The Association Between Age at Diagnosis and Disease Characteristics and Damage in Patients With ANCA-Associated Vasculitis.

OBJECTIVE: This study examined the relationship between age at diagnosis and disease characteristics and damage in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: Analysis of a prospective longitudinal cohort of patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic GPA (EGPA) in the Vasculitis Clinical Research Consortium (2013-2021). Disease cohorts were divided by age at diagnosis (years): children (<18), young adults (18-40), middle-aged adults (41-65), and older adults (>65). Data included demographics, ANCA type, clinical characteristics, Vasculitis Damage Index (VDI) scores, ANCA Vasculitis Index of Damage (AVID) scores, and novel disease-specific and non-disease-specific damage scores built from VDI and AVID items. RESULTS: Analysis included data from 1020 patients with GPA/MPA and 357 with EGPA. Female predominance in GPA/MPA decreased with age at diagnosis. AAV in childhood was more often GPA and proteinase 3-ANCA positive. Children with GPA/MPA experienced more subglottic stenosis and alveolar hemorrhage; children and young adults with EGPA experienced more alveolar hemorrhage, need for intubation, and gastrointestinal involvement. Older adults (GPA/MPA) had more neurologic manifestations. After adjusting for disease duration, medications, tobacco, and ANCA, all damage scores increased with age at diagnosis for GPA/MPA (P < 0.001) except the disease-specific damage score, which did not differ (P = 0.44). For EGPA, VDI scores increased with age at diagnosis (P < 0.009), whereas all other scores were not significantly different. CONCLUSION: Age at diagnosis is associated with clinical characteristics in AAV. Although VDI and AVID scores increase with age at diagnosis, this is driven by non-disease-specific damage items.

Single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus tiotropium monotherapy in patients with COPD.

Chronic obstructive pulmonary disease (COPD) treatment guidelines do not currently include recommendations for escalation directly from monotherapy to triple therapy. This 12-week, double-blind, double-dummy study randomized 800 symptomatic moderate-to-very-severe COPD patients receiving tiotropium (TIO) for ≥3 months to once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 mcg via ELLIPTA (n = 400) or TIO 18 mcg via HandiHaler (n = 400) plus matched placebo. Study endpoints included change from baseline in trough forced expiratory volume in 1 s (FEV1) at Days 85 (primary), 28 and 84 (secondary), health status (St George's Respiratory Questionnaire [SGRQ] and COPD Assessment Test [CAT]) and safety. FF/UMEC/VI significantly improved trough FEV1 at all timepoints (Day 85 treatment difference [95% CI] 95 mL [62-128]; P < 0.001), and significantly improved SGRQ and CAT versus TIO. Treatment safety profiles were similar. Once-daily single-inhaler FF/UMEC/VI significantly improved lung function and health status versus once-daily TIO in symptomatic moderate-to-very-severe COPD patients, with a similar safety profile.

Once-daily single-inhaler versus twice-daily multiple-inhaler triple therapy in patients with COPD: lung function and health status results from two replicate randomized controlled trials.

BACKGROUND: The comparative efficacy of inhaled corticosteroid/long-acting muscarinic antagonist/long-acting ß2-agonist (ICS/LAMA/LABA) triple therapy administered via single or multiple inhalers in patients with chronic obstructive pulmonary disease (COPD) has not been evaluated comprehensively. We conducted two replicate trials comparing single- with multiple-inhaler ICS/LAMA/LABA combination in COPD. METHODS: 207608 and 207609 were Phase IV, 12-week, randomized, double-blind, triple-dummy non-inferiority trials comparing once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 µg via Ellipta inhaler, with twice-daily budesonide/formoterol (BUD/FOR) 400/12 µg via metered-dose inhaler plus once-daily tiotropium (TIO) 18 µg via HandiHaler. Patients had symptomatic COPD and forced expiratory volume in 1 s (FEV1) < 50% predicted, or FEV1 < 80% predicted and ≥ 2 moderate or 1 severe exacerbations in the prior year. The primary endpoint in both trials was weighted mean change from baseline (wmCFB) in 0-24-h FEV1 at Week 12. Secondary endpoints included CFB in trough FEV1 at Day 84 and 85. Other endpoints included serial FEV1 and health status outcomes at Week 12. Safety was evaluated descriptively. RESULTS: The modified per-protocol population included 720 and 711 patients in studies 207608 and 207609 (intent-to-treat population: 728 and 732). FF/UMEC/VI was non-inferior to BUD/FOR+TIO for wmCFB in 0-24-h FEV1 at Week 12 (Study 207608 treatment difference [95% confidence interval]: 15 mL [- 13, 43]; Study 207609: 11 mL [- 20, 41]). FF/UMEC/VI improved trough FEV1 CFB versus BUD/FOR+TIO at Day 84 and 85 (Day 85 treatment difference: Study 207608: 38 mL [10, 66]; Study 207609: 51 mL [21, 82]) and FEV1 at 12 and 24 h post-morning dose at Week 12 in both studies. No treatment differences were seen in health status outcomes. Safety profiles were similar between treatments; pneumonia occurred in 7 (< 1%) patients with FF/UMEC/VI and 9 (1%) patients with BUD/FOR+TIO, across both studies. CONCLUSIONS: FF/UMEC/VI was non-inferior to BUD/FOR+TIO for wmCFB in 0-24-h FEV1 at Week 12 in patients with COPD. Greater improvements in trough and serial FEV1 measurements at Week 12 with FF/UMEC/VI versus BUD/FOR+TIO, together with similar health status improvements and safety outcomes including the incidence of pneumonia, suggest that once-daily single-inhaler FF/UMEC/VI triple therapy is a viable option for patients looking to simplify their treatment regimen. TRIAL REGISTRATION: GSK (207608/207609; NCT03478683/NCT03478696).

Current evidence for COPD management with dual long-acting muscarinic antagonist/long-acting ß2-agonist bronchodilators.

Long-acting inhaled bronchodilator medications are recommended as initial maintenance therapy for many patients with COPD. These medications include long-acting muscarinic antagonists (LAMA) and long-acting ß2-agonists (LABA). Combinations of long-acting bronchodilator agents (LAMA/LABA) and inhaled corticosteroids combined with LABA (ICS/LABA) are also used as initial or follow-up therapy in patients with more severe symptoms or at risk of COPD exacerbations. This review summarizes the position of LAMA/LABA combinations in treatment recommendations, and the evidence supporting their placement relative to LAMA monotherapy and ICS/LABA combination therapy, as well as differences within the LAMA/LABA class. Most studies show that LAMA/LABA treatment leads to greater improvements in lung function and symptoms than LAMA monotherapy or ICS/LABA treatment. There are fewer studies comparing the impact of different medication classes on patients' risk of exacerbations; however, the available evidence suggests that LAMA/LABA treatment and LAMA monotherapy lead to a similar reduction in exacerbation risk, while the effect of LAMA/LABA compared with ICS/LABA remains unclear. The incidence of adverse events is similar with LAMA/LABA and LAMA alone. There is a lower risk of pneumonia with LAMA/LABA compared with ICS/LABA. This evidence supports the use of LAMA/LABA combinations as an initial maintenance therapy option for symptomatic patients with low exacerbation risk and severe breathlessness or patients with severe symptoms who are at risk of exacerbations, and as follow-up treatment in patients with uncontrolled symptoms or exacerbations on bronchodilator monotherapy.

Invasive Mechanical Ventilation.

Invasive mechanical ventilation is a potentially lifesaving intervention for acutely ill patients. The goal of this review is to provide a concise, clinically focused overview of basic invasive mechanical ventilation for the many clinicians who care for mechanically ventilated patients. Attention is given to how common ventilator modes differ in delivering a mechanical breath, evaluation of respiratory system mechanics, how to approach acute changes in airway pressure, and the diagnosis of auto-positive end-expiratory pressure. Waveform interpretation is emphasized throughout the review.

Chugging in patients on veno-venous extracorporeal membrane oxygenation: An under-recognized driver of intravenous fluid administration in patients with acute respiratory distress syndrome?

BACKGROUND: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is increasingly utilized in the management of severe acute respiratory distress syndrome (ARDS). Providers who care for patients on VV-ECMO should be familiar with common circuit complications. OBJECTIVES: To provide an example of a common complication, circuit "chugging," and suggest a management algorithm which aims to avoid excessive fluid administration to patients with ARDS. METHODS: We use a clinical case to illustrate chugging and discuss potential management strategies. RESULTS: Our patient received frequent boluses of albumin for intermittent circuit chugging contributing to a net positive fluid balance of roughly 6 liters 4 days after cannulation. CONCLUSIONS: Chugging is a common complication for patients on VV ECMO. A thoughtful approach to management may help limit potentially harmful fluid administration for patients with ARDS.

Description and Early Outcomes of a Comprehensive Curriculum Redesign at the Northwestern University Feinberg School of Medicine.

In 2012, the Northwestern University Feinberg School of Medicine launched a redesigned curriculum addressing the four primary recommendations in the 2010 Carnegie Foundation for the Advancement of Teaching report on reforming medical education. This new curriculum provides a more standardized evaluation of students' competency achievement through a robust portfolio review process coupled with standard evaluations of medical knowledge and clinical skills. It individualizes learning processes through curriculum flexibility, enabling students to take electives earlier and complete clerkships in their preferred order. The new curriculum is integrated both horizontally and vertically, combining disciplines within organ-based modules and deliberately linking elements (science in medicine, clinical medicine, health and society, professional development) and threads (medical decision making, quality and safety, teamwork and leadership, lifestyle medicine, advocacy and equity) across the three phases that replaced the traditional four-year timeline. It encourages students to conduct research in an area of interest and commit to lifelong learning and self-improvement. The curriculum formalizes the process of professional identity formation and requires students to reflect on their experiences with the informal and hidden curricula, which strongly shape their identities.The authors describe the new curriculum structure, explain their approach to each Carnegie report recommendation, describe early outcomes and challenges, and propose areas for further work. Early data from the first cohort to progress through the curriculum show unchanged United States Medical Licensing Examination Step 1 and 2 scores, enhanced student research engagement and career exploration, and improved student confidence in the patient care and professional development domains.

First-year residents outperform third-year residents after simulation-based education in critical care medicine.

INTRODUCTION: Previous research shows that gaps exist in internal medicine residents' critical care knowledge and skills. The purpose of this study was to compare the bedside critical care competency of first-year residents who received a simulation-based educational intervention plus clinical training with third-year residents who received clinical training alone. METHODS: During their first 3 months of residency, a group of first-year residents completed a simulation-based educational intervention. A group of traditionally trained third-year residents who did not receive simulation-based training served as a comparison group. Both groups were evaluated using a 20-item clinical skills assessment at the bedside of a patient receiving mechanical ventilation at the end of their medical intensive care unit rotation. Scores on the skills assessment were compared between groups. RESULTS: Simulator-trained first-year residents (n = 40) scored significantly higher compared with traditionally trained third-year residents (n = 27) on the bedside assessment (91.3% [95% confidence interval, 88.2%-94.3%] vs. 80.9% [95% confidence interval, 76.8%-85.0%]; P < 0.001). CONCLUSIONS: First-year residents who completed a simulation-based educational intervention demonstrated higher clinical competency compared with third-year residents who did not undergo simulation training. Critical care competency cannot be assumed after clinical intensive care unit rotations; simulation-based curricula can help ensure residents are proficient to care for critically ill patients.

Retention of critical care skills after simulation-based mastery learning.

BACKGROUND: Whether cognitive and patient care skills attained during simulation-based mastery learning (SBML) are retained is largely unknown. OBJECTIVE: We studied retention of intensive care unit (ICU) clinical skills after an SBML boot camp experience. METHODS: Forty-seven postgraduate year (PGY)-1 residents completed SBML intervention designed to increase procedural, communication, and patient care skills. The intervention included ICU skills such as ventilator and hemodynamic parameter management. Residents were required to meet or exceed a minimum passing score (MPS) on a clinical skills examination before starting actual patient care. Skill retention was assessed in 42 residents who rotated in the medical ICU. Residents received a standardized 15-minute booster teaching session reviewing key concepts during the first week of the rotation. During the fourth week of their rotation, PGY-1 residents completed a clinical skills examination at the bedside of an actual ICU patient. Group mean examination scores and the proportion of subjects who met or exceeded the MPS at each testing occasion were compared. RESULTS: Residents scored a mean 90% (SD  =  6.5%) on the simulated skills examination immediately after training. Residents retained skills obtained through SBML as the mean score at bedside follow-up testing was 89% (SD  =  8.9%, P  =  .36). Thirty-seven of 42 (88%) PGY-1 residents met or exceeded the MPS at follow-up. CONCLUSION: SBML leads to substantial retention of critical care knowledge, and patient care skills PGY-1 boot camp is a highly efficient and effective model that can be administered at the beginning of the academic year.

Use of simulation-based education to improve resident learning and patient care in the medical intensive care unit: a randomized trial.

PURPOSE: The purpose of this study is to determine the effect of simulation-based education on the knowledge and skills of internal medicine residents in the medical intensive care unit (MICU). METHODS AND MATERIALS: From January 2009 to January 2010, 60 first-year residents at a tertiary care teaching hospital were randomized by month of rotation to an intervention group (simulator-trained, n = 26) and a control group (traditionally trained, n = 34). Simulator-trained residents completed 4 hours of simulation-based education before their medical intensive care unit (MICU) rotation. Topics included circulatory shock, respiratory failure, and mechanical ventilation. After their rotation, residents completed a standardized bedside skills assessment using a 14-item checklist regarding respiratory mechanics, ventilator settings, and circulatory parameters. Performance of simulator-trained and traditionally trained residents was compared using a 2-tailed independent-samples t test. RESULTS: Simulator-trained residents scored significantly higher on the bedside skills assessment compared with traditionally trained residents (82.5% ± 10.6% vs 74.8% ± 14.1%, P = .027). Simulator-trained residents were highly satisfied with the simulation curriculum. CONCLUSIONS: Simulation-based education significantly improved resident knowledge and skill in the MICU. Knowledge acquired in the simulated environment was transferred to improved bedside skills caring for MICU patients. Simulation-based education is a valuable adjunct to standard clinical training for residents in the MICU.

Pressure modes of invasive mechanical ventilation.

Pressure modes of invasive mechanical ventilation generate a tidal breath by delivering pressure over time. Pressure control ventilation (PC) is the prototypical pressure mode and is patient- or time-triggered, pressure-limited, and time-cycled. Other pressure modes include pressure support ventilation (PSV), pressure-regulated volume control (PRVC, also known as volume control plus [VC+]), airway pressure release ventilation (APRV), and biphasic ventilation (also known as BiLevel). Despite their complexity, modern ventilators respond to patient effort and respiratory system mechanics in a fairly predictable fashion. No single mode has consistently demonstrated superiority in clinical trials; however, empiric management with a pressure mode may achieve the goals of patient-ventilator synchrony, effective respiratory system support, adequate gas exchange, and limited ventilator-induced lung injury.

Asthma in adolescents and adults.

OVERVIEW: More than 16 million U.S. adults have asthma, a condition that prompts 2 million ED visits and nearly half a million hospital admissions annually. Management of this potentially deadly, chronic inflammatory disease depends on early diagnosis, accurate classification, appropriate treatment, and targeted patient education. This article outlines current guideline recommendations for asthma and reviews what clinicians need to teach patients about its pathophysiology, pharmacotherapy, self monitoring, and environmental control. The authors discuss the classic clinical presentation of the disease, describe how to assess severity and control, and explain how such assessments can guide management.

Online learning versus simulation for teaching principles of mechanical ventilation to nurse practitioner students.

Patient simulation is increasingly used in the education of healthcare providers, yet few studies have compared simulation to other teaching modalities. The purpose of this study was to determine differences in knowledge acquisition and student satisfaction between two methods of teaching the principles of mechanical ventilation to advanced practice nursing (APN) students: high-fidelity patient simulation (including face-to-face instruction) versus an online, narrated PowerPoint presentation. Twenty APN students were randomized to either the simulation or online teaching method in this pre/posttest study. Measures included a 12-item knowledge questionnaire and a 5-item satisfaction survey. Both groups had significant improvement in knowledge scores from pretest to posttest, but knowledge scores were not significantly different at posttest between groups. Student satisfaction with their learning method was significantly higher in the simulation group. Students choosing to participate in the alternative teaching method after study completion preferred the simulation to the online method.

Basic invasive mechanical ventilation.

Invasive mechanical ventilation is a lifesaving intervention for patients with respiratory failure. The most commonly used modes of mechanical ventilation are assist-control, synchronized intermittent mandatory ventilation, and pressure support ventilation. When employed as a diagnostic tool, the ventilator provides data on the static compliance of the respiratory system and airway resistance. The clinical scenario and the data obtained from the ventilator allow the clinician to provide effective and safe invasive mechanical ventilation through manipulation of the ventilator settings. While life-sustaining in many circumstances, mechanical ventilation may also be toxic and should be withdrawn when clinically appropriate.

Utility of [18F]2-fluoro-2-deoxyglucose-PET in sporadic and tuberous sclerosis-associated lymphangioleiomyomatosis.

Mutations in tuberous sclerosis complex (TSC) genes are associated with dysregulated mammalian target of rapamycin (mTOR)/Akt signaling and unusual neoplasms called perivascular epithelioid cell tumors (PEComas), including angiomyolipomas (AMLs) and lymphangioleiomyomatosis (LAM). Tools that quantify metabolic activity and total body burden of AML and LAM cells would be valuable for the assessment of disease progression and the response to therapy in patients with TSC and LAM. Our hypothesis was that constitutive activation of mTOR in LAM and AML cells would result in increased glucose uptake of [(18)F]2-fluoro-2-deoxyglucose (FDG) on PET scanning, as has been suggested by a single prior case report. After institutional review board approval, FDG-PET scanning was performed in six LAM patients. Six additional LAM patients underwent FDG-PET scanning for clinical evaluation of suspected malignancy. Pleural uptake related to prior therapy was identified in four individuals with a remote history of talc pleurodesis. Focal increased uptake was observed in a supraclavicular lymph node in a patient with Hodgkin lymphoma and in a lung nodule in a patient with a biopsy-documented primary lung adenocarcinoma. In one TSC-LAM patient with a biopsy-documented malignant uterine PEComa, robust uptake was noted in metastatic nodules in the lung but not in the LAM-involved lung parenchyma or the patient's massive abdominal lymphangioleiomyomas. No abnormal uptake was identified in the AMLs or LAM lesions in any patients. This pilot study suggests that FDG-PET scans are negative in patients with benign PEComas and therefore are not likely to be useful for estimating the burden of disease in patients with TSC or LAM, but that FDG-PET scans can be used to identify or exclude other neoplasms in these patients.