Spatial Distribution of Temporalis Pressure Pain Sensitivity in Men with Episodic Cluster Headache

Background: Spatial changes in pressure sensitivity have been described in migraine and tension-type headaches. Our aim was to determine differences in the spatial distribution of pressure pain sensitivity of the temporalis muscle between cluster headache (CH) patients and headache-free controls. Methods: Pressure pain thresholds (PPTs) were determined over nine points covering the temporalis muscle in 40 men with episodic CH and 40 matched headache-free controls in a blinded fashion. Topographical pressure pain sensitivity maps were constructed based on interpolation of the PPTs. Patients were evaluated in a pain-free period (remission phase), at least 3 months from the last attack and without medication. Results: The analysis of covariance (ANCOVA) found significant difference between points (F = 21.887; P 0.8). Conclusions: Bilateral pressure pain hypersensitivity to pressure pain in the temporalis muscle and an anterior-to-posterior gradient to pressure pain was observed in men with episodic CH.s

Guided Weekly Reflection Papers

The experience gained by our team of educational innovation with the implementation of the “Weekly Reflection Papers” has led us to diversify and make more flexible the employed methodology. The modified tool, applied during the academic year 2010-2011, was called “Guided Weekly Reflection Papers”. The aim of this modification has been the development of certain abilities and skills of the students, with particular emphasis on their ability to integrate, review and apply knowledge in a critical and reflective way. The professors guide the student´s work through a series of questions on which the students must apply the most significant concepts studied each week, to prove the acquisition of such aptitudes and skills

Guided Weekly Reflection Papers

The experience gained by our team of educational innovation with the implementation of the “Weekly Reflection Papers” has led us to diversify and make more flexible the employed methodology. The modified tool, applied during the academic year 2010-2011, was called “Guided Weekly Reflection Papers”. The aim of this modification has been the development of certain abilities and skills of the students, with particular emphasis on their ability to integrate, review and apply knowledge in a critical and reflective way. The professors guide the student´s work through a series of questions on which the students must apply the most significant concepts studied each week, to prove the acquisition of such aptitudes and skills

Epicrania fugax with backward radiation: clinical characteristics of nine new cases

Epicrania fugax (EF) is a novel syndrome, described as a paroxysmal and brief head pain, starting in posterior cranial regions and rapidly spreading forward ipsilateral eye, nose or forehead. Two patients with comparable clinical features stemming from frontal scalp to ipsilateral posterior regions have been recently described and proposed as backward radiation epicrania fugax (BREF). We report a new series of nine BREF and compare their clinical characteristics with 18 forward radiation EF (FREF). Since first description of BREF in February 2010 we have assessed nine patients (four males, five females) with this clinical picture at an outpatient headache office in a Tertiary Hospital. Comparison is established with 18 FREF patients (6 males, 12 females), attended since the publication of first series of EF in March 2008. We found no differences between BREF and FREF, respectively, in age at onset (43.4 ± 13.1 vs. 42.5 ± 17.7 years), female/male ratio (5/4 vs. 12/6), pain intensity (6.9 ± 2.1 vs. 6.8 ± 2.1 in a 0–10 visual analogical scale), duration (7.1 ± 4.9 vs. 5.7 ± 4.3 s) and frequency of episodes per day (7 ± 8.4 vs. 9.9 ± 15.4). Patients in BREF group presented less frequently interictal pain in stemming point (22.2 vs. 55.5%) and accompanying autonomic signs (33.3 vs. 55.5%), but without statistical significance in both the cases. This series reinforces the proposal of EF as a new headache variant or a new headache syndrome. Clinical picture of brief pain paroxysms starting in the anterior scalp and radiating backwards does not fit known headaches or neuralgias and might correspond to a reverse variant of EF, clinical characteristics of which are comparable to FREF

Increased MRI-based Brain Age in chronic migraine patients

Introduction: Neuroimaging has revealed that migraine is linked to alterations in both the structure and function of the brain. However, the relationship of these changes with aging has not been studied in detail. Here we employ the Brain Age framework to analyze migraine, by building a machine-learning model that predicts age from neuroimaging data. We hypothesize that migraine patients will exhibit an increased Brain Age Gap (the difference between the predicted age and the chronological age) compared to healthy participants. Methods: We trained a machine learning model to predict Brain Age from 2,771 T1-weighted magnetic resonance imaging scans of healthy subjects. The processing pipeline included the automatic segmentation of the images, the extraction of 1,479 imaging features (both morphological and intensity-based), harmonization, feature selection and training inside a 10-fold cross-validation scheme. Separate models based only on morphological and intensity features were also trained, and all the Brain Age models were later applied to a discovery cohort composed of 247 subjects, divided into healthy controls (HC, n=82), episodic migraine (EM, n=91), and chronic migraine patients (CM, n=74). Results: CM patients showed an increased Brain Age Gap compared to HC (4.16 vs -0.56 years, P=0.01). A smaller Brain Age Gap was found for EM patients, not reaching statistical significance (1.21 vs -0.56 years, P=0.19). No associations were found between the Brain Age Gap and headache or migraine frequency, or duration of the disease. Brain imaging features that have previously been associated with migraine were among the main drivers of the differences in the predicted age. Also, the separate analysis using only morphological or intensity-based features revealed different patterns in the Brain Age biomarker in patients with migraine. Conclusion: The brain-predicted age has shown to be a sensitive biomarker of CM patients and can help reveal distinct aging patterns in migraine

Inclusion of non-inferiority analysis in superiority-based clinical trials with single-arm, two-stage Simon's design

Non-inferiority (NI) analysis is not usually considered in the early phases of clinical development. In some negative phase II trials, a post-hoc NI analysis justified additional phase III trials that were successful. However, the risk of false positive achievements was not controlled in these early phase analyses. We propose to preplan NI analyses in superiority-based Simon's two-stage designs to control type I and II error rates. Simulations have been proposed to assess the control of type I and II errors rates with this method. A total of 12,768 two-stage Simon's design trials were constructed based on different assumptions of rejection response probability, desired response probability, type I and II errors, and NI margins. P-value and type II error were calculated with stochastic ordering using Uniformly Minimum Variance Unbiased Estimator. Type I and II errors were simulated using the Monte Carlo method. The agreement between calculated and simulated values was analyzed with Bland-Altman plots. We observed the same level of agreement between calculated and simulated type I and II errors from both two-stage Simon's superiority designs and designs in which NI analysis was allowed. Different examples has been proposed to explain the utility of this method. Inclusion of NI analysis in superiority-based single-arm clinical trials may be useful for weighing additional factors such as safety, pharmacokinetics, pharmacodynamic, and biomarker data while assessing early efficacy. Implementation of this strategy can be achieved through simple adaptations to existing designs for one-arm phase II clinical trials

Interfacial exchange-coupling induced chiral symmetry breaking of spin-orbit effects

We demonstrate that the interfacial exchange coupling in ferromagnetic/antiferromagnetic (FM/AFM) systems induces symmetry breaking of the spin-orbit (SO) effects. This has been done by studying the field and angle dependencies of anisotropic magnetoresistance and vectorial-resolved magnetization hysteresis loops, measured simultaneously and reproduced with numerical simulations. We show how the induced unidirectional magnetic anisotropy at the FM/AFM interface results in strong asymmetric transport behaviors, which are chiral around the magnetization hard-axis direction. Similar asymmetric features are anticipated in other SO-driven phenomenaThis work was supported in part by the Spanish MINECO through Projects No. MAT2012-39308, No. FIS2013-40667-P, No. MAT2011-25598, and No. MAT2014-52477-C5-3-P, and by the Comunidad de Madrid through Project No. S2013/MIT-2850 (NANOFRONTMAG-CM). P.P. and A.B. acknowledge support through the Marie Curie AMAROUT EU Programme, and through MINECO “Juan de la Cierva” (JCI-2011-09602) and “Ramón y Cajal” contract

GEICAM Guidelines for the Management of Patients with Breast Cancer During the COVID-19 Pandemic in Spain

Breast cancer (BC) is the most common cancer in women in Spain. During the COVID-19 pandemic caused by the SARSCoV-2 virus, patients with BC still require timely treatment and follow-up; however, hospitals are overwhelmed with infected patients and, if exposed, patients with BC are at higher risk for infection and serious complications if infected. Thus, health care providers need to evaluate each BC treatment and in-hospital visit to minimize pandemic-associated risks while maintaining adequate treatment efficacy. Here we present a set of guidelines regarding available options for BC patient management and treatment by BC subtype in the context of the COVID-19 pandemic. Owing to the lack of evidence about COVID-19 infection, these recommendations are mainly based on expert opinion, medical organizations’ and societies’ recommendations, and some published evidence. We consider this a useful tool to facilitate medical decision making in this health crisis situation we are facing

Viability of AMURA biomarkers from single-shell diffusion MRI in clinical studies

Diffusion Tensor Imaging (DTI) is the most employed method to assess white matter properties using quantitative parameters derived from diffusion MRI, but it presents known limitations that restrict the evaluation of complex structures. The objective of this study was to validate the reliability and robustness of complementary diffusion measures extracted with a novel approach, Apparent Measures Using Reduced Acquisitions (AMURA), with a typical diffusion MRI acquisition from a clinical context in comparison with DTI with application to clinical studies. Fifty healthy controls, 51 episodic migraine and 56 chronic migraine patients underwent single-shell diffusion MRI. Four DTI-based and eight AMURA-based parameters were compared between groups with tract-based spatial statistics to establish reference results. On the other hand, following a region-based analysis, the measures were assessed for multiple subsamples with diverse reduced sample sizes and their stability was evaluated with the coefficient of quartile variation. To assess the discrimination power of the diffusion measures, we repeated the statistical comparisons with a region-based analysis employing reduced sample sizes with diverse subsets, decreasing 10 subjects per group for consecutive reductions, and using 5,001 different random subsamples. For each sample size, the stability of the diffusion descriptors was evaluated with the coefficient of quartile variation. AMURA measures showed a greater number of statistically significant differences in the reference comparisons between episodic migraine patients and controls compared to DTI. In contrast, a higher number of differences was found with DTI parameters compared to AMURA in the comparisons between both migraine groups. Regarding the assessments reducing the sample size, the AMURA parameters showed a more stable behavior than DTI, showing a lower decrease for each reduced sample size or a higher number of regions with significant differences. However, most AMURA parameters showed lower stability in relation to higher coefficient of quartile variation values than the DTI descriptors, although two AMURA measures showed similar values to DTI. For the synthetic signals, there were AMURA measures with similar quantification to DTI, while other showed similar behavior. These findings suggest that AMURA presents favorable characteristics to identify differences of specific microstructural properties between clinical groups in regions with complex fiber architecture and lower dependency on the sample size or assessing technique than DTI