Design of a brain-machine interface for reducing false activations of a lower-limb exoskeleton based on error related potential.

BACKGROUND AND OBJECTIVE: Brain-Machine Interfaces (BMIs) based on a motor imagination paradigm provide an intuitive approach for the exoskeleton control during gait. However, their clinical applicability remains difficulted by accuracy limitations and sensitivity to false activations. A proposed improvement involves integrating the BMI with methods based on detecting Error Related Potentials (ErrP) to self-tune erroneous commands and enhance not only the system accuracy, but also its usability. The aim of the current research is to characterize the ErrP at the beginning of the gait with a lower limb exoskeleton to reduce the false starts in the BMI system. Furthermore, this study is valuable for determining which type of feedback, Tactile, Visual, or Visuo-Tactile, achieves the best performance in evoking and detecting the ErrP. METHODS: The initial phase of the research concentrates on detecting ErrP at the beginning of gait to improve the efficiency of an asynchronous BMI based on motor imagery (BMI-MI) to control a lower limb exoskeleton. Initially, an experimental protocol is designed to evoke ErrP at the start of gait, employing three different stimuli: Tactile, Visual, and Visuo-Tactile. An iterative selection process is then utilized to characterize ErrP in both time and frequency domains and fine-tune various parameters, including electrode distribution, feature combinations, and classifiers. A generic classifier with 6 subjects is employed to configure an ensemble classification system for detecting ErrP and reducing the false starts. RESULTS: The ensembled system configured with the selected parameters yields an average correction of false starts of 72.60 % ± 10.23, highlighting its corrective efficacy. Tactile feedback emerges as the most effective stimulus, outperforming Visual and Visuo-Tactile feedback in both training types. CONCLUSIONS: The results suggest promising prospects for reducing the false starts when integrating ErrP with BMI-MI, employing Tactile feedback. Consequently, the security of the system is enhanced. Subsequent, further research efforts will focus on detecting error potential during movement for gait stop, in order to limit undesired stops.

Exploring management and outcomes of elderly patients with glioblastoma using data from two randomised trials (GEINO1401/EX-TEM).

PURPOSE: The impact of age on optimal management of glioblastoma remains unclear. A recent combined analysis of two randomised trials, GEINO14-01 and EX-TEM, found no benefit from extending post-radiation temozolomide in newly diagnosed glioblastoma. Here, we explore the impact of age. METHODS: Relevant intergroup statistics were used to identify differences in tumour, treatment and outcome characteristics based on age with elderly patients (EP) defined as age 65 years and over. Survival was estimated using the Kaplan Meier method. RESULTS: Of the combined 205 patients, 57 (28%) were EP. Of these, 95% were ECOG 0-1 and 65% underwent macroscopic resection compared with 97% and 61% of younger patients (YP) respectively. There were numerically less MGMT-methylated (56% vs. 63%, p = 0.4) and IDH-mutated (4% vs. 13%, p = 0.1) tumours in EP vs. YP. Following surgery, EP were more likely to receive short course chemoradiation (17.5% vs. 6%, p = 0.017). At recurrence, EP tended to receive or best supportive care (28.3% vs. 15.4%, p = 0.09) or non-surgical options (96.2% vs. 84.6%, p = 0.06), but were less likely to receive bevacizumab (23.1% vs. 49.5%, p < 0.01). Median PFS was similar at 9.3months in EP and 8.5months in YP, with similar median OS at 20months. CONCLUSION: In this trial population of predominantly fit EP, survival was similar to YP despite a proportion receiving less aggressive therapy at diagnosis and recurrence. Advancing age does not appear to be an adverse prognostic factor for glioblastoma when patients are fit for treatment, and a less aggressive approach in selected patients may not compromise outcomes.

[Translated article] Requirements for Accessing New Dermatology Drugs in Spain: Results of the EQUIDAD Study.

BACKGROUND: Although the Spanish Ministry of Health prepares national therapeutic positioning reports (TPRs) and drug reimbursement policies, each of the country's 17 autonomous communities (ACs) is responsible for health care services and prescription requirements in its territory. The aim of the EQUIDAD study was to describe and explore potential differences in prescription requirements for new dermatology drugs across the autonomous communities. MATERIAL AND METHODS: Cross-sectional study conducted in April and May, 2023. Two dermatologists with management responsibilities from each autonomous community reported on territorial and more local prescription requirements for drugs covered by national TPRs issued between 2016 and 2022. RESULTS: Thirty-three researchers from 17 autonomous communities participated. The data submitted revealed between-community inequities in access to new drugs. Overall, 64.7% of the regions imposed additional prescription requirements to those mentioned in the TPRs for psoriasis. This percentage was lower for atopic dermatitis (35.3%) and melanoma (11.8%). The most common requirement for accessing a new drug was a previous prescription for another drug. Differences and additional requirements were also detected at the local level (i.e., differences between hospitals within the same autonomous community). CONCLUSIONS: Spain's autonomous communities have multiple regional and local prescription requirements that are not aligned with national TPR recommendations. These differences result in inequitable access to new drugs for both patients and practitioners across Spain.

Requirements for Accessing New Dermatology Drugs in Spain: Results of the EQUIDAD Study. / Condicionantes de acceso a nuevos medicamentos dermatológicos en España: resultados del proyecto EQUIDAD.

BACKGROUND: Although the Spanish Ministry of Health prepares national therapeutic positioning reports (TPRs) and drug reimbursement policies, each of the country's 17 autonomous communities (ACs) is responsible for health care services and prescription requirements in its territory. The aim of the EQUIDAD study was to describe and explore potential differences in prescription requirements for new dermatology drugs across the autonomous communities. MATERIAL AND METHODS: Cross-sectional study conducted in April and May, 2023. Two dermatologists with management responsibilities from each autonomous community reported on territorial and more local prescription requirements for drugs covered by national TPRs issued between 2016 and 2022. RESULTS: Thirty-three researchers from 17 autonomous communities participated. The data submitted revealed between-community inequities in access to new drugs. Overall, 64.7% of the regions imposed additional prescription requirements to those mentioned in the TPRs for psoriasis. This percentage was lower for atopic dermatitis (35.3%) and melanoma (11.8%). The most common requirement for accessing a new drug was a previous prescription for another drug. Differences and additional requirements were also detected at the local level (i.e., differences between hospitals within the same autonomous community). CONCLUSIONS: Spain's autonomous communities have multiple regional and local prescription requirements that are not aligned with national TPR recommendations. These differences result in inequitable access to new drugs for both patients and practitioners across Spain.

A combined analysis of two prospective randomised studies exploring the impact of extended post-radiation temozolomide on survival outcomes in newly diagnosed glioblastoma.

PURPOSE: The optimal duration of post-radiation temozolomide in newly diagnosed glioblastoma remains unclear, with no published phase III randomised trials. Standard-of-care stipulates 6 months. However, in routine care, it is often extended to 12 months, despite lacking robust supporting data. METHODS: GEINO14-01 (Spain) and EX-TEM (Australia) studies enrolled glioblastoma patients without progression at the end of 6 months post-radiation temozolomide. Participants were randomised 1:1 to six additional months of temozolomide or observation. Primary endpoint was 6-month progression free survival from date of randomisation (6mPFS). Secondary endpoints included overall survival (OS) and toxicity. 204 patients were required to detect an improvement in 6mPFS from 50 to 60% (80% power). Neither study recruited sufficient patients. We performed a combined analysis of individual patient data. RESULTS: 205 patients were recruited: 159 in GEINO14-01 (2014-2018) and 46 in EX-TEM (2019-2022). Median follow-up was 20.0 and 14.5 months. Baseline characteristics were balanced. There was no significant improvement in 6mPFS (57.2% vs 64.0%, OR0.75, p = 0.4), nor across any subgroups, including MGMT methylated; PFS (HR0.92, p = 0.59, median 7.8 vs 9.7 months); or OS (HR1.03, p = 0.87, median 20.1 vs 19.4 months). During treatment extension, 64% experienced any grade adverse event, mainly fatigue and gastrointestinal (both 54%). Only a minority required treatment changes: 4.5% dose delay, 7.5% dose reduction, 1.5% temozolomide discontinuation. CONCLUSION: For glioblastoma patients, extending post-radiation temozolomide from 6 to 12 months is well tolerated but does not improve 6mPFS. We could not identify any subset that benefitted from extended treatment. Six months should remain standard-of-care.

Analysis of Error Potentials generated by a lower limb exoskeleton feedback in a BMI for gait control.

Brain-machine interfaces (BMIs) based on motor imagery (MI) for controlling lower-limb exoskeletons during the gait have been gaining importance in the rehabilitation field. However, these MI-BMI are not as precise as they should. The detection of error related potentials (ErrP) as a self-tune parameter to prevent wrong commands could be an interesting approach to improve their performance. For this reason, in this investigation ErrP elicited by the movement of a lower-limb exoskeleton against subject's will is analyzed in the time, frequency and time-frequency domain and compared with the cases where the exoskeleton is correctly commanded by motor imagery (MI). The results of the ErrP study indicate that there is statistical significative evidence of a difference between the signals in the erroneous events and the success events. Thus, ErrP could be used to increase the accuracy of BMIs which commands exoskeletons.Clinical Relevance- This investigation has the purpose of improving brain-machine interfaces (BMIs) based on motor imagery (MI) by means of the detection of error potentials. This could promote the adoption of robotic exoskeletons commanded by BMIs in rehabilitation therapies.

Transfer Learning with CNN Models for Brain-Machine Interfaces to command lower-limb exoskeletons: A Solution for Limited Data.

This study evaluates the performance of two convolutional neural networks (CNNs) in a brain-machine interface (BMI) based on motor imagery (MI) by using a small dataset collected from five participants wearing a lower-limb exoskeleton. To address the issue of limited data availability, transfer learning was employed by training models on EEG signals from other subjects and subsequently fine-tuning them to specific users. A combination of common spatial patterns (CSP) and linear discriminant analysis (LDA) was used as a benchmark for comparison. The study's primary aim is to examine the potential of CNNs and transfer learning in the development of an automatic neural classification system for a BMI based on MI to command a lower-limb exoskeleton that can be used by individuals without specialized training.Clinical Relevance- BMI can be used in rehabilitation for patients with motor impairment by using mental simulation of movement to activate robotic exoskeletons. This can promote neural plasticity and aid in recovery.

Durvalumab with or without tremelimumab versus the EXTREME regimen as first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck: KESTREL, a randomized, open-label, phase III study.

BACKGROUND: Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have a poor prognosis. The phase III KESTREL study evaluated the efficacy of durvalumab [programmed death-ligand 1 (PD-L1) antibody] with or without tremelimumab [cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody], versus the EXTREME regimen in patients with R/M HNSCC. PATIENTS AND METHODS: Patients with HNSCC who had not received prior systemic treatment for R/M disease were randomized (2 : 1 : 1) to receive durvalumab 1500 mg every 4 weeks (Q4W) plus tremelimumab 75 mg Q4W (up to four doses), durvalumab monotherapy 1500 mg Q4W, or the EXTREME regimen (platinum, 5-fluorouracil, and cetuximab) until disease progression. Durvalumab efficacy, with or without tremelimumab, versus the EXTREME regimen in patients with PD-L1-high tumors and in all randomized patients was assessed. Safety was also assessed. RESULTS: Durvalumab and durvalumab plus tremelimumab were not superior to EXTREME for overall survival (OS) in patients with PD-L1-high expression [median, 10.9 and 11.2 versus 10.9 months, respectively; hazard ratio (HR) = 0.96; 95% confidence interval (CI) 0.69-1.32; P = 0.787 and HR = 1.05; 95% CI 0.80-1.39, respectively]. Durvalumab and durvalumab plus tremelimumab prolonged duration of response versus EXTREME (49.3% and 48.1% versus 9.8% of patients remaining in response at 12 months), correlating with long-term OS for responding patients; however, median progression-free survival was longer with EXTREME (2.8 and 2.8 versus 5.4 months). Exploratory analyses suggested that subsequent immunotherapy use by 24.3% of patients in the EXTREME regimen arm contributed to the similar OS outcomes between arms. Grade 3/4 treatment-related adverse events (TRAEs) for durvalumab, durvalumab plus tremelimumab, and EXTREME were 8.9%, 19.1%, and 53.1%, respectively. CONCLUSIONS: In patients with PD-L1-high expression, OS was comparable between durvalumab and the EXTREME regimen. Durvalumab alone, and with tremelimumab, demonstrated durable responses and reduced TRAEs versus the EXTREME regimen in R/M HNSCC.

Prenatal neurosurgical counseling for conditions affecting the fetal nervous system.

OBJECTIVE: The aim of this study was to share a single center's experience of prenatal neurosurgical counseling and explore pregnant women's experiences with counseling. MATERIAL AND METHODS: This retrospective study analyzed data for 81 women who received prenatal counseling in a single institution (same senior pediatric neurosurgeon) over a 6-year period. Additionally, a retrospective questionnaire study was conducted with 33 women who chose to continue their pregnancy, to assess the strengths and weaknesses of counseling and analyze the reasons for their decision. RESULTS: Spinal dysraphism was the most frequent condition leading to prenatal counseling, followed by conditions affecting the cerebrospinal fluid. 57.6% of the women did not follow the French national recommendations on folic acid supplementation in the periconceptional period, and 38.3% underwent termination of pregnancy (TOP). One-third of the 33 women who answered our questionnaire changed their mind about TOP after counseling, and 50% reported that the information provided influenced their decision. CONCLUSION: Prenatal neurosurgical counseling is nowadays an important part of a pediatric neurosurgeon's practice. It provides specific information to the woman to decide whether to continue the pregnancy. Urological concerns are frequent among the malformations encountered. Hence, we conclude that these women should be offered the possibility of seeing a urologist. Areas for improvement include greater awareness regarding folic acid supplementation and improved psychological care. The advantage for a woman of consulting a neurosurgeon consists in receiving information that is as accurate as possible about the level of disability of the future child and about surgery and follow-up.

SEOM clinical guideline for management of adult medulloblastoma (2020).

Recent advances in molecular profiling, have reclassified medulloblastoma, an undifferentiated tumor of the posterior fossa, in at least four diseases, each one with differences in prognosis, epidemiology and sensibility to different treatments. The recommended management of a lesion with radiological characteristics suggestive of MB includes maximum safe resection followed by a post-surgical MR < 48 h, LCR cytology and MR of the neuroaxis. Prognostic factors, such as presence of a residual tumor volume > 1.5 cm2, presence of micro- or macroscopic dissemination, and age > 3 years as well as pathological (presence of anaplastic or large cell features) and molecular findings (group, 4, 3 or p53 SHH mutated subgroup) determine the risk of relapse and should guide adjuvant management. Although there is evidence that both high-risk patients and to a lesser degree, standard-risk patients benefit from adjuvant craneoespinal radiation followed by consolidation chemotherapy, tolerability is a concern in adult patients, leading invariably to dose reductions. Treatment after relapse is to be considered palliative and inclusion on clinical trials, focusing on the molecular alterations that define each subgroup, should be encouraged. Selected patients can benefit from surgical rescue or targeted radiation or high-dose chemotherapy followed by autologous self-transplant. Even in patients that are cured by chemorradiation presence of significant sequelae is common and patients must undergo lifelong follow-up.

Rationale, design and methodology of TESEO study: a registry of thrombosis and neoplasia of SEOM (Spanish Society of Medical Oncology).

BACKGROUND AND RATIONALE: Thromboembolic complications are a serious, preventable and common event in cancer patients that contributes to increasing morbidity and mortality. Despite increasing knowledge on cancer-associated thrombosis (CAT), there are still several aspects of diagnosis, clinical management, treatment and prognosis with uncertainties that are under-represented in randomized clinical trials. For this reason, the Spanish Society of Medical Oncology (SEOM) launched in June 2018 a registry of CAT. METHODS/DESIGN: TESEO is an ongoing prospective, non-interventional, multicentric study in consecutive cancer patients with newly diagnosed of thromboembolic event (TEE). Eligibility criteria include being > 18 years with a histologically confirmed diagnosis of cancer and a symptomatic or incidental TEE confirmed with an imaging technique in the previous month or any time after the cancer diagnosis and signing of informed consent. The study consists of two types of integrated but independent prospective registries. Regular CAT sub-registry includes information on patient's cancer´s characteristics, anticoagulant treatment provided and outcome data. Special CAT sub-registry includes variables related to special situations of CAT that comprise patients with severe kidney failure, thrombocytopenia, high risk of bleeding related to the cancer or with coexistence of bleeding and patients who receive new treatments such a targeted therapy, antiangiogenics agents and immunotherapy. The registry considers the status of the cancer and the time to assess how the prognosis is changed based on when the thrombus occurs. Some outcomes such as rethrombosis, major bleeding, tumor progression and survival will be valued in various time intervals including 1, 3, 6 and 12 months after the even in the first year; and then every 6 months until the patient's death. RESULTS: After 18 months and with 35 centers and researchers, the registry has 1128 patients. CONCLUSION: TESEO registry will provide clinical real-world evidence for prevention, treatment and complications of CAT in different scenarios that are under-represented in randomized clinical trials.

Uncommon tumors in multiple endocrine neoplasia (MEN) type 1: Do they have a relationship with the prognosis of these patients?

INTRODUCTION: The prognosis of MEN 1 patients is not only determined by pancreatic disease; it is also related to other uncommon tumors. The objective of this study is to analyze the tumors associated with MEN 1 outside the classic triad and to investigate their relationship with mortality. MATERIALS AND METHODS: One hundred and five MEN 1 patients were studied in a tertiary referral hospital (1980-2019). RESULTS: With a follow-up of 11 ± 4 years, seven patients died (8%), four as a consequence MEN syndrome. Thirty-three percent had adrenal gland tumors. One patient died of adrenal cancer. Eight percent presented with a neuroendocrine thoracic neoplasm, and one patient died. Another patient died due to cutaneous T-cell lymphoma. A further patient died because of a gastrinoma with liver metastasis. CONCLUSIONS: To conclude, 75% of MEN-related deaths were the result of an uncommon pathology, and we, therefore, recommend that these tumors should be taken into account in the screening and follow-up of these patients.

Dermatologists' Role in the Early Diagnosis of Psoriatic Arthritis: Expert Recommendations. / El papel del dermatólogo en el diagnóstico precoz de la artritis psoriásica: recomendaciones de un grupo de expertos.

Psoriatic arthritis is a common type of inflammatory arthritis found in up to 40% of patients with psoriasis. Because skin involvement usually precedes joint involvement, dermatologists play a key role in early detection. Early diagnosis is important for reducing the risk of irreversible structural damage, attenuating the deterioration of physical function, and improving patients' quality of life. This consensus statement was drafted by a group of 9 dermatologists and 1 rheumatologist to provide simple recommendations to help dermatologists screen for psoriatic arthritis in patients with psoriasis. The experts offer consensus-based guidelines that draw on a review of available scientific evidence and on experience acquired in routine clinical practice.

Dosificación de tratamiento en terapia vestibular para lesiones vestibulares periféricas: una revisión / Treatment dosage in vestibular therapy for peripheral vestibular lesions: a review

La terapia vestibular ha mostrado una evolución constante hacia la práctica basada en evidencia principalmente en los últimos años, sin embargo, actualmente no existe consenso sobre la dosificación de tratamiento necesaria para generar resultados deseados en los usuarios. Por ello, el presente estudio pretende analizar la evidencia científica sobre la dosificación de tratamiento en la terapia vestibular para patologías vestibulares periféricas y su impacto en la práctica clínica. Se realizó una búsqueda bibliográfica en las bases de datos PubMed y Cochrane Library de acuerdo a términos claves. Los estudios incluidos fueron ensayos clínicos, revisiones sistemáticas y metaanálisis, publicados desde el año 2009 y realizado en seres humanos. Se encontraron 60 artículos relacionados con los términos claves utilizados, de los cuales 52 fueron eliminados por cumplir con los criterios de exclusión. Existe escasa literatura sobre la dosificación de tratamiento en terapia vestibular, demostrando formatos de aplicación muy disímiles. Resulta complejo establecer estándares para la dosis terapéutica producto de la heterogeneidad de las patologías vestibulares.

Recently, vestibular rehabilitation therapy has shown constant development towards evidence-based practice, however, at the present time, there is lack of consensus about treatment dosage needed to produce the desired results for the users. Therefore, the present study aimed to analyze scientific evidence relating to treatment dosage of vestibular rehabilitation therapy for peripheral vestibular pathologies, and its impact on clinical practice. We conducted a bibliographic search in PubMed, and Cochrane Library according to previously defined MeSH terms. Included studies were clinical trials, systematic revisions, and meta-analyses, that were published since 2009, and conducted with human participants. The initial search yielded 60 articles related to the MeSH terms chosen, from which 52 were eliminated according to exclusion criteria. There is a scarce number of scientific articles regarding treatment dosage, and also a heterogeneous application format. It is a complex task to establish standards regarding therapeutic doses, mainly due to the heterogeneity of vestibular pathologies.

Linguistic and Cultural Adaptation to Spanish of the Screening Tool Psoriatic Arthritis UnclutteRed Screening Evaluation (PURE4). / Adaptación lingüística y cultural al español del cuestionario Psoriatic arthritis UnclutteRed screening Evaluation (PURE-4).

BACKGROUND AND OBJECTIVE: The 4-item Psoriatic arthritis UnclutteRed screening Evaluation (PURE-4) questionnaire is a useful tool for identifying patients with suspected psoriatic arthritis before referring them to a rheumatology department for confirmation. The original English version has good discriminant validity (sensitivity, 85.7%; specificity, 83.6%). We aimed to produce an adapted Spanish version of the PURE-4 for validation and use in Spain. MATERIAL AND METHOD: We applied the method recommended by the International Society for Pharmacoeconomic and Outcome Research for the cultural adaptation of patient-centered measurement tools. The phases in the processes involved forward translation, reconciliation, back translation review, harmonization, cognitive debriefing and review, and proofreading. RESULTS: We obtained the permission of the author of the original questionnaire. Two native-speaking translators translated the questionnaire into Spanish. Small changes, mainly in the way the items were expressed, were then made in order to reconcile the 2 translations. The questionnaire was then back translated to English and revised to achieve a version equivalent to the original. A Spanish translation derived from the revision was tested for understandability in 7 patients, and the final Spanish version was then produced. During the translation phases, the project manager and a scientific committee made up of a dermatologist and a rheumatologist reviewed the different versions. Team members exchanged information throughout the process, providing for harmonization and the quality control that guaranteed conceptual equivalence. CONCLUSIONS: This adaptation of the PURE-4 questionnaire for use in Spain has been the first step toward using it in routine clinical practice. The standardized method we used ensures that the Spanish and the original versions are equivalent.

Update of the recommendations for the determination of biomarkers in colorectal carcinoma: National Consensus of the Spanish Society of Medical Oncology and the Spanish Society of Pathology.

In this update of the consensus of the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica-SEOM) and the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica-SEAP), advances in the analysis of biomarkers in advanced colorectal cancer (CRC) as well as susceptibility markers of hereditary CRC and molecular biomarkers of localized CRC are reviewed. Recently published information on the essential determination of KRAS, NRAS and BRAF mutations and the convenience of determining the amplification of human epidermal growth factor receptor 2 (HER2), the expression of proteins in the DNA repair pathway and the study of NTRK fusions are also evaluated. From the pathological point of view, the importance of analysing the tumour budding and poorly differentiated clusters, and its prognostic value in CRC is reviewed, as well as the impact of molecular lymph node analysis on lymph node staging in CRC. The incorporation of pan-genomic technologies, such as next-generation sequencing (NGS) and liquid biopsy in the clinical management of patients with CRC is also outlined. All these aspects are developed in this guide, which, like the previous one, will remain open to any necessary revision in the future.

SEOM clinical guideline of venous thromboembolism (VTE) and cancer (2019).

In 2011, the Spanish Society of Medical Oncology (SEOM) first published a clinical guideline of venous thromboembolism (VTE) and cancer. This guideline was updated in 2014, and since then, multiple studies and clinical trials have changed the landscape of the treatment and prophylaxis of VTE in cancer patients. To incorporate the most recent evidence, including data from direct oral anticoagulants (DOACs) randomized clinical trials, SEOM presents a new update of the guideline.