Highlights • We report real-world data from 464 patients treated with perampanel over 1 year. • Efficacy and tolerability of perampanel were comparable with clinical trial data. • Patients ≥65 years, ...vascular aetiology or fewer prior AEDs had a superior response. • Patients with psychiatric comorbidities (hyperactivity and personality disorder) were more likely to experience psychiatric AEs. • Patients with slower titration schedules were less likely to experience an AE
Seventeen Middle Pleistocene crania from the Sima de los Huesos site (Atapuerca, Spain) are analyzed, including seven new specimens. This sample makes it possible to thoroughly characterize a Middle ...Pleistocene hominin paleodeme and to address hypotheses about the origin and evolution of the Neandertals. Using a variety of techniques, the hominin-bearing layer could be reassigned to a period around 430,000 years ago. The sample shows a consistent morphological pattern with derived Neandertal features present in the face and anterior vault, many of which are related to the masticatory apparatus. This suggests that facial modification was the first step in the evolution of the Neandertal lineage, pointing to a mosaic pattern of evolution, with different anatomical and functional modules evolving at different rates.
Although central nervous system (CNS) involvement in adult myotonic dystrophy type 1 (DM1) was described long ago, the large number of variables affecting the cognitive and personality profile have ...made it difficult to determine the effect of DM1 on the brain. The aim of this study was to define the cognitive and personality patterns in adult DM1 patients, and to analyse the relationship between these clinical patterns and their association with the underlying molecular defect.
We examined 121 adult DM1 patients with confirmed molecular CTG repeat expansion and 54 control subjects using comprehensive neuropsychological tests and personality assessments with the Millon Clinical Multiaxial Inventory (MCMI)-II. We used a multiple linear regression model to assess the effect of each variable on cognition and personality adjusted to the remainders.
Patients performed significantly worse than controls in tests measuring executive function (principally cognitive inflexibility) and visuoconstructive ability. In the personality profile, some paranoid and aggressive traits were predominant. Furthermore, there was a significant negative correlation between the CTG expansion size and many of the neuropsychological and personality measures. The molecular defect also correlated with patients' daytime somnolence.
Besides muscular symptomatology, there is significant CTG-dependent involvement of the CNS in adult DM1 patients. Our data indicate that the cognitive impairment predominantly affects the fronto-parietal lobe.
•We generated background incidence rates for 41 AESIs across a network of 10 European healthcare databases, which included a population of 63 million individuals.•We highlighted the importance of the ...nature of the event and the setting in which it is diagnosed, which should be captured by the data banks that are used to calculate rates, otherwise underestimation is likely.•The background incidence rates are used to monitor the safety of COVID-19 vaccines by the EMA, national health authorities and vaccine manufacturers.
In May 2020, the ACCESS (The vACCine covid-19 monitoring readinESS) project was launched to prepare real-world monitoring of COVID-19 vaccines. Within this project, this study aimed to generate background incidence rates of 41 adverse events of special interest (AESI) to contextualize potential safety signals detected following administration of COVID-19 vaccines.
A dynamic cohort study was conducted using a distributed data network of 10 healthcare databases from 7 European countries (Italy, Spain, Denmark, The Netherlands, Germany, France and United Kingdom) over the period 2017 to 2020. A common protocol (EUPAS37273), common data model, and common analytics programs were applied for syntactic, semantic and analytical harmonization. Incidence rates (IR) for each AESI and each database were calculated by age and sex by dividing the number of incident cases by the total person-time at risk. Age-standardized rates were pooled using random effect models according to the provenance of the events.
A total number of 63,456,074 individuals were included in the study, contributing to 211.7 million person-years. A clear age pattern was observed for most AESIs, rates also varied by provenance of disease diagnosis (primary care, specialist care). Thrombosis with thrombocytopenia rates were extremely low ranging from 0.06 to 4.53/100,000 person-years for cerebral venous sinus thrombosis (CVST) with thrombocytopenia (TP) and mixed venous and arterial thrombosis with TP, respectively.
Given the nature of the AESIs and the setting (general practitioners or hospital-based databases or both), background rates from databases that show the highest level of completeness (primary care and specialist care) should be preferred, others can be used for sensitivity. The study was designed to ensure representativeness to the European population and generalizability of the background incidence rates.
The project has received support from the European Medicines Agency under the Framework service contract nr EMA/2018/28/PE.
Melatonin in sleep disorders Poza, J J; Pujol, M; Ortega-Albás, J J ...
Neurología (Barcelona, English ed. ),
09/2022, Letnik:
37, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Melatonin is the main hormone involved in the control of the sleep-wake cycle. It is easily synthesisable and can be administered orally, which has led to interest in its use as a treatment for ...insomnia. Moreover, as production of the hormone decreases with age, in inverse correlation with the frequency of poor sleep quality, it has been suggested that melatonin deficit is at least partly responsible for sleep disorders. Treating this age-related deficit would therefore appear to be a natural way of restoring sleep quality, which is lost as patients age. However, despite the undeniable theoretical appeal of this approach to insomnia, little scientific evidence is available that supports any benefit of this substitutive therapy. Furthermore, the most suitable dose ranges and pharmaceutical preparations for melatonin administration are yet to be clearly defined. This review addresses the physiology of melatonin, the different pharmaceutical preparations, and data on its clinical usefulness.
Summary
Objective
To assess the risk of non‐fatal ischemic stroke associated with non‐steroidal anti‐inflammatory drugs (NSAIDs) and paracetamol. The effects of dose, duration of treatment, ...background cardiovascular (CV) risk and use of concomitant aspirin were studied.
Methods
We performed a population‐based case‐control study. Patients were considered exposed if they were on treatment within a 30‐day window before the index date. We estimated adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) using logistic regression.
Results
Two thousand eight hundred and eighty‐eight cases and 20 000 controls were included. No increased risk was observed with traditional NSAIDs as a group (OR = 1.03; 95% CI, 0.90–1.19), but results varied across individual agents and conditions of use. An increased risk was found with diclofenac (OR = 1.53; 95% CI, 1.19–1.97), in particular when used at high doses (OR = 1.62; 1.06–2.46), over long‐term periods (> 365 days; OR = 2.39; 1.52–3.76) and in patients with a high background CV risk (OR = 1.78; 1.23–2.58), as well as with aceclofenac when used at high doses (OR = 1.67; 1.05–2.67), in long‐term treatments (OR = 2.00; 1.14–3.53) and in patients with CV risk factors (OR = 2.33; 1.40–3.87). No association was found with ibuprofen (OR = 0.94; 0.76–1.17) or naproxen (OR = 0.68; 0.36–1.29). The concomitant use of aspirin did not show a significant effect modification. Paracetamol did not increase the risk overall (OR = 0.97; 0.85–1.10) or in patients at high CV risk (OR = 0.94; 0.78–1.14).
Conclusions
Diclofenac and aceclofenac increase the risk of ischemic stroke while ibuprofen and naproxen do not. Dose, duration and baseline CV risk, but not aspirin use, appear to modulate the risk. Paracetamol does not increase the risk, even in patients with a high background CV risk.
Monocytes and neutrophils play key roles in the cytokine storm triggered by SARS-CoV-2 infection, which changes their conformation and function. These changes are detectable at the cellular and ...molecular level and may be different to what is observed in other respiratory infections. Here, we applied machine learning (ML) to develop and validate an algorithm to diagnose COVID-19 using blood parameters. In this retrospective single-center study, 49 hemogram parameters from 12,321 patients with clinical suspicion of COVID-19 and tested by RT-PCR (4239 positive and 8082 negative) were analysed. The dataset was randomly divided into training and validation sets. Blood cell parameters and patient age were used to construct the predictive model with the support vector machine (SVM) tool. The model constructed from the training set (5936 patients) achieved an accuracy for diagnosis of SARS-CoV-2 infection of 0.952 (95% CI: 0.875-0.892). Test sensitivity and specificity was 0.868 and 0.899, respectively, with a positive (PPV) and negative (NPV) predictive value of 0.896 and 0.872, respectively (prevalence 0.50). The validation set model (4964 patients) achieved an accuracy of 0.894 (95% CI: 0.883-0.903). Test sensitivity and specificity was 0.8922 and 0.8951, respectively, with a positive (PPV) and negative (NPV) predictive value of 0.817 and 0.94, respectively (prevalence 0.34). The area under the receiver operating characteristic curve was 0.952 for the algorithm performance. This algorithm may allow to rule out COVID-19 diagnosis with 94% of probability. This represents a great advance for early diagnostic orientation and guiding clinical decisions.
Chitin is the second most abundant biopolymer in nature after cellulose, and it forms an integral part of insect exoskeletons, crustacean shells, krill and the cell walls of fungal spores, where it ...is present as a high-molecular-weight molecule. In this study, we showed that a chitin oligosaccharide of lower molecular weight (tetramer) induced genes in
that are principally related to vegetative growth, development and carbon and nitrogen metabolism. Based on plant responses to this chitin tetramer, a low-molecular-weight chitin mix (CHL) enriched to 92% with dimers (2mer), trimers (3mer) and tetramers (4mer) was produced for potential use in biotechnological processes. Compared with untreated plants, CHL-treated plants had increased in vitro fresh weight (10%), radicle length (25%) and total carbon and nitrogen content (6% and 8%, respectively). Our data show that low-molecular-weight forms of chitin might play a role in nature as bio-stimulators of plant growth, and they are also a known direct source of carbon and nitrogen for soil biomass. The biochemical properties of the CHL mix might make it useful as a non-contaminating bio-stimulant of plant growth and a soil restorer for greenhouses and fields.
To quantify the risk of non-fatal acute myocardial infarction (AMI) among users of allopurinol.
We carried out a population-based case-control study over the period 2001-2007 in patients aged 40-90 ...years. Patients who had prescriptions of allopurinol or an episode of AMI before the start date of follow-up were excluded from the main analysis. Allopurinol initiators were classified as current users if their last prescription ended in the 30-day window before the recorded date of AMI for cases and a random date for controls. The association between use of allopurinol and non-fatal AMI was measured through an OR and adjusted for confounding factors by an unconditional logistic regression.
We identified 3171 cases of non-fatal AMI and 18 525 controls. Cases had a lower prevalence of current use of allopurinol (0.82%) than controls (1.03%), yielding to an OR of 0.52 (95% CI 0.33 to 0.83). The decreased risk was driven by men (OR in men=0.44; 95% CI 0.25 to 0.76; OR in women=0.90; 0.36 to 2.23). No difference by age was observed. The effect was only observed at higher doses (300 mg or greater OR=0.30; 0.13 to 0.72; <300 mg OR=0.67; 0.37 to 1.23) and with prolonged treatments (<31 days, OR=1.12 (0.55 to 2.29); 31-180 days, OR=0.61; 0.29 to 1.29; >180 days OR=0.21; 0.08 to 0.53; p for trend=0.001). Among those with a previous AMI, allopurinol use also showed a significant reduced risk of recurrence (OR=0.16; 0.04 to 0.76).
The present study supports the hypothesis that allopurinol is associated with a reduced risk of non-fatal AMI, which seems to be dose-dependent and duration-dependent.
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