Effectiveness and Safety of Teriflunomide in Relapsing-Remitting Multiple Sclerosis and Improvements in Quality of Life: Results from the Real-World TERICARE Study.

INTRODUCTION: Teriflunomide is a once-daily oral immunomodulator approved for relapsing forms of multiple sclerosis (MS) or relapsing-remitting multiple sclerosis (RRMS; depending on the local label), based on extensive evidence from clinical trials and a real-world setting on efficacy, tolerability and patient-reported benefits. The TERICARE study assessed the impact of teriflunomide treatment over 2 years on health-related quality of life (HRQoL) and some of the most common and disabling symptoms of MS, such as fatigue and depression. METHODS: This prospective observational study in Spain included RRMS patients treated with teriflunomide for ≤ 4 weeks. The following patient-reported outcomes (PROs) were collected at baseline and every 6 months for 2 years: the 29-item Multiple Sclerosis Impact Scale version 2 (MSIS-29), the 21-item Modified Fatigue Impact Scale (MFIS-21), the Beck Depression Inventory (BDI-II), the Short Form (SF)-Qualiveen and the Treatment Satisfaction Questionnaire for Medication v1.4 (TSQM). Annualised relapse rate (ARR), disability progression according to the Expanded Disability Status Scale (EDSS), and no evidence of disease activity (NEDA-3) were also assessed. RESULTS: A total of 325 patients were analysed. Patients had a mean (SD) age of 43.2 years (10.4), a mean baseline EDSS score of 1.75 (1.5), a mean number of relapses in the past 2 years of 1.5 (0.7), and 64% had received prior disease-modifying therapy (DMT). Patients showed significant improvements in the psychological domain of MSIS-29 from 35.9 (26.6) at baseline to 29.4 (25.5) at 18 months (p = 0.004) and 29.0 (24.6) at 24 months (p = 0.002). Levels of fatigue and depression were also reduced. After 2 years of treatment with teriflunomide, ARR was reduced to 0.17 (95% CI 0.14-0.21) from the baseline of 0.42 (95% CI 0.38-0.48), representing a 60.1% reduction. Mean EDSS scores remained stable during the study, and 79.9% of patients showed no disability progression. 54.7% of patients achieved NEDA-3 in the first 12 months, which increased to 61.4% during months 12-24. Patients reported increased satisfaction with treatment over the course of the study, regardless of whether they were DMT naive or not. CONCLUSION: Teriflunomide improves psychological aspects of HRQoL and maintains low levels of fatigue and depression. Treatment with teriflunomide over 2 years is effective in reducing ARR and disability progression.

Reports of Symptoms Associated with Supraventricular Arrhythmias as a Serious Adverse Drug Reaction in the Spanish Pharmacovigilance Database.

This study aimed to determine the type of drugs reported as suspected of causing severe supraventricular arrhythmias from the Spanish Human Pharmacovigilance System database. A total of 1053 reports were analysed, of which 526 (50%) were on men and 516 (49%) were on women. The most affected age group was the over-65s, with 593 reports (56%). Of the 1613 drugs, those belonging to the cardiovascular system (ATC Group C) were the most numerous (414 reports, 26%), with digoxin being the most frequent drug (49 reports, 12%). Other common groups were antiinfectives for systemic use (ATC Group J; 306 reports, 19%), antineoplastic and immunomodulating agents (ATC Group L; 198 reports, 12%), and nervous system drugs (ATC Group N; 185 reports, 11%). The most common supraventricular arrhythmia was atrial fibrillation (561 reports, 51%). Regarding outcomes, 730 (66%) patients recovered, 76 (7%) did not recover, 25 (3%) recovered but with sequelae, and 23 (2%) resulted in death. This study revealed that certain drugs have reported to be associated more frequently to supraventricular arrhythmias as serious adverse reactions, especially in the older population. Proper clinical management and effective strategies to ensure medication appropriateness should always be considered to improve patient safety when prescribing drugs.

Prescribed Drugs and Self-Directed Violence: A Descriptive Study in the Spanish Pharmacovigilance Database.

Self-inflicted violence is a major and growing public health problem and its prediction and prevention is challenging for healthcare systems worldwide. Our aim was to identify prescribed drugs associated with self-directed violent behaviors in Spain. A descriptive, longitudinal and retrospective study of spontaneous reports of adverse drug reactions corresponding to self-directed violence was recorded in the Spanish Pharmacovigilance Database (FEDRA®) from 1984 to 31 March 2021. A total of 710 cases were reported in the study period. The mean age was 45.52 years (range 1-94). There were no gender differences except in children, where most reports were of male children. The main therapeutic groups that were involved included drugs for the nervous system (64.5%) and anti-infectives for systemic use (13.2%). The most commonly reported drugs were varenicline, fluoxetine, lorazepam, escitalopram, venlafaxine, veralipride, pregabalin, roflumilast and bupropion. There were reports of montelukast, hydroxychloroquine, isotretinoin, methylphenidate, infliximab, natalizumab, ribavirin and efavirenz, which were less known to be involved in self-directed violence. This study shows that self-directed violence is a rare adverse drug reaction, and can be related to the use of some medicines. It is important for healthcare professionals to consider this risk in their clinical praxis, implementing person-centred approaches. Further studies are needed, considering comorbidities and potential interactions.

Treatment of multiple sclerosis with rituximab: A Spanish multicenter experience.

Introduction: Rituximab (RTX) is considered a potential therapeutic option for relapsing-remitting (RRMS) and progressive forms (PMS) of multiple sclerosis (MS). The main objective of this work was to investigate the effectiveness and safety of rituximab in MS. Patients and methods: Observational multicenter study of clinical and radiological effectiveness and safety of rituximab in RRMS and PMS. Results: A total of 479 rituximab-treated patients were included in 12 Spanish centers, 188 RRMS (39.3%) and 291 (60.7%) PMS. Despite standard treatment, the annualized relapse rate (ARR) the year before RTX was 0.63 (SD: 0.8) and 156 patients (41%) had at least one gadolinium-enhanced lesion (GEL) on baseline MRI. Mean EDSS had increased from 4.3 (SD: 1.9) to 4.8 (SD: 1.7) and almost half of the patients (41%) had worsened at least one point. After a median follow-up of 14.2 months (IQR: 6.5-27.2), ARR decreased by 85.7% (p < 0.001) and GEL by 82.9%, from 0.41 to 0.07 (p < 0.001). A significant decrease in EDSS to 4.7 (p = 0.046) was observed after 1 year of treatment and this variable remained stable during the second year of therapy. There was no evidence of disease activity in 68% of patients. Infusion-related symptoms were the most frequent side effect (19.6%) and most were mild. Relevant infections were reported only in 18 patients (including one case of probable progressive multifocal leukoencephalopathy). Conclusion: Rituximab could be an effective and safe treatment in RRMS, including aggressive forms of the disease. Some selected PMS patients could also benefit from this treatment.

Case Report: Exacerbation of Relapses Following mRNA COVID-19 Vaccination in Multiple Sclerosis: A Case Series.

Introduction: mRNA coronavirus disease 2019 (COVID-19) vaccination has been widely used to arrest the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Rarely, autoimmune events such as relapses in patients with multiple sclerosis (MS) have been reported after vaccination. However, the possible effects of vaccination in a patient already experiencing the symptoms of a relapse represent an unusual scenario that has not been described. Patients and Methods: This is a retrospective case series of four patients from three major tertiary referral centers that received mRNA COVID-19 vaccination after starting with symptoms of acute demyelination of the central nervous system due to non-recognized MS. A detailed description of each case, including MRI studies, serum light-neurofilament levels, and cerebrospinal fluid (CSF) cytokine profile, is provided. Case Description: All patients presented exacerbation of ongoing symptoms after vaccination (range 14-112 days first dose). All patients presented MRI features suggestive of highly active MS and fulfilled McDonald 2017 criteria at the time of presentation. All patients presented high serum light-neurofilament levels and oligoclonal G bands restricted to the CSF. Higher levels of interleukin-6 in the CSF were present in the more severe cases. Discussion: We describe exacerbation of relapses after mRNA COVID-19 vaccination. We hypothesize RNA sensors such as Toll-like receptor 7 may be activated and contribute to amplify the inflammatory response during a relapse. Conclusion: Patients should seek medical attention if experiencing acute neurological symptoms, especially before vaccination. Fast diagnostic procedures and prompt treatment should be performed in these patients. Pharmacovigilance and further study are warranted to confirm causality.

Baseline Inflammatory Status Reveals Dichotomic Immune Mechanisms Involved In Primary-Progressive Multiple Sclerosis Pathology.

Objective: To ascertain the role of inflammation in the response to ocrelizumab in primary-progressive multiple sclerosis (PPMS). Methods: Multicenter prospective study including 69 patients with PPMS who initiated ocrelizumab treatment, classified according to baseline presence [Gd+, n=16] or absence [Gd-, n=53] of gadolinium-enhancing lesions in brain MRI. Ten Gd+ (62.5%) and 41 Gd- patients (77.4%) showed non-evidence of disease activity (NEDA) defined as no disability progression or new MRI lesions after 1 year of treatment. Blood immune cell subsets were characterized by flow cytometry, serum immunoglobulins by nephelometry, and serum neurofilament light-chains (sNfL) by SIMOA. Statistical analyses were corrected with the Bonferroni formula. Results: More than 60% of patients reached NEDA after a year of treatment, regardless of their baseline characteristics. In Gd+ patients, it associated with a low repopulation rate of inflammatory B cells accompanied by a reduction of sNfL values 6 months after their first ocrelizumab dose. Patients in Gd- group also had low B cell numbers and sNfL values 6 months after initiating treatment, independent of their treatment response. In these patients, NEDA status was associated with a tolerogenic remodeling of the T and innate immune cell compartments, and with a clear increase of serum IgA levels. Conclusion: Baseline inflammation influences which immunological pathways predominate in patients with PPMS. Inflammatory B cells played a pivotal role in the Gd+ group and inflammatory T and innate immune cells in Gd- patients. B cell depletion can modulate both mechanisms.

Cognitive impairment in multiple sclerosis: diagnosis and monitoring.

INTRODUCTION: Cognitive impairment (CI) has a prevalence of 45-70% in people with multiple sclerosis (MS), producing a negative impact on their quality of life, personal life, and work. Early detection of CI has become an important aspect to be considered for an adequate follow-up, to optimize social adaptation and to implement specific cognitive rehabilitation strategies. The aim of this work is to propose a suitable cognitive evaluation of patients with MS based on available and efficient tools for diagnosis and monitoring purposes well supported by literature review and clinical experience. METHODS: A multidisciplinary panel of professionals from the field of neurology, neuropsychology, and neuroimaging performed a literature review of the topic of cognitive impairment assessment. This was combined and completed with their clinical experience to produce a set of recommendations. RESULTS: Some limitations to cognitive evaluation are described: shortage of time and resources during the neurology consultation, scarceness or absence of specialized professionals' availability, importance of tests adaptation, and doubts about its use to define therapeutic efficiency. We recommend a baseline and annual screening evaluation, and we suggest a baseline and periodic neuropsychological assessment. The latter ought to change to a recommendation with the presence of either positive screening test, or subjective to cognitive complaints, screening-test results and patient or family report mismatch, or in specific social/work situations. CONCLUSIONS: Cognitive evaluation should be performed on all patients diagnosed with MS and throughout follow-up. It is necessary to support the creation of multidisciplinary MS teams to optimize the evaluation and follow-up of MS patients.

Short-term data on disease activity, cognition, mood, stigma and employment outcomes in a cohort of patients with primary progressive multiple sclerosis (UPPMS study).

BACKGROUND: Primary progressive multiple sclerosis (PPMS) has long been defined by progressive disability accrual in the absence of initial relapses. However, its underlying neurodegenerative process seems to be accompanied by central nervous system inflammation. A new classification defined multiple sclerosis courses according to clinical/radiological activity and progression. We provide further insight into PPMS activity according to this classification and other daily living aspects. METHODS: This was a multicentre, prospective, cohort study including 55 adult patients with PPMS according to 2010 McDonald criteria, within ten years from neurologic symptom onset and not receiving disease-modifying therapies during the past six months, who were followed up for 12 months. The primary study endpoint was the percentage of patients with active disease based on clinical relapses and/or magnetic resonance activity. Disability progression, cognitive function, physical/psychological impact, depression symptoms, stigma and employment were secondary endpoints. RESULTS: Eleven (25.6%) patients exhibited multiple sclerosis activity throughout the 12-month study follow-up. Fourteen showed non-active multiple sclerosis without progression, 11 non-active multiple sclerosis with progression, 6 active multiple sclerosis without progression and 4 active multiple sclerosis with progression; one patient with disease activity was not assessable for progression. Cognitive function scores remained unchanged or increased, disease physical impact was maintained and disease psychological impact significantly decreased. The proportion of patients with depression symptoms or stigma remained without significant changes as well as employment outcomes. CONCLUSION: This study shows that one-fourth of PPMS patients may exhibit disease activity over one year, with disability progression in approximately one-third but without worsening of cognitive function, disease impact, depression, stigma or employment outcomes.

Brain region volumes and their relationship with disability progression and cognitive function in primary progressive multiple sclerosis.

BACKGROUND AND PURPOSE: Evidence on regional changes resulting from neurodegenerative processes underlying primary progressive multiple sclerosis (PPMS) is still limited. We assessed brain region volumes and their relationship with disability progression and cognitive function in PPMS patients. METHODS: This was an MRI analysis of 43 patients from the prospective Understanding Primary Progressive Multiple Sclerosis (UPPMS) cohort study. MRI scans were performed within 3 months before enrollment and at month 12. RESULTS: Gray matter volume of declive and white matter volumes adjacent to left straight gyrus, right calcarine sulcus, and right inferior occipital gyrus significantly decreased from baseline to month 12. Baseline white matter volumes adjacent to right amygdala and left cuneus significantly differed between patients with and without disability progression, as well as baseline gray matter volumes of left cuneus, right parahippocampal gyrus, right insula, left superior frontal gyrus, declive, right inferior temporal gyrus, right superior temporal gyrus (pole), and right calcarine sulcus. Baseline gray matter volumes of right cuneus and right superior temporal gyrus positively correlated with 12-month Selective Reminding Test and Word List Generation performance, respectively. Gray matter changes in right superior semilunar lobe and white matter adjacent to left declive and right cerebellar tonsil also positively correlated with Word List Generation scores, while white matter change in left inferior semilunar lobe positively correlated with Symbol Digit Modalities Test performance after 12 months. CONCLUSIONS: White and gray matter volumes of specific brain regions could predict disability progression and cognitive performance of PPMS patients after one year.

Effect of Ocrelizumab in Blood Leukocytes of Patients With Primary Progressive MS.

OBJECTIVE: To analyze the changes induced by ocrelizumab in blood immune cells of patients with primary progressive MS (PPMS). METHODS: In this multicenter prospective study including 53 patients with PPMS who initiated ocrelizumab treatment, we determined effector, memory, and regulatory cells by flow cytometry at baseline and after 6 months of therapy. Wilcoxon matched paired tests were used to assess differences between baseline and 6 months' results. p Values were corrected using the Bonferroni test. RESULTS: Ocrelizumab reduced the numbers of naive and memory B cells (p < 0.0001) and those of B cells producing interleukin (IL)-6, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNFα) (p < 0.0001 in all cases). By contrast, the proportions of plasmablasts and B cells producing GM-CSF and TNFα increased significantly, suggesting the need for treatment continuation. We also observed a decrease in CD20+ T-cell numbers (p < 0.0001) and percentages (p < 0.0001), and a clear remodeling of the T-cell compartment characterized by relative increases of the naive/effector ratios in CD4+ (p = 0.002) and CD8+ (p = 0.002) T cells and relative decreases of CD4+ (p = 0.03) and CD8+ (p = 0.004) T cells producing interferon-gamma. Total monocyte numbers increased (p = 0.002), but no changes were observed in those producing inflammatory cytokines. The immunologic variations were associated with a reduction of serum neurofilament light chain (sNfL) levels (p = 0.008). The reduction was observed in patients with Gd-enhanced lesions at baseline and in Gd- patients with baseline sNfL >10 pg/mL. CONCLUSIONS: In PPMS, effector B-cell depletion changed T-cell response toward a low inflammatory profile, resulting in decreased sNfL levels.

Time Constraint Increases Mental Load and Influences in the Performance in Small-Sided Games in Basketball.

Purpose: In team sports like basketball, small-sided games have received much scientific attention because of their capacity to simulate competitive environments. The purpose of this study was to explore the impact of different task constraints on mental load, and its consequences for individual and team performance in basketball small-sided games. Method: Twenty-four university students voluntarily took part in this study (Mage = 20.81 years [± 1.76]). Four different 3 × 3 basketball games were played: (A) free game, (B) seven seconds possession, (C) three passes maximum per attack phase, (D) conditions B and C combined. Results: Statistical analysis showed that constraints B, C and D produce more mental load, provoke differences in the affect response and the performance is worse. Conclusion: These results demonstrate the mental cost of restricting the time and number of passes, separately and combined to decide and act.

CSF chitinase 3-like-1 association with disability of primary progressive MS.

OBJECTIVE: To assess the role of CSF chitinase 3-like-1 (CHI3L1), chitinase 3-like-2 (CHI3L2), and neurofilament light chain (NfL) in predicting the course of primary progressive MS (PPMS). METHODS: We analyzed CSF CHI3L1, CHI3L2, and NfL levels in 25 patients with PPMS with disease duration ≤10 years and no disease-modifying therapy for ≥6 months from the prospective Understanding Primary Progressive Multiple Sclerosis cohort study. CSF samples taken at disease diagnosis were analyzed using commercial ELISAs and following the manufacturer's instructions. Data on Expanded Disability Status Scale (EDSS) scores, disability progression, and cognitive function according to the Brief Repeatable Neuropsychological Battery were also assessed throughout the 1-year study follow-up. RESULTS: Increasing CHI3L1 levels correlated with higher EDSS scores at baseline (ρ = 0.490, 95% CI 0.118-0.742, p = 0.013) and month 12 (ρ = 0.455, 95% CI 0.063-0.725, p = 0.026) and tended to be associated with a higher risk of disability progression according to EDSS scores (OR = 1.008, 95% CI 0.999-1.017, p = 0.089). Increasing CHI3L2 levels also tended to correlate with lower baseline EDSS scores (ρ = -0.366, 95% CI -0.676-0.054, p = 0.086). There was no correlation with regard to NfL levels. CONCLUSIONS: This analysis supports the association between CSF CHI3L1 levels and neurologic disability according to EDSS scores in patients with PPMS. Other chitinase-like proteins such as CHI3L2 may also be involved. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that CSF CHI3L1 is associated with neurologic disability in patients with PPMS.

Natural Language Generation Model for Mammography Reports Simulation.

Extending the size of labeled corpora of medical reports is a major step towards a successful training of machine learning algorithms. Simulating new text reports is a key solution for reports augmentation, which extends the cohort size. However, text generation in the medical domain is challenging because it needs to preserve both content and style that are typical for real reports, without risking the patients' privacy. In this paper, we present a conditioned LSTM-RNN architecture for simulating realistic mammography reports. We evaluated the performance by analyzing the characteristics of the simulated reports and classifying them into benign and malignant classes. An average classification AUC was calculated over two distinct test sets. A qualitative analysis was also performed in which a masked radiologist classified 0.75 of the simulated reports as real reports, showing that both the style and content of the simulated reports were similar to real reports. Finally, we compared our RNN-LSTM generative model with Markov Random Fields. The RNN-LSTM provided significantly better and more stable performance than MRFs ( , Wilcoxon).

A Probabilistic Model to Support Radiologists' Classification Decisions in Mammography Practice.

We developed a probabilistic model to support the classification decisions made by radiologists in mammography practice. Using the feature observations and Breast Imaging Reporting and Data System (BI-RADS) classifications from radiologists examining diagnostic and screening mammograms, we modeled their decisions to understand their judgments. Our model could help improve the decisions made by radiologists using their own feature observations and classifications while maintaining their observed sensitivities. Based on 112,433 mammographic cases from 36,111 patients and 13 radiologists at 2 separate institutions with a 1.1% prevalence of malignancy, we trained a probabilistic Bayesian network (BN) to estimate the malignancy probabilities of lesions. For each radiologist, we learned an observed probabilistic threshold within the model. We compared the sensitivity and specificity of each radiologist against the BN model using either their observed threshold or the standard 2% threshold recommended by BI-RADS. We found significant variability among the radiologists' observed thresholds. By applying the observed thresholds, the BN model showed a 0.01% (1 case) increase in false negatives and a 28.9% (3612 cases) reduction in false positives. When using the standard 2% BI-RADS-recommended threshold, there was a 26.7% (47 cases) increase in false negatives and a 47.3% (5911 cases) reduction in false positives. Our results show that we can significantly reduce screening mammography false positives with a minimal increase in false negatives. We find that learning radiologists' observed thresholds provides valuable information regarding the conservativeness of clinical practice and allows us to quantify the variability in sensitivity across and within institutions. Our model could provide support to radiologists to improve their performance and consistency within mammography practice.

Multi-centre validation of a flow cytometry method to identify optimal responders to interferon-beta in multiple sclerosis.

BACKGROUND AND OBJECTIVES: Percentages of blood CD19+CD5+ B cells and CD8+perforin+ T lymphocytes can predict response to Interferon (IFN)-beta treatment in relapsing-remitting multiple sclerosis (RRMS) patients. We aimed to standardize their detection in a multicenter study, prior to their implementation in clinical practice. METHODS: Fourteen hospitals participated in the study. A reference centre was established for comparison studies. Peripheral blood cells of 105 untreated RRMS patients were studied. Every sample was analyzed in duplicate in the participating centre and in the reference one by flow cytometry. When needed, participating centres corrected fluorescence compensations and negative cut-off position following reference centre suggestions. Concordance between results obtained by participating centres and by reference one was evaluated by intraclass correlation coefficients (ICC) and Spearman correlation test. Centre performance was measured by using z-scores values. RESULTS: After results review and corrective actions implementation, overall ICC was 0.86 (CI: 0.81-0.91) for CD19+CD5+ B cell and 0.89 (CI: 0.85-0.93) for CD8+ perforin+ T cell quantification; Spearman r was 0.92 (0.89-0.95; p <0.0001) and 0.92 (0.88-0.95; p <0.0001) respectively. All centres obtained z-scores≤0.5 for both biomarkers. CONCLUSION: Homogenous percentages of CD19+CD5+ B cells and CD8 perforin+ T lymphocytes can be obtained if suitable compensation values and negative cut-off are pre-established.

[A study of incidence and clinical characteristics of adverse drug reactions in hospitalized patients.] / Análisis de la incidencia y de las características clínicas de las reacciones adversas a medicamentos de uso humano en el medio hospitalario.

OBJECTIVE: Adverse drug reactions (ADR) are one of the ten main causes of mortality in the world, as a cause of hospital admissions or prolongation hospitalizations days created an important health and economic impact. This study aimed to detect incidence and characterize ADRs that occurred during hospitalization and associated with admission in Internal Medicine service. METHODS: Observational and prospective study of intensive RAM monitoring patients admitted in Internal Medicine services in a third level hospital over a twelve months period in 2014. The assessment consisted of a complete and protocol collecting information about the patients and related to suspected ADRs during hospitalization. Statistical analysis was performed using SPSS v.20.0. RESULTS: The study included 253 patients and in 54 (21,34%) ADR were detected, the risk of experiencing an ADR was associated with the age (p=0.012). ADR-related hospitalizations incidence were 7,11%, and fatal ADR incidence were 1,97%. With regard to severity 81,2% were severe. Gastrointestinal disorders represented the most common ADRs followed by metabolism and nutrition disorders and vascular disorders. The drugs most frequently associated with ADRs were cardiovascular agents, antiinfective drugs and central nervous system agents. 72.2% of the patients who suffered ADR had polypharmacy. CONCLUSIONS: In our study incidence of adverse drug reactions in hospitalized patients was 21,34%, this data and ADR´s related to admission to hospital or fatal ADR´s are mainly suffered by pluripathology and polymedicated elderly patients with worst renal function values. In these patients a more careful prescription should be made.

OBJETIVO: Las reacciones adversas a medicamentos de uso humano (RAM) son una de las diez principales causas de mortalidad a nivel mundial, siendo las que causan ingreso o prolongan la estancia hospitalaria las de mayor impacto sanitario y económico. Los objetivos de este estudio fueron conocer la incidencia y las características de las RAM en pacientes hospitalizados en los servicios de Medicina Interna. METODOS: Estudio observacional y prospectivo de monitorización intensiva de RAM de los pacientes ingresados en los servicios de Medicina Interna en un hospital de tercer nivel durante el año 2014. Se protocolizó la recogida de datos relativos al paciente así como las características de las RAM. El análisis estadístico se realizó con el software SPSS v.20.0. RESULTADOS: Se monitorizaron 253 pacientes. Se detectaron RAM en 54 pacientes (21,34%), encontrándose una asociación positiva entre la edad y la presencia de RAM (p=0.012). La incidencia de ingresos causados por una RAM fue de 7,11% y las RAM mortales fueron un 1,97%. Las RAM fueron graves en el 81,2% de los casos. Los órganos más afectados fueron el gastrointestinal, trastornos del metabolismo y de la nutrición y el vascular. Los grupos terapéuticos causantes de RAM más frecuentes fueron los agentes cardiovasculares, los antinfecciosos y los del sistema nervioso. El 72,2% de los pacientes que sufrieron RAM presentaban polimedicación. CONCLUSIONES: La incidencia de RAM en nuestro estudio se sitúa en el 21,34%. La carga de ingresos o de mortalidad derivados de una RAM la sufren, fundamentalmente, pacientes ancianos, pluripatológicos, polimedicados y con peores valores de función renal por lo que es en ellos en quien fundamentalmente se debería realizar una prescripción más cuidadosa.

A curated mammography data set for use in computer-aided detection and diagnosis research.

Published research results are difficult to replicate due to the lack of a standard evaluation data set in the area of decision support systems in mammography; most computer-aided diagnosis (CADx) and detection (CADe) algorithms for breast cancer in mammography are evaluated on private data sets or on unspecified subsets of public databases. This causes an inability to directly compare the performance of methods or to replicate prior results. We seek to resolve this substantial challenge by releasing an updated and standardized version of the Digital Database for Screening Mammography (DDSM) for evaluation of future CADx and CADe systems (sometimes referred to generally as CAD) research in mammography. Our data set, the CBIS-DDSM (Curated Breast Imaging Subset of DDSM), includes decompressed images, data selection and curation by trained mammographers, updated mass segmentation and bounding boxes, and pathologic diagnosis for training data, formatted similarly to modern computer vision data sets. The data set contains 753 calcification cases and 891 mass cases, providing a data-set size capable of analyzing decision support systems in mammography.

Tratamiento de la esclerosis múltiple remitente recurrente con fingolimod en la práctica clínica habitual / Treatment of relapsing-remitting multiple sclerosis with fingolimod in routine clinical practice

Introducción. El fingolimod es un inmunosupresor selectivo dirigido contra el receptor SP-1, indicado en el tratamiento de la esclerosis múltiple remitente recurrente (EMRR) agresiva y tras el fracaso del tratamiento con fármacos de primera línea. Objetivo. Investigar la seguridad y efectividad del fingolimod en condiciones de práctica clínica habitual. Pacientes y métodos. Estudio observacional con seguimiento prospectivo de pacientes con EMRR que recibieron fingolimod desde enero de 2011 hasta febrero de 2014. Se evaluó la tasa anual de brotes (TAB), la discapacidad medida por la escala expandida del estado de discapacidad (EDSS), la actividad en la resonancia magnética y la aparición de efectos adversos. Resultados. Incluimos 122 pacientes, el 79,5% mujeres y con una edad media de 26,8 años. Se clasificaron según el último tratamiento recibido en: naïve (EMRR agresiva; n = 17), fracaso a terapias previas (n = 67) y retirada de natalizumab por riesgo de leucoencefalopatía multifocal progresiva (n = 38). Tras un seguimiento medio de 29,9 ± 15,9 meses, se redujo de forma significativa la TAB y la aparición de nuevas lesiones con realce de gadolinio en el grupo naïve y el de fracaso a terapias previas. No ha habido diferencias en la evolución de la EDSS ni en el tiempo hasta el primer brote o el fracaso terapéutico entre los diferentes subgrupos. El riesgo a fracaso terapéutico es mayor con la EDSS basal > 3 (hazard ratio: 4,24; p = 0,001) y presencia de bandas oligoclonales IgM (hazard ratio: 2,45; p < 0,022). Conclusiones. El fingolimod es un fármaco eficaz y seguro en la EMRR en condiciones de práctica clínica habitual. Tener una EDSS basal > 3 y bandas oligoclonales IgM predice una mala respuesta al fingolimod (AU)

Introduction. Fingolimod is a selective immunosuppressant that targets the S1P receptor, and is indicated in the treatment of aggressive relapsing-remitting multiple sclerosis (RRMS) and following treatment failure with first-order drugs. Aim. To investigate the safety and effectiveness of fingolimod under the conditions of routine clinical practice. Patients and methods. We conducted an observational study with prospective follow-up of patients with RRMS who received fingolimod from January 2011 until February 2014. Data assessed were the annualised relapse rate (ARR), disability measured by the Expanded Disability Status Scale (EDSS), magnetic resonance activity and the appearance of side effects. Results. Our sample consisted of 122 patients, 79.5% of them females and with a mean age of 26.8 years. They were classified, according to the last treatment received, as being: naïve (aggressive RRMS; n = 17), previous treatment failure (n = 67) and withdrawal of natalizumab due to risk of progressive multifocal leukoencephalopathy (n = 38). After a mean follow-up of 29.9 ± 15.9 months, the ARR and the appearance of new lesions with gadolinium enhancement were reduced in both the naïve and the previous treatment failure groups. There were no differences between the various subgroups as regards the progression of EDSS or the time elapsed until the first attack or treatment failure. The risk of treatment failure is higher with a baseline EDSS > 3 (hazard ratio: 4.24; p = 0.001) and presence of IgM oligoclonal bands (hazard ratio: 2.45; p < 0.022). Conclusions: Fingolimod is an effective and well-tolerated drug under conditions of routine clinical practice. Having a baseline EDSS > 3 and IgM oligoclonal bands is predictive of a poor response to fingolimod (AU)

Descripción de la consulta neurológica ambulatoria en el Hospital Distrital de Villa Elisa, Paraguay

RESUMEN Introducción: en los últimos años, la demanda neurológica ambulatoria ha ido creciendo constantemente. Existen muy pocos datos estadísticos sobre las patologías neurológicas en nuestra población. Nos planteamos conocer las características de la consulta neurológica ambulatoria. Materiales y métodos: se recogieron en forma retrospectiva fichas de los pacientes que acudieron a la consulta externa neurológica en el Hospital Distrital de Villa Elisa, Paraguay, en un periodo de 6 meses, del 1 enero del 2016 al 30 de junio del 2016. Se incluyeron a 400 pacientes, de los cuales se extrajeron los siguientes datos: edad, sexo, procedencia, diagnóstico. Resultado: se incluyó una muestra de 400 pacientes, 280 (70%) son mujeres, 120 (30%) son varones. La edad media fue de 44,7 años. Los diagnósticos neurológicos más frecuentes fueron: cefalea (46,2 %), epilepsia (22,2%), trastornos del estado del ánimo (7%), enfermedad de Parkinson (4%), enfermedad cerebro vascular (3,8%), trastorno cognitivos (3,8%). Conclusión: los pacientes neurológicos son predominantemente jóvenes y de sexo femenino. Las patologías más frecuentes fueron cefalea y epilepsia.

ABSTRACT Introduction: In the last years, the ambulatory neurological demand has been growing constantly. There are few statistical data about neurological pathologies in our population. The objective was to determine the characteristics of the ambulatory neurological consultation. Materials and methods: Records of patients attending the external neurological consultation of the District Hospital of Villa Elisa, Paraguay were collected retrospectively during a 6-month period from January 1st to June 30, 2016. Four hundred patients were included and the following data were collected: age, gender, origin, diagnosis. Results: A sample of 400 patients were included, 280 (70%) were women, and 120 (30%) men while mean age was 44.7 years. The most frequent diagnoses were: cephalea (46,2 %), epilepsy (22,2%), mood disorders (7%), Parkinson's disease (4%), cerebrovascular diseases (3,8%) and cognitive disorders (3,8%). Conclusion: Neurologic patients were mainly young women. The most frequent pathologies were cephalea and epilepsy.