Concordance of Treatment Effect: An Analysis of The Society of Thoracic Surgeons Intermacs Database

BACKGROUND: The Society of Thoracic Surgeons (STS) Intermacs Registry represents a real-world data source of durable, left ventricular assist devices that can address knowledge gaps not informed through randomized clinical trials. We sought to compare survival with contemporary left ventricular assist device technologies using multiple analytic approaches to assess concordance of treatment effects and to validate prior STS Intermacs observations. METHODS: Patients (aged \u3e 19 years) enrolled into STS Intermacs between August 2017 - June 2019 were stratified by device type (centrifugal device with hybrid levitation [CF-HL] or full magnetic levitation [CF-FML]). The primary outcome was 1-year survival assessed by three statistical methodologies (multivariable regression, propensity score matching, and instrumental variable analysis). RESULTS: Of 4,448 patients, 2,012 (45.2%) received CF-HL and 2,436 (54.8%) received CF-FML. One-year survival for CF-FML was 88% vs. 79% for CF-HL (overall p \u3c .001), with a hazard ratio for mortality of 3.18 for CF-HL (p\u3c0.0001) after risk adjustment. With propensity score matching (n=1400 each cohort), 1-year survival was 87% for CF-FML vs. 80% for CF-HL, with a hazard ratio of 3.20 for mortality with CF-HL (p\u3c0.0001) after risk adjustment. With an instrumental variable analysis, the probability of receiving CF-HL was associated with a hazard ratio of 3.11 (p\u3c0.0001). CONCLUSIONS: Statistical methodology using propensity score matching and instrumental variable analysis increased the robustness of observations derived from real-world data and demonstrates the feasibility of performing comparative effectiveness research using STS Intermacs. These analyses provide additional evidence supporting a survival benefit of CF-FML versus CF-HL

Real-world experience of nintedanib for progressive fibrosing interstitial lung disease in the UK

Background Nintedanib slows progression of lung function decline in patients with progressive fibrosing (PF) interstitial lung disease (ILD) and was recommended for this indication within the United Kingdom (UK) National Health Service in Scotland in June 2021 and in England, Wales and Northern Ireland in November 2021. To date, there has been no national evaluation of the use of nintedanib for PF-ILD in a real-world setting.Methods 26 UK centres were invited to take part in a national service evaluation between 17 November 2021 and 30 September 2022. Summary data regarding underlying diagnosis, pulmonary function tests, diagnostic criteria, radiological appearance, concurrent immunosuppressive therapy and drug tolerability were collected via electronic survey.Results 24 UK prescribing centres responded to the service evaluation invitation. Between 17 November 2021 and 30 September 2022, 1120 patients received a multidisciplinary team recommendation to commence nintedanib for PF-ILD. The most common underlying diagnoses were hypersensitivity pneumonitis (298 out of 1120, 26.6%), connective tissue disease associated ILD (197 out of 1120, 17.6%), rheumatoid arthritis associated ILD (180 out of 1120, 16.0%), idiopathic nonspecific interstitial pneumonia (125 out of 1120, 11.1%) and unclassifiable ILD (100 out of 1120, 8.9%). Of these, 54.4% (609 out of 1120) were receiving concomitant corticosteroids, 355 (31.7%) out of 1120 were receiving concomitant mycophenolate mofetil and 340 (30.3%) out of 1120 were receiving another immunosuppressive/modulatory therapy. Radiological progression of ILD combined with worsening respiratory symptoms was the most common reason for the diagnosis of PF-ILD.Conclusion We have demonstrated the use of nintedanib for the treatment of PF-ILD across a broad range of underlying conditions. Nintedanib is frequently co-prescribed alongside immunosuppressive and immunomodulatory therapy. The use of nintedanib for the treatment of PF-ILD has demonstrated acceptable tolerability in a real-world setting

Reforming Teacher Education: Something Old, Something New

Evaluates the Teachers for a New Era initiative, which supported eleven colleges and universities in applying new practices to their teacher education programs and organizational culture. Assesses the sustainability of the practices beyond the initiative

Comparison of antifibrotic availability for patients on the BTS IPF registry using existing and new prescribing criteria

Antifibrotic prescribing is changing significantly in the UK with new National Institute for Health and Care Excellence (NICE) guidelines for nintedanib prescribing in IPF set to be published in February 2023 (NICE, 2022). There are also inconsistencies in prescribing between patients with IPF and PF-ILD.Our aim was to evaluate discrepancies in anti-fibrotic availability for patients on a national IPF registry using current, future and PF-ILD UK prescribing criteria.Permission was obtained from the British Thoracic Society (BTS) Information Governance Committee to access FVC readings for patients with IPF on the National BTS ILD registry. As of December 2022, 3,652 patients were on the registry. Of these, 987 had serial FVC readings. We compared anti-fibrotic eligibility in this cohort using three UK prescribing criteria; current NICE guidelines (FVC 50-80% predicted), new NICE guidelines (FVC ≥50%) and PF-ILD criteria (≥10% FVC decline in a 2 year period).Based on first FVC results, 60.5% (n=2185) of patients met current NICE guidelines for antifibrotics. Using new NICE guidelines, 97.5% (n=3519) would be eligible, an increase of 36.9%. Of the patients with serial FVC results who were ineligible for antifibrotics based on current NICE guidelines, 109 met PF-ILD criteria for nintedanib (median FVC drop of 13.9% over 298 days).There is significant variation in antifibrotic availability for patients depending on the prescribing criteria applied. Changes to current UK prescribing guidelines in IPF will significantly increase anti-fibrotic availability. This data highlights the need to upscale current UK ILD services

Supporting Literacy Across the Sunshine State: A Study of Florida Middle School Reading Coaches

Evaluates the implementation of a reading coach program to provide on-site support to teachers in Florida middle schools and its impact on teachers, principals, school climate, and student achievement. Includes literature review and recommended models

Constitutive activation of natural killer cells in Primary Biliary Cholangitis

Natural killer (NK) cells are innate immune cells that interface with the adaptive immune system to generate a pro-inflammatory immune environment. Primary Biliary Cholangitis (PBC) is a hepatic autoimmune disorder with extrahepatic associations including systemic sclerosis, Sjogren's syndrome and thyroiditis. Immunogenetic studies have identified polymorphisms of the IL-12/STAT4 pathway as being associated with PBC. As this pathway is important for NK cell function we investigated NK cells in PBC. Circulating NK cells from individuals with PBC were constitutively activated, with higher levels of CD49a and the liver-homing marker, CXCR6, compared to participants with non-autoimmune chronic liver disease and healthy controls. Stimulation with minimal amounts of IL-12 (0.005 ng/ml) led to significant upregulation of CXCR6 (p &lt; 0.005), and enhanced IFNγ production (p &lt; 0.02) on NK cells from PBC patients compared to individuals with non-autoimmune chronic liver disease, indicating dysregulation of the IL-12/STAT4 axis. In RNAseq studies, resting NK cells from PBC patients had a constitutively activated transcriptional profile and upregulation of genes associated with IL-12/STAT4 signaling and metabolic reprogramming. Consistent with these findings, resting NK cells from PBC patients expressed higher levels of pSTAT4 compared to control groups (p &lt; 0.001 vs. healthy controls and p &lt; 0.05 vs. liver disease controls). In conclusion NK cells in PBC are sensitive to minute quantities of IL-12 and have a "primed" phenotype. We therefore propose that peripheral priming of NK cells to express tissue-homing markers may contribute to the pathophysiology of PBC.</p

Concordance of Treatment Effect: An Analysis of The Society of Thoracic Surgeons Intermacs Database

BACKGROUND: The Society of Thoracic Surgeons (STS) Intermacs Registry represents a real-world data source of durable, left ventricular assist devices that can address knowledge gaps not informed through randomized clinical trials. We sought to compare survival with contemporary left ventricular assist device technologies using multiple analytic approaches to assess concordance of treatment effects and to validate prior STS Intermacs observations. METHODS: Patients (aged \u3e 19 years) enrolled into STS Intermacs between August 2017 - June 2019 were stratified by device type (centrifugal device with hybrid levitation [CF-HL] or full magnetic levitation [CF-FML]). The primary outcome was 1-year survival assessed by three statistical methodologies (multivariable regression, propensity score matching, and instrumental variable analysis). RESULTS: Of 4,448 patients, 2,012 (45.2%) received CF-HL and 2,436 (54.8%) received CF-FML. One-year survival for CF-FML was 88% vs. 79% for CF-HL (overall p \u3c .001), with a hazard ratio for mortality of 3.18 for CF-HL (p\u3c0.0001) after risk adjustment. With propensity score matching (n=1400 each cohort), 1-year survival was 87% for CF-FML vs. 80% for CF-HL, with a hazard ratio of 3.20 for mortality with CF-HL (p\u3c0.0001) after risk adjustment. With an instrumental variable analysis, the probability of receiving CF-HL was associated with a hazard ratio of 3.11 (p\u3c0.0001). CONCLUSIONS: Statistical methodology using propensity score matching and instrumental variable analysis increased the robustness of observations derived from real-world data and demonstrates the feasibility of performing comparative effectiveness research using STS Intermacs. These analyses provide additional evidence supporting a survival benefit of CF-FML versus CF-HL