Novel approaches to the treatment of Pseudomonas aeruginosa infections in cystic fibrosis

Pseudomonas aeruginosa chronically infects patients with cystic fibrosis and is associated with greater morbidity. There has been limited progress on the clinical development of new antibiotics with novel modes of action. This review addresses some of the latest research developments on the exploitation of candidate adjuvant therapeutic agents that may act alongside conventional antibiotics as an alternative therapeutic strategy. After considering key mechanisms this opportunistic pathogen employs to control virulence, the progress of various strategies including the inhibition of quorum sensing, efflux pumps and lectins, and the use of iron chelators, bacteriophages, immunisation and immunotherapy is reviewed. Both therapeutic approaches in early development and clinical phase are discussed

Compliance with mandatory reporting of clinical trial results on ClinicalTrials.gov: cross sectional study

Objective To examine compliance with mandatory reporting of summary clinical trial results (within one year of completion of trial) on ClinicalTrials.gov for studies that fall under the recent Food and Drug Administration Amendments Act (FDAAA) legislation. Design Registry based study of clinical trial summaries. Data sources ClinicalTrials.gov, searched on 19 January 2011, with cross referencing with Drugs@FDA to determine for which trials mandatory reporting was required within one year. Selection criteria Studies registered on ClinicalTrials.gov with US sites which completed between 1 January and 31 December 2009. Main outcome measure Proportion of trials for which results had been reported. Results The ClinicalTrials.gov registry contained 83 579 entries for interventional trials, of which 5642 were completed within the timescale of interest. We identified trials as falling within the mandatory reporting rules if they were covered by the FDAAA (trials of a drug, device, or biological agent, which have at least one US site, and are of phase II or later) and if they investigated a drug that already had approval from the Food and Drug Administration. Of these, 163/738 (22%) had reported results within one year of completion of the trial compared with 76/727 (10%) trials that were not subject to mandatory reporting (95% confidence interval for the difference in proportions 7.8% to 15.5%; χ2 test, P=2.6×10−9). Later phase trials were more likely to report results (P=4.4×10−11), as were industry funded trials (P=2.2×10−16). Conclusion Most trials subject to mandatory reporting did not report results within a year of completion

Magnetoluminescence

Pulsar Wind Nebulae, Blazars, Gamma Ray Bursts and Magnetars all contain regions where the electromagnetic energy density greatly exceeds the plasma energy density. These sources exhibit dramatic flaring activity where the electromagnetic energy distributed over large volumes, appears to be converted efficiently into high energy particles and gamma-rays. We call this general process magnetoluminescence. Global requirements on the underlying, extreme particle acceleration processes are described and the likely importance of relativistic beaming in enhancing the observed radiation from a flare is emphasized. Recent research on fluid descriptions of unstable electromagnetic configurations are summarized and progress on the associated kinetic simulations that are needed to account for the acceleration and radiation is discussed. Future observational, simulation and experimental opportunities are briefly summarized.Comment: To appear in "Jets and Winds in Pulsar Wind Nebulae, Gamma-ray Bursts and Blazars: Physics of Extreme Energy Release" of the Space Science Reviews serie

The top 10 research priorities in cystic fibrosis developed by a partnership between people with CF and health care providers

There remain many treatment uncertainties in cystic fibrosis (CF). With limited resources, research should focus on questions which are most important to the CF community. We conducted a James Lind Alliance Priority Setting Partnership in CF. Research questions were elicited and then prioritised in successive surveys. A workshop agreed the final Top 10. Online methods avoided cross infection and widened participation. The elicitation survey had 482 respondents (1080 questions) and prioritisation survey 677 respondents. Participants were drawn equally from the patient and clinical communities globally. We have achieved a consensus on ten research priorities which will be attractive to funders

Delayed publication of clinical trials in cystic fibrosis☆

Background: When the publication of important trial data is delayed, or data are never published, this will prevent the proper practice of evidence based medicine through robust systematic reviews. Clinical trial registries allow researchers to interrogate the trial protocol and afford the opportunity to identify studies that have been completed and so determine the time lag between completion and publication. Methods: We searched ClinicalTrials.gov with the keywords ‘cystic fibrosis’. Intervention trials which had completed 1st Jan 1998–31st Dec 2010 were selected. Time to publication in a peer-reviewed journal was calculated. Survival analyses using the log rank test were undertaken. Results: We identified 142 records. Of these, 62 had full paper publications. The median time to publication was 3.25 years. Phase of study (phase one studies more delayed, p = 0.024) but not source of funding (p = 0.34) was associated with time to publication. Conclusions: Clinical trials in cystic fibrosis take a considerable amount of time to report their findings. More importantly, a large number of trials fail to report at all