A Randomized, Crossover Trial Evaluating Patient Handling, Preference, and Ease of Use of the Fluticasone Propionate/Formoterol Breath-Triggered Inhaler.

BACKGROUND: Appropriate inhaler selection is of fundamental importance in obstructive lung disease management. Key factors in device selection include a patient's capacity to operate a particular device and their preference for it. METHODS: This randomized, open-label, two-period, crossover study (NCT01739387) compared the ability of adolescent and adult patients with obstructive lung disease to correctly handle the fluticasone propionate/formoterol fumarate (FP/FORM; Flutiform®) pressurized metered-dose inhaler (pMDI) and FP/FORM K-haler®, a novel breath-triggered inhaler (BTI), following a simple, standardized training regimen. The primary endpoint was the ability to perform all steps correctly at the first attempt. Secondary endpoints included the ability to perform all critical steps correctly at the first attempt, the requisite number of attempts to successfully use the inhaler, the ability to be trained within 15 minutes, and the ability to trigger the K-haler BTI to actuate at the first attempt. Ease of device use and device preference versus patients' usual maintenance inhalers were also assessed. RESULTS AND CONCLUSIONS: At the first attempt, an identical proportion (77.2% [95% confidence interval [CI]: 72.1, 81.8]) of 307 patients performed all pMDI and K-haler BTI handling steps correctly, whereas the corresponding proportions performing all critical steps correctly were 82.4% (95% CIs: 77.7, 86.5) and 87.0% (95% CI: 82.7, 90.5), respectively. For both devices, >90% of patients required only two attempts to master device usage; >99% of patients could be trained to correctly use each device within 15 minutes. Virtually all patients (99.0% [95% CIs: 97.2, 99.8]) were able to successfully trigger the K-haler BTI's dose-release mechanism at first attempt. Ease of use and preference data for FP/FORM pMDI challenged the perceived wisdom that dry powder inhalers are necessarily simpler to use, whereas the corresponding data for FP/FORM K-haler strongly favored this novel BTI over the Turbuhaler®, Accuhaler®, and other pMDIs.

Sequence and functional analyses of Haemophilus spp. genomic islands.

BACKGROUND: A major part of horizontal gene transfer that contributes to the diversification and adaptation of bacteria is facilitated by genomic islands. The evolution of these islands is poorly understood. Some progress was made with the identification of a set of phylogenetically related genomic islands among the Proteobacteria, recognized from the investigation of the evolutionary origins of a Haemophilus influenzae antibiotic resistance island, namely ICEHin1056. More clarity comes from this comparative analysis of seven complete sequences of the ICEHin1056 genomic island subfamily. RESULTS: These genomic islands have core and accessory genes in approximately equal proportion, with none demonstrating recent acquisition from other islands. The number of variable sites within core genes is similar to that found in the host bacteria. Furthermore, the GC content of the core genes is similar to that of the host bacteria (38% to 40%). Most of the core gene content is formed by the syntenic type IV secretion system dependent conjugative module and replicative module. GC content and lack of variable sites indicate that the antibiotic resistance genes were acquired relatively recently. An analysis of conjugation efficiency and antibiotic susceptibility demonstrates that phenotypic expression of genomic island-borne genes differs between different hosts. CONCLUSION: Genomic islands of the ICEHin1056 subfamily have a longstanding relationship with H. influenzae and H. parainfluenzae and are co-evolving as semi-autonomous genomes within the 'supragenomes' of their host species. They have promoted bacterial diversity and adaptation through becoming efficient vectors of antibiotic resistance by the recent acquisition of antibiotic resistance transposons.

Demonstration of the Rb1 lipopolysaccharide core structure in Salmonella strains with the monoclonal antibody M105.

The lipopolysaccharide (LPS) from 42 strains representing 19 Salmonella serogroups was differentiated into characteristic ladder-like profiles by SDS-PAGE analysis. The core-specific antibody M105 (Ra, Rb1 and Rb2) was used in an immunoblot assay of SDS-PAGE-separated LPS molecules. The M105 antibody bound to the R-type LPS of 18 of the 20 Salmonella strains tested. The results demonstrate that S. enterica serotype Godesberg, S. Adelaide (one of two strains), S. Milwaukee, S. Niarembe, S. Bere and S. Arizonae (serogroup 63) have an atypical LPS core structure which is Rb1 type.