High-Dose Inactivated Influenza Vaccine is Associated with Cost Savings and Better Outcomes Compared to Standard-Dose Inactivated Influenza Vaccine in Canadian Seniors

Seasonal influenza infects approximately 10-20% of Canadians each year, causing an estimated 12,200 hospitalizations and 3,500 deaths annually, mostly occurring in adults ≥65 years old (seniors). A 32,000-participant, randomized controlled clinical trial (FIM12; Clinicaltrials.gov NCT01427309) showed that high-dose inactivated influenza vaccine (IIV-HD) is superior to standard-dose vaccine (SD) in preventing laboratory-confirmed influenza illness in seniors. In this study, we performed a cost-utility analysis (CUA) of IIV-HD versus SD in FIM12 participants from a Canadian perspective. Healthcare resource utilization data collected in FIM12 included: medications, non-routine/urgent care and emergency room visits, and hospitalizations. Unit costs were applied using standard Canadian cost sources to estimate the mean direct medical and societal costs associated with each vaccine (2014 CAD). Clinical illness data from the trial were mapped to quality-of-life data from the literature to estimate differences in effectiveness between vaccines. Time horizon was one influenza season, however, quality-adjusted life-years (QALYs) lost due to death during the study were captured over a lifetime. A probabilistic sensitivity analysis (PSA) was also performed. Average per-participant medical costs were $47 lower and societal costs$60 lower in the IIV-HD arm. Hospitalizations contributed 91% of the total cost and were less frequent in the IIV-HD arm. IIV-HD provided a gain in QALYs and, due to cost savings, dominated SD in the CUA. The PSA indicated that IIV-HD is 89% likely to be cost saving. In Canada, IIV-HD is expected to be a less costly and more effective alternative to SD, driven by a reduction in hospitalizations

The broad-spectrum activity of perampanel: state of the art and future perspective of AMPA antagonism beyond epilepsy

Glutamate is the brain’s main excitatory neurotransmitter. Glutamatergic neurons primarily compose basic neuronal networks, especially in the cortex. An imbalance of excitatory and inhibitory activities may result in epilepsy or other neurological and psychiatric conditions. Among glutamate receptors, AMPA receptors are the predominant mediator of glutamate-induced excitatory neurotransmission and dictate synaptic efficiency and plasticity by their numbers and/or properties. Therefore, they appear to be a major drug target for modulating several brain functions. Perampanel (PER) is a highly selective, noncompetitive AMPA antagonist approved in several countries worldwide for treating different types of seizures in various epileptic conditions. However, recent data show that PER can potentially address many other conditions within epilepsy and beyond. From this perspective, this review aims to examine the new preclinical and clinical studies—especially those produced from 2017 onwards—on AMPA antagonism and PER in conditions such as mesial temporal lobe epilepsy, idiopathic and genetic generalized epilepsy, brain tumor-related epilepsy, status epilepticus, rare epileptic syndromes, stroke, sleep, epilepsy-related migraine, cognitive impairment, autism, dementia, and other neurodegenerative diseases, as well as provide suggestions on future research agenda aimed at probing the possibility of treating these conditions with PER and/or other AMPA receptor antagonists

Seca dos ponteiros do eucalipto em Arapoti-PR.

Em 1988 e 1992, no municipio de Arapoti-PR, foram efetuados os primeiros registros da ocorrencia, em arvores de Eucalyptus grandis, de uma anomalia de crescimento denominada Seca dos Ponteiros de Eucalipto do Vale do Rio Doce (SPEVRD), apesar de que apenas a SPEA manifesta sintomas em plantas com idade inferior a sete meses e ocorre indistintamente em plantios de topos, encostas e baixadas. Com o presente trabalho procurou-se definir os componentes do mecanismo que desencadeia a SPEA, identificar respectivas interacoes e contribuicoes na manifestacao de sintomas. Pretendeu-se, assim, contribuir para a visao interativa e para o controle da SPEA e anomalias semelhantes. O trabalho foi conduzido em areas da INPACEL e, em laboratorios e casa de vegetacao da Embrapa/Florestas. As arvores com Spea reuniram sintomas, sinais e disturbios que evidenciaram ou sugeriram bloqueios na movimentacao e/ou na sintese de materia ou seja, disturbios no intercambio interno de agua, ions e hormonios, tais sejam: (a) injurias, intumecimentos, fissuras, cancros, anelamentos e oviposicao de insetos, atingindo tecidos vasculares, (b) granulos, estruturas de fungos e bacterias como agentes potenciais foliares, baixos de Ca, Mg e N incrementando o potencial injurioso do excesso de Cu e (d) como consequencias, dos eventos anteriores, geonastia dos ponteiros, brotacoes epicormicas, proliferacoes de ramos, malformacoes e manchas foliares. As analises estatisticas associaram a dispersao de insetos principalmente da ordem Thysanoptera..

MicroRNA expression profiles in pediatric dysembryoplastic neuroepithelial tumors.

© Springer Science+Business Media New York 2015Among noncoding RNAs, microRNAs (miRNAs) have been most extensively studied, and their biology has repeatedly been proven critical for central nervous system pathological conditions. The diagnostic value of several miRNAs was appraised in pediatric dysembryoplastic neuroepithelial tumors (DNETs) using miRNA microarrays and receiving operating characteristic curves analyses. Overall, five pediatric DNETs were studied. As controls, 17 samples were used: the FirstChoice Human Brain Reference RNA and 16 samples from deceased children who underwent autopsy and were not present with any brain malignancy. The miRNA extraction was carried out using the mirVANA miRNA Isolation Kit, while the experimental approach included miRNA microarrays covering 1211 miRNAs. Quantitative real-time polymerase chain reaction was performed to validate the expression profiles of miR-1909* and miR-3138 in all samples initially screened with miRNA microarrays. Our findings indicated that miR-3138 might act as a tumor suppressor gene when down-regulated and miR-1909* as a putative oncogenic molecule when up-regulated in pediatric DNETs compared to the control cohort. Subsequently, both miRNA signatures might serve as putative diagnostic biomarkers for pediatric DNETs.Peer reviewedFinal Accepted Versio

Perampanel Confirms to Be Effective and Well-Tolerated as an Add-On Treatment in Patients With Brain Tumor-Related Epilepsy (PERADET Study)

Background: Epilepsy is one of the most common symptoms of brain tumors. It is often drug resistant and generally worsen patients' quality of life (QoL). Brain tumors release glutamate among other mediators, contributing to seizures onset, and this is accompanied by an increased AMPA receptors' expression on neuronal cells' membrane. Perampanel (PER) is a relatively new antiseizure medication (ASM) that acts as a selective non-competitive AMPA receptors' antagonist. Given its mechanism of action, we aimed to evaluate through a prospective, observational study, the efficacy and safety of PER as an add-on treatment in patients with brain tumor-related epilepsy (BTRE). The study was called PERADET. Methods: Thirty-six adult patients (intention to treat population-ITT) affected by BTRE, with uncontrolled focal-onset seizures treated with 1–3 ASMs were recruited from four Italian epilepsy centers. Perampanel was added-on, titrated from 2 mg/day up to a maximum of 12 mg/day. Tumor history and therapy, type, and seizures frequency, previous ASMs were collected at 6 and 12 months. A battery of QoL tests were administered at baseline, 6 and 12 months. The primary endpoint was to assess the efficacy of PER by calculating the percent change in seizure frequency and the responder rate. The secondary endpoints were tolerability, retention rate at 12 months, and improvement in quality of life. Results: At the end of 12 months, 21 patients (per protocol population-PP) were available for evaluation. In this population the responder rate (percentage of patients who experienced a 50% or greater reduction in seizure frequency) was 90.4 with 33.3% of patients being seizure-free. In the ITT group the responder rate at the end of 12 months was 66.6 with 25% of patients being seizure free. PER was well tolerated (30.6% of patients experienced an adverse event, none was severe; three needed a treatment interruptions). Conclusions: Our study indicate that PER may be efficacious against BTRE as suggested by its mechanism of action and our current knowledge on mechanisms of brain tumor epileptogenicity. Trial Registration Number (TRN): (Prot. n° 0008872.25-06-2019); RS 919/17

Coeficientes de cultivo do feijão-caupi em sistemas monocultivo e consorciado com milho.

O presente trabalho teve por objetivo determinar o Kc do feijão-caupi em cultivo solteiro e consorciado com o milho, em seus diferentes estádios de desenvolvimento, visando ao manejo racional da irrigação e a definição de parâmetros para o zoneamento de risco climático de culturas consorciadas...1 CD-ROM

autologous pancreatic islet transplantation in human bone marrow diabetes 2013 62 3523 3531

In the article listed above, there is an error in Fig. 3. In panel B , the immunohistochemical staining of insulin ( top middle panel