Doug Brunk/MDedge News more sleep Atleast someAmericansare getting SLEEP MEDICINE MDedge News BYBRUNK DOUG therapy canwithdraw steroids on triple patients Most COPD therapy to indacaterol/glycopyrronium (IND/ and safety of switch the from long-term triple group multicenter study to assess efficacy the a 26-week, randomized, double-blind, parallel- or bronchodilator as-needed use. (COPD) exacerbations, disease monary dyspnea, difference rates inthe of chronic pul- obstructive was not clinically important, with no associated (ICS) inlung decrease to led asmall that function year, withdrawal the ofcorticosteroids inhaled apy and up to one exacerbation previous inthe SAN DIEGO Those areThose key findings from SUNSET the trial, PAID U.S. Postage U.S. Permit No. 384 No. Permit Lebanon Jct. KY Lebanon Presorted Standard Presorted // – In patients on long-term triple ther- 14 frequent exacerbations, it’s safe to‘de-escalate,’” Dr. Kenneth R.Chapman said. withCOPD are“When patients receiving tripletherapy butare nothaving CHANGE SERVICE REQUESTED CHANGE SERVICE mortality mortality In IPF,gait speed 4-meterpredicts PULMONARY MEDICINE

// 26 move cautiously.” eosinophilblood counts, one should make the Society. “In aminority of patients with high ternational conference of American the Thoracic MD, FCCP, prior said inan interview to an in- LAMA,” study lead author Kenneth Chapman, R. lator foundation of second generation LABA/ tions, it’s safe to ‘de-escalate’ to bronchodi- the therapy but are not having frequent exacerba- combination 50/500mcg b.i.d. and salmeterol/fluticasone propionate fixed-dose triple therapy with tiotropium 18mcg once daily GLY, 110/50mcg once daily) or continuation of Dr. Chapman, director of asthma the and “When patients with COPD are receiving triple CHEST Physician 10255 W Higgins Road, Road, 10255 W Higgins Suite 280 IL 60018 Rosemont, WITHDRAWING STEROIDS Registration NowOpen CHEST 2018isEARLIER October 6-10 NSCLC ofdelayingThe dangers surgery in LUNG CANCER // continued // on page 6 // 41 journal authors wrote. The analysis was published inthe achieved with alowbe rate of hypoglycemia, the protocol study, inthe used target strict the could sults of aretrospective cohort analysis. with atarget of 90-140mg/dL, according to re- risk of 30-day mortality compared with patients of 80-110mg/dL was associated with alower patients, treating with glucose alow blood target FROM THEJOURNAL CHEST MDedge News BY ANDREWD. BOWSER death risk lower target linkedto lower glucose ill, In critically technologies rates to led which high of severe “may have accurate been only setting inthe of intensive insulin therapy and excess mortality er investigations finding an association between MedicalMilitary Center, and his coauthors. of pulmonary and care critical at San Antonio apy, noted Andrew M.Hersh, MD, of division the recommendwhich against intensive insulin ther- should practice counter to current guidelines, With computerized the intravenous insulin However, it raise possibility the does that earli- findings donotThese suggest that clinicians REDUCING THE GLUCOSE TARGET // CHEST INSIDE HIGHLIGHT negative bacteremias examined // Antibiotics schedule for gram- MEDICINE CARE CRITICAL ® . PULMONARY PERSPECTIVES VOL. 13 Discharge Post-ICU ® Clinics

n Page 57 • In ill critically NO. 6 continued on page 7 • JUNE 2018 48 ® NEWS FDA expands indication for COPD therapy BY KATIE WAGNER LENNON obstructive pulmonary disease statement from two pharmaceutical tember 2017. Those were defined as MDedge News therapy fluticasone furoate/umecli- companies. COPD patients who were already us- dinium/vilanterol (Trelegy Ellipta), This triple-therapy inhaler was ing the corticosteroid and long-acting he Food and Drug Adminis- which allows physicians to pre- approved for use as a long-term, beta2-agonist (LABA) drug combi- tration has approved a new scribe the drug to a broader class once-daily maintenance treatment nation fluticasone furoate/vilanterol Tindication for the chronic of COPD patients, according to a in some COPD patients back in Sep- (Breo Ellipta) but required additional

4 • JUNE 2018 • CHEST PHYSICIAN bronchodilation or those who were al- acute worsening of respiratory symp- a single-inhaler triple therapy with corticosteroid, 100 mcg fluticasone ready using the same drugs contained toms, according to the statement that two dual therapies, were published furoate; the LAMA, 62.5 mcg of in Trelegy Ellipta by taking both of GlaxoSmithKline and Innoviva re- on April 18 (N Engl J Med. 2018. umeclidinium; and the LABA, 25 the following two therapies: Breo El- leased on April 24. In this new popu- doi: 10.1056/NEJMoa1713901). mcg of vilanterol; or dual inhaled lipta and the long-acting muscarinic lation of COPD patients who are now This study randomized 10,355 therapy involving either 100 mcg antagonist (LAMA) umeclidinium approved to use Trelegy Ellipta, the symptomatic COPD patients with fluticasone furoate plus 25 mcg of (Incruse Ellipta). Physicians can now drug will continue to serve as a long- a history of moderate to severe ex- vilanterol, or 62.5 mcg of umeclidin- use fluticasone Trelegy Ellipta to treat term once-daily maintenance therapy. acerbations patients to 52 weeks of ium plus 25 mcg of vilanterol. all COPD patients who have airflow The results of the IMPACT trial, either triple inhaled therapy involv- After 1 year, the rate of moder- limitation or have experienced an which was the first study to compare ing a once-daily combination of the ate to severe COPD exacerbations in the triple-therapy group was 0.91 per year, compared with 1.07 in the fluticasone furoate–vilan- terol group and 1.21 in the vilan- terol-umeclidinium group. This translated to a 15% reduction with tri- ple therapy compared with fluticasone furoate–vilanterol and a 25% reduc- tion, compared with vilanterol-ume- clidinium (P less than .001 for both). [email protected]

VIEW ON THE NEWS Daniel Ouellette, MD, FCCP, comments: Mr. Brown came to my clinic this week. He has severe COPD manifested by exertion- al dyspnea, chronic cough, and frequent exacerbations of his disease. I have been treating him with tiotropium (LAMA), flu- ticasone (inhaled corticoste- roid), and salmeterol (LABA). The latter two medicines are contained in a combination inhaler. He also has a rescue inhaler. He has quit smok- ing and completed a course of pulmonary rehabilitation, but still has daily symptoms. What else can I do? I recently read a report about a new combination inhaler that was a “three-in- one” device: LAMA, LABA, and ICS all in the same deliv- ery system. I was glad to see that “triple therapy” now has more robust objective, sci- entific support. I figured that a combination inhaler might be more convenient and may facilitate compliance. I won- dered, though, whether this new device represents truly novel therapy or a re-packag- ing of existing therapies? Will other companies spend their research dollars to develop their own “triple threat,” or will they develop truly new drugs to help my patient with his breathing?

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2018 • 5 NEWS FROM CHEST // 53 Withdrawing steroids // continued from page 1 airways clinic at University Health chodilator FEV1 was 1.6 L. CRITICAL CARE COMMENTARY Network, Toronto, noted that rela- The researchers found that ICS // 43 tively few patients with COPD ben- withdrawal led to a mean reduction efit from inhaled steroids. “Given in trough FEV1 of –26 mL, which the risk of adverse events (pneu- exceeded the noninferiority margin. CHEST PHYSICIAN monia, osteoporosis, etc.), we’d This difference between treatments IS ONLINE rather not give them when they’re on trough FEV was driven by the David A. Schulman, MD, 1 CHEST Physician is available at FCCP, is Medical Editor in not needed,” he said. “Inhaled ste- subset of patients with high blood chestphysician.org. Chief of CHEST Physician. roids seem to play only one role in eosinophil counts at baseline (a COPD: They tend to reduce exac- mean of –68 mL for patients with at erbations in the exacerbation-prone least 300 cells/mcL and a mean of COPD patient. That’s about 20% –13 mL for patients with fewer than of the COPD population. Despite 300 cells/mcL). The two treatments this, a great many patients end up showed similar annualized rates of American College of Chest CHEST Physician, the newspaper of the American College on triple therapy [long-acting bron- moderate/severe COPD exacerba- Physicians (CHEST) of Chest Physicians, provides cutting-edge reports from clinical meetings, FDA coverage, results, expert chodilators/long-acting muscarinic tions (rate ratio, 1.08) and all (mild/ EDITOR IN CHIEF David A. Schulman, MD, FCCP commentary, and reporting on the business and politics of antagonist (LABA/LAMA) and moderate/severe) exacerbations chest medicine. Each issue also provides material exclusive to ICS] needlessly.” (RR, 1.07). ICS withdrawal led to a PRESIDENT CHEST members. Content for CHEST Physician is provided by John Studdard, MD, FCCP For the study, Dr. Chapman small difference in SGRQ-C (1.4 U Frontline Medical Communications Inc. Content for News From EXECUTIVE VICE PRESIDENT & CEO Chest is provided by the American College of Chest Physicians. and his associates enrolled 1,053 on week 26), but no differences in Stephen J. Welch The statements and opinions expressed in CHEST Physician patients with moderate to severe Transition Dyspnea Index or use of do not necessarily reflect those of the American College of MANAGER, EDITORIAL RESOURCES Chest Physicians, or of its officers, regents, members, and COPD who’d had no more than one rescue medication over 26 weeks. Pamela L. Goorsky employees, or those of the Publisher. The American College of exacerbation in the previous year Safety and tolerability were balanced PUBS & DIGITAL CONTENT EDITOR Chest Physicians, its officers, regents, members, and employees, Martha Zaborowski and Frontline Medical Communications Inc. do not assume who had used triple therapy for at across the two treatment groups. responsibility for damages, loss, or claims of any kind arising least 6 months prior to study inclu- “Although we found no overall SECTION EDITORS from or related to the information contained in this publication, Nitin Puri, MD, FCCP including any claims related to products, drugs, or services sion. The primary endpoint of the increase in exacerbations with ® Pulmonary Perspectives mentioned herein. study was noninferiority on change ‘de-escalation,’ there were, of Angel Coz, MD, FCCP POSTMASTER: Send change of address (with old from baseline in postdose trough course, exacerbations that occurred Critical Care Commentary mailing label) to CHEST Physician, Subscription Services, 10255 W Higgins Road, Suite 280, forced expiratory volume in 1 sec- during the trial,” Dr. Chapman Christopher Lettieri, MD, FCCP Rosemont, IL 60018-9914. ond (FEV1) (with a noninferiority said. “We found that they tended Sleep Strategies RECIPIENT: To change your address, margin of –50 mL) after 26 weeks. to occur in the minority of patients contact Subscription Services Exacerbations, health-related qual- who had elevated blood eosinophil Editorial Advisory Board at 1-800-430-5450. For paid G. Hossein Almassi, MD, FCCP, Wisconsin subscriptions, single issue purchases, ity of life as measured by the St. counts, especially if the counts were Jennifer Cox, MD, FCCP, Florida and missing issue claims, call Customer Service at 1-833-836-2705 Scan this QR George’s Respiratory Questionnaire elevated persistently (at screening Jacques-Pierre Fontaine, MD, FCCP, or e-mail [email protected] Code to visit Florida chestnet.org/ (SGRQ-C), and breathlessness as and randomization). The relevant CHEST PHYSICIAN (ISSN 1558- Eric Gartman, MD, FCCP, Rhode Island chestphysician measured by the Transition Dysp- cut-point was blood eosinophil 6200) is published monthly for nea Index also were evaluated. Of counts above 300/UL. If exacerba- Octavian C. Ioachimescu, MD, PhD, the American College of Chest Physicians by FCCP, Georgia Frontline Medical Communications Inc., 7 Century the 1,053 patients, 527 were ran- tions did occur in this easily iden- Jason Lazar, MD, FCCP, New York Drive, Suite 302, Parsippany, NJ 07054-4609. domized to IND/GLY and 526 to tifiable subpopulation, they tended Susan Millard, MD, FCCP, Michigan Subscription price is $244.00 per year. Phone 973- triple therapy. Their mean age was to occur early, in the first month Michael E. Nelson, MD, FCCP, Kansas 206-3434, fax 973-206-9378. Daniel Ouellette, MD, FCCP, Michigan EDITORIAL OFFICES 2275 Research Blvd, Suite 400, Rockville, MD 20850, 240-221-2400, fax 240-221- 65 years and their mean postbron- after de-escalation. This gives phy- Frank Podbielski, MD, FCCP, Massachusetts 2548 sicians a simple way to identify M. Patricia Rivera, MD, FCCP, ADVERTISING OFFICES 7 Century Drive, Suite 302, North Carolina a population they might exercise Parsippany, NJ 07054-4609 973-206-3434, fax caution and a period when careful Nirmal S. Sharma, MD, California 973-206-9378 monitoring is useful.” Krishna Sundar, MD, FCCP, Utah ©Copyright 2018, by the American College of E-mail: Chest Physicians He acknowledged certain lim- [email protected] itations of the study, including its FRONTLINE MEDICAL COMMUNICATIONS CHEST 6-month duration, which is shorter Corporate SEEK™ Library than most exacerbation studies. PRESIDENT/CEO Alan J. Imhoff “But by recruiting at multiple sites CFO Douglas E. Grose in multiple countries and across SVP, FINANCE Steven J. Resnick seasons, we don’t think this was an Frontline Medical VP, OPERATIONS Jim Chicca Communications CME and MOC Now Available importation limitation,” he said. “Of VP, SALES Mike Guire Society Partners VP, SOCIETY PARTNERS Mark Branca course, like most investigators, I can VP/GROUP PUBLISHER; DIRECTOR, CHIEF DIGITAL OFFICER Lee Schweizer always think of things I wish I had FMC SOCIETY PARTNERS Mark Branca VP, DIGITAL CONTENT & STRATEGY Amy Pfeiffer tracked. My personal hunch is that EDITOR IN CHIEF Mary Jo M. Dales VP, MARKETING & CUSTOMER ADVOCACY Jim McDonough EXECUTIVE EDITORS Denise Fulton, VP, HUMAN RESOURCES & FACILITY OPERATIONS Carolyn FeNO [exhaled nitric oxide levels] Kathy Scarbeck Caccavelli might offer some useful information EDITOR Katie Wagner Lennon DATA MANAGEMENT DIRECTOR Mike Fritz but that will be a hunch to explore CREATIVE DIRECTOR Louise A. Koenig CIRCULATION DIRECTOR Jared Sonners DIRECTOR, PRODUCTION/MANUFACTURING in another study.” CORPORATE DIRECTOR, RESEARCH & COMMS. Lori Raskin Rebecca Slebodnik EDITOR IN CHIEF Mary Jo M. Dales SUNSET was sponsored by No- DIRECTOR, BUSINESS DEVELOPMENT vartis. Dr. Chapman disclosed that Angela Labrozzi, 973-206-8971, New Ventures cell 917-455-6071, PRESIDENT Douglas E. Grose he has received fees for research, [email protected] VP, SALES Josh Prizer consulting and lectures from No- DIGITAL ACCOUNT MANAGER EDITORIAL DIRECTOR/COO Carol Nathan Rey Valdivia 973-206-8094 vartis, as well as from several other Custom Solutions [email protected] PRESIDENT JoAnn Wahl Improve Your Clinical Skills pharmaceutical companies. CLASSIFIED SALES REPRESENTATIVE VP, CUSTOM SOLUTIONS Wendy Raupers in Recall, Interpretation, [email protected] Drew Endy 215-657-2319, cell 267-481-0133 DIRECTOR, CUSTOM PROGRAMS Patrick Finnegan [email protected] and Problem-Solving SOURCE: Chapman KR et al. ATS In affiliation with Global Academy for Medical Education, LLC SENIOR DIRECTOR OF CLASSIFIED SALES VP, MEDICAL EDUCATION & CONFERENCES Sylvia H. 2018, Abstract A1009. Tim LaPella, 484-921-5001, Reitman, MBA [email protected] VP, EVENTS David J. Small, MBA 6 • JUNE 2018 • CHEST PHYSICIAN NEWS Female physicians face enduring wage gap

BY RICHARD FRANKI the 50 largest metro areas, there Five largest gaps MDedge News were none where women earn as 1. Charleston, S.C. 37% much as men, according to a new 2. Kansas City, Mo. 32% ale physicians make more survey by the medical social net- 3. Nashville, Tenn. 32% 2 money than female physi- work Doximity. 4. Providence, R.I. 31% 4 4 Mcians, and that seems to be The metro area that comes the 5. Riverside, Calif. 31% 3 a rule with few exceptions. Among closest is Las Vegas, where female 5 physicians earned 20% less – that 2 works out to $73,654 – than their 1 VIEW ON THE NEWS 5 3 male counterparts in 2017. Roch- Five smallest gaps Michael E. Nelson, MD, ester, N.Y., had the smallest gap in 1. Las Vegas 20% 1 FCCP, comments: This is terms of dollars ($68,758) and the 2. Rochester, N.Y. 21% a rather damning revelation second-smallest percent difference 3. Hartford, Conn. 22% about pay parity in medicine, (21%), Doximity said in its 2018 4. Detroit 23% 5. Sacramento 23% but not unexpected given Physician Compensation Report. News MDedge similar findings in non-med- The largest wage gap on both ical corporate America. As I measures can be found in Charles- Note: Compensation surveys were completed by more than 65,000 physicians in 2016 and 2017. do not sit on any compensa- ton, S.C., where women earned 37%, Source: Doximity tion committees or negotiate or $134,499, less than men in 2017. contracts for female employ- The other members of the largest- more than 65,000 full-time, licensed trained field, and as such, one might ees, I am at a loss to explain wage-gap club are as follows: Kansas U.S. physicians who practice at least expect the gender wage gap to be how these levels of inequality, City, Mo., and Nashville, Tenn., both 40 hours per week.” less prominent here than in other in ALL 50 metropolitan areas, had differences of 32%, and Prov- A quick look at the 2016 data industries. However, the gap en- can exist unchecked. I would idence, R.I., and Riverside, Calif., shows that the wage gap between dures, despite the level of education suggest that it is time for all had differences of 31%, Doximity female and male physicians in- required to practice medicine and male physicians to advocate said in the report, which was based creased from 26.5% to 27.7% in market forces suggesting that this for our female colleagues. on data from “compensation sur- 2017, going from more than $92,000 gap should shrink,” Doximity said. veys completed in 2016 and 2017 by to $105,000. “Medicine is a highly [email protected]

Reducing the glucose target // continued from page 1 Two therapies hypoglycemia,” they wrote. mg/dL (odds ratio 0.65; 95% confidence inter- The retrospective cohort analysis by Dr. Hersh val, 0.43-0.98; P = .04). equally effective in and his colleagues included 1,809 adult patients These results advance the debate over appro- treated at three different ICUs in two hospitals priate blood glucose targets in critically ill pa- between January 2010 and De- tients, as they suggest that the obese OSA patients cember 2015. Treatment was de- effects of targeting blood glu- livered with a computerized ICU While patients in the cose and the effects of severe BY KATIE WAGNER LENNON insulin infusion protocol that hypoglycemia “can be separat- MDedge News allows clinicians to choose be- low blood glucose ed,” the investigators wrote. tween two blood glucose targets: target group had a Current guidelines on in- he mortality rates were similar between patients 80-110 mg/dL or 90-140 mg/dL. higher rate of moderate tensive insulin therapy are Tusing two different therapeutic regimens to The lower target was chosen for based in part on findings of treat obesity hypoventilation syndrome with severe 951 patients, and the moderate hypoglycemia, both the NICE-SUGAR trial, which obstructive sleep apnea, according to new research target for 858 patients. groups had a low rate of found that, among adults that was presented at the American Thoracic Society The most common primary treated in the ICU, intensive International Conference in San Diego. admission diagnoses in the co- severe hypoglycemia. glucose control increased In this multicenter open-label, randomized, hort included chest pain or acute mortality. However, a post hoc controlled trial, Sanchez Quiroga et al. compared coronary syndrome in 43.3%, analysis suggested the mortal- the long-term effectiveness of noninvasive ven- cardiothoracic surgery in 31.9%, heart failure ity increase in NICE-SUGAR was “largely driven tilation (NIV) with continuous positive airway (including cardiogenic shock) in 6.8%, and vas- by a significant incidence of moderate hypogly- pressure (CPAP). The researchers analyzed the cular surgery in 6.0%. cemia, and to a greater degree severe hypoglyce- results for 202 patients who used one of the two While patients in the low blood glucose target mia,” Dr. Hersh and his coauthors noted in their treatments for at least 3 years. group had a higher rate of moderate hypoglyce- report. Among this study’s findings were that the mortali- mia, both groups had a low rate of severe hypo- “Given improvements in insulin delivery and ty rates and the number of cardiovascular events that glycemia, at 1.16% in the low target group and glucose monitoring, a reassessment of potential occurred were similar in the two treatment groups. 0.35% in the moderate target group (P = .051). benefits of [intensive insulin therapy] should The mortality rate for patients who used CPAP was Unadjusted 30-day mortality was significantly once again be evaluated in a prospective ran- 14.7%, compared with 11.3% for the patients who lower in the 80- to 110-mg/dL group compared domized trial,” they wrote. received NIV (adjusted hazard ratio, 0.73; P = .439), with the 90- to 140-mg/dL group (4.3% vs. Dr. Hersh and his coauthors declared no fi- and the cardiovascular events per 100 person-years 9.2%, respectively; P less than .001), according nancial or nonfinancial disclosures related to were 5.1 for CPAP and 7.46 for NIV (P = .315). to the investigators. the study. The researchers concluded that both treatments Furthermore, logistic regression analysis [email protected] are equally effective for the long term, but that CPAP showed that patients treated with a target of 80- should be “the preferred treatment modality,” be- 110 mg/dL had a lower risk of 30-day mortality SOURCE: Hersh AM et al. CHEST 2018. doi: cause it’s cheaper and easier to implement. compared with patients with a target of 90-140 10.1016/j.chest.2018.04.025. [email protected]

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2018 • 7 NEWS Two more and counting: Suicide in medical trainees

BY MICHAEL F. MYERS, MD not receive the life-saving care they deserved; some, fearing assaults to their medical license, ike everyone in the arc of social media im- hospital privileges, or insurance, refused to see pact, I was shocked and terribly saddened by anyone. They died untreated. Lthe recent suicides of two New York women • May 8: Still at the APA, a psychiatrist colleague Dr. Myers is a professor in medicine – a final-year medical student on and I collaborate on a clinical case conference. of clinical psychiatry at May 1 and a second-year resident on May 5. As Each of us describes losing a physician patient State University of New a specialist in physician health, a former training to suicide. We walk the attendees through the York, Brooklyn, and the director, a long-standing member of our insti- clinical details of assessment, treatment, and author of “Why Phy- tution’s medical student admissions committee, the aftermath of their deaths. We talk openly sicians Die by Suicide: and the ombudsman for our medical students, I and frankly about our feelings, grief, outreach Lessons Learned From am finding these tragedies harder and harder to to colleagues and the family, and our own per- Their Families and Oth- reconcile. Something isn’t working. But before I sonal journeys of learning, growth, and healing. ers Who Cared.” get to that, what follows is a bulleted list of some The clinician audience members give construc- events of the past couple of weeks that may give a tive feedback, and some share their own stories context for my statements and have informed my of losing patients to suicide. Like the day be- In psychiatry, we need to redouble our efforts two recommendations. fore, some psychiatrists are grieving the loss of a physician son or sibling to suicide. As mental in fighting the stigma attached to psychiatric • May 3, 2018: I give an invited GI grand rounds health professionals, they suffer from an addi- illness in trainees. It is unconscionable that on stress, burnout, depression, and suicide in tional layer of failure and guilt that a loved one physicians. The residents are quiet and say noth- died “under their watch.” medical students and residents are dying ing. Faculty members seem concerned about • May 8: I rush across the Javits Center to catch of treatable disorders. Too many are not preventing and eradicating only burnout – and the discussant for a concurrent symposium on availing themselves of services we provide. not that interested in anything more severe. physician burnout and depression. She foregoes • May 5: A psychiatry resident from Melbourne any prepared remarks to share her previous 48 arrives to spend 10 days with me to do an elec- hours with the audience. She is the training di- let me make only two suggestions: tive in physician health. As in the , rector of the program that lost the second-year 1. We need to come together and talk about there is a significant suicide death rate in med- resident on May 5. She did not learn of the death this – medical students and residents and training ical students and residents Down Under. In the until 24 hours later. We are all on the edge of our directors and deans. A town hall forum would be afternoon, I present a paper at the annual meet- seats as we listen to this grieving, courageous ideal. Although there are amazing innovations on ing of the American Academy of Psychody- woman, a seasoned psychiatrist and educator, wellness emanating from the Association of Amer- namic Psychiatry and Psychoanalysis on the use who has been blindsided by this tragedy. She ican Medical Colleges and Accreditation Council of psychotherapy in treatment-resistant suicidal has not slept. She called all of her residents and for Graduate Medical Education, many current depression in physicians. There is increasing broke the news personally as best she could. Aid- medical students and residents feel frustrated – hope that this essential modality of care will re- ed by “After A Suicide: A Toolkit for Residency/ “This is taking too long” or “This is top down and turn to the contemporary psychiatrist’s toolbox. Fellowship Programs” (American Foundation being imposed on us” or “What about our voices • May 6: At the annual meeting of the Ameri- for Suicide Prevention), she and her colleagues … don’t they count?” Although students and resi- can Psychiatric Association in New York, I’m instituted a plan of action and worked with dents have representatives on faculty committees, the discussant for powerful heartfelt papers administration and faculty. Her strength and feedback is not universal, and not all residents be- of five psychiatrists (mostly early-career psy- commitment to the well-being of her trainees is lieve that their senior peers truly convey their con- chiatrists and one resident) that talked about palpable and magnanimous. When the session cerns to those in power. They want to be present at living with a psychiatric illness. The audience ends, many of us stand in line to give her a hug. the table and speak for themselves. Too many do is huge, and we hear narratives about internal It is a stark reminder of how many lives are af- not feel they have a voice. stigma, self-disclosure, external stigma, shun- fected when someone you know or care about 2. In psychiatry, we need to redouble our efforts ning, bullying, acceptance, rejection, alienation, takes his/her own life – and how, in the house of in fighting the stigma attached to psychiatric ill- connection, and love by peers and family. The medicine, medical students and residents really ness in trainees. It is unconscionable that medical authenticity and valor of the speakers create an are part of an institutional family. students and residents are dying of treatable disor- atmosphere of safety, which enables psychia- • May 10: I facilitate a meeting of our 12 second- ders (I’ve never heard of a doctor dying of cancer trists in attendance from all over the world to year residents, many of whom knew of or had who didn’t go to an oncologist at least once), yet share their personal stories – some at the mi- met the resident who died. Almost everyone too many are not availing themselves of services crophone, some privately. speaks, shares their feelings, poses questions, and we provide – even when they’re free of charge or • May 7: Again at the APA, I chair and facili- calls for answers and change. There is disbelief, covered by insurance. And are we certain that, tate a workshop on physician suicide. We hear sadness, confusion, some guilt, and lots of an- when they knock on our doors, we are providing from four speakers, all women, who have lost ger. Also a feeling of disillusionment or paradox them with state-of-the-art care? Is it possible that a loved one to suicide – a husband, a father, a about the field of psychiatry: “Of all branches of unrecognized internal stigma and shame deep brother, a son – all doctors. Two of the speakers medicine, shouldn’t residents who are struggling within us might make us hesitant to help our are psychiatrists. The stories are gripping, de- with psychiatric issues feel safe, protected, cared trainees in their hour of need? Or cut corners? Or tailed, and tender. Yes, the atmosphere is very for in psychiatry?” There is also a feeling of lip not get a second opinion? Very few psychiatrists sad, but there is not a pall. We learn how these service being paid to personal treatment, as in on faculty of our medical schools divulge their doctors lived, not just how they died. They all quoted statements: “By all means, get treatment personal experiences of depression, posttraumatic loved medicine; they were creative; they cared for your issues, but don’t let it encroach on your stress disorders, substance use disorders, and more deeply; they suffered silently; and with shame, duty hours” or “It’s good you’re getting help, but (with the exception of being in therapy during res- they lost hope. Again, a big audience of psychi- do you still have to go weekly?” idency, which is normative and isn’t stigmatized). atrists, many of whom share their own stories, Coming out is leveling, humane, and respectful that they, too, had lost a physician son, wife, In the immediate aftermath of suicide, feelings – and it shrinks the power differential in the teach- or mother to suicide. Some of their deceased run high, as they should. But rather than wait it ing dyad. It might even save a life. family members fell through the cracks and did out – and fearing a return to “business as usual” – [email protected]

8 • JUNE 2018 • CHEST PHYSICIAN CHPH_9.indd 1 2/28/2018 8:16:17 AM SLEEP MEDICINE Americans are getting more sleep BY KATIE WAGNER LENNON MDedge News VIEW ON THE NEWS ly more during weeknights David A. Schulman, MD, FCCP, com- than weekend nights), it ome Americans began getting more sleep ments: For more than 15 years, we have is at least a move in the over the period of 2003 through 2016, an had evidence that sleep deprivation is as- right direction. In a related Sanalysis of data from the American Time sociated with not only increased accident editorial in the same issue Use Survey (ATUS) has suggested. risk, but also other common causes of of SLEEP, Ogilvie and Patel Many people living in the United States habit- mortality, including cardiovascular disease identify some possible prob- ually sleep less than the recommended 7-9 hours and cancer. Despite this knowledge, de- lems with the paper; these each day. “Experimental studies have demon- cades of trending in sleep patterns of the include a nonvalidated tool strated that both acute total and chronic partial US population have continued to show de- for data collection, and sleep restriction in healthy adults are associated clines in total sleep time, which have been the possible conflation of time in bed and with physiological changes that can be considered attributed to multiple factors, including sleep time. Even if the data are accurate, precursors of manifest diseases (e.g., decreased longer work hours and the pervasive use it is difficult to imagine that such a modest insulin sensitivity),” noted Mathias Basner, MD, of electronics, which can serve both as a improvement in sleep duration would yield PhD, and David F. Dinges, PhD, both of the divi- distraction from sleep and a contributor to meaningful benefits in terms of daytime sion of sleep and chronobiology at the University circadian dysrhythmia. function and sleep-related morbidity. of Pennsylvania, Philadelphia, in their paper. The recent article by Basner and Ding- While our work in improving public This new study, which was published in the es suggests, for the first time, that this awareness of sleep deprivation is far from journal Sleep, is the first to have demonstrated trend may be reversing. Although the data done, perhaps this study is the first sign that large parts of the U.S. population significant- suggest a minimal bump in sleep time (of that a new day is dawning on improved ly increased their sleep between 2003 and 2016. approximately 1 minute per night, slight- sleep health for the country. The investigators analyzed ATUS responses from 181,335 Americans aged 15 years and older; respondents included in the analysis were not ac- ganizations, such as the American Academy of bed times by 1.1 min/year across survey years, tive in the military or residing in institutions such Sleep Medicine, the Sleep Research Society, and which was comparable to the shift observed on as nursing homes or prisons. In 15- to 20-min- the Centers for Disease Control and Prevention, weekdays.” ute computer-assisted telephone interviews, the that have been campaigning for years to increase Study participants aged 18-24 slept the most, survey participants reported the activities they sleep time among Americans. with hours slept having “decreased with increas- performed over a 24-hour period on a min- The researchers also observed that the percent- ing age.” On weekdays, adults aged 45-54 years ute-by-minute basis. In-depth analyses included age of respondents in short sleep duration catego- slept the least, and on weekends, adults aged 55- only groups “that showed a significant increase ries decreased significantly, and the percentage of 64 years got the least shuteye. Hispanic, Asian, in sleep duration across survey years either on respondents in long sleep duration categories in- and black respondents slept more than white and weekdays or weekends (or both): employed re- creased significantly across survey years. One of “other race/ethnicity” survey participants. The re- spondents, full-time students, and retirees.” the “most pronounced changes” occurred in the searchers also found that women overall got more Using this data from ATUS, Dr. Basner and Dr. size of the group of patients receiving 6-7 hours sleep than men. Dinges found that on workdays the prevalence of of sleep. This group decreased by 0.23% per year. Dr. Basner and Dr. Dinges expressed optimism people who were sleeping 7 hours or less a day The biggest change was seen in the category of about Americans’ ongoing battle against chronic decreased by 0.44% per year (P less than .0001), patients receiving 9-10 hours of sleep, which in- sleep deficiency. “These findings presented here while the percentage people who were sleeping creased by 0.24% per year. suggest that we are on the right track ... even if more than 9 hours a day increased by 0.48% per “[The] change in sleep duration across survey there is still a long way to go,” they said. year (P less than .0001). years on weekdays can mostly be explained by The authors reported no conflicts of interest. Overall, respondents’ sleep increased by an av- respondents going to bed earlier at night and, to [email protected] erage of 1.40 minutes during a weekday and 0.83 a lesser degree, by getting up later in the morn- minutes during a weekend day every year. ing,” the researchers said. “On weekends/holi- SOURCE: Basner M et al. Sleep. 2018 Apr 1;41(4):1- These findings will be welcome news for or- days, ‘time to bed’ shifted significantly to earlier 16. 8-Isoprostane levels predict OSA in children

BY MADHU RAJARAMAN ing (PS) and controls. 8-IsoP values The investigators studied 66 chil- sleep. Exclusion criteria included MDedge News were also correlated with apnea dren aged 4.5-15.1 years, of whom acute respiratory in the 4 hypopnea index (AHI) (r, 0.40; P 46 had sleep-disordered breathing weeks preceding the study, chronic he oxidative stress biomarker = .003) and oxygen saturation, also (SDB) and were enrolled in the respiratory comorbidities, and ther- T8-isoprostane (8-IsoP) predicted apy with corticosteroids or other obstructive sleep apnea (OSA) and anti-inflammatory drugs for at least disease severity in children better Patients with OSA had higher levels of 8-IsoP in exhaled 3 weeks. than the fractional concentration breath condensate upon waking than patients with primary Patients with SDB had a medical of exhaled nitric oxide (FeNO), ac- examination followed by over- cording to results published in Sleep snoring and controls. 8-IsoP values were also correlated night standard polysomnography Medicine. with apnea hypopnea index and oxygen saturation. (PSG), and EBC 8-IsoP and FeNO In an analysis of 46 patients with measurements were collected the sleep-disordered breathing and 20 next morning upon waking. The controls, patients with OSA had known as SaO2 (r, –0.50; P = .001), hospital’s Pediatric Sleep Center. SDB group also had spirometry higher levels of 8-IsoP in exhaled reported Mario Barreto, MD, of the The 20 healthy controls had no and skin prick testing for com- breath condensate (EBC) upon wak- Pediatric Unit at Sant’Andrea Hospi- history of sleep problems, includ- mon allergens. The children in the ing than patients with primary snor- tal in Rome and his coauthors. ing snoring, apneas, and restless Continued on following page

14 • JUNE 2018 • CHEST PHYSICIAN Continued from previous page variables (mean, 53.1; P = .008). The dictor of OSA (.839; 95% confidence ers of atopic-eosinophilic airway in- control group had the same tests difference in FeNO levels between interval, .744-.933, P = .000). The flammation,” the authors concluded. and measurements done, except SDB patients and controls was not sensitivity and specificity of cutoff No disclosures or conflicts of in- for PSG, Dr. Barreto and his col- statistically significant (mean, 1.67; values of 8-IsoP concentrations terest were reported. leagues wrote. P = .358) and did not change signifi- above the 50th percentile were [email protected] Central, obstructive, and mixed cantly when adjusted for confound- 76.5% and 78.1%, respectively. apnea events were counted accord- ing variables. “[It] seems that biomarkers of ox- SOURCE: Barreto M et al. Sleep ing to American Academy of Sleep High area under the curve values idative stress reflect OSA severity in Medicine. 2018. doi: 10.1016/j. Medicine (AASM) criteria. AHI were observed for 8-IsoP as a pre- children more closely than biomark- sleep.2018.01.011. was defined as the average number of apnea and hypopnea events per hour of sleep. OSA was diagnosed with an AHI of one episode per hour and confirmed by the presence of SDB symptoms with AHI of one episode per hour. Children with snoring and an AHI of less than one episode per hour were diagnosed with primary snoring (PS). Patients with an AHI greater than one episode per hour and less than five episodes per hour were diagnosed with mild OSA. Children with an AHI of greater than five episodes per hour were diagnosed with moderate to severe OSA, the authors said. While 8-IsoP concentrations cor- related with OSA severity for AHI and SaO2, FeNO did not, Dr. Barre- to and colleagues reported. The difference in 8-IsoP concen- trations for children with SDB and controls (mean, 39.6; P = .006) was increased when adjusted using mul- tiple linear regression (mean, 43.2; P = .007), and the difference was even more pronounced when ad- justed for all potential confounding

VIEW ON THE NEWS Susan Millard, MD, FCCP, comments: The field of biomarkers in different dis- ease states has exploded over the last few years and this article is fascinating. Barreto et al. analyzed a biomarker for oxidative stress in pe- diatric patients who present- ed to their sleep lab. The concentration of 8-isopros- tane in the exhaled breath condensate correlated with the severity of the OSA in these patients who were 4.5 years of age to 15.1 years of age. We screen for OSA in difficult-to-control asth- ma patients, so it would be interesting to repeat this study in that population, too!

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2018 • 15 SLEEP MEDICINE Disrupted sleep tied to alexithymia BY GINA L. HENDERSON Alexithymia is a condition char- include increased nocturnal arousal and her associates recruited 86 men MDedge News acterized by difficulty identifying as a result of poor verbalization of and women; 70 were included in and expressing one’s emotions. “The emotions and increased light sleep,” the analyses. Participants’ alexithy- eightened alexithymia may mechanism by which alexithymia wrote Jennifer Murphy, citing previ- mia scores were measured using explain poor sleep quality, a confers risk of disrupted sleep re- ous research. the Toronto Alexithymia Scale, or Hpair of studies shows. mains unclear, [but] suggestions In the first study, Ms. Murphy TAS-20, which consists of three sub-

16 • JUNE 2018 • CHEST PHYSICIAN scales – difficulty describing feel- “The mechanism by which alexithymia confers risk of disrupted The researchers found associ- ings, difficulty identifying feelings, sleep remains unclear, [but] suggestions include increased ations between total alexithymia and externally oriented thinking. scores and reduced sleep quality (P Sleep quality was measured using nocturnal arousal as a result of poor verbalization of emotions less than .001). They also found a the Pittsburgh Sleep Quality Index, and increased light sleep,” wrote Jennifer Murphy. significant association between the or PSQI, a self-report measure that TAS-20 subscales and reduced sleep asks numerous questions, including: PSQI “indicate elevated alexithymic developmental psychiatry at King’s quality (all P less than .006). “During the past month, when have traits and poor sleep quality, respec- College London, and her associates In the second study, in which 73 you usually gone to bed at night?” tively,” wrote Ms. Murphy, a doctor- in the journal Personality and Indi- men and women participated, Ms. High scores on the TAS-20 and al candidate in social, genetic, and vidual Differences. Continued on following page

s

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2018 • 17 Continued from previous page DASS-21 correlate with greater lev- ance in sleep quality. While further research is needed Murphy and her associates sought to els of depression, anxiety, and stress. Ms. Murphy said in an interview to confirm the direction of causality determine whether the association None of the questionnaires asked that, although it might be too early between disrupted sleep and alex- found in the first study was tied to about any aspects of sleep. to make a clear clinical recom- ithymia and how these subjective depression or anxiety. Participants Using a regression model, Ms. mendation, the results suggest that sleep reports in alexithymia map went online and completed three Murphy and her associates found “clinicians should be aware of the onto objectively measured sleep questionnaires: the TAS-20; the that all of the measures correlated possibility of sleep problems char- problems, these data suggest a link PSQI; and the Depression, Anxiety, with poor sleep quality. But only de- acterized by heightened alexithymia that is independent of depression & Stress Scale, or DASS-21, in a ran- pression (P = .011) and alexithymia and more generally in those with and anxiety, she said. domized order. Higher scores on the (P = .004) explained unique vari- alexithymia.” Meanwhile, other researchers

18 • JUNE 2018 • CHEST PHYSICIAN report that alexithymia is becom- logica. 2018;11:229-40). and the relatively small sample sizes. ing more clinically relevant. Ris- Ms. Murphy and her associates The research was supported by ing rates of alexithymia are being cited several limitations of their the Economic and Social Research reported in psychiatric conditions research. One is that they did not Council and the Baily Thomas such as autism, eating disorders, control for factors that affect sleep Charitable Trust. No conflicts of in- schizophrenia, and alcohol and quality and alexithymia such as terest were reported. substance abuse. The condition is body composition. They also cited [email protected] also seen in neurologic conditions reports of discrepancies between such as multiple sclerosis and trau- objective and subjective measures – SOURCE: Murphy J et al. Pers Individ matic brain injury (Neuropsycho- such as those made by self-report – Dif. 2018 Mar 27;129:175-8.

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2018 • 19 SLEEP MEDICINE Insomnia, major depressive episode linked in U.S. BY CHRISTOPHER PALMER current major depressive episode, lems, suggesting the psychiatric dis- importance of considering both in- Frontline Medical News according to a cross-sectional anal- orders contribute unique variance to somnia and psychiatric disorders in ysis. cognitive problems,” wrote Janeese the diagnosis and treatment of cog- nsomnia is prevalent among U.S. “Psychiatric disorders moderated A. Brownlow, PhD, of the University nitive deficits in military soldiers.” soldiers, and the highest preva- the relationship between insomnia of Pennsylvania, Philadelphia, and The researchers used the All Ilence rate is among those with and memory/concentration prob- her associates. “Results highlight the Army Study of the Army Study to Assess Risk and Resilience in Ser- vicemembers as their data source. They used the Composite Interna- tional Diagnostic Interview (CIDI) and the Posttraumatic Stress Disor- Badmanproduction/Thinkstock

der Checklist to assess psychiatric disorders; the CIDI also helped as- sess cognitive problems. One of the strengths of this study was its large sample size: It had an unweighted sample of 21,449 soldiers. Dr. Brownlow and her associates found that the prevalence of insom- nia among soldiers with current major depressive episode was 85%. The prevalence was 82.6% among soldiers with generalized anxiety disorder and 69.7% among those with PTSD. The likelihood of having insomnia grew with the number of comorbid psychiatric disorders. One of the limitations of the study was that many of the measures were self-reported; for example, the psychiatric diagnoses and the deter- minations regarding insomnia were based on surveys and questionnaires rather than clinical interviews and assessments. Furthermore, the ab- sence of a comprehensive neuro- cognitive battery might have limited the study’s ability to assess cognitive problems. Nevertheless, the re- searchers wrote, “addressing insom- nia may increase resiliency and the ability to perform and cope with the complexities of active duty.” Read more about the study in the Journal of Affective Disorders. [email protected]

20 • JUNE 2018 • CHEST PHYSICIAN SLEEP MEDICINE Vehicle crash risk linked to various sleep disorders BY TARA HAELLE ers with RLS and any drivers with insomnia had The only drivers with a sleeping disorder who MDedge News a higher risk of crashes or near-crashes (adjusted were more likely to be involved in crashes of odds ratio, 2.26 and 1.49, respectively, P less than greater severity were those with periodic limb ndividuals with certain sleeping disorders .05 for both). Drivers with narcolepsy had 9 times movement disorder (AOR, 1.43, P less than .05). may have a higher risk of crashes, near-crash- greater odds of being involved in a crash or near- However, young drivers, senior drivers, and Ies, or unsafe maneuvering prior to such crash, but the finding was not statistically signifi- nighttime drivers also all had higher odds of events, suggests a study. cant (AOR, 10.24, P less than .1). being involved in more severe crashes and in “The results confirm that some sleep disor- “Drivers who reported frequency of sleepy performing unsafe maneuvers prior to a crash or ders generally increase driving risk as defined by near-crash. Nighttime drivers seemed to be most our dependent measures,” wrote Shu-Yuan Liu, at risk for these, and they were linked to having a doctoral student, and two colleagues at Vir- more than 5 times greater odds of unsafely ma- ginia Tech, Blacksburg (Sleep. 2018 Apr 1. doi: neuvering their vehicles prior to getting into a 10.1093/sleep/zsy023). “Furthermore, the results crash or near-crash (AOR, 6.71, P less than .05). also provide some insights into how risk varies “This is a strong piece of evidence that night- across specific types of sleep disorder and some time driving is less safe than daytime driving and moderating factors.” limiting amount of nighttime driving could be The researchers analyzed data collected by the one method to moderate road risk for some indi- Second Strategic Highway Research Program viduals,” the authors wrote. (SHRP 2), the nation’s largest Naturalistic Driving The study’s limitations include its observational Study, on 3,541 drivers between ages 16 and 98. nature, low numbers of participants with several The participants’ cars were outfitted with small of the sleeping disorders (at levels below the dis-

cameras and other instruments that collected Images GummyBone/Getty order’s prevalence in the general population), and information on driver behavior, the driving en- the complexities involved in what causes a crash vironment, and the vehicle’s movements, such as driving as ‘never,’ ‘rarely,’ and ‘sometimes’ also or near crash. speed and braking data. had higher a risk, indicating that crash or near- One limitation of this study was that sleep hy- The study involved licensed drivers who drove at crash risk is also associated with sources other giene and sleep quality were not examined, even least 3 days a week, had an eligible vehicle in good than these sleeping disorders,” the authors noted. though these might contribute significantly to working condition, and agreed to participate for These drivers’ increased odds of getting into or roadway safety, the researchers noted. This study 1-2 years. At the start and end of the study, par- nearly getting into a crash ranged from 31% to also did not take into account what medications or ticipants filled out a questionnaire on any medical 53% greater (P less than .05). other treatment (such as continuous positive air- conditions they had or had been treated for in the All drivers with shift-work sleep disorder, ex- way pressure for those with sleep apnea) the par- past year, any medications they were taking, and cept for those aged 20-24, had a crash or near- ticipants might be receiving for their condition. any aids they were using for a medical condition. crash rate that was 7.5 times greater than that of The study’s implications include the need for phy- Among the conditions they were able to select drivers without any sleeping disorders. The rate sicians to advise patients with insomnia or females were narcolepsy, sleep apnea, insomnia, shift- among drivers aged 20-24 with this disorder had with sleep apnea to use caution while driving with- work sleep disorder, restless legs syndrome (RLS), a 90% lower rate (risk ratio, 0.1, P less than .05) out “exaggerating risks that introduce undue fear to periodic limb movement disorder, and migraine. compared with control drivers. patients with other sleep disorders and thereby lim- All of these conditions have been linked in previ- When the researchers analyzed the drivers’ iting mobility unnecessarily,” the authors wrote. The ous studies to a higher risk of vehicle collisions. maneuvers just before a crash or near-crash, they researchers also suggested that employers consider A total of 646 participants, 18.2% of the sam- found females with sleep apnea had a 36% greater providing alternative transportation to shift workers ple, had one of those disorders: 0.14% had narco- odds of doing an unsafe maneuver in crash/near- and/or that insurance companies offer employers lepsy, 7.4% had sleep apnea, 4.8% had insomnia, crash circumstances (AOR, 1.36). Females with lower rates for offering such alternatives. 3.4% had RLS, 0.37% had shift-work sleep disor- RLS and any drivers with shift-work sleep disor- [email protected] der, 0.23% had periodic limb movement disorder, der were more than twice as likely to perform un- and 8.4% had migraine. safe maneuvers (AOR, 3.38 and 3.53, respectively, SOURCE: Liu S-Y et al. Sleep J. 2018 Apr 1. doi: Analysis of vehicle data found that female driv- P less than .05). 10.1093/sleep/zsy023. Uvulopalatopharyngoplasty may cut CV events in OSA

BY BIANCA NOGRADY UPPP – and 961,590 controls. farction, congestive heart failure, with the average success rate for the MDedge News The individuals who had had and atrial fibrillation, respectively. surgery being low for most patients,” UPPP had a significantly lower in- These figures were after account- wrote Heung-Man Lee, MD, PhD, urgical remodeling of the tissues cidence of all three cardiovascular ing for confounding factors, such as then from the Guro Hospital at Korea Sof the throat using uvulopalato- events, compared with those who age, sex, diabetes, and dyslipidemia. University, Seoul, and his coauthors. pharyngoplasty (UPPP) could sig- had not undergone the procedure. The authors wrote that the most “However, the current study nificantly reduce the cardiovascular The hazard ratios for myocardial distinctive finding of their study suggests that the effects of UPPP, complications of obstructive sleep infarction, congestive heart failure, was that uvulopalatopharyngoplasty regardless of the effects on AHI, can apnea (OSA), according to a study and atrial fibrillation among indi- lowered the incidence of congestive significantly reduce cardiac morbid- published in Sleep Medicine. viduals with OSA who had uvu- heart failure and atrial fibrillation ity in patients with OSA.” Researchers examined the inci- lopalatopharyngoplasty, compared in patients with obstructive sleep Patients without diabetes showed dence of newly diagnosed myo- with controls, were 1.002, 0.757, apnea to the point that they had more benefit from UPPP in reduc- cardial infarction, congestive heart and 1.117, respectively. By compar- the same level of risk as individuals ing the incidence of congestive heart failure, and atrial fibrillation in ison, those hazard ratios in patients without obstructive sleep apnea. failure, compared with those with 192,316 patients with a new diag- with OSA who had not had UPPP, “Prior studies have evaluated the diabetes. However, those with diabe- nosis of obstructive sleep apnea compared with controls, were 1.070, success of UPPP based on reductions tes showed greater reductions in the – 22,213 of whom had undergone 1.165, and 1.39 for myocardial in- of AHI [apnea-hypopnea index], Continued on following page

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2018 • 21 PULMONARY MEDICINE Three-pronged plan for universal flu proposed BY NICK ANDREWS essential to advancing these three months after scientists from aca- last year in the journal Immunity MDedge News research areas that [the] NIAID will demia, industry, and government (2017;47: 599-603). The scientists at develop, support, and provide for convened for the NIAID Pathway the workshop developed criteria that hree specific research areas the scientific community,” wrote Dr. to a Universal would define a universal vaccine and were proposed by the Na- Erbelding and her coauthors. workshop to address knowledge gaps decided that a universal vaccine for Ttional Institute of Allergy and The development plan comes 8 and strategy, which was summarized influenza should do three things: be Infectious Diseases (NIAID) in its development plan for a universal influenza vaccine, as detailed in a report published online in the Journal of Infec- tious Diseases. Anthony S. Fauci, MD, di- rector of the NI- AID, spoke with MDedge News in an interview DR. FAUCI regarding the plan and noted that he and his colleagues felt that it was important to accelerate the ef- fort for a universal vaccine. The plan will focus on transmis- sion, natural history, and patho- genesis studies utilizing prospective cohorts; influenza immunity and correlates of immune protection; and strategies in rational vaccine design to elicit broad, protective im- mune responses, according to Emily J. Erbelding, MD, MPH, director of microbiology and infectious diseas- es at the NIAID, and her associates in their report. They noted that the three research areas are not priori- tized and that advances in each are expected to be interdependent. “The strategic plan also includes a description of research resources

Continued from previous page risk of atrial fibrillation, compared with those without diabetes. Similarly, the incidence of atrial fibrillation was reduced after uvu- lopalatopharyngoplasty but only in patients with hypertension or dys- lipidemia and not in those with nor- mal blood pressure or lipid levels. “These differences in outcomes after UPPP are probably due to the differ- ent etiologies of cardiovascular dis- ease,” the authors wrote. Limitations included the absences of polysomnog- raphy information and information on whether patients used other sleep apnea therapies, such as CPAP or a mandibular advancing device. The study was supported by the Korean Society of Otorhinolaryn- gology Head and Neck Surgery. [email protected]

SOURCE: Lee H-M et al. Sleep Med. 2018 May;45:11-6.

22 • JUNE 2018 • CHEST PHYSICIAN at least 75% effective against symp- desirable,” wrote Catharine I. Paules, next step will be doing the research place a year ago, it would have had tomatic influenza ; protect MD, of the University of Maryland, and finding more resources. ... The an impact on this flu season,” he said. against group I and II influenza A Baltimore, and her coauthors in the work is yet to be done.” The authors reported no relevant viruses; and have durable protections workshop summary. The development plan was pub- financial conflicts and that the Na- that lasts at least 1 year and prefera- Dr. Fauci told MDedge News how lished amid an ongoing historic flu tional Institutes of Health produced bly through multiple seasons. “experts from all over the coun- season. this plan. “Clearly, a vaccine that would try addressed their thoughts and Dr. Fauci noted that this season cover most or all seasonal strains concerns with us last year [at the had particular circumstances that SOURCE: Erbelding EJ et al. J Infect of influenza and also provide pro- workshop], and now we have a de- made it worse than normal. “I don’t Dis. 2018 Feb 28. doi: 10.1093/infdis/ tection during a pandemic is highly velopment plan,” he said. “But the think that, had we had this plan in jiy103.

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2018 • 23 PULMONARY MEDICINE Let clinical scenario guide sarcoidosis treatment BY MICHELE G. SULLIVAN “Sometimes, the worst-looking of this tenet, he said in an interview. things drive your decision to treat: MDedge News patients [on imaging] have the best Scans can look alarming, with multi- danger to an organ, and quality of prognosis,” Daniel Culver, DO, said ple widespread granulomas. But Löf- life,” said Dr. Culver, a pulmonolo- SANDESTIN, FLA. – Don’t be a slave at the annual Congress of Clinical gren’s is generally a benign condition, gist and director of the Sarcoidosis to imaging when evaluating the pa- Rheumatology. Patients with Löfgren’s despite its threatening mien. Center of Excellence at the Cleve- tient with sarcoidosis. syndrome are a very good example Instead of imaging, “Let two land Clinic in Ohio; he is also pres- ident of the World Association for Sarcoidosis. He agrees with a decision schema published in 2015 (Clin Chest Med. 2015;36[4]:751-67).

“Sometimes, the worst- looking patients [on imaging] have the best prognosis,” said Daniel Culver, DO, of the Cleveland Clinic.

Six factors weigh in favor of treat- ment: • Symptomatic disease. • Impaired organ function. • Disease endangering an organ. • Progressive disease. • Clear-cut disease activity. • Low likelihood of remission. These must be balanced – with patient input as the fulcrum – against five factors that favor con- servative management: • Minimal symptoms. • Good organ function. • Low risk of danger to organs. • Inactive disease. • Higher likelihood of remission. The decision to embark on a treat- ment program, usually starting with a steroid-based regimen, can’t be taken lightly, Dr. Culver said. A 2017 study showed that steroids pose a cumulative risk of toxicities for sar- coidosis patients (Respir Med. 2017 Nov;132:9-14). Patients who started steroids faced more than a doubling in the risk of a toxic side effect by 96 months when compared with those who didn’t. But even short-term ste- roid use increased the risk of a toxic- ity, Dr. Culver said. The study noted that problems can begin to occur in as little as 1 month, at a cumulative dose as low as 1 g. For patients who fall onto the “treat” side of the risk teeter-totter, Dr. Culver recommended starting with an initial course of prednisone at 20-30 mg daily for no more than 4 weeks. Responders can taper to less than 10 mg/day. Those who continue to do well can maintain low-dose prednisone for up to 12 months and then complete the ta- per. Patients who relapse can add an immune modulator (methotrexate, Continued on following page

24 • JUNE 2018 • CHEST PHYSICIAN PULMONARY MEDICINE Three days of beta-lactam beat clinically stable CAP BY MICHELE G. SULLIVAN in practice might lead to reduced cough, and 39% had purulent spu- Despite the positive results, Dr. MDedge News rates of multidrug-resistant bacte- tum. The median PSI/PORT Score Dinh cautioned against using the ria, fewer adverse events, and surely was 82. study as justification for a one-size- MADRID – Three days of beta-lac- lower costs.” After 3 days of treatment, clinical fits-all treatment for community-ac- tam therapy was just as effective as The French PTC Trial (Short cure was not significantly different quired pneumonia. 8 days for clinically stable patients Duration Treatment of Non-Severe between the 3- and 8-day groups, “Although I think we demon- presenting with community-ac- Community-Acquired Pneumonia) either in the intent-to-treat anal- strated that 3 days of treatment quired pneumonia. randomized 310 patients (mean age, ysis (69.9% vs. 61.2%) or in the with beta-lactam is not inferior In a randomized, placebo-con- 73.5 years) to either short- or long- per-protocol analysis (75.7% vs. to 8 days, this cannot be imposed trolled trial, 15-day cure rates were course treatment with a beta-lactam 68.7%). without regard to individual pa- antibiotic. Patients were eligible tient status,” he cautioned. Such a for the study if they were admitted “Reducing treatment time now treatment paradigm would not be to the hospital for community-ac- advisable for patients with mod- quired pneumonia based on respira- appears to be manageable erately severe pneumonia, who tory signs, fever of 38° C or higher, and effective in a number of were excluded from the study, or and evidence of new infiltrate on those with compromised immune chest radiograph. infectious diseases. [This] systems. All patients were treated with 3 change in practice might lead Nor does Dr. Dinh expect whole- days of amoxicillin/clavulanic acid to reduced rates of multidrug- sale clinical embracing of the en- (Augmentin) or third-generation couraging results, which bolster the cephalosporin. Those who had resistant bacteria, fewer adverse ever-accumulating data in favor of responded clinically by day 3 en- events, and surely lower costs.” shorter courses of antibiotics for tered the 5-day randomization pe- some infectious diseases. riod, receiving placebo or 5 more “I think there is a chance that days of active therapy with the Because the trial had closed days clinicians who normally treat for 9 same agent. before the ECCMID meeting, only or 10 days may now feel comfort- Clinical requirements for random- the primary endpoints were avail- able reducing to 7,” he said with a ization included being afebrile with able for discussion, Dr. Dinh said. chuckle. stable heart and respiratory rate, a Investigators are analyzing the The French Ministry of Health systolic blood pressure of at least 90 secondary endpoint data, which he sponsored the study. Dr. Dinh had mm Hg, and oxygen saturation of at said would be published at a later no competing financial interests. least 90%. date. [email protected]

Michele G. Sullivan/MDedge News Michele G. Sullivan/MDedge The primary endpoint was clini- Dr. Aurélien Dinh cal cure at day 15: no fever, absence of or improvement in respiratory 69.9% in patients who took 3 days symptoms (dyspnea, cough, puru- of antibiotics and 61.2% in those lent sputum, and cackles), and no who took 8 days – a nonsignificant need for additional antibiotic treat- difference, Aurélien Dinh, MD, said ment for any indication. at the European Society of Clinical Secondary endpoints were cure Microbiology and Infectious Diseas- at day 30, 30-day mortality, adverse es annual congress. events, length of stay, return to usual The French study was one of a activities by day 30, and quality of series at the meeting demonstrating life at day 30. that, for some groups of patients, Many of the generally elderly pa- short-term antibiotic therapy is a tient cohort had comorbid illnesses, viable – and probably healthy – al- including diabetes (about 20%), ternative to the traditional longer chronic obstructive pulmonary dis- courses, said Dr. Dinh of the Uni- ease (about 35%), and coronary in- CHEST e-Learning versity of Paris Hospital. sufficiency (about 14%). About 20% “Reducing treatment time now ap- were active smokers. Less than 10% pears to be manageable and effective had gotten a Earn CME credits and MOC points and in a number of infectious diseases,” in the past 5 years. sharpen your skills with CHEST e-Learning Dr. Dinh explained. “Although there At admission, more than half of products. Easily accessible modules are are some limits, surely, this change patients were dyspneic, 80% had now available in: n NEW! Pulmonary hypertension Continued from previous page it’s necessary to proceed imme- n NEW! Lung cancer screening azathioprine, leflunomide, or myco- diately to an immunosuppressive n Critical care ultrasound phenolate). regimen to prevent irreversible Those who have an inadequate fibrosis. n Cystic fibrosis response to the initial prednisone Dr. Culver noted associations with n Cardiopulmonary exercise testing course should then get an immune multiple pharmaceutical companies, modulator. If they do well, that can but said none were relevant to his be maintained; a second modulator talk. A video interview with Dr. Visit chestnet.org/elearning for our full list of e-Learning modules. can be brought on board if necessary. Culver is available on mdedge.com/ For those who don’t respond at chestphysician. all to the initial prednisone course, [email protected]

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2018 • 25 PULMONARY MEDICINE Four-meter gait speed predicts mortality in IPF BY DOUG BRUNK test, and King’s Brief Interstitial Medical Research Council dyspnea to treatment. Now we know that it MDedge News Lung Disease questionnaire. Ms. score was 3. In addition, mean has predictive capacity as well.” Nolan, a respiratory physiothera- body mass index was 27.2 kg/m2, During her presentation, she cit- SAN DIEGO – Among patients with pist with the Harefield Pulmonary mean 4-meter gait speed was 0.92 ed potential reasons why change in idiopathic pulmonary fibrosis (IPF), Rehabilitation and Muscle Research meters per second, mean incremen- gait speed is associated with sur- an improvement in 4-meter gait Group, Royal Brompton and Hare- vival. “Firstly, gait speed has been speed with pulmonary rehabilita- field NHS Foundation Trust, Lon- described as a clinical indicator tion is an independent predictor of don, and her associates drew from of multisystem well-being and the all-cause mortality at 1 year, suggest national databases to obtain data on ‘sixth vital sign,’ ”she said. “Walking results from a multicenter study pre- all-cause mortality 1 year following ability and speed rely on multiple sented at an international conference pulmonary rehabilitation. factors and the integration of many of the American Thoracic Society. “We also identified a cutpoint, so systems, cardiovascular and oth- The authors of the study found if patients improved their walking erwise. We know that pulmonary that patients who improved their speed by 0.009 meters per second rehab has multiple benefits and im- gait speed had a longer survival or above, that was associated with a proves these systems, and it’s plausi- time. In all, 11% of patients died longer survival time at 1 year (area ble that change in gait speed may be within 1 year of completing pulmo- under the curve of 0.76, for sensitiv- a surrogate marker for, say, improve- nary rehabilitation. ity of 69.6% and a specificity of 70%; ment in exercise capacity or health “Mortality is an attractive end- P less than 0.01),” she said. “Among status. But the precise mechanism point in IPF clinical research but patients who achieved that cutpoint requires verification.” requires large sample sizes and long or exceeded it, only 5% of them died Ms. Nolan acknowledged certain

follow-up duration, making clinical in the 1-year follow-up period, com- News Brunk/MDedge Doug limitations of the study, including the trials expensive and challenging pared with 23% in the group that “[It’s] plausible that change in gait fact that contemporaneous measure- to undertake,” lead study author didn’t achieve that cutpoint. That’s speed may be a surrogate marker for, ment of full lung function testing and Claire M. Nolan, MSc, said at the quite a big difference, but this re- say, improvement in exercise capacity pulmonary hypertension diagnosis conference. “Consequently, there quires external validation in another or health status. But the precise were not available at the time of the is much interest in surrogate end- population.” mechanism requires verification,” study. “Therefore, we were unable points of mortality. In the elderly To determine the 4-meter gait noted Claire M. Nolan. to account for [diffusing capacity of population, a lot of work has been speed change cut-off that best dis- the lung for carbon monoxide] and done on performance measures, in criminated between patients who tal shuttle walk test measurement pulmonary hypertension diagnosis,” particular the 4-meter gait test. It’s a died and survived, the investigators was 271 meters, and mean King’s she said. “Secondly, we were unable simple test to do from the assessor’s plotted receiver operating charac- Brief Interstitial Lung Disease to identify the precise cause of death perspective, because you just need teristic curves. For validation, they total score was 56.4. Following 8 from the national database of harm a 4-meter corridor and a stopwatch. conducted a Kaplan-Meier analysis weeks of pulmonary rehabilitation, and care records, but this corrob- From the patient’s perspective, they to assess time to death, with signifi- the patients’ 4-meter gait speed orates previous data which suggest only have to walk at their usual cance assessed via the log-rank test. improved significantly by a mean that it’s difficult to reliably discern if speed, making it feasible in most Finally, they used a multivariate Cox of 0.15 meters per second (P less a death is IPF- or non-IPF related. settings.” proportional hazards model to char- than .001). All other variables also Lastly, we know that the benefits of The study by Ms. Nolan, a Na- acterize the relationship between improved significantly, with the ex- pulmonary rehab experienced by IPF tional Institute for Health Research 4-meter gait speed change and all- ception of forced vital capacity. patients tend to wane after 6 months. fellow, and her associates, involved cause mortality, adjusting for inde- In an interview, Ms. Nolan char- It would be interesting to compare recruiting 90 IPF patients referred pendent predictors of mortality (age, acterized the results as “one piece the short-term improvements in to three outpatient pulmonary reha- previous respiratory hospitalizations of the puzzle in answering whether gait speed that we observed to more bilitation programs in London. All in the past year, forced vital capac- 4-meter gait speed is a useful test for sustained improvements, to identify patients underwent the following ity percent predicted) and baseline clinicians and researchers. It needs whether this impacts prognostability.” assessments before and after 8 weeks 4-meter gait speed. to be taken in the context of 4-meter National Institute for Health Re- of pulmonary rehabilitation: spirom- At baseline, 70% of the 90 pa- gait speed in other populations as search funded the study. etry, Medical Research Council dys- tients were male, mean age was 74 well as with what we’re finding in Ms. Nolan reported having no fi- pnea score; anthropometry, 4-meter years, mean forced vital capacity patients with IPF. We know that this nancial disclosures. gait speed, incremental shuttle walk was 72.8% predicted, and mean test is reliable, valid, and responsive [email protected] New ILD diagnostic test now available

BY KATIE WAGNER LENNON misdiagnosed at least once, according to a study ment,” Bonnie Anderson, chairman and CEO of MDedge News published by the Pulmonary Fibrosis Foundation. Veracyte, said in the statement. The new test, known as the Envisia Genomic A benefit of the new test is that its use does 190-gene test for interstitial lung diseases (ILD), Classifier, combines RNA sequencing and ma- not require patients to undergo risky, expensive Aincluding idiopathic pulmonary fibrosis (IPF), chine learning to help physicians differentiate IPF surgery, which may not even be possible for some is now available through an early-access program. from ILDs in samples obtained through trans- patients, noted Dr. Weigt. “We are pleased to be IPF can be difficult to distinguish from other bronchial biopsy. Its specificity and sensitivity for one of the few medical facilities in the country to ILDs, S. Samuel Weigt, MD, of the University of detecting the genomic pattern of usual interstitial have access to this breakthrough technology.” California, Los Angeles, and director of UCLA pneumonia, are 88% and 70%, respectively, ac- More information about the Envisia Genomic Health’s Interstitial Lung Disease Center, said in a cording to the Veracyte statement. Classifier and how to enter the early-access program statement from Veracyte, the company marketing “Multiple studies have demonstrated that the can be obtained through emailing Veracyte at sup- the test. Envisia Genomic Classifier supports more confi- [email protected] or by calling 844-464-5864. In fact, more than half of patients with ILDs were dent IPF diagnosis and optimal patient manage- [email protected]

26 • JUNE 2018 • CHEST PHYSICIAN PULMONARY MEDICINE Ivacaftor reduced hospitalizations in CF BY MADHU RAJARAMAN tion. For each period, the numbers person-year. Data were analyzed for initiated use between Feb. 22, 2014, MDedge News and percentages of patients hospital- two subcohorts: the 86 patients who and Dec. 31, 2015, under the ex- ized were calculated, for any reason started using ivacaftor between Feb. panded FDA label, which included vacaftor, a therapy that targets the and for cystic fibrosis–related reasons. 6, 2012, and Feb. 21, 2014, under the nine additional genetic mutations. G551D CFTR gene mutation to Hospitalization rates also were calcu- initial Food and Drug Administra- Of the 143 patients who had filled Itreat cystic fibrosis, significantly lated as numbers of admissions per tion label; and the 57 patients who reduced hospital admission rates in patients with cystic fibrosis with a va- riety of mutations, according to results published May 7 in Health Affairs. The study involved 143 pa- tients being treated with ivacaftor (Kalydeco), which is manufactured for Vertex Pharmaceuticals, be- tween February 2012 and February 2015. In 2014, the FDA expanded its approval for the use of ivacaftor by cystic fibrosis patients to include nine additional mutations, and pa- tients with these mutations were included in this study. The overall rate of inpatient ad- missions dropped by 55%, and cys- tic fibrosis–related admissions rates fell by 78% (P less than .0001) be- tween the period 12 months before treatment and 12 months after the first filled prescription, wrote Lisa B. Feng and her coauthors. Ms. Feng, who is senior direc- tor for policy and advocacy at the

Declines in hospital admissions also were similar between the initial label and the expanded FDA label groups, with declines in overall admissions of 59% and 57%, respectively. Hospital admissions related to cystic fibrosis decreased by 78%.

Cystic Fibrosis Foundation and her colleagues analyzed administrative claims data from the Truven Health Analytics Market Scan Commercial Research Database. All of the claims were for patients from the United States with employer-sponsored insurance plans. Eligibility criteria included an ICD-9 CM diagnosis of cystic fibrosis on one or more inpatient claims or two or more out- patient claims at least 30 days apart, a prescription claim for ivacaftor monotherapy, being at least 6 years of age at the time of the first filled prescription, and 12 months of con- tinuous enrollment before and after the first filled prescription. The “pre-ivacaftor” period was defined as the 12 months before the first filled prescription. The “post-iva- caftor” period was defined as the 12 months after the first filled prescrip-

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2018 • 27 PULMONARY MEDICINE RSV immunoprophylaxis doesn’t prevent asthma BY CATHERINE COOPER infants does not appear to prevent healthy premature infants who were group had parent-reported asthma, NELLIST asthma at age 6 years, reported Nien- randomized to receive palivizumab compared with 24% of the 196 in MDedge News ke M. Scheltema, MD, of Wilhelmina for respiratory syncytial virus (RSV) the placebo group (absolute risk re- Children’s Hospital, Utrecht, the immunoprophylaxis or placebo and duction, 9.9%). This was explained espiratory syncytial virus im- Netherlands, and associates. followed for 6 years, 14% of the mostly by differences in infrequent Rmunoprophylaxis in premature In a study of 395 otherwise 199 infants in the RSV prevention wheeze, the researchers said. How- ever, physician-diagnosed asthma in the past 12 months was not sig- nificantly different between the two groups at 6 years: 10.3% in the RSV prevention group and 9.9% in the placebo group. [email protected]

SOURCE: Scheltema NM et al. Lancet. Comes in Digital too! 2018 Feb 27. doi: 10.1016/S2213- 2600(18)30055-9. www.chestphysician.org Continued from previous page prescriptions for ivacaftor, 63% were aged 18 years or older. The rate of overall inpatient admissions de- creased 55%, from 0.57 admissions per person-year in the pre-ivacaftor period to 0.26 admissions per per- son-year in the post-ivacaftor period. The declines in hospital admissions also were similar between the initial label and the expanded FDA label groups, with declines in overall admis- sions of 59% and 57%, respectively. Hospital admissions related to cystic fibrosis also decreased sig- nificantly, by 78%. Admissions with principal diagnosis codes for cystic fibrosis decreased from 42 in the preprescription period, to 8 after filling the prescription. Rates per person per year decreased by 82% in patients aged 6-17 years and 80% among adults aged 18 years and older. Additionally, patients who filled at least 10 pre- scriptions during the study period experienced a 68% reduction in inpatient admissions, compared with 45% for those with 3-9 pre- scriptions filled. Ivacaftor also was associated with 60% lower per-person inpatient spending overall, with a greater pro- portional reduction in hospital costs for adults (68%) than for children (45%), and an absolute per-person reduction of $10,567. “To deliver the right care to the right patient,” the authors con- Disease state cluded, “cystic fibrosis care must self-assessment quizzes continue to account for other as- Compilation of journal summaries pects unique to individuals such as environment, physiology, patients’ preferences, and lifestyle.” [email protected]

SOURCE: Feng LB et al. Health Aff. 2018 May 8. doi: 10.1377/ hlthaff.2017.1554.

28 • JUNE 2018 • CHEST PHYSICIAN PULMONARY MEDICINE As-needed budesonide-formoterol prevented exacerbations in mild asthma

BY AMY KARON naire, compared with as-needed MDedge News budesonide-formoterol recipients. Finally, lung function assessments ormoterol plus budesonide favored as-needed budesonide-for- prevented exacerbations when moterol over terbutaline but not Finhaled as needed by patients over maintenance budesonide. SYG- with mild persistent asthma, ac- MA1, mean changes (from baseline) cording to the results of two large, in FEV1 before bronchodilator use double-blind, 52-week, randomized were 11.2 mL with terbutaline, phase 3 trials. 65.0 mL with budesonide-formo- In the SYGMA1 (Symbicort Given terol, and 119.3 mL with mainte- as Needed in Mild Asthma) trial, nance budesonide. In SYGMA2, the regimen outperformed as-need- these values were 104 mL with ed terbutaline in terms of asthma budesonide-formoterol and 136.6 control (34.4% vs. 31.1% of weeks; mL with maintenance budesonide. P = .046) and exacerbations (rate AstraZeneca provided funding.

ratio, 0.36; 95% confidence interval, Stockbyte/Thinkstock For SYGMA1, Dr. Byrne disclosed 0.27-0.49). In the SYGMA2 study, ties to AstraZeneca, Novartis, it was noninferior to twice-daily of having well-controlled asthma by on the Asthma Control Ques- GlaxoSmithKline, Medimmune, budesonide for preventing severe ex- about 14%, when compared with us- tionnaire-5 (ACQ-5) favored and Genentech. For SYGMA2, Dr. acerbations (RR, 0.97; upper one-sid- ing terbutaline as needed (odds ratio, budesonide-formoterol over terbu- Bateman disclosed ties to AstraZen- ed 95% CI, 1.16). The findings were 1.14; 95% CI, 1.00-1.30; P = .046). taline by an average of 0.15 units eca, Novartis, Cipla, Vectura, Boeh- published in two reports in the New Although maintenance budesonide and similarly favored twice-daily ringer Ingelheim, and a number of England Journal of Medicine. controlled asthma best (44.4% of budesonide over budesonide-formo- other pharmaceutical companies. Asthma often is undertreated be- weeks; OR vs. budesonide-formo- terol. In SYGMA2, the budesonide [email protected] cause many patients adhere poorly terol, 0.64; 95% CI, 0.57-0.73), 21% maintenance group averaged 0.11 to maintenance glucocorticoids, of patients did not adhere to it, the units greater improvement on SOURCES: O’Byrne PM et al. N noted Paul M. O’Byrne, MD, of researchers reported. “Patients are the ACQ-5 and 0.10 better im- Engl J Med. 2018;378(20):1865-76. McMaster University in Hamilton, often more concerned [than their provement on the standardized Bateman ED et al. N Engl J Med. Ont., and his associates from SYG- health care providers] about adverse Asthma Quality of Life Question- 2018;378(20):1877-87. MA1 (NCT02149199). Instead, effects of inhaled glucocorticoids, patients often rely on short-acting even when low inhaled doses are VIEW ON THE NEWS beta2-agonists for symptom control, used,” they wrote. Notably, the but these drugs don’t stop exacer- budesonide-formoterol as-needed ‘Two out of three ain’t bad’ bations or treat underlying inflam- group received a median daily dose mation. “One potential strategy to of only 57 mcg inhaled glucocor- In the SYGMA1 and SYGMA2 trials, as-needed budesonide-formo- address these issues is the use of a ticoid, 17% of that received by the terol (Symbicort) prevented exacerbations and loss of lung function, combination of a fast-acting beta2- budesonide maintenance group. the two worst outcomes of poorly controlled asthma, concluded agonist and an inhaled glucocor- In SYGMA2 (NCT02224157), Stephen C. Lazarus, MD, FCCP, in an editorial accompanying the ticoid taken only on an as-needed 4,215 patients with mild persistent studies in the New England Journal of Medicine. basis,” the researchers wrote. asthma aged 12 years and up were “As-needed treatment was similar, or at least noninferior, to Accordingly, they randomly as- randomly assigned to receive either regular maintenance therapy with inhaled glucocorticoids with signed 3,849 patients aged 12 years twice-daily placebo plus as-needed regard to the prevention of exacerbations, and exacerbations are and up who had mild persistent budesonide-formoterol or twice-dai- the main contributor to loss of lung function, death, and cost,” asthma (mean forced expiratory ly maintenance budesonide plus wrote Dr. Lazarus. volume in 1 second [FEV1] be- as-needed terbutaline. Doses were Patients typically received only 17%-25% as much inhaled fore bronchodilator use, 84% of the same as in the SYGMA1 tri- glucocorticoid as did those on maintenance budesonide, which predicted value) to receive one of al. The regimens resembled each would help prevent side effects and would make the regimen three regimens: twice-daily placebo other in terms of severe exacer- more acceptable to “glucocorticoid-averse patients,” he added. plus terbutaline (0.5 mg) used as bations (annualized rates, 0.11 Another benefit to patients with mild persistent asthma using needed, twice-daily placebo plus and 0.12, respectively) and time as-needed budesonide-formoterol instead of inhaled glucocorti- budesonide-formoterol (200 mcg of to first exacerbation, even though coid maintenance therapy is that it would result in nearly $1 bil- budesonide and 6 mcg of formoter- budesonide-formoterol patients lion in cost savings in the United States yearly. ol) used as needed, or maintenance received a 75% lower median dai- Budesonide-formoterol did not control symptoms as well as did twice-daily budesonide (200 mcg) ly dose of inhaled glucocorticoid, maintenance budesonide, but patients might accept “occasional plus as-needed terbutaline (0.5 mg), reported Eric D. Bateman, MD, of mild symptoms and inhaler use if it [freed] them from daily use all for 52 weeks. the University of Cape Town, South of inhaled glucocorticoids while preventing loss of lung function In the final analysis of 3,836 Africa, and his associates. and exacerbations,” he concluded. “For these patients, ‘Two out patients, annual rates of severe Results from both trials suggested of three ain’t bad!’ ” exacerbations were 0.20 with ter- that as-needed budesonide-for- Dr. Lazarus is in the department of medicine and at the Car- butaline, significantly worse than moterol provided better symptom diovascular Research Institute, University of California, San Fran- with budesonide-formoterol (0.07) control than did terbutaline but cisco. He reported having no conflicts of interest. This comments or maintenance budesonide (0.09). worse symptom control than did are from his editorial (N Engl J Med. 2018 May 17. doi: 10.1056/ Using budesonide-formoterol (Sym- twice-daily budesonide. In SYG- NEJMe1802680). bicort) as needed improved the odds MA1, the change from baseline

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2018 • 29 CARDIOVASCULAR MEDICINE In PAH trials, clinical worsening risk rose with time BY ANDREW D. BOWSER hypertension (PAH) may be longer of clinical worsening beyond 6-12 requirement for longer-term MDedge News than what is needed to demonstrate months was relatively constant, event-driven trials beyond that du- treatment benefit, results of a recent according to results of the study ration in an orphan disease such as FROM THE JOURNAL CHEST® n Cur- meta-analysis suggest. published in the May issue of the PAH,” wrote investigator Annie C. rent clinical trials evaluating combi- In PAH trials of combination journal Chest®. Lajoie, MD, of the Pulmonary Hy- nation therapy for pulmonary artery therapy, the absolute risk reduction That finding “questions the pertension Research Group, Quebec

VIEW ON THE NEWS Long-term follow- up questioned

Results of this study by Lajoie and colleagues question the need for long-term follow-up beyond 12 months in clinical trials of combination therapy in pulmonary arterial hyper- tension (PAH), according to authors of an editorial. “While very short term follow-up trials fail to detect important patient-centered outcomes and adverse events, very long term follow-up may impact trial feasibility without improving power to detect meaningful efficacy,” wrote Rogerio Souza, MD, PhD, and Juliana C. Ferreira, MD, PhD. The study also shows that relative risk of worsening is influenced by the duration of the trial. That suggests look- ing at relative risk in isolation may not be the optimal ap- proach to evaluating the ben- efits of combination therapies for PAH, the authors added. These findings, collectively, should inform the develop- ment of future clinical trials, they said. In particular, those trials could evaluate multiple markers of PAH improvement and a “time-limited observa- tion” of morbidity events. That “potential alternative” approach could make future studies more feasible, without compromising the robustness of findings, Dr. Souza and Dr. Ferreira said in their editorial.

Rogerio Souza, MD, PhD, and Juliana C. Ferreira, MD, PhD, are with the University of São Paulo, pulmonary division. These comments are derived from their editorial appearing in the journal Chest®. Dr. Fer- reira reported speaker fees from Medtronic, and Dr. Sou- za reported speaker and con- sultancy fees from Actelion, Bayer, GSK, and Pfizer.

30 • JUNE 2018 • CHEST PHYSICIAN City, and her coauthors. For the long-term, event-driven tors reported. After that, the relative The meta-analysis by Dr. Lajoie trials, the mean number needed to risk progressively increased to 0.54 and her colleagues included 3,801 treat (NNT) was 17.4 at week 16, at 52 weeks and 0.68 at 104 weeks. patients enrolled in 1 of 15 previously gradually decreasing to 8.8 at 52 Looking at all trials combined, Dr. published randomized clinical trials. weeks of follow-up, remaining stable Lajoie and her colleagues observed Of those trials, four were long-term, after that, according to investigators. that longer trial duration had a pos- event-driven studies, with a mean du- Consistent with that finding, the itive correlation with relative risk of ration of 87 weeks, while the remain- mean relative risk of clinical wors- clinical worsening (P = .0002). der were shorter studies with a mean ening was 0.38 at 16 weeks, and Pragmatically, these results raise

duration of 15 weeks. Images Rawpixel/iStock/Getty similarly, 0.41 at 26 weeks, investiga- Continued on following page

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2018 • 31 Continued from previous page as a simple measure of treatment the possibility that PAH combina- Longer trial duration had a positive correlation impact. tion therapy trials could be shorter with relative risk of clinical worsening. Dr. Lajoie’s coauthors had in duration. Some recent event-driv- disclosures related to Actelion en studies have lasted up to 6 years, Pharmaceuticals, Bayer, and with patients on treatment for about ly changing treatment paradigm in They also cautioned that NNT, GlaxoSmithKline, among others. 2 of those years, investigators noted. PAH, the optimal duration of future a measure of how many patient [email protected] “In the context of an orphan dis- trials should be revisited,” Dr. Lajoie treatments are needed to prevent ease with limited and competing and her colleagues wrote in a dis- one additional adverse event, could SOURCE: Lajoie AC et al. Chest. 2017 recruitment for trials and the rapid- cussion of their findings. be “misleading” despite its value May;153(5):1142-52.

32 • JUNE 2018 • CHEST PHYSICIAN CARDIOVASCULAR MEDICINE Stroke-smoking link is dose-dependent in young men BY JIM KLING may decrease the risk of ischemic with nonsmokers, and 5.24 for those the researchers decided to conduct MDedge News stroke, according to a population- who smoked 40 or more per day, a follow-up study in men in order based, case-control study. reported Janina Markidan and her to eliminate hormonal confound- n men younger than 50 years, The odds ratio for a stroke was coinvestigators in Stroke. ers (Stroke. 2008 Sep;39[9]:2439- even just a reduction in the 1.21 for men who smoked fewer A prior study showed a similar 43). Inumber of cigarettes smoked than 11 cigarettes per day, compared relationship in young women, but Ms. Markidan and her colleagues used data from the Stroke Preven- tion in Young Men Study, which recruited 615 men who had expe- rienced a stroke in the previous 3 years, and compared these men with 530 age-, ethnicity-, and geography- matched controls. There were some statistically significant differences in the two populations: Cases had lower levels of education and had greater inci- dences of hypertension, diabetes, myocardial infarction, angina, and obesity (all P < .05). Current smokers were identified as those who had smoked more than 100 cigarettes in their lifetime and who had smoked a cigarette in the 30 days preceding the stroke. Never smokers were those who had smoked fewer than 100 cigarettes in their lifetime or who had never smoked five packs. Compared with never smokers, current smokers had an odds ratio for stroke of 1.88 (95% confidence interval, 1.44-2.44). When the re- searchers stratified smokers by the number of cigarettes smoked, the stroke risk appeared to be dose de- pendent in the fully adjusted mod- els: The OR for 1-10 cigarettes/day was 1.21 (95% CI, 0.83-1.77), 1.64 for 11-20 cigarettes/day (95% CI, 1.10-2.43), 3.51 for 21-39 cigarettes/ day (95% CI, 1.65-7.45), and 5.24 for 40 or more cigarettes/day (95% CI, 1.90-14.42). The study cannot prove causation and did not include smoking of nontobacco products, alcohol con- sumption, or physical activity. [email protected]

SOURCE: Markidan J et al. Stroke. 2018 May;49(5):1276-8.

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2018 • 33 PEDIATRIC PULMONARY MEDICINE ED visits higher among pediatric asthma patients with comorbid depression, anxiety

BY DOUG BRUNK to measure the rate of asthma-relat- and 21.5 ED visits per 100 child- MDedge News ed ED visits. This measure identifies years, respectively; P less than .01 VIEW ON THE NEWS patients aged 2-21 years with asth- for both associations.) Susan Millard, TORONTO – Children with asthma ma using ICD 9 and 10 codes and “We were surprised to see that MD, FCCP, com- who have a comorbid diagnosis of tracks ED utilization over the mea- anxiety and depression seemed to ments: This is anxiety or depression are signifi- surement year. Next, the researchers increase asthma emergency depart- a robust study cantly more likely to make asthma- conducted univariate and multivar- ment visits as much as other medical and I am not related visits to the emergency iate analyses to assess the relation- chronic illnesses like cystic fibrosis surprised at department, compared with their ship between ED visit rate and an or sickle cell disease, and that kids all. Adding in peers who do not have a mental established diagnosis of comorbid on Medicaid, who tend to be our the informa- health condition, results from a anxiety or depression. poorer kids, also had an indepen- tion about pe- large administrative data analysis dent risk of going to the diatric patients showed. emergency department,” who have “We were surprised to see “There has been a fair bit of re- Ms. Neel said. “Having Medicaid and anxiety or de- search on how comorbid mental that anxiety and depression Medicaid as well as anx- pression is also not surprising. health conditions can affect health seemed to increase asthma iety or depression were This is why the Cystic Fibrosis care utilization for asthma in adults, emergency department visits as independently related to Foundation now recommends but few studies have examined how much as other medical chronic going to the emergency that adolescent CF patients comorbid mental health conditions illnesses,” said Caroline Neel, a room for asthma, so the should be screened at every like anxiety or depression can affect clinical research coordinator. study suggests that some routine visit to a CF clinic. children with asthma,” one of the of our highest-risk kids Maybe we should do the same study authors, Caroline Neel, said in for asthma have multiple for our asthma patients. an interview in advance of the Pedi- In all, the researchers identified different contributors to getting sick atric Academic Societies meeting. 71,326 patients with asthma, with and needing to go to the emergency In an effort to assess whether an overall rate of 16.3 ED visits per room for an asthma attack.” she said. “However, we still saw a anxiety or depression is associated 100 child-years. Among these, chil- She acknowledged certain limita- significant association between a with asthma-related ED usage in pe- dren with a diagnosis of depression tions of the analysis, including its re- comorbid mental health condition diatric patients, Ms. Neel, a clinical had significantly higher rates of ED liance on administrative claims data and emergency department use for research coordinator in the depart- visits (21.5 visits per 100 child-years; to identify whether or not children asthma, despite the potential that ment of pediatrics at the University P less than .01), as did those with a had a diagnosis of anxiety or depres- mental health conditions may have of California, San Francisco, and diagnosis of anxiety (19.5 ED visits sion. “This doesn’t necessarily iden- been under reported.” her associates evaluated data from per 100 child-years; P less than .01). tify all the kids who may have these The study’s senior author was the Massachusetts All Payer Claims Being enrolled in a Medicaid man- mental health conditions, since Naomi Bardach, MD. The research- Database for 2014-2015. They used aged care plan or Medicaid fee-for- sometimes providers are less likely ers reported having no financial the technical specifications from the service plan also increased the rates to document a diagnosis of a men- disclosures. Pediatric Quality Measures Program of asthma-related ED visits (20.3 tal health conditions for children,” [email protected] Interferon-gamma release assay trumps tuberculin skin test in school-aged children BY HEIDI SPLETE IGRAs have shown greater specificity than do of mainly enzyme-linked immunosorbent as- MDedge News TSTs, but data on their sensitivity to TB in chil- say–based IGRA, which limited the data on en- dren are limited, wrote Alexander W. Kay, MD, of zyme-linked immunospot tests, the researchers he interferon-gamma release assay (IGRA) the California Department of Public Health and said. The findings also were limited by the small Twas significantly more sensitive than a tuber- his colleagues in a study published in Pediatrics. number of children younger than 5 years. culin skin test (TST) as an adjunct tuberculosis The researchers reviewed data on children and However, the study is the largest North Amer- diagnosis of children aged 5 years and older, ac- teens aged 18 years and younger from the Cali- ican analysis of IGRA in children, and based on cording to data from a population-based study of fornia TB registry for 2010-2015. Of 778 reported the findings, “we argue that an IGRA should be 778 cases. cases of TB, 360 were laboratory confirmed, and considered the test of choice when evaluating 95 children had both an IGRA and TST with children 5-18 years old for TB disease in high-re- complete results. Of these, IGRA was significant- source, low-TB burden settings,” Dr. Kay and his VIEW ON THE NEWS ly more sensitive than TST (96% vs. 83%) in chil- associates wrote. Susan Millard, MD, FCCP, comments: dren aged 5-18 years. The sensitivities of IGRA The study was funded by the Centers for Dis- Our pediatric infectious disease col- and TST were similar in children aged 2-4 years ease Control and Prevention. Coauthor Shamim leagues are using the IGRA test for the (91% for both) and not significantly different in Islam, MD, disclosed financial support from specific age groups cited in this article. children younger than 2 years (80% vs. 87%, re- Qiagen, maker of the QuantiFERON test. Dr. Kay The TB skin test has such variability in spectively). and the other investigators had no financial con- regards to how it is placed and read, so Children younger than 1 year of age and those flicts to disclose. this is a welcomed method for the di- with CNS disease were significantly more likely [email protected] agnosis of tuberculosis at least in many to have indeterminate IGRA results, the research- parts of the United States. ers noted. SOURCE: Kay AW et al. Pediatrics. 2018 May 4. doi: The study results were limited by the use 10.1542/peds.2017-3918.

38 • JUNE 2018 • CHEST PHYSICIAN How can you help the 64% of patients who are unconcerned about proper device technique?1

Explore Delivery Makes a Difference, an online program with a variety of educational resources.

A slide presentation with A podcast highlighting Newsletters exploring Videos explaining how surprising results from the health care provider and how to improve to match a patient to an Delivery Makes a Difference patient responses from inhalation-device use and inhalation device and how to (DMaD) surveys the DMaD survey steps aimed at reducing watch for common errors in hospital readmissions inhalation-device technique

Delivery Makes a Difference Individualizing Delivery and Device in COPD Treatment

Visit www.chestphysician.org/deliverymakesadifference

The Delivery Makes a Difference initiative examines patient and provider perspectives on inhalation-device use and education in COPD.

Reference: 1. Hanania NA, Braman S, Adams SG, et al. The role of inhalation delivery devices in COPD: perspectives of patients and health care providers. Submitted manuscript.

This promotional, non-CME program is intended only for US health care professionals involved in the treatment of patients with COPD and is provided by Sunovion Pharmaceuticals Inc.

© 2018 Sunovion Pharmaceuticals Inc. All rights reserved. 02/18 RESP193-17

PROPERTY OF SUNOVION PHARMACEUTICALS INC. PROPRIETARY AND NONTRANSFERABLE. NOT FOR FURTHER DISSEMINATION.

CHPH_39.indd 1 2/28/2018 3:19:09 PM LUNG CANCER Lung cancer palliative care may reduce suicides BY KATIE WAGNER LENNON commit suicide, according to new among lung cancer patients and the OHSU Knight Cancer Institute, MDedge News research presented at the interna- among veterans,” said lead author, in a statement. tional conference of the American Donald R. Sullivan, MD, of the Dr. Sullivan, who also is a core eterans with advanced-stage Thoracic Society. division of pulmonary and critical investigator at the Center to Im- lung cancer who received pal- “Suicide is a significant national care medicine at Oregon Health & prove Veteran Involvement in Vliative care were less likely to public health problem, especially University and a member of Care at Portland Veterans Affairs, and his colleagues analyzed data on patients in the VA Healthcare System who were diagnosed with advanced-stage lung cancer (IIIB & IV) from January 2007 to Decem- AVAILABLE ONLINE! ber 2013. The investigators found that vet- erans who experienced at least one “palliative care encounter” after

The suicide rate for the advanced stage lung cancer CHEST 2017 patients was 200/100,000 patient-years, five times higher than for all veterans Highlights using VA health care.

learning they had lung cancer were 82% less likely to die by suicide (odds ratio, 0.18; 95% confidence Visit online to view articles interval, 0.07-0.46; P less than .001), and web-exclusive content when compared with veterans who CHEST 2017 were diagnosed with lung cancer but such as interviews and did not receive palliative care. The suicide rate for the advanced- video coverage. Highlights stage lung cancer patients was 200/100,000 patient-years, which A supplement to CHEST ® Physician - March 2018 was more than five times higher Summaries of key clinical sessions from the CHEST 2017 Annual Meeting than the suicide rate – adjusted for Toronto, Canada • October 28–November 1 age, sex, and year – for all veterans using VA health care (37.5/100,000), according to the study abstract. Of the 20,900 lung cancer patients analyzed, 30 committed suicide. Only six (20%) of the patients who died by suicide had received pal- liative care. Overall, most patients (18,192 or 87%) in the registry died of lung cancer. Other cancers, heart disease, and chronic obstructive pulmonary disease were some of the other common causes of death for the lung cancer patients, according to the abstract. While several medical societ- ies recommend palliative care for all patients with advanced-stage lung cancer, there is a gap between those recommendations and prac- tice, noted Dr. Sullivan. “There are many barriers to palliative care, and unfortunately, some are related to clinician referrals. Not all doctors mdedge.com/chestphysician/CHESTHighlights are aware of the benefits of palliative care,” he said in the statement. [email protected]

40 • JUNE 2018 • CHEST PHYSICIAN LUNG CANCER Delay of NSCLC surgery can lead to worse prognosis BY RANDY DOTINGA Society, and Dr. Soukiasian said tients in a cancer database who had pendent predictors of upstaging.” MDedge News surgery offers a chance at a cure for stage I NSCLC but had not under- The study design doesn’t provide those diagnosed at stage I. gone preoperative chemotherapy. insight into why surgery is often SAN DIEGO – A study suggests a “National Cancer Comprehen- The researchers tracked their clin- delayed. However, “we can theorize delay of surgery in certain cases of sive Network (NCCN) Guidelines ical stages for up to 12 weeks from factors associated with delays to sur- non–small cell lung cancer recommend surgery within 8 weeks initial staging. gery may be due to patient factors (NSCLC) can mean patients will Researchers found that, while (personal scheduling, availability of be upstaged and consequently have “Although these staging levels rose with each succes- support systems, etc.), delays in fol- worse prognoses. guidelines are ... sive week, just 25% of patients un- low-up, operating room availability “There is significant upstaging widely adopted, derwent surgery by 1 week, and only or scheduling, and issues with insur- with time from completion of clin- our study performs 79% had surgery in accordance with ance approval,” Dr. Soukiasian said. ical staging to surgical resection, a more granular NSCLC guidelines by week 8. At 12 In his presentation, Dr. Soukiasian with a 4% increase of upstaging analysis,” said weeks, 9% had still not undergone emphasized the role of the medias- per week for the overall study pop- surgery. tinum. “Given the clinical impact Dr. Harmik J. ulation,” said study coauthor Har- Upstaging was common: 22% at of stage III disease, we analyzed mik J. Soukiasian, MD, FACS, of Soukiasian. 1 week, 32% after 8 weeks, and 33% upstaging rates of stage I NSCLC Cedars-Sinai Medical Center, Los after 12 weeks. to stage IIIA and revealed a 1.3% Angeles, in an interview. “Upstaging of completed clinical staging for “We demonstrate that patients increase per week of upstaging spe- impacts lung cancer prognosis as NSCLC to limit cancer progression diagnosed with stage I NSCLC ben- cifically to stage IIIA. Additionally, more advanced stages portend to a or upstaging,” Dr. Soukiasian said. efit from surgery sooner than the almost 5% of patients initially diag- poorer prognosis.” “Although these guidelines are well 8-week window recommended by nosed with stage I NSCLC upstaged Dr. Soukiasian presented the study established and widely adopted, our the NCCN guidelines,” Dr. Souki- to IIIA disease. The significant rate findings at the annual meeting of study performs a more granular asian said. “Exclusive of the rate of of upstaging to IIIA disease makes the American Association for Tho- analysis, studying time as a predic- progression and in addition to time the case for more accurate and ag- racic Surgery. tor of upstaging for those patients to surgery, our study also demon- gressive mediastinal staging prior to An estimated 80%-85% of lung diagnosed with stage I NSCLC.” strated academic centers, higher surgical resection.” cancer patients have NSCLC, ac- For the new study, Dr. Soukiasian lymph node yield during surgery, No disclosures were reported. cording to the American Cancer and colleagues tracked 52,406 pa- and left-sided tumors to be inde- [email protected] Nivolumab shows promise in early-stage resectable NSCLC

BY AMY KARON linked major pathologic response with higher MDedge News tumor mutational burden (P = .01). Mutational burden did not correlate with tumor programmed eoadjuvant nivolumab did not delay surgery death ligand 1 expression. Deep sequencing of Nand produced at least 90% tumor regression T-cell receptor–beta chain CDR3 regions also cor- in nearly half of early-stage, resectable non–small related major pathologic response with increased cell lung cancers (NSCLC), according to the re- clonality of tumor-infiltrating T-cell clones that sults of a 21-patient pilot trial. also expanded into peripheral blood. “Many of Eighty percent of patients were alive and re- these clones were not detected in peripheral blood currence free a year after surgery, said Patrick M. before treatment,” the investigators wrote. Forde, MBBCh, and his colleagues from Johns In all, five (23%) patients developed treatment-re-

Hopkins University, Baltimore. The only grade 3 or Sebastian Kaulitzki/Thinkstock lated adverse events, and many developed more higher adverse event was treatment-related pneu- than one side effect. Grade 1-2 anorexia, taste dis- monia, which did not prevent surgery. The findings disease, and 86% were current or former smok- tortion, vomiting, and diarrhea were most common, were reported at the annual meeting of the Ameri- ers. Patients were followed for a median of 12 with isolated cases of grade 1-2 fever, infusion reac- can Association for Cancer Research and simultane- months after surgery (range, 0.8-19.7 months), tion, abdominal pain, abnormal liver function, dry ously in the New England Journal of Medicine. and the researchers assessed safety, tumor re- skin, and delirium. The case of grade 3 pneumonia Nivolumab targets the programmed cell death sponse, programmed death ligand 1 mutational developed after the first dose of nivolumab. 1 (PD-1) pathway and is approved in several tu- burden, and T-cell response. The funders included Cancer Research Institute– mor types, including advanced NSCLC that has Among 20 patients with evaluable resected Stand Up 2 Cancer; Johns Hopkins Bloomberg– progressed despite platinum-based or epidermal primary tumors, nine (45%) showed a major Kimmel Institute for Cancer Immunotherapy; growth factor receptor or anaplastic lymphoma ki- pathologic response, defined as having 10% or Bristol-Myers Squibb; International Immuno- nase–targeted therapy. That approval was based on fewer residual viable tumor cells. Twelve-month, Oncology Network, LUNGevity Foundation; Inter- the CHECKMATE-057 trial, in which nivolumab recurrence-free survival was 83% (95% confi- national Association for the Study of Lung Cancer; significantly outperformed docetaxel in metastat- dence interval, 66%-100%). The three progressors and Lung Cancer Foundation of America. Bristol- ic NSCLC (median overall survival, 12.2 vs. 9.4 included one patient with 75% residual tumor at Myers Squibb makes nivolumab and supplied the months; P = .002). However, programmed cell resection who subsequently developed a brain study drug. Dr. Forde disclosed study grant support death 1 inhibition in resectable NSCLC remained lesion, a patient with 5% residual tumor at resec- from Bristol-Myers Squibb. He reported ties to unexplored, Dr. Forde and his colleagues noted. tion who developed mediastinal lymph node re- Bristol-Myers Squibb, AbbVie, and other pharma- For the study (NCT02259621), 21 patients currence, and a patient with 80% residual tumor ceutical companies outside the submitted work. with treatment-naive, stage I, II, or III NSCLC at resection. The first two patients had durable [email protected] received two preoperative doses of nivolumab (3 responses to stereotactic radiotherapy or chemo- mg/kg) 2 weeks apart, with surgery timed for 4 radiotherapy, while the third patient developed SOURCE: Forde PM. AACR Annual Meeting 2018. weeks after the first dose. In all, 62% of patients fatal distal metastatic disease. Forde PM et al. N Engl J Med. 2018 Apr 16. doi: had adenocarcinoma, 81% had stage II or IIIa Sequencing of 11 completely resected tumors 10.1056/NEJMoa1716078.

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2018 • 41 LUNG CANCER Malignant pleural mesothelioma guidelines 2018 Education Calendar often ignored

BY RANDY DOTINGA lines, which recommend surgery in MDedge News resectable epithelioid MPM. “Our study revealed significant SAN DIEGO – National guidelines lack of compliance with NCCN for the treatment of malignant pleu- guidelines, as well as many dispar- Live Learning Courses ral mesothelioma (MPM) often are ities in the management of MPM,” not followed, a new study showed, Dr. Soukiasian said. “For the overall Courses held at the CHEST Innovation, Simulation, and Training Center in Glenview, Illinois. with fewer than a third of patients cohort, 32.3% of patients did not Advanced Critical Care Ultrasonography: Essentials receiving cancer-directed surgery. receive any treatment, 18.1% had Echocardiography in Critical Care Another 32% received no treatment, surgery plus chemotherapy, 38.6% June 1-3 September 13-15 November 29-December 1 although that didn’t seem to have an chemotherapy alone, and only 7% Difficult Airway Management impact on median months of survival. received trimodality therapy. In pa- June 8-10 | September 7-9 Comprehensive Bronchoscopy With Endobronchial Ultrasound Still, “there can be a wide vari- tients with epithelial histology, sur- Lung Cancer: A Multidisciplinary September 20-22 ation in median survival time, gery was significantly underutilized, Course for Pulmonologists Covering Current Paradigms for Diagnosis Comprehensive Pleural Procedures depending on clinical factors and with only 30% of patients receiving and Management November 3-4 tumor characteristics,” said study cancer-directed surgery.” July 13-15 Critical Care Ultrasound: Integration coauthor Harmik Soukiasian, MD, In addition, he said, “our study Bronchoscopy and Pleural Into Clinical Practice of Cedars-Sinai Medical Center, Los reveals several disparities that affect Procedures for Pulmonary and November 9-11 Angeles, at the annual meeting of compliance with NCCN guidelines. Critical Care Medicine Fellows Extracorporeal Support for the American Association for Tho- Treatment disparities were observed July 20 Respiratory and Cardiac Failure racic Surgery. “Given the variation in women, octogenarians, the unin- Mechanical Ventilation: Advanced in Adults in prognosis, it is quite astonishing sured, the Medicaid-insured, and in Critical Care Management December 7-9 July 26-28 that over 30% of MPM patients are patients with comorbidities. Guide- Advanced Critical Care Board not receiving any form of treatment. line adherence was significantly Cardiopulmonary Exercise Review Exam Course Testing (CPET) December 7-9 As clinicians armed with these data, increased in academic and high-vol- August 10-12 we need to investigate why that is.” ume hospitals with an associated Critical Skills for Critical Care: MPM, a rare cancer, is mainly increase in survival.” A State-of-the-Art Update and linked to asbestos exposure. “MPM But the study also found that me- Procedures for ICU Providers is almost always a fatal disease, and dian survival estimates were similar August 24-26 the prognosis can only be modestly regardless of treatment: 10 months influenced by oncological treatments,” for no treatment, 15 months for Learn More livelearning.chestnet.org according to the authors of guidelines chemotherapy only, 17 months for released in 2013. “The diagnostic surgery only, and 22 months for sur- process can be complex, with highly gery plus chemotherapy. specialized advice frequently required During the AATS presentation, an to arrive at a definite diagnosis. Treat- audience member asked about how ment varies from therapeutic nihilism performance status – a measure of a to radical combined-modality treat- person’s ability to perform everyday ment approaches” (J Thorac Dis. 2013 activities – affects the eligibility for CHEST Board Review 2018 Dec;5[6]:E254-307). surgery. August 10-19 | Austin, Texas Surgical resection is a contro- “It’s quite common for low per- CRITICAL CARE PEDIATRIC PULMONARY PULMONARY versial treatment for MPM, Dr. formance status to exclude someone AUGUST 10-13 AUGUST 10-13 AUGUST 15-19 Soukiasian said. It is “based on the from surgery,” the audience member principle of macroscopic resection said. of solid tumor with adjuvant therapy Dr. Soukiasian acknowledged that to treat micrometastatic disease,” he performance status was not included explained. “Cancer-directed surgery in the data. The study was focused for MPM is usually reserved for lo- on the gap between guidelines and calized epithelial type histology and real-world practice, and generated Mark your is associated with a 5-year survival questions of why and about the CALENDARS rate of 15%.” potential opportunity for improved CHEST 2018 starts For the new study, the investiga- treatment of these patients. early this year. tors tracked 3,834 patients in the “Although our research does not National Cancer Database (2004- provide data or conclusions on qual- 2014) diagnosed with MPM clinical ity of life or cost, these topics will be stages I-III. Most had epithelioid important to address in follow-up MPM (69%), with sarcomatoid studies to elucidate possible barri- (17%) and mixed subtype (15%) ers in the treatment of MPM and Calendar subject to change. For most current course list and more making up the rest. They examined the initiation of future educational information, visit livelearning.chestnet.org. whether patient treatment complied opportunities for our patients,” Dr. with the National Comprehensive Soukiasian noted. Cancer Network (NCCN) guide- [email protected]

42 • JUNE 2018 • CHEST PHYSICIAN CRITICAL CARE COMMENTARY Diagnosis and management of Critical Illness-Related Corticosteroid Insufficiency (CIRCI): Updated guidelines 2017

BY STEPHEN M. PASTORES, MD, FCCP However, they acknowledged that a delta cortisol less than or equal to 9 µg/dL at 60 minutes after Dr. Pastores is Program ritical illness-related corticosteroid insuffi- administration of 250 µg of cosyntropin and a ran- Director, Critical Care ciency (CIRCI) was first introduced in 2008 dom plasma cortisol level of less than or equal to 10 Medicine, Vice-Chair of Cby a task force convened by the Society of µg/dL may be used by clinicians. They also suggest- Education, Department Critical Care Medicine (SCCM) to describe the ed against the use of plasma-free cortisol or salivary of Anesthesiology and impairment of the hypothalamic-pituitary-adre- cortisol level over plasma total cortisol. Unequivo- Critical Care Medicine, nal (HPA) axis during critical illness (Marik PE, cally, the panel acknowledged the limitations of the Memorial Sloan Ketter- et al. Crit Care Med. 2008;36(6):1937). current diagnostic tools to identify patients at risk ing Cancer Center; Pro- CIRCI is characterized by dysregulated systemic for CIRCI and how this may impact the way corti- fessor of Medicine and inflammation resulting from inadequate cellular costeroids are used in clinical practice. Anesthesiology, Weill corticosteroid activity for the severity of the pa- Cornell Medical College, tient’s critical illness. Signs and symptoms of CIRCI Sepsis and Septic Shock New York, NY. include hypotension poorly responsive to fluids, Despite dozens of observational studies and ran- decreased sensitivity to catecholamines, fever, al- domized controlled trials (RCTs), the benefit-to-risk tered mental status, hypoxemia, and laboratory ab- ratio of corticosteroids to treat sepsis and septic hours in APROCCHSS and given as a continuous normalities (hyponatremia, hypoglycemia). CIRCI shock remains controversial with systematic reviews infusion of 200 mg/day for 7 days or until death or can occur in sepsis and septic shock, acute respira- and meta-analyses either confirming (Annane D, et ICU discharge in ADRENAL. It is noteworthy that tory distress syndrome (ARDS), severe communi- al. Cochrane Database Syst Rev. 2015;12:CD002243) the subjects in ADRENAL had a higher rate of sur- ty-acquired pneumonia, and non-septic systemic or refuting (Volbeda M, et al. Intensive Care Med. gical admissions (31.5% vs 18.3%), a lower rate of inflammatory response syndrome (SIRS) states as- 2015;41:1220) the survival benefit of corticosteroids. renal-replacement therapy (12.7% vs 27.6%), lower sociated with shock, such as trauma, cardiac arrest, Based on the best available data, the task force rec- rates of lung infection (35.2% vs 59.4%) and uri- and cardiopulmonary bypass surgery. Three major ommended using corticosteroids in adult patients nary tract infection (7.5% vs 17.7%), and a higher pathophysiologic events constitute CIRCI: dysregu- with septic shock that is not responsive to fluids and rate of abdominal infection (25.5% vs 11.5%). Pa- lation of the HPA axis, altered cortisol metabolism, moderate-to-high vasopressor therapy but not for tients in APROCCHSS had high Sequential Organ and tissue resistance to glucocorticoids (Annane D, patients with sepsis who are not in shock. Intrave- Failure Assessment (SOFA) scores and Simplified Pastores SM, et al. Crit Care Med. 2017;45(12):2089; nous hydrocortisone less than or equal to 400 mg/ Acute Physiology Score (SAPS) II values suggesting Intensive Care Med. 2017;43(12):1781). Plasma day for at least greater than or equal to 3 days at full a sicker population and probably accounting for clearance of cortisol is markedly reduced during dose was recommended rather than high dose and the higher mortality rates in both hydrocortisone critical illness, due to suppressed expression and short course. The panel emphasized the consistent and placebo groups compared with ADRENAL. In activity of the primary cortisol-metabolizing en- benefit of low-dose corticosteroids on shock rever- view of the current evidence, the author believes zymes in the liver and kidney. Furthermore, despite sal and the low risk for superinfection. that survival benefit with corticosteroids in septic the elevated cortisol levels during critical illness, Since the publication of the updated CIRCI shock is dependent on several factors: dose (hydro- tissue resistance to glucocorticoids is believed to guidelines, two large RCTs (more than 5,000 com- cortisone less than or equal to 400 mg/day), longer occur because of insufficient glucocorticoid recep- bined patients) of low-dose corticosteroids for duration (at least 3 or more days), and severity of tor alpha-mediated anti-inflammatory activity. septic shock were reported: The Adjunctive Corti- sepsis. “The more severe the sepsis, the more sep- costeroid Treatment in Critically Ill Patients with tic shock the patient is in, the more likely it is for Reviewing the Updated Guidelines Septic Shock (ADRENAL) trial (Venkatesh B, et corticosteroids to help these patients get off vaso- Against this background of recent insights into al. N Engl J Med. 2018;378:797) and the Activated pressors and mechanical ventilation. I consider the the understanding of CIRCI and the widespread Protein C and Corticosteroids for Human Septic addition of fludrocortisone as optional.” use of corticosteroids in critically ill patients, a Shock (APROCCHSS) trial (Annane D, et al. N panel of experts of the SCCM and the Europe- Engl J Med. 2018;378:809). The ADRENAL trial ARDS an Society of Intensive Care Medicine (ESICM) included 3,800 patients in five countries and did In patients with early moderate-to-severe ARDS recently updated the guidelines for the diag- not show a significant difference in 90-day mor- (PaO2/FIO2 of less than or equal to 200 and within nosis and management of CIRCI in a two-part tality between the hydrocortisone and the placebo 14 days of onset), the task force recommended the guideline document (Annane D, Pastores SM, groups (27.9% vs 28.8%, respectively, P=.50). In use of IV methylprednisolone in a dose of 1 mg/kg/ et al. Crit Care Med. 2017;45(12):2078; Inten- contrast, the APROCCHSS trial, involving 1,241 day followed by slow tapering over 2 weeks to pre- sive Care Med. 2017;43(12):1751; Pastores SM, patients, reported a lower 90-day mortality in the vent the development of a rebound inflammatory Annane D, et al. Crit Care Med. 2018;46(1):146; hydrocortisone-fludrocortisone group compared response, and adherence to infection surveillance. Pastores SM, Annane D, et al. Intensive Care with the placebo group (43% vs 49.1%, P=.03). In patients with major trauma and influenza, the Med. 2018;44(4):474). For this update, the multi- Both trials showed a beneficial effect of hydrocor- panel suggested against the use of corticosteroids. disciplinary task force used the Grading of Rec- tisone in the number of vasopressor-free and me- Corticosteroids were recommended for severe CAP ommendations Assessment, Development, and chanical ventilation-free days. Blood transfusions (less than or equal to 400 mg/day of IV hydrocor- Evaluation (GRADE) methodology to formulate were less common in the hydrocortisone group tisone or equivalent for 5 to 7 days), meningitis, actionable recommendations. The recommenda- than those who received placebo in ADRENAL. adults undergoing cardiopulmonary bypass surgery, tions and their strength (strong or conditional) Besides hyperglycemia, which was more common and adults who suffer a cardiac arrest. The task required the agreement of at least 80% of the in the hydrocortisone group in both trials, the force highlighted that the quality of evidence for use members. The task force spent considerable time overall rates of adverse events were relatively low. of corticosteroids in these disease states was often and spirited discussions on the diagnosis of CIR- It is important to highlight the key differences low and that additional well-designed RCTs with CI and the use of corticosteroids for clinical dis- between these two RCTs. First, in APROCCHSS, carefully selected patients were warranted. orders that most clinicians associate with CIRCI: oral fludrocortisone (50-μg once daily for 7 days) To conclude, as with any clinical practice guide- sepsis/septic shock, ARDS, and major trauma. was added to hydrocortisone to provide additional line, the task force reiterated that the updated mineralocorticoid potency, although a previous CIRCI guidelines were not intended to define a Diagnosis study had shown no added benefit (Annane D, et standard of care and should not be interpreted as The task force was unable to reach agreement al. JAMA. 2010;303:341). Second, hydrocortisone prescribing an exclusive course of management. on a single test that can reliably diagnose CIRCI. was administered as a 50-mg IV bolus every 6 Good clinical judgment should always prevail!

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2018 • 43 CRITICAL CARE MEDICINE Seven days of antibiotics is enough BY MICHELE G. SULLIVAN which is consistent with everything we know MDedge News about natural selection, the driver of antibiot- ic resistance,” he noted. “In only a few types of MADRID – Seven days of antibiotic therapy infections does resistance emerge at the site of was just as effective as 14 days for patients with infection; rather, resistance typically emerges off gram-negative bacteremias. target, among colonizing flora away from the site The shorter course was associated with similar of infection. Thus, all that is achieved by treat- cure rates and a faster return to normal activities, ing an infection with antibiotics for longer than Dafna Yahav, MD, said at the European Society the patient has symptoms is increased selective of Clinical Microbiology and Infectious Diseases pressure driving antibiotic resistance among our annual congress. colonizing microbial flora.” “In patients hospitalized with gram-negative The European Union and Infectious Diseases bacteremia and sepsis, a course of 7 antibiotic Society of America and the Society for Health- days was not inferior to 14 days, and resulted in care of America have all recently a more rapid return to baseline activity, “ said Dr. updated their antibiotic stewardship guidelines to Yahav of the Rabin Medical Center, Petah Tikva, include a strong recommendation for the shortest Israel. “This could lead to a change in accepted effective duration of antimicrobial therapy. management algorithms and shortened antibiotic However, most of the supporting data were therapy. Potentially, though we did not show this drawn from randomized, controlled studies of in our trial, it may lead to reduced cost, reduced patients with lung, skin, and kidney infections. development of resistance, and fewer adverse Short-course treatments have not been adequate- events.” ly studied in bacteremia patients, Dr. Yahav said. During the past few years, a new dogma has The aim of her study, which was investigator emerged in antibiotic treatment paradigms, initiated and received no external funding, was to she said: Shorter is better. Brad Spellberg, MD, demonstrate the noninferiority of 7 days of anti- described this concept in his 2016 editorial in biotic therapy, compared with 14 days, in patients JAMA Internal Medicine, “The new antibiotic with bacteremia arising from gram-negative in- mantra” (Sep 1;176[9]:1254-5). fections. In it, Dr. Spellberg, of the University of South- The randomized, open-label study comprised

ern California, Los Angeles, addressed the long- 604 patients in three hospitals: two in Israel and Michele G. Sullivan/MDedge News held view that a full 10- or 14-day course of one in Italy. Patients were eligible if they had an For gram-negative bacteremia and sepsis, 7 days of antibiotics was necessary to decrease the risk of aerobic gram-negative bacteremia of any infec- antibiotics was not inferior to 14 days, noted creating a resistant strain, even if clinical symp- tion source that was either community or hospi- Dr. Dafna Yahav. toms were long resolved. tal acquired. The medication choice was left up to However, he noted, there is little evidence sup- the treating physician. Patients were assessed at days were significantly less in the 7-day group, (5 porting the idea that longer courses suppress the discharge, and at days 30 and 90. days) than in the 14-day group (10 days). Patients rise of resistance – and, in fact, some data sup- The primary outcome was a composite 90-day in the short-duration group returned to their port the opposite. endpoint of all-cause mortality, clinical failure normal activities a day earlier than those in the “To the contrary, specifically for pneumonia, (relapse, new local complications, or distant longer-term group (2 days vs. 3 days), a differ- studies have shown that longer courses of therapy complications), and readmission or hospital stay ence that was statistically significant. result in more emergence of antibiotic resistance, longer than 14 days. There were a number of sec- The total hospital stay from randomization to ondary outcomes, including new infection, emer- day 90 was only half a day shorter in the short- gence of antibiotic resistance, total hospital and term group (mean, 3 days vs. 3.5 days). That was total antibiotic days, time to return to baseline not a significant finding. activity, and adverse events. There were some differences in adverse events, The cohort was a mean of 71 years old. About although none was statistically significant. The 60% were functionally independent, and the short-duration arm had slightly more cases of mean Charlson comorbidity score was 2. Most kidney injury (0.5%), fewer cases of liver function of the infections (90%) were nosocomial. The abnormalities (–1.5%), and half as many rashes urinary tract was the largest source of infection (two vs. four). There were two cases of Clostridium (69%). Other sources were abdominal, respirato- difficile in the short-use arm and one in the long- ry, central venous catheter, and skin or soft tissue. use arm, also not a significant difference. Escherichia coli was the most common infective A subgroup analysis looked at outcomes among organism (62%), followed by Klebsiella species the different sources of infection (urinary tract and Enterobacteriaceae. A small number of pa- vs. other), whether empirical antibiotics were tients had Acinetobacter and Pseudomonas infec- used, and whether the induced resistance was tions. multidrug or non-multidrug. All of those differ- In the intent-to-treat analysis, the primary ences hovered close to the null, but generally fa- composite outcome of all-cause mortality or ex- vored short antibiotic treatment, Dr. Yahav noted. tended hospital stay occurred in 46% of the 7-day “I would conclude from these data that it is group and 50% of the 14-day group – not signifi- generally safe to stop antibiotics after 7 days of cantly different. The results were nearly identical covering antibiotics for gram-negative bacteremia in the per-protocol analysis (46% vs. 49.6%). patients, if they are hemodynamically stable and Likewise, none of the secondary outcomes nonneutropenic at 7 days, and have no uncon- posted a significant difference in favor of one trolled source of infection,” she concluded. treatment arm, including relapse (2.9% vs. 2.7%) The investigator-initiated study had no outside and resistance development (10.8% vs. 9.7%). funding.

BrianAJackson/Thinkstock Dr. Yahav pointed out that total antibiotic-use [email protected]

48 • JUNE 2018 • CHEST PHYSICIAN CHPH_49.indd 1 5/17/2018 2:00:01 PM CRITICAL CARE MEDICINE Adding vasopressin in distributive shock may cut AF risk BY ANDREW D. BOWSER may translate into a reduction in ad- rolled a total of 3,088 patients with study is one of the first to directly MDedge News verse events, including atrial fibril- distributive shock, a condition in compare the combination of va- lation, injury to other organs, and which widespread vasodilation sopressin and catecholamine to n patients with distributive death,” they said in their report. lowers vascular resistances and catecholamines alone, which is the shock, the risk of atrial fibrilla- Dr. McIntyre and his colleagues mean arterial pressure. Sepsis is its current standard of care, the inves- Ition may be lower when vaso- included 23 trials that had en- most common cause. The current tigators wrote. pressin is administered along with catecholamine vasopressors, results of a recent systematic review and meta-analysis suggest. The relative risk of atrial fibril- lation was reduced for the com- bination of vasopressin and catecholamines versus the current standard of care, which is catechol- amines alone, according to study results published in JAMA. Beyond atrial fibrillation, how- ever, findings of the meta-analysis were consistent with regard to oth- er endpoints, including mortality, according to William F. McIntyre, MD, of McMaster University, Hamilton, Ont., and his coinvesti- gators.

The current study is one of the first to directly compare the combination of vasopressin and catecholamine to catecholamines alone, which is the current standard of care, wrote William F. McIntyre, MD, of McMaster Univeristy, and his coinvestigators, in their paper published in JAMA.

Mortality was lower with the combination approach when all studies were analyzed together. Yet, when the analysis was limited to the studies with the lowest risk of bias, the difference in mortality versus catecholamines alone was not statistically significant, investi- gators said. Nevertheless, the meta-analysis does suggest that vasopressin may offer a clinical advantage regarding prevention of atrial fibrillation in patients with distributive shock, a frequently fatal condition most of- ten seen in patients with sepsis. Vasopressin is an endogenous peptide hormone that decreases stimulation of certain myocardial receptors associated with cardiac ar- rhythmia, the authors noted. “This, among other mechanisms,

50 • JUNE 2018 • CHEST PHYSICIAN They found that the administra- Pooled data showed administration of vasopressin along Mortality data were less consis- tion of vasopressin was associated with catecholamines was associated with an 11% relative tent, they said. with a significant 23% reduction Pooled data showed administra- in risk of atrial fibrillation. reduction in mortality, according to the investigators. tion of vasopressin along with cat- “The absolute effect is that 68 echolamines was associated with fewer people per 1,000 patients will an 11% relative reduction in mor- experience atrial fibrillation when and his coauthors said of the results. idence, they said, noting that two tality. In absolute terms, 45 lives vasopressin is added to catecholami- The atrial fibrillation finding separate sensitivity analyses con- would be saved for every 1,000 pa- nergic vasopressors,” Dr. McIntyre was judged to be high-quality ev- firmed the benefit. Continued on following page

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2018 • 51 Continued from previous page Studies show patients with dis- help raise mean arterial pressure disclosures related to Tenax Ther- tients receiving vasopressin, they tributive shock have a relative to target or adding vasopressin apeutics, Orion Pharma, Ferring noted. vasopressin deficiency, providing to decrease the dosage of norepi- Pharmaceuticals, GlaxoSmithKline, However, the mortality findings a theoretical basis for vasopressin nephrine. Those are considered and Bristol-Myers Squibb, among were different when the analysis was administration as part of care, inves- weak recommendations based on other entities. limited to the two studies with low tigators said. moderate quality of evidence, Dr. [email protected] risk of bias. That analysis yielded a The current Surviving Sepsis McIntyre and colleagues noted in relative risk of 0.96 and was not sta- guidelines suggest either adding their report. SOURCE: McIntyre WF et al. JAMA. tistically significant. vasopressin to norepinephrine to Authors of the study reported 2018;319(18):1889-900.

52 • JUNE 2018 • CHEST PHYSICIAN NEWS FROM CHEST CHEST past president honored by AACN

urtis Sessler, MD, FCCP, Visionary Leadership Awards, it mission, vision, and values. Richmond. He also serves as di- has been honored with the recognizes significant contributions Dr. Sessler is the Orhan Muren rector of VCU’s Center for Adult CAmerican Association of Crit- that influence high-acuity and Distinguished Professor of Medi- Critical Care, medical director of ical-Care Nurses (AACN) Pioneer- critical care nursing regionally and cine at the Virginia Commonwealth critical care, and medical director ing Spirit Award. As one of AACN’s nationally and relates to AACN’s University (VCU) Health System, of the medical respiratory ICU. He has enjoyed a long career in critical care medicine focusing on patient care, teaching, clinical research, and advancing collaborative care of criti- cally ill patients. He has a long-term collaboration with research col- leagues from VCU School of Nurs- ing, studying a variety of clinical problems, including ICU sedation,

DR. SESSLER

prevention of nosocomial infection, mechanical ventilation, and proce- dural competency. Under his lead- ership, the interprofessional group created and validated the Richmond Agitation-Sedation Scale, which is used worldwide to help improve the management of pain, sedation, and delirium in critically ill patients. Besides serving as CHEST Pres- ident in 2014-2015, Dr. Sessler has held numerous leadership roles at CHEST and has been recognized for his research, leadership, and service with many honors, including the 2017 Distinguished CHEST Educator Award, 2016 Art Wheeler Memorial Lecture Award, and 2010 Roger C. Bone Memorial Lecture Award. Dr. Sessler has also participated in many activities of the Critical Care Societies Collaborative, which links the leaders of AACN, CHEST, the American Thoracic Society, and the Society of Critical Care Medicine. This group has addressed numerous issues central to critical care, such as research priorities, workforce short- age, clinical competencies, Choosing Wisely in Critical Care, and, most recently, burnout among critical care health-care professionals. CHEST congratulates Dr. Sessler on this distinguished honor!

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2018 • 53 NEWS FROM CHEST NAMDRC legislative and regulatory agenda once again focuses on patient access

BY PHIL PORTE standards of care, peer reviewed is) a challenge, as the term does not Spin forward to 2018 and numer- Executive Director, NAMDRC literature, etc. Even defining a “re- appear in the medical literature or ous realities come into play. Physi- spiratory assist device” was (and still in FDA vernacular. cians still struggle with the concept NAMDRC’s Mission Statement declares, “NAMDRC’s primary mis- sion is to improve access to quality care for patients with respiratory disease by removing regulatory and legislative barriers to appropriate treatment.” This mission is clear as we review our legislative and reg- ulatory agenda on an ongoing and continuing basis.

Home Mechanical Ventilation: Close to 20 years ago, HCFA (now CMS) was faced with an important reality: advances in technology

DR. PORTE related to home mechanical ven- tilation are triggering an expo- nential growth in availability of these life supporting devices, but a price would be paid. At that time, Medicare law was quite explicit, indicating that certain ventilators would be paid under a “frequent and substantial servicing” payment methodology, authorizing payment on an ongoing basis as long as the prescribing physician documented medical necessity. To circumvent that statutory reality, the agency created a new category of medical device – a respiratory assist device/ RAD – and declared that these de- vices are no longer ventilators and are now subject to capped rental rules and regulations. NAMDRC was determined to work within the system, but road- blocks were consistently encoun- tered, ie, contractor policies that did not reflect current medical

54 • JUNE 2018 • CHEST PHYSICIAN NEWS FROM CHEST of RADs without a definitive, NAMDRC was determined to work within the system, but need of the patient, changes in poli- consistent definition and no FDA roadblocks were consistently encountered, such as contractor cy are necessary. While CMS clearly language to guide usage. Today, it has the authority to act to improve is easier to secure a ventilator if a policies that did not reflect current medical standards of care. policy and match clinical need to physician documents the patient patient access, years and years of experiences some level of respira- rate. Because of that dichotomy, the If one takes the approach that a back and forth have signaled a defi- tory failure than it is to prescribe growth of life support ventilator us- device should be paired with the ac- nite unwillingness of the agency to a simple ventilator with a back-up age is well documented. tual clinical characteristics/medical Continued on following page

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2018 • 55 NEWS FROM CHEST

Continued from previous page Senate Legislative Counsel to craft home oxygen. Pondering the reality patients and physicians experience move in that direction; therefore, legislative language to address the of a segment of pulmonary medicine ongoing frustration trying to match the only genuine recourse is to seek myriad of issues associated with that has seen dramatic technological a patient’s needs with an oxygen sys- legislative relief. home mechanical ventilation. improvements and enhancements tem that reflects the patient’s needs. NAMDRC is working closely with over the past 30-plus years, coupled It’s a challenge to even consider the United States Senate, particular- Home Oxygen Therapy: In 1986, with a payment system that is stuck where to start a reasonable discus- ly the Finance Committee, Senator Congress revamped the statute gov- with e-cylinders and competitive sion of home oxygen therapy. While Cassidy (R-LA), and the Office of erning coverage and payment of bidding, it is no wonder that both the concept of supplemental oxygen is well accepted, the actual clinical evidence relies heavily on a very small number of studies. While vir- tually no one challenges the concept of the therapy, the actual science has progressed modestly in 30-plus years. But the technology surround- ing oxygen therapy has become an industry all to itself. There are NAMDRC is working with the Senate Finance Committee, Senator Cassidy (R-LA), and the Office of Senate Legislative Counsel to craft legislative language to address the myriad of issues associated with home mechanical ventilation.

concentrators, portable oxygen con- centrators, liquid systems, transfill systems, transtracheal oxygen thera- py, and so on. Add to the environment the grow- ing demand for high flow systems that would deliver continuous flow oxygen at rates in excess of 4 L/min, and you begin to realize that the current payment system is a barrier to access. After all, the current pay- ment system has problematic char- acteristics:

1. A flawed competitive bidding methodology; 2. Payment tied to liter flow pegged at a baseline of 2 L/min, regard- less of actual patient need; 3. The major shift from a “delivery model” of care to a nondelivery model that reflects these newer technologies; 4. Virtual disappearance of liquid system availability as an option for physicians/patients; 5. The total failure of CMS to mon- itor, let alone act on, patient con- cerns.

Again, taking the NAMDRC Mis- sion Statement into context, NAM- DRC is working with all the key societies to craft a broad strategy to address these problems, acknowl- edging that it will likely take a mix of legislative and regulatory actions to bring home oxygen therapy into the 21st century, let alone to reflect realities of care in 2018.

56 • JUNE 2018 • CHEST PHYSICIAN NEWS FROM CHEST

PULMONARY PERSPECTIVES® From ECMO to post-ICU discharge clinics BY JOHN MADARA, MD, AND contributes to long-term cognitive remains sedated with MICHAEL BARAM, MD, FCCP deficits. anti-anxiety, analgesics, Once these critically ill patients and amnesic medica- s extracorporeal membrane are discharged from the hospital, tions throughout their oxygenation (ECMO) is uti- they are left with a multitude of ICU stay, the family Dr. Madara and Alized more frequently,1 there long-term medical, psychological, members and caregivers Dr. Baram (pictured) will be more survivors of prolonged and cognitive deficits. Post-Inten- of the patient remain at are with the Division hospitalizations with new challeng- sive Care Unit Syndrome (PICS) bedside, often for hours, of Pulmonary Care, es that they will need to face. As is becoming more recognized as days, or weeks on end. Department of Medicine, health-care providers, we must be a group of health problems that It is sometimes difficult Jefferson University, Phil- involved with establishing a system patients suffer after a prolonged to explain the nuisances, adelphia, Pennsylvania. to deal with the longitudinal effects course of treatment in the ICU. risks, and details of the of the expanding treatment options. Recent studies have shown the care of ECMO patients Some of the interventions to im- long-term negative deficits in to other health-care practitioners, To further hospital-based strat- prove post-ECMO quality of life critically ill patients. Iwashyna yet alone family members who are egies to reduce PICS, there have require hospital-based initiatives but and colleagues demonstrated that undergoing one of the most stress- been several interventions pro- also should incorporate post-hospi- survivors of severe sepsis revealed ful periods of their life, leaving posed and implemented to decrease tal discharge care. increased rates of cognitive im- anxiety amongst decision makers. these long-term negative outcomes. The ECMO patient population pairments and functional disabil- An article published in 2016,10 Daily rounds are performed to represents some of the sickest ities.6 The same phenomena that demonstrated that the long-term identify who may benefit from patients in the hospital. With the patients with septic shock suffer negative outcomes affect not only physical therapy, and patients are average ECMO patient having are seen in ECMO survivors, as the patients but their caregivers, receiving early treatments. Em- an APACHE II score of greater well. ECMO survivors are fre- as well. Primary caregivers of crit- phasis is placed on minimizing than 25, this carries an estimated quently left with residual cogni- ically ill patient survivors suffered sedation, as well as daily sedation mortality rate of at least 55%.2, 3 tive, psychological, and medical from high rates of depression that holidays to decrease the amount When the decision is made that complications. persisted for the year of the study. of pharmacologics that patients the patient no longer needs ECMO It is known that patients who It has been shown that including are receiving. Family members are support and is removed from the survive long ICU stays suffer from family members in daily discus- incorporated into rounds and up- circuit, there still remains a possi- PICS, and patients who survive sions and scheduling frequent dated daily to decrease uncertainty bility of a multitude of complica- ECMO are at high risk for devel- family meetings helps to avoid con- in their loved one’s care. Time is tions during their hospitalization. oping complications, but there fusion and stress. Continued on following page One of the more common occur- is a dirth of literature examining rences after ECMO is a continued the long-term outcomes in these systemic inflammatory response patients. High levels of sedation syndrome (SIRS).4 A meta-analysis are required while on pump in- published in 2013 reported fre- creases delirium that is a known quent ECMO complications, such risk factor for cognitive impair- as renal failure requiring hemodial- ments in the long term. Prolonged ysis (52%), pneumonia (33%), liver bedrest, paralytics, and steroids disease (16%), and GI bleeding are frequently needed for these (7%).5 Many patients require tra- patients, all risk factors in devel- cheostomy for prolonged mechan- oping ICU-acquired weakness. An ical ventilation and percutaneous article published by Schmidt and enteral access. There are high rates colleagues7 in 2013 showed that of critical care-related myopathies survivors of ECMO had decreased

and neuropathies that usually re- SF-36 scores, which is a single NEW for Lung Cancer: A Multidisciplinary Course for quire prolonged treatment courses measure patient health-related 2018 Pulmonologists Covering Current Paradigms of physical therapy and occupation- quality of life questionnaire, indi- for Diagnosis and Management al therapy. This is not to mention cating worse quality of life when Attend to: one of the more dreaded compli- compared with the general popu- Pulmonologists, 8 n Discuss the current multidiscipline knowledge base regarding cations of prolonged ICU stays— lation. Hodgson and colleagues interventional lung cancer diagnosis options for patients with early and delirium, leading to posttraumatic also noted a similar decrease in pulmonologists, critical late-stage lung cancer. stress disorder (PTSD). Due to the SF-36 scores in ECMO survivors care physicians/ n pharmacokinetics of the ECMO at 8 months postdischarge. Beyond intensivists, pulmonary Develop hands-on skills directed toward physiologic evaluation and critical care fellows, of patients with lung cancer, EBUS, navigational bronchoscopy, circuit and high levels of discom- the cognitive and quality of life hospitalists, advanced pleurx catheters, and malignant effusion pleurodesis. fort, higher amounts of opioids and impairments, significant long- practice providers, n Capture new ideas on how to optimize the multidisciplinary benzodiazepines are required when term psychiatric issues develop. radiologists, oncologists, conference approach to outstanding lung cancer care. pathologists, and compared with the general critical A case-series published in 2013 n Interpret multimodality images in the care of patients with lung palliative care providers care population. It is common to showed an extremely high preva- cancer, and utilize newer tumor markers for oncologic planning. are encouraged to see patients receiving high doses of lence (71%) of mental disorders in attend. n Optimize your interdisciplinary skills with regards to lung cancer 9 continuous IV infusions of loraze- ECMO survivors. diagnosis, therapy, and patient care. pam, fentanyl, and ketamine. ICU During a long and complicated delirium leads to increased days in hospital course for these patients, Complete Details | chestnet.org/live-learning the ICU, adds the additional risks there is often a major component of developing complications seen to the care of the patient that goes from long hospitalizations, and overlooked. While the patient

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2018 • 57 NEWS FROM CHEST

Continued from previous page are having more patients survive addressed directly in clinic, the goal ical Care Medicine (SCCM) has spent to make sure medications critical illness, our focus should is to refer patients to specialists who embraced the idea of treating PICS. are reconciled, specialist recom- broaden on how to deal with the can provide long-term care. In many As intensivists we embrace the idea mendations are incorporated, and complications that our survivors ways, the goal of the clinic is to offer of helping our survivors regain in- then patients are discharged from are left with. We can work together patients recognition/substantiation of dependence in life, support family the hospital with follow-up plans to help our patients and their fam- what they have gone through (which members through their needs, and usually to their primary care phy- ilies in their most vulnerable time is a plus in itself) but also refers pa- help fulfill our own need to see sur- sician. Historically, the intensivist in their lives. Patients should be tients to subspecialty services that vivors achieve a higher quality of life. role in caring for the patient classi- provided an ongoing service after our university program can provide. cally ends there—this is changing. they leave the ICU and focus on Each person in the clinic has a References The newest literature about PICS improving their quality of life. unique role. The physician presence 1. Extracorporeal Life Support Organization, supports longer engagement by in- Models for a post-ICU clinic vary is to describe to the patient and ECLS Registry Report International Summary, January, 2017. tensivists. Intensivists are the ones per site. But the goals of these clinics their loved ones the ongoing medi- 2. Lin CY, Tsai FC, Tian YC, et al. Evaluation who have identified this is an issue are to help bridge the gaps as patients cal complications from the hospital- of outcome scoring systems for patients on and increasingly are involved with try to rebuild their lives. A prolonged ization. Families are informed that extracorporeal membrane oxygenation. Ann the patient care and family after critical illness can leave a devastated cognitive and psychological prob- Thoracic Surg. 2007;84:1256-62. discharge. life that needs to be restructured. Us- lems are common in this particular 3. Natt BS, Desai H, Singh N, et al. Extracor- poreal membrane oxygenation for ARDS: Na- ing multiple services, the goal of the condition. A critical care pharma- tional trends in the United States 2008-2012. Post-ICU discharge clinic clinic is to recognize the difficulties cist can review lists of medications Respir Care. 2016;61(10):1293-98. We have begun a post-ICU dis- of recovering from critical care. In- and doses to ensure no problems 4. Thangappan K, Cavarocchi NC, Baram M, charge clinic at our institution ternists often do not realize the stress occurred in the transition to out- et al. Systemic inflammatory response syn- drome (SIRS) after extracorporeal membrane to start screening our patient that surviving ICU can leave. Some patient. Physical and occupational oxygenation (ECMO): Incidence, risks, and population for the cognitive, psy- people look at surviving ARDS as a therapy are present to screen for survivals. Heart Lung. 2016;45;449-53. chological, and medical disease miracle, while others carry financial, both neuromuscular and cognitive 5. Zangrillo A, Landoni G, Biondi-Zoccai G, et processes that are common, yet social, physical, and emotional scars defects and provide tips and exercis- al. A meta-analysis of complications and mor- underrecognized. Incorporating as indicated by SF-36 scores. The es to help rebuild patients’ strength tality of extracorporeal membrane oxygen- ation. Crit Care Resusc. 2013;15(3);172-78. the health-care providers who care goal of the clinic is to acknowledge of muscle and mind. We also in- 6. Iwashyna TJ, Ely EW, Smith DM, et al. for the critically ill patients in the deficits left by a prolonged stay with volve one of the most important Long-term cognitive impairment and function- hospital will help give us an under- multidisciplinary services being in- parts of the patients care while in al disability among survivors of severe sepsis. standing of what challenges and volved. There are screening tools to the ICU, critical care-trained nurses JAMA. 2010;304(16):1787-94. difficulties these patients may face identify PTSD; rehabilitation medi- and nurse practitioners. These are 7. Schmidt M, Zogheib E, Rozé H, et al. The once discharged. A lot of focus in cine specialists; and pharmacists to the members of the team who the PRESERVE Mortality Risk Score and analysis of long-term outcomes after extracorporeal the medical literature is on mor- help address issues. Although many patients and families are always hap- membrane oxygenation for severe acute re- tality benefits. We argue that if we of the identified issues will not be piest to see. Also, seeing patients in spiratory distress syndrome. Intensive Care the outpatient setting, after signifi- Med. 2013;39(10):1704-13. cant recovery has occurred, comes 8. Hodgson CL, Hayes K, Everard T, et al. Long-term quality of life in patients with as a significant morale booster for acute respiratory distress syndrome re- the health-care practitioners who quiring extracorporeal membrane oxygen- deal with so much stress and anxiety ation for refractory hypoxemia. Crit Care. on a daily basis. The team feels grat- 2012;16(5):R202. ified that all of their energy spent 9. Risnes I, Heldal A, Wagner K, et al. Psychiatric outcome after severe cardiore- in the ICU yields very meaningful spiratory failure treated with extracorporeal outcomes. membrane oxygenation: A case-series. Psy- Utilizing the expertise of multiple chosomatics. 2013;54(5): 418-27. disciplines, our post-ICU clinic is 10. Cameron JI, Chu LM, Matte A, et al. One- Year outcomes in caregivers of critically ill to help ICU survivors gain control patients. N Engl J Med. 2016;374:1831-41. over their lives. The Society of Crit- Board Review 2018 August 10-19 | Austin, Texas

How will you prep for your 2018 board exams? Let CHEST help you prepare live and in-person for next year’s pulmonary, This month in the critical care, and pediatric pulmonary exams ® with our comprehensive review courses. journal CHEST As always, CHEST board review courses offer thorough exam prep you can put to the test. Editor’s Picks

BY RICHARD S. IRWIN, MD, Original Investigations MASTER FCCP Beta-Blockers in COPD: A Cohort Editor in Chief, the journal CHEST® Study From the CRITICAL CARE PEDIATRIC PULMONARY PULMONARY TONADO Research Program. AUGUST 10-13 AUGUST 10-13 AUGUST 15-19 Giants in Chest Medicine By Dr. F. Maltais, et al. Dirkje S. Postma, MD, PhD. Reserve Your Seat By Dr. Huib A. M. Kerstjens. The Risk of TB in Patients With boardreview.chestnet.org Type 2 Diabetes Initiating Met- formin vs Sulfonylurea Treatment. By Dr. S-W Pan, et al.

58 • JUNE 2018 • CHEST PHYSICIAN NEWS FROM CHEST

CHEST NetWorks Sinus rhythm, physician burnout, difficult-to-treat pulmonary infections, and more Cardiovascular Medicine Engl J Med. 2008;359[17]:1778-85; AFib burden, increased 6MWD, complications - the consequence and Surgery Hunter et al. Circ Arrhythm Electro- and improved LVEF with ablation. of the perilous imbalance between Sinus rhythm is superior physiol. 2014[1];7:31-8; DiBiase et al. Post-ablation patients received an- thrombosis and bleeding (Kirklin et for heart failure with Circulation. 2016;133[17]:1637-44). ticoagulation therapy for at least 6 al. JHLT 2017;36 atrial fibrillation The AFFIRM trial demonstrated a months. However, the study did have [10]:1080). It is a question that is frequently reduced mortality in those achieving some limitations: it was not blinded, In this context, asked: is rhythm or rate control sinus rhythm, but this was negated by there was no sham group, the sample the MOMEN- better for non-valvular atrial fibrilla- adverse effects from antiarrhythmic size was relatively small, and experi- TUM 3 trial tion (AFib)? The Atrial Fibrillation medications. The Catheter Ablation enced, high volume medical centers (Mehra et al. Follow-up Investigation of Rhythm versus Standard Conventional Ther- performed the procedures (N Engl J N Engl J Med. Management (AFFIRM) [N Engl J apy in Patients with Left Ventricular Med. 2018;378:468-469). CASTLE-AF 2018;378:1386), Med. 2002;347[23]:1825-33) and Rate Dysfunction and Atrial Fibrillation provides additional evidence for the a head-to-head Control versus Electrical Cardiover- (CASTLE-AF) trial examined the benefits of reducing the burden of study of the sion for Persistent Atrial Fibrillation benefits of rhythm control in patients AFib in congestive heart failure while DR. SHAH HeartMate 3 (RACE) (Van Gelder et al. N Engl J with AFib and CHF via pulmonary avoiding the detrimental effects of (newest durable Med. 2002;347[23]:1834-40] trials vein ablation (Marrouche et al. N antiarrhythmic medications. LVAD) vs HeartMate II (the first and demonstrated that the strategies are Engl J Med. 2018;378[5]:417-27). This David J. Nagel, MD, PhD most popular model) is a significant equivalent. However, AFib and heart was a multicenter, randomized, open Steering Committee Member milestone. In this trial, compared failure are concurrent in up to 50% label trial that included patients with with the HM II, patients with HM of patients (Santhanakrishnan et symptomatic AFib, an LVEF less than Follow-up study of 3 had fewer strokes and reoperation al. Circulation. 2016;133[5]:484-92) or equal to 35%, and at least NYHA HeartMate 3 LVAD for pump malfunction at 2 years. and several trials have shown that class II heart failure. Results demon- Since commercially available in Although rate of severe strokes was decreasing the time spent in AFib strated a significant reduction in 2008, enthusiasm for continuous similar in both arms, HM 3 has the leads to improved left ventricular all-cause mortality and heart failure flow LVADs as treatment of end- lowest rate of overall strokes or pump ejection fraction (LVEF), 6-minute hospitalizations in those undergoing stage heart failure has increased with thrombosis compared with other walk distance (6MWD), quality of ablation (NNT of 9). Exploratory over 22,000 implantations to date. continuous flow device trials thus life, and may even reduce mortality results also demonstrated reduced However, the 2-year survival rate of far. The rates of bleeding were the and hospitalizations (Khan et al. N cardiovascular death, decreased 70% is limited mostly by neurologic Continued on following page

Target Audience Advanced practice providers—such as nurse practitioners and physician assis- tants—and others practicing critical care or emergency medicine are encour- aged to attend.

August 24-26 Join us in San Antonio, Texas, for CHEST 2018, the Critical Skills for Critical Care premier education event in clinical chest medicine. A State-of-the-Art Update and Procedures for ICU Providers

Join an expert panel of nurse practitioners, physician assistants, This year’s Learn by Doing-focused program is built by and physicians for this state-of-the-art update in critical care expert faculty, and includes cutting-edge educational medicine for the whole team, featuring intensive, hands-on, sessions and hands-on opportunities designed with the and simulation-based experience in high-yield ultrasound, me- goal of learning through active participation. chanical ventilation, and airway management procedure skills. Join us for: Attend to: CHEST 2018 n Over 400 general and simulation sessions designed n Study the latest evidence in critical care medicine from has a new date a team-based perspective. with the whole critical care team in mind. OCTOBER 6-10 n Get hands-on training in ultrasound imaging and interpreta- n Full- and half-day postgraduate courses, featuring tion, mechanical ventilator modes and settings, and airway topics such as pulmonary hypertension, thoracic management for the critically ill patient. ultrasound, interstitial lung disease, and others.

n Participate in concise, evidence-based reviews, case-based n Inspirational keynote addresses focused on discussions, audience response, and expert debates in areas team-building and leadership. of clinical controversy. n Networking and meet-up opportunities, so you can View Complete Details visit with colleagues, faculty, and leadership from livelearning.chestnet.org/critical-care around the world.

CHEST Innovation, Simulation, and Training Center Learn More and Register Now | chestmeeting.chestnet.org

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2018 • 59 NEWS FROM CHEST

Continued from previous page safe and efficacious in small subsets of rates also increase health-care costs. ECPR when standard measures fail. same among the two models in this patients with CF and non-CF bron- Replacing a critical care nurse and A two-physician model has been de- trial, but given the low rate of pump chiectasis (Yagi, et al. BMC Infect Dis. primary care physician is estimated scribed; however, this resource may thrombosis, lower anticoagulation 2018;17[1]:558). Other inhaled ther- to cost at least $65,000 and $250,000, not always be available. Models have targets might be considered for the apies currently under investigation respectively. Drivers of burnout (ie, been described whereby advanced HM 3. Whether new modifications for use in CF pulmonary infections excessive workload, lack of work sup- practice providers (APPs) can be of the anticoagulation strategy reduce include fosfomycin/tobramycin inha- port, lack of work-home integration, key leaders in bleeding complications down the lation and a new inhaled glycopoly- loss of control and autonomy, and loss critical care and road remains to be seen. Current- mer (SNSP113) that disrupts bacterial of meaning from work) can be solved to initiate ECPR ly, the HM 3 is FDA-approved for biofilms. with organizational (ie, optimizing (Baeten, et al. bridge to transplant only, but, after In non-CF bronchiectasis, the electronic medical records) and in- Shifting the par- this trial, the indication will likely ex- evidence showing benefit for use dividual solutions (ie, prioritizing adigm towards pand to include destination therapy. of inhaled antibiotics is not as well tasks and mindfulness) (West, et al. J advanced prac- As technological breakthroughs lead established. A recent Cochrane re- Intern Med. 2018; Mar 5. doi: 10.1111/ tice providers to improved long-term patient surviv- view reported no evidence indicating joim.12752 [Epub ahead of print]). managing the al, we will inevitably be tending to a whether oral or inhaled antibiotics The American College of Chest coronary care growing number of LVAD implanted are better for non-CF bronchiectasis Physicians is part of the Critical Care DR. BAETEN units. SCAI 40th patients in our clinics and units. (Spencer, et al. Cochrane Database Societies Collaborative (CCSC), Annual Scientif- Nimesh S. Shah, MD, FCCP Syst Rev. 2018; Mar 27;3:CD012579). which was convened to acknowledge ic Sessions, May 10-13, 2017, New Steering Committee Member The heterogeneity of this population and raise awareness of burnout in Orleans, LA). Limiting factors for limits the ability to extend positive the healthcare community (Moss M, expedient cannulation can include Chest Infections findings in a small subgroup to the et al. Chest. 2016;150[1]:17-26). To the time for arrival of a perfusionist Inhaled antibiotics population at large; however, investi- combat this crisis, all stakeholders and/or ECMO-capable physician. for difficult-to-treat gation in this area is ongoing. in healthcare must work together to A multiprofessional approach, in- pulmonary infections Inhaled antibiotics have been stud- develop evidence-based strategies to cluding RTs, RNs, APPs, and MDs That the lungs constantly interface ied and used for decades in patients prevent and treat burnout. can be used to optimize appropriate with the environment is both a with chronic infections, and interest Saiprakash B. Venkateshiah, resources. In-house staff, including blessing and a in the development of even more MD, FCCP a respiratory therapist to secure and curse: while the efficacious and better-tolerated med- Vice-Chair manage the airway, nurses ensure ap- lungs are contin- ications is stronger than ever. Look Kathleen Doo, MD propriate compressions or operation ually exposed to for more information on this topic at Fellow-in-Training Member of a chest compression device, and environmental the upcoming CHEST 2018 Annual APPs to determine ECMO/ECPR pathogens and Meeting in San Antonio this October. Interprofessional Team candidacy in conjunction with the irritants, this Holly Keyt, MD When standard appropriate physician. While the also provides a Steering Committee Member ACLS fails for the physician is en route, ACLS contin- relatively unique hospitalized patient ues; however, the patient is prepped route for deliv- Clinical Pulmonary Medicine The current standard of care for the and draped and initial femoral ve- DR. KEYT ery of effective Prevent and treat management of hospitalized adult no-arterial access is achieved. This medications burnout now patients who suffer cardiac arrest facilitates rapid catheter exchange to directly to the site of disease. For Burnout is a work-related syndrome is standard ACLS. This population large peripheral VA-ECMO cannu- chronic lung diseases characterized that manifests with symptoms of emo- still suffers significant mortality las immediately upon arrival of the by recurrent infections, such as cys- tional exhaustion, even after the incorporation of ECMO physician. tic fibrosis (CF) and non-CF bron- depersonaliza- rapid response teams (Solomon et Robert Baeten II, PA-C chiectasis, this means delivery of tion, and a sense al. J Hosp Med. 2016 Jun;11(6):438- Steering Committee Member antimicrobials via inhalation. of reduced 45. doi: 10.1002/jhm.2554. Epub For individuals with CF, inhaled personal accom- 2016 Feb 1). Addition of technol- antibiotics are considered standard of plishment (Moss, ogy and mechanical support with INDEX OF care in the management of Pseudo- et al. Chest. chest compression devices has also monal infections. A recent Cochrane 2016;150[1]:17- demonstrated survival improve- ADVERTISERS review concluded that inhaled an- 26). In a 2018 ment (Couper, et al. Resuscitation. Actelion Pharmaceuticals US, Inc. ti-pseudomonal treatments improve Medscape sur- 2016 Jun;103:24-31. doi: 10.1016/j. Corporate 27 lung function and reduce exacerba- DR. DOO vey, critical care resuscitation.2016.03.004. Epub Allergan tion rates in this population (Smith, physicians had 2016 Mar 11). As ECMO becomes Avycaz 50-53 et al. Cochrane Database Syst Rev. the highest rates of burnout at 48%, more commonplace in various AstraZeneca 2018;Mar 30;3:CD001021). with pulmonary medicine physicians centers (Abrams and Brodie. Chest. Symbicort 9-13 Fasenra 34-37 What is the next frontier for in- reporting rates at 41% (Medscape. 2017;152[3]:639–649), expanding BEVESPI AEROSPHERE 44-47 haled antimicrobial therapies in CF? https://www.medscape.com/sites/ those programs to provide E-CPR Boehringer Ingelheim Pharmaceuticals, The focus is now on increasingly public/lifestyle/2018. Accessed Apr services has become the next step Inc. common and difficult-to-treat patho- 13, 2018). Studies show approximately in some facilities. ELSO registry re- OFEV 15-20 gens, such has methicillin-resistant 25% to 33% of critical care nurses ports demonstrate an approximate EKOS Corporation Corporate 64 Staphylococcus aureus (MRSA) and experience burnout (Shanafelt, et al. 40% survival rate for adults treated Genentech USA, Inc. nontuberculous mycobacteria (NTM). Arch Intern Med. 2012;172[18]:1377- with ECPR (Extracorporeal Life Esbriet 2-5 Vancomycin inhalation powder 1385). Resident and fellow trainees Support Organization. 2017. ECLS GSK group of companies (AeroVanc TM) is an inhaled dry also have a high prevalence (60%) of Registry Reports. Retrieved from BREO 61 powder version of vancomycin, which burnout (Dyrbye, et al. Acad Med. https://www.elso.org/Portals/0/Files/ Sanofi and Regeneron Pharmaceuticals, significantly reduced sputum MRSA 2014;89[3]:443-451). Burnout has Reports/2017/US%20Summary%20 Inc. density in a recent phase 2 trial; a been shown to contribute to staff July%202017.pdf). This potentially Corporate 49 phase 3 trial is currently underway. turnover and, thus, impact access to represents fertile ground hospi- Sunovion Pharmaceuticals Inc. Lonhala Magnair 22-24 For infections caused by NTM, in- care, patient satisfaction, and qual- tals to improve in-hospital arrests. Utibron Neohaler 30-33 haled amikacin has been shown to be ity of care. Excessive staff turnover Guidelines exist for consideration of Seebri 54-56

60 • JUNE 2018 • CHEST PHYSICIAN CHPH_61.indd 1 5/17/2018 1:56:30 PM NEWS FROM CHEST Catching up with our CHEST past presidents

Where are they now? What have they been up dollars, and TSET has been able to effect many to? CHEST’s Past Presidents each forged the way positive changes toward helping tobacco control for the many successes of the American College of in Oklahoma. One of these was to fund the Okla- Chest Physicians, leading to enhanced patient care homa Tobacco Research Center (OTRC) as part around the globe. Their outstanding leadership and of the Stephenson Cancer Center at Oklahoma vision are evidenced today in many of CHEST’s University. I stepped off the TSET Board to join strategic initiatives. Let’s check in with Dr. D. Rob- Dr. Laura Beebe in this endeavor, which start- ert McCaffree, Master FCCP. ed with two people and one office and has now grown to occupy over 15,000 square feet with D. Robert McCaffree, MD, MSHA, Master FCCP nine faculty and several postdoctoral students. CHEST President 1997 - 1998 Among other activities, I was Chief of Staff at the Oklahoma City VAMC for 18 years, retiring received the chain of office (yes, there is an from that position in 2009. I was honored by actual chain) from Dr. Bart Chernow in New having the MICU at the VA named after me. In IOrleans during CHEST 1997. I remember Dr. Mary Anne McCaffree and Dr. D. Robert the community, I helped start the Hospice of this time as being a time of beginnings, chal- McCaffree Oklahoma County and then the Hospice Foun- lenges, and changes. Bart had been the stimulus dation of Oklahoma, both of which I served as for the CHEST Foundation and the form and of national health groups, such as the American first chairman. I also helped start Palliative Care function of this foundation was being developed. Cancer Society), as well as on the Koop-Kessler Week on the OUHSC campus. I am currently the The women’s caucus (probably not the official Congressional Advisory Committee. I also testi- vice-chair of the Health Alliance for the Unin- name) was becoming more organized and more fied before Congress on the tobacco issues and sured in Oklahoma City, which helps support the of a force under the leadership of Dr. Diane Sto- met at the White House with DHHS Secretary many free clinics in our city. My wonderful wife, ver and Dr. Deborah Shure and others, and the Donna Shalala. On a different front, our interna- Mary Anne, is also involved in many community Woman, Girls, Tobacco, and Lung Cancer edu- tional activities were not as developed as now, but activities. On a personal level, we try to see our cational program was being refined. It was this we did make two memorable trips to India. Many two children and two grandchildren as often as program that got my wife, Mary Anne, involved thanks to Dr. Kay Guntupalli for helping make possible, which is not often enough. My free time with CHEST, and she became a Fellow (FCCP). those trips so memorable. After this absolutely activities include reading, playing the piano, fly The American College of Chest Physicians was wonderful year, I passed the chain to Dr. Allen fishing (not often enough), and exercise. in the midst of the national tobacco settlement Goldberg in Toronto. My time as President of the American College efforts at this time. Our involvement began when My experiences with tobacco control continue of Chest Physicians was one of the best and most Mike Moore, Attorney-General of Mississippi, to influence my life. After the national tobacco important experiences of my life. My memories filed the first suit against the tobacco industry in settlement failed, there was enacted the multistate of working with Al Lever, David Eubanks, Mari- 1994. Under the stimulus of Dr. John Studdard, tobacco settlement. Oklahoma was the only state lyn Lederer, Lynne Marcus, Steve Welch, and all our current President, the college was the only to place the majority of those settlement dollars the other staff and physician leaders during that medical organization to file an amicus curiae into a constitutionally protected trust fund, the time remain very dear to me. The influence of brief supporting this, thus thrusting us into the Oklahoma Tobacco Settlement Endowment Trust CHEST continues to this very day. I can never midst of the tobacco settlement debates and in a Fund (TSET). I was fortunate to be appointed to repay all that I have gained from this experience. leadership position. During the time I was Presi- the Board of Directors of TSET by our Attorney I wish I had the space allowance to expand on my dent-elect and President, I was fortunate to repre- General and was elected the first chair. Since experiences. But while my word allowance is lim- sent us both in the ENACT Coalition (composed then, the corpus has grown to over one billion ited, my gratitude is unlimited. Explore the Culture in San Antonio During CHEST 2018

ith the level of history and cul- Centro de Artes south bank of the San Antonio River crafted art and the gourmet Mex- Wture in San Antonio, there are 101 S. Santa Rosa Avenue where some have been preserved ican cuisine of old Mexico at over plenty of options when experiencing Monday: Closed and reincarnated into cafes, art gal- 100 locally owned shops and stalls, what the city has to offer. Here are a Tuesday to Sunday: 11:00 a.m. to leries, museums, and shops. all at a festive indoor mall. There’s few ways you can enjoy the arts and 6:00 p.m. also the Farmers Market Food Court culture of San Antonio. Head over to Centro de Artes to GO RIO River Shuttle where you can enjoy a show on the experience local and regional art, as Daily: 10:00 a.m. to 9:00 p.m. stage. San Antonio Museum of Art well as history and culture, revealing Want an open tour of San Antonio? 200 West Jones Avenue the story of the Latino experience in Look for the GO RIO River Shuttle City Sightseeing San Antonio The San Antonio Museum of Art the United States with a focus on San signs and boats (labeled with GO Bus Tours contains the largest and most Antonio and South Texas. RIO) along the River Walk from Get a double decker view starting comprehensive collection of an- downtown to Museum Reach. Shut- from Alamo Plaza, then head north cient Egyptian, Greek, Roman, King William Historic District tles run approximately every 60 toward the San Antonio Museum and Asian art in the southern 122 Madison Street minutes with tickets available for of Art, the Pearl Brewery Entertain- United States. The museum also Historic King William District purchase on the boat, online, or at ment Complex, and more. There are has a significant collection of spans 25 blocks of downtown San any GO RIO ticket booth. 18 stops where you can get off and Latin American art. Also, check Antonio. In the late 1800s, the King explore. Then, just go back to where out the growing contemporary art William District was considered Market Square you were dropped off, and wait for collection with notable Texan and the most elegant residential area in 514 W. Commerce Street the next bus to arrive. There’s a bus regional art, special exhibitions, the city and zoned as the state’s first Open Daily: 10:00 a.m. to 6:00 p.m. every 20 minutes at each stop during films, concerts, gallery talks, and historic district. You can now view Explore the Historic Market Square the operating hours from 8:40 a.m. to more! these 19th century residences on the where you’ll find authentic hand- 5:30 p.m..

62 • JUNE 2018 • CHEST PHYSICIAN CLASSIFIEDS Also available at MedJobNetwork.com

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THE SECTION OF PULMONARY, CRITICAL CARE & SLEEP Southern Indiana Physicians MEDICINE, YALE SCHOOL OF MEDICINE, IS SEEKING OUTSTANDING INDIVIDUALS FOR THE FOLLOWING POSITIONS: Indiana University Health Associate Clinic Director Southern Indiana Physicians has SecƟ on of Pulmonary, CriƟ cal Care and Sleep Medicine, Yale School of Medicine (Yale an employment opportunity for PCCSM), is seeking candidates for Associate Director of our rapidly growing Ambulatory Pulmonary program (Winchester Chest Clinic). This academic posiƟ on will be fi lled at a Pulmonology and Critical Care a rank of: Instructor, Assistant Professor, or Associate Professor commensurate with Physician to join their dynamic qualifi caƟ ons. The successful candidate is expected to assist the Clinic director with the day to day management of the Winchester Chest Clinic, as well as develop iniƟ aƟ ves to team in the beautiful college town improve and opƟ mize paƟ ent care and experience in the clinic. The candidate is expected of Bloomington, Indiana. to see paƟ ents in the Comprehensive Pulmonary Program but may also work in our sub- Ɵ specialty prac ces as well dependent on interest. All candidates are expected to have Practice Highlights: Hospital Highlights: outstanding skills in the clinical and educaƟ onal arena, will take an acƟ ve role teaching and mentoring fellows and residents and other opportuniƟ es for career development in • Schedule: M-F, 8AM-5PM • Beautiful Regional Academic the thriving academic environment of Yale PCCSM. Successful applicants are expected to • 50% outpatient/50% inpatient Health Center opening in 2020 with make a signifi cant contribuƟ on to the clinical, educaƟ onal, and research missions of the • Call rotation between four the latest and greatest technologies Ɵ Ɵ Ɵ sec on. Minimum requirements include: board eligibility or cer fi ca on in pulmonary Physicians • IU Health has been nationally diseases and criƟ cal care medicine. Experience in pulmonary ambulatory care, medical educaƟ on and management is encouraged. ranked by U.S. News & World All applicaƟ ons materials should be submiƩ ed electronically to: Compensation Highlights: Report for the past 20 years hƩ p://apply.interfolio.com/41048 • We off er a strong compensation Review of applicaƟ ons will begin immediately, and will conƟ nue unƟ l the posiƟ on is fi lled. model with a 3 year guarantee and For more information or to submit Yale University is an affi rmaƟ ve acƟ on/equal opportunity employer. Yale values diversity bonus eligibility your CV, please forward to: in its faculty, students, and staff and especially welcomes applicaƟ ons from women, • Sign-on bonus of $30,000 for a 3 Gretchen Nolte persons with disabiliƟ es, protected veterans and members of minority groups. year commitment Physician Recruiter For more informaƟ on on Yale PCCSM • Comprehensive benefi ts package Indiana University Health Ʃ Website h ps://medicine.yale.edu/intmed/pulmonary/ including 6 weeks of time off for [email protected] Facebook hƩ ps://www.facebook.com/yalepccsm/ TwiƩ er @YalePCCSM vacations, sick days, CME days, etc 317.962.6681 YouTube hƩ ps://www.youtube.com/channel/UC12y2CWB9774zxNZwy1TmbA/videos

FIND YOURYOUR NEXT JOBJOB AT MEDJOBNETWORK com Physician NP/PA Career Center THE SECTION OF PULMONARY, The fi rst mobile job board for Physicians, NPs, and PAs CRITICAL CARE & SLEEP MEDICINE, Mobile Job Searches—access MedJobNetwork.com on the go from your smartphone or tablet YALE SCHOOL OF MEDICINE, Advanced Search Capabilities—search for jobs by specialty, job title, geographic location, employers, and more IS SEEKING OUTSTANDING INDIVIDUALS FOR THE FOLLOWING POSITION Scan this QR code to access the mobile version of MedJobNetwork.com Ambulatory Clinician SecƟ on of Pulmonary, CriƟ cal Care and Sleep Medicine at Yale School of Medicine (Yale PCCSM), is seeking applicants to pracƟ ce in our Ambulatory Pulmonary program (Winchester Chest Clinic) and satellite pracƟ ces. The successful candidate is expected to see the majority of their paƟ ents in the general comprehensive pulmonary pracƟ ce but may also work in our sub-specialty pracƟ ces as well dependent on interest. All candidates are expected to have outstanding skills in the clinical and educaƟ onal arena and will have the opportunity to take an acƟ ve role teaching and mentoring fellows and residents. Successful applicants are expected to make a signifi cant contribuƟ on to the clinical, educaƟ onal, and research missions of the secƟ on. Minimum requirements include: board eligibility or cerƟ fi caƟ on in pulmonary diseases and criƟ cal care medicine. Review of applicaƟ ons will begin immediately, and will conƟ nue unƟ l the posiƟ on is fi lled. For Deadlines and More Information, Yale University is an affi rmaƟ ve acƟ on/equal opportunity employer. Yale values diversity in its faculty, students, and staff and especially welcomes applicaƟ ons from women, persons with Contact: Drew Endy disabiliƟ es, protected veterans and members of minority groups. Tel: (215) 657-2319 For more informaƟ on please contact Dr. Jonathan Siner, Clinical Chief, Yale PCCSM e-mail, Email: [email protected] [email protected] or phone 203-737-4523 For more informaƟ on on Yale PCCSM Website hƩ ps://medicine.yale.edu/intmed/pulmonary/ Facebook hƩ ps://www.facebook.com/yalepccsm/ TwiƩ er @YalePCCSM YouTube hƩ ps://www.youtube.com/channel/UC12y2CWB9774zxNZwy1TmbA/videos

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CHPH_64.indd 1 4/26/2018 11:48:31 AM