Seroconversion rate following HBV vaccination in clinical practice: The role of age and DMT treatment.

HBV screening and immunization is recommended in all MS patients and is mandatory before the start of some DMT. However, studies evaluating the immune response to HBV vaccine in MS patients are scarce. We aimed to evaluate the seroprotection rate following HBV immunization in MS patients and to assess if older age and DMT-treatment influenced seroprotection. We conducted a cohort study between 2016 and 2020 and compared the immune response to HBV vaccine in MS patients under different DMTs and in patients 50 years old or younger and older than 50. We found that patients under non-injectable DMT presented lower rates of seroprotection comparing to patients under injectable DMT's or without treatment. In patients older than 50, although the seroprotection rate was similar to the remaining patients, the antibody anti-HBV surface antigen titers following HBV immunization were lower and patients were more likely to require a 4th dose of the vaccine to achieve seroprotection. Our findings highlight to need to consider HBV immunization in MS patients early in the disease course, in order to ensure a proper immune response to the vaccine.

Neurologists' Diagnostic Accuracy and Interspecialties' Diagnostic Concordance of Acute Vertigo: Observational Study at the Emergency Department in a Tertiary Center.

BACKGROUND: Acute vertigo (AV) is often a challenging condition. Because of its multiple causes, patients are frequently observed by neurologists and physicians from other areas of specialites, particularly Ear, Nose, and Throat (ENT). We aimed to assess the diagnostic accuracy of AV in patients observed by Neurology and other medical specialties. MATERIALS AND METHODS: Retrospective cross-sectional study with the selection of all patients with AV observed by Neurology at the Emergency Department (ED) of a tertiary center in 2019, regarding demographic data, imaging studies, diagnosis by Neurology and ENT at the ED, and diagnosis after ED discharge by different medical specialties. RESULTS: In all, 54 patients were selected, 28 (52%) of them were women. The mean age was 59.96±14.88 years; 48% had a history of AV and 89% underwent imaging studies (computed tomography scan and/or magnetic resonance imaging scan). The most frequent diagnosis established by Neurology was benign paroxysmal positional vertigo, followed by vestibular neuronitis; 28 patients were also observed by ENT with an overall concordance rate of diagnosis of 39%. After ED discharge, most patients were observed at the Balance Disorders Outpatient Clinic. Diagnosis by Neurology at the ED was not significantly different from observation by other medical specialties after ED discharge regarding the distinction between peripheral and central causes of AV (κ=0.840, 95% confidence interval: 0.740 to 0.941, P<0.005). CONCLUSIONS: Neurologists can effectively differentiate central and peripheral causes of AV at the ED. Patients with AV should be primarily evaluated by Neurology at the ED, avoiding redundant observations and allowing faster patient management.

Real-Word Effectiveness and Safety of Dimethyl Fumarate in a Multiple Sclerosis Portuguese Population.

OBJECTIVES: The aim of this study was to evaluate postmarketing dimethyl fumarate (DMF) safety and effectiveness in a real-world population with relapsing-remitting multiple sclerosis (RRMS). METHODS: This was a retrospective, single-center study with RRMS patients treated with DMF. Demographic, clinical, and imagiological characteristics were analyzed, including annualized relapse rate (ARR), Expanded Disability Status Scale, "No Evidence of Disease Activity 3," previous treatment, adverse events, treatment duration, and reason for discontinuation. We investigated which baseline variables were associated with clinical and radiological outcomes. RESULTS: We included 176 patients (70.4% females) with a median on-treatment follow-up time of 25.5 months. In total, 139 patients received prior disease-modifying therapies, and 37 were treatment-naive. Annualized relapse rate decreased by 77.1% in the total population (P < 0.001) and also decreased in the naive, tolerability switch, and efficacy switch groups by 95.8%, 56.7%, and 76.6% (P < 0.001). No Evidence of Disease Activity 3 status after 12 months of DMF treatment was maintained in 69.2% patients. Thirty patients (17%) discontinued treatment because of adverse drug reactions, and 21 (11.9%) because of lack of effectiveness. The occurrence of first relapse during follow-up was associated with higher ARR in the year before DMF start (hazard ratio, 4.833; P < 0.001) and prior exposure to multiple sclerosis treatments (tolerability and efficacy switchers). CONCLUSIONS: In this real-world audit, DMF appeared to be effective and safe for RRMS. Additionally, the study suggested that naive patients strongly benefit from DMF, and DMF also improves ARR in patients who switched from injectable therapies due to tolerability and efficacy issues.

Simple behavioral criteria for the diagnosis of disorders of arousal.

STUDY OBJECTIVES: This case-control study aimed to identify and validate behavioral markers supporting the diagnosis of disorders of arousal (DOA) with video polysomnography. METHODS: All behaviors associated with 1,335 episodes of N3 interruptions were compared in 52 adult patients with DOA versus 52 participants without DOA (healthy control patients and patients with insomnia, hypersomnia, or sleep apnea syndrome). RESULTS: Patients with DOA had more frequent (5.1 ± 2.4 versus 3.4 ± 1.9 interruptions/N3 time) and longer (35.8 ± 33 versus 23.1 ± 21.4 sec) arousals and awakenings from N3 than control patients. In the DOA group, the onset of behaviors was more abrupt, and behaviors including eye opening (69% versus 16%), head raising (41% versus 9%), visually exploring the environment (27% versus 1%), expression of fear/surprise (21% versus zero), speaking (18% versus 0.3%), trunk raising (13% versus 0.3%), and interacting with the environment (13% versus 0.5%), were (unlike quiet, comfort behaviors) more frequent than in control patients. A cutoff of two or more N3 interruptions containing eye opening yielded a sensitivity of 94.2% and a specificity of 76.9% for a DOA diagnosis. This accuracy was confirmed in a second set of data (second night of monitoring). Behaviors including an expression of fear/surprise (67.3%), sitting (32.7%), screaming, and standing up were specific to patients with DOA. CONCLUSIONS: A simple, behavioral video marker of behavioral reactions during N3 interruption (ie, opening the eyes at least two times in the same night) was sensitive, specific, and reproducible for discriminating patients with DOA from sleep laboratory control patients. CLINICAL TRIAL REGISTRATION: This study is a surrogate study of NCT02648568 and NCT03074578 on ClinicalTrials.gov.

Visible-light reduced silver nanoparticles' toxicity in Allium cepa test system.

Silver nanoparticles (AgNPs) are widely used in consumer products due to their antibacterial property; however, their potential toxicity and release into the environment raises concern. Based on the limited understanding of AgNPs aggregation behavior, this study aimed to investigate the toxicity of uncoated (uc-AgNP) and coated with polyvinylpyrrolidone (PVP-AgNP), at low concentrations (0.5-100 ng/mL), under dark and visible-light exposure, using a plant test system. We exposed Allium cepa seeds to both types of AgNPs for 4-5 days to evaluate several toxicity endpoints. AgNPs did not cause acute toxicity (i.e., inhibition of seed germination and root development), but caused genotoxicity and biochemical alterations in oxidative stress parameters (lipid peroxidation) and activities of antioxidant enzymes (superoxide dismutase and catalase) in light and dark conditions. However, the light exposure decreased the rate of chromosomal aberration and micronuclei up to 5.60x in uc-AgNP and 2.01x in PVP-AgNP, and 2.69x in uc-AgNP and 3.70x in PVP-AgNP, respectively. Thus, light exposure reduced the overall genotoxicity of these AgNPs. In addition, mitotic index alterations and morphoanatomical changes in meristematic cells were observed only in the dark condition at the highest concentrations, demonstrating that light also reduces AgNPs cytotoxicity. The light-dependent aggregation of AgNPs may have reduced toxicity by reducing the uptake of these NPs by the cells. Our findings demonstrate that AgNPs can be genotoxic, cytotoxic and induce morphoanatomical and biochemical changes in A. cepa roots even at low concentrations, and that visible-light alters their aggregation state, and decreases their toxicity. We suggest that visible light can be an alternative treatment to remediate AgNP residues, minimizing their toxicity and environmental risks.

Diagnostic Delay of Multiple Sclerosis in a Portuguese Population.

INTRODUCTION: Multiple sclerosis is a chronic inflammatory disease, in which a diagnostic delay could reduce the available therapeutic options. Therefore, it is important to monitor the time to diagnosis and understand factors that may potentially reduce it. The objective of this study was to determine the time between the first symptoms and the diagnosis of multiple sclerosis and which factors may contribute to a diagnostic delay. MATERIAL AND METHODS: Cross-sectional multicenter study, with retrospective data analysis, conducted in five tertiary Portuguese hospitals. Patients were consecutively selected from each local multiple sclerosis patients´ database. Sociodemographic and initial clinical data were collected through a questionnaire. Date of final diagnosis and multiple sclerosis classification was obtained from clinical files. RESULTS: A total of 285 patients were included with mean age at diagnosis of 36 years. The median time between first clinical manifestation and multiple sclerosis diagnosis was nine months (IQR 2 - 38). Diagnostic delay was associated with an older age (p < 0.001; r = 0.35), motor deficit at onset [26.5 months (IQR 4.5 - 56.5); p = 0.0005], higher number of relapses before diagnosis (p < 0.001; r = 0,626), first observation by other medical specialty [11 months (IQR 2 - 48); p < 0.001], prior alternative diagnosis [20 months (IQR 4 - 67.5); p < 0.001] and primary progressive subtype [37 months (IQR 25 - 64.5); p < 0.001]. The most significant delay occurred between the initial symptom and neurological observation. DISCUSSION: A significant delay occurred between initial symptoms and the diagnosis of multiple sclerosis, reflecting the need toincrease awareness of this entity and its diverse symptom presentation.

Introdução: A esclerose múltipla é uma doença inflamatória crónica na qual um atraso no diagnóstico poderá reduzir as opções terapêuticas, sendo importante monitorizar o tempo até ao diagnóstico e compreender os fatores que potencialmente o reduzam. Foi objetivo deste estudo determinar o tempo entre os primeiros sintomas e o diagnóstico de esclerose múltipla e quais os fatores que podem contribuir para o atraso no diagnóstico. Material e Métodos: Estudo multicêntrico transversal retrospetivo, realizado em cinco hospitais portugueses. Os doentes foram selecionados, consecutivamente, a partir de bases de dados locais. Os dados sociodemográficos e clínicos iniciais foram adquiridos através de questionário individual. A data do diagnóstico final e a classificação da esclerose múltipla foram obtidas por consulta do processo clínico. Resultados: Foram incluídos 285 doentes com média de idade ao diagnóstico de 36 anos. A mediana do tempo entre a primeira manifestação clínica e o diagnóstico foi de nove meses (IQR 2 - 38). O atraso no diagnóstico foi associado a idade avançada (p < 0,001; r = 0,35), défice motor inicial [26,5 meses (IQR 4,5 - 56,5), p = 0,0005], maior número de surtos previamente ao diagnóstico (p < 0,001; r = 0,626), primeira observação por outra especialidade médica [11 meses (IQR 2 - 48); p < 0,001], diagnóstico prévio alternativo [20 meses (IQR 4 - 67,5); p < 0,001] e esclerose múltipla primária progressiva [37 meses (IQR 25 - 64,5), p < 0,001]. O atraso mais significativo ocorreu entre o primeiro sintoma e a observação por neurologista. Discussão: Ocorreu um atraso significativo entre o primeiro sintoma e o diagnóstico de esclerose múltipla, refletindo uma necessidade de maior acuidade na identificação dos seus principais sintomas.

Safety and Effectiveness of Fingolimod in Real-World Multiple Sclerosis Portuguese Patients.

OBJECTIVES: The aim of this study was to evaluate postmarketing fingolimod safety and effectiveness in a real-world clinical population. METHODS: This was a retrospective, single-center study with active multiple sclerosis patients treated with fingolimod with at least 12 months of follow-up. Demographic and clinical and imaging characteristics, including annualized relapse rate (ARR), Expanded Disability Status Score, previous treatment, adverse events, treatment duration, and reason for discontinuation, were analyzed. RESULTS: Sixty-three patients were included; 61.9% were females. Mean age and mean disease duration were 30.9 ± 9.3 years and 11.4 ± 6.9 years, respectively. Fifty-one patients received prior first-line disease-modifying therapies, 11 patients were previously treated with natalizumab, and 1 was treatment naive. The ARR decreased by 75.3% for the total population at the end of the first year of treatment (P < 0.0001). The proportion of relapse-free patients improved significantly. All patients previously treated with natalizumab switched because of safety concerns, although the ARR kept low after treatment initiation. Only 3 patients (4.8%) discontinued treatment because of adverse drug reactions, and 2 (3.2%) because of lack of effectiveness. CONCLUSIONS: In this real-world audit, fingolimod appeared to be effective after first-line treatment failure in reducing disease activity and progression of disability throughout the observational period and may be an effective option after natalizumab. Fingolimod was well tolerated with low rates of discontinuation and adverse events.