Spectrum of practice in the routine management of cervical dystonia with abobotulinumtoxinA: findings from three prospective open-label observational studies.

Background: Cervical dystonia is a heterogeneous disorder with several possible presentations, for which first-line therapy is often botulinum toxin (BoNT). In routine clinical practice the success of each BoNT injection is dependent on several variables, including individual presentation and injection technique. Large multicenter, observational studies provide important information on individualized administration strategies that cannot be otherwise ascertained from controlled clinical trials. In this meta-analysis of patient level data, we aimed to evaluate the clinical characteristics of patients with cervical dystonia undergoing routine treatment with botulinum toxin, specifically abobotulinumtoxinA. We also aimed to characterize current abobotulinumtoxinA injection techniques and parameters and to explore international differences in patient presentation and treatment. Methods: This was a meta-analysis of baseline data from three prospective, international, multicenter, observational studies (NCT01314365, NCT00833196 and NCT01753349) of botulinum toxin treatment for the routine management of adult cervical dystonia. Results: Data presented illustrate the significant heterogeneity of CD presentation in routine practice. Most subjects presented with a complex pattern of dystonic movements and the majority had additional components of shoulder elevation, tremor and/or jerk. Dosing was generally in accordance with that recommended in the abobotulinumtoxinA prescribing information, although the range of dosing also indicates that injections are tailored to individual presentation. Sub-group analyses at the country level revealed distinct differences in injection practice. Conclusions: This meta-analysis is based on the largest dataset of subjects with cervical dystonia studied to date. The heterogeneity revealed in our baseline findings support the need to develop consistent, practical and comprehensive best practice guidelines

Correction to: Economic evaluation of AbobotulinumtoxinA vs OnabotulinumtoxinA in real-life clinical management of cervical dystonia.

[This corrects the article DOI: 10.1186/s40734-020-0083-0.]

Factors influencing response to Botulinum toxin type A in patients with idiopathic cervical dystonia: results from an international observational study

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)

Lanreotide Autogel 120 mg at extended dosing intervals in patients with acromegaly biochemically controlled with octreotide LAR: The LEAD study

Objective: To evaluate extended dosing intervals (EDIs) with lanreotide Autogel 120 mg in patients with acromegaly previously biochemically controlled with octreotide LAR 10 or 20 mg. Design and methods: Patients with acromegaly had received octreotide LAR 10 or 20 mg/4 weeks for R6 months and had normal IGF1 levels. Lanreotide Autogel 120 mg was administered every 6 weeks for 24 weeks (phase 1); depending on week-24 IGF1 levels, treatment was then administered every 4, 6 or 8 weeks for a further 24 weeks (phase 2). Hormone levels, patient-reported outcomes and adverse events were assessed. Primary endpoint: proportion of patients on 6- or 8-week EDIs with normal IGF1 levels at week 48 (study end). Results: 107/124 patients completed the study (15 withdrew from phase 1 and two from phase 2). Of 124 patients enrolled, 77.4% were allocated to 6- or 8-week EDIs in phase 2 and 75.8% (95% CI: 68.3-83.3) had normal IGF1 levels at week 48 with the EDI (primary analysis). A total of 88.7% (83.1-94.3) had normal IGF1 levels after 24 weeks with 6-weekly dosing. GH levels were ≤2.5 mg/l in >90% of patients after 24 and 48 weeks. Patient preferences for lanreotide Autogel 120 mg every 4, 6 or 8 weeks over octreotide LAR every 4 weeks were high. Conclusions: Patients with acromegaly achieving biochemical control with octreotide LAR 10 or 20 mg/4 weeks are possible candidates for lanreotide Autogel 120 mg EDIs. EDIs are effective and well received among such patients

Mapping Patent Classifications: Portfolio and Statistical Analysis, and the Comparison of Strengths and Weaknesses

The Cooperative Patent Classifications (CPC) jointly developed by the European and US Patent Offices provide a new basis for mapping and portfolio analysis. This update provides an occasion for rethinking the parameter choices. The new maps are significantly different from previous ones, although this may not always be obvious on visual inspection. Since these maps are statistical constructs based on index terms, their quality--as different from utility--can only be controlled discursively. We provide nested maps online and a routine for portfolio overlays and further statistical analysis. We add a new tool for "difference maps" which is illustrated by comparing the portfolios of patents granted to Novartis and MSD in 2016.Comment: Scientometrics 112(3) (2017) 1573-1591; http://link.springer.com/article/10.1007/s11192-017-2449-

Differential and holomorphic differential operators on noncommutative algebras

Abstract This paper deals with sheaves of differential operators on noncommutative algebras, in a manner related to the classical theory of D-modules. The sheaves are defined by quotienting the tensor algebra of vector fields (suitably deformed by a covariant derivative). As an example we can obtain enveloping algebra like relations for Hopf algebras with differential structures which are not bicovariant. Symbols of differential operators are defined, but not studied. These sheaves are shown to be in the center of a category of bimodules with flat bimodule covariant derivatives. Also holomorphic differential operators are considered

Histopathological differences of myotonic dystrophy type 1 (DM1) and PROMM/DM2

Muscle biopsy findings in DM2 have been reported to be similar to those in DM1. The authors used myosin heavy chain immunohistochemistry and enzyme histochemistry for fiber type differentiation on muscle biopsies. Their results show that DM2 patients display a subpopulation of type 2 nuclear clump and other very small fibers and, hence, preferential type 2 fiber atrophy in contrast to type 1 fiber atrophy in DM1 patients

Complete event-by-event α/γ(β) separation in a full-size TeO2 CUORE bolometer by simultaneous heat and light detection

The CUORE project began recently a search for neutrinoless double-beta decay ($0\nu\beta\beta$) of $^{130}$Te with a $\mathcal{O}$(1 ton) TeO$_2$ bolometer array. In this experiment, the background suppression relies essentially on passive shielding, material radiopurity and anti-coincidences. The lack of particle identification in CUORE makes $\alpha$ decays at the detector surface the dominant background, at the level of $\sim$0.01 counts/(keV kg y) in the region of interest ($Q$-value of $0\nu\beta\beta$ of the order of 2.5 MeV). In the present work we demonstrate, for the first time with a CUORE-size (5$\times$5$\times$5 cm) TeO$_2$ bolometer and using the same technology as CUORE for the readout of the bolometric signals, an efficient $\alpha$ particle discrimination (99.9\%) with a high acceptance of the $0\nu\beta\beta$ signal (about 96\%). This unprecedented result was possible thanks to the superior performance (10 eV RMS baseline noise) of a Neganov-Luke-assisted germanium bolometer used to detect a tiny (70 eV) light signal dominated by $\gamma$($\beta$)-induced Cherenkov radiation in the TeO$_2$ detector. The obtained results represent a major breakthrough towards the TeO$_2$-based version of CUPID, a ton-scale cryogenic $0\nu\beta\beta$ experiment proposed as a follow-up to CUORE with particle identification

Optimizing EDELWEISS detectors for low-mass WIMP searches

The physics potential of EDELWEISS detectors for the search of low-mass weakly interacting massive particles (WIMPs) is studied. Using a data-driven background model, projected exclusion limits are computed using frequentist and multivariate analysis approaches, namely, profile likelihood and boosted decision tree. Both current and achievable experimental performances are considered. The optimal strategy for detector optimization depends critically on whether the emphasis is put on WIMP masses below or above ∼5  GeV/c2. The projected sensitivity for the next phase of the EDELWEISS-III experiment at the Modane Underground Laboratory (LSM) for low-mass WIMP search is presented. By 2018 an upper limit on the spin-independent WIMP-nucleon cross section of σSI=7×10−42  cm2 is expected for a WIMP mass in the range 2–5  GeV/c2. The requirements for a future hundred-kilogram-scale experiment designed to reach the bounds imposed by the coherent scattering of solar neutrinos are also described. By improving the ionization resolution down to 50  eVee, we show that such an experiment installed in an even lower background environment (e.g., at SNOLAB) together with an exposure of 1000   kg⋅yr, should allow us to observe about 80 8B neutrino events after discrimination