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Objective: The evidence‐based DETECT pulmonary arterial hypertension (PAH) algorithm is frequently used in patients with systemic sclerosis (SSc) to help clinicians screen for PAH by using noninvasive data to recommend patient referral to echocardiography and, if applicable, for a diagnostic right‐sided heart catheterization. However, the hemodynamic definition of PAH was recently updated in the 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines. The performance of DETECT PAH in identifying patients with a high risk of PAH according to this new definition was assessed. Methods: In this post hoc analysis of DETECT, which comprised 466 patients with SSc, the performance of the DETECT PAH algorithm in identifying patients with a high risk of PAH as defined in the 2022 ESC/ERS guidelines (mean pulmonary arterial pressure [mPAP] >20 mm Hg, pulmonary capillary wedge pressure [PCWP] ≤15 mm Hg, and pulmonary vascular resistance >2 Wood units) was assessed using summary statistics and was descriptively compared to the known performance of DETECT PAH as defined in 2014, when it was developed (mPAP ≥25 mm Hg and PCWP ≤15 mm Hg). Results: The sensitivity of DETECT PAH in identifying patients with a high risk of PAH according to the 2022 ESC/ERS definition was lower (88.2%) compared to the 2014 definition (95.8%). Specificity improved from 47.8% to 50.8%. Conclusion: The performance of the DETECT algorithm to screen for PAH in patients with SSc is maintained when PAH is defined according to the 2022 ESC/ERS hemodynamic definition, indicating that DETECT remains applicable to screen for PAH in patients with SSc. [ABSTRACT FROM AUTHOR]

Background: Crohn's disease (CD) and ulcerative colitis (UC) are the two most prevalent forms of inflammatory bowel disease (IBD) causing frequent diarrhea, rectal bleeding, fatigue, and abdominal pain. IBD may result in complications requiring hospitalizations and surgical procedure, hence IBD can negatively impact patients' quality of life, work productivity, and increase societal economic burden. Limited data exists assessing epidemiologic trends and population-level health outcomes among patients with IBD in Sweden. This study assessed the trends in annual incidence and prevalence of CD, annual inpatient and outpatient visits, employment status and sickness absence among adults with IBD in Sweden from 2001 to 2017., Methods: Data were acquired from four nationwide registers provided by the National Board of Health and Welfare in Sweden and linked through the unique personal identity number. Individuals aged ≥18 years with ≥2 primary diagnoses of CD (ICD-10 K50) or ≥2 primary diagnoses of UC (ICD-10 K51) from 01/01/2001 to 12/30/2017 were selected. Date of the first CD or UC diagnosis was designated as index date. All individuals were followed until death, lost to follow up or end of study., Results: A total of 30,895 patients with CD and 50,415 with UC were included in the analysis, respectively. The mean follow-up for patients was 10.1 (±5.33) and 10.4 (±5.21) years for CD and UC. The mean (±SD) age among CD patients was 40.4 (±18.4) years and 42.6 (±18.2) years for UC. The most frequently observed comorbid condition was noninfective enteritis and colitis for patients with CD (24.2%) and UC (15.7%). The annual incidence of CD was 10 per 100,000 person-years in 2017, while the incidence of UC was 3 per 100,000 in 2017. 40.6% of CD patients and 30.8% of UC patients had ≥ 1 inpatient admission during 1-year post-index period, of which 53.5% and 51.2% had inpatient care lasting more than 1 week. Among patients with ≥ 1 outpatient services (CD: n = 30,675; UC: n = 50,183), 41.7% and 29.2% of patients had more than 5 visits during 1-year post-index period. Among patients who were eligible for employment and disability benefit analyses who had at least 1-year follow-up (CD: n = 23,731; UC: n = 39,391), 27.9% of CD patients and 23.1% of UC patients were not in employment; among those who were in employment (CD: n = 17,039; UC: n=30,302), 30% and 24.6% reported sickness absence within the calendar year after the index date, respectively., Conclusion: Findings from this study of a large national cohort of patients followed for many years demonstrates the significant epidemiological, clinical, and socioeconomic impact of patients with CD and UC. Further research is needed to understand underlying factors driving inpatient admissions among patients with IBD. With an increasing annual prevalence, IBD continues to impose a substantial public health burden to patients, their families and health care services., (Copyright © 2021 by The American College of Gastroenterology.)

Introduction: Exercise limitation, dynamic hyperinflation, and exertional dyspnea are key features of symptomatic chronic obstructive pulmonary disease (COPD). We assessed the effects of glycopyrronium bromide (NVA237), a once-daily, long-acting muscarinic antagonist, on exercise tolerance in patients with moderate to severe COPD., Methods: Patients were randomized to a cross-over design of once-daily NVA237 50 μg or placebo for 3 weeks, with a 14-day washout. Exercise endurance, inspiratory capacity (IC) during exercise, IC and expiratory volumes from spirometry, plethysmographic lung volumes, leg discomfort and dyspnea under exercise (Borg scales), and transition dyspnea index were measured on Days 1 and 21 of treatment. The primary endpoint was endurance time during a submaximal constant-load cycle ergometry test on Day 21., Results: A total of 108 patients were randomized to different treatment groups (mean age, 60.5 years; mean post-bronchodilator, forced expiratory volume in 1 second [FEV(1)] 57.1% predicted). Ninety-five patients completed the study. On Day 21, a 21% difference in endurance time was observed between patients treated with NVA237 and those treated with placebo (P < 0.001); the effect was also significant from Day 1, with an increase of 10%. Dynamic IC at exercise isotime and trough FEV(1) showed significant and clinically relevant improvements from Day 1 of treatment that were maintained throughout the study. This was accompanied by inverse decreases in residual volume and functional residual capacity. NVA237 was superior to placebo (P < 0.05) in decreasing leg discomfort (Borg CR10 scale) on Day 21 and exertional dyspnea on Days 1 and 21 (transition dyspnea index and Borg CR10 scale at isotime). The safety profile of NVA237 was similar to that of the placebo., Conclusion: NVA237 50 μg once daily produced immediate and significant improvement in exercise tolerance from Day 1. This was accompanied by sustained reductions in lung hyperinflation (indicated by sustained and significant improvements in IC at isotime), and meaningful improvements in trough FEV(1) and dyspnea. Improvements in exercise endurance increased over time, suggesting that mechanisms beyond improved lung function may be involved in enhanced exercise tolerance. (ClinicalTrials.gov Identifier: NCT01154127).

Purpose: To evaluate the activity of imatinib in treating advanced, life-threatening malignancies expressing one or more imatinib-sensitive tyrosine kinases., Experimental Design: This was a phase II, open-label, single arm study. Patients > or = 15 years old with malignancies showing histologic or molecular evidence of expression/activation of imatinib-sensitive tyrosine kinases were enrolled. Patients were treated with 400 or 800 mg/d imatinib for hematologic malignancy and solid tumors, respectively. Treatment was continued until disease progression or unacceptable toxicity. The primary objective was to identify evidence of imatinib activity with tumor response as the primary end point., Results: One hundred eighty-six patients with 40 different malignancies were enrolled (78.5% solid tumors, 21.5% hematologic malignancies). Confirmed response occurred in 8.9% of solid tumor patients (4 complete, 9 partial) and 27.5% of hematologic malignancy patients (8 complete, 3 partial). Notable activity of imatinib was observed in only five tumor types (aggressive fibromatosis, dermatofibrosarcoma protuberans, hypereosinophilic syndrome, myeloproliferative disorders, and systemic mastocytosis). A total of 106 tumors were screened for activating mutations: five KIT mutations and no platelet-derived growth factor receptor mutations were found. One patient with systemic mastocytosis and a partial response to therapy had a novel imatinib-sensitive KIT mutation (D816T). There was no clear relationship between expression or activation of wild-type imatinib-sensitive tyrosine kinases and clinical response., Conclusion: Clinical benefit was largely confined to diseases with known genomic mechanisms of activation of imatinib target kinases. Our results indicate an important role for molecular characterization of tumors to identify patients likely to benefit from imatinib treatment.