Publications by authors named "B R Saville"

178 Publications

Therapy development for the mucopolysaccharidoses: Updated consensus recommendations for neuropsychological endpoints.

Mol Genet Metab 2020 Sep - Oct;131(1-2):181-196. Epub 2020 Aug 31.

Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Shapiro Neuropsychology Consulting LLC, Portland, OR, USA. Electronic address:

Neurological dysfunction represents a significant clinical component of many of the mucopolysaccharidoses (also known as MPS disorders). The accurate and consistent assessment of neuropsychological function is essential to gain a greater understanding of the precise natural history of these conditions and to design effective clinical trials to evaluate the impact of therapies on the brain. In 2017, an International MPS Consensus Panel published recommendations for best practice in the design and conduct of clinical studies investigating the effects of therapies on cognitive function and adaptive behavior in patients with neuronopathic mucopolysaccharidoses. Based on an International MPS Consensus Conference held in February 2020, this article provides updated consensus recommendations and expands the objectives to include approaches for assessing behavioral and social-emotional state, caregiver burden and quality of life in patients with all mucopolysaccharidoses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ymgme.2020.08.007DOI Listing
August 2020

Oseltamivir bij infectie door een humaan coronavirus: Post-hocanalyse van gegevens uit 2016-2018.

Huisarts Wet 2020 Jul 4:1-3. Epub 2020 Jul 4.

Hoogleraar klinische epidemiologie, Universiteit Antwerpen, Vakgroep Eerstelijns- en Interdisciplinaire Zorg, Antwerpen, Nederland.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12445-020-0792-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335764PMC
July 2020

Oseltamivir for coronavirus illness: post-hoc exploratory analysis of an open-label, pragmatic, randomised controlled trial in European primary care from 2016 to 2018.

Br J Gen Pract 2020 07 25;70(696):e444-e449. Epub 2020 Jun 25.

Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter, Oxford, UK.

Background: Patients infected with the novel coronavirus (SARS-CoV-2) are being treated empirically with oseltamivir, but there is little evidence from randomised controlled trials to support the treatment of coronavirus infections with oseltamivir.

Aim: To determine whether adding oseltamivir to usual care reduces time to recovery in symptomatic patients who have tested positive for coronavirus (not including SARS-CoV-2).

Design And Setting: Exploratory analysis of data from an open-label, pragmatic, randomised controlled trial during three influenza seasons, from 2016 to 2018, in primary care research networks, in 15 European countries.

Method: Patients aged ≥1 year presenting to primary care with influenza-like illness (ILI), and who tested positive for coronavirus (not including SARS-CoV-2), were randomised to usual care or usual care plus oseltamivir. The primary outcome was time to recovery defined as a return to usual activities, with minor or absent fever, headache, and muscle ache.

Results: Coronaviruses (CoV-229E, CoV-OC43, CoV-KU1 and CoV-NL63) were identified in 308 (9%) out of 3266 randomised participants in the trial; 153 of these were allocated to usual care and 155 to usual care plus oseltamivir; the primary outcome was ascertained in 136 and 147 participants, respectively. The median time to recovery was shorter in patients randomised to oseltamivir: 4 days (interquartile range [IQR] 3-6) versus 5 days (IQR 3-8; hazard ratio 1.31; 95% confidence interval = 1.03 to 1.66; = 0.026).

Conclusion: Primary care patients with ILI testing positive for coronavirus (not including SARS-CoV-2) recovered sooner when oseltamivir was added to usual care compared with usual care alone. This may be of relevance to the primary care management of COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3399/bjgp20X711941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311109PMC
July 2020

The role of reactive oxygen species in the virulence of wheat leaf rust fungus Puccinia triticina.

Environ Microbiol 2020 07 2;22(7):2956-2967. Epub 2020 Jun 2.

Forensic Science Program Trent University, Peterborough, Ontario, K9J 7B8, Canada.

Reactive oxygen species (ROS) play an important role during host-pathogen interactions and are often an indication of induced host defence responses. In this study, we demonstrate for the first time that Puccinia triticina (Pt) generates ROS, including superoxide, H O and hydroxyl radicals, during wheat infection. Through pharmacological inhibition, we found that ROS are critical for both Pt urediniospore germination and pathogenic development on wheat. A comparative RNA-Seq analysis of different stages of Pt infection process revealed 291 putative Pt genes associated with the oxidation-reduction process. Thirty-seven of these genes encode known proteins. The expressions of five Pt genes, including PtNoxA, PtNoxB, PtNoxR, PtCat and PtSod, were subsequently verified using RT-qPCR analysis. The results show that the expressions of PtNoxA, PtNoxB, PtNoxR, PtCat and PtSod are up-regulated during urediniospore germination. In comparison, the expressions of PtNoxA, PtNoxB, PtNoxR and PtCat are down-regulated during wheat infection from 12 to 120 h after inoculation (HAI), whereas the expression of PtSod is up-regulated with a peak of expression at 120 HAI. We conclude that ROS are critical for the full virulence of Pt and a coordinate down-regulation of PtNox genes may be important for successful infection in wheat.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1462-2920.15063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496513PMC
July 2020

Safety, Performance, and Efficacy of Cardiac Contractility Modulation Delivered by the 2-Lead Optimizer Smart System: The FIX-HF-5C2 Study.

Circ Heart Fail 2020 04 8;13(4):e006512. Epub 2020 Apr 8.

Cardiovascular Research Foundation, New York (D.B.).

Background: Prior studies of cardiac contractility modulation (CCM) employed a 3-lead Optimizer system. A new 2-lead system eliminated the need for an atrial lead. This study tested the safety and effectiveness of this 2-lead system compared with the 3-lead system.

Methods: Patients with New York Heart Association III/IVa symptoms despite medical therapy, left ventricular ejection fraction 25% to 45%, and not eligible for cardiac resynchronization therapy could participate. All subjects received an Optimizer 2-lead implant. The primary end point was the estimated difference in the change of peak VO from baseline to 24 weeks between FIX-HF-5C2 (2-lead system) subjects relative to control subjects from the prior FIX-HF-5C (3-lead system) study. Changes in New York Heart Association were a secondary end point. The primary safety end point was a comparison of device-related adverse events between FIX-HF-5C2 and FIX-HF-5C subjects.

Results: Sixty subjects, 88% male, 66±9 years old with left ventricular ejection fraction 34±6% were included. Baseline characteristics were similar between FIX-HF-5C and FIX-HF-5C2 subjects except that 15% of FIX-HF-5C2 subjects had permanent atrial fibrillation versus 0% in FIX-HF-5C. CCM delivery did not differ significantly between 2- and 3-lead systems (19 892±3472 versus 19 583±4998 CCM signals/day, CI of difference [-1228 to 1847]). The change of peak VO from baseline to 24 weeks was 1.72 (95% Bayesian credible interval, 1.02-2.42) mL/kg per minute greater in the 2-lead device group versus controls. 83.1% of 2-lead subjects compared with 42.7% of controls experienced ≥1 class New York Heart Association improvement (<0.001). There were decreased Optimizer-related adverse events with the 2-lead system compared with the 3-lead system (0% versus 8%; =0.03).

Conclusions: The 2-lead system effectively delivers comparable amount of CCM signals (including in subjects with atrial fibrillation) as the 3-lead system, is equally safe and improves peak VO and New York Heart Association. Device-related adverse effects are less with the 2-lead system. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03339310.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCHEARTFAILURE.119.006512DOI Listing
April 2020