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Biomedical subjects

Shawn D Aaron

Publications and source records attributed to Shawn D Aaron.

6 recordsLinked to original sources

Genomic analysis of the liverpool epidemic strain of pseudomonas aeruginosa infecting persons with cystic fibrosis reveals likely Canadian origins.

INTRODUCTION: The Liverpool Epidemic Strain (LES) of Pseudomonas aeruginosa is one of several known strains to be transmissible between persons with cystic fibrosis (CF) (pwCF) and the only known strain to have infected large proportions of CF populations on two continents. Despite its prevalence, efforts to understand its spread have proven elusive. METHODS: We leveraged a prospective collection of P. aeruginosa isolates from pwCF attending the Southern Alberta Adult CF clinic from 1986 to 2020 to identify all individuals with LES infection. LES isolates collected every 1-2 years from each pwCF were sequenced and compared with 171 published LES genomes by phylogenetic analysis. RESULTS: Of 395 pwCF screened, ten pwCF infected with the LES were identified, from whom 46 LES isolates were sequenced. The earliest LES isolate was recovered in 1986, ∼2 years earlier than the previously oldest published LES isolate recovered in the UK. Phylogenetic analysis identified a diverse set of isolates at the root of the LES phylogeny that formed four clades, one of which gave rise to a "classic LES" clade. Canadian isolates formed a paraphyletic group that included the root of this clade and out of which the UK LES clade emerged. We estimated the date of the most recent common ancestor (MRCA) of the UK LES clade as 1977. CONCLUSIONS: Our study provides genomic evidence in support of a silent epidemic of LES infection occurring in the late 1970s among pwCF first originating in Canada and being spread to the UK, where transmission markedly accelerated.

Humans↗

Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease.

BACKGROUND: In this randomized, double-blind, placebo-controlled trial, we studied the effectiveness of prednisone in reducing the risk of relapse after outpatient exacerbations of chronic obstructive pulmonary disease (COPD). METHODS: We enrolled 147 patients who were being discharged from the emergency department after an exacerbation of COPD and randomly assigned them to 10 days of treatment with 40 mg of oral prednisone once daily or identical-appearing placebo. All patients received oral antibiotics for 10 days, plus inhaled bronchodilators. The primary end point was relapse, defined as an unscheduled visit to a physician's office or a return to the emergency department because of worsening dyspnea, within 30 days after randomization. RESULTS: The overall rate of relapse at 30 days was lower in the prednisone group than in the placebo group (27 percent vs. 43 percent, P=0.05), and the time to relapse was prolonged in those taking prednisone (P=0.04). After 10 days of therapy, patients in the prednisone group had greater improvements in forced expiratory volume in one second than did patients in the placebo group (mean [+/-SD] increase from base line, 34+/-42 percent vs. 15+/-31 percent; P=0.007). Patients in the prednisone group also had significant improvements in dyspnea, as measured by the transitional dyspnea index (P=0.04) and by the dyspnea domain of the Chronic Respiratory Disease Index Questionnaire (P=0.02), but not in health-related quality of life (P=0.14). CONCLUSIONS: Outpatient treatment with oral prednisone offers a small advantage over placebo in treating patients who are discharged from the emergency department with an exacerbation of COPD.

Acute Disease↗

A spirometry-based algorithm to direct lung function testing in the pulmonary function laboratory.

OBJECTIVE: To design a spirometry-based algorithm to predict pulmonary restrictive impairment and reduce the number of patients undergoing unnecessary lung volume testing. DESIGN: Two prospective studies of 259 consecutive patients and 265 consecutive patients used to derive and validate the algorithm, respectively. SETTING: A pulmonary function laboratory of a tertiary care hospital. PATIENTS: Consecutive adults referred to the laboratory for lung volume measurements and spirometry. MEASUREMENTS: The sensitivity of the algorithm for predicting pulmonary restriction and the cost savings associated with its use. RESULTS: Total lung capacity correlated strongly with FVC (r = 0.66) and showed an inverse correlation with the FEV(1)/FVC ratio (r = - 0.41). According to the algorithm, only patients with an FVC < 85% of predicted and an FEV(1)/FVC ratio >or= 55% required lung volume measurements following spirometry. The algorithm had a high sensitivity for predicting restriction and a high negative predictive value (NPV) for excluding restriction (sensitivity, 96%; NPV, 98%). The diagnostic properties of the algorithm were reproducible in the validation study. Application of the algorithm would eliminate the need for lung volume testing in 48 to 49% of patients referred to the pulmonary function test (PFT) laboratory, reducing costs by 33%. CONCLUSIONS: A spirometry-based algorithm accurately excludes pulmonary restriction and reduces unnecessary lung volume testing in the PFT laboratory almost in half.

Algorithms↗

Single and combination antibiotic susceptibilities of planktonic, adherent, and biofilm-grown Pseudomonas aeruginosa isolates cultured from sputa of adults with cystic fibrosis.

Evidence suggests that Pseudomonas aeruginosa bacteria form biofilms within the airways of adults with cystic fibrosis (CF). The objective of this study was to determine whether clinical isolates of P. aeruginosa recovered from adults with CF have similar susceptibilities to individual antibiotics and to antibiotic combinations when grown as adherent monolayers or as biofilms compared to when they are grown using planktonic methods. Twelve multiresistant P. aeruginosa isolates, one mucoid and one nonmucoid from each of six CF patients, were grown conventionally under planktonic conditions, as adherent bacterial monolayers, and as biofilms. Each bacterial isolate remained genotypically identical despite being cultured under planktonic, adherent, or biofilm growth conditions. Isolates grown as adherent monolayers and as biofilms were less susceptible to bactericidal killing by individual antibiotics compared to those grown planktonically. More importantly, biofilm-grown bacteria, but not adherent monolayer-grown bacteria, were significantly less susceptible to two- and three-drug combinations of antibiotics than were planktonically grown bacteria (P = 0.005). We conclude that biofilm-grown bacteria derived from patients with CF show decreased susceptibility to the bactericidal effects of antibiotic combinations than do adherent and planktonically grown bacteria.

Anti-Bacterial Agents↗

Measurement of short-term changes in dyspnea and disease-specific quality of life following an acute COPD exacerbation.

STUDY OBJECTIVE: To determine whether currently available measurement tools can be used to obtain valid measurements of short-term changes in dyspnea and disease-specific quality of life (QOL) in outpatients with an acute COPD exacerbation. DESIGN: Prospective cohort study. METHODS: Sixty-six patients with an acute COPD exacerbation who presented to the emergency department completed the chronic respiratory disease index questionnaire (CRQ) and the baseline dyspnea index (BDI) and were discharged home receiving 10 days of medical therapy. Reassessment with the CRQ and the transitional dyspnea index (TDI) occurred within 48 h of relapse (defined as an urgent hospital revisit within 10 days because of worsening respiratory symptoms), or 10 days later if relapse did not occur. RESULTS: Patients who did not relapse (n = 49) showed moderate-to-large improvements in disease-specific QOL across all four CRQ domains (improvements in each domain of 1.4 to 1.9 U; p < 0.001 for all domains) and large positive changes in the TDI (total TDI score, + 5.02 plus minus 0.55 U; p = 0.0001). In contrast, patients who had a relapse (n = 17) did not have improved CRQ or TDI scores (mean negative change in three of four CRQ domains, total TDI score - 3.06 plus minus 1.14 U; p = 0.02). Changes in the CRQ dyspnea score and TDI correlated with each other (r = 0.78; p = 0.0001) and with changes in FEV(1) (CRQ, r = 0.48 and p = 0.0001; TDI, r = 0.46 and p = 0.0002). Ten control patients with stable COPD showed no changes in the CRQ or TDI over 10 days. CONCLUSION: The CRQ and BDI/TDI can be used to obtain valid, responsive measures of acute changes in QOL and dyspnea associated with a COPD exacerbation. The direction and magnitude of change in these scores was highly correlated with clinical outcome and with other health measures. Most outpatients treated for a COPD exacerbation experience significant short-term improvements in QOL and dyspnea, with the exception of patients who have a clinical relapse of symptoms.

Aged↗