Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

Background Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. Methods Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. Results A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). Conclusions Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Arrythmic markers affected by clozapine treatment in patients with schizophrenia: heart rate variability, late potentials and QT dispersion

Magnetic quadrupole moment of $W$-boson in Kobayashi-Maskawa model, I.B.Khriplovich and M.E. Pospelov, BUDKERINP 93--88 Due to CP-invariance violationa vector particle can acquire T- and P-odd electromagnetic moment, magneticquadrupole one. The W-boson magnetic quadrupole moment is calculated in theKobayashi-Maskawa model. This is the only known CP-odd moment arising in thismodel in two-loop approximation

Cochlear and vestibular effects of combined intratympanic gentamicin and dexamethasone

OBJECTIVE: The aim of this study is to evaluate the effects of an intratympanic gentamicin-dexamethasone combination on the inner ear. MATERIALS and METHODS: Twenty-six Wistar albino rats were divided into four groups: Group I (Control), group II (Intratympanic dexamethasone; ITD), group III (Intratympanic gentamicin; ITG), and group IV (Intratympanic gentamicin and dexamethasone; ITGD). On the first day after basal auditory brainstem response (ABR) measurements, the ITG group received 0.03 mL of intratympanic gentamicin (26.7 mg/mL). Intratympanic injection of 0.06 mL of a solution containing 13.35 mg/mL gentamicin and 2 mg/mL dexamethasone was performed in the ITGD group. 0.03 mL of physiological intratympanic serum and dexamethasone (4 mg/mL) was applied in control and ITD groups, respectively. On the 7th day, ABR measurements were repeated and vestibular functions were evaluated. On the 21th day, ABR and vestibular tests were repeated, and the animals were sacrificed for histopathological investigation. RESULTS: The ITG group’s hearing thresholds deteriorated in all frequencies. The ITGD group’s hearing thresholds were significantly better than the ITG group, except at 8 kHz on the 7th day and in all frequencies at the 21th day measurements. The vestibular function scores of the ITG and ITGD groups were higher than the controls. Apoptotic changes were seen in cochlea, spiral ganglion, and vestibule of the ITG group. Cochlear and vestibular structures were well preserved in the ITGD group, similar to the controls. CONCLUSION: The ITGD combination led to a significant hearing preservation. Although in subjective vestibular tests, it seemed that vestibulotoxicity was present in both ITG and ITGD groups the histopathological investigations revealed no signs of vestibulotoxicity in the ITGD group in contrast to the ITG group. Further studies using a combination of different concentrations of gentamicin and dexamethasone are needed

Identificación de necesidades de intervención psicológica: estudio piloto en la educación superior portuguesa

Este estudo analisa as necessidades de intervenção psicológica dos estudantes da Faculdade de Ciências Humanas da Universidade Católica Portuguesa. Participaram 157 alunos, avaliados nas suas preocupações e necessidades pessoais, de carreira e de aprendizagem, bem como nas preferências relativas ao apoio, por meio do questionário de identificação de necessidades de intervenção psicológica. Os resultados indicam necessidade de apoio nas áreas: (i) controlo de ansiedade e nervosismo, (ii) medo de falhar, (iii) estratégias de procura de emprego, (iv) escolha de uma carreira e (v) competências de gestão do tempo. Verifica-se uma preferência, no apoio pretendido, pelas modalidades de aconselhamento individual e cursos breves. Registram-se diferenças em função do sexo, da média no curso, da regularidade de contato com a família e dos níveis de satisfação acadêmica e satisfação global com a vida. Retiram-se implicações para a disponibilização de sistemas, estratégias e atividades de apoio psicológico que possam responder às preocupações dos estudantes.This study aims to explore the psychological intervention needs of the students attending the Faculty of Human Sciences of the Portuguese Catholic University. 157 students were evaluated on their personal, career and learning needs and concerns, as well as on their possible support preferences, through the questionnaire of identification of psychological intervention needs. The results indicate that participants need more information or support in the following areas: (i) management of anxiety and nervousness, (ii) fear of failure, (iii) job search, (iv) career choice and (v) time management skills. There is a preference for individual counseling and workshops. There are differences according to sex, academic grades, regularity of family contact and academic and global life satisfaction. Implications are drawn for the availability of systems, strategies and activities of psychological support for students that can respond appropriately to their different needs.Cette étude vise à explorer le besoin d’intervention psychologique des élèves qui fréquentent la Faculté des Sciences Humaines de l’Université Catholique Portugaise. Ont participé 157 étudiants lesquels ont été évalués sur leurs besoins et préoccupations personnelles, de carrière et d’apprentissage, ainsi que sur leur préférences concernant le support désiré et déjà reçu, à travers The Survey of Student Needs. Les résultats indiquent que les participants ont besoin de plus d’information et d’un appui dans les domaines suivants: (i) gérer l’anxiété et la nervosité, (ii) la peur de l’échec, (iii) les stratégies de recherche d’emploi, (iv) le choix d’une carrière, et (v) des compétences pour la gestion du temps. On remarque une préférence pour le conseil individuel et les cours de courte durée . On remarque des différences selon le sexe, le grade universitaire, la régularité du contact avec la famille et la satisfaction avec la vie universitaire et la vie en général. Les résultats évoquent la création des systèmes, stratégies et activités de soutien psychologique, qui puissent répondre à les différentes préoccupations des étudiants.Este estudio tiene como objetivo explorar las necesidades de intervención psicológica de los estudiantes de la Facultad de Ciencias Humanas de la Universidad Católica Portuguesa. Participaron 157 estudiantes, se les evaluaron sus necesidades y preocupaciones, así como las preferencias relacionadas con el apoyo deseado y previamente recibido de la carrera y del aprendizaje, a través del cuestionario de identificación de las necesidades de intervención psicológica. Los resultados indican que los participantes necesitan más información o ayuda en las siguientes áreas: (i) manejo de la ansiedad y del nerviosismo, (ii) miedo al fracaso, (iii) estrategias de búsqueda de empleo, (iv) elección de una carrera y (v) habilidades de gestión del tiempo. Hay una preferencia por asesoramiento individual y cursos cortos. Existen diferencias en función del sexo, grado académico, regularidad de contacto con la familia y satisfacción con la vida académica y global. De los resultados provienen implicaciones para la disponibilidad de sistemas, estrategias y actividades de apoyo psicológico para que los estudiantes puedan contestar adecuadamente a sus diferentes intereses.(undefined)info:eu-repo/semantics/publishedVersio