Using PROGRESS-Plus to identify current approaches to the collection and reporting of equity-relevant data: a scoping review

Objectives: Our objectives were to identify what and how data relating to the social determinants of health are collected and reported in equity-relevant studies and map these data to the PROGRESS-Plus framework. Study Design and Setting: We performed a scoping review. We ran two systematic searches of MEDLINE and Embase for equityrelevant studies published during 2021. We included studies in any language without limitations to participant characteristics. Included studies were required to have collected and reported at least two participant variables relevant to evaluating individual-level social determinants of health. We applied the PROGRESS-Plus framework to identify and organize these data. Results: We extracted data from 200 equity-relevant studies, providing 962 items defined by PROGRESS-Plus. A median of 4 (interquartile range 5 2) PROGRESS-Plus items were reported in the included studies. 92% of studies reported age; 78% reported sex/gender; 65% reported educational attainment; 49% reported socioeconomic status; 45% reported race; 44% reported social capital; 33% reported occupation; 14% reported place and 9% reported religion. Conclusion: Our synthesis demonstrated that researchers currently collect a limited range of equity-relevant data, but usefully provides a range of examples spanning PROGRESS-Plus to inform the development of improved, standardized practices.Emma L. Karrana, Aidan G. Cashina, Trevor Barker, Mark A. Boyd, Alessandro Chiarotto, Omar Dewidar, Vina Mohabir, Jennifer Petkovic Saurab Sharma, Sinan Tejani, Peter Tugwell, G. Lorimer Mosele

Evolving Project ECHO: delivery of pediatric pain core competency learning for interprofessional healthcare providers

IntroductionHealthcare providers (HCPs) practicing in community settings are critical to improving access to pain care, yet there are significant gaps in training opportunities designed for interprofessional learners. Project Extension for Community Healthcare Outcomes (Project ECHO®) is an established model for delivering online HCP education through virtual clinics and cultivating a community of practice. However, to our knowledge, the integration of pain core competency education into the ECHO® model has not been previously attempted. This innovation could enhance the ECHO® model while also addressing the growing calls for more accessible interprofessional pain curricula. This paper describes efforts to implement and evaluate core competency curricula within the context of Pediatric Project ECHO for Pain, one of the first pediatric-pain focused ECHO programs in the world.MethodsNeeds assessments informed curricula development. The first delivered core competency model consisted of synchronous webinar-style sessions while the second model included a mixture of asynchronous (eLearning course) and synchronous (virtual clinical debrief) elements. A convenience sample of HCPs was recruited from ECHO program registrants. Participants completed baseline and follow-up surveys to assess core competency acceptability as well as impact on knowledge and self-efficacy related to managing pediatric pain. Usability of the eLearning platform (model 2 only) was also evaluated. Surveys used 5-point Likert scales to capture outcomes. A priori targets included mean scores ≥4/5 for acceptability and ≥80% of learners reporting knowledge and self-efficacy improvements. The study received local research ethics approval.ResultsThe core competency was found to be highly acceptable to interprofessional learners (n = 31) across delivery models, surpassing a priori targets. Specifically, it was characterized as a worthwhile and satisfactory experience that was helpful in supporting learning. The core competency was also associated with improvements in knowledge and self-efficacy by 97% and 90% of learners, respectively. The eLearning platform was reported to have high usability with clinically realistic cases (100% of respondents) that were helpful to inform care delivery (94% of respondents).ConclusionThe integration of core competency learning within the Project ECHO® model was a successful approach to deliver pediatric pain education to interprofessional HCPs

Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease

BACKGROUND: Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis and a leading cause of systemic sclerosis-related death. Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of nintedanib in patients with ILD associated with systemic sclerosis. Patients who had systemic sclerosis with an onset of the first non-Raynaud's symptom within the past 7 years and a high-resolution computed tomographic scan that showed fibrosis affecting at least 10% of the lungs were randomly assigned, in a 1:1 ratio, to receive 150 mg of nintedanib, administered orally twice daily, or placebo. The primary end point was the annual rate of decline in forced vital capacity (FVC), assessed over a 52-week period. Key secondary end points were absolute changes from baseline in the modified Rodnan skin score and in the total score on the St. George's Respiratory Questionnaire (SGRQ) at week 52. RESULTS: A total of 576 patients received at least one dose of nintedanib or placebo; 51.9% had diffuse cutaneous systemic sclerosis, and 48.4% were receiving mycophenolate at baseline. In the primary end-point analysis, the adjusted annual rate of change in FVC was 1252.4 ml per year in the nintedanib group and 1293.3 ml per year in the placebo group (difference, 41.0 ml per year; 95% confidence interval [CI], 2.9 to 79.0; P=0.04). Sensitivity analyses based on multiple imputation for missing data yielded P values for the primary end point ranging from 0.06 to 0.10. The change from baseline in the modified Rodnan skin score and the total score on the SGRQ at week 52 did not differ significantly between the trial groups, with differences of 120.21 (95% CI, 120.94 to 0.53; P=0.58) and 1.69 (95% CI, 120.73 to 4.12 [not adjusted for multiple comparisons]), respectively. Diarrhea, the most common adverse event, was reported in 75.7% of the patients in the nintedanib group and in 31.6% of those in the placebo group. CONCLUSIONS: Among patients with ILD associated with systemic sclerosis, the annual rate of decline in FVC was lower with nintedanib than with placebo; no clinical benefit of nintedanib was observed for other manifestations of systemic sclerosis. The adverse-event profile of nintedanib observed in this trial was similar to that observed in patients with idiopathic pulmonary fibrosis; gastrointestinal adverse events, including diarrhea, were more common with nintedanib than with placebo

Identification of binding sites for ivacaftor on the cystic fibrosis transmembrane conductance regulator

Summary: Ivacaftor (VX-770) was the first cystic fibrosis transmembrane conductance regulator (CFTR) modulatory drug approved for the treatment of patients with cystic fibrosis. Electron cryomicroscopy (cryo-EM) studies of detergent-solubilized CFTR indicated that VX-770 bound to a site at the interface between solvent and a hinge region in the CFTR protein conferred by transmembrane (tm) helices: tm4, tm5, and tm8. We re-evaluated VX-770 binding to CFTR in biological membranes using photoactivatable VX-770 probes. One such probe covalently labeled CFTR at two sites as determined following trypsin digestion and analysis by tandem-mass spectrometry. One labeled peptide resides in the cytosolic loop 4 of CFTR and the other is located in tm8, proximal to the site identified by cryo-EM. Complementary data from functional and molecular dynamic simulation studies support a model, where VX-770 mediates potentiation via multiple sites in the CFTR protein

Macitentan for the treatment of idiopathic pulmonary fibrosis: the randomised controlled MUSIC trial.

Idiopathic pulmonary fibrosis is a progressive, fatal disease. This prospective, randomised, double-blind, multicentre, parallel-group, placebo-controlled phase II trial (NCT00903331) investigated the efficacy and safety of the endothelin receptor antagonist macitentan in idiopathic pulmonary fibrosis. Eligible subjects were adults with idiopathic pulmonary fibrosis of <3 years duration and a histological pattern of usual interstitial pneumonia on surgical lung biopsy. The primary objective was to demonstrate that macitentan (10 mg once daily) positively affected forced vital capacity versus placebo. Using a centralised system, 178 subjects were randomised (2:1) to macitentan (n=119) or placebo (n=59). The median change from baseline up to month 12 in forced vital capacity was -0.20 L in the macitentan arm and -0.20 L in the placebo arm. Overall, no differences between treatments were observed in pulmonary function tests or time to disease worsening or death. Median exposures to macitentan and placebo were 14.5 months and 15.0 months, respectively. Alanine and/or aspartate aminotransferase elevations over three times upper limit of normal arose in 3.4% of macitentan-treated subjects and 5.1% of placebo recipients. In conclusion, the primary objective was not met. Long-term exposure to macitentan was well tolerated with a similar, low incidence of elevated hepatic aminotransferases in each treatment group

Macitentan for the treatment of idiopathic pulmonary fibrosis: The randomised controlled MUSIC trial

PubMed ID: 23682110Idiopathic pulmonary fibrosis is a progressive, fatal disease. This prospective, randomised, double-blind, multicentre, parallel-group, placebo-controlled phase II trial (NCT00903331) investigated the efficacy and safety of the endothelin receptor antagonist macitentan in idiopathic pulmonary fibrosis. Eligible subjects were adults with idiopathic pulmonary fibrosis of <3 years duration and a histological pattern of usual interstitial pneumonia on surgical lung biopsy. The primary objective was to demonstrate that macitentan (10 mg once daily) positively affected forced vital capacity versus placebo. Using a centralised system, 178 subjects were randomised (2:1) to macitentan (n=119) or placebo (n=59). The median change from baseline up to month 12 in forced vital capacity was -0.20 L in the macitentan arm and -0.20 L in the placebo arm. Overall, no differences between treatments were observed in pulmonary function tests or time to disease worsening or death. Median exposures to macitentan and placebo were 14.5 months and 15.0 months, respectively. Alanine and/or aspartate aminotransferase elevations over three times upper limit of normal arose in 3.4% of macitentan-treated subjects and 5.1% of placebo recipients. In conclusion, the primary objective was not met. Long-term exposure to macitentan was well tolerated with a similar, low incidence of elevated hepatic aminotransferases in each treatment group. Copyright © ERS 2013.Actelion Pharmaceuticals Ltd