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Background: Concern exists that frequent use of topically-applied fusidic acid (FA) and chlorhexidine (CHX) for canine pyoderma is driving clinically relevant resistance, despite rare description of FA and CHX genetic resistance determinants in canine-derived staphylococci. This study aimed to determine minimum inhibitory concentrations (MICs) and investigate presence of putative resistance determinants for FA and CHX in canine-derived methicillin-resistant (MR) and -susceptible (MS) staphylococci. Plasmid-mediated resistance genes (fusB, fusC, fusD, qacA/B, smr; PCR) and MICs (agar dilution) of FA and CHX were investigated in 578 staphylococci (50 MR S. aureus [SA], 50 MSSA, 259 MR S. pseudintermedius [SP], 219 MSSP) from Finland, U.S.A., North (NUK) and South-East U.K. (SEUK) and Germany. In all isolates with FA MIC ≥64 mg/L (n = 27) fusA and fusE were amplified and sequenced. Results: FA resistance determinants (fusA mutations n = 24, fusB n = 2, fusC n = 36) were found in isolates from all countries bar U.S.A. and correlated with higher MICs (≥1 mg/L), although 4 SP isolates had MICs of 0.06 mg/L despite carrying fusC. CHX MICs did not correlate with qacA/B (n = 2) and smr (n = 5), which were found in SEUK SA, and SP from NUK and U.S.A. Conclusions: Increased FA MICs were frequently associated with fusA mutations and fusC, and this is the first account of fusB in SP. Despite novel description of qacA/B in SP, gene presence did not correlate with CHX MIC. Selection pressure from clinical use might increase prevalence of these genetic determinants, but clinical significance remains uncertain in relation to high skin concentrations achieved by topical therapy. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to investigate the suitability of the North Star Ambulatory Assessment as a possible outcome measure in multicentric clinical trials. More specifically we wished to investigate the level of training needed for achieving a good interobserver reliability in a multicentric setting. The scale was specifically designed for ambulant children with Duchenne Muscular Dystrophy and includes 17 items that are relevant for this cohort. Thirteen Italian centers participated in the study. In the first phase of the study we provided two training videos and an example of the scale performed on a child. After the first session of training, all the 13 examiners were asked to send a video with an assessment performed in their centre and to score all the videos collected. There were no difficulties in performing the items and in obtaining adequate videos with a hand held camera but the results showed a poor interobserver reliability (<.5). After a second training session with review and discussion of the videos previously scored, the same examiners were asked to score three new videos. The results of this session had an excellent interobserver reliability (.995). The level of agreement was maintained even when the same videos were rescored after a month, showing a significant intra-observer reliability (.95). Our results suggest that the NSAA is a test that can be easily performed, completed in 10min and can be used in a multicentric setting, providing that adequate training is administered. [Copyright &y& Elsevier]

In the last few years a number of therapeutical approaches have become available for patients affected by Duchenne muscular dystrophy (DMD). The majority of the approaches proposed so far are specifically targeting distinct group of mutations, such as stop codon point mutations or groups of deletions as in exon skipping studies. Because of this, the number of patients eligible for these studies is limited to those having specific mutations or groups of mutations. This has raised the question of whether natural history data should be used as controls in studies with few eligible patients and, more specifically, whether individual groups of mutations follow the general natural history of boys of DMD or have distinct profiles of progression of functional impairment. The aim of this study was to report 12month longitudinal changes of the 6min walk test (6MWT) in a large cohort of DMD ambulant patients subdivided according to type and site of mutations. 6MWT was performed in 198 DMD ambulant boys, older than 4years at baseline and repeated after 12months. 137 had deletions, 18 had duplications and 43 point mutations. Patients with deletions were further subdivided into subgroups according to whether they had mutations eligible for skipping in different exons, selecting those who were currently or likely to be part of clinical trials, eligible for skipping 44 (n =18), eligible for skipping 45 (n =16), eligible for skipping 51 (n =27), eligible for skipping 53 (n =28). Patients with point mutations were also subdivided identifying those with stop codon mutations. The 6MWD showed 12months changes between −325 and 175 (mean −10)m. There was no significant difference between deletions, duplications and point mutations neither at baseline nor in the 12month changes. When patients were subdivided into different subgroups of deletions according to their eligibility to skip specific exons, there was little difference between the individual subgroups and the patients with the whole cohort. The subgroup eligible for skipping exon 44 however had a trend to perform better at baseline and to show less deterioration than the other subgroups. [Copyright &y& Elsevier]

While there have been considerable advances for ambulant children with Duchenne Muscular Dystrophy (DMD), no prospective study has so far been devoted to outcome measures in non ambulant patients, with increasing complaints from families and patients. This information appears to be relevant not only for a better understanding of the disease progression but also for possible enrolment of patients in future trials. As a result of an international effort, a new tool, the Performance of Upper Limb (PUL) was specifically designed to assess upper limb function in DMD boys. The purpose of the PUL is to assess changes that occurs in motor performance of the upper limb over time from when a boy is still ambulant to the time he loses all arm function when non-ambulant. The aim of the present study was to use the PUL in: [(1)] a cohort of typically developing children from the age of 3years onwards in order to identify the age when the activities assessed in the individual items are consistently achieved. [(2)] a cohort of DMD children and young adults to assess the range of findings at different ages. We collected normative data for the scale validation on 258 typically developing children from 3 to 14years old. A full score was consistently achieved (>85%) by the age of 3.5years. Below the age of 3.5years there was a significant number (>15%) who had difficulties in the items involving stacking cans, opening a Ziploc container, tearing a piece of paper and in lifting the heavier weights. After the age of 3.5years difficulties were only occasionally found in tearing a sheet of paper. When the PUL was performed in the 211 DMD patients (age range 2.8–23years), we observed a progressive deterioration of scores with age, with early involvement of the proximal muscles that was more obvious after the age of 10years. Even the oldest and weakest DMD patients were still able to perform some of the distal items, suggesting that the scale is capable of measuring small. [Copyright &y& Elsevier]

Abstract: Six minute walk test (6MWT), timed items and North Star Ambulatory Assessment (NSAA) are increasingly used as possible outcome measures in clinical trials in Duchenne Muscular Dystrophy (DMD). Longitudinal data have previously been reported following changes in their scores over a 12month period. The aim of the study was to assess 6MWT and NSAA in a cohort of 119 ambulant DMD boys over 24months in order to establish the spectrum of possible changes over a longer period of time. The study is a longitudinal multicentric cohort study. 119 ambulant DMD patients were assessed using 6MWT, NSAA at baseline 12 and 24months. Clinical data including age and steroid treatment were collected. During the 24months of the study, we observed a progressive decline in both measures that was more obvious in the second year. Not all the DMD boys in our cohort showed a decline as young boys showed some improvement in their 6MWT and NSAA scores up to the age of 7. Fifteen patients (12.6%) lost the ability to walk independently: 2/15 by the end of the first year and the other 13 in the second year. Another 22 patients (21.1%) were still able to walk independently but were unable to get up from supine (8/22 at baseline, 4 at 12months, 10 at 24months). Four children also lost the ability to perform the 6MWT (2 at 12months and the other 2 at 24months). This study provides longitudinal data of NSAA and 6MWT over a 24month period. These data can be useful when designing a clinical trial. [Copyright &y& Elsevier]