Mark R. Elkins

Antibiotic Susceptibilities of Pseudomonas aeruginosa Isolates Derived from Patients with Cystic Fibrosis under Aerobic, Anaerobic, and Biofilm Conditions

ABSTRACT Recent studies have determined that Pseudomonas aeruginosa can live in a biofilm mode within hypoxic mucus in the airways of patients with cystic fibrosis (CF). P. aeruginosa grown under anaerobic and biofilm conditions may better approximate in vivo growth conditions in the CF airways, and combination antibiotic susceptibility testing of anaerobically and biofilm-grown isolates may be more relevant than traditional susceptibility testing under planktonic aerobic conditions. We tested 16 multidrug-resistant isolates of P. aeruginosa derived from CF patients using multiple combination bactericidal testing to compare the efficacies of double and triple antibiotic combinations against the isolates grown under traditional aerobic planktonic conditions, in planktonic anaerobic conditions, and in biofilm mode. Both anaerobically grown and biofilm-grown bacteria were significantly less susceptible (P < 0.01) to single and combination antibiotics than corresponding aerobic planktonically grown isolates. Furthermore, the antibiotic combinations that were bactericidal under anaerobic conditions were often different from those that were bactericidal against the same organisms grown as biofilms. The most effective combinations under all conditions were colistin (tested at concentrations suitable for nebulization) either alone or in combination with tobramycin (10 μg ml−1), followed by meropenem combined with tobramycin or ciprofloxacin. The findings of this study illustrate that antibiotic sensitivities are dependent on culture conditions and highlight the complexities of choosing appropriate combination therapy for multidrug-resistant P. aeruginosa in the CF lung.

There was evidence of convergent and construct validity of Physiotherapy Evidence Database quality scale for physiotherapy trials

OBJECTIVE To evaluate the convergent and construct validity of the Physiotherapy Evidence Database (PEDro) scale used to rate the methodological quality of randomized trials in physiotherapy. STUDY DESIGN AND SETTING PEDro total scores and individual-item scores were extracted from 9,456 physiotherapy trials indexed on PEDro. Convergent validity was tested by comparing PEDro total scores with three other quality scales. Construct validity was tested by regressing the PEDro score and individual-item scores with the Institute for Scientific Information Web of Knowledge impact factors (IF) and SCImago journal rankings (SJR) for the journals in which the trials were published. RESULTS Testing of convergent validity revealed correlations with the other quality scales ranging from 0.31 to 0.69. The PEDro total score was weakly but significantly associated with IF and SJR (P < 0.0001). Eight of the 10 individual scale items that contribute to the PEDro total score were significantly associated with IF. CONCLUSION This study provides preliminary evidence of the convergent and construct validity of the PEDro total score and the construct validity of eight individual scale items.

Cochrane reviews used more rigorous methods than non-Cochrane reviews: survey of systematic reviews in physiotherapy.

OBJECTIVE To describe the quality and methods of systematic reviews of physiotherapy interventions, compare Cochrane and non-Cochrane reviews, and establish the interrater reliability of the Overview Quality Assessment Questionnaire (OQAQ) quality assessment tool. STUDY DESIGN AND SETTING A survey of 200 published systematic reviews was done. Two independent raters assessed the search strategy, assessment of trial quality, outcomes, pooling, conclusions, and overall quality (OQAQ). The study was carried out in the University research center. RESULTS In these reviews, the five most common databases searched were MEDLINE, EMBASE, Cochrane Library, CINAHL, and Cochrane Review Group Registers. The Cochrane allocation concealment system and Jadad Scale were most frequently used to assess trial quality. Cochrane reviews searched more databases and were more likely to assess trial quality, report dichotomous outcomes for individual trials, and conduct a meta-analysis than non-Cochrane reviews. Non-Cochrane reviews were more likely to conclude that there was a beneficial effect of treatment. Cochrane reviews were of higher quality than non-Cochrane reviews. There has been an increase in the quality of systematic reviews over time. The OQAQ has fair to good interrater reliability. CONCLUSION The quality of systematic reviews in physiotherapy is improving, and the use of Cochrane Collaboration procedures appears to improve the methods and quality.

A Description of the Trials, Reviews, and Practice Guidelines Indexed in the PEDro Database

This perspective provides an overview of the randomized controlled trials, systematic reviews, and evidence-based clinical practice guidelines in physical therapy. Data from the Physiotherapy Evidence Database (PEDro) are used to describe key events in the history of physical therapy research and the growth of evidence of effects of interventions used in the various subdisciplines of physical therapy. The 11,494 records that were identified reveal a rich history of physical therapy research dating back to the first trial in 1929. Most of the randomized controlled trials, systematic reviews, and evidence-based clinical practice guidelines in physical therapy have been published since the year 2000. This rapid growth presents a challenge for physical therapists who want to keep up to date in clinical practice.

Genetic analysis of Pseudomonas aeruginosa isolates from the sputa of Australian adult cystic fibrosis patients.

ABSTRACT Genetic investigations were carried out with 50 phenotypically selected strains of Pseudomonas aeruginosa from 18 patients attending an Australian cystic fibrosis (CF) center. The isolates were analyzed by restriction fragment length polymorphism (RFLP) analysis by pulsed-field gel electrophoresis (PFGE). Phylogenetic analysis of the macrorestriction patterns showed rates of genetic similarity ranging from 76 to 100%; 24 (48%) of the strains from 11 patients had greater than 90% similarity. A dominant strain emerged: 15 isolates from seven patients had identical PFGE patterns, and 4 other isolates were very closely related. The 50 isolates were grouped into 21 pulsotypes on the basis of visual delineation of a three-band difference. Ten of the 18 (56%) patients were infected with clonal or subclonal strains. Sequence analysis of PCR products derived from the mucA gene showed 20 mutations, with the number of mutations in individual isolates ranging from 1 to 4; 19 of these changes are reported here for the first time. Potentially functional changes were found in 22 (44%) isolates. Eight changes (five transversions and three single base deletions) led to premature stop codons, providing support for the presence of mucA mutations as one pathway to mucoidy. There was a trend toward an association between the dominant strain and lack of potentially functional mucA mutations (P = 0.09 by the χ2 test) but no relationship between genotype and phenotype. This is the first study of genetic variation in P. aeruginosa isolates from adult Australian CF patients. The findings highlight the need for further investigations on the transmissibility of P. aeruginosa in CF patients.

Phenotypic Characterization of Clonal and Nonclonal Pseudomonas aeruginosa Strains Isolated from Lungs of Adults with Cystic Fibrosis

ABSTRACT The emergence of virulent Pseudomonas aeruginosa clones is a threat to cystic fibrosis (CF) patients globally. Characterization of clonal P. aeruginosa strains is critical for an understanding of its clinical impact and developing strategies to meet this problem. Two clonal strains (AES-1 and AES-2) are circulating within CF centers in eastern Australia. In this study, phenotypic characteristics of 43 (14 AES-1, 5 AES-2, and 24 nonclonal) P. aeruginosa isolates were compared to gain insight into the properties of clonal strains. All 43 isolates produced bands of the predicted size in PCRs for vfr, rhlI, rhlR, lasA, lasB, aprA, rhlAB, and exoS genes; 42 were positive for lasI and lasR, and none had exoU. Thirty-seven (86%) isolates were positive in total protease assays; on zymography, 24 (56%) produced elastase/staphylolysin and 22 (51%) produced alkaline protease. Clonal isolates were more likely than nonclonal isolates to be positive for total proteases (P = 0.02), to show elastase and alkaline protease activity by zymography (P = 0.04 and P = 0.01, respectively), and to show elastase activity by the elastin-Congo red assay (P = 0.04). There were no other associations with genotype. Overall, increasing patient age was associated with decreasing elastase activity (P = 0.03). Thirty-two (74%) isolates had at least one N-acylhomoserine lactone (AHL) by thin-layer chromatography. rhl-associated AHL detection was associated with the production and level of total protease and elastase activity (all P < 0.01). Thirty-three (77%) isolates were positive for ExoS by Western blot analysis, 35 (81%) produced rhamnolipids, and 34 (79%) showed chitinase activity. Findings suggest that protease activity during chronic infection may contribute to the transmissibility or virulence of these clonal strains.

The effect of body position on maximal expiratory pressure and flow

Positioning combined with coughing and huffing is frequently used to promote secretion clearance. Maximum expiratory pressure (MEP) and peak expiratory flow rate (PEFR) have been used as surrogate measures of cough and huff strength. This study investigated the effect of body position on MEP and PEFR. Repeated measures of MEP and PEFR were performed across seven randomised positions (standing, chair sitting, sitting in bed with backrest vertical, sitting in bed with backrest at 45 degrees, supine, side lying, and side lying with head down tilt 20 degrees) on 25 adults with normal respiratory function (NRF) and 11 adults with chronic airflow limitation (CAL). For the NRF group, MEP in standing (143+/-10cmH2O, mean+/-SEM) was significantly higher than MEP in chair sitting (133+/-10cmH2O) which in turn was significantly higher than in the remaining positions. The MEP in head down tilt (108+/-9cmH2O) was significantly lower than in all other positions. The PEFR in standing (571+/-24L/min) was significantly higher and head down tilt (486+/-23L/min) was significantly lower than in all other positions. For the CAL group, MEP in standing (134+/-18cmH2O) was significantly higher, while in head down tilt (96+/-15cmH2O) was significantly lower, than in most other positions. For the CAL group, PEFR in standing (284+/-40ml/sec) was significantly higher, while in head down tilt (219+/-38ml/sec) was significantly lower, than in most other positions. Body position has a significant effect on MEP and PEFR in NRF and CAL subjects, with the lowest values in the head down position. Thus, to maximise the strength of expiratory manoeuvres during treatments that use the head down position, patients should be encouraged to adopt a more upright position when coughing or huffing.

Inspiratory muscle training increases inspiratory muscle strength in patients weaning from mechanical ventilation: a systematic review

QUESTION Does inspiratory muscle training improve inspiratory muscle strength and endurance, facilitate weaning, improve survival, and reduce the rate of reintubation and tracheostomy in adults receiving mechanical ventilation? DESIGN Systematic review of randomised or quasi-randomised controlled trials. PARTICIPANTS Adults over 16 years of age receiving mechanical ventilation. INTERVENTION Inspiratory muscle training versus sham or no inspiratory muscle training. OUTCOME MEASURES Data were extracted regarding inspiratory muscle strength and endurance, the duration of unassisted breathing periods, weaning success and duration, reintubation and tracheostomy, survival, adverse effects, and length of stay. RESULTS Three studies involving 150 participants were included in the review. The studies varied in time to commencement of the training, the device used, the training protocol, and the outcomes measured. Inspiratory muscle training significantly increased inspiratory muscle strength over sham or no training (weighted mean difference 8 cmH(2)O, 95% CI 6 to 9). There were no statistically significant differences between the groups in weaning success or duration, survival, reintubation, or tracheostomy. CONCLUSION Inspiratory muscle training was found to significantly increase inspiratory muscle strength in adults undergoing mechanical ventilation. Despite data from a substantial pooled cohort, it is not yet clear whether the increase in inspiratory muscle strength leads to a shorter duration of mechanical ventilation, improved weaning success, or improved survival. Further large randomised studies are required to clarify the impact of inspiratory muscle training on patients receiving mechanical ventilation. REVIEW REGISTRATION PROSPERO CRD42011001132.

CENTRAL, PEDro, PubMed, and EMBASE Are the Most Comprehensive Databases Indexing Randomized Controlled Trials of Physical Therapy Interventions

Background Many bibliographic databases index research studies evaluating the effects of health care interventions. One study has concluded that the Physiotherapy Evidence Database (PEDro) has the most complete indexing of reports of randomized controlled trials of physical therapy interventions, but the design of that study may have exaggerated estimates of the completeness of indexing by PEDro. Objective The purpose of this study was to compare the completeness of indexing of reports of randomized controlled trials of physical therapy interventions by 8 bibliographic databases. Design This study was an audit of bibliographic databases. Methods Prespecified criteria were used to identify 400 reports of randomized controlled trials from the reference lists of systematic reviews published in 2008 that evaluated physical therapy interventions. Eight databases (AMED, CENTRAL, CINAHL, EMBASE, Hooked on Evidence, PEDro, PsycINFO, and PubMed) were searched for each trial report. The proportion of the 400 trial reports indexed by each database was calculated. Results The proportions of the 400 trial reports indexed by the databases were as follows: CENTRAL, 95%; PEDro, 92%; PubMed, 89%; EMBASE, 88%; CINAHL, 53%; AMED, 50%; Hooked on Evidence, 45%; and PsycINFO, 6%. Almost all of the trial reports (99%) were found in at least 1 database, and 88% were indexed by 4 or more databases. Four trial reports were uniquely indexed by a single database only (2 in CENTRAL and 1 each in PEDro and PubMed). Limitations The results are only applicable to searching for English-language published reports of randomized controlled trials evaluating physical therapy interventions. Conclusions The 4 most comprehensive databases of trial reports evaluating physical therapy interventions were CENTRAL, PEDro, PubMed, and EMBASE. Clinicians seeking quick answers to clinical questions could search any of these databases knowing that all are reasonably comprehensive. PEDro, unlike the other 3 most complete databases, is specific to physical therapy, so studies not relevant to physical therapy are less likely to be retrieved. Researchers could use CENTRAL, PEDro, PubMed, and EMBASE in combination to conduct exhaustive searches for randomized trials in physical therapy.

Inhaled hypertonic saline as a therapy for cystic fibrosis.

Purpose of review The beneficial effect of a short course of nebulized hypertonic saline on lung function for people with cystic fibrosis was first identified in 1996. At that time, competing hypotheses about the pathogenesis of cystic fibrosis lung disease predicted very different responses to long-term inhalation of hypertonic saline. Recent findings Recent benchtop research supports the hypothesis that the liquid layer lining the airways is depleted in cystic fibrosis. In addition to osmotically restoring this liquid layer, hypertonic saline improves the rheological properties of the mucus and stimulates cough. The net result is accelerated mucus clearance that is short-lived for single doses but sustained with regular inhalation. Long-term use improves lung function mildly but has marked benefits with respect to exacerbations, quality of life and absenteeism, without promoting infection or inflammation. Summary Hypertonic saline appears broadly applicable as an inexpensive therapy for most patients with cystic fibrosis.