Fremanezumab for the Preventive Treatment of Chronic Migraine.

BACKGROUND: Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP), is being investigated as a preventive treatment for migraine. We compared two fremanezumab dose regimens with placebo for the prevention of chronic migraine. METHODS: In this phase 3 trial, we randomly assigned patients with chronic migraine (defined as headache of any duration or severity on ≥15 days per month and migraine on ≥8 days per month) in a 1:1:1 ratio to receive fremanezumab quarterly (a single dose of 675 mg at baseline and placebo at weeks 4 and 8), fremanezumab monthly (675 mg at baseline and 225 mg at weeks 4 and 8), or matching placebo. Both fremanezumab and placebo were administered by means of subcutaneous injection. The primary end point was the mean change from baseline in the average number of headache days (defined as days in which headache pain lasted ≥4 consecutive hours and had a peak severity of at least a moderate level or days in which acute migraine-specific medication [triptans or ergots] was used to treat a headache of any severity or duration) per month during the 12 weeks after the first dose. RESULTS: Of 1130 patients enrolled, 376 were randomly assigned to fremanezumab quarterly, 379 to fremanezumab monthly, and 375 to placebo. The mean number of baseline headache days (as defined above) per month was 13.2, 12.8, and 13.3, respectively. The least-squares mean (±SE) reduction in the average number of headache days per month was 4.3±0.3 with fremanezumab quarterly, 4.6±0.3 with fremanezumab monthly, and 2.5±0.3 with placebo (P CONCLUSIONS: Fremanezumab as a preventive treatment for chronic migraine resulted in a lower frequency of headache than placebo in this 12-week trial. Injection-site reactions to the drug were common. The long-term durability and safety of fremanezumab require further study. (Funded by Teva Pharmaceuticals; ClinicalTrials.gov number, NCT02621931 .)

Desarrollo de anticuerpos e interrelación leptospirosis y rinotraqueitis en ganado de carne en los Llanos de Colombia.

Ganado de carne-Ganadería carn

First-in-human, double-blind, placebo-controlled, randomized, dose-escalation study of BG00010, a glial cell line-derived neurotrophic factor family member, in subjects with unilateral sciatica

OBJECTIVE: To evaluate the safety, tolerability, and pharmacokinetics of single doses of BG00010 (neublastin, artemin, enovin) in subjects with unilateral sciatica. METHODS: This was a single-center, blinded, placebo-controlled, randomized Phase 1 sequential-cohort, dose-escalation study (ClinicalTrials.gov identifier NCT00961766; funded by Biogen Idec). Adults with unilateral sciatica were enrolled at The Royal Adelaide Hospital, Australia. Four subjects were assigned to each of eleven cohorts (intravenous BG00010 0.3, 1, 3, 10, 25, 50, 100, 200, 400, or 800 μg/kg, or subcutaneous BG00010 50 μg/kg) and were randomized 3:1 to receive a single dose of BG00010 or placebo. The primary safety and tolerability assessments were: adverse events; clinical laboratory parameters and vital signs; pain as measured by a Likert rating scale; intra-epidermal nerve fiber density; and longitudinal assessment of quantitative sensory test parameters. Blood, serum, and plasma samples were collected for pharmacokinetic and pharmacodynamic assessments. Subjects were blinded to treatment assignment throughout the study. The investigator was blinded to treatment assignment until the Data Safety Review Committee review of unblinded data, which occurred after day 28. RESULTS: Beyond the planned enrollment of 44 subjects, four additional subjects were enrolled into to the intravenous BG00010 200 μg/kg cohort after one original subject experienced mild generalized pruritus. Therefore, a total of 48 subjects were enrolled between August 2009 and December 2011; all were included in the safety analyses. BG00010 was generally well tolerated: in primary analyses, the most common treatment-emergent adverse events were changes in temperature perception, pruritus, rash, or headache; no trends were observed in clinical laboratory parameters, vital signs, intra-epidermal nerve fiber density, or quantitative sensory testing. BG00010 was not associated with any clear, dose-dependent trends in Likert pain scores. BG00010 was rapidly distributed, with a prolonged terminal elimination phase. CONCLUSIONS: These data support the development of BG00010 for the treatment of neuropathic pain. TRIAL REGISTRATION: ClinicalTrials.gov NCT00961766.Paul E. Rolan, Gilmore O, Neill, Eve Versage, Jitesh Rana, Yongqiang Tang, Gerald Galluppi, Ernesto Aycard

Níveis de anticorpos anti-Babesia Bigemina e Babesia bovis em bezerros da raça Nelore, Ibagé e cruzamentos de nelore.

Foram analisados pela tecnica de anticorpos fluorescentes, os soros dos bezerros da raca Nelore, Ibage e cruzamentos de Nelore x Fleckvieh, Nelore x chianina e Nelore x Charoles, do nascimento ao desmame, com a finalidade de determinar os niveis de imunoglobolinas anti-Babesia bigemina e Babesia bovis. No periodo de tres a quatorze dias de vida foi observa correlacao positiva e significnate entre os niveis de imunoglobulinas circulantes das vacas e os anticorpos serios dos bezerros contra B. bigemina e/ou B. bovis, em algumas racas e cruzamentos. A media do titulo sorologico dos grupos experimentais apresentou um descrecimo nos niveis de anticorpos colostrais entre 28 e 56 dias de idade contra B. bigemina e entre 56 e 84 dias anti-B.bovis. A producao ativa deanticorpos contra B bigemina foi observada aos 84 dias e aos 112 contra B.bovis. Em geral os niveis de anticorpos anti-B bigemina foram mais elevados que o da B. bovis e houve maior semelhanca na curva de anticorpos dos bezerros da raca Nelore e seus cruzamentos que os da raca Ibage. Embora a regiao seja considerada area de estabilidade enzootica, conclui-se que existe um periodo critico de baixa resistencia humural, no qual podem ocorrer casos clinicos de babesiose.Título em inglês: Antibody levels anti-babesia bigemina and babesia bovis in calves of Nelore and Ibagé breeds and Nelore crosses

Efficacy and Safety of XEN1101, a Novel Potassium Channel Opener, in Adults with Focal Epilepsy A Phase 2b Randomized Clinical Trial

IMPORTANCE Many patients with focal epilepsy experience seizures despite treatment with currently available antiseizure medications (ASMs) and may benefit from novel therapeutics. OBJECTIVE To evaluate the efficacy and safety of XEN1101, a novel small-molecule selective Kv7.2/Kv7.3 potassium channel opener, in the treatment of focal-onset seizures (FOSs). DESIGN, SETTING, AND PARTICIPANTS This phase 2b, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging adjunctive trial investigated XEN1101 over an 8-week treatment period from January 30, 2019, to September 2, 2021, and included a 6-week safety follow-up. Adults experiencing 4 or more monthly FOSs while receiving stable treatment (1-3 ASMs) were enrolled at 97 sites in North America and Europe. INTERVENTIONS Patients were randomized 2:1:1:2 to receive XEN1101, 25, 20, or 10mg, or placebo with food once daily for 8 weeks. Dosage titration was not used. On completion of the double-blind phase, patients were offered the option of entering an open-label extension (OLE). Patients not participating in the OLE had follow-up safety visits (1 and 6 weeks after the final dose). MAIN OUTCOMES AND MEASURES The primary efficacy end pointwas the median percent change from baseline in monthly FOS frequency. Treatment-emergent adverse events (TEAEs) were recorded and comprehensive laboratory assessments were made. Modified intention-to-treat analysis was conducted. RESULTS A total of 325 patients who were randomized and treated were included in the safety analysis; 285 completed the 8-week double-blind phase. In the 325 patients included, mean (SD) age was 40.8 (13.3) years, 168 (51.7%) were female, and 298 (91.7%) identified their race as White. Treatment with XEN1101 was associated with seizure reduction in a robust dose-response manner. The median (IQR) percent reduction from baseline in monthly FOS frequency was 52.8%(P < .001 vs placebo; IQR, -80.4%to -16.9%) for 25mg, 46.4% (P < .001 vs placebo; IQR, -76.7%to -14.0%) for 20mg, and 33.2%(P = .04 vs placebo; IQR, -61.8%to 0.0%) for 10mg, compared with 18.2%(IQR, -37.3%to 7.0%) for placebo. XEN1101 was generally well tolerated and TEAEs were similar to those of commonly prescribed ASMs, and no TEAEs leading to death were reported. CONCLUSIONS AND RELEVANCE The efficacy and safety findings of this clinical trial support the further clinical development of XEN1101 for the treatment of FOSs

Pharmacokinetics and pharmacodynamics of multiple doses of BG00010, a neurotrophic factor with anti-hyperalgesic effects, in patients with sciatica

AIMS: BG00010 is a protein in the glial cell line-derived neurotrophic factor (GDNF) family. It is a selective ligand for the GDNF family receptor alpha-3 (GFRα3) co-receptor that normalizes cellular changes resulting from damage or disease, and potentially alleviates neuropathic pain. The main objectives of this study were to evaluate the pharmacokinetic and safety profiles and to determine the effects on pain of ascending doses of intravenous injections of BG00010 in patients with sciatica.METHODS: This was a randomized, blinded, placebo-controlled multiple-dose study in subjects with sciatica. In Part I (16 patients), four IV dose levels were examined (50, 150, 400, 800 μg kg(-1) ) and in Part II (12 patients), three dose levels were examined (400, 600 and 1200 μg kg(-1) ). Safety and efficacy assessments were used as endpoints.RESULTS: The BG00010 concentration-time data indicated relatively low inter-patient variability and there was a dose-dependent (not dose-proportional) increase in serum exposure from 150 to 1200 μg kg(-1) . The effective half-life was between 40 and 60 h. The most frequently occurring adverse events (AEs) reported by patients receiving BG00010 were headache (67-83%), feeling hot (50-100%), and pruritus (42-67%). Most AEs were mild; no serious AEs or AEs leading to discontinuation occurred. Higher dose regimens of BG00010 resulted in greater pain reduction than placebo or lower dose regimens, although a clear dose-response relationship was not seen.CONCLUSIONS: The pharmacokinetic profile of BG00010 was characterized by low intra-patient variability. These data from a small sample suggest that BG00010 may have a benefit for patients with sciatica.TRIAL REGISTRATION: ClinicalTrials.gov NCT00961766 NCT01405833.Perioperative Medicine: Efficacy, Safety and Outcom

Perceptions about the biology of Rhipicephalus (Boophilus) microplus among milk producers in Divinópolis, Minas Gerais

One hundred semi-systematized interviews were applied with the aim of surveying the perceptions of milk producers in the municipality of Divinópolis, Minas Gerais regarding the biology of the tick Rhipicephalus (Boophilus) microplus. Content analysis was conducted on each of the variables surveyed and their descriptions, highlighting the higher frequencies in order to construct profiles of perceptions about each of the matters surveyed. In addition, each of the producers was categorized regarding their readiness to proceed with efficient control, from the assessment of their responses. Among the variables surveyed were the tick lifespan, duration of parasitic life, time of greatest incidence, survival in pastures and egg-laying volume. These questions are considered important for defining the knowledge needed for rational combat. It was concluded that the information needed for adopting effective practices to combat ticks was insufficient among the milk farm properties in Divinópolis. Moreover, the producers interviewed had a good perception of what they observed in their daily routine, but did not have complementary information about the tick life cycle

PATHOGENY OF AVIAN COCCIDIOSIS : BIOMETRICAL ANALYSIS AND EXPERIMENTAL STUDY OF NON SPECIFIC RESISTANCE

International audienc

Preservación de la patogenicidad de Beauveria bassiana (Bálsamo) Vuillemin (Moniliales Moniliaceae) contra la broca del café en diferentes sistemas

The objective of this study is to find preservation techniques of Beauveria bassiana pathogenicity in the laboratory. Long term storage of B. bassiana cultures is very important to prepare industrial products. Preservation techniques for pathogenicity would replace the need to pass B. bassiana spores frequently in the target insect. Studies on B. bassiana pathogenicity are almost nonexistent. Viability of B. bassiana was evaluated in comparison with pathogenicity when subjected to different preservation temperatures with various protectors. The most succesful procedures were silica gel and mineral oil in refrigeration; glicerol and dimethilsulfoxide in liquid nitrogen; liophilization with skim milk at 10% and 20% and skim milk with inositol at 5%. The tests were carried our during 24 weeks at 6 weeks intervals. A monosporic B. bassiana culture (Bb. 9620) isolated by Cenicafé research center was used for the study. The mean value for the preservation of pathogenicity was influenced by the protectors used.Este trabajo tiene como objetivo evaluar técnicas de preservación de patogenicidad en el laboratorio, que permitan almacenar por tiempos prolongados cultivos de B. bassiana de manera que se puedan utilizar en la preparación de un producto industrial sin tener que recurrir tan frecuentemente a pases sobre poblaciones de Hypothenemus hampei (Ferrari) (Coleóptera: Scolytidae) para mantener su efectividad en el control de esta plaga. Existen numerosos trabajos sobre la preservación de la viabilidad, pero prácticamente son inexistentes los trabajos sobre la preservación de la patogenicidad de B. bassiana. Se evaluó la viabilidad de B. Bassiana, en comparación con su patogenicidad, en cultivos madres sometidos a diferentes temperaturas de preservación con silica gel anhidra y aceite mineral para refrigeración, glicerol y dimetilsulfóxido para preservación en nitrógeno líquido y leche descremada al 10% y 20%, leche descremada con inositol al 5%, y dos medios de cultivo de un centro de referencia internacional como protectores para la preservación por liofilización. Durante 24 semanas, cada 6 semanas se realizaron las evaluaciones. En el análisis inferencial, donde se compararon los protectores de conservación y sistemas de conservación versus patogenicidad y viabilidad, se encontró que sí existen diferencias significativas y que los protectores influyen en la preservación de la patogenicidad, principalmente