Age-related changes in EEG coherence

Background and purpose Coherence changes can reflect the pathophysiological processes involved in human ageing. We conducted a retrospective population study that sought to analyze the age-related changes in EEG coherence in a group of 17,722 healthy professional drivers. Materials and methods The EEGs were obtained using a standard 10–20 electrode configuration on the scalp. The recordings from 19 scalp electrodes were taken while the participants’ eyes were closed. The linear correlations between the age and coherence were estimated by linear regression analysis. Results Our results showed a significant decrease in coherence with age in the theta and alpha bands, and there was an increasing coherence with the beta bands. The most prominent changes occurred in the alpha bands. The delta bands contained movement artefacts, which most likely do not change with age. Conclusions The age-related EEG desynchrony can be partly explained by the age-related reduction of cortical connectivity. Higher frequencies of oscillations require less cortical area of high coherence. These findings explain why the lowest average coherence values were observed in the beta and sigma bands, as well as why the beta bands show borderline statistical significance and the sigma bands show non-significance. The age-dependent decrease in coherence may influence the estimation of age-related changes in EEG energy due to phase cancellation

PPI Long Term Use: Risk of Neurological Adverse Events?

The purpose of this review study is to reveal a potential threat of one type of such widely used and freely distributed drugs, which are proton pump inhibitors that might be the cause of the onset of both dementia and depression. The authors performed a literature review of available studies on the research topic describing the adverse effect of proton pum inhibitors (PPIs) (omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, pantoprazole, dexrabeprazole, ilaprazole). For a long time, PPIs were considered to be completely safe drug substances for both short and long-term use. In recent years, there have been a few contradictory studis of absolute safety, especially in patients, who have long been using PPIs. At this time when depression and dementia are rising in the population, this is a very worrying fact that needs to be highlighted, and which needs to be carefully studied and evaluated, ideally trying to prevent it. The findings of most research studies described in this review indicate that there is a direct association between the onset of dementia and depression on one side and the long-term use of PPIs on the other

Nitrendipine and Dementia: Forgotten Positive Facts?

Nowadays, there are about 50 million people suffering from dementia worldwide. In 2030, it is expected that there will be 82 million people living with dementia and in 2050, their number should reach 152 million. This increase in the number of people with dementia results in significant social and economic problems. Therefore, researchers attempt to reduce risk factors causing the development of dementia such as high blood pressure. Epidemiological studies have shown that hypertension increases the risk of dementia at an older age. It can, therefore, be assumed that hypertension therapy will reduce the risk of dementia. However, previous clinical studies have shown that the efficacy of different antihypertensive drugs differs in this respect. The drug group that appears to be the most effective in these analyses is calcium channel blockers (CCBs). The most significant preventive efficacy in terms of protection against dementia has been demonstrated with nitrendipine. Its use is, therefore, particularly advantageous in elderly patients with systolic hypertension who are at high risk of dementia. The purpose of this study is to restore the discussion on the prevention of vascular dementia and Alzheimer’s dementia with nitrendipine in indicated hypertonic patients. The authors performed a literature search of available sources describing the issue of dementia, hypertension and its treatment with nitrendipine. In addition, they made a comparison and evaluation of relevant findings. The results of the detected research studies indicate that nitrendipine is able to reduce the incidence of dementia [Alzheimer’s disease (AD), vascular and mixed] by 55%. The treatment of 1,000 patients with nitrendipine for 5 years may prevent 20 cases of dementia. However, what has not yet been explained is the temporal link between hypertension and dementia due to the long-time intervals between hypertension and the development of dementia

Delayed-Release Dimethyl Fumarate Safety and Efficacy in Pediatric Patients With Relapsing-Remitting Multiple Sclerosis

Background: Pediatric multiple sclerosis (MS) is rare: only 1.5-5% of MS cases are diagnosed before 18 years of age, and data on disease-modifying therapies (DMTs) for pediatric MS are limited. The CONNECTED study assessed the long-term safety and efficacy of treatment with delayed-release dimethyl fumarate (DMF), an oral MS DMT, in pediatric patients with MS. Methods: CONNECTED is the 96-week extension to FOCUS, a 24-week phase 2 study of patients aged 13-17 years;participants received DMF 240 mg twice daily. Endpoints included (primary) incidence of adverse events (AEs), serious AEs, and DMF discontinuations due to an AE, and (secondary) T2 hyperintense lesion incidence by magnetic resonance imaging and annualized relapse rate (ARR). Results: Twenty participants [median (range) age, 17 (14-18) years;65% female] who completed FOCUS enrolled into CONNECTED;17 (85%) completed CONNECTED. Eighteen participants (90%) experienced AEs: the most frequent was flushing (25%). None experienced infections or fever related to low lymphocyte counts. Three participants experienced four serious AEs;none led to DMF discontinuation. Twelve of 17 participants (71%) had no new/newly enlarged T2 lesions from weeks 16-24, two (12%) had one, and one each (6%) had two, three, or five or more lesions [median (range), 0 (0-6)]. Over the full 120-week treatment period, ARR was 0.2, an 84.5% relative reduction (n = 20;95% confidence interval: 66.8-92.8;p < 0.0001) vs. the year before DMF initiation. Conclusions: The long-term safety and efficacy observed in CONNECTED was consistent with adults, suggesting pediatric and adolescent patients with MS might benefit from DMF treatment

Venous Thromboembolism as an Adverse Effect During Treatment With Olanzapine: A Case Series

Objective: Venous thromboembolism (VTE) is a serious multifactorial disorder. Patients with severe mental illness have a higher risk of developing the condition compared to the general population.Methods: We observed 10 cases of VTE in patients with mental illness who were treated with the antipsychotic drug olanzapine. The diagnosis of VTE was made at the University Hospital Hradec Kralove (UH HK) from 2004 to 2013. VTE was objectively determined by imaging techniques (duplex ultrasonography, CT angiography) and laboratory tests (D-dimer). The average age was 46 years. The clinical manifestation of VTE was deep vein thrombosis in nine cases, including one case of simultaneous pulmonary embolism and one case of a concurrent ischemic cerebrovascular accident (iCVA). None of our patients had a history of malignant disease, trauma, or surgery.Results: Apart from antipsychotic medication, all the patients had clinical or laboratory risk factors for VTE. The most frequent clinical risk factors were obesity (n = 7) and smoking (n = 6). The most frequent laboratory risk factors were increased levels of FVIII (n = 4), mild hyperhomocysteinemia (n = 3), and factor V Leiden mutation (n = 2). VTE developed within 3 months after antipsychotic drug initiation in three patients and within 6 months in three patients.Conclusion: Olanzapine can be considered a precipitating factor for VTE formation. When olanzapine is administered, we need to monitor for clinical signs and symptoms of VTE, especially when other risk factors are present

Binocular video head impulse test: Normative data study

IntroductionThe video head impulse test (vHIT) evaluates the vestibulo-ocular reflex (VOR). It’s usually recorded from only one eye. Newer vHIT devices allow a binocular quantification of the VOR.Purpose (Aim)To investigate the advantages of simultaneously recorded binocular vHIT (bvHIT) to detect the differences between the VOR gains of the adducting and the abducting eye, to define the most precise VOR measure, and to assess gaze dys/conjugacy. We aimed to establish normative values for bvHIT adducting/abducting eye VOR gains and to introduce the VOR dysconjugacy ratio (vorDR) between adducting and abducting eyes for bvHIT.MethodsWe enrolled 44 healthy adult participants in a cross-sectional, prospective study using a repeated-measures design to assess test–retest reliability. A binocular EyeSeeCam Sci 2 device was used to simultaneously record bvHIT from both eyes during impulsive head stimulation in the horizontal plane.ResultsPooled bvHIT retest gains of the adducting eye significantly exceeded those of the abducting eye (mean (SD): 1.08 (SD = 0.06), 0.95 (SD = 0.06), respectively). Both adduction and abduction gains showed similar variability, suggesting comparable precision and therefore equal suitability for VOR asymmetry assessment. The pooled vorDR here introduced to bvHIT was 1.13 (SD = 0.05). The test–retest repeatability coefficient was 0.06.ConclusionOur study provides normative values reflecting the conjugacy of eye movement responses to horizontal bvHIT in healthy participants. The results were similar to a previous study using the gold-standard scleral search coil, which also reported greater VOR gains in the adducting than in the abducting eye. In analogy to the analysis of saccade conjugacy, we propose the use of a novel bvHIT dysconjugacy ratio to assess dys/conjugacy of VOR-induced eye movements. In addition, to accurately assess VOR asymmetry, and to avoid directional gain preponderance between adduction and abduction VOR-induced eye movements leading to monocular vHIT bias, we recommend using a binocular ductional VOR asymmetry index that compares the VOR gains of only the abduction or only the adduction movements of both eyes

Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis : APLIOS, a randomized phase-2 study

Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). Objective: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. Methods: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUCτ) and maximum plasma concentration (Cmax) for Weeks 8-12. B-cell depletion and safety/tolerability were assessed. Results: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUCτ, 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. Conclusion: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion

Designing of SiO2 mesoporous nanoparticles loaded with mometasone furoate for potential nasal drug delivery: Ex vivo evaluation and determination of pro-inflammatory interferon and interleukin mRNA expression

The main objective of the current research work was to synthesize mesoporous silica nanoparticles for controlled delivery of mometasone furoate for potential nasal delivery. The optimized sol–gel method was used for the synthesis of mesoporous silica nanoparticles. Synthesized nanoparticles were processed through Zeta sizer, SEM, TEM, FTIR, TGA, DSC, XRD, and BET analysis for structural characterization. The in vitro dissolution test was performed for the inclusion compound, while the Franz diffusion experiment was performed for permeability of formulation. For the determination of expression levels of anti-inflammatory cytokines IL-4 and IL-5, RNA extraction, reverse transcription, and polymerase chain reaction (RT-PCR) were performed. The MTT assay was also performed to determine cell viability. Synthesized and functionalized mesoporous silica nanoparticles showed controlled release of drugs. FT-IR spectroscopy confirmed the presence of the corresponding functional groups of drugs within mesoporous silica nanoparticles. Zeta sizer and thermal analysis confirmed the delivery system was in nano size and thermally stable. Moreover, a highly porous system was observed during SEM and TEM evaluation, and further it was confirmed by BET analysis. Greater cellular uptake with improved permeability characteristics was also observed. As compared to the crystalline drug, a significant improvement in the dissolution rate was observed. It was concluded that stable mesoporous silica nanoparticles with significant porosity were synthesized, efficiently delivering the loaded drug without any toxic effect