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Toulouse, France

Misra V.P.,National Hospital for Neurology and Neurosurgery | Ehler E.,County Hospital Pardubice | Zakine B.,Ipsen | Maisonobe P.,Data Management | Simonetta-Moreau M.,Hopitaux de Toulouse
BMJ Open | Year: 2012

Objectives: Real-life data on response to Botulinum toxin A (BoNT-A) in cervical dystonia (CD) are sparse. An expert group of neurologists was convened with the overall aim of developing a definition of treatment response, which could be applied in a non-interventional study of BoNT-A-treated subjects with CD. Design: International, multicentre, prospective, observational study of a single injection cycle of BoNT-A as part of normal clinical practice. Setting: 38 centres across Australia, Belgium, Czech Republic, France, Germany, The Netherlands, Portugal, Russia and the UK. Participants: 404 adult subjects with idiopathic CD. Most subjects were women, aged 41-60 years and had previously received BoNT-A. Outcome measures: Patients were classified as responders if they met all the following four criteria: magnitude of effect (≥25% improvement Toronto Western Spasmodic Torticollis Rating Scale), duration of effect (≥12-week interval between the BoNT-A injection day and subject-reported waning of treatment effect), tolerability (absence of severe related adverse event) and subject's positive Clinical Global Improvement (CGI). Results: High rates of response were observed for magnitude of effect (73.6%), tolerability (97.5%) and subject's clinical global improvement (69.8%). The subjective duration of effect criterion was achieved by 49.3% of subjects; 28.6% of subjects achieved the responder definition. Factors most strongly associated with response were age (<40 years; OR 3.9, p<0.05) and absence of baseline head tremor (OR 1.5; not significant). Conclusions: Three of four criteria were met by most patients. The proposed multidimensional definition of response appears to be practical for routine practice. Unrealistically high patient expectation and subjectivity may influence the perception of a quick waning of effect, but highlights that this aspect may be a hurdle to response in some patients. Clinical registration number: (NCT00833196; ClinicalTrials.gov). Source


Bounes V.,Hopitaux de Toulouse | Bounes V.,University Paul Sabatier | Palmaro A.,University Paul Sabatier | Lapeyre-Mestre M.,University Paul Sabatier | Roussin A.,University Paul Sabatier
Pain Physician | Year: 2013

Background: Acute and chronic pains are reported to be highly prevalent in patients under opioid maintenance treatment (OMT). Lack of knowledge concerning the complex relationship between pain, opioid use, and their impact on OMT efficacy can account for the barriers encountered for pain management. Objectives: To assess the impact of acute pain exposure on long-term OMT retention in a cohort of patients under buprenorphine or methadone followed up during 12 months. Study Design: Prospective, multi-center observational cohort clinical study. Setting: Emergency departments, surgery departments, and specialized addiction care centers in an outpatient setting in south-western France (Midi-Pyrénées area), from April 2008 to January 2010. Methods: Patients aged 18 or more under OMT for at least 3 months, and followed up by a physician were recruited. Acute pain was assessed using the Visual Analog Scale (VAS) or the Verbal Rating Scale (VRS). Exposed patients were those with a pain score greater than 0 at the time of admission on any of the rating scales. The OMT rate after 12 months was compared among exposed and unexposed patients. OMT retention was also investigated after 3 and 6 months follow-up. Results: A total of 151 patients, 81 exposed and 70 unexposed, were recruited; among them, respectively, 26 (32%) and 34 (49%) completed 12-months follow-up. Acute pain exposure appeared to be significantly and negatively associated with retention in treatment (crude OR: 0.44; 95% CI [0.22 - 0.87]; adjusted OR: 0.46; 95% CI [0.23 - 0.93]). Compared to methadone users, patients under buprenorphine were less likely to have their OMT maintained after 12 months (OR 0.37; 95% CI [0.18 - 0.75]; adjusted OR 0.38; 95% CI [0.18 - 0.80]). Limitations: Follow-up rate was 40 % (60/151). Conclusion: This study demonstrates the strong negative impact of acute pain on OMT in a population mainly composed of patients under buprenorphine, as well as differential response depending on the OMT medication. The findings highlight the need to consider the characteristics of pain in the population under OMT and to develop evidence-based guidelines for pain management. Trial registration: The study was registered at www.clinical.trials.gov with the study identifier: NCT00738036. Ethics Committee approval was received on February 11, 2008. Participants' written consent was not required. Source


Lourdusamy A.,South London and Maudsley NHS Foundation Trust and Institute of Psychiatry | Newhouse S.,South London and Maudsley NHS Foundation Trust and Institute of Psychiatry | Lunnon K.,South London and Maudsley NHS Foundation Trust and Institute of Psychiatry | Proitsi P.,Kings College London | And 13 more authors.
Human Molecular Genetics | Year: 2012

Proteins are central to almost all cellular processes, and dysregulation of expression and function is associated with a range of disorders. A number of studies in human have recently shown that genetic factors significantly contribute gene expression variation. In contrast, very little is known about the genetic basis of variation in protein abundance in man. Here, we assayed the abundance levels of proteins in plasma from 96 elderly Europeans using a new aptamer-based proteomic technology and performed genome-wide local (cis-) regulatory association analysis to identify protein quantitative trait loci (pQTL). We detected robust cis-associations for 60 proteins at a false discovery rate of 5%. The most highly significant single nucleotide polymorphism detected was rs7021589 (false discovery rate, 2.5 × 10-12), mapped within the gene coding sequence of Tenascin C (TNC). Importantly, we identified evidence of cis-regulatory variation for 20 previously disease-associated genes encoding protein, including variants with strong evidence of disease association show significant association with protein abundance levels. These results demonstrate that common genetic variants contribute to the differences in protein abundance levels in human plasma. Identification of pQTLs will significantly enhance our ability to discover and comprehend the biological and functional consequences of loci identified from genome-wide association study of complex traits. This is the first large-scale genetic association study of proteins in plasma measured using a novel, highly multiplexed slow off-rate modified aptamer (SOMAmer) proteomic platform. © The Author 2012. Published by Oxford University Press. All rights reserved. Source


Thambisetty M.,U.S. National Institute on Aging | Simmons A.,Kings College London | Hye A.,Kings College London | Campbell J.,Proteome science Plc | And 13 more authors.
PLoS ONE | Year: 2011

Peripheral biomarkers of Alzheimer's disease (AD) reflecting early neuropathological change are critical to the development of treatments for this condition. The most widely used indicator of AD pathology in life at present is neuroimaging evidence of brain atrophy. We therefore performed a proteomic analysis of plasma to derive biomarkers associated with brain atrophy in AD. Using gel based proteomics we previously identified seven plasma proteins that were significantly associated with hippocampal volume in a combined cohort of subjects with AD (N = 27) and MCI (N = 17). In the current report, we validated this finding in a large independent cohort of AD (N = 79), MCI (N = 88) and control (N = 95) subjects using alternative complementary methods-quantitative immunoassays for protein concentrations and estimation of pathology by whole brain volume. We confirmed that plasma concentrations of five proteins, together with age and sex, explained more than 35% of variance in whole brain volume in AD patients. These proteins are complement components C3 and C3a, complement factor-I, γ-fibrinogen and alpha-1-microglobulin. Our findings suggest that these plasma proteins are strong predictors of in vivo AD pathology. Moreover, these proteins are involved in complement activation and coagulation, providing further evidence for an intrinsic role of these pathways in AD pathogenesis. Source


Hartmann T.,Saarland University | van Wijk N.,Nutricia Research | Wurtman R.J.,Massachusetts Institute of Technology | Olde Rikkert M.G.,Radboud University Nijmegen | And 4 more authors.
Journal of Alzheimer's disease : JAD | Year: 2014

Recently, a biomarker panel of 10 plasma lipids, including 8 phosphatidylcholine species, was identified that could predict phenoconversion from cognitive normal aged adults to amnestic mild cognitive impairment or Alzheimer's disease (AD) within 2-3 years with >90% accuracy. The reduced levels of these plasma phospholipids could reflect altered phospholipid metabolism in the brain and periphery. We show that a 24-week nutritional intervention in drug-naïve patients with very mild to mild AD significantly increased 5 of the 7 measured biomarker phosphatidylcholine species. By providing nutrients which normally rate-limit phospholipid synthesis, this nutritional intervention could be useful in asymptomatic subjects with a plasma lipid biomarker profile prognostic of AD. Source

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