Contemporary definitions of medical professionalism recognize that clinical practice "rests on the integrity of scientific standards grounded in research evidence and the translation of evidence into practice guidelines, which define the proper use and implementation of diagnostic testing and therapeutics."1Qaseem A. Snow V. Gosfield A. et al.Pay for performance through the lens of medical professionalism.Ann Intern Med. 2010; 152: 366-369Crossref PubMed Scopus (30) Google Scholar Such calls for professionalism have become as much an administrative mandate as an aspirational goal now that guideline recommendations inform the development of physician performance measures created in response to society's recognition that health care commonly diverges from best practices and too often wastes resources, thereby driving up costs and threatening our ability to deliver effective care.2Shaneyfelt T.M. Mayo-Smith M.F. Rothwangl J. Are guidelines following guidelines? The methodological quality of clinical practice guidelines in the peer-reviewed medical literature.JAMA. 1999; 281: 1900-1905Crossref PubMed Scopus (748) Google Scholar, 3Kahn J.M. Scales D.C. Au D.H. et al.An official American Thoracic Society policy statement: pay-for-performance in pulmonary, critical care, and sleep medicine.Am J Respir Crit Care Med. 2010; 181: 752-761Crossref PubMed Scopus (43) Google Scholar Clinical practice guidelines (CPGs), therefore, represent a critical resource for improving patient care and also helping physicians succeed within reimbursement schemas (eg, pay-for-performance).3Kahn J.M. Scales D.C. Au D.H. et al.An official American Thoracic Society policy statement: pay-for-performance in pulmonary, critical care, and sleep medicine.Am J Respir Crit Care Med. 2010; 181: 752-761Crossref PubMed Scopus (43) Google Scholar Guidelines have not always enjoyed such a preeminent role in health care. In the 1970s, for example, negligible high-quality research was available in the field of thrombotic disorders to inform decision-making for the limited diagnostic (lung scans and contrast venography for venous thrombosis) and therapeutic (unfractionated heparin, streptokinase, warfarin, and aspirin) resources available. With the explosion of scientific research in the 1980s, professional societies looked to CPGs as a way to help harried clinicians navigate complex and often conflicting primary studies to make informed medical decisions and counter administrative pressures to alter their practices in ways that might not be in their patients' best interests.4Heffner J.E. The overarching challenge.Chest. 2000; 118: 1S-3SAbstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar As recently as 1994, however, a survey of American College of Physicians members found that 43% of respondents believed CPGs would drive up health-care costs, 68% predicted guidelines would be used punitively to discipline physicians, and 34% believed guidelines would degrade the pleasure found in practicing medicine.5Tunis S.R. Hayward R.S. Wilson M.C. et al.Internists' attitudes about clinical practice guidelines.Ann Intern Med. 1994; 120: 956-963Crossref PubMed Scopus (409) Google Scholar Some professional societies at that time questioned the value of CPGs, especially in light of calls to increase the rigor—and consequently the cost—of methodologies for their development and implementation.6Heffner J.E. Does evidence-based medicine help the development of clinical practice guidelines.Chest. 1998; 113: 172S-178SAbstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar With remarkable foresight, the American College of Chest Physicians (CHEST) in 2000 convened a workshop that examined the value of CPGs, decided they were worth the effort and expense, and set methodologic standards for their development and implementation.4Heffner J.E. The overarching challenge.Chest. 2000; 118: 1S-3SAbstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar Since then, physicians have accepted CPGs as the terminus of the "knowledge funnel" through which research flows into systematic reviews and on to the development of guidelines, which are the "action" arm of science for improving clinical practice.7Grimshaw J.M. Schünemann H.J. Burgers J. et al.Disseminating and implementing guidelines: article 13 in Integrating and coordinating efforts in COPD guideline development. An official ATS/ERS workshop report.Proc Am Thorac Soc. 2012; 9: 298-303Crossref PubMed Scopus (42) Google Scholar Fifteen years after the American College of Chest Physicians' guideline workshop,4Heffner J.E. The overarching challenge.Chest. 2000; 118: 1S-3SAbstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar I can think of no better way to assess the College's success in implementing its lofty goals for CPGs then by reflecting on the remarkable history of the American College of Chest Physicians' antithrombotic (AT) guidelines. Through nine editions spanning 30 years, the AT guidelines have convened the leading international experts on AT therapy. These experts adopted nonbiased consensus development processes, utilized rigorous methods to review existing research using trained methodologists, standardized the grading of evidence and clinical recommendations, and safeguarded the final product from commercial conflict of interests.8Neumann I. Karl R. Rajpal A. Akl E.A. Guyatt G.H. Experiences with a novel policy for managing conflicts of interest of guideline developers: a descriptive qualitative study.Chest. 2013; 144: 398-404Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar These innovations have stimulated other professional societies to adopt more rigorous evidence-based approaches to guideline development. The latter has been an especially important side benefit of the AT guidelines, considering the historically low quality of many published CPGs.2Shaneyfelt T.M. Mayo-Smith M.F. Rothwangl J. Are guidelines following guidelines? The methodological quality of clinical practice guidelines in the peer-reviewed medical literature.JAMA. 1999; 281: 1900-1905Crossref PubMed Scopus (748) Google Scholar, 9Shaneyfelt T.M. Centor R.M. Reassessment of clinical practice guidelines: go gently into that good night.JAMA. 2009; 301: 868-869Crossref PubMed Scopus (246) Google Scholar, 10Sniderman A.D. Furberg C.D. Why guideline-making requires reform.JAMA. 2009; 301: 429-431Crossref PubMed Scopus (167) Google Scholar Moreover, guidelines have been criticized as a Tower of Babel because multiple, often poorly constructed, overlapping, and conflicting guidelines on the same disease confuse clinical practice.11Hibble A. Kanka D. Pencheon D. Pooles F. Guidelines in general practice: the new Tower of Babel?.BMJ. 1998; 317: 862-863Crossref PubMed Scopus (130) Google Scholar However, the American College of Chest Physicians' AT guidelines, through the sheer breadth of AT topics addressed and their authoritative methodology, have "cornered" the market on AT guidelines, which fulfills the goals of international organizations that call for harmonization of guidelines into coherent and consistent clinical recommendations.12Schünemann H.J. Woodhead M. Anzueto A. et al.A vision statement on guideline development for respiratory disease: the example of COPD.Lancet. 2009; 373: 774-779Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar Finally, the AT guidelines were prescient in incorporating patient perspectives into shared decision-making, such as the recommended patient-physician discussions to determine the duration of warfarin therapy in managing idiopathic DVT. Observers have criticized other guidelines for too often taking the physician's perspective solely rather than including patient wishes and values.2Shaneyfelt T.M. Mayo-Smith M.F. Rothwangl J. Are guidelines following guidelines? The methodological quality of clinical practice guidelines in the peer-reviewed medical literature.JAMA. 1999; 281: 1900-1905Crossref PubMed Scopus (748) Google Scholar Thus, a new update for AT therapy begins with the publication of the first topic on Antithrombotic Therapy for VTE Disease (see page 315), in what will be a serialized publication of the newly updated AT guidelines.13Kearon C. Akl E.A. Ornelas J. et al.Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report.Chest. 2016; 149: 315-352Abstract Full Text Full Text PDF PubMed Scopus (3369) Google Scholar As a clinician interested in AT therapy and also as someone who has followed the field of guideline development and implementation closely, I—like most physicians—am eager to see what's new. As for new management recommendations, this update of the AT guidelines is especially newsworthy. To name a few of the revised recommendations, the guidelines outline an expanded role for nonvitamin K oral anticoagulants to help physicians assess the role of these emerging therapies. An important departure from traditional management of subsegmental pulmonary emboli is offered. New recommendations are provided for the treatment of cancer-associated thrombosis. Of equal newsworthiness is the plan to publish these guidelines online in a serialized "Living Guidelines Model." This model will address criticisms that guidelines become outdated in 3 to 5 years, and organizations that develop guidelines lack mechanisms for updating their recommendations in synchrony with new scientific discoveries.9Shaneyfelt T.M. Centor R.M. Reassessment of clinical practice guidelines: go gently into that good night.JAMA. 2009; 301: 868-869Crossref PubMed Scopus (246) Google Scholar The CHEST Guidelines Oversight Committee has again harkened to the 2000 American College of Chest Physicians' workshop report that encouraged the College to devise processes for "frequent modification of guidelines to maintain their currency."14Heffner J.E. Alberts W.M. Irwin R. Wunderink R. Translating guidelines into clinical practice: recommendations to the American College of Chest Physicians.Chest. 2000; 118: 70S-73SAbstract Full Text Full Text PDF PubMed Google Scholar This new model fundamentally raises the bar for guideline development, dissemination, and implementation by focusing on specific portions of the AT guideline that require updating and will most likely alter approaches to guideline development for other professional societies in coming years. The 2000 American College of Chest Physicians' guidelines workshop noted that "guidelines are the substrate for experienced clinicians who interpret science with an intention to practice the art of medicine for the benefit of individual patients."4Heffner J.E. The overarching challenge.Chest. 2000; 118: 1S-3SAbstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar Many barriers exist, however, to the optimal translation of guideline recommendations into physician actions that improve care.7Grimshaw J.M. Schünemann H.J. Burgers J. et al.Disseminating and implementing guidelines: article 13 in Integrating and coordinating efforts in COPD guideline development. An official ATS/ERS workshop report.Proc Am Thorac Soc. 2012; 9: 298-303Crossref PubMed Scopus (42) Google Scholar There is little empiric research with regard to AT therapy specifically for determining the most effective methods to overcome these barriers and implementing AT guideline recommendations.15Schünemann H.J. Cook D. Grimshaw J. et al.Antithrombotic and thrombolytic therapy: from evidence to application: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.Chest. 2004; 126: 688S-696SAbstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar Now that CHEST has honed its methods for guideline development, they are embarking on discovering new processes (eg, the Living Guidelines Model, mobile applications, E-learning approaches) for guideline implementation designed to turn recommendations into action and improve patient care. These efforts highlight the College's commitment to medical professionalism and will hopefully stimulate research into whether these novel approaches for updating guidelines will improve health for patients with thrombotic disease. /cms/asset/c70da263-0d59-494b-a910-8d7f44e075fd/mmc1.mp3Loading ... Download .mp3 (24.17 MB) Help with .mp3 files Audio Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel ReportCHESTVol. 149Issue 2PreviewWe update recommendations on 12 topics that were in the 9th edition of these guidelines, and address 3 new topics. Full-Text PDF

Objectives: We hypothesized performance improvement interventions would improve COPD guideline-recommended care and decrease COPD exacerbations in primary care clinic practices.Methods: We initiated a performance improvement project in 12 clinics to improve COPD outcomes incorporating physician education, case management, web-based decision support (CareManager(TM)), and performance feedback. We collected baseline and one-year follow up data on 242 patients who had COPD with acute exacerbations. We analyzed data by two methods. First, the 12 clinics were cluster randomized to 4 intervention (117 patients) and 8 control (125 patients) clinics which all had access to CareManager(TM) but only intervention clinic physicians received case management, academic detailing, and decision support assistance. Exacerbation rates and guideline adherence were compared. Second, data from all 12 clinics were pooled in a quasi-experimental design comparing baseline and post-implementation of CareManager(TM) to determine the value of system-wide performance improvement during the study period.Results: In the randomized analysis, baseline demographics were similar. No differences (p=0.79) occurred in exacerbation rates between intervention and control clinics although both groups had decreased numbers of exacerbations from baseline to follow up (p<0.05). The pooled data from all 12 clinics demonstrated a reduction (p<0.05) in mean exacerbations/patient from 2.3 (CI 2.0-2.6) during baseline to 1.4 (CI 1.1-1.7) at one-year follow up. Emergency department visits and hospitalizations/patient decreased (p=0.003). Patients naive at study start to depression screening, pneumococcal vaccination, inhaled control medications or smoking cessation had fewer (p<0.05) exacerbations after these interventions.Conclusion: We observed no difference in exacerbation rates between clinics receiving case management, academic detailing, and ongoing assistance with decision support and controls. Implementation of a web-based disease management system (CareManager(TM)) along with health system-wide COPD performance improvement efforts was associated with fewer COPD exacerbations and increased adherence to guideline recommendations.

There are no controlled clinical trials to determine the duration of corticosteroid therapy for idiopathic acute eosinophilic pneumonia (AEP). Consequently, current practice derives from expert opinion without the assistance of clinical practice guidelines, which would help clinicians weigh the benefits relative to the potential harm of various durations of therapy. Recommended therapy varies between published sources, but typically entails intravenous or oral corticosteroids, depending on the severity of initial respiratory compromise, followed by 40–60 mg of prednisone for at least 2 weeks beyond complete resolution of symptoms and radiographic abnormalities at which time slow tapering at a rate of 5 mg of prednisone a week can begin. Although recommendations for short 2-week courses of total therapy exist, all current protocols monitor patients’ clinical response to determine when to discontinue therapy. Goals of therapy for AEP centre on controlling a dysregulated hypersensitivity response to an unknown stimulus, which is considered the probable underlying pathophysiology of AEP, resolving respiratory symptoms and preventing a relapse, which may be rapid in onset and severe. Unfortunately, what logic suggests would represent conservative and therefore safe therapy—giving corticosteroids long enough to ensure full recovery and prevent a relapse—may actually cause harm if patients would have recovered sooner, but developed side effects from unnecessarily prolonged drug therapy. Of note, some patients with AEP recover spontaneously without corticosteroid treatment so it seems implausible that all patients who clinicians choose to treat will require a minimum of 2 weeks or more of drug therapy. We welcome, therefore, the study by Jhun published in this issue of Respirology. The author recognized the importance of shortening corticosteroid therapy for AEP and the paucity of relevant high quality studies that address this issue. Based on previous observations of Jhun et al. that peripheral eosinophilia counts (PEC) inversely correlate with markers of systemic inflammation and appear to identify patients with milder disease, they hypothesized that patients with initial absolute PEC of >500/μL require corticosteroid therapy only to clinical stabilization—not full recovery. To address this hypothesis, they prospectively allocated patients with AEP to normal PEC versus elevated PEC (eosinophilia) study arms. The normal PEC group was treated with a 2-week corticosteroid protocol that prescribed an initial fixed-dose, 7-day course of methylprednisolone (3 days) followed by prednisolone (4 days) if respiratory failure existed or prednisolone alone in the absence of respiratory failure. Corticosteroids were then tapered over the following 7 days and discontinued if clinical stabilization, as defined by pre-defined targets, occurred. The high PEC arm was started on the same 2-week protocol but corticosteroids were discontinued abruptly when the pre-defined targets for clinical stabilization were achieved. Exceptionally encouraging was the study’s findings that all patients survived and stabilized within 14 days of therapy, but the eosinophilia arm required a median of 4 days of corticosteroids in contrast to 14 days for the normal PEC group. The shorter duration of therapy in the eosinophilia arm tended toward less minor corticosteroid-related side effects, but the differences were not statistically significant. So what have we learned? An important observation not mentioned by the authors is that both study arms departed drastically from some contemporary expert-based recommendations for prolonged corticosteroids with slow drug tapering until complete resolution of AEP occurs. The entire 59-subject cohort in the Jhun et al. study achieved eventual recovery with 14 days or less of corticosteroid therapy although one patient had a minor relapse. So stabilization rather than full recovery may become the target for discontinuing corticosteroids. But before embracing short-course (<14 days) therapy, recall that the study results have limited generalizability being conducted in males in a single military centre. Although no patient had a severe relapse, the small sample size and short follow up do not allow assessment of the actual risk for harm. A rare complication as represented by respiratory failure in an underlying rare condition, such as AEP, requires larger studies by several magnitudes to make assessments of benefits versus harm upon which clinical practice guidelines—and clinical decisionmaking—are based. But have we learned that PEC accurately identifies patients who tolerate short-course therapy? As with all biologic markers and prognostic models, when evaluated in large cohort validation studies as compared with initial small derivation studies, prognostic performance degrades. We anticipate that this will be the case with PEC as suggested by the present study bs_bs_banner

In 2009, the American Thoracic Society (ATS) funded an assembly project, Palliative Management of Dyspnea Crisis, to focus on identification, management, and optimal resource utilization for effective palliation of acute episodes of dyspnea. We conducted a comprehensive search of the medical literature and evaluated available evidence from systematic evidence-based reviews (SEBRs) using a modified AMSTAR approach and then summarized the palliative management knowledge base for participants to use in discourse at a 2009 ATS workshop. We used an informal consensus process to develop a working definition of this novel entity and established an Ad Hoc Committee on Palliative Management of Dyspnea Crisis to further develop an official ATS document on the topic. The Ad Hoc Committee members defined dyspnea crisis as "sustained and severe resting breathing discomfort that occurs in patients with advanced, often life-limiting illness and overwhelms the patient and caregivers' ability to achieve symptom relief." Dyspnea crisis can occur suddenly and is characteristically without a reversible etiology. The workshop participants focused on dyspnea crisis management for patients in whom the goals of care are focused on palliation and for whom endotracheal intubation and mechanical ventilation are not consistent with articulated preferences. However, approaches to dyspnea crisis may also be appropriate for patients electing life-sustaining treatment. The Ad Hoc Committee developed a Workshop Report concerning assessment of dyspnea crisis; ethical and professional considerations; efficient utilization, communication, and care coordination; clinical management of dyspnea crisis; development of patient education and provider aid products; and enhancing implementation with audit and quality improvement.

We are witnessing a rapid transformation of clinical practice as more of what we do in medicine becomes informed by an increasingly accelerated application of scientific knowledge derived from basic science research. This process represents the essence of what is now termed clinical translational research, which entails the infusion of sound scientific knowledge, wherever appropriate, into clinical practice. The ultimate aim of clinical translational research centres is advancing our understanding of the mechanisms of disease and improving targeted therapeutics and approaches to make meaningful improvements in patient outcomes. In order to achieve this, the collaborative efforts of investigators and practitioners upon which such research is based would benefit from reviewing the progress achieved in linking scientific evidence to clinical experience so as to chart future research goals and directions.1 Based on this premise, we planned a series of invited reviews published over the last year or so in Respirology on ‘Translating research into practice’. The series identified leading translational experts who span broad areas of respiratory medicine that include topics of diagnostic and predictive biomarkers, respiratory physiology in terms of lung function testing, basic pathophysiology of sleep-related breathing disorders, and respiratory infections. Our authors provided advanced and evidence-based reviews on their areas of expertise. Despite the recent publication of a revised version of the Global Initiative on Obstructive Lung Diseases guidelines, a variety of areas in chronic obstructive pulmonary disease (COPD) deserve further research and discussion, such as COPD in non-smokers, COPD staging, the multi-system nature of COPD and assessing the severity of exacerbations. Piera Boschetto and colleagues reviewed the relationship of COPD with one of its most important comorbidities, namely cardiovascular diseases.2 GuangQiao Zeng and colleagues contributed a concise review on non-smoking COPD,3 an emerging area of concern in the areas of COPD and asthma. Understanding the anatomical structure of the respiratory system provides a critical foundation for advancing respiratory research. George Washko and colleagues gave a comprehensive review on research in computed tomography and magnetic resonance imaging both for the lung parenchyma and the airways, with examples of the application of advanced imaging to specific disorders, such as interstitial lung disease, asthma and COPD.4 Hiroshi Kubo reviewed current developments in pulmonary tissue engineering and regeneration, which represent key areas of basic research in pulmonary and stem cell research,5 and gave insights into potential areas for further research and development. Respiratory physiology provides paramount insights into understanding lung function that are essential for advancing both clinical research and respiratory care. BinMiao Liang and colleagues revisited various aspects of lung function testing, offering a forward-looking perspective on areas ripe for new test development.6 Keishi Ohtani and colleagues reviewed futuristic bronchoscopic imaging techniques that included autofluorescence imaging, optical coherence tomography, confocal endomicroscopy and Raman spectroscopy, and their clinical and research applications in respiratory medicine.7 Kasia Czarnecka and Kazuhiro Yasufuku reviewed recent advances in interventional pulmonology, with a focus on diagnostic tools like endobronchial ultrasonography, pleuroscopy and navigational bronchoscopy.8 The challenges of pulmonary infections were approached by Jeannina Smith and Carol Kauffman, who contributed an overview of fungal lung infections that included cryptococcosis, aspergillosis and histoplasmosis, along with recent advances in clinical care.9 With the emergence of multi-drug-resistant tuberculosis and extended drug-resistant tuberculosis, Nicholas Walter and colleagues authored a timely review on the epidemiology, diagnosis and treatment of these highly resistant and increasingly lethal pathogens.10 S. Rodrigo Burguete and colleagues reviewed pulmonary infections that occur in patients undergoing lung transplantation.11 The new staging system for lung cancer was released by the International Society for the Study of Lung Cancer and is now widely adopted by clinicians engaged in the management of lung cancer patients. It is essential to have a thorough understanding of the rationale behind the various modifications of the new staging system. Henry Marshall and colleagues accepted the complex task of reviewing the scientific evidence in support of the recommendations proposed by the new staging system.12 With advances in the understanding of the pathobiology of lung adenocarcinoma, the International Society for the Study of Lung Cancer committee has also revised the classification of pulmonary adenocarcinoma recently. Humam Kadara and colleagues provided a timely review on how this classification evolved into its present form.13 HsuanYu Chen and colleagues reviewed recently expanded knowledge of biomarkers and transcriptomic profiling of lung cancer and resulting opportunities for further research in this area.14 The availability of targeted therapy for patients with lung cancer over the past decade has transformed the management of this persistently lethal disease, moving clinicians from rigid protocols into personalized treatment. David Lam reviewed the current applications of molecular testing that have ushered in personalized care for lung cancer, including testing for the epidermal growth factor receptor gene mutations and the anaplastic lymphoma kinase gene rearrangement.15 Screening for lung cancer remains an area of continued debate, even though recent screening trials provide support for computed tomography screening in selected populations. Stephen Spiro and Neal Navani provided a comprehensive review on the current progress of various screening studies in lung cancer.16 Mitsuo Sato and colleagues selected a frontier area of scientific research in lung cancer—epithelial mesenchymal transition—for review.17 Recent research into sleep-related breathing disorders has provided extensive data in support of translational knowledge. Romola Bucks and colleagues authored an in-depth review on our current understanding of neurocognitive aspects of obstructive sleep apnoea.18 Macy Lui and colleagues discussed the importance of endothelial dysfunction in obstructive sleep apnoea.19 Fang Han reviewed a sometimes neglected yet important area of sleep medicine research,20 namely narcolepsy and cataplexy, helping physicians develop practical approaches to these increasingly recognized clinical problems. Francoise Roux reviewed yet another often under-diagnosed sleep-related breathing disorder, that is, restless leg syndrome.21 The aforementioned topics represent only a small sliver of the translational clinical research that is increasingly informing our broad field of respiratory medicine. Conditions left out include interstitial lung disease, bronchiectasis and cystic fibrosis to name but a few. The manuscripts published in this series, however, create a clear image of the new landscape for research and clinical practice that is moving knowledge from the bench to the clinic along a remarkably streamlined trajectory. We hope to revisit this topic in future editions of Respirology to catch up on how other respiratory conditions have benefited from translational research as well. In the meantime, we thank the authors of the present series for sharing their expertise and setting us off on a course towards a more rapid translation of science to improved patient care.

An enduring memory for those of us trained during the 1970s in pulmonary and critical care recalls the daily ritual of concluding bedside rounds by walking to radiology, where we suspended our patients' cut films on a vast wall of view boxes. As our huddle of physicians moved down the illuminated rows, we trainees were mesmerized by the ability of master attending physicians to synthesize the clinical findings we presented with the shadows they saw to create a cohesive diagnosis and plan. The annual CHEST conference was even more memorable. There, a roomful of attending physicians routinely “solved” the most challenging clinical dilemmas we could throw their way as unknowns. We trainees left both dazzled by the clinical pearls we learned, but also committed to honing our own diagnostic skills. Helping patients by solving tough clinical questions in arguably the most diverse and difficult-to-learn specialty in medicine, pulmonary critical care, is not only professionally gratifying but also a lot of fun. As Sherlock Holmes enthused when facing a new mystery, “Come Watson, come!…The game is afoot.”1Doyle AC The Adventure of the Abbey Grange. Educational Technology Clearinghouse. University of South Florida website.http://etc.usf.edu/lit2go/178/the-return-of-sherlock-holmes/3238/chapter-xii-the-adventure-of-the-abbey-grange/Google Scholar In 1985 at the Medical University of South Carolina, two of us (J. E. H. and S. A. S.) began a handwritten log of interesting cases collected from the CHEST conference with a listing of one or two pearls for each. After a couple of years, the book became swollen with teaching points and dog-eared by the many fellows who used it. We decided that the CHEST conference and its pearls were too good not to share. So in 1988, we published Pulmonary Pearls,2Sahn SA Heffner JE Pulmonary Pearls. Hanley & Belfus, Philadelphia, PA1988Google Scholar which was followed over the years by 18 subsequent books in the Pearls series that followed a similar format: case presentation, question posed, answer provided, discussion of the underlying entity, patient follow-up, and listing of the most valuable learning points, which we all know as “pearls.” We were gratified that the “game was [still] afoot” in the minds of many of our readers who enjoyed reading case studies and solving medical mysteries. We think it true that pulmonary/critical care physicians share in common the “Sherlock Holmes gene” that binds our profession together. Because of the readability of the format, some colleagues confessed, when we met them at annual meetings, that they kept the books close at hand near their nightstand or commode. (We took the latter as a compliment.) Even more satisfying was the invitation in 1992 from Al Soffer, MD, Master FCCP, then the editor-in-chief of CHEST, to reprise our Pearls books into a new Pulmonary and Critical Care Pearls section in the journal. Over the following 2 decades, not only have CHEST readers demonstrated they have the “Holmes gene” by their support of the section, but they have also proven over and over again that they are the true master clinicians. Since November 1992, we have published 335 extraordinary manuscripts authored by CHEST readers from around the world in every practice setting imaginable. These authors face tough clinical problems daily and regularly demonstrate their remarkable problem-solving skills. Reading and editing these manuscripts has been quite a learning experience for the both of us (J. E. H. and S. A. S.), and we sincerely thank our long list of authors. As radiology became digitized and long rows of view boxes gradually disappeared, our specialty has similarly changed. The satisfaction that physicians gain from solving diagnostic dilemmas remains intact, but pulmonary critical care has become even more challenging and diverse with the inclusion of sleep medicine. Master clinicians versed in mechanical ventilation, pressor support, interstitial lung disease, asthma, and the like, now commonly manage obstructive sleep apnea, central hypoventilation, overlap syndrome, cataplexy, and restless leg syndrome, to name a few. The requisite toolbox of pearls that clinicians must keep at hand has similarly grown in size. For this reason, we are welcoming a new Pearls Section co-editor, Susan Harding, MD, FCCP, to help us expand the scope of the CHEST section, now titled “Pulmonary, Critical Care, and Sleep Pearls.” Since the early research of A. J. Block that explored the pathophysiologic roots of obstructive sleep apnea, sleep medicine has grown into a complex field with >90 sleep-related disorders, each of which has a unique set of diagnostic and management strategies. Because sleep disorders affect respiratory function and outcomes in the ICU, it comes as no surprise that two-thirds of board-certified sleep physicians are pulmonologists.3Quan SF Buysse DJ Ward SL et al.Development and growth of a large multispecialty certification examination: sleep medicine certification—results of the first three examinations.J Clin Sleep Med. 2012; 8: 221-224PubMed Google Scholar In response, CHEST, under the stewardship of Richard Irwin, MD, Master FCCP, its editor-in-chief, and Nancy Collop, MD, FCCP, an associate editor with considerable sleep-medicine expertise, has successfully moved toward becoming a leading journal in sleep medicine. Adding sleep to the Pearls Section will further strengthen the educational value of the journal. Sleep deprivation impacts society to a remarkable degree. New observations appear almost daily that link sleep disorders with hypertension, cardiovascular disease, diabetes, and even cancer, which underscore the central importance of sleep to health and the mechanistic role of abnormal sleep in causing or contributing to disease.4Redline S Quan SF Sleep apnea: a common mechanism for the deadly triad—cardiovascular disease, diabetes, and cancer?.Am J Respir Crit Care Med. 2012; 186: 123-124Crossref PubMed Scopus (24) Google Scholar We anticipate receiving a wealth of challenging sleep-medicine manuscripts. A word to potential authors: Keep in mind that we seek interesting cases, from the routine to the arcane, that challenge readers with figures that display polysomnographic epochs, imaging studies, actigraphs, or other sleep-related laboratory findings. Previously unreported observations belong in in the Selected Reports section of CHEST; we will be looking for illustrative examples of known entities. It is all about the “pearls” and homing in on clinical problem-solving skills. In preparing manuscripts for Sleep Medicine Pearls, please be sure to review the instructions to authors (http://journal.publications.chestnet.org/ss/forauthors.aspx#PulmonaryCritCareSleepPearls) and use the formatting that Pearls manuscripts require. It has been a wonderful experience having the privilege for 2 decades to tap the wealth of knowledge our CHEST authors possess and publish their “lessons learned” as pulmonary and critical care pearls. With the addition of sleep medicine, we look forward to publishing an even broader array of medical mysteries to stimulate our readers' “Holmes gene.” We keenly await discovering what sleep-related pearls we will read, and how they will help us all become master clinicians. The game is afoot!

To the Editor The risk of hypovitaminosis D in antiretroviral-treated patients living in northern climes is underreported.1 In this observational, cross-sectional cohort study of 122 human immunodeficiency-virus (HIV)-infected outpatients in Portland, Oregon between March and October 2011, we compared vitamin D levels stratified by the use of Atripla (efavirenz, tenofovir, and emtricitabine), non-Atripla antiretroviral therapy (ART) regimens, and multivitamins (600–1000 IU vitamin D). After Providence Health Systems institutional review board approval, patients’ demographics (age, sex, race, weight, height, and body mass index [BMI]) and laboratory parameters (complete blood count, metabolic panel, CD4, and quantitative HIV RNA polymerase chain reaction) were extracted from the electronic medical records. Serum 25[OH]D was measured by chemiluminescent immunoassay. Vitamin D status was defined according to 25[OH]D level as severely deficient (<10 ng/mL), deficient (10–20 ng/mL), insufficient (20–30 ng/mL), or optimal (>30 ng/mL). Antiretroviral therapy regimens consisted of the following: A, Atripla (n = 56); B, Truvada (tenofovir and emtricitabine) plus other ART (n = 35); C, other ART (n = 18); and no ART drugs (n = 13). All patients receiving regimen C had previously failed or were intolerant to regimens A and/or B. Descriptive statistics were used to characterize populations and summarize results. Frequencies and proportions described dichotomous and categorical variables, whereas means and standard deviations described continuous variables. An analysis of covariance under the generalized linear model framework was used to model hypovitaminosis D. The full model included both continuous and categorical predictors: patient’s age (49.2 ± 10.2 years), BMI (26.3 ± 5.2 kg/m2), CD4 cells (538 ± 244), quantitative HIV RNA polymerase chain reaction (13,449 ± 81,652), race (white, n = 106 vs. other, n = 16), vitamin consumption (yes, n = 65; no, n = 57), and ART (regimens A, n = 56; B, n = 35; C, n = 18; or no drug, n = 13). In the backward stepwise elimination process, patient’s age, BMI, and HIV RNA values were excluded as nonsignificant predictors (P > 0.05). 25[OH]D levels (mean, 27.1 ± 13.0 ng/mL) were severely deficient in 8%, deficient in 24%, insufficient in 32%, and optimal in 36%. Vitamin consumption was kept as a clinically important independent variable. The least square means for hypovitaminosis D associated with different ART regimens were calculated, adjusting for the other effects in the model, using the Tukey-Kramer pairwise comparison. The CD4 cell count was inversely associated with 25[OH]D levels (P = 0.04). The adjusted mean level of 25[OH]D was 4 IU lower in the group without vitamin supplements (P = 0.09). Race was a statistically significant predictor of hypovitaminosis D; the adjusted mean level of 25[OH]D vitamin D for nonwhite race was 8 IU lower than for white race (P = 0.03). The adjusted mean 25[OH]D vitamin D levels for ART regimens A and C were statistically lower than the no ART drug group (P = 0.02 and P = 0.03, respectively). Atripla was associated with an increased risk of suboptimal 25[OH]D level of less than 30 ng/mL (odds ratio, 5.86; 95% confidence interval, 1.30–26.4). In pairwise comparisons, statistical significance of these differences was not as strong. No differences in electrolyte, renal function, or alkaline phosphatase values were detected among the treatment groups; no influence of tenofovir on renal function was seen. No tuberculosis or deep infection was diagnosed, nor were any deaths recorded. A high prevalence of hypovitaminosis D (64%) among HIV-infected adults exists in the Pacific Northwest, despite multivitamin use in 53% of patients in the current study; and testing during nonwinter months of peak sunlight exposure. The significant association between hypovitaminosis D and Atripla seen in our population mirrors that recently found in the largest studies to date.2,3 The mechanism may involve induction of cytochrome P450 metabolism by efavirenz.4 Vitamin D insufficiency may be mitigated by multivitamin supplementation, particularly for patients on Atripla. Our finding of a 4 IU improvement on multivitamin supplement parallels that expected with a 400 IU vitamin D supplement. We recommend more aggressive screening of vitamin D levels in HIV patients, especially those in northern regions.5 James E. Leggett Jr, MD Department of Medical Education Providence Portland Medical Center Department of Internal Medicine Oregon Health & Science University, Portland, OR [email protected] Vincent Au, MD Daniel Norfleet, MD Department of Medical Education Providence Portland Medical Center Portland, OR Yelena Rozenfeld, MPH Department of Outcome and Evaluation Providence Portland Medical Center Portland, OR John E. Heffner, MD Department of Medical Education Providence Portland Medical Center and Department of Internal Medicine Oregon Health & Science University Portland, OR The authors have no funding or conflicts of interest to disclose.

The history of oxygen from discovery to clinical application for patients with chronic lung disease represents a long and storied journey. Within a relatively short period, early investigators not only discovered oxygen but also recognized its importance to life and its role in respiration. The application of oxygen to chronic lung disease, however, took several centuries. In the modern era, physiologists pursued the chemical nature of oxygen and its physiologic interaction with cellular metabolism and gas transport. It took brazen clinicians, however, to pursue oxygen as a therapeutic resource for patients with chronic lung disease because of the concern in the 20th century of the risks of oxygen toxicity. Application of ambulatory oxygen devices allowed landmark investigations of the long-term effects of continuous oxygen that established its safety and efficacy. Although now well established for hypoxic patients, many questions remain regarding the benefits of oxygen for varying severity and types of chronic lung disease.