Results from Randomized Trial of Pirfenidone in Patients with Chronic Rejection (STOP-CLAD Study)

Chronic lung allograft dysfunction (CLAD) is the leading long-term cause of poor outcomes after transplant and manifests by fibrotic remodeling of small airways and/or pleuroparenchymal fibroelastosis. This study evaluated the effect of pirfenidone on spirometric and radiographic progression in patients with CLAD. We performed a single-center, 6-month, randomized, placebo-controlled trial of pirfenidone on patients with CLAD. Treatment allocation was stratified by CLAD phenotype. The primary spirometric outcome measures were change FEV1 and FVC relative to post-transplant baseline values, and the primary radiographic outcome was small airways disease, quantified as percentage of lung volume via parametric response mapping analysis of CT scans (PRMfSAD). Linear mixed models were used to evaluate treatment effect of the longitudinal outcome measures. We enrolled 24 patients, 13 of whom received pirfenidone (the study was terminated prior to reaching target enrollment of 60 patients due to the COVID pandemic). The pirfenidone and placebo groups were similar with regards to age, pre-transplant diagnosis, lung function, and CLAD phenotypes. There was no significant difference between the pirfenidone vs. placebo groups with regards to expected change in FEV1 (-3.1 vs. -3.7, p =0.90, Figure Panel A), FVC (-2.5 vs. -4.6, p =0.63, Figure Panel B), or PRMfSAD (+3.7 vs. -0.6, p =0.28). Subgroup analysis found that pirfenidone attenuated the spirometric decline among female patients, but there was no difference in treatment effect with regards to age, pre-transplant diagnosis, or CLAD phenotype. Tolerance of study drug and adverse events did not differ between groups, although the rate of grade 2 or higher adverse events was higher in the placebo vs. pirfenidone group (13 vs. 7, p =0.001). Pirfenidone did not attenuate spirometric or radiographic decline in a single-center randomized trial of CLAD patients, but had an acceptable tolerance and side effect profile. [ FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Allelic variation in class I HLA determines CD8(+) T cell repertoire shape and cross-reactive memory responses to SARS-CoV-2

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Sleep disorders in neuromuscular diseases: Adaption in care provision during the covid-19 pandemic

P atients with neuromuscular disease frequently have comorbid sleep disorders. Hypoventilation, upper airway issues, central apnoeas and paroxysmal leg movements are all common in this patient population. It is imperative that these patients undergo a formal evaluation. However, the COVID-19 pandemic has presented many challenges that have necessitated adaptations in the provision of their care. Despite the hurdles created by infection control measures to completing evaluations, such as polysomnography and advanced pulmonary function testing, they generally can be accomplished in a safe manner. Care providers should exhibit caution to avoid the temptation to make clinical decisions based on substandard testing or prescribe suboptimal therapies in this population of patients. Finally, the challenges of the pandemic have also affected the availability of in-person clinical follow-up and assessment of treatment efficacy. The utility of telehealth in this manner has proven invaluable and has allowed for reliable high-quality care to be delivered to a potentially vulnerable population of patients.

Identifying and addressing psychosocial determinants of adherence to physical distancing guidance during the COVID-19 pandemic - project protocol

Optimising public health physical distancing measures has been a critical part of the global response to the spread of COVID-19. Evidence collected during the current pandemic shows that the transmission rate of the virus is significantly reduced following implementation of intensive physical distancing measures. Adherence to these recommendations has been poorer than adherence to other key transmission reduction behaviours such as handwashing. There are a complex range of reasons that are likely to predict why people do not or only partially adhere to physical distancing recommendations. In the current project we aim to address the following research questions: (1) What are the psychosocial determinants of physical distancing for the general public and for key socio-demographic sub-groups (e.g., young adults, older adults, etc.)?;(2) Do current Government of Ireland COVID-19 physical distancing communications address the determinants of physical distancing?;and (3) How can communications be optimised and tailored to sub-groups to ensure maximum adherence to guidelines? These will be addressed by conducting three work packages (WPs). In WP1, we will work closely with the iCARE international study, which includes a large online survey of public responses to measures established to reduce and slow the spread of COVID-19, including physical distancing. We will analyse Irish data, comparing it to data from other countries, to identify the key psychosocial determinants of physical distancing behaviour. This will be followed by a qualitative study to explore in depth the barriers and facilitators of physical distancing behaviour among the Irish public (WP2). In WP3, we will conduct a content analysis and evidence mapping of current government messaging around physical distancing, to ensure the findings from this research feed into the development of ongoing communication and future messaging about physical distancing.