2017 • 21 Continued from previous page of inhaled controller medications, provided with asthma action plans. related to adverse exposures, and patients rehospitalized or who re- from 50% in May 2008 to 90% in This was associated with an in- augmenting self-management and turned to the ED for asthma with- May 2010, and the percentage of crease in the percentage of patients collaborative relationships between in 30 days declined from 12% to patients discharged with a short with well-controlled asthma from the family and the health care sys- 7%, “within 3 years of implemen- course of oral corticosteroids in- 48% to 54%. tem was associated with improved tation of the inpatient care inter- creased from 0% to 70% by March “Implementation of an integrat- asthma outcomes,” the authors ventions,” the researchers noted. 2011. ed, multilevel approach focused on wrote. There was also a significant in- Outpatient processes ensured that enhancing availability and accessi- Noting that previous research has crease in the percentage of patients Asthma Control Test scores were bility of treatments, removing bar- found 38%-70% of patients do not discharged with a 30-day supply collected and that patients were riers to adherence, mitigating risks get their prescribed medications at hospital discharge, the authors said they believed giving a 30-day sup- ply of all daily asthma medications at discharge was a key part of their success. The study was supported by the Cincinnati Children’s Hospital Med- . ical Center and one author received a grant from the National Institutes of Health. One author declared compensation for a committee role on a study of asthma treatments in children. No other conflicts of inter- est were declared.

VIEW ON THE NEWS Biopsychosocial model can improve pediatric asthma outcomes Of importance, any future efforts to replicate this work in a patient-centered way should include consideration . of how information on asth- ma management is commu- nicated to and understood by patients. Standard tools such . as asthma action plans often contain language and other information that is inacces- sible to populations with low health literacy levels. After years of elevat- ed morbidity, the work of Kercsmar et al. is a demon- stration of how interdisci- plinary care focused within a biopsychosocial model can improve outcomes for vulnerable children. Future efforts to replicate these re- sults in other communities should continue to empha- size this patient-centered, biopsychosocial philosophy, with heightened attention to the challenges that remain for children and families.

Sean M. Frey, MD, and Jill S. Halterman, MD, MPH, are in the department of pediatrics at the University of Rochester (N.Y.) School of Medicine and Dentistry. These comments are taken from an accompanying editorial (JAMA Pediatrics. 2017, Sep 18. doi: 10.1001/jamapedi- atrics.2017.2609). No conflicts of interest were declared.

22 • OCTOBER 2017 • CHEST PHYSICIAN PULMONARY MEDICINE FDA approves new therapy for COPD Three COPD treatments are now available in one inhaler.

BY LUCAS FRANKI Ellipta include headache, back Frontline Medical News pain, dysgeusia, diarrhea, cough, VIEW ON THE NEWS oropharyngeal pain, and gastro- Vera A. De Palo, MD, MBA, FCCP, comments: For our he Food and Drug Ad- enteritis, and the inhaler is contra- Global Initiative for Chronic Obstructive Lung Dis- ministration has approved indicated for people with “severe ease 3 and 4 patients who have had hospitaliza- T Trelegy Ellipta (fluticasone hypersensitivity to milk proteins.” tions, the prescription of multiple classes of inhaled furoate/umeclidinium/vilanterol), Trelegy Ellipta is not indicated medication is common. These patients are often a triple-therapy inhaler for the for people with asthma or acute receiving other medications, with complicated reg- treatment of chronic obstructive bron chospasm. imens. A patient’s medication list can become the pulmonary disease (COPD) in “This approval represents a sig- time-schedule-map that consumes much of the adult patients, according to a press nificant therapeutic convenience for day. This has significant impact on the patient’s life, release from GlaxoSmithKline and those appropriate patients already finances, and the likelihood of compliance with medications. For Innoviva. on Breo Ellipta, that require addi- those on triple therapy, the approval of this triple-therapy combina- Trelegy Ellipta combines an tional bronchodilation or for those tion inhaler may offer hope for increased compliance with therapy. inhaled corticosteroid, a long-act- patients already on a combination ing muscarinic antagonist, and a of Breo Ellipta and Incruse Ellipta,” long-acting beta2-adrenergic agonist Mike Aguiar, CEO of Innoviva said and a 15% reduction in moderate “This is the first study to report a into an inhaler meant for once-daily in the press release. to severe exacerbations, compared comparison of a single inhaler triple use in people with COPD. Chronic In results supporting the FDA with patients receiving Relvar/ therapy with two dual therapies, bronchitis and/or emphysema pa- approval, the IMPACT study, a 52- Breo Ellipta. Change from baseline providing much needed clinical tients are also indicated for treat- week phase 3 clinical trial including FEV1, change from baseline scores evidence about the ability of a sin- ment. The FDA-approved dosage is 10,355 COPD patients sponsored on the St George’s Respiratory gle inhaler triple therapy to reduce 100 mcg of fluticasone furoate, 62.5 by GSK, found that patients re- Questionnaire, and time to first exacerbations,” Patrick Vallance, mcg of umeclidinium, and 25 mcg ceiving Trelegy Ellipta experienced moderate/severe COPD exacer- president of R&D at GSK, noted in a of vilanterol. a 25% reduction in moderate to bation also were improved in the press release announcing the results The most common adverse severe exacerbations compared to Trelegy Ellipta study group com- of the IMPACT study. events associated with Trelegy patients receiving Anoro Ellipta, pared to the others. [email protected] Vaccine reduced risk for flu Small study: Patients prefer visits by 42% microneedle flu vaccine BY MARY ANN MOON Vaccines and Related Biological BY ELI ZIMMERMAN of 24 participants given the patch by Frontline Medical News Products Advisory Commit- Frontline Medical News a health care worker, 18-24 (75%- tee, based on data from global 100%) of 24 in the group of patients ast year’s influenza vaccination influenza virologic and epide- nfluenza vaccinations given who gave themselves the patch, and Lreduced the overall risk for miologic surveillance, genetic Ithrough a microneedle patch 20-25 (80%-100%) of 25 in the in- flu-related medical visits by 42%, and antigenic characterization, (MNP) received higher patient ap- jection group having achieved sero- according to the Centers for Dis- human serology studies, antiviral proval compared with traditional protection against the three influenza ease Control and Prevention. susceptibility, and the availability inoculation methods, according to a strains 6 months after vaccination. In an article summarizing influ- of candidate influenza viruses small study funded by the National When measuring reactogenicity, the enza activity in the United States (MMWR. 2017;66[25]:668-76). Institutes of Health. investigators did find more patients during October 2016–May 2017, Preliminary data show that, In a phase 1, randomized, place- (41 of 50) reported cases of pruritis investigators said that most of the during the 2016-2017 flu sea- bo-controlled study, 100 patients in the microneedle group than in the viral strains antigenically charac- son, there were 18,184 labo- between the ages of 18 and 49 years injection group (4 of 25). However, terized at the CDC “were similar to ratory-confirmed, flu-related were split into four groups: one giv- these cases were mostly mild, while the reference viruses representing hospitalizations, for an overall en the patch by a health care worker, the injection group reported more the recommended components for incidence of 65 per 100,000 one instructed to apply the patch at grade 2 and grade 3 reactions, with the 2016-2017 vaccine.” population, more than double home, one given a vaccine through a grade 4 being the most severe. In addition, none of the thou- that for the 2015-2017 season traditional intramuscular injection, There may also be potential for sands of samples tested showed (31/100,000). Broken down by and one given a placebo. use among pediatric patients, who resistance to the antivirals osel- age groups, the rates per 100,000 Of those who took the patch, 70% may be resistant to vaccinations be- tamivir, zanamivir, and peramivir, population in this past season (33 of 47) preferred the patch to in- cause of the injection method, the said epidemiologist Lenee Blanton, were 44 at ages 0-4 years, 17 at tramuscular injection (The Lancet. researchers noted. MD, and her associates in the in- ages 5-17 years, 20 at ages 18-49 2017 Jun 27. doi: 10.1016/S0140- Some of the researchers are em- fluenza division, National Center years, and 65 at ages 50-64 years, 6736[17]30575-5). ployees of Micron Biomedical, a for Immunization and Respiratory compared with 291 at ages 65 All nonplacebo groups were given company that manufactures mi- Diseases in Atlanta. years and older. Finalized esti- Fluvirin, the 2014-2015 licensed tri- croneedle products, and are listed The 2017-2018 influenza mates of the number of influenza valent inactivated influenza vaccine, as inventors on the licensed patents vaccine has been updated to illnesses, medical visits, and hos- according to the researchers. of these products. The investigators include an additional influen- pitalizations averted by vaccina- Protection against the virus 6 reported no other relevant financial za A (H1N1) component. This tion during the 2016-2017 season months after vaccination was simi- disclosures. change was recommended by the will be published in December, lar across all groups other than the [email protected] Food and Drug Administration’s the investigators said. placebo group: 20-24 (83%-100%) On Twitter@eaztweets

CHESTPHYSICIAN.ORG • OCTOBER 2017 • 23 PRACTICE ECONOMICS No increased mortality with readmission declines BY SHARON WORCESTER pneumonia between 2008 and 2014. mortality rates after discharge, During the study period, a total Frontline Medical News In fact, reductions in 30-day re- according to Kumar Dharmarajan, of 2.96 million hospitalizations for admission rates among Medicare MD, of Yale New Haven (Conn.) heart failure, 1.2 million for acute oncerns that efforts to reduce fee-for-service beneficiaries are Health, and colleagues (JAMA. MI, and 2.5 million for pneumo- 30-day hospital readmission weakly but significantly correlated 2017 Jul 18;318[3]:270-8. doi: nia were identified at 5,106 (heart Crates under the Affordable Care with reductions in hospital 30-day 10.1001/jama.2017.8444). failure), 4,772 (MI), and 5,057 Act’s Hospital Readmission Reduc- tion Program might lead to unin- tended increases in mortality rates appear to be unfounded, according to a review of more than 6.7 million hospitalizations for heart failure, acute myocardial infarction, or

VIEW ON THE NEWS Time to reexamine, reengineer HRRP? The findings by Dharmara- jan and colleagues are “cer- tainly good news,” Karen E. Joynt Maddox, MD, wrote in an editorial. The study provides support for strategies that hospitals are using to reduce readmis- sions, and also underscores the importance of evaluating unintended consequences of policy changes such as the Affordable Care Act’s Hospital Readmissions Re- duction Program (HRRP), she said (JAMA. 2017 Jul 18;318[3]:243-4). The study did not address the possibility that attention to reducing readmissions has taken priority over reducing mortality, which could have the unintended consequence of slowing improvements in mortality, she noted, sug- gesting that for this and oth- er reasons it may be “time to reexamine and reengineer the HRRP to avoid unin- tended consequences and to ensure that its incentives are fully aligned with the ul- timate goal of improving the health outcomes of patients. “Only with full knowledge of the advantages and disad- vantages of a particular poli- cy decision can policy makers and advocates work to craft statutes and rules that max- imize benefits while minimiz- ing harms,” she wrote.

Dr. Joynt Maddox is with Brigham and Women’s Hos- pital, Boston. She is sup- ported by a grant from the National Heart, Lung, and Blood Institute.

24 • OCTOBER 2017 • CHEST PHYSICIAN (pneumonia) short-term acute care From 2008 to 2014, the RARRs For heart failure, acute MI, and consultant and scientific advisory hospitals, respectively. In January declined in aggregate across hos- pneumonia, there was an increase of board member for Clover Health 2008, the mean hospital 30-day pitals (–0.053% for heart failure, 0.008%, a decrease of 0.003%, and at the time this research was per- risk-adjusted readmission rates –0.044% for acute MI, and –0.033% an increase of 0.001%, respectively, formed. He is supported by grants (RARRs) and risk-adjusted mortal- for pneumonia). they said. from the National Institute on Ag- ity rates (RAMRs) after discharge “In contrast, monthly aggregate The authors work under contract ing and the American Federation for were 24.6% and 8.4% for heart fail- trends across hospitals in 30-day with the Centers for Medicare & Aging Research, and the Yale Claude ure, 19.3% and 7.6% for acute MI, risk-adjusted mortality rates after Medicaid Services to develop and D. Pepper Older Americans Inde- and 18.3% and 8.5% for pneumonia, discharge varied by admitting con- maintain performance measures. Dr. pendence Center. respectively, the investigators said. dition” the investigators said. Dharmarajan reported serving as a [email protected]

CHESTPHYSICIAN.ORG • OCTOBER 2017 • 25 PRACTICE ECONOMICS FDA tries to curtail abuse of ‘orphan drug’ program BY SARAH JANE TRIBBLE, tions that drugmakers may be abus- incentives are granted “in a way tax credits, user-fee waivers, and 7 KAISER HEALTH NEWS ing a law intended to help patients that’s consistent with the manner years of market exclusivity if they with rare diseases. Congress intended” when the Or- developed medicines for rare dis- he Food and Drug Adminis- In a blog post Sept. 12, FDA phan Drug Act was passed in 1983. eases. Ttration is changing the way it Commissioner Scott Gottlieb, MD, That legislation gave drugmakers A Kaiser Health News investi- approves orphan drugs after revela- said he wants to ensure financial a package of incentives, including gation published in January 2017

26 • OCTOBER 2017 • CHEST PHYSICIAN found many drugs that now have Dr. Gottlieb announced plans to increase in precision medicine and which often carry six-figure price orphan status aren’t entirely new. close a loophole that allows man- biologics. tags. Nearly half of the new drugs Of about 450 drugs that have won ufacturers to skip pediatric testing “We need to make sure our pol- approved by the FDA are now for orphan approval since 1983, more requirements when developing a icies take notice of all of these new rare diseases – even though many of than 70 were drugs first approved common-disease drug for orphan challenges and opportunities,” he them also treat and are marketed for by the FDA for mass-market use in children. He also signaled wrote. Dr. Gottlieb, through his common diseases. use. Those include rosuvastatin that bigger changes are being agency, declined multiple requests Dr. Gottlieb became commission- (Crestor), aripiprazole (Abilify), and considered, announcing a public for interviews. er in May, a few months after three adalimumab (Humira), the world’s meeting to explore issues raised Over the years, drugmakers have key Republican senators called for a best-selling drug. by scientific advances, such as the fueled a boom in orphan drugs, federal investigation into potential abuses of the Orphan Drug Act, and the Government Accountability Of- fice agreed to investigate. The GAO has yet to begin its in- vestigation, saying it doesn’t expect to start work until late this year, when staff is available. Regardless, in late June, Dr. Gottlieb announced what would be the first in a series of updates that shift the way the FDA handles orphan drugs. Those include: • Eliminating a backlog in drug ap- plications for orphan designation or status. Getting a designation is a critical first step if a company wants to win orphan incentives once the drug is approved for treatment use. And, much like the rise in approvals, the requests by companies to get drugs designated with orphan status has also sky- rocketed. Dr. Gottlieb said in June that he wanted to get rid of the backlog; his blog post noted the effort was complete. About half of the 200 applications from drug- makers won orphan status. • Mandating that drugmakers prove their medicine is clinically superior before getting the mar- ket exclusivity that comes with orphan drug status. The agency had lost a lawsuit in which a company said it was owed the exclusivity period regardless of whether its medicine was better. And two more lawsuits had been filed by Eagle Pharmaceuticals and United Therapeutics. The FDA Reauthorization Act, which passed in August, made it law that a drug has to be clinically su- perior to get the incentives. • Closing the loophole for pedi- atric orphan drugs by requiring all drugs approved for common adult diseases, like inflammatory bowel disease, undergo pediatric testing when getting approval as a pediatric orphan drug. Pediatric testing is not required for orphan drugs, and Congress recently mandated that orphan drugs for cancer be tested for children. Still, the American Academy of Pe- diatrics celebrated the proposed change but warned it was only a first step. Bridgette Jones, MD, chair of American Academy of Pediatrics Committee on Drugs, Continued on following page

CHESTPHYSICIAN.ORG • OCTOBER 2017 • 27 PRACTICE ECONOMICS Medicare payments may be lower than promised BY GREGORY TWACHTMAN “While the reductions in penal- The proposed fee schedule also proposal outlines the payment Frontline Medical News ties represent a move in the right seeks feedback from physicians structure and supplier enrollment direction, the [American College and organizations on how Medi- requirements and compliance stan- hysicians will likely see a 0.31% of Rheumatology] believes CMS care Part B pays for biosimilars. dards, as well as beneficiary engage- uptick in their Medicare pay- should establish a value modifier Under the 2016 fee schedule, the ment incentives. Pments in 2018 and not the 0.5% adjustment of zero for 2018,” ACR average sales prices (ASPs) for all Physicians would be paid based promised in the Medicare Access officials said in a statement. “This biosimilar products assigned to on performance goals being met by and CHIP Reauthorization Act. would align with the agency’s the same reference product are patients, including meeting certain Officials at the Centers for Medi- policy to ‘zero out’ the impact of included in the same CPT code, numbers of service and mainte- care & Medicaid Services were not the resource use meaning the ASPs nance sessions with the program as able to find adequate funding in so- component of the ‘While the reductions in for all biosimilars well as achieving specific weight- called misvalued codes to support Merit-based In- penalties represent a move of a common ref- loss goals. For beneficiaries who the larger increase, as required by centive Payment erence product are are able to lose at least 5% of body law, according to the proposed Medi- System in 2019, in the right direction, used to determine weight, physicians could receive up care physician fee schedule for 2018. the successor to the [American College of a single reimburse- to $810. If that weight-loss goal is CMS also failed to hit its misval- the value mod- ment rate. not achieved, the most a physician ued code target in 2016, resulting in ifier program. Rheumatology] believes That CMS is look- could receive is $125, according to a 0.18% across-the-board reduction This provides CMS should establish a ing deeper at this is a CMS fact sheet. Currently, DPP to the physician fee schedule in 2017 additional time to value modifier adjustment being seen as a plus. can only be employed via office instead of the statutorily promised continue refining Biosimilars “tied visit; however, the proposal would 0.5% increase. the cost measures of zero for 2018.’ to the same refer- allow virtual make-up sessions. Other provisions in the pro- and gives physi- ence product may “The new proposal provides posed Medicare physician fee cians more time to understand the not share all indications with one more flexibility to DPP providers schedule may be more palatable program.” another or the reference product in supporting patient engagement than the petite pay raise. The proposed fee schedule also [and] a blended payment model and attendance and by making per- The proposal would roll back would delay implementation of the may cause significant confusion in formance-based payments available data reporting requirements of the appropriate use criteria (AUC) for im- a multitiered biosimilars market if patients meet weight-loss targets Physician Quality Reporting System aging services, a program that would that may include both interchange- over longer periods of time,” accord- (PQRS), to better align them with deny payments for imaging services able and noninterchangeable prod- ing to the AMA. the new Quality Payment Program unless the ordering physician consult- ucts,” the Biosimilars Forum said The fee schedule also proposes (QPP), and will waive half of penal- ed the appropriate use criteria. in a statement. The current situa- more telemedicine coverage, spe- ties assessed for not meeting PQRS The American Medical Associa- tion “may lead to decreased phy- cifically for counseling to discuss requirements in 2016. tion “appreciates CMS’ decision to sician confidence in how they are the need for lung cancer screening, “We are proposing these changes postpone the implementation of this reimbursed and also dramatically including eligibility determination based on stakeholder feedback and requirement until 2019 and to make reduce the investment in the devel- and shared decision making, as well to better align with the MIPS [Mer- the first year an opportunity for opment of biosimilars and thereby psychotherapy for crisis, with codes it-Based Incentive Payment System testing and education where con- limit treatment options available to for the first 60 minutes of intervention track of the QPP] data submission sultation would not be required as patients.” and a separate code for each addi- requirements for the quality per- a condition of payment for imaging Both the Biosimilars Forum and tional 30 minutes. Four add-on codes formance category,” according to a services,” according to a statement. the ACR support unique codes for have been proposed to supplement CMS fact sheet on the proposed fee “We also applaud the proposed each biosimilar. existing codes that cover interactive schedule. delay in implementing AUC for di- “Physicians can better track and complexity, chronic care management “This will allow some physicians agnostic imaging studies,” ACR said monitor their effectiveness and en- services, and health risk assessment. who attempted to report for the 2016 in its statement. “We will be gauging sure adequate pharmacovigilance in For clinicians providing behavioral performance period to avoid penal- the readiness of our members to the area of biosimilars” by employ- health services, CMS is proposing ties and better align PQRS with MIPS use clinical support systems. ... We ing unique codes, according to ACR an increased payment for providing as physicians transition to QPP,” of- support simplifying and phasing-in officials. face-to-face office-based services that ficials from the American College of the program requirements. The The fee schedule proposal also better reflects overhead expenses. Physicians said in a statement. ACR also strongly supports larger would expand the Medicare Dia- Comments on the fee schedule Other physician organizations said exemptions to the program,” such as betes Prevention Program (DPP), update were due Sept. 11. The final they believed the proposal did not physicians in small groups and rural currently a demonstration project, rule is expected in early November. go far enough. and underserved areas. taking it nationwide in 2018. The [email protected]

Continued from previous page submit orphan drug applications, noted that the In an interview, FDA confirmed that Dr. Gott- said Sept. 12 that orphan drugs are “still most- approval process for designations definitely sped lieb’s orphan modernization plan is part of a ly exempt from pediatric study requirements up over the summer, and “we are absolutely get- larger effort to increase competition and decrease … children deserve access to safe, effective ting responses from the FDA back in 90 days. drug prices. One focus is on targeted drugs – es- medications.” That has come through.” pecially those that affect rare diseases or diseases Martin Makary, MD, who wrote a critical 2015 Other changes to the agency, though, will for which there is no effective therapy, the agency paper on orphan approvals, said the changes at evolve slowly. For example, the orphan drug of- said. the agency indicate that Dr. Gottlieb seems “con- fice has begun reaching across the FDA’s divisions “Such drugs present some of the biggest oppor- cerned about all the right things. The govern- for help in reviewing drugs. In May, the FDA’s tunities in medicine to treat and cure debilitating ment does a lot of lip service in general. This is orphan reviews began to work with the office of and very costly diseases,” the agency stated. not lip service.” pediatric therapeutics to review pediatric appli- The restructuring has been swift in some ways. cations – ideally increasing the expertise applied Kaiser Health News is a national health policy Sandra Heibel, PhD, a senior consultant at when considering a company’s request for orphan news service that is part of the nonpartisan Henry Haffner Associates, a firm that helps companies drug use in children. J. Kaiser Family Foundation.

28 • OCTOBER 2017 • CHEST PHYSICIAN DISASTER RESPONSE Hurricane Harvey tests hospital teams’ mettle

BY ELI ZIMMERMAN be, particularly with the flooding,” geries during the disaster, including caring for veterans, treating “home- Frontline Medical News Dr. Kuy said. “We had staff going 5, laparoscopic treatment of ruptured less folks and nonveterans who were 6 days here at the hospital, working appendicitis and replacement of an brought here by the Coast Guard, or s Houston-area citizens evac- continuously, sleeping on the floor, infected aortic graft, which required the ambulances, or by air.” uated or hunkered down at and because of that, we were able to massive transfusion.” The VA hos- At Texas Children’s Hospital, Dr. Ahome in anticipation of Hur- perform multiple emergency sur- pital broke from its core mission of Continued on page 34 ricane Harvey, doctors like Mary L. Brandt, MD, packed a bag and headed to work. “I came in on Saturday morning [Aug. 23] – I was on call – and so I packed a big suitcase and a big bag of food because I anticipated I would be here until Thursday,” Dr. Brandt said in an interview, “So I became part of the ‘ride-out crew.’ ” Hospitals were hit hard by Hur- ricane Harvey, and many struggled against the effects of the Category 4 storm, which made landfall then stalled over Texas for almost a week, pummeling the area. Preparations began well before the hurricane arrived. As weather experts and government officials warned of the storm’s imminent arrival, Houston’s Texas Children’s Hospital wasted no time making necessary plans in addition to the safeguards their facilities already had in place, Dr. Brandt said. “We all know this [flooding] could happen, so all the facilities in the medical center have flood gates, and generators are out of the base- ment so that there is not any risk of losing all electricity, but then the issue becomes the staff,” Dr. Brandt said. “They can’t get to and from the facility, and that’s particularly true if they live in the periphery of Hous- ton, which is common.” The situation was the same for many area hospitals. Just 2 miles away from Texas Children’s Hos- pital, SreyRam Kuy, MD, associate chief of staff at the Michael E. De- Bakey VA Medical Center, and her colleagues prepared to run the hos- pital with a skeleton crew. “We were preparing when it was still a tropical storm, and we talked to the staff ahead of time to let them know this would be a marathon, not a sprint,” Dr. Kuy said in an in- terview. “We had people staying in the hospital ahead of time because we were worried that when the hur- ricane hit, we would not be able to have people return.” But when Harvey made landfall with Category 4 intensity, many medical facilities were caught by surprise. “We didn’t know how bad it would be, I honestly don’t think anyone in the city or the state had any idea of how tremendous the impact would

CHESTPHYSICIAN.ORG • OCTOBER 2017 • 29 2017 Education Calendar

Live Learning Courses Military The National Guard Malcolm McClendon/Texas Courses held at the CHEST Innovation, Simulation, and Training Center in Continued from page 29 and what struck me was as I walk Glenview, Illinois. Brandt and her colleagues were in I see these big smiles on their dealing with similar situations, stay- faces; I absolutely did not expect Critical Care Ultrasound: Ultrasonography: ing on their feet and moving quickly that,” Dr. Kuy said. “They had been Integration Into Clinical Essentials in Critical as rescued patients arrived by air. in the hospital for 5 days; they were “We were near the area that was exhausted. It just makes me so Practice Care flooding really terribly, and so the proud to serve along these kinds of November 10-12 December 1-3 Coast Guard had been coming in p e op l e .” and bringing kids,” Dr. Brandt said. As travel became possible, Dr. > Learn More livelearning.chestnet.org “Sometimes, we knew what was Kuy and other area physicians – as coming and sometimes we didn’t. It well as volunteers from across the was pretty much controlled chaos.” country – began to shift their focus Staff shared responsibilities, often to evacuation shelters, treating am- 2018 Live Learning taking on tasks far outside their bulatory patients there. course dates coming soon! usual roles. “The response has been phenome- “We didn’t have enough people nal,” said Dr. Kuy. “I met an ER doc- working the cafeteria, and so, at one tor from North Carolina who came point, I put on my hair net, grabbed to volunteer, we have FEMA [Feder- a ladle, and served in the lunch al Emergency Management Agency] line,” Dr. Kuy said. doctors from all across the state, and Throughout the storm and flood- then of course, all the people from ing, medical professionals fought the different VA [hospitals].” through exhaustion and depleting Pediatricians have sent their sup- supplies, all with little or no knowl- port as well, offering time and sup- edge of how their own homes and plies to help take care of the patients families were faring. at Texas Children’s Hospital, Dr. “We had people here for so long, Brandt said. and they had no idea what was At presstime, volunteers were still happening in their own homes,” Dr. needed. The Texas Department of Kuy said. “They were watching on State Health Services opened a web the news, seeing the reports and portal for volunteer opportunities, watching their own neighborhoods and lifted restriction on out-of-state flooded.” doctors from practicing medicine Dr. Brandt and her colleagues without state registration. would watch as reports came in of While there is still much that what was happening beyond the needs to be done to recover, those hospital walls. on the ground said that they feel an “We have some meeting areas, we overwhelming feeling of community would watch the weather together as people face what will inevitably Register Now and that goes from the janitors to be a tough road ahead. chestmeeting.chestnet.org the head of the hospital who was in “Houston has a reputation and a the hospital with us,” she said. culture of helping neighbors and it Despite the chaos outside, morale has been astounding to watch what’s did not waiver for either Dr. Kuy’s happening,” said Dr. Brandt. “No or Dr. Brandt’s crew. matter how tired people are or how Calendar subject to change. For most current course list and more “I remember walking through- stressful any cases are, everyone’s information, visit livelearning.chestnet.org. out the hospital, doing my rounds, morale stays high.” checking up on the units. I went to [email protected] talk with some of the staff nurses, On Twitter @eaztweets

34 • OCTOBER 2017 • CHEST PHYSICIAN TECHNOLOGY Health IT: Cybercrime risks are real

BY ELI ZIMMERMAN nearly 60 million attacks had been Frontline Medical News conducted, Salim Neino, CEO of Kryptos Logic, testified June 15 at ging equipment, valuable data, a joint hearing of two subcommit- and an improperly trained tees of the House Science, Space Aworkforce make health care & Technology Committee. Mr. IT extraordinarily vulnerable to ex- Hutchins is employed by Kryptos ternal malfeasance, as demonstrated Logic. by the WannaCry virus episode that U.S. officials are keenly aware that occurred this spring in the United a similar attack could happen here. Kingdom. In June, the federally sponsored Computer hackers used a weak- Health Care Industry Cybersecurity

ness in the operating system em- Task Force issued a report on their Thinkstock compilation ployed by the U.K. National Health year-long look at the state of the Service, allowing the WannaCry health care IT in this country. The the good of patients and used to someone else’s problem; however, virus to spread quickly across task force was mandated by the Cy- develop new treatments can be unsafe day-to-day interactions with connected systems. The ransom- bersecurity Act of 2015 and formed used for nefarious purposes such connected devices and patient EHRs ware attack locked clinicians out in March 2016. as fraud, identity theft, supply were among the task force’s primary of patient records and diagnostic “The health care system can- chain disruptions, the theft of re- concerns. machines that were connected, not deliver effective and safe care search and development, and stock For many, creating a safe pass- bringing patient care to a near without deeper digital connec- manipulation. Most importantly, word or not giving out critical standstill. tivity. If the health care system cybersecurity attacks disrupt pa- information may seem like com- The attack lasted 3 days until is connected, but insecure, this tient care.” mon sense, but many physicians Marcus Hutchins, a 22-year-old se- connectivity could betray patient Specifically, the task force made are not able or willing to take the curity researcher, stumbled onto a safety, subjecting them to unnec- the following recommendations: time to make sure they are inter- way to slow the spread of the virus essary risk,” according to the task • Define and streamline leader- acting with systems safely, or they enough to manage it, but not before force report. “Data collected for ship, governance, and expecta- are overconfident in their security tions for health care industry system, according to task force cybersecurity. member Mark Jarrett, MD, senior VIEW ON THE NEWS • Increase the security and resil- vice president and chief quality WannaCry provides wake-up call ience of medical devices and officer at Northwell Health in When computer hackers took control of the United Kingdom’s health IT. New York. National Health Service using a virus known as WannaCry, doc- • Develop the health care work- “Most physicians now will try tors and nurses were left helpless, blocked from the files they force capacity necessary to pri- to access medical records of their would need to treat their patients until they paid to get those oritize and ensure cybersecurity patients who have been in the hos- files back. awareness and technical capabil- pital because that’s good care,” Dr. Doctors were forced to revert to older methods, slowing every- ities. Jarrett said in an interview. thing to a snail’s pace. • Increase health care industry But they have to recognize that The media coverage of the event was dramatic, but there is no readiness through improved “they cannot give these passwords doubt the effects made it justifiably so. cybersecurity awareness and ed- to other people and they need to NHS hospitals had not achieved their goal of being paperless; ucation. make these passwords complex,” had they been, the service would have been completely unable • Identify mechanisms to protect noted Dr. Jarrett. to stop the attack. It was not just software that was affected research and development efforts “Phishing” is another concern. In but medical devices as well. Physicians were unable to perform and intellectual property from a phishing scam, cybercriminals will x-rays, and some hospitals found that the refrigerators used to attacks or exposure. pose as a fraudulent institution or store blood products were shut down. • Improve information sharing of individual in order to trick a target While the NHS was particularly vulnerable to the WannaCry industry threats, weaknesses, and into downloading a virus, sending because of budget cuts, this cybercrime could have happened to mitigations. additional valuable information, or any hospital, and its lessons are applicable for all. Health care cybercrime is a sig- even paying money directly to the Doctors do understand the value of patients records, but they nificant problem in the United criminals. seem to be unaware of the physical harm that could befall pa- States. In 2016, 328 U.S. health “Physicians checking their tients from a cyberattack. care firms reported data breaches, emails need to be aware of pos- This attack needs to serve as a wake-up call for health care up from 268 in 2015, with a total sible phishing episodes, because professionals who are not invested in their facilities’ cybersecuri- of 16.6 million Americans affect- they could be infected, and then ty practices. ed, according to a report conduct- there is the possibility that infec- Underfunding left NHS hospitals terribly exposed and, if phy- ed by Bitglass, a security software tion could be introduced into the sicians continue to be complacent with how to handle this issue, company. In February 2016, a system, Dr. Jarrett said. the results are sure to be more severe. hospital in California was forced “I think the disconnect is [that to pay about $17,000 in Bitcoin, an physicians] are not used to [cyber- Rachel Clarke, MD, is at Oxford (England) University Hospitals NHS Foun- electronic currency that is known security]. It’s not part of their daily dation Trust, and Taryn Youngstein, MD, is at Imperial College Healthcare to be favored by cybercriminals, life and they also, up until recently, NHS Trust, London. They reported having no relevant financial conflicts of to access electronic health records thought ‘it’s never going to happen interest. Their remarks were make in a perspective published in the New that were held in a similar manner to me.’ ” England Journal of Medicine (doi: 10.1056/NEJMp1706754). to last month’s attack on the NHS. [email protected] For physicians, this may seem like On Twitter @eaztweets

CHESTPHYSICIAN.ORG • OCTOBER 2017 • 35 CARDIOVASCULAR MEDICINE New data update guidance on nonstatin LDL lowering BY SHARON WORCESTER • Consideration of new randomized ther Cardiovascular Outcomes were published in early 2017. Frontline Medical News clinical trial data for the PCSK9 Research With PCSK9 Inhibition • An adjustment in the ECDP algo- inhibitors evolocumab and boco- in Subjects With Elevated Risk) rithms with respect to thresholds he American College of Car- cizumab. Namely, they included and SPIRE-1 and SPIRE-2 (Studies for consideration of net ASCVD diology Task Force on Expert results from the cardiovascular of PCSK9 Inhibition and the Re- risk reduction. The 2016 ECDP TConsensus Decision Pathways outcomes trials FOURIER (Fur- duction of Vascular Events), which thresholds for risk-reduction has released a “focused update” for the 2016 ACC Expert Consensus Decision Pathway (ECDP) on the role of nonstatin therapies for LDL cholesterol lowering in the manage- ment of atherosclerotic cardiovascu- lar disease (ASCVD) risk. The update was deemed by the ECDP writing committee to be desirable given the additional ev-

‘This ECDP addresses current gaps in care for LDL-C lowering to reduce ASCVD risk.’ DR. LLOYD-JONES idence and perspectives that have emerged since the publication of the 2016 version, particularly with respect to the efficacy and safety of proprotein convertase subtilisin/ kexin 9 (PCSK9) inhibitors for the secondary prevention of ASCVD, as well as the best use of ezetimibe in addition to statin therapy after acute coronary syndrome. “This ECDP addresses current gaps in care for LDL-C lowering to reduce ASCVD risk and provides recommendations that build on the evidence base established by the 2013 [American College of Cardi- ology/American Heart Association] cholesterol guideline,” explained the committee, which was chaired by Donald M. Lloyd-Jones, MD, of Northwestern University, Chica- go (J Am Coll Cardiol. 2017. doi: 10.1016/j.jacc.2017.07.745) The ECDP algorithms endorse the four evidence-based statin benefit groups identified in the 2013 guide- lines (adults aged 21 and older with clinical ASCVD, adults aged 21 and older with LDL-C of 190 mg/dL or greater, adults aged 40-75 years without ASCVD but with diabetes and with LDL-C of 70-189 mg/dL, and adults aged 40-75 without AS- CVD or diabetes but with LDL-C of 70-189 mg/dL and an estimated 10-year risk for ASCVD of 7.5% or greater) and assume that the patient is currently taking or has attempted to take a statin, they noted. Among the changes in the 2017 focused update are:

40 • OCTOBER 2017 • CHEST PHYSICIAN benefit were percent reduction in 2017 ECDP update, the thresholds After an Acute Coronary Syn- when considering the addition of LDL-C with consideration of ab- are percent reduction in LDL-C drome During Treatment With nonstatin therapies for patients solute LDL-C level in patients with with consideration of absolute Alirocumab), and the SPIRE-2 in each of the four statin benefit clinical ASCVD, baseline LDL-C LDL-C or non-HDL-C levels for trial, all of which included non- groups” the update explained. of 190 mg/dL or greater, and pri- patients in each of the four statin HDL-C thresholds. “In alignment • An expansion of the threshold mary prevention. In patients with benefit groups. This change was with these inclusion criteria, the for consideration of net ASCVD diabetes with or without clinical based on the inclusion criteria of 2017 Focused Update includes risk-reduction benefit from a re- ASCVD, clinicians were allowed to the FOURIER trial, the ongoing both LDL-C and non-HDL-C duction of LDL C of at least 50%, consider absolute LDL-C and/or ODYSSEY Outcomes trial (Evalu- thresholds for evaluation of net as well as consideration of LDL-C non-HDL-cholesterol levels. In the ation of Cardiovascular Outcomes ASCVD risk-reduction benefit Continued on following page

CHESTPHYSICIAN.ORG • OCTOBER 2017 • 41 Continued from previous page based on findings from the FOU- creased risk of recurrent events,” addition of ezetimibe as the ini- less than 70 mg/dL or non-HDL-C RIER trial and IMPROVE-IT (Im- they said. tial agent and a PCSK9 inhibitor less than 100 mg/dL for all pa- proved Reduction of Outcomes: • An expanded recommendation as the second agent.” However, tients (that is, both those with and Vytorin Efficacy International Tri- on the use of ezetimibe and based on the FOURIER findings, those without comorbidities) who al).“Based on consideration of all PCSK9 inhibition. The 2016 the ongoing ODYSSEY Out- have clinical ASCVD and baseline available evidence, the consensus ECDP stated that, “if a decision comes trial, and IMPROVE-IT, LDL-C of 70-189 mg/dL. The 2016 of the writing committee mem- is made to proceed with the ad- the 2017 Focused Update states ECDP had different thresholds for bers is that lower LDL-C levels are dition of nonstatin therapy to that, if such a decision is made those with versus those without safe and optimal in patients with maximally tolerated statin thera- in patients with clinical ASCVD comorbidities. This change was clinical ASCVD due to [their] in- py, it is reasonable to consider the with comorbidities and baseline

42 • OCTOBER 2017 • CHEST PHYSICIAN LDL-C of 70-189 mg/dL, it is initial choice of ezetimibe versus of higher-risk patients with clin- baseline LDL-C of at least 190 mg/ reasonable to weigh the addition a PCSK9 inhibitor (such as re- ical ASCVD. The 2016 ECDP dL not due to secondary causes. of either ezetimibe or a PCSK9 quiring less than 25% additional included on this list diabetes, a The 2017 update added being 65 inhibitor in light of “consider- lowering of LDL-C, an age of recent ASCVD event, an ASCVD years or older, prior MI or non- ations of the additional percent over 75 years, cost, and other pa- event while already taking a sta- hemorrhagic stroke, current daily LDL-C reduction desired, patient tient factors and preferences). tin, poorly controlled other major cigarette smoking, symptomatic preferences, costs, route of ad- • Additional factors, based on ASCVD risk factors, elevated peripheral artery disease with pri- ministration, and other factors.” the FOURIER trial results and lipoprotein, chronic kidney dis- or MI or stroke, history of non-MI The update also spells out con- inclusion criteria, that may be ease, symptomatic heart failure, related coronary revascularization, siderations that may favor the considered for the identification maintenance hemodialysis, and residual coronary artery disease with at least 40% stenosis in at least two large vessels, HDL-C less than 40 mg/dL for men and less than 50 mg/dL for women, high-sensitivity C-reactive protein greater than 2 mg/L, and metabol- ic syndrome. The content of the full ECDP has been changed in accordance with

‘The 2017 Focused Update includes both LDL-C and non- HDL-C thresholds for evaluation of net ASCVD risk-reduction benefit when considering the addition of nonstatin therapies for patients in each of the four statin benefit groups.’

these updates and now includes more extensive and detailed guid- ance for decision making – both in the text and in treatment algo- rithms. Aspects that remain unchanged include the decision pathways and algorithms for the use of ezetimibe or PCSK9 inhibitors in primary prevention patients with LDL-C less than 190 mg/dL or in those without ASCVD and LDL-C of 190 mg/dL or greater unattributable to second- ary causes. In addition to other changes made for the purpose of clarification and consistency, recommendations re- garding bile acid–sequestrant use were downgraded; these are now only recommended as optional sec- ondary agents for consideration in patients who cannot tolerate ezeti- mibe. “[These] recommendations at- tempt to provide practical guidance for clinicians and patients regard- ing the use of nonstatin therapies to further reduce ASCVD risk in situations not covered by the guide- line until such time as the scientific evidence base expands and cardio- vascular outcomes trials are com- pleted with new agents for ASCVD risk reduction,” the committee concluded. Dr. Lloyd-Jones reported having no disclosures. [email protected]

CHESTPHYSICIAN.ORG • OCTOBER 2017 • 43 CARDIOVASCULAR MEDICINE Rivaroxaban plus aspirin ‘In the future, rivaroxaban cut cardiovascular events will take its place among the other foundational in stable patients treatments for long-term, secondary prevention.’ BY MITCHEL L. ZOLER by a statistically significant 20%, Frontline Medical News compared with aspirin alone. Other notable benefits document- BARCELONA – Combined treatment ed by the findings included a statis- with a very low dosage of the anti- tically significant 42% relative risk coagulant rivaroxaban plus low-dose reduction for stroke and a statistically aspirin produced significant cuts in significant 46% relative risk reduc- major adverse coronary, cerebral, tion in the incidence of major ad- and peripheral artery disease events verse limb events among the roughly

with just a modest rise in major one-quarter of enrolled patients who Medical News Mitchel L. Zoler/Frontline bleeding events in patients with sta- entered the study with evidence of Dr. John W. Eikelboom ble disease in the COMPASS pivotal, peripheral artery disease. randomized trial with more than These risk reductions are similar in disease,” commented Eugene Braun- carotid, or peripheral artery disease, 27,000 patients. magnitude to the secondary-preven- wald, MD, designated discussant for or a combination of two or more of The benefits from the rivarox- tion benefits produced by controlling Dr. Eikelboom’s report. The results these, at 602 centers in 33 countries. aban plus aspirin regimen included hypertension or dyslipidemia, not- are “an important step for throm- About 90% of enrolled patients had a statistically significant 24% rel- ed Dr. Eikelboom, a researcher at bocardiology,” said Dr. Braunwald, coronary artery disease and 27% ative risk reduction in the study’s McMaster University in Hamilton, professor of medicine at Harvard had peripheral artery disease. The primary, combined endpoint, and Ont. “In the future, rivaroxaban will Medical School in Boston. enrolled patients averaged 68 year a significant 18% relative risk re- take its place among the other foun- Concurrently with Dr. Eikelboom’s old and were an average of 7 years duction in all-cause death, com- dational treatments for long-term, report the results appeared in an removed from their index arteri- pared with a standard regimen of secondary prevention,” he predicted article published online (N Engl J al event. Randomization assigned aspirin only, John W. Eikelboom, in a video interview, available on Med. 2017 Aug 27. doi: 10.1056/NE- patients to receive 2.5 mg rivarox- MD, said at the annual congress of CHEST Physician’s web site at http:// JMoa1709118). This publication also aban (Xarelto) twice daily plus 100 the European Society of Cardiolo- www.mdedge.com/chestphysician/ include an editorial by Dr. Braunwald mg aspirin daily, 5 mg rivaroxaban gy. In addition, analysis of the net article/145492/cad-atherosclerosis/ (N Engl J Med. 2017 Aug 27. doi: twice daily, or 100 mg aspirin once clinical benefit from treatment that video-rivaroxaban-plus-aspirin-cut- 10.1056/NEJMe1710241). daily. The trial stopped early, after took into account both the major cardiovascular. The Rivaroxaban for the Preven- an average follow-up of 23 months, adverse cardiovascular events pre- The COMPASS trial produced tion of Major Cardiovascular Events because of the overwhelming ben- vented and major bleeding events “unambiguous results that should in Coronary or Peripheral Artery efit seen for the rivaroxaban plus induced, showed that the rivarox- change guidelines and the man- Disease (COMPASS) trial enrolled aspirin combination. The rivarox- aban-plus-aspirin regimen cut these agement of stable coronary artery 27,395 patients with stable coronary, Continued on page 46

VIEW ON THE NEWS an intervention that can reduce critical limb crease bleeding risk, and so Low-dose rivaroxaban benefits ischemia events in addition to reducing cor- they may hesitate to use this despite increased bleeding onary events, stroke, and overall mortality. combination of rivaroxaban The key message from COMPASS was The very low dosage of rivaroxaban used plus aspirin in patients with a that, although adding a very low dosage in COMPASS, 2.5 mg twice daily, seems to high bleeding risk. of rivaroxaban to aspirin in patients with be a very important part of the study’s de- The success of the ap- stable coronary or peripheral artery dis- sign. This dosage appeared to hit the sweet proach used in COMPASS ease resulted in a clear increase in major spot of being large enough to reduce events became possible with the bleeding events, patients received an over- but with a gentle enough anticoagulation introduction of the new oral all net beneficial effect from the combined effect to avoid a significant increase in fa- anticoagulant drugs. Now regimen. The finding that clinches the net tal, intracerebral, or critical organ bleeds. that this class of agents has been avail- benefit from the rivaroxaban plus aspirin However, the patients enrolled in COMPASS, able for a few years, clinicians have grown combination, compared with aspirin alone, like most patients who enter trials, were increasingly comfortable with them, com- was that the combined regimen produced generally at a lower risk for bleeding com- pared with warfarin. When the new oral a statistically significant relative risk reduc- plications than we usually see in routine anticoagulants first came out, many consid- tion of 18% for all-cause mortality. This practice in patients with stable coronary or ered them similar to warfarin. Today, there finding reinforces the idea that the primary peripheral artery disease. Presuming that is a better appreciation that these drugs outcome was beneficial despite an increase the Food and Drug Administration will soon are distinct from warfarin by really causing in major bleeding events. approve the 2.5-mg formulation of rivarox- fewer bleeding complications. The finding that rivaroxaban plus aspirin aban used in COMPASS, clinicians will need produced benefit with a modest increase to be careful using this regimen on patients Christopher B. Granger, MD, is a cardiologist in bleeding risk in patients with peripheral at increased risk for bleeding, such as frail and professor of medicine at Duke Univer- artery disease (PAD) is especially import- or elderly patients with a history of bleeding sity in Durham, N.C. He has been a consul- ant because PAD is really difficult to treat. events or taking other treatments that could tant to and has received research support Very few interventions have previously been increase bleeding risk, such as nonsteroidal from Bayer and from other drugs compa- proven to have a beneficial effect for pa- anti-inflammatory drugs. In general, clini- nies that market new oral anticoagulants. tients with PAD. It’s very important to find cians are wary of using treatments that in- He made these comments in an interview.

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CHPH_45.indd 1 9/26/2017 11:46:52 AM Continued from page 44 aban-monotherapy arm failed to show any statistically significant benefits, compared with the aspi- rin-monotherapy control group. The study’s primary endpoint – the combined rate of cardiovascular disease death, nonfatal stroke, and nonfatal MI – occurred in 4.1% of patients in the rivaroxaban-plus-as- pirin group and in 5.4% of patients on aspirin alone. The rate of major bleeding events was 3.1% among patients on rivaroxaban plus aspi- rin and 1.9% in those who received aspirin only, a 51% relative increase among patients on the dual regimen, Dr. Sonia Anand Dr. Eugene Braunwald but the results showed no statistical- ly significant increase in the rates of adverse limb events and a signifi- acute coronary syndrome event (N rivaroxaban formulation used in fatal bleeds, intracerebral bleeds, or cant 70% relative reduction in the Engl J Med. 2012 Jan 5;366[1]:9- both trials would allow “a treatment bleeding in other critical organs. incidence of major lower-extremity 19). Despite this evidence, the Food strategy that could start early after Sonia Anand, MD, a colleague amputations, reported Dr. Anand, and Drug Administration never an acute coronary syndrome event of Dr. Eikelboom’s at McMaster, professor of medicine and director approved the 2.5-mg formulation of and then extend long term,” he said. presented a separate set of analyses of the vascular medicine clinic at rivaroxaban, nor did it approve mar- COMPASS was sponsored by that focused on the 7,470 enrolled McMaster. keting of rivaroxaban for this acute Bayer, which markets rivaroxaban patients who had been diagnosed The COMPASS findings follow coronary syndrome population. This (Xarelto). Dr. Eikelboom has re- at enrollment with peripheral ar- a 2012 published report from the decision may have been driven in ceived research support from Bayer tery disease. In this subgroup, the ATLAS ACS 2-TIMI 51 trial show- part by a problem with incomplete and also from Boehringer Ingel- rivaroxaban-plus-aspirin regimen ing that treatment with the same follow-up of several of the enrolled heim, Bristol-Myers Squibb, Daiichi, produced a statistically signifi- low-dose rivaroxaban regimen plus patients. Janssen, Pfizer, Portola, and Sanofi. cant 28% relative risk reduction in aspirin and a thienopyridine (clopi- The COMPASS results were “very Dr. Anand has received speaking the rate of the primary endpoint, dogrel or ticlopidine) reduced the consistent” with the ATLAS ACS honoraria from several drug comp- compared with the aspirin control same combined triple endpoint by 2-TIMI 51 results. noted Dr. Eikel- nies. Dr. Braunwald had no relevant group. The dual regimen also pro- a statistically significant 16%, com- boom. “I think it’s time to look at financial disclosures. duced a statistically significant 46% pared with aspirin and a thienopyri- these two trials in combination,” he [email protected] relative risk reduction in major dine alone, in patients with a recent suggested. Availability of the 2.5-mg On Twitter @mitchelzoler

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46 • OCTOBER 2017 • CHEST PHYSICIAN CARDIOVASCULAR MEDICINE Idarucizumab reversed dabigatran completely, rapidly BY AMY KARON have already licensed the human- received idarucizumab, based on About 19% of patients in both Frontline Medical News ized monoclonal antibody fragment diluted thrombin time and ecarin groups died within 90 days. “Pa- based on interim results for the first clotting time. tients enrolled in this study were ne IV 5-g dose of idarucizum- 90 patients enrolled in the Reversal The median maximum percentage elderly, had numerous coexisting ab completely, rapidly, and Effects of Idarucizumab on Active reversal of dabigatran was 100% conditions, and presented with se- O safely reversed the anticoag- (95% confidence interval, 100%- rious index events, such as intracra- ulant effect of dabigatran, according 100%) in more than 98% of patients, nial hemorrhage, multiple trauma, to final results for 503 patients in the Uncontrolled and the effect usually lasted 24 sepsis, acute abdomen, or open frac- multicenter, prospective, open-label, bleeding stopped hours. Among patients who under- ture,” the investigators wrote. “Most uncontrolled RE-VERSE AD study. a median of 2.5 went procedures, intraprocedural of the deaths that occurred within Uncontrolled bleeding stopped a hours after 134 hemostasis was considered normal 5 days after enrollment appeared median of 2.5 hours after 134 pa- in 93% of cases, mildly abnormal in to be related to the severity of the patients received tients received idarucizumab. In a 5% of cases, and moderately abnor- index event or to coexisting con- separate group of 202 patients, 197 idarucizumab. mal in 2% of cases, the researchers ditions, such as respiratory failure were able to undergo urgent proce- DR. POLLACK noted. Seven patients received an- or multiple organ failure, whereas dures after a median of 1.6 hours, other dose of idarucizumab after de- deaths that occurred after 30 days Charles V. Pollack Jr., MD, and his Dabigatran (RE-VERSE AD) study veloping recurrent or postoperative were more likely to be independent associates reported at the Interna- (NCT02104947), noted Dr. Pollack, bleeding. events or related to coexisting con- tional Society on Thrombosis and of Thomas Jefferson University, A total of 24 patients had an adju- ditions.” Haemostasis congress. The report Philadelphia. dicated thrombotic event within 30 Boehringer Ingelheim Pharma- was simultaneously published in the The final RE-VERSE AD cohort days after receiving idarucizumab. ceuticals provided funding. Dr. Pol- New England Journal of Medicine. included 301 patients with uncon- These events included pulmonary lack disclosed grant support from The study uncovered no serious trolled gastrointestinal, intracranial, embolism, systemic embolism, isch- Boehringer Ingelheim during the safety signals, and rates of thrombo- or trauma-related bleeding and emic stroke, deep vein thrombosis, course of the study and ties to Daii- sis were 4.8% and 6.8% at 30 and 90 202 patients who needed urgent and myocardial infarction. The fact chi Sankyo, Portola, CSL Behring, days, respectively, which resembled procedures. Participants from both that many patients did not restart Bristol-Myers Squibb/Pfizer, Janssen other reports of these patient popu- groups typically were white, in their anticoagulation could have contrib- Pharma, and AstraZeneca. Eighteen lations (N Engl J Med. 2017 Jul 11. late 70s (age range, 21-96 years), uted to these thrombotic events, the coinvestigators also disclosed ties to doi: 10.1056/NEJMoa1707278). and receiving 110 mg (75-150 mg) researchers asserted. They noted Boehringer Ingelheim and a number Idarucizumab was specifically de- dabigatran twice daily. The primary that idarucizumab had no procoag- of other pharmaceutical companies. veloped to reverse the anticoagulant endpoint was maximum percentage ulant activity in studies of animals Two coinvestigators had no relevant effect of dabigatran. Many countries reversal within 4 hours after patients and healthy human volunteers. financial disclosures.

Bad news keeps piling up Build Your for Absorb coronary scaffold Ultrasound Portfolio BY BRUCE JANCIN ous Cardiovascular Interventions. Frontline Medical News Importantly, the AIDA investiga- Innovation, Simulation, and Training Center • Glenview, Illinois tors could not identify any predictors PARIS – Device thrombosis occurred of increased device thrombosis risk nearly four times more frequently in Absorb recipients other than the Build your critical care ultrasonography skills in recipients of the Absorb everoli- device itself. Neither age, presenting with courses designed to help you in diagnosis mus-eluting bioresorbable vascular symptoms, lesion characteristics, ves- and management of critically ill patients. scaffold than with the Xience evero- sel size, cardiovascular risk factors, limus-eluting metallic stent during 2 nor residual percentage stenosis de- Ultrasonography: Essentials in Critical Care years of prospective follow-up in the fined a subgroup of scaffold recipients September 15-17 • December 1-3 randomized AIDA trial. at particularly increased risk for this Discover key elements of critical care AIDA (the Amsterdam Inves- complication, said Dr. Wykrzykowska ultrasonography in this intensive 3-day course. tigator-Initiated Absorb Strategy of the University of Amsterdam. Practice image acquisition with human models using high-quality ultrasound machines. All-Comers Trial) was the first ran- The device was approved by the domized trial designed to compare Food and Drug Administration in Critical Care Ultrasonography: Integration the Absorb scaffold to a drug-eluting July 2016. In March 2017 the agency Into Clinical Practice metallic stent in a broad patient pop- issued a safety alert regarding the Ab- November 10-12 ulation reflecting routine real-world sorb scaffold after release of the 2-year Study whole body ultrasonography for diagnosis clinical practice. The disturbing data from the 2,008-patient ABSORB and management of the critically ill patient in a AIDA finding follows upon earlier III trial showing a significantly higher hands-on learning environment using human serious concerns raised regarding an rate of target-lesion failure than with models and state-of-the-art simulators. increased risk of scaffold thrombo- the Xience stent. Both devices are sis – and the particularly worrisome marketed by Abbott Vascular. complication of late thrombosis – in AIDA was a single-blind multi- > Learn More and Register the ABSORB Japan and ABSORB II center Dutch trial that randomized livelearning.chestnet.org/ultrasonography trials, Joanna J. Wykrzykowska, MD, 1,845 patients undergoing PCI, 55% reported at the annual congress of the of whom presented with acute cor- European Association of Percutane- Continued on page 52

CHESTPHYSICIAN.ORG • OCTOBER 2017 • 47 CARDIOVASCULAR MEDICINE New-onset AF after AVR did not affect long-term survival

BY MARK S. LESNEY significant difference between the two survival “New-onset POAF after AVR does not affect Frontline Medical News curves. The Kaplan-Meier overall cumulative long-term survival when treatment is aimed survival rates at 15 years of follow-up in the pa- to restore sinus rhythm before the patient is ew-onset atrial fibrillation after aortic valve tients with new-onset POAF vs. those without discharged home. Future studies with a pro- replacement was not an independent risk were not statistically different (41.5% vs. 41.3%, spective, randomized design should be done to Nfactor for decreased long-term survival, respectively). confirm this finding in patients undergoing dif- according to the results of a single-center, retro- In addition, the 18-year probability of long- ferent kinds of cardiac surgery,” the researchers spective study reported by Ben M. Swinkels, MD, term first adverse events, including recurrent concluded. of St. Antonius Hospital, Nieuwegein, and his AF, transient ischemic attack, ischemic or hem- The study was funded by the authors’ home in- colleagues in the Netherlands. orrhagic stroke, peripheral venous thrombo- stitution; the authors reported they had nothing Key to this success, however, is restoring normal embolism, or major or minor bleeding was not to disclose. sinus rhythm before hospital discharge, they said. significantly different between the two groups. [email protected] In this retrospective, longitudinal cohort study, 569 consecutive patients with no history of AF who underwent AVR with or without concomi- VIEW ON THE NEWS of patients who had isolated tant coronary artery bypass grafting during 1990- Results contradict previous AVR. Dr. Antunes also adds 1993 were followed for a mean of 17.8 years (J studies, but can still reassure that another important as- Thorac Cardiovasc Surg. 2017;154:492-8). The incidence of atrial fibrillation after valve pect to consider is that the Thirty-day and long-term survival rates were surgery has been described to be as high antiarrhythmic drugs used determined in the 241 patients (42%) with and the as 50%, Manuel J. Antunes, MD, said in an prophylactically or therapeu- 328 patients (58%) without new-onset postopera- editorial commentary. “The adverse effect tically for this patient cohort tive atrial fibrillation (POAF), which was defined on long-term survival may not be related to (treated during 1990-1993) as electrocardiographically documented AF last- the short-lived new-onset AF but rather to are no longer used or have ing for at least several hours, and occurring after the underlying pathology associated to the been replaced by new and more efficacious AVR while the patient was still admitted. Standard arrhythmia, especially pathology that affects pharmacologic agents. therapy to prevent new-onset POAF was the use of the myocardium, principally in atheroscle- “This contribution from Swinkels and col- sotalol in patients who were not on beta-blocker rotic coronary artery disease,” he wrote. “It leagues reassures us that new-onset AF, therapy, and continuation of beta-blocker therapy is not survival alone, however, that should common after heart surgery, may have no for those who were already on it. be cause for concern; AF, even in episodes significant impact on early and late survival There were no significant differences between of limited duration, may result in transient if sinus rhythm is effectively and permanent- the two groups in demographic characteristics. ischemic attacks, ischemic, or hemorrhagic ly restored early after the onset of the ar- There were also no significant differences be- strokes, and peripheral thromboembolism, rhythmia and before the patient’s discharge tween the two groups in operative characteristics, which is why affected patients should im- from the hospital.” postoperative in-hospital adverse events, and mediately be anticoagulated.” This study, postoperative hospital lengths of stay until dis- however, is at odds with previously published Manuel J. Antunes, MD, of the University charge home, except for mechanical ventilation studies, with opposite conclusions, according Hospital and Faculty of Medicine, Coimbra, time, which was significantly longer in the pa- to Dr. Antunes. Swinkels and his colleagues Portugal, made these remarks in an in- tients with new-onset POAF (P = .011). suggest that one of the reasons for the dis- vited editorial (J Thorac Cardiovasc Surg. Thirty-day mortality was 1.2% in the patients crepancy was the homogeneous character of 2017;154:490-1). He reported having noth- with POAF, and 2.7% in those without, a non- their series, which consisted almost entirely ing to disclose. significant difference. There was no statistically

Continued from page 47 drug-induced increased bleeding risk stents. But it needs more work. The onary syndrome, and 26% of whom of prolonged DAPT might cancel or company tells me they are going to had ST-elevation MI. The primary perhaps even outweigh the potential launch a newer one, maybe next year, endpoint was target vessel failure, a protection against device thrombosis. with thinner struts and more expand- composite of cardiac death, target ves- On top of all this, implantation of ability.” sel MI, or target-vessel revasculariza- the scaffold entails a longer procedure Asked about the likely mechanism tion. The 2-year cumulative rate did time and a greater volume of contrast of prolonged thrombosis risk with not differ significantly between the material. Absorb, Dr. Wykrzykowska was quick two study arms: 11.7% in the scaffold Discussant Mahmoud Hashemian, to say no one really knows at this group and 10.7% in the metallic stent MD, observed that, while bioresorb- point. recipients. able vascular scaffolds are “physiolog- “Technique [predilation at a 1:1 However, definite or probable de- ically ideal” because – unlike metallic balloon-to-artery ratio with an appro- vice thrombosis occurred in 3.5% of stents – theoretically they leave no priately sized balloon] can obviously the scaffold group compared with permanent implant to impede va- improve things in the short term for 0.9% of metallic stent recipients, for a Dr. Joanna J. Wykrzykowska somotion and serve as a nidus for early events, but I don’t think we un- highly significant 3.9-fold increased neoatherosclerosis, to date they have derstand the biology of late events. risk. This was associated with a sig- continuously for up to 3 years, Dr. shown no real-world benefits over We don’t understand the interaction nificantly increased 2-year cumulative Wykrzykowska and her coinvestiga- current-generation drug-eluting me- between the device and the vessel. It’s risk of MI: 5.5% versus 3.2%. tors have informed AIDA participants tallic stents, but only disadvantages. extremely complex,” she said. On the basis of this unsettling find- of their treatment assignment. They “This doesn’t mean we have to feel AIDA was funded by an unrestrict- ing, coupled with the fact that AB- have also recommended that the Ab- hopeless. I’m not hopeless at all,” said ed educational grant from Abbott SORB II investigators did not find any sorb recipients go on extended DAPT, Dr. Hashemian, an interventional car- Vascular. Dr. Wykrzykowska reported instance of very late scaffold thrombo- even though there is no high-grade diologist at Day General Hospital in receiving consulting and lecture fees sis among 63 patients who remained evidence as yet that this will prevent Tehran. “I’m sure this [bioresorbable from the company. on dual-antiplatelet therapy (DAPT) late scaffold thrombosis or that the scaffolds] will be the future of our [email protected]

52 • OCTOBER 2017 • CHEST PHYSICIAN CARDIOVASCULAR MEDICINE Preventive upstream therapy curbs atrial fib progression

BY BRUCE JANCIN group. They also showed significant differ significantly in body mass in- by the Netherlands Heart Foun- Frontline Medical News reductions in systolic and diastolic dex or left atrial volume. dation and the Netherlands Heart blood pressure, N-terminal pro-brain The lack of impact on left atrial Institute. Dr. van Gelder reported BARCELONA – Aggressive treat- natriuretic peptide, and LDL choles- volume was disappointing, Dr. van having no relevant financial ment of known risk factors for atrial terol, compared with controls. How- Gelder said. interests. fibrillation resulted in improved ever, at 1 year, the two groups didn’t The RACE 3 trial was supported [email protected] 1-year maintenance of sinus rhythm in patients with recent-onset atrial fibrillation and heart failure in the randomized multicenter RACE 3 trial, Isabelle C. van Gelder, MD, re- ported at the annual congress of the European Society of Cardiology. “We now screen for AF, making it possible to catch patients early. That’s what we’ve learned from this trial: If we start treating patients after their first episode of AF and aggressively reduce risk factors for AF, it may help the sinus rhythm. I think that’s an important message: Do not wait too long; start treatment early,” said Dr. van Gelder, professor of cardiology at the University of Groningen (the Netherlands). She calls the interventional strat- egy tested in RACE 3 “risk fac- tor-driven upstream therapy.” The four-pronged strategy consisted of statin therapy, a mineralcorticoid receptor antagonist, an ACE inhib- itor and/or an angiotensin recep- tor blocker, and a 9- to 11-week supervised cardiac rehabilitation program emphasizing lifestyle mod- ification through physical training and dietary changes supported by professional counseling to promote adherence. RACE 3 (Routine Versus Aggres- sive Upstream Rhythm Control for Prevention of Early Atrial Fibrilla- tion in Heart Failure 3) was a mul- ticenter, randomized, nonblinded clinical trial including 245 patients with, on average, a 3-month history of AF, a 2-month history of per- sistent AF, and a 2-month history of mild to moderate heart failure, either with preserved or reduced ejection fraction. All participants received guideline-directed rhythm control and heart failure therapies. In addition, half of participants were randomized to the upstream intervention. Three weeks after enrollment, all patients underwent electrical cardioversion. The primary outcome was main- tenance of sinus rhythm at 1 year as determined by 7-day Holter monitor- ing analyzed in blinded fashion at a central laboratory. The rate was 75% in the upstream intervention group, significantly better than the 63% in controls. This represented a 76% greater likelihood of sinus rhythm at 1 year in the upstream intervention

CHESTPHYSICIAN.ORG • OCTOBER 2017 • 53 LUNG CANCER Cancer screening in elderly: When to just say no BY BRUCE JANCIN guide to physiologic age as part of Colorado at Denver. It’s probably more useful than blood Frontline Medical News of individualized decision making “If you have one measurement to pressure in some of the older adults about when to stop cancer screen- assess ‘am I aging well?’ it’s your gait coming into our clinics,” he said at ESTES PARK, COLO. – A simple ing in elderly patients, according speed. A lot of us in geriatrics are a conference on internal medicine walking speed measurement over to Jeff Wallace, MD, professor of advocating evaluation of gait speed sponsored by the University of Col- a 20-foot distance is an invaluable geriatric medicine at the University in all patients as a fifth vital sign. orado.

54 • OCTOBER 2017 • CHEST PHYSICIAN Dr. Wallace also gave a shout-out to functional status, and body mass index, that nongeriatricians understand the seri- the ePrognosis cancer-screening decision and then spits out data-driven estimated ous limitations of those guidelines. tool, available free at www.eprognosis. benefits and harms a patient can expect “We’re not guidelines followers in the org, as an aid in shared decision-making from advanced-age screening for colon or geriatrics world because the guidelines conversations regarding when to stop breast cancer. don’t apply to most of our patients,” he ex- cancer screening. This tool, developed by Of course, guidelines as to when to stop plained. “We hate guidelines in geriatrics researchers at the University of California, screening for various cancers are available because few studies – and no lung cancer San Francisco, allows physicians to plug from the U.S. Preventive Services Task or breast cancer trials – enroll patients key individual patient characteristics into Force, the American Cancer Society, and over age 75 with comorbid conditions. its model, including comorbid conditions, specialty societies. However, it’s important Continued on following page DR. WALLACE

CHESTPHYSICIAN.ORG • OCTOBER 2017 • 55 Continued from previous page country. We’re doing a lot more than gone prostate cancer screening, Oct;174[10]:1558-65). Also, most of these guidelines do we should,” said Dr. Wallace. and 53% of women had recently All of that is clearly overscreening. not incorporate patient preferences, He highlighted a University of had a mammogram. Up to 56% of Experts unanimously agree that, which probably should be a primary North Carolina study of more than women who underwent a hysterec- if someone is not going to live for goal. So we’re left extrapolating.“ 27,000 participants aged 65 years tomy for benign reasons had a Pap 10 years, the person is not likely to Regrettably, though, “it turns out or older in the population-based test within the previous 3 years. benefit from cancer screening. The most Americans are drinking the National Health Interview Survey. Moreover, more than one-third of one exception is lung cancer screen- Kool-Aid when it comes to patient Among those deemed at very high women with less than a 5-year life ing of high-risk patients, where preferences. It’s amazing how much risk of mortality within 9 years, expectancy had a recent mammo- there are data to show that annual cancer screening is going on in this 55% of men had recently under- gram (JAMA Intern Med. 2014 low-dose CT screening is beneficial

56 • OCTOBER 2017 • CHEST PHYSICIAN in those with even a 5-year life ex- That’s where gait speed and eProg- 6-21 years of follow-up. Investiga- men age 75, the Pittsburgh investi- pectancy. nosis come in handy in discussions tors at the University of Pittsburgh gators found, gait speed predicted As part of the Choosing Wisely with patients regarding what they identified a strong relationship be- 10-year survival across a range of program, the American Geriatric can realistically expect from cancer tween gait speed and survival. Every 19%-87%. The median speed was Society has advocated that physi- screening at an advanced age. 0.1-m/sec made a significant differ- 0.8 m/sec, or about 1.8 mph, so a cians “don’t recommend screening The importance of gait speed was ence (JAMA. 2011 Jan 5;305[1]:50- middle-of-the-pack walker ought for breast, colorectal, prostate, or highlighted in a pooled analysis of 8). to stop all cancer screening by age lung cancer without considering life nine cohort studies totaling more A gait speed evaluation is simple: 75. A fast-walking older man won’t expectancy and the risks of testing, than 34,000 community-dwelling The patient is asked to walk 20 feet reach a 10-year remaining life overdiagnosis, and overtreatment.” adults aged 65 years and older with at a normal speed, not racing. For Continued on following page

CHESTPHYSICIAN.ORG • OCTOBER 2017 • 57 Continued from previous page upon whether she is a faster- or recommends selective screening for population-based, prospective, ob- expectancy until he’s in his early slower-than-average walker, Dr. those aged 76-85, with a weaker C servational study included 1,355,692 to mid-80s; a slow walker reaches Wallace explained. recommendation (JAMA. 2016 Jun Medicare beneficiaries aged 70-79 that life expectancy as early as his The U.S. Preventive Services Task 21;315[23]:2564-75). years at average risk for colorectal late 60s, depending upon just how Force currently recommends colon What are the practical implica- cancer who had not had a colonos- slow he walks. A woman at age cancer screening routinely for 50- to tions of that recommendation for copy within the previous 5 years. 80 with an average gait speed has 75-year-olds, declaring in accord selective screening after age 75? The investigators demonstrated roughly 10 years of remaining life, with other groups that this strategy Investigators at Harvard Medical that the benefit of screening colo- factoring in plus or minus 5 years has a high certainty of substantial School and the University of Oslo noscopy decreased with age. For from that landmark depending net benefit. But the USPSTF also recently took a closer look. Their patients aged 70-74, the 8-year risk of colorectal cancer was 2.19% in those who were screened, compared with 2.62% in those who weren’t, for an absolute 0.43% difference. The number needed to be screened to detect one additional case of colorectal cancer was 283. Among those aged 75-79, the number needed to be screened climbed to 714 (Ann Intern Med. 2017 Jan 3;166[1]18-26). Moreover, the risk of colonos- copy-related adverse events also climbed with age. These included perforations, falls while racing to the bathroom during the preprocedural bowel prep, and the humiliation of fecal incontinence. The excess 30- day risk for any adverse event in the colonoscopy group was 5.6 events per 1,000 patients aged 70-74 and 10.3 per 1,000 in 75- to 79-year- olds. In a similar vein, Mara A. Schon- berg, MD, of Harvard Medical School, Boston, has shed light on the risks and benefits of biannu- al mammographic screening for breast cancer in 70- to 79-year- olds, a practice recommended in American Cancer Society guide- lines for women who are in overall good health and have at least a 10- year life expectancy. She estimated that 2 women per 1,000 screened would avoid death due to breast cancer, for a num- ber needed to screen of 500. But roughly 200 of those 1,000 women would experience a false-pos- itive mammogram, and 20-40 of those false-positive imaging studies would result in a breast biopsy. Also, roughly 30% of the screen-detected cancers would not otherwise become apparent in an older woman’s lifetime, yet nearly all of the malignancies would undergo breast cancer therapy (J Am Geriatr Soc. 2016 Dec;64[12]:2413-8). Dr. Schonberg’s research speaks to Dr. Wallace. “It’s breast cancer therapy: It’s procedures; it’s medicalizing the pa- tient’s whole life and creating a high degree of angst when she’s 75 or 80,” he said. Dr. Wallace reported having no financial conflicts regarding his pre- sentation. [email protected]

58 • OCTOBER 2017 • CHEST PHYSICIAN NEWS FROM CHEST An interview with incoming CHEST President, John Studdard, MD, FCCP

Born and raised in Mississippi, So work-life balance, particularly in ly as I do when I look back at my time Dr. Studdard says there were today’s world, is more difficult than just being a part of our CHEST Foun- four factors that inspired ever for everyone. I am blessed that dation, I will feel incredibly fulfilled. him to become a physician: my wife is the daughter of a general 1. I have always loved people and surgeon, and she understood a little What made you want to working with them, and I always bit about stressors in a physician’s be President of CHEST? admired the respect that physi- life – sometimes she seems to un- I believe it is always important to cians received in my community. derstand more than others—she is a give back to the people who gave 2. We generally enjoy doing what unique person. Work-life balance is all you something. CHEST has given we are pretty good at...I am pretty about priorities – our priority was our me a ton over the last 36 years, so good at math and science, and family. We spent a ton of time with giving back to CHEST is easy. these were important components our children, great vacations, rarely in pre-med curriculum in my day. missed a program or ballgame (there What are you looking forward John Studdard, MD, FCCP, has been 3. I am competitive and decided if were lots of them), and frequently to as President of CHEST? a member of the American College it was going to be hard to get into that involved going to work early in On a personal level, I am looking of Chest Physicians for 36 years, and, medical school, then I wanted to the morning, coming home early in forward to what we are doing right this November, he will be inaugurat- go to medical school. the evening, and going back to the now, meeting new people, and ed as CHEST President. This will not 4. My dad always told my brother hospital to finish up late at night. A lot learning from young people. be Dr. Studdard’s first time in a pres- and me that we would be doctors of being a good parent is being lucky. Because of my background and idential role for CHEST, as he served when we grew up, because we were We either did a lot of things right, or upbringing, I have a passion for as CHEST Foundation President going to be our own boss. I have were lucky, or a combination of both, diversity and inclusion; I think we in 2013 and 2014. Currently, Dr. been in private practice for 36 because I think our kids turned out need to continue to talk about, learn Studdard serves as a pulmonologist years, and that is not the case, not pretty darn well. about, care about, be open about, at Jackson Pulmonary in Jackson, if you are doing it right. I obvious- and be transparent about diversity of Mississippi. Being a physician and ly love medicine, and my dad was What has been your favorite thought, inclusion, and care disparity. being as heavily involved with an great in that he paid for our educa- project throughout your The word “diversity” means some- organization as Dr. Studdard is takes tion…but he called the shots. involvement with CHEST? thing different to every person, and, a lot of prioritizing, hard work, and Early in my days as a member of for that, we have to have respect. dedication. Get to know CHEST’s What are some of the biggest CHEST, a mentor of mine from Continued on page 62 new President through this interview. challenges you have encountered training at the Mayo Clinic, Dr. Doug throughout your career? Gracey, gave me the opportunity to Private practice makes you gain join the CHEST Government Rela- more independence and autonomy; tions Committee, which he chaired. you have to become more agile, After a few years, I was given the op- more efficient, and you have aw- portunity to serve as its Chair. We be- 2017 fully big workloads. However, you came heavily involved in the tobacco give up the academic stimulation wars, as some people called them. Our of being in an academic center. It Attorney General in Mississippi at the is a tough discipline in the private time, Mike Moore, and a plaintiff’s practice of medicine to try to stay attorney in Mississippi, Dick Scruggs, up to date. Whether going to the whom I knew from some work I had CHEST Annual Meeting, reading done from the defense side of asbes- our journal CHEST, or looking at tos litigation, took a lead role in the CHEST education online products, Attorney General’s Master Settlement those of us in the clinical practice of - a group of attorney generals suing pulmonary, critical care, and sleep the tobacco industry (basically, state’s medicine are more dependent than Medicaid was suing the tobacco in- any group on what our clinical edu- dustry for reimbursement of funds). It cators write and teach. was a completely different approach. The tobacco industry turned its nose How do/did you balance work up at it at first – they did not think it and your personal life? had a chance to fly, but it did. CHEST We are busy in practice, particularly got involved early on, and then a big CHEST 2017 Early Education Opportunities when taking on volunteer opportu- a group of people, including Tobacco Planning on arriving to Toronto a day early? Attend one of our postgraduate course nities, and that time comes out of Free Kids, the American Cancer So- tracks happening Saturday, October 28. (Full- and half-day options available.) something: time with family, hobbies, ciety, and many others in the public Topics include: n Thoracic Ultrasound it has to come from somewhere. But health space, got involved. CHEST n Pulmonary Medicine Literature Review and Update it is not unique to those of us in med- represented the public health commu- n Critical Care: Things Your Fellows Do But You Might Not icine. My daughter is a 33-year-old nity during part of the negotiations n Interstitial Lung Disease mother to a 20-month-old beautiful that led to the Attorney General’s n Sleep Medicine: Board Review granddaughter of ours and is pregnant Master Settlement. We should be with another child, and she and her very proud of the role CHEST played husband both work full time. Our son in this critical public health effort. If Seats are filling quickly, reserve yours today. chestmeeting.chestnet.org and his wife also both work and must I can look back at my time spent in find ways to balance work/life issues. CHEST leadership, and see it as fond-

CHESTPHYSICIAN.ORG • OCTOBER 2017 • 59 NEWS FROM CHEST #Winning: Are you in it to win it at CHEST 2017?

CHEST 2017 offers several contests colleagues! Be sure to find them all ture with our social media followers. opportunities in the Exhibit Hall and opportunities to win great prizes! and share your images on Twitter or Don’t miss your chance to be featured! during CHEST. Play CHEST Bingo Are you ready to take home the prize? Instagram using our #CHEST2017 daily, starting Monday, October 30, hashtag. We’ll choose our favorite Don’t miss out on CHEST Bingo through Wednesday, November 1, CHEST Events App photo of the day and reshare your pic- Take advantage of one of the many for a chance to win a prize! Game: Click Game Do you like scavenger hunts? How about prizes? In our CHEST Events app, you will find the game Click filled with a list of photo challeng- es. To participate, simply log in and earn your challenge badges by

submitting photos to your profile. As you complete each challenge throughout the duration of CHEST 2017, your badges will accumulate, and we will award sweet treats to the person(s) with the highest num- ber of badges on the last day of the annual meeting. Winners can stop by the press room, Metro Toronto Convention Centre, Room 706, to collect prizes on Wednesday, No- vember 1, by 2:00 PM local time.

Rules of participation • To participate, you must be a reg- istered attendee on-site at CHEST 2017. • The contest begins Saturday, Octo- ber 28 at 12:00 PM EST, and ends Wednesday, November 1, at 10:00 AM EST. • Prize must be picked up in the Press Room, Room 706, between the hours of 10:00 AM and 2:00 PM, November 1. • Questions about the Click photo contest should be directed to so- [email protected]

Are you a VITweep? Get active on Twitter, and share your latest highlights for #CHEST2017! Sitting in on an inter- esting session? Having a great time visiting the posters? Let us know! The most active tweeters for the day will receive a special prize!

Share your selfies! See a selfie spot and take advantage of it! We know there’s more to your trip than lectures and keynote speakers, and we want to see it! Throughout the convention center, you’ll find many designated areas to snap and share photos of yourself and

60 • OCTOBER 2017 • CHEST PHYSICIAN NEWS FROM CHEST

How to play: CHEST bookstore. There will be a Augmenting Medical Education). • One each day for whoever has Find your bingo card in the pro- winner drawn every night! Last year, we gave away 15 refur- played the most games and Virtual gram guide that you will receive bished iPad 2s; this year, we hope to Patient Tours (VPTs). during registration. Get each bingo Win an iPad®! give away 30 refurbished iPad 2s! • Several for playing the games Peer letter to spell out C-H-E-S-T as This year, attendees will have the op- iPads will be awarded for the fol- Pressure and Nodal Nemesis. you visit each of the five sponsors’ portunity to win a refurbished iPad lowing: Please refer to the program sched- booths. You will then have a chance for playing one of our Simulation • One each day for the fastest time on ule in the CHEST Events app for dates to win a $75 gift certificate to the Center’s arcade style GAMEs (Games Aspirated! and times of the GAMEs and VPTs.

CHESTPHYSICIAN.ORG • OCTOBER 2017 • 61 NEWS FROM CHEST Changes to CPT® codes coming January 2018

BY MIKE NELSON, MD, FCCP gy (CPT®) codes of interest to pulmo- the services described by these codes. eg, removal of viscous, copious or CHEST Physician Editorial Board Member nary/critical care providers in January There are two changes in the CPT tenacious secretions from the airway. 2018. A thorough understanding of codes for bronchoscopy involving It had previously included wording here will be a number of changes these changes is important for appro- 31645 and 31646. CPT code 31645 that suggested it was used for abscess Tto Current Procedural Terminolo- priate coding and reimbursement for describes a therapeutic bronchoscopy, drainage, and this has been removed. If a therapeutic bronchoscopy pro- cedure is repeated during the same hospital stay, then CPT code 31646 should be utilized. If a therapeutic bronchoscopy procedure is performed in the non-hospital setting and lat- er repeated, then CPT code 31646 would be used for both procedures. CPT code 94620 Pulmonary stress testing; simple (eg, 6-minute walk test, prolonged exercise test for broncho- spasm with pre- and post-spirometry and oximetry) has been deleted and replaced by two new codes. CPT code 94617 Exercise test for bronchospasm, including pre- and postspirometry, elec- trocardiographic recording(s), and pulse oximetry describes the procedure used to assess for exercise-induced bron- chospasm. CPT code 94618 Pulmo- nary stress testing (eg, 6-minute walk test), including measurement of heart rate, oximetry, and oxygen titration, when performed, describes the typical simple pulmonary stress test. After January 1, 2018, if CPT code 94620 is used, the claim will be denied. CPT code 94621 Cardiopulmonary exercise testing, including measurements of minute ventilation, CO2 production, O2 uptake, and electrocardiographic recordings has been reworded to better describe the procedure of cardiopul- monary exercise testing. Additionally, there are numerous parentheticals appended that list the CPT codes that may not be used in conjunction with 94617, 94618, and 94621. Please refer to the 2018 CPT manual for further . information on these exclusions.

NEW PRESIDENT // continued from page 59 As Dr. Studdard prepares to take on his new role in CHEST leadership this October, he is optimistic about what the future will bring and about the things that he will learn. He considers himself incredibly lucky to be in the position that he is in, and he values each relationship he has made during his involvement with CHEST. He is looking forward to all that is in store during his time as President. He left us with a quote from Wyatt Cooper: “The only immortality we can be sure of is that part of ourselves we invest in others—the contribution we make to the totality of man, the knowledge we have shared, the truths we have found, the causes we have served, the lessons we have lived.”

62 • OCTOBER 2017 • CHEST PHYSICIAN NEWS FROM CHEST

NETWORKS Transbronchial cryobiopsy, updated guidelines for chronic cough in children, PD-1 inhibition Interventional Chest/ (DiBardino DM, et al. Ann Am (Chest. 2017;151(4):884-890) and algorithms outcomes of children Thorac Soc. 2017;14[6]:851). The Use of Management Pathways or Al- with chronic cough. Both articles Diagnostic Procedures authors pointed to lack of a pre- gorithms in Children with Chronic can be found on the guidelines sec- defined procedural protocol, as well Cough (Chest. 2017;151(4):875-873) tion of the CHEST site. Cryobiopsy for ILD: Careful as several choices relating to the are updates from the 2006 CHEST John Bishara, DO stewardship needed specific technique used, including guidelines on chronic cough in chil- Fellow-in-Training Member Interest in transbronchial cryobiop- inconsistent use of fluoroscopy, lack dren. sy has accelerated rapidly in recent of prophylactic bronchial blocker The present updates utilized the years. This procedure is performed placement, and predominant use of CHEST methodological guidelines Pulmonary Physiology, by advancing a cryoprobe into the laryngeal mask airways as potential with chronic wet or productive Function, and peripheral lung via flexible bron- contributing factors. Indeed, many cough and Grading of Recommen- variations of the basic cryobiopsy dations Assessment, Development, Rehabilitation procedure have been described and Evaluation framework and Functional imaging of the lung (Lentz RJ, et al. J Thoracic Dis. also performed a systematic review Quantifying heterogeneity of 2017;9[7]:2186), with no formal addressing key questions concern- ventilation and gas exchange in guidance or training available to ing the management of childhood lung diseases remains a clinical inform advanced bronchoscopists disease for children 14 years and challenge. Conventional pulmo- interested in this procedure. younger. nary function test is insensitive It is incumbent on the inter- Guidance provided by the expert to regional changes. The multiple ventional pulmonology and ILD panel focused on recommendations inert gas elimination technique specialist communities to be re- to answer six key questions con- can quantify ventilation-perfusion DR. LENTZ DR. MALDONADO sponsible stewards of this prom- cerning the management of children distribution, but it requires invasive ising procedure. Implementation 14 years and younger with a chronic instrumentation (eg, pulmonary choscopy, where lung tissue freezes of three parallel efforts to stan- wet cough unrelated to established artery catheterization) and is not and adheres to the probe and is sub- dardize and rigorously study this chronic lung disease. The recom- practical for clinical use. Computed sequently extracted as a cryobiopsy. procedure should be considered as mendations are: tomography (CT) scans delineate The number of cryobiopsy-related soon as possible: creation of expert 1. Chronic cough is defined as the spatial changes in lung structures publications has increased expo- consensus guidelines establishing presence of a cough 4 weeks or but do not directly measure chang- nentially since it was described in best-practices for safe and effec- longer in duration. es in ventilation and gas exchange. 2009 (Babiak A, et al. Respiration. tive biopsy technique; a training 2. Assessment of the effect of the With its radiation, it is difficult 2009;78[2]:203). This interest stems requirement before independent cough on the child and the family to apply CT scanning repeatedly from reports of high diagnostic performance of the procedure; and be undertaken as part of clinical in patients. More recently, MR yields in patients with interstitial creation of an international cryo- consultation. imaging techniques have been de- lung disease (ILD) while maintain- biopsy registry to facilitate high- 3. Evaluation of a chronic cough veloped to directly “visualize” and ing complication rates similar to er-quality research into optimal should be done with a systematic quantify regional lung function that of conventional bronchoscopic technique and outcomes. We owe approach with pediatric-specific (Kruger SJ, et al. J Magn Reson Im- biopsy. this to our patients. cough management protocols or aging. 2016;43(2):295; Roos JE, et Traditional bronchoscopic biop- Robert J. Lentz, MD algorithms. al. Magn Reson Imaging Clin N Am. sies are notoriously insensitive; a NetWork Member 4. Chest radiograph and, when age 2015;23(2):217). These techniques specific diagnosis can be established Fabien Maldonado, MD, FCCP appropriate, spirometry with employ inhalation of gases, such as in fewer than a third of cases (Sheth NetWork Member bronchodilator be undertaken oxygen, perfluorinated gases, and JS, et al. Chest. 2017;151[2]:389). As as evaluation; tests for pertussis hyperpolarized 3He and 129Xe. Hy- such, surgical lung biopsy continues infection only to be performed if perpolarized 3He has been studied to be recommended but is associat- Pediatric Chest clinically suspected. the most; however, the dwindling ed with significant mortality (2%) Medicine 5. Chronic wet cough with no supply of 3He gas and its rising cost and morbidity (30%) in patients specific clinical features should have prevented its further develop- with ILD (Hutchinson JP, et al. AR- Chronic cough in children: receive antibiotics for 2 weeks ment. 129Xe has abundant supply JCCM. 2016;193[10]:1161). Cryobi- New guidelines targeted for common respiratory and has emerged to be the inert gas opsy, which appears to rival surgical A chronic cough is a common bacteria (Streptococcus pneumoni- of choice for MR imaging. Hyper- lung biopsy in terms of ability to complaint among children whose ae, Haemophilus influenzae, and polarized 129Xe can measure venti- contribute to a specific diagnosis, is, parents seek medical evaluation. Moraxella catarrhalis). lation, like hyperpolarized 3He. In therefore, a highly promising alter- Chronic wet cough can indicate an 6. When cough persists despite 2 addition, Xe diffuses into alveolar native (Tomassetti S, et al. AJRCCM. underlying illness; therefore, an ear- weeks of appropriate antibiotics, barrier (interstitium and plasma) 2016;193[7]:745). ly diagnosis can lead to prevention it is recommended to continue for and red blood cells, where it ex- As cryobiopsy is increasingly ad- of complications of the disease and an additional 2 weeks. hibits distinct resonant frequency opted around the world, however, improvement in quality of life. 7. Additional tests (eg skin prick shifts that can be captured by MR. troubling reports of serious compli- CHEST is a leading resource test, Mantoux, bronchoscopy, Therefore, in one test, information cations have surfaced. Most notable in evidence and consensus-based chest CT scan) should be indi- on pulmonary ventilation and gas is the recently reported experience guidelines on important topics af- vidualized in accordance with the transfer can be obtained. To date, of the initial 25 cases performed at fecting children. The most recent clinical setting and child’s clinical the results from MR imaging stud- the University of Pennsylvania, in guidelines entitled Management of symptoms and signs. ies have provided new insights into which almost one in four patients Children with Chronic Wet Cough The panel recognizes the need for the pathophysiology of obstructive suffered serious complications and Protracted Bacterial Bronchitis prospective studies to assess current Continued on page 68

CHESTPHYSICIAN.ORG • OCTOBER 2017 • 63 NEWS FROM CHEST

Continued from page 63 Thoracic Oncology sion of indications for use of these tis secondary to PD-1 inhibitions and restrictive lung diseases. With agents, the number of patients is reported to occur in 2% to 5% continuous development, MR im- Immune-mediated pneumonitis treated will continue to grow. Clini- of patients and can present at any aging of the lung could become a and PD-1 inhibition cians must be aware of their poten- time during therapy, with 1% of clinically useful tool in the near Inhibitors of the programmed tial for serious adverse side effects, patients developing grade 3 or future. cell death 1 receptor (PD-1) have including dermatitis, colitis, and higher pneumonitis.1,2 The most Yuh-Chin T. Huang, MD, MHS, shown significant promise in the potentially life-threatening pneu- common symptoms are dyspnea FCCP treatment of advanced stage ma- monitis. and cough, though one-third Steering Committee Member lignancy. With the recent expan- The development of pneumoni- Continued on page 71

SATURDAY OCTOBER 28

2:00 pm – 4:00 pm (Open Invitation) Lung Health Experience—Community COPD Screening Nathan Phillips Square 100 Queen St W, Toronto, ON M5H 2N2, Canada

SUNDAY Connect with the OCTOBER 29

9:00 am - 5:00 pm CHEST Foundation Donor Lounge Convention Center, 803B at CHEST 2017 3:15 pm - 4:15 pm Foundation Session: Severe Asthma Care at Its Best: Shared Decision Making” Convention Center, 716A

4:30 pm - 5:30 pm Foundation Session: No Money, No Mission: Tips for Getting Your Grant Funded Convention Center, 716B

MONDAY OCTOBER 30

9:00 am - 5:00 pm Donor Lounge Be sure to check out our ever-growing presence at CHEST 2017, Convention Center, 803B showcasing the numerous ways we support CHEST members, patients, 8:45 am – 10:00 am Opening Session / CHEST Foundation and the community. Have time for a break or interested in networking Awards Convocation with leaders in CHEST medicine? Stop by one of our many open invitation Convention Center, Hall G, Level 800 activities to the right to learn more about how the CHEST Foundation 6:30 pm - 8:00 pm can support you in your efforts to champion lung health, through clinical Boehringer Ingelheim and CHEST Foundation Patient Engagement Summit research grants, community service and patient education. Sheraton, Grand Ballroom Centre 8:00 pm – 10:00 pm Young Professionals Reception (RSVP chestfoundation.org/youngprofessionals) The Fifth Social Club 225 Richmond St W Suite 100 Thank you for your support Toronto, ON M5V 1W2, Canada of the CHEST Foundation and ADD YOUR VOICE and champion lung health at our mission of championing TUESDAY lung health! the Actelion Booth #1322. OCTOBER 31 For every addition to the graffiti 9:00 am - 5:00 pm wall, Actelion will donate $25 to Donor Lounge the CHEST Foundation. Convention Center, 803B

WEDNESDAY NOVEMBER 1

9:00 am - 12:00 pm Donor Lounge Convention Center, 803B

68 • OCTOBER 2017 • CHEST PHYSICIAN CLASSIFIEDS Also available at MedJobNetwork.com

PROFESSIONAL OPPORTUNITIES

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330 Brookline Avenue, Boston, MA

CHESTPHYSICIAN.ORG • OCTOBER 2017 • 69 CLASSIFIEDS Also available at MedJobNetwork.com

PROFESSIONAL OPPORTUNITIES

Coastal Virginia Opportunities Outpatient and Inpatient: Enjoy a Busy Practice with an Exceptional Quality of Life in Pulmonary and Critical Care the “City of Four Seasons” Hendersonville, North Carolina! Join our 560+ multi-specialty clinical team (RMG) at the heart of one of America’s Excellent Pulmonary/Critical Care Medicine Physician Practice Opportunity strongest healthcare delivery organizations – Riverside Health System. It is with Carolina Lung and Sleep at Pardee. Sleep Medicine practice optional. a system well-prepared to help you face the challenging growth of current Physician must be BC in Pulmonary and Critical Care. Sleep Fellowship/BC and future healthcare demands. Over 100 years old, it has an established required if practice includes Sleep Medicine. reputation for strength in many specialties including neurosciences, cardiac, orthopedic care, elder care, wellness and mental health support. Competitive base + wRVU incentive, annual bonus based on quality measures, comprehensive benefi ts and retirement package, professional liability insurance, Each role allows you the opportunity to work with highly respected teams Paid Time Off, sign-on, relocation. Epic EMR. offering a variety of cases, collaborative environments and solid referral patterns. Locations include: Pardee Hospital is a 222-bed not-for-profi t community hospital affi liated with UNC Health Care. New cancer center adjacent to practice with Hematology/ • Newport News: hamptonroads.com • Williamsburg: visitWilliamsburg.com Oncology and Radiation Oncology, clinical trials, registry, and survivorship • Gloucester: gloucesterva.info • Tappahannock: essex-virginia.org program. Lung Nodule Clinic under development. Ebus and Navigational Ideal candidates understand and welcome the importance of their roles as Bronchoscopy added in 2015. Beautiful community in the WNC mountains care providers, team members, and major infl uencers of our community’s located between Greenville, SC, and Asheville, NC. impression of Riverside’s quality and service. Discover the lifestyle of southeastern Virginia where social and cultural opportunities abound with No Visa Sponsorships — No Recruitment Firm Inquiries moderate climate and easy access to the Chesapeake Bay, the majestic James Send CV for consideration to: Lilly Bonetti River, and Atlantic Ocean. Pardee UNC Health Care Please forward your CV to: 800 North Justice Street Nicole Laroche, CPC, CERS Hendersonville, NC 28791 Physician Development (828) 694-7687 [email protected] [email protected] Offi ce: (757) 224-4990, Cell: (757) 544-6069 www.pardeehospital.org

Pulmonary/Critical Care with Sleep Cambridge Health Alliance • Cambridge, MA Cambridge Health Alliance (CHA) an award-winning public healthcare system, has an opportunity for a Pulmonary/ Critical Pulmonology/Critical Care Care Physician to join our existing Pulmonary team. Our system is comprised of three hospital campuses and an integrated network of Outstanding opportunity for pulmonary critical care on the Mississippi Gulf Coast. This both primary and specialty care practices in the Boston area. CHA is is a well-established group which is hospital employed. Coverage is provided to two a teaching affiliate of both Harvard Medical School (HMS) and Tufts University School of Medicine. hospitals within the system. This group runs the only Pulmonary Hypertension Center on the Mississippi Gulf Coast. Advanced bronchoscopy including EBUS, radial EBUS, and Candidate will practice Pulmonary/CC medicine and ideally incorporate dedicated Sleep Medicine time, as well as possess a navigational bronchoscopy is available. Additional pulmonary interventions provided by strong interest in resident and medical student teaching. Incoming thoracic surgeons. Active Lung Cancer Screening program is operational in the system. physician should possess excellent clinical/communication skills ASSM accredited sleep center with 6 beds is run by three sleep board certifi ed physicians. and a strong commitment to serve our multicultural safety net Intensivist coverage provided for 24 bed multidisciplinary ICU. Physician extenders are also patient population. This position has both inpatient and outpatient part of the group and assist in the ICUs and clinic. Visa sponsorship available. responsibilities. We offer a supportive and collegial environment with a strong infrastructure, inclusive of an electronic medical records system (EPIC). Candidates will have the opportunity to Benefits Available: work in a team environment with dedicated colleagues similarly • The most competitive incentive • Annual pledge towards licensure committed to providing high quality healthcare. Our employees package with a guaranteed base and fees receive competitive salary and excellent benefits. plus performance and production • Malpractice Coverage Please send CV’s to Lauren Anastasia, Department of Physician incentives • Paid Time Off per Human Resources Recruitment, Cambridge Health Alliance, 1493 Cambridge Street, • Relocation Assistance or Sign-on policy and procedure Cambridge, MA 02139, via e-mail: [email protected], via Bonus fax (617) 665-3553 or call (617) 665-3555. www.challiance.org. We are an equal opportunity employer and all qualified applicants • Student Loan Assistance singingriverhealthsystem.com • Annual CME Allowance will receive consideration for employment without regard to race, color, religion, sex, sexual orientation, gender identity, national Please forward your CV to: Physician Relations Department, origin, disability status, protected veteran status, or any other [email protected] 228-818-4023 or [email protected] 228-818-4024 characteristic protected by law. www.challiance.org Jackson County is a coastal community that is the perfect place to work, live and raise a family. With small town values, excellent schools, community events and recreational activities. This area is great for outdoorsmen with beaches, boating, fi shing and hunting. We off er a small town atmosphere but are nestled in between two larger cities, New Orleans, Louisiana and Mobile, Alabama. Both are just about an hour away and have big city amenities. Moving? Look to Classifi ed Notices for practices available in your area.

70 • OCTOBER 2017 • CHEST PHYSICIAN NEWS FROM CHEST

NETWORKS // continued from page 68 Pulmonary Vascular ing but require confirmation in larger of patients are asymptomatic at clinical studies. This Month presentation.2 Radiographic and Disease Stephen Mathai, MD, FCCP pathologic features vary greatly Pulmonary Arterial Chair in CHEST and include organizing pneu- Hypertension Associated Leena Palwar, MD monia, interstitial pneumonitis, With SLE Fellow-in-Training Member hypersensitivity pneumonitis, or While pulmonary arterial hyperten- Editor’s Picks diffuse alveolar damage.3 sion (PAH) commonly complicates References While pneumonitis due to PD-1 scleroderma (SSc), it is a rare compli- Hachulla E, Jais X, Cinquetti G, et al. Pulmo- inhibition is reportedly uncom- cation of other connective tissue dis- nary arterial hypertension associated with SLE: Results from the French pulmonary mon, the increasing number of eases (CTD), such as systemic lupus hypertension registry. Chest. 2017 Aug 26. patients expected to receive these erythematosus (SLE). In the few pro- pii: S0012-3692(17)31430-7. doi: 10.1016/j. medications will predictably result spective studies that utilize right-sid- chest.2017.08.014. [Epub ahead of print] Chung L, Liu J, Parsons L, et al. Characteriza- in increasing overall frequency of ed heart catheterization (RHC), the tion of connective tissue disease-associated pneumonitis cases. In addition, the estimated prevalence of PAH in SLE pulmonary arterial hypertension from REVEAL: lack of large prospective random- is about 4%. However, since the prev- identifying systemic sclerosis as a unique ized trials and reliance on radio- alence of SLE is 10 to 15 times great- phenotype. Chest. 2010;138:1383-1394. Shirai Y, Yasuoka H, Okano Y, Takeuchi T, Sa- graphic rather than pathologic data er than SSc in the United States, the toh T, Kuwana M. Clinical characteristics and in diagnosing immune-mediated true prevalence of SLE-PAH may be survival of Japanese patients with connective BY RICHARD S. IRWIN, MD, pneumonitis gives one pause. Giv- higher than previously thought, and, tissue disease and pulmonary arterial hyper- MASTER FCCP tension: a singlecentre cohort. Rheumatolo- CHEST en the variability of presentation, thus, clinically relevant. Despite this, gy. 2012;51:1846-1854. Editor in Chief, lack of routine pathologic data, little is known about SLE-PAH. Hao YJ, Jiang X, Zhou W, et al. Connective and increasing use of dual agents A recent retrospective study from tissue disease-associated pulmonary arterial A Multicenter, Randomized (eg, PD-1 and CTLA-4), chest the French Pulmonary Hypertension hypertension in Chinese patients. Eur Respir Trial of Ramped Position J. 2014;44: 963-972. physicians and medical oncolo- Registry has added significantly to our Huang C, Li M, Liu Y, et al. Baseline charac- vs Sniffing Position During gists should have a high index of understanding of this complication of teristics and risk factors of pulmonary arterial Endotracheal Intubation of suspicion yet practice equipoise in SLE. Hachulla and colleagues studied hypertension in systemic lupus erythematosus Critically Ill Adults. patients receiving immunotherapy 51 patients with RHC-proven SLE- patients. Medicine. 2016;95:e2761. By Dr. M. W. Semler, et al. Pérez-Peñate GM, Rúa-Figueroa I, Juliá- Serdá who develop unexplained pulmo- PAH compared with 101 SLE control G, et al. Pulmonary arterial hypertension in nary symptoms or infiltrates. More subjects without PAH. While the systemic lupus erythematosus: prevalence and Sleep Apnea and research is needed to help improve authors did not find any relevant dif- predictors. J Rheumatol. 2016;43:323-329. Hypertension: Are There the multidisciplinary diagnosis and ferences in the demographics between Alpert MA, Goldberg SH, Sindem BH, et al. Sex Differences? The Vitoria Cardiovascular manifestations of mixed con- treatment of this potentially serious groups, they did find a significantly nective tissue disease in adults. Circulation. Sleep Cohort. complication. higher prevalence of SSA and SSB 1983;63:1182-1193. By Dr. I. Cano-Pumarega, et al. David Maurice Chambers, MD antibodies in SLE-PAH. Interestingly, Fellow-in-Training Member the presence of anti-U1 RNP antibody Jason Atticus Akulian, MD, MPH appeared to be less common in SLE- Steering Committee Member PAH patients; this lack of association is in contrast to prior studies in mixed References CTD patients with anti-U1 RNP 1. Nishino M, et al. Incidence of programmed antibodies in which the prevalence cell death 1 inhibitor-related pneumonitis of PAH can be as high as 60%. Fur- in patients with advanced cancer: a sys- ther, none of the SLE-PAH patients tematic review and meta-analysis. JAMA Conquer the CHALLENGE. Oncology. 2016;2(12):1607. demonstrated an acute response to va- 2. Naidoo J, et al. Pneumonitis in patients sodilator challenge during RHC, em- treated with anti-programmed death-1/ phasizing that this maneuver does not programmed death ligand 1 therapy. J Clin need to be performed in SLE patients Oncol. 2017;35(7):709. at risk of PAH. Trends toward im- 3. Nishino M, et al. PD-1 inhibitor-related proved survival in SLE-PAH patients pneumonitis in advanced cancer patients: radiographic patterns and clinical course. treated with hydroxychloroquine are Clin Cancer Res. 2016;22(24):6051. preliminary and hypothesis-generat- NETWORKS CHALLENGE INDEX OF ADVERTISERS Actelion Pharmaceuticals US, Inc. EKOS Corporation Uptravi 60-62 Corporate 72 Allergan Genentech USA, Inc. Avycaz 7 Esbriet 2-5 AstraZeneca Gilead Sciences, Inc. Fasenra 9 Letairis 24-27 Symbicort 53-58 BEVESPI AEROSPHERE 64-67 GSK group of companies Nucala 48-51 Bayer Sanofi and Regeneron Pharmaceuticals, Champion Adempas 36-39 Inc. BioFire Diagnostics Corporate 15 Corporate 45 Sunovion Pharmaceuticals Inc. Lung Health. Boehringer Ingelheim Pharmaceuticals, Utibron 11-13 Inc. Seebri 29 OFEV 17-22 SPIRIVA RESPIMAT 40-43 chestfoundation.org/networkschallenge Bristol-Myers Squibb Eliquis 30-33

CHESTPHYSICIAN.ORG • OCTOBER 2017 • 71 Faster and even safer.

Bilateral PE treatment just got better.1,2,3,4

Get the same EKOS® efficacy in 1/2 the time or less, with 1/2 the dose or less. The 2017 OPTALYSE PE randomized, multi-center study showed EKOS® two, four and six-hour treatments all relieved right heart strain, with efficacy similar to EKOS® current 12/24-hour treatment and r-tPA doses as low as 4 mg per catheter.1,4 Shorter treatments give physicians same-day scheduling options and lower doses enhance safety.1 Visit www.ekoscorp.com to learn more about the only endovascular device cleared by the FDA for the treatment of pulmonary embolism. EKOS® — Setting the standard in PE treatment.

1 Tapson, et al, “Optimum Duration and Dose of r-tPA with the Acoustic Pulse Thrombolysis Procedure for Submassive Pulmonary Embolism: OPTALYSE PE,” American Thoracic Society (ATS) Meeting, Washington, DC, May 2017. 2 Lin, P., et al., “Comparison of Percutaneous Ultrasound-Accelerated Thrombolysis versus Catheter-Directed Thrombolysis in Patients with Acute Massive Pulmonary Embolism.” Vascular, Vol. 17, Suppl. 3, 2009, S137-S147. 3 Nykamp M., et al. “Safety and effi cacy of ultrasound-accelerated catheter-directed lytic therapy in acute pulmonary embolism with and without hemodynamic instability.” J Vascular Surgery: Venous and Lymphatic Disorders 2015; 3(5): 251-7. 4 Piazza, G., et al., A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism: the Seattle II study.” Journal of the American College of Cardiology: Cardiovascular Interventions 2015; 8: 1382-92.

FDA CLEARED INDICATIONS: The EkoSonic® Endovascular System is indicated for the ultrasound-facilitated, controlled, and selective infusion of physician-specifi ed fl uids, including thrombolytics, into the vasculature for the treatment of pulmonary embolism; the controlled and selective infusion of physician-specifi ed fl uids, including thrombolytics, into the peripheral vasculature; and the infusion of solutions into the pulmonary arteries. Instructions for use, including warnings, precautions, potential complications, and contraindications can be found at www.ekoscorp.com. Caution: Federal (USA) law restricts these devices to sale by or on the order of a physician. THE CE MARK (CE0086) HAS BEEN AFFIXED TO THE EKOSONIC® PRODUCT WITH THE FOLLOWING INDICATIONS: Peripheral Vasculature: The EkoSonic® Endovascular Device, consisting of the Intelligent Drug Delivery Catheter (IDDC) and the MicroSonic™ Device (MSD), is intended for controlled and selective infusion of physician-specifi ed fl uids, including thrombolytics, into the peripheral vasculature. All therapeutic agents utilized with the EkoSonic® Endovascular System should be fully prepared and used according to the instruction for use of the specifi c therapeutic agent. Pulmonary Embolism: The EKOS EkoSonic® Endovascular System is intended for the treatment of pulmonary embolism patients with ≥ 50% clot burden in one or both main pulmonary arteries or lobar pulmonary arteries, and evidence of right heart dysfunction based on right heart pressures (mean pulmonary artery pressure ≥ 25mmHg) or echocardiographic evaluation.

EKOS CORPORATION | 11911 N. Creek Pkwy S. | Bothell, WA 98011 | 888.400.3567 | EKOSCORP.COM EKOS and EkoSonic are registered trademarks of EKOS Corporation, a BTG International group company. “Acoustic pulse thrombolysis” is a trademark of EKOS Corporation. BTG and the BTG roundel logo are registered trademarks of BTG International Ltd in US, EU, and certain other territories and trademarks of BTG International Ltd elsewhere. © 2017 EKOS Corporation. NA-EKO-2017-0604

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