Inflammation and smooth muscle dysfunction are integral components of severe asthma that contribute to luminal obstruction causing airflow limitation, ventilation heterogeneity, and symptoms. This is ...important for guiding treatment decisions directed at the inflammatory (e.g., anti-T-helper cell type 2 monoclonal antibodies) and noninflammatory, smooth muscle-mediated (e.g., bronchial thermoplasty) components of severe asthma.
To investigate the contribution of eosinophilic bronchitis and smooth muscle dysfunction to magnetic resonance imaging (MRI) ventilation heterogeneity in patients with severe asthma.
We measured the inhaled hyperpolarized gas MRI response to salbutamol as a marker of smooth muscle dysfunction, and sputum eosinophils as a marker of airway inflammation, and their contributions to ventilation heterogeneity (quantified as the ventilation defect percent VDP) in 27 patients with severe asthma. Spirometry and forced oscillation airway resistance measurements were also acquired pre- and postsalbutamol. Patients were dichotomized on the basis of sputum eosinophilia, and pre- and postsalbutamol VDP and physiological measurements were evaluated.
MRI VDP improved with salbutamol inhalation in patients in whom sputum eosinophilia was uncontrolled (≥3%, n = 16) (P = 0.002) and in those in whom it was controlled (<3%, n = 11) (P = 0.02), independent of improvements in FEV
, indicating smooth muscle response. In those patients in whom sputum eosinophilia was uncontrolled, greater VDP persisted postsalbutamol (P = 0.004). Postsalbutamol VDP correlated with sputum eosinophils (r = 0.63; P = 0.005).
In patients with severe asthma, MRI regionally identifies the inflammatory and noninflammatory components of airway disease. Ventilation heterogeneity persists postsalbutamol in patients with uncontrolled eosinophilic bronchitis, which may be the functional consequence of airway inflammation.
Progressive fibrosing interstitial lung disease (PF-ILD) is characterised by progressive physiological, symptomatic and/or radiographic worsening. The real-world prevalence and characteristics of ...PF-ILD remain uncertain.
Patients were enrolled from the Canadian Registry for Pulmonary Fibrosis between 2015 and 2020. PF-ILD was defined as a relative forced vital capacity (FVC) decline ≥10%, death, lung transplantation or any two of: relative FVC decline ≥5% and <10%, worsening respiratory symptoms or worsening fibrosis on computed tomography of the chest, all within 24 months of diagnosis. Time-to-event analysis compared progression between key diagnostic subgroups. Characteristics associated with progression were determined by multivariable regression.
Of 2746 patients with fibrotic ILD (mean±sd age 65±12 years; 51% female), 1376 (50%) met PF-ILD criteria in the first 24 months of follow-up. PF-ILD occurred in 427 (59%) patients with idiopathic pulmonary fibrosis (IPF), 125 (58%) with fibrotic hypersensitivity pneumonitis (HP), 281 (51%) with unclassifiable ILD (U-ILD) and 402 (45%) with connective tissue disease-associated ILD (CTD-ILD). Compared with IPF, time to progression was similar in patients with HP (hazard ratio (HR) 0.96, 95% CI 0.79-1.17), but was delayed in patients with U-ILD (HR 0.82, 95% CI 0.71-0.96) and CTD-ILD (HR 0.65, 95% CI 0.56-0.74). Background treatment varied across diagnostic subtypes, with 66% of IPF patients receiving antifibrotic therapy, while immunomodulatory therapy was utilised in 49%, 61% and 37% of patients with CHP, CTD-ILD and U-ILD, respectively. Increasing age, male sex, gastro-oesophageal reflux disease and lower baseline pulmonary function were independently associated with progression.
Progression is common in patients with fibrotic ILD, and is similarly prevalent in HP and IPF. Routinely collected variables help identify patients at risk for progression and may guide therapeutic strategies.
PILLARS OF CHANGE Sustainable change that can empower VHA frontline teams to provide reliably safe care for veterans starts with three pillars of HRO: leadership commitment; a culture of safety; and ...continuous process improvement (CPI) To provide a solid foundation for these pillars, we rolled out baseline training for all new employees to cover HRO concepts, just culture, and safety behaviors; NCPS team training in which unit-level teams learn communication tools and decision-making strategies for managing human error, along with safe responses to operational threats (e.g., staff not complying with infection prevention protocols or not holding a time-out before a surgical procedure); the development of frontline teams to lead safety and reliability improvement projects; site-specific assessments and planning to identify HRO maturity, strengths, and gaps to form strategies for sustained improvement; HRO coaching led by trained HRO experts with military and/or VHA leadership experience to provide feedback and guidance on how to demonstrate and apply appropriate behaviors and practices; and experiential learning to spread strong safety and improvement practices across the enterprise through regional and national communities of practice and learning events. For outcome metrics, the targeted categories are zero harm (e.g., surgical inpatient deaths, falls with injury, perioperative pulmonary embolism, deep vein thrombosis, Clostridium difficile infections, postoperative sepsis), culture of safety (e.g., employee survey data reflecting transparency, trust, and teamwork), and employee health and safety (e.g., workplace safety assessments). With sensitivity to safety concerns, leaders moderated the pace of change, prioritized some activities over others, and adapted content to enable the adoption of HRO principles and practices. ...we integrate input from assessments into broader operational plans.
ABSTRACT
Introduction
In 2019, the Veteran’s Health Administration began its journey in pursuit of becoming an enterprise-wide High Reliability Organization (HRO). Improving the delivery of safe, ...high quality patient care is a central focus of HROs. Requisite to meeting this goal is the timely identification and resolution of problems. This is best achieved by empowering and engaging both clinical and non-clinical staff across the healthcare organization through the promotion of robust collaboration and communication between various disciplines. Improved care coordination and increased accountability are two important subsequent outcomes. One method for accomplishing this is through the implementation of tiered huddles.
Materials and Methods
An extensive review of the current literature from 2013 until June 2021 was conducted for evidence highlighting the experiences of other healthcare organizations during implementation of huddles. Following the review, a tiered huddle proposal was developed and presented to the executive leadership team of a healthcare system for approval. Pilot testing of the tiered huddle implementation plan began in October 2021 over a 12-week period with three services. On average, the pilot services had between three to four tiers from frontline staff to the executive level of leadership.
Results
Over the 12-week period, out of the possible 120 tiered huddles that could have been conducted, 68% (n = 81) were completed. Of the tiered huddles conducted, 99% (n = 80) started and ended on time. During the pilot test, seven issues were identified by frontline staff: coordination of pre-procedural coronavirus testing, equipment/computer issues, rooms out of service, staffing levels, and lack of responsiveness from other departments. Issues related to staffing, unresponsiveness from other departments, and equipment concerns required elevation to a higher-level tier with no issues remaining open. Delays in patient care, or prolongation of shift hours for staff because of tiered huddles, was low at 2.5% (n = 2). For the duration of the pilot test, a total of 75 minutes accounted for shifts being extended among five staff members.
Conclusions
The success of this initiative demonstrates the importance of thoughtfully creating a robust process when planning for the implementation of tiered huddles. The findings from this initiative will be of immense value with the implementation of tiered huddles across our healthcare system. We believe that this approach can be used by other healthcare institutions along their journey to improving patient safety and quality.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The clinical management of idiopathic pulmonary fibrosis (IPF) remains a major challenge due to lack of effective drug therapy or accurate indicators for disease progression. Fibrocytes are ...circulating mesenchymal cell progenitors that are involved in tissue repair and fibrosis.
To test the hypothesis that assay of these cells may provide a biomarker for activity and progression of IPF.
Fibrocytes were defined as cells positive for CD45 and collagen-1 by flow cytometry and quantified in patients with stable IPF and during acute exacerbation of the disease. We investigated the clinical and prognostic value of fibrocyte counts by comparison with standard clinical parameters and survival. We used healthy age-matched volunteers and patients with acute respiratory distress syndrome as control subjects.
Fibrocytes were significantly elevated in patients with stable IPF (n = 51), with a further increase during acute disease exacerbation (n = 7; P < 0.001 vs. control subjects). Patients with acute respiratory distress syndrome (n = 10) were not different from healthy control subjects or stable patients with IPF. Fibrocyte numbers were not correlated with lung function or radiologic severity scores, but they were an independent predictor of early mortality. The mean survival of patients with fibrocytes higher than 5% of total blood leukocytes was 7.5 months compared with 27 months for patients with less than 5% (P < 0.0001).
Fibrocytes are an indicator for disease activity of IPF and might be useful as a clinical marker for disease progression. This study suggests that quantification of circulating fibrocytes may allow prediction of early mortality in patients with IPF.
Summary COPD is characterized by increased cough, mucus production, and airway inflammation. Beating epithelial cell cilia contribute to mucociliary clearance with ciliary beat frequency (CBF) an ...important measure of cilia function. However, whether CBF varies with COPD severity is unknown. Aims: 1) to compare nasal cilia samples and their CBF from healthy non-smokers (Control), COPD and At Risk (cough and sputum production) subjects. 2) to determine the effect of pharmacologic agents that modulate mediators implicated in the pathogenesis of COPD on nasal CBF. Nasal brushings of ciliated cells were obtained from Control, At Risk and COPD subjects. Using high speed digital imaging, we measured baseline CBF ex vivo . Then, CBF was re-measured after 30 min perfusion with pharmacologic agents that modulate mediators implicated in COPD (salmeterol xinafoate, tiotropium bromide, licofelone, luteolin, YM976, Defensin HNP-1) and again after 30 min washout. CBF was significantly depressed in moderate and severe COPD compared to At Risk and Control subjects. There was an evident and persistent rise in CBF with all agents tested in COPD cilia except that YM976 effects persisted only in severe COPD. Only YM976 and tiotropium caused a persistent increase in CBF in At Risk cilia. The reduction of nasal CBF in moderate and severe COPD implies that impaired ciliary function may impact mucociliary clearance in COPD, potentially contributing to retention of secretions and infection. Pharmacologic agents with different mechanisms of action can increase CBF of COPD cilia. Further investigation of the signalling pathways influencing CBF of COPD cilia is needed.
Infliximab is a monoclonal antibody that binds and neutralizes circulating tumor necrosis factor-alpha, a key inflammatory cytokine in the pathophysiology of sarcoidosis. Despite the paucity of ...randomized clinical trials, infliximab is often considered a therapeutic option for refractory disease. Our study aimed to investigate the effectiveness of infliximab in patients with refractory sarcoidosis.
Sarcoidosis patients from three tertiary centres were retrospectively identified by pharmacy records based on treatment with infliximab. Treatment with Infliximab was initiated in patients who failed first and second line immunomodulators as determined by a multidisciplinary team of Respirologists, Dermatologists, ENT specialists, Rheumatologists, and Neurologists. Participants were characterized by the primary organ for which infliximab was initiated and the total number of organs involved. Clinical outcomes were categorized as treatment success versus failure. We defined treatment success as (A) improvement of cutaneous, upper airway, lymph node, gastrointestinal, eye, or joint manifestations; or (B) improvement or no change in central nervous system (CNS) or pulmonary manifestations.
33 patients with refractory sarcoidosis were identified. The proportion of treatment success was 100% (95% CI 54.1-100) in CNS, 91.7% (95% CI 61.5-99.8) in cutaneous, 78.6% (95% CI 49.2-95.3) in pulmonary and 71.5% (95% CI 29.0-96.3) in upper airway disease. The use of infliximab was associated with a reduction prednisone dose by 50%.
Infliximab is possibly an effective therapy for refractory sarcoidosis, with the greatest value in neurologic and cutaneous manifestations. Across all disease presentations, infliximab facilitated a clinically relevant reduction in corticosteroid dose. Relapse is common after discontinuation of infliximab.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Malignant pleural mesothelioma is a highly aggressive tumor associated with asbestos exposure. There are few effective treatment options for mesothelioma, and patients have a very poor ...prognosis. Mesothelioma has the potential to represent an appropriate disease to prevent because of its strong association with asbestos exposure and the long latency from exposure to the disease on-set. Methods In the present study, we tested biological activity and toxicity of an artichoke freeze-dried extract (AWPC) as potential complementary preventive/early stage treatment agent for mesothelioma. This phase II clinical study then was conducted in 18 male-patients with evidence of radiographic characteristics related to asbestos exposure such as asbestosis or benign pleural disease as surrogate disease for mesothelioma clinical model. Results We investigate AWPC biological activity assessing its effect on mesothelin serum level, a glycoprotein with low expression in normal mesothelial cells and high expression in mesothelioma and asbestos related diseases. We also assess the AWPC effect on circulating miRNAs, as novel biomarkers of both cancer risk and response to therapeutic targets. While we found a small and not significant effect of AWPC on mesothelin serum levels, we observed that AWPC intake modulated 11 serum miRNAs related to gene-pathways connected to mesothelioma etiology and development. In terms of toxicity, we also did not observe any severe adverse effects associated to AWPC treatment, only gastro-intestinal symptoms were reported by five study participants. Conclusions We observed an interesting AWPC effect on miRNAs which targets modulate mesothelioma development. New and much larger clinical studies based on follow-up of workers exposed to asbestos are needed to corroborate the role of AWPC in prevention and early treatment of mesothelioma. Trial registration ClinicalTrials.gov, NCT02076672. Registered 03/03/2014. Keywords: Asbestosis, Malignant pleura mesothelioma, Artichoke, Biomarker, miRNA, Mesothelin
Bronchial thermoplasty (BT) is a bronchoscopic procedure that improves asthma control by reducing excess airway smooth muscle. Treated patients have been followed out to 5 years to evaluate long-term ...safety of this procedure.
Patients enrolled in the Asthma Intervention Research Trial were on inhaled corticosteroids ≥200 μg beclomethasone or equivalent + long-acting-beta2-agonists and demonstrated worsening of asthma on long-acting-β2-agonist withdrawal. Following initial evaluation at 1 year, subjects were invited to participate in a 4 year safety study. Adverse events (AEs) and spirometry data were used to assess long-term safety out to 5 years post-BT.
45 of 52 treated and 24 of 49 control group subjects participated in long-term follow-up of 5 years and 3 years respectively. The rate of respiratory adverse events (AEs/subject) was stable in years 2 to 5 following BT (1.2, 1.3, 1.2, and 1.1, respectively,). There was no increase in hospitalizations or emergency room visits for respiratory symptoms in Years 2, 3, 4, and 5 compared to Year 1. The FVC and FEV1 values showed no deterioration over the 5 year period in the BT group. Similar results were obtained for the Control group.
The absence of clinical complications (based on AE reporting) and the maintenance of stable lung function (no deterioration of FVC and FEV1) over a 5-year period post-BT in this group of patients with moderate to severe asthma support the long-term safety of the procedure out to 5 years.
Asthmatic exacerbations result in part from constriction of airway smooth muscle. In this controlled trial, the use of bronchoscopically delivered thermoplasty to reduce the mass of airway smooth ...muscle resulted in fewer exacerbations among subjects with moderate or severe asthma. The incidence of adverse events was higher among subjects undergoing bronchial thermoplasty than among control subjects during the first 3 weeks after treatment.
The use of bronchoscopically delivered thermoplasty to reduce the mass of airway smooth muscle resulted in fewer exacerbations among subjects with moderate or severe asthma.
Many of the variable symptoms of asthma are thought to be due to the contraction of airway smooth muscle, leading to bronchoconstriction.
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Increased airway smooth-muscle mass is a characteristic feature of asthma, particularly in persons with severe or fatal asthma.
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Bronchial thermoplasty is a novel intervention in which controlled thermal energy is delivered to the airway wall during a series of bronchoscopies, resulting in a prolonged reduction of airway smooth-muscle mass.
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In previous studies, we determined the amount and duration of energy to be delivered that result in modest thermal injury.
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The treatment in humans of airways . . .
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