RESUMO
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.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Temozolomida/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Estudos Prospectivos , Dacarbazina/efeitos adversos , Intervalo Livre de Doença , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Antineoplásicos Alquilantes/efeitos adversosRESUMO
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.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/terapia , Glioblastoma/mortalidade , Idoso , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Temozolomida/uso terapêutico , Adulto , Antineoplásicos Alquilantes/uso terapêutico , Fatores Etários , Terapia Combinada , Resultado do Tratamento , Gerenciamento ClínicoRESUMO
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.
Assuntos
Dermatologia , Humanos , Espanha , Estudos TransversaisRESUMO
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.
Assuntos
Dermatologia , Humanos , Espanha , Estudos TransversaisRESUMO
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.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/etiologia , Antígeno B7-H1 , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia , Neoplasias de Cabeça e Pescoço/etiologiaRESUMO
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.
Assuntos
Neoplasias das Glândulas Suprarrenais , Gastrinoma , Linfoma Cutâneo de Células T , Neoplasia Endócrina Múltipla Tipo 1 , Tumores Neuroendócrinos , Neoplasias Torácicas , Neoplasias das Glândulas Suprarrenais/mortalidade , Neoplasias das Glândulas Suprarrenais/patologia , Causas de Morte , Estudos de Coortes , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/normas , Feminino , Seguimentos , Gastrinoma/mortalidade , Gastrinoma/patologia , Humanos , Linfoma Cutâneo de Células T/mortalidade , Linfoma Cutâneo de Células T/patologia , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 1/diagnóstico , Neoplasia Endócrina Múltipla Tipo 1/mortalidade , Neoplasia Endócrina Múltipla Tipo 1/patologia , Estadiamento de Neoplasias , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Prognóstico , Espanha/epidemiologia , Neoplasias Torácicas/mortalidade , Neoplasias Torácicas/patologiaRESUMO
BACKGROUND: There is increasing evidence of the key role that the gut microbiota plays in inflammatory diseases. OBJECTIVES: To identify differences in the faecal microbial composition of patients with psoriasis compared with healthy individuals in order to unravel the microbiota profiling in this autoimmune disease. METHODS: 16S rRNA gene sequencing and bioinformatic analyses were performed with the total DNA extracted from the faecal microbiota of 19 patients with psoriasis and 20 healthy individuals from the same geographic location. RESULTS: Gut microbiota composition of patients with psoriasis displayed a lower diversity and different relative abundance of certain bacterial taxa compared with healthy individuals. CONCLUSIONS: The gut microbiota profile of patients with psoriasis displayed a clear dysbiosis that can be targeted for microbiome-based therapeutic approaches. What's already known about this topic? Psoriasis is a chronic inflammatory immune-mediated skin disease, the aetiology of which remains unclear. The human microbiota is a complex microbial community that inhabits our body and has been related with the maintenance of a healthy status. Several studies have focused on the skin microbiome and its connection with psoriasis although less attention has been focused on the potential role of the gut microbiota in psoriatic disease. What does this study add? This study unravels the gut microbiome dysbiosis present in a cohort of patients with psoriasis, compared with a healthy control group from the same geographical location. This study shows a lower bacterial diversity and different relative abundance of certain bacterial taxa in patients with psoriasis. We gain knowledge and insight into the microbiome alterations in psoriatic disease, opening new avenues for therapeutic approaches to reshape the human microbiome towards a healthy status.
Assuntos
Disbiose/complicações , Microbioma Gastrointestinal/imunologia , Psoríase/imunologia , Adulto , Estudos de Coortes , DNA Bacteriano/isolamento & purificação , Disbiose/diagnóstico , Disbiose/imunologia , Disbiose/microbiologia , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/microbiologia , RNA Ribossômico 16S/genéticaRESUMO
Polymorphisms at genes encoding proteins involved in the pathogenesis of psoriasis (Psor) or in the mechanism of action of biological drugs could influence the treatment response. Because the interleukin (IL)-17 family has a central role in the pathogenesis of Psor, we hypothesized that IL17RA variants could influence the response to anti-TNF drugs among Psor patients. To address this issue we performed a cross-sectional study of Psor patients who received the biological treatments for the first time, with a follow-up of at least 6 months. All of the patients were Caucasian, older than 18 years old, with chronic plaque Psor, and had completed at least 24 weeks of anti-TNF therapy (adalimumab, etanercept or infliximab). The treatment response to anti-TNF agents was evaluated according to the achievement of PASI50 and PASI75 at weeks 12 and 24. Those who achieved PASI75 at week 24 were considered good responders. All patients were genotyped for the selected single-nucleotide polymorphisms (SNPs) at IL17RA gene. A total of 238 patients were included (57% male, mean age 46 years). One hundred and five patients received adalimumab, 91 patients etanercept and 42 infliximab. The rs4819554 promoter SNP allele A was significantly more common among responders at weeks 12 (P=0.01) and 24 (P=0.04). We found a higher frequency of AA versus AG+GG among responders, but the difference was only significant at week 12 (P=0.03, odd ratio=1.86, 95% confidence of interval=1.05-3.27). Thus, in the study population, the SNP rs4819554 in the promoter region of IL17RA significantly influences the response to anti-TNF drugs at week 12.
Assuntos
Polimorfismo de Nucleotídeo Único/genética , Psoríase/genética , Receptores de Interleucina-17/genética , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/uso terapêutico , Alelos , Estudos Transversais , Etanercepte/uso terapêutico , Feminino , Genótipo , Humanos , Infliximab/uso terapêutico , Interleucina-17/genética , Masculino , Pessoa de Meia-Idade , Psoríase/tratamento farmacológicoAssuntos
Vacina BNT162/efeitos adversos , Toxidermias/etiologia , Dermatopatias Vesiculobolhosas/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , COVID-19/prevenção & controle , Toxidermias/metabolismo , Toxidermias/patologia , Humanos , Masculino , Dermatopatias Vesiculobolhosas/metabolismo , Dermatopatias Vesiculobolhosas/patologiaRESUMO
BACKGROUND: Sentinel lymph node biopsy and wide local excision of the primary melanoma (SLNB) is now a standard staging procedure for patients with melanomas 1 mm or more in thickness, but its therapeutic benefit is not clear. OBJECTIVE: To determine whether there is an association between performance of SLNB and patient prognosis. METHODS: Studies assessing the association between performance of SLNB and patient prognosis were pooled from MEDLINE, EMBASE, PubMed, Cochrane Database of Systematic Reviews and Google Scholar. From each study, first author's last name, publication year, origin country, type of study design, characteristics of participants and the Hazard risk (HR) for melanoma specific survival (MSS) with the corresponding 95% confidence interval (95% CI) were collected. Methodological assessment of the studies was evaluated using the Newcastle-Ottawa scale (NOS) and the 'Risk of bias' tool detailed in the Cochrane Handbook for Systematic Reviews of Interventions. Meta-analyses for the global HR were performed. In addition, in order to explore the sources of heterogeneity among the studies, sensitivity analyses are also provided. RESULTS: A total of six studies with 8764 patients who had undergone SLNB and 11054 patients who had undergone wide location excision alone (WLEA) were identified for the analysis. The indicators suggest that the heterogeneity is low: τ2 = 0; H = 1 [1; 1.74]; I2 = 0% [0%; 66.5%]. Evidence for publication bias was not found (Egger's test P = 0.4654). The pooled MSS HR from fixed effects analysis was determined to be 0.88 (95% CI = 0.80-0.96). CONCLUSIONS: Although no significant survival difference was observed in four of the six series, the pooling summary data from all the studies that deal with this issue suggested that SLNB is associated with a significantly better outcome compared with WLEA for localized melanoma.
Assuntos
Melanoma/patologia , Melanoma/cirurgia , Biópsia de Linfonodo Sentinela/métodos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Humanos , PrognósticoRESUMO
BACKGROUND: The CARD14 gene encodes a protein that enhances nuclear factor (NF)-κB activation and the upregulation of proinflammatory pathway genes. CARD14 is upregulated in psoriatic vs. normal skin, and rare and common CARD14 variants have been associated with the risk of developing psoriasis. Our hypothesis was that CARD14 variants could also influence the response to antitumour necrosis factor (anti-TNF) therapies among patients with psoriasis. OBJECTIVES: To determine whether CARD14 gene variants were linked to a significant positive anti-TNF response in patients with psoriasis. METHODS: DNA from 116 patients with psoriasis was subjected to next-generation sequencing of the CARD14 gene. All of the patients were nonresponders or had contraindications to conventional systemic treatments. RESULTS: A reduction of at least 75% in Psoriasis Area and Severity Index (PASI 75) at week 24 was considered a positive response to treatment. In total 116 patients (79 responders and 37 nonresponders) were next-generation sequenced, and we identified five nucleotide variants that would result in missense amino acid changes. These variants were determined in all of the patients, and allele and genotype frequencies were compared between the two groups. We found a significantly higher frequency of rs11652075 CC (p.Arg820Trp) among the group with a positive response (P = 0.01, odds ratio 3.71, 95% confidence interval 1.30-10.51). Furthermore, among responders, six patients were heterozygous carriers of the rare p.Glu422Lys variant, and two patients were heterozygous for p.Arg682Trp (P = 0.04). CONCLUSIONS: The common CARD14 p.Arg820Trp variant might have a significant effect on the response to anti-TNF therapies among patients with psoriasis. In addition, rare CARD14 missense variants could also predispose to a better response.
Assuntos
Proteínas Adaptadoras de Sinalização CARD/genética , Guanilato Ciclase/genética , Proteínas de Membrana/genética , Mutação de Sentido Incorreto/genética , Psoríase/genética , Adalimumab/uso terapêutico , Etanercepte/uso terapêutico , Feminino , Genótipo , Humanos , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
Methotrexate (MTX) is the most frequently used conventional systemic drug in the treatment of psoriasis. Despite over 50years of experience in this setting, certain aspects of the use of this drug in clinical practice are still little standardized and poorly understood. For this reason, a group of 15 experts took part in a consensus development conference to achieve consensus on a series of recommendations on the use of MTX in psoriasis. The guidelines, which were developed on the basis of a systematic review of the literature, were validated by 2 rounds of voting and categorized by level of evidence and grade of recommendation. Before MTX can be used to treat moderate to severe psoriasis, the patient must be evaluated to assess the suitability of the treatment, including consideration of vaccination status and screening for tuberculosis and pregnancy. The recommended starting dose for a patient with no risk factors is 10 to 20mg/wk, the therapeutic dose for most patients is 15mg/wk, and the maximum dose is 20mg/wk. Most patients who respond to treatment will show improvement within 8weeks. Parenteral administration of MTX is desirable when there is a risk of erroroneous dosing, nonadherence, gastrointestinal intolerance, or inadequate response to the therapeutic dose taken orally. Noninvasive methods are preferred for monitoring hepatotoxicity. MTX is a good treatment option for patients with a history of cancer, but is not recommended in patients with chronic hepatitisB infection or individuals who are seropositive for human immunodeficiency virus.
Assuntos
Metotrexato/uso terapêutico , Psoríase/tratamento farmacológico , Contraindicações , Infecções por HIV , Hepatite B Crônica , Humanos , Neoplasias , Guias de Prática Clínica como Assunto , Fatores de RiscoRESUMO
Several observational studies have assessed the correlation between Merkel cell carcinoma and Merkel cell polyomavirus with variable results. The objective of this systematic review was to determine whether there is a correlation between Merkel cell carcinoma and Merkel cell polyomavirus. Studies assessing the relationship between Merkel cell carcinoma and Merkel cell polyomavirus from January 2008 to August 2014 were pooled from Medline, Embase, PubMed, Cochrane Database of Systemic Reviews and Google Scholar. From each study we collected the first author's last name, publication year, country of origin, type of study design, characteristics of participants, possible variables incorporated into the multivariable analyses and the risk ratio (RR) for Merkel cell carcinoma associated with Merkel cell polyomavirus combined with the corresponding 95% confidence interval (CI). Methodological assessment of the study was evaluated using the Newcastle-Ottawa scale. Crude RR was calculated from the data provided in each article. Meta-analyses for the global RR and for the proportion of positives in both case and control samples were performed. In addition, in order to explore the sources of heterogeneity among the studies, meta-regression and sensitivity analyses are also provided. A total of 22 studies were identified for the analysis. The pooled RR from random-effects analysis was determined to be 6.32 (95% CI, 4.02-9.93). Global proportions of positive samples were 0.79 (95% CI, 0.72-0.84) and 0.12 (95% CI, 0.08-0.19) in the case and control groups, respectively. The findings support the association between Merkel cell carcinoma and Merkel cell polyomavirus. However, a non-negligible percentage of positive results have been identified in controls. Some caution must be taken in the interpretation of these results because heterogeneity between studies was found.
Assuntos
Carcinoma de Célula de Merkel/complicações , Poliomavírus das Células de Merkel , Infecções por Polyomavirus/complicações , Neoplasias Cutâneas/complicações , Infecções Tumorais por Vírus/complicações , HumanosRESUMO
Epidermal growth factor receptor gene (EGFR) alteration is a common feature in most of glioblastoma multiforme (GBM). Robust response of anti-EGFR treatments has been mostly associated with the EGFR deletion mutant variant III (EGFRvIII) and expression of PTEN. We have performed a prospective trial in order to confirm the efficacy of erlotinib treatment in patients with relapsed GBM who expressed EGFRvIII and PTEN. All patients included in the trial were required to be PTEN (+++), EGFR (+++) and EGFRvIII (+++) positives by immunohistochemistry. This new phase II trial enrolled 40 patients and was design to be stopped in case of fewer than two responses in the first 13 patients. Patient eligibility included histopathology criteria, radiological progression, more than 18 years old, Karnofsky performed status, KPS > 50, and adequate bone marrow and organ function. There was no limit to the number of prior treatments for relapses. No enzyme-inducing antiepileptic drugs were allowed. The primary endpoints were response and progression-free survival at 6 months (PFS6). Thirteen patients (6 men, 7 women) with recurrent GBM received erlotinib 150 mg/day. Median age was 53 years, median KPS was 80, and median prior treatments for relapses were 2. There was one partial response and three stable diseases (one at 18 months). PFS at 6 months was 20 %. Dose reduction for toxicity was not needed in any patient. Dermatitis was the main treatment-related toxicity, grade 1 in 8 patients and grade 2 in 5 patients. No grade 3 toxicity was observed. Median survival was 7 months (95 % IC 1.41-4.7). As conclusion, monotherapy with erlotinib in GBM relapses patients with high protein expression for PTEN (+++), EGFR (+++), and EGFRvlII (+++) showed low toxicity but minimal efficacy and the trial stopped.
Assuntos
Neoplasias Encefálicas/terapia , Hemangiopericitoma/terapia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/etiologia , Radiocirurgia/métodosRESUMO
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.
Assuntos
Interfaces Cérebro-Computador , Exoesqueleto Energizado , Marcha , Extremidade Inferior , Humanos , Extremidade Inferior/fisiologia , Masculino , Marcha/fisiologia , Adulto , Eletroencefalografia , Adulto Jovem , FemininoRESUMO
Several observational studies have assessed the association between psoriasis, psoriatic arthritis (PsA) and type 2 diabetes mellitus, with inconclusive results. We set out to investigate the association between psoriasis, PsA and type 2 diabetes mellitus. Observational studies assessing the relationship between psoriasis or PsA and type 2 diabetes mellitus up to December 2012 were identified by electronic and hand searches in Medline, Embase, PubMed, the Cochrane Database of Systematic Reviews and Google Scholar. For each study we collected the first author's last name, publication year, country of origin, study design, characteristics of participants (sample size, age and sex), the variables incorporated into the multivariable analyses, and the odds ratios (ORs) of psoriasis associated with diabetes along with the corresponding 95% confidence intervals (CIs). From the data provided in each article, the crude OR was also calculated. Forty-four observational studies (in 37 articles) were identified for the final analysis. The pooled OR from random-effects analysis was determined to be 1·76 (95% CI 1·59-1·96). The highest risk was for patients suffering from PsA (OR 2·18, 95% CI 1·36-3·50). We also observed a dose effect in the risk of suffering from type 2 diabetes mellitus, as patients considered as having severe psoriasis had higher risk (OR 2·10, 95% CI 1·73-2·55) than the pooled OR. We perform meta-regression and sensitivity analyses to explore sources of heterogeneity among the studies and to determine how they would influence the estimates, and found no significant influence in the results of the meta-analyses. The findings support the association between psoriasis, PsA and type 2 diabetes mellitus. Some caution must be taken in the interpretation of these results because there may be heterogeneity between studies.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Psoríase/etiologia , Artrite Psoriásica/etiologia , Humanos , Estudos Observacionais como Assunto , Viés de Publicação , Fatores de RiscoRESUMO
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.
Assuntos
Eletroencefalografia , Exoesqueleto Energizado , Eletroencefalografia/métodos , Retroalimentação , Índice de Massa Corporal , Extremidade Inferior , MarchaRESUMO
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.
Assuntos
Interfaces Cérebro-Computador , Exoesqueleto Energizado , Humanos , Eletroencefalografia , Redes Neurais de Computação , Aprendizado de MáquinaRESUMO
BACKGROUND: Several studies stated that patient with psoriasis carried an increased risk of psoriasis but some studies did not demonstrate this association. OBJECTIVES: The aim of this study was to evaluate the prevalence of hypertension in psoriasis based on a sample of Spanish population. METHODS: This was a hospital-based case-control study involving 661 psoriatic patients (cases) and 661 control matched by gender and age. Meta-analysis of the previous studies was made. RESULTS: The prevalence of hypertension was significantly higher in psoriasis patients than controls (30.3%, 21.3%, respectively, P < 0.001). In a multivariate analysis, hypertension was associated with psoriasis after controlling for age, gender, diabetes, obesity and smoking (OR = 1.44, 95% confidence interval: 1.07-1.94). CONCLUSION: The results of this study support the association between psoriasis and hypertension.