Pirfenidone and Nintedanib for Treatment of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis is one of the most common entities of the family of disorders known as the interstitial lung diseases. It is a chronic, progressive, and often-fatal disease with a median survival time of 3 to 5 years. In 2014 the US Food and Drug Administration approved pirfenidone and nintedanib, two antifibrotic agents for the treatment of idiopathic pulmonary fibrosis. Because these are the only drugs approved that can alter the course of this rare but fatal disease, this article reviews the major studies that led to the approval of these drugs and examines the indications for treatment and the expected outcomes of therapy.

Hb Grove City [ß38(C4)Thr→Ser, ACC>AGC; HBB: c.116C>G]: a new low oxygen affinity ß chain variant.

A previously unreported ß chain hemoglobin (Hb) variant, Hb Grove City [ß38(C4)Thr→Ser, ACC>AGC; HBB: c.116C>G], was discovered in a woman who presented with hypoxia and mild anemia. Her young daughter also tested positive for the variant and displayed similar symptoms. Hemoglobin-oxygen dissociation testing confirmed right-shifted oxygen dissociation curves. A corresponding Hb variant was detected by high performance liquid chromatography (HPLC) and intact mass spectrometry (MS) but was not detected by capillary electrophoresis (CE), isoelectrofocusing (IEF) or alkaline or acid electrophoresis. DNA sequencing analysis confirmed a ß-globin gene mutation. All three previous mutations at this locus affect oxygen affinity, as does this new variant. This newly described variant showed variable stability results and therefore may be mildly unstable but is not associated with microcytosis, significant hemolysis or clinically evident cyanosis. It is important to consider hemoglobinopathies in patients who are anemic and have unexplained hypoxia. Arterial blood gas and p50 evaluations may prevent unnecessary diagnostic interventions. Additionally, Hb variants with altered oxygen affinity can be electrophoretically silent; therefore, multiple methods including MS and/or DNA sequencing are warranted when clinical suspicion is high.

A Systematic Review of Metrics Utilized in the Selection and Prediction of Future Performance of Residents in the United States.

Background Aligning resident and training program attributes is critical. Many programs screen and select residents using assessment tools not grounded in available evidence. This can introduce bias and inappropriate trainee recruitment. Prior reviews of this literature did not include the important lens of diversity, equity, and inclusion (DEI). Objective This study's objective is to summarize the evidence linking elements in the Electronic Residency Application Service (ERAS) application with selection and training outcomes, including DEI factors. Methods A systematic review was conducted on March 30, 2022, concordant with PRISMA guidelines, to identify the data supporting the use of elements contained in ERAS and interviews for residency training programs in the United States. Studies were coded into the topics of research, awards, United States Medical Licensing Examination (USMLE) scores, personal statement, letters of recommendation, medical school transcripts, work and volunteer experiences, medical school demographics, DEI, and presence of additional degrees, as well as the interview. Results The 2599 identified unique studies were reviewed by 2 authors with conflicts adjudicated by a third. Ultimately, 231 meeting inclusion criteria were included (kappa=0.53). Conclusions Based on the studies reviewed, low-quality research supports use of the interview, Medical Student Performance Evaluation, personal statement, research productivity, prior experience, and letters of recommendation in resident selection, while USMLE scores, grades, national ranking, attainment of additional degrees, and receipt of awards should have a limited role in this process.

The Virtual Interview Experience: Perspectives of Pulmonary and Critical Care Fellowship Applicants.

Background: Because of the coronavirus disease (COVID-19) pandemic, graduate medical education programs adopted virtual interviews (VIs) as the default modality for the 2020 recruitment season. It is unknown whether VIs allowed applicants to effectively evaluate programs, and the best interview format for the future is unclear. Objective: To 1) assess pulmonary and critical care applicants' perceived ability to evaluate programs using VIs, 2) determine the attitudes of applicants toward the components of VIs, and 3) identify applicants' preferences for the future fellowship interview format. Methods: After the National Residency Matching Program medical subspecialty match, an electronic survey was sent to 1,067 applicants to pulmonary and critical care medicine programs asking them to compare their fellowship VI experience with their residency in-person interview (IPI) experience. Results: Three hundred six (29%) applicants responded to the survey, and 289 completed it (27%). There were 117 (40%) women and 146 (51%) White individuals. Most respondents believed that VIs hindered their ability to evaluate programs' culture, faculty-fellow relationships, location, facilities, and their own fit within the program. They believed they were able to evaluate the clinical experience, curriculum, and potential for academic development equally well compared with IPIs. The most helpful elements of VIs were the interview with the program director, meetings with the fellows, and interviews with faculty members. Less helpful elements included conference access, prerecorded program director presentations, virtual hospital and city tours, and video testimonials. One hundred twenty-three respondents (43%) chose VIs with an optional visit as their preferred future interview format, 85 (29%) chose IPIs, 54 (19%) wanted a choice between VIs and IPIs, and 27 (9%) chose VIs only. Conclusion: Most pulmonary and critical care medicine applicants preferred future interviews to include both VIs and the option of an in-person visit or interview. This study can assist programs in designing their future interview formats in a trainee-centric fashion.

Virtual Interviews and Their Effect on Cognitive Load for Graduate Medical Education Applicants and Programs.

The impact of coronavirus disease (COVID-19) has dramatically affected virtually all aspects of health care use, including patient care, research, and education. Among the groups affected were prospective applicants to graduate medical education training programs. To ensure a safe and equitable process for residency and fellowship application, multiple accrediting bodies strongly recommended that training programs conduct fellowship and residency interviews in a virtual format. With little experience in virtual interviewing, most programs, including ours, were compelled to make substantial changes to the traditional interview format. We present some of the unanticipated challenges we experienced with virtual interviewing in the context of cognitive load theory. We use cognitive load theory to highlight why the challenges existed. We also offer practical tips to minimize the cognitive load experienced with virtual interviewing so that trainees and programs alike derive maximal benefit when using virtual communication platforms.

A National Survey of Burnout and Depression Among Fellows Training in Pulmonary and Critical Care Medicine: A Special Report by the Association of Pulmonary and Critical Care Medicine Program Directors.

BACKGROUND: The prevalence of burnout and depressive symptoms is high among physician trainees. RESEARCH QUESTION: What is the burden of burnout and depressive symptoms among fellows training in pulmonary and critical care medicine (PCCM) and what are associated individual fellow, program, and institutional characteristics? STUDY DESIGN AND METHODS: We conducted a cross-sectional electronic survey of fellows enrolled in pulmonary, PCCM, and critical care medicine training programs in the United States to assess burnout and depressive symptoms. Burnout symptoms were measured using the Maslach Burnout Index two-item measure. The two-item Primary Care Evaluation of Mental Disorders Procedure was used to screen for depressive symptoms. For each of the two outcomes (burnout and depressive symptoms), we constructed three multivariate logistic regression models to assess individual fellow characteristics, program structure, and institutional polices associated with either burnout or depressive symptoms. RESULTS: Five hundred two of the 976 fellows who received the survey completed it-including both outcome measures-giving a response rate of 51%. Fifty percent of fellows showed positive results for either burnout or depressive symptoms, with 41% showing positive results for depressive symptoms, 32% showing positive results for burnout, and 23% showing positive results for both. Reporting a coverage system in the case of personal illness or emergency (adjusted OR [aOR], 0.44; 95% CI, 0.26-0.73) and access to mental health services (aOR, 0.14; 95% CI, 0.04-0.47) were associated with lower odds of burnout. Financial concern was associated with higher odds of depressive symptoms (aOR, 1.13; 95% CI, 1.05-1.22). Working more than 70 hours in an average clinical week and the burdens of electronic health record (EHR) documentation were associated with a higher odds of both burnout and depressive symptoms. INTERPRETATION: Given the high prevalence of burnout and depressive symptoms among fellows training in PCCM, an urgent need exists to identify solutions that address this public health crisis. Strategies such as providing an easily accessible coverage system, access to mental health resources, reducing EHR burden, addressing work hours, and addressing financial concerns among trainees may help to reduce burnout or depressive symptoms and should be studied further by the graduate medical education community.

Balancing Demands: Determinants of Burnout Reported by Fellows in Pulmonary and Critical Care Medicine.

Background: Burnout is common among physicians who care for critically ill patients and is known to contribute to worse patient outcomes. Fellows training in pulmonary and critical care medicine (PCCM) have risk factors that make them susceptible to burnout; for example, clinical environments that require increased intellectual and emotional demands with long hours. The Accreditation Council for Graduate Medical Education has recognized the increasing importance of trainee burnout and encourages training programs to address burnout. Objective: To assess factors related to training and practice that posed a threat to the well-being among fellows training in PCCM and to obtain suggestions regarding how programs can improve fellow well-being. Methods: We conducted a qualitative content analysis of data collected from a prior cross-sectional electronic survey with free-response questions of fellows enrolled in pulmonary, PCCM, and critical care medicine training programs in the United States. Fellows were asked what factors posed a threat to their well-being and what changes their training program could implement. Responses were qualitatively coded and categorized into themes using thematic analysis. Results: A total of 427 fellows (44% of survey respondents) completed at least one free-response question. The majority of respondents (60%) identified as male and white/non-Hispanic (59%). The threats to well-being and burnout were grouped into five themes: clinical burden, individual factors, team culture, limited autonomy, and program resources. Clinical burden was the most common threat discussed by fellows. Fellows highlighted factors contributing to burnout that specifically pertained to trainees including challenging interpersonal relationships with attending physicians and limited protected educational time. Fellows proposed solutions addressing clinical care, changes at the program or institution level, and organizational culture changes to improve well-being. Conclusion: This study provides insight into factors fellows report as contributors to burnout and decreased well-being in addition to investigating fellow-driven solutions toward improving well-being. These solutions may help pulmonary, PCCM, and critical care medicine program directors better address fellow well-being in the future.

Lessons on Outbreak Preparedness From the Cleveland Clinic.

Disasters, including infectious disease outbreaks, are inevitable. Hospitals need to plan in advance to ensure that their systems can adapt to a rapidly changing environment if necessary. This review provides an overview of 10 general principles that hospitals and health-care systems should consider when developing disaster plans. The principles are consistent with an "all-hazards" approach to disaster mitigation. This approach is adapted to planning for a multiplicity of threats but emphasizes highly relevant scenarios, such as the coronavirus disease 2019 pandemic. We also describe specific ways these principles helped prepare our hospital for this pandemic. Key points include acting quickly, identifying and engaging key stakeholders early, providing accurate information, prioritizing employee safety and mental health, promoting a fully integrated clinical response, developing surge plans, preparing for ethical dilemmas, and having a cogent exit strategy for post-disaster recovery.

Salvage therapies for refractory hypoxemia in ARDS.

Acute Respiratory Distress Syndrome (ARDS) is a condition of varied etiology characterized by the acute onset (within 1 week of the inciting event) of hypoxemia, reduced lung compliance, diffuse lung inflammation and bilateral opacities on chest imaging attributable to noncardiogenic (increased permeability) pulmonary edema. Although multi-organ failure is the most common cause of death in ARDS, an estimated 10-15% of the deaths in ARDS are caused due to refractory hypoxemia, i.e.- hypoxemia despite lung protective conventional ventilator modes. In these cases, clinicians may resort to other measures with less robust evidence -referred to as "salvage therapies". These include proning, 48 h of paralysis early in the course of ARDS, various recruitment maneuvers, unconventional ventilator modes, inhaled pulmonary vasodilators, and Extracorporeal membrane oxygenation (ECMO). All the salvage therapies described have been associated with improved oxygenation, but with the exception of proning and 48 h of paralysis early in the course of ARDS, none of them have a proven mortality benefit. Based on the current evidence, no salvage therapy has been shown to be superior to the others and each of them is associated with its own risks and benefits. Hence, the order of application of these therapies varies in different institutions and should be applied following a risk-benefit analysis specific to the patient and local experience. This review explores the rationale, evidence, advantages and risks behind each of these strategies.

Modeling of Lung Function Recovery in Neuralgic Amyotrophy With Diaphragm Impairment.

BACKGROUND: Neuralgic amyotrophy is an inflammatory peripheral nerve disorder in which phrenic nerve involvement can lead to diaphragm paralysis. The prevalence, magnitude, and time course of diaphragm recovery are uncertain. METHODS: This study modeled the course of recovery of lung function in 16 subjects with diaphragm impairment from neuralgic amyotrophy. The first and last available vital capacity, sitting-to-supine decline in vital capacity, and maximal inspiratory pressures were compared. RESULTS: An asymptotic regression model analysis in 11 subjects with at least partial recovery provided estimates of the vital capacity at onset (47%, 95% CI 25-68%), the final vital capacity (81%, 95% CI 62-101%), and the half-time to recovery (22 months, 95% CI 15-43 months). In those subjects, there was a significant improvement between the first and last measured FVC (median 44-66%, P = .004) and maximal inspiratory pressure (mean 34-51%, P = .004). Five subjects (31%) with complete recovery had a final sitting-to-supine drop of vital capacity of 16% and a maximal predicted inspiratory pressure of 63%. CONCLUSIONS: Sixty-nine percent of subjects with diaphragm impairment from neuralgic amyotrophy experience recovery of lung function and diaphragm strength, but recovery is slow and may be incomplete.

Screening for non-small cell lung cancer.

Lung cancer is the leading cause of cancer mortality and is usually discovered at an advanced stage, when treatment is generally not effective. Many researchers have investigated the value of screening for lung cancer, which would theoretically allow earlier detection and more effective treatment. Unfortunately, no trials of screening strategies for lung cancer have shown a mortality benefit, and as a result, no major medical organization currently recommends screening. Research continues to seek proof of the benefit of screening as new techniques are developed, including low-dose spiral computed tomography (CT), autofluorescence bronchoscopy, and advanced techniques of sputum analysis. Although there are promising data on the sensitivity of these newer screening methods, especially low-dose CT, for detecting early lung cancer, none of the published trials are controlled, and they have not yet proven a decrease in mortality. There are ongoing randomized, controlled trials aiming to demonstrate a mortality benefit. Patients who are interested in being screened for lung cancer should be encouraged to participate in well-designed clinical trials whenever possible.

Septic pulmonary embolism: presenting features and clinical course of 14 patients.

BACKGROUND: Septic pulmonary embolism (SPE) is an uncommon disorder with an insidious onset and is difficult to diagnose. STUDY OBJECTIVES: To characterize the presenting features and clinical course of patients with SPE. DESIGN: Retrospective study. SETTING: Tertiary care, referral medical center. PATIENTS: Fourteen subjects with SPE diagnosed during a 6-year period between 1996 and 2002. INTERVENTIONS: None. RESULTS: The median age of these patients was 37.5 years (range, 14 to 81 years) and included five women. Presenting symptoms included fever (93%), dyspnea (36%), pleuritic chest pain (29%), cough (14%), and hemoptysis (7%). The median duration of symptoms before diagnosis was 18 days (range, 5 to 180 days). A potential source or underlying condition that predisposed to SPE was identified in all 14 patients and included Lemierre syndrome (4 patients), central venous catheter infection (3 patients), prosthetic cardiac valve (2 patients), and pacemaker infection (2 patients). Two patients had a focal extrapulmonary infection, and one patient was an IV drug user. Most common pathogens were staphylococcal species (eight patients) and fusobacterium (four patients). Chest radiographic presentation was usually nonspecific, but CT was more helpful and revealed multiple nodular opacities peripherally, often with cavitation. Transesophageal echocardiography was performed in eight patients and demonstrated infectious vegetations in four cases. Aside from antimicrobial therapy and removal of infected devices, the management of these patients included cardiac surgery (two patients), thoracoscopic surgery with decortication (one patient), and tube thoracostomy (one patient). All 14 patients recovered from their illness. CONCLUSIONS: We conclude that SPE presents with variable and often nonspecific clinical and radiographic features. The diagnosis is usually suggested by the presence of a predisposing factor, febrile illness, and CT findings of multiple, nodular lung infiltrates peripherally, with or without cavitation.

Engendering enthusiasm for sustainable disaster critical care response: why this is of consequence to critical care professionals?

Disaster medical response has historically focused on the pre-hospital and initial treatment needs of casualties. In particular, the critical care component of many disaster response plans is incomplete. Equally important, routinely available critical care resources are almost always insufficient to respond to disasters that generate anything beyond a 'modest' casualty stream. Large-scale monetary funding to effectively remedy these shortfalls is unavailable. Education, training, and improved planning are our most effective initial steps. We suggest several areas for further development, including dual usage of resources that may specifically augment critical care disaster medical capabilities over time.

Noninfectious lung pathology in patients with Crohn's disease.

Lung involvement in Crohn's disease is not well characterized. We reviewed our experience with 11 lung biopsies (seven wedge and four transbronchial) from patients with Crohn's disease to study this association further. Negative cultures, special stains for organisms Gomori-methenamine-silver [GMS], acid fast), and polymerase chain reaction for (four cases) were required for inclusion. The group included five women and six men with a mean age of 47 years (range 13-84 years). A diagnosis of Crohn's disease preceded the lung disease in nine patients. In two patients the diagnosis of Crohn's disease followed the diagnosis of their pulmonary disease 1 and 15 months later. Radiologically, eight patients had diffuse infiltrates, two had bilateral nodular infiltrates, and one had a mass. Chronic bronchiolitis with nonnecrotizing granulomatous inflammation was present in four patients, one of whom was taking mesalamine. Two patients had an acute bronchiolitis associated with a neutrophil-rich bronchopneumonia with suppuration and vague granulomatous features. One patient on mesalamine had cellular interstitial pneumonia with rare giant cells. Four patients demonstrated organizing pneumonia with focal granulomatous features, two of whom were taking mesalamine, and one of these two responded to infliximab (anti-tumor necrosis factor) monoclonal antibody therapy. Noninfectious pulmonary disease in patients with Crohn's disease has variable histologic appearances, including granulomatous inflammation and airway-centered disease resembling that seen in patients with ulcerative colitis. Drugs may contribute to pulmonary disease in some patients.