No abstract

Rationale: Methicillin resistant Staphylococcus aureus (MRSA) is prevalent and consequential in cystic fibrosis (CF). Whole genome sequencing (WGS) could reveal genomic differences in MRSA associated with poorer outcomes or detect MRSA transmission.Objectives: To identify MRSA genes associated with low lung function and potential MRSA transmission in CF.Methods: We collected 97 MRSA isolates from 74 individuals with CF from 2017 and performed short-read WGS. We determined sequence type (ST) and the phylogenetic relationship between isolates. We aligned accessory genes from 25 reference genomes to genome assemblies, classified isolates by accessory gene content, and correlated the accessory genome to clinical outcomes. Results:The most prevalent ST were ST5 (N = 55), ST8 (N = 15), and ST105 (N = 14).Closely related MRSA strains were shared by family members with CF, but rarely between unrelated individuals. Three clusters of MRSA were identified by accessory genome content. Cluster A, including ST5 and ST105, was highly prevalent at all ages. Cluster B, including ST8, was more limited to younger patients. Cluster C included 6 distantly related strains. Patients 20 years old and younger infected with Cluster A had lower forced expiratory volume in the first second (FEV 1 ) and higher sputum biomass compared to similar-aged patients with Cluster B. Conclusions:In this CF cohort, we identified MRSA subtypes that predominate at different ages and differ by accessory gene content. The most prevalent cluster of MRSA, including ST5 and ST105, was associated with lower FEV 1 . ST8 MRSA was more common in younger patients and thus has the potential to rise in prevalence as these patients age.

Rigorous experimental design with transparent reporting in biomedical science reduces risk of bias and allows for scientists to judge the quality of the research. Basic factors of rigor such as blinding, randomization, power analysis, and inclusion of both sexes impact the reproducibility by reducing experimental bias. We designed a systematic study to analyze basic factors of rigor, inclusion of sex, and whether data were analyzed or disaggregated by sex over the past 10 years in the journal PAIN. Studies that included humans reported randomization in 81%, blinding in 48%, and the use of a power analysis calculation in 27% over the past 10 years. Studies that included mice reported randomization in 35%, blinding in 70%, and the use of a power analysis in 9%. Studies that included rats reported randomization in 38%, blinding in 63%, and the use of power analysis in 12%. This study also found that human studies consistently included both sexes over the past decade, but less than 20% of data were disaggregated or analyzed for sex differences. Although mouse and rat studies predominately used males only, there has been a slight increase in inclusion of both sexes over the past few years. Justification for single-sex studies was below 50% in both human and rodent data. In both human and animal studies, transparency in reporting of experimental design and inclusion of both sexes should be considered standard practice and will result in improved quality and reproducibility of published research.

Introduction: Cystic Fibrosis Foundation guidelines recommend people with CF perform daily airway clearance. This can be difficult for patients to complete, as some find it time consuming or uncomfortable. Data comparing airway clearance methods are limited. We surveyed patients and families to understand which methods are preferred and identify obstacles performing airway clearance. Methods: We designed a REDCap survey and enrolled participants in 2021. Respondents reported information on airway clearance usage, time commitment, and medication use. They rated airway clearance methods for effectiveness, comfort, time commitment, importance, and compatibility with other treatments. Analysis included descriptive statistics and clustering. Results: 60 respondents started and 52 completed the survey. The median patient age was 20 years. Respondents experienced a median of four airway clearance methods in their lifetime, including chest wall oscillation (vest, 92%), manual chest physical therapy (CPT, 88%), huff coughing (77%), and exercise (75%). Past 30-day use was highest for exercise (62%) and vest (57%). Time commitment was generally less than 2 hours daily. Of those eligible for CFTR modulators, 53% reported decreased time commitment to airway clearance after starting treatment. On a scale of 0-100, respondents rated CFTR modulators as their most important treatment (median 99.5), followed by exercise (88). Discussion: Patients and caregivers are familiar with several methods of airway clearance for CF. They report distinct strengths and limitations of each method. Exercise and vest are the most common methods of airway clearance. Use of CFTR modulators may reduce patient-reported time commitment to airway clearance.

Rationale: Methicillin resistant Staphylococcus aureus (MRSA) is prevalent and consequential in cystic fibrosis (CF). Whole genome sequencing (WGS) could reveal genomic differences in MRSA associated with poorer outcomes or detect MRSA transmission. Objectives: To identify MRSA genes associated with low lung function and identify potential MRSA transmission in CF. Methods: We collected 97 MRSA isolates from 74 individuals with CF from 2017 and performed short-read WGS. We determined sequence type (ST) and the phylogenetic relationship between isolates. We aligned accessory genes from 25 reference genomes to genome assemblies. We classified the MRSA by accessory gene content and correlated the accessory genome to clinical outcomes. Results: The most prevalent ST were ST5 (N=55), ST105 (N=14), and ST8 (N=14). Closely related MRSA strains were shared by family members with CF, but rarely between unrelated individuals. Three distinct clusters of MRSA were identified by accessory genome content. The first included ST5 and ST105 strains and was common among older patients with lower FEV. The second cluster included ST8, which was generally identified in younger patients. Sputum density of MRSA and Pseudomonas aeruginosa was higher in cultures from patients with ST5/ST105 compared to patients with ST8 at similar ages. Conclusions: In this CF cohort, we identified MRSA subtypes that predominate at different ages and differ by accessory gene content. ST5 and ST105 represented the most prevalent cluster of MRSA. ST8 MRSA was more common in younger patients and thus has the potential to rise in prevalence as these patients age.