Safety assessment of nebulized xylitol in beagle dogs

Xylitol, a potential cystic fibrosis treatment, lowers the salt concentration of airway surface liquid and enhances innate immunity of human airways. The study objective was to evaluate the potential toxicity/recovery from a 14-consecutive day (7 days/week), facemask inhalation administration of nebulized xylitol solution in Beagle dogs. Aerosolized xylitol was generated through three Aerotech II nebulizers operating at approximately 40 psi driving pressure. Test article groups were exposed to the same concentration of aerosolized xylitol for 1, 0.5, or 0.25 h for the high, mid, and low exposures, respectively. A control group was exposed for 1 h to a nebulized normal saline solution. Animals were sacrificed the day following the last exposure or subsequently after 14 non-exposure days. Study endpoints included clinical observations, body weights, ophthalmology, and physical examinations, food consumption, clinical pathology, urinalyses, organ weights, and histopathology. Mean xylitol aerosol concentrations for all groups were approximately 3.5 mg/l. Mean total deposited doses to the pulmonary region were estimated as 21, 11, and 5 mg/kg, for the high-, mid-, and low-exposure groups, respectively. All dogs survived to the scheduled necropsy. No treatment-related findings were observed due to xylitol exposure in any end point examined. Lung findings (mild interstitial infiltration, macrophage hyperplasia, alveolitis, and bronchitis) were consistent among exposed and control groups. No exposure-related effect of xylitol in any parameter assessed was seen during or after the 14-day exposure in Beagle dogs. The No Observed Effect Level was the high-exposure level and suggests that inhaled xylitol is safe for clinical administration.     

Medical device evaluation in the United Kingdom: past,present and future

The evaluation of medical devices in the UK has been through many changes since the early hospital equipment assessments in the 1960s. The range of medical devices evaluated has increased and the evaluation reports published have changed, but the evaluation programme continues to be a respected service for the NHS and social care. This review documents the history of the Device Evaluation Service, from its beginnings to the present day, and looks forward to its future. Following an independent strategic review and the Healthcare Industries Task Force (HITF) recommendations, the Device Evaluation Service is now entering a new and exciting developmental phase.     

Using Tree-Based Recursive Partitioning Methods to Group Haplotypes for Increased Power in Association Studies

Motivated by the increasing availability of high‐density single nucleotide polymorphism (SNP) markers across the genome, various haplotype‐based methods have been developed for candidate gene association studies, and even for genome‐wide association studies. Although haplotype approaches dramatically reduce the multiple comparisons problem (as compared to single SNP analysis), even the number of existing haplotypes is relatively large, which increases the degrees of freedom and decreases the power for the corresponding test statistic. Grouping haplotypes is a way to reduce the degrees of freedom. We propose a procedure that uses a tree‐based recursive partitioning algorithm to group haplotypes into a small number of clusters, and conducts the association test based on groups of haplotypes instead of individual haplotypes. The method can be used for both population‐based and family‐based association studies, with known or ambiguous phase information. Simulation studies suggest that the proposed method has the right type I error rate, and is more powerful than some existing haplotype‐based tests.