Adverse events with botulinum toxin treatment in cervical dystonia: How much should we blame placebo?

INTRODUCTION: Botulinum toxin (BoNT) is the first line therapy for cervical dystonia (CD), with most patients receiving many treatment sessions, and so come to recognize and expect the benefits and harms of BoNT, making it difficult to separate which adverse events (AEs) are driven by BoNT and which come from patients' expectations. METHODS: Using the results of three Cochrane systematic reviews of randomized controlled trials (RCTs) we pooled results to calculate the risk of general and specific AEs associated with BoNT, and the proportion of AEs that cannot be pharmacologically attributed to BoNT. RESULTS: Fifteen RCTs, enrolling 1604 patients, were included. BoNT was associated with an increased risk of AEs, but 79% of this increased risk cannot be pharmacologically attributed to BoNT. CONCLUSIONS: Patients with CD attach a considerable expectation of harm due to BoNT, reflected in the large proportion of non-pharmacologically-mediated AEs

Meta-research metrics matter: letter regarding article “indirect tolerability comparison of Deutetrabenazine and Tetrabenazine for Huntington disease”

Here we discuss the report by Claassen and colleagues describing an indirect treatment comparison between tetrabenazine and deutetrabenazine for chorea in Huntington’s disease using individual patient data. We note the potential for discrepancies in apparently statistically significant findings, due to the rank reversal phenomenon. We provide some cautionary observations and suggestions concerning the limitations of indirect comparisons and the low likelihood that good quality evidence will become available to guide clinical decision comparing these two agents

Tetrabenazine versus deutetrabenazine for Huntington's disease: twins or distant cousins?

BACKGROUND: Tetrabenazine is the only US Food and Drug Administration-approved drug for Huntington's disease, and deutetrabenazine was recently tested against placebo. A switching-trial from tetrabenazine to deutetrabenazine is underway, but no head-to-head, blinded, randomized controlled trial is planned. Using meta-analytical methodology, the authors compared these molecules. METHODS: RCTs comparing tetrabenazine or deutetrabenazine with placebo in Huntington's disease were searched. The authors assessed the Cochrane risk-of-bias tool, calculated indirect treatment comparisons, and applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. RESULTS: The evidence network for this report comprised 1 tetrabenazine trial and 1 deutetrabenazine trial, both against placebo. Risk of bias was moderate in both. Participants in the tetrabenazine and deutetrabenazine trials did not differ significantly on motor scores or adverse events. Depression and somnolence scales significantly favored deutetrabenazine. CONCLUSION: There is low-quality evidence that tetrabenazine and deutetrabenazine do not differ in efficacy or safety. It is important to note that these results are likely to remain the only head-to-head comparison between these 2 compounds in Huntington's disease

Endovascular treatment versus medical care alone for ischaemic stroke: systematic review and meta-analysis

Objectives: To evaluate the efficacy and safety of endovascular treatment, particularly adjunctive intra-arterial mechanical thrombectomy, in patients with ischaemic stroke. / Design: Systematic review and meta-analysis. / Data sources: Medline, Embase, Cochrane Central Register of Controlled Trials, Web of Science, SciELO, LILACS, and clinical trial registries from inception to December 2015. Reference lists were crosschecked. / Eligibility criteria for selecting studies: Randomised controlled trials in adults aged 18 or more with ischaemic stroke comparing endovascular treatment, including thrombectomy, with medical care alone, including intravenous recombinant tissue plasminogen activator (rt-PA). Trial endpoints were functional outcome (modified Rankin scale scores of ≤2) and mortality at 90 days after onset of symptoms. No language or time restrictions applied. / Results: 10 randomised controlled trials (n=2925) were included. In pooled analysis endovascular treatment, including thrombectomy, was associated with a higher proportion of patients experiencing good (modified Rankin scale scores ≤2) and excellent (scores ≤1) outcomes 90 days after stroke, without differences in mortality or rates for symptomatic intracranial haemorrhage, compared with patients randomised to medical care alone, including intravenous rt-PA. Heterogeneity was high among studies. The more recent studies (seven randomised controlled trials, published or presented in 2015) proved better suited to evaluate the effect of adjunctive intra-arterial mechanical thrombectomy on its index disease owing to more accurate patient selection, intravenous rt-PA being administered at a higher rate and earlier, and the use of more efficient thrombectomy devices. In most of these studies, more than 86% of the patients were treated with stent retrievers, and rates of recanalisation were higher (>58%) than previously reported. Subgroup analysis of these seven studies yielded a risk ratio of 1.56 (95% confidence interval 1.38 to 1.75) for good functional outcomes and 0.86 (0.69 to 1.06) for mortality, without heterogeneity among the results of the studies. All trials were open label. Risk of bias was moderate across studies. The full results of two trials are yet to be published. / Conclusions: Moderate to high quality evidence suggests that compared with medical care alone in a selected group of patients endovascular thrombectomy as add-on to intravenous thrombolysis performed within six to eight hours after large vessel ischaemic stroke in the anterior circulation provides beneficial functional outcomes, without increased detrimental effects. / Systematic review registration: PROSPERO CRD42015019340

Huntington’s Disease Clinical Trials Corner: June 2019

In this edition of the Huntington’s Disease Clinical Trials Corner we expand on the HD-DBS and on the TRIHEP3 trials, and we list all currently registered and ongoing clinical trials in Huntington’s disease

Phosphorus removal by a fixed-bed hybrid polymer nanocomposite biofilm reactor

Eutrophication is one of the main challenges regarding the ecological quality of surface waters, phosphorus bioavailability being its main driver. In this context, a novel hybrid polymer nanocomposite (HPN-Pr) biofilm reactor aimed at integrated chemical phosphorus adsorption and biological removal was conceived. The assays pointed to removal of 1.2 mg P/g of reactive phosphorus and 1.01 mg P/g of total phosphorus under steady-state conditions. A mathematical adsorption–biological model was applied to predict reactor performance, which indicated that biological activity has a positive effect on reactor performance, increasing the amount of reactive phosphorus removed.The authors acknowledge the Portuguese Foundation for Science and Technology for the financial support under Project SFRH/BD/39085/2007

Luminance, colour, viewpoint and border enhanced disparity energy model

The visual cortex is able to extract disparity information through the use of binocular cells. This process is reflected by the Disparity Energy Model, which describes the role and functioning of simple and complex binocular neuron populations, and how they are able to extract disparity. This model uses explicit cell parameters to mathematically determine preferred cell disparities, like spatial frequencies, orientations, binocular phases and receptive field positions. However, the brain cannot access such explicit cell parameters; it must rely on cell responses. In this article, we implemented a trained binocular neuronal population, which encodes disparity information implicitly. This allows the population to learn how to decode disparities, in a similar way to how our visual system could have developed this ability during evolution. At the same time, responses of monocular simple and complex cells can also encode line and edge information, which is useful for refining disparities at object borders. The brain should then be able, starting from a low-level disparity draft, to integrate all information, including colour and viewpoint perspective, in order to propagate better estimates to higher cortical areas.Portuguese Foundation for Science and Technology (FCT); LARSyS FCT [UID/EEA/50009/2013]; EU project NeuroDynamics [FP7-ICT-2009-6, PN: 270247]; FCT project SparseCoding [EXPL/EEI-SII/1982/2013]; FCT PhD grant [SFRH-BD-44941-2008

The ρ(1S,2S)\rho(1S,2S), ψ(1S,2S)\psi(1S,2S), Υ(1S,2S)\Upsilon(1S,2S) and ψt(1S,2S)\psi_t(1S,2S) mesons in a double pole QCD Sum Rule

We use the method of double pole QCD sum rule which is basically a fit with two exponentials of the correlation function, where we can extract the masses and decay constants of mesons as a function of the Borel mass. We apply this method to study the mesons: $\rho(1S,2S)$, $\psi(1S,2S)$, $\Upsilon(1S,2S)$ and $\psi_t(1S,2S)$. We also present predictions for the toponiuns masses $\psi_t(1S,2S)$ of m(1S)=357 GeV and m(2S)=374 GeV.Comment: 14 pages, 11 figures in Braz J Phys (2016