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BackgroundSkeletal muscle dysfunction is a common extrapulmonary manifestation of chronic obstructive pulmonary disease (COPD). Alterations in skeletal muscle myosin heavy chain expression, with reduced type I and increased type II myosin heavy chain expression, are associated with COPD severity when studied in largely male cohorts. The objectives of this study were (1) to define an abnormal myofibre proportion phenotype in both males and females with COPD and (2) to identify transcripts and transcriptional networks associated with abnormal myofibre proportion in COPD.MethodsForty-six participants with COPD were assessed for body composition, strength, endurance and pulmonary function. Skeletal muscle biopsies from the vastus lateralis were assayed for fibre-type distribution and cross-sectional area via immunofluorescence microscopy and RNA-sequenced to generate transcriptome-wide gene expression data. Sex-stratified k-means clustering of type I and IIx/IIax fibre proportions was used to define abnormal myofibre proportion in participants with COPD and contrasted with previously defined criteria. Single transcripts and weighted co-expression network analysis modules were tested for correlation with the abnormal myofibre proportion phenotype.ResultsAbnormal myofibre proportion was defined in males with COPD (n = 29) as 22% type IIx/IIax fibres and in females with COPD (n = 17) as 12% type IIx/IIax fibres. Half of the participants with COPD were classified as having an abnormal myofibre proportion. Participants with COPD and an abnormal myofibre proportion had lower median handgrip strength (26.1 vs. 34.0 kg, P = 0.022), 6-min walk distance (300 vs. 353 m, P = 0.039) and forced expiratory volume in 1 s-to-forced vital capacity ratio (0.42 vs. 0.48, P = 0.041) compared with participants with COPD and normal myofibre proportions. Twenty-nine transcripts were associated with abnormal myofibre proportions in participants with COPD, with the upregulated NEB, TPM1 and TPM2 genes having the largest fold differences. Co-expression network analysis revealed that two transcript modules were significantly positively associated with the presence of abnormal myofibre proportions. One of these co-expression modules contained genes classically associated with muscle atrophy, as well as transcripts associated with both type I and type II myofibres, and was enriched for genetic loci associated with bone mineral density.ConclusionsOur findings indicate that there are significant transcriptional alterations associated with abnormal myofibre proportions in participants with COPD. Transcripts canonically associated with both type I and type IIa fibres were enriched in a co-expression network associated with abnormal myofibre proportion, suggesting altered transcriptional regulation across multiple fibre types.

BackgroundClinical decision support (CDS) tools improve clinical diagnostic decision making and patient safety. The availability of CDS to health care professionals has grown in line with the increased prevalence of apps and smart mobile devices. Despite these benefits, patients may have safety concerns about the use of mobile devices around medical equipment. ObjectiveThis research explored the engagement of junior doctors (JDs) with CDS and the perceptions of patients about their use. There were three objectives for this research: (1) to measure the actual usage of CDS tools on mobile devices (mCDS) by JDs, (2) to explore the perceptions of JDs about the drivers and barriers to using mCDS, and (3) to explore the perceptions of patients about the use of mCDS. MethodsThis study used a mixed-methods approach to study the engagement of JDs with CDS accessed through mobile devices. Usage data were collected on the number of interactions by JDs with mCDS. The perceived drivers and barriers for JDs to using CDS were then explored by interviews. Finally, these findings were contrasted with the perception of patients about the use of mCDS by JDs. ResultsNine of the 16 JDs made a total of 142 recorded interactions with the mCDS over a 4-month period. Only 27 of the 114 interactions (24%) that could be categorized as on-shift or off-shift occurred on-shift. Eight individual, institutional, and cultural barriers to engagement emerged from interviews with the user group. In contrast to reported cautions and concerns about the impact of clinicians’ use of mobile phone on patient health and safety, patients had positive perceptions about the use of mCDS. ConclusionsPatients reported positive perceptions toward mCDS. The usage of mCDS to support clinical decision making was considered to be positive as part of everyday clinical practice. The degree of engagement was found to be limited due to a number of individual, institutional, and cultural barriers. The majority of mCDS engagement occurred outside of the workplace. Further research is required to verify these findings and assess their implications for future policy and practice.