108 research outputs found

    Lee Silverman voice treatment versus standard NHS speech and language therapy versus control in Parkinson's disease (PD COMM pilot):study protocol for a randomized controlled trial

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    Background: Parkinson’s disease is a common movement disorder affecting approximately 127,000 people in the UK, with an estimated two thirds having speech-related problems. Currently there is no preferred approach to speech and language therapy within the NHS and there is little evidence for the effectiveness of standard NHS therapy or Lee Silverman voice treatment. This trial aims to investigate the feasibility and acceptability of randomizing people with Parkinson’s disease-related speech or voice problems to Lee Silverman voice treatment or standard speech and language therapy compared to a no-intervention control. Methods/Design: The PD COMM pilot is a three arm, assessor-blinded, randomized controlled trial. Randomization will be computer-generated with participants randomized at a ratio of 1:1:1. Participants randomized to intervention arms will be immediately referred to the appropriate speech and language therapist. The target population are patients with a confirmed diagnosis of idiopathic Parkinson’s disease who have problems with their speech or voice. The Lee Silverman voice treatment intervention group will receive the standard regime of 16 sessions between 50 and 60 minutes in length over four weeks, with extra home practice. The standard speech and language therapy intervention group will receive a dose determined by patients’ individual needs, but not exceeding eight weeks of treatment. The control group will receive standard care with no speech and language therapy input for at least six months post-randomization. Outcomes will be assessed at baseline (pre-randomization) and post- randomization at three, six, and 12 months. The outcome measures include patient-reported voice measures, quality of life, resource use, and assessor-rated speech recordings. The recruitment aim is at least 60 participants over 21 months from 11 sites, equating to at least 20 participants in each arm of the trial. This trial is ongoing and recruitment commenced in May 2012. Discussion: This study will provide information on the feasibility and acceptability of randomizing participants to different speech and language therapies or control/deferred treatment. The findings relating to recruitment, treatment compliance, outcome measures, and effect size will inform a future phase III randomized controlled trial

    Characterization of the impact of rpoB mutations on the in vitro and in vivo competitive fitness of Clostridium difficile and susceptibility to fidaxomicin

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    ObjectivesTo establish the role of specific, non-synonymous SNPs in the RNA polymerase ÎČ subunit (rpoB) gene in reducing the susceptibility of Clostridium difficile to fidaxomicin and to explore the potential in vivo significance of rpoB mutant strains.MethodsAllelic exchange was used to introduce three different SNPs into the rpoB gene of an erythromycin-resistant derivative (CRG20291) of C. difficile R20291. The genome sequences of the created mutants were determined and each mutant analysed with respect to growth and sporulation rates, toxin A/B production and cytotoxicity against Vero cells, and in competition assays. Their comparative virulence and colonization ability was also assessed in a hamster infection model.ResultsThe MIC of fidaxomicin displayed by three mutants CRG20291-TA, CRG20291-TG and CRG20291-GT was substantially increased (>32, 8 and 2 mg/L, respectively) relative to that of the parent strain (0.25 mg/L). Genome sequencing established that the intended mutagenic substitutions in rpoB were the only changes present. Relative to CRG20291, all mutants had attenuated growth, were outcompeted by the parental strain, had lower sporulation and toxin A/B production capacities, and displayed diminished cytotoxicity. In a hamster model, virulence of all three mutants was significantly reduced compared with the progenitor strain, whereas the degree of caecum colonization was unaltered.ConclusionsOur study demonstrates that particular SNPs in rpoB lead to reduced fidaxomicin susceptibility. These mutations were associated with a fitness cost in vitro and reduced virulence in vivo

    Lee Silverman Voice Treatment versus standard speech and language therapy versus control in Parkinson's disease: a pilot randomised controlled trial (PD COMM pilot)

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    Background: Speech-related problems are common in Parkinson's disease (PD), but there is little evidence for the effectiveness of standard speech and language therapy (SLT) or Lee Silverman Voice Treatment (LSVT LOUDÂź). Methods: The PD COMM pilot was a three-arm, assessor-blinded, randomised controlled trial (RCT) of LSVT LOUDÂź, SLT and no intervention (1:1:1 ratio) to assess the feasibility and to inform the design of a full-scale RCT. Non-demented patients with idiopathic PD and speech problems and no SLT for speech problems in the past 2 years were eligible. LSVT LOUDÂź is a standardised regime (16 sessions over 4 weeks). SLT comprised individualised content per local practice (typically weekly sessions for 6-8 weeks). Outcomes included recruitment and retention, treatment adherence, and data completeness. Outcome data collected at baseline, 3, 6, and 12 months included patient-reported voice and quality of life measures, resource use, and assessor-rated speech recordings. Results: Eighty-nine patients were randomised with 90% in the therapy groups and 100% in the control group completing the trial. The response rate for Voice Handicap Index (VHI) in each arm was ≄ 90% at all time-points. VHI was highly correlated with the other speech-related outcome measures. There was a trend to improvement in VHI with LSVT LOUDÂź (difference at 3 months compared with control: - 12.5 points; 95% CI - 26.2, 1.2) and SLT (difference at 3 months compared with control: - 9.8 points; 95% CI - 23.2, 3.7) which needs to be confirmed in an adequately powered trial. Conclusion: Randomisation to a three-arm trial of speech therapy including a no intervention control is feasible and acceptable. Compliance with both interventions was good. VHI and other patient-reported outcomes were relevant measures and provided data to inform the sample size for a substantive trial. Trial registration: International Standard Randomised Controlled Trial Number Register: ISRCTN75223808. registered 22 March 2012

    Designing an environmental flow framework for impounded river systems through modelling of invertebrate habitat quality

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    Many rivers have undergone flow modification by impoundments to provide services such as water supply and hydropower. There is an established consensus that typical modified flow regimes do not sufficiently cater to the needs of downstream ecosystems, and more must be done to understand and mitigate their associated impacts. This study presents a novel, transferable framework by which a small-scale impoundment in North West England is assessed through the use of linked hydro-ecological modelling in SRH-2D and CASiMiR, utilising flow velocity measurements and macroinvertebrate sampling data. Model predictions of habitat quality were supplemented by established ecological principles such as the importance of flow heterogeneity. Results are used to design environmental flow regimes, with the aim of improving ecological metrics whilst considering conflicting water demands. Based on an analysis of historical flow records, the implementation of designer flows over a 12 month period demonstrated increased peak species habitat qualities of 23–26%, characteristics such as flow heterogeneity were more naturalised, and 22% less water was released from the impoundment. Should outcomes be validated by in-stream flow experiment, there is great potential for further development and application of this method, including regional transferability for the rapid designation of environmental flows across a number of sites of similar magnitude and geography

    Habitat Assessment of Non-Wadeable Rivers in Michigan

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    Habitat evaluation of wadeable streams based on accepted protocols provides a rapid and widely used adjunct to biological assessment. However, little effort has been devoted to habitat evaluation in non-wadeable rivers, where it is likely that protocols will differ and field logistics will be more challenging. We developed and tested a non-wadeable habitat index (NWHI) for rivers of Michigan, where non-wadeable rivers were defined as those of order ≄5, drainage area ≄1600 km 2 , mainstem lengths ≄100 km, and mean annual discharge ≄15 m 3 /s. This identified 22 candidate rivers that ranged in length from 103 to 825 km and in drainage area from 1620 to 16,860 km 2 . We measured 171 individual habitat variables over 2-km reaches at 35 locations on 14 rivers during 2000–2002, where mean wetted width was found to range from 32 to 185 m and mean thalweg depth from 0.8 to 8.3 m. We used correlation and principal components analysis to reduce the number of variables, and examined the spatial pattern of retained variables to exclude any that appeared to reflect spatial location rather than reach condition, resulting in 12 variables to be considered in the habitat index. The proposed NWHI included seven variables: riparian width, large woody debris, aquatic vegetation, bottom deposition, bank stability, thalweg substrate, and off-channel habitat. These variables were included because of their statistical association with independently derived measures of human disturbance in the riparian zone and the catchment, and because they are considered important in other habitat protocols or to the ecology of large rivers. Five variables were excluded because they were primarily related to river size rather than anthropogenic disturbance. This index correlated strongly with indices of disturbance based on the riparian (adjusted R 2 = 0.62) and the catchment (adjusted R 2 = 0.50), and distinguished the 35 river reaches into the categories of poor (2), fair (19), good (13), and excellent (1). Habitat variables retained in the NWHI differ from several used in wadeable streams, and place greater emphasis on known characteristic features of larger rivers.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41269/1/267_2004_Article_141.pd
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