Formulation and Stability Study of Eslicarbazepine Acetate Oral Suspensions for Extemporaneous Compounding

Eslicarbazepine acetate is an anticonvulsant drug with a recent U.S. Food and Drug Administration approval for expanded use in children and adolescents. Currently, eslicarbazepine acetate is only available in the U.S. as 200-mg to 800-mg strength tablets (Aptiom), which are not easy to administer for pediatric patients. This study was initiated to develop an oral suspension formulation for extemporaneous compounding by pharmacists and to generate stability data for storage recommendations. Nine suspension formulations of eslicarbazepine acetate were prepared from Aptiom tablets and commercially available liquid vehicles using the standard mortar/pestle method. The vehicles varied mainly in their solvents, viscosities, and sweeteners. The formulations were evaluated for ease of preparation, physical properties, and initial potency. Two lead formulations were selected for a two-month stability study at room temperature or under refrigeration (2°C to 8°C). The stability samples were withdrawn at pre-determined time points and analyzed by visual inspection, pH measurement, and a stability-indicating high-performance liquid chromatographic assay. The majority of the 9 formulations were found to be easy to prepare and administer at a concentration of 40-mg/mL eslicarbazepine acetate. Particle settling was observed in several formulations over time, but they were re-suspended satisfactorily upon shaking. Two suspensions in 50:50 v/v mixtures of Ora-Sweet or Ora-Sweet SF with Ora-Plus were selected as the lead formulations for the two-month stability study. At the initiation of the study, all samples appeared as white and smooth suspensions with pH ranging from 4.39 to 4.46. The high-performance liquid chromatographic results confirmed that the initial samples contained 100.4% to 102.2% of the label claim strength. Over two months of storage at room temperature or refrigeration, there were no significant changes in visual appearance, re-suspendability, pH, or potency for any samples. No new degradation peaks were observed in any highperformance liquid chromatograms. Based on the study results, two eslicarbazepine acetate suspensions are recommended for extemporaneous compounding from Aptiom tablets. The formulations consist of 40 mg/mL eslicarbazepine acetate in 50:50 v/v Ora-Sweet:Ora-Plus or Ora-Sweet SF:Ora-Plus. Once prepared, these suspensions can be stored at room temperature or under refrigeration for up to two months

Design and numerical evaluation of full-authority flight control systems for conventional and thruster-augmented helicopters employed in NOE operations

The development and methodology is presented for development of full-authority implicit model-following and explicit model-following optimal controllers for use on helicopters operating in the Nap-of-the Earth (NOE) environment. Pole placement, input-output frequency response, and step input response were used to evaluate handling qualities performance. The pilot was equipped with velocity-command inputs. A mathematical/computational trajectory optimization method was employed to evaluate the ability of each controller to fly NOE maneuvers. The method determines the optimal swashplate and thruster input histories from the helicopter's dynamics and the prescribed geometry and desired flying qualities of the maneuver. Three maneuvers were investigated for both the implicit and explicit controllers with and without auxiliary propulsion installed: pop-up/dash/descent, bob-up at 40 knots, and glideslope. The explicit controller proved to be superior to the implicit controller in performance and ease of design

Endovascular repair for acute traumatic transection of the descending thoracic aorta: experience of a single centre with a 12-years follow up

Background: Most blunt aortic injuries occur in the proximal proximal descending aorta causing acute transection of this vessel. Generally, surgical repair of the ruptured segment of aorta is associated with high rates of morbidity and mortality and in this view endovascular treatment seems to be a valid and safer alternative. Aim of this article is to review our experience with endovascular approach for the treatment of acute traumatic rupture of descending thoracic aorta. Methods: From April 2002 to November 2014, 11 patients (9 males and 2 females) were referred to our Department with a diagnosis of acute transection of thoracic aorta. Following preoperative Computed Tomography (CT) evaluation, thoracic endovascular aortic repair (TEVAR) with left subclavian artery coverage was performed. Follow-up consisted clinical and instrumental (CT, Duplex ultrasound) controls at discharge, 1, 3 and 6 months and yearly thereafter. Results: At 12-year follow up, the overall survival for the entire patients cohort was 100 %, no major or minor neurological complications and no episode of left arm claudication occurred. Cardiovascular, respiratory and bleeding complications, in the early period, was represented by minor, non fatal events. No stent graft failure, collapse, leak or distal migration were detected at CT scan during the entire follow up period. Conclusions: According to our experience, despite the small number of patient population, TEVAR procedure with with left subclavian artery coverage, performed in emergency settings, seems to provide excellent long term results. Trials registration: The protocol was registered at a public trials registry, www.clinicaltrials.gov (trial identifier NCT02376998)

Benefits and Risks of Weight-Loss Treatment for Older, Obese Women

Background: A key issue in the treatment of obesity in older adults is whether the health benefits of weight loss outweigh the potential risks with respect to musculoskeletal injury. Objective: To compare change in weight, improvements in metabolic risk factors, and reported musculoskeletal adverse events in middle-aged (50-59 years) and older (65-74 years), obese women. Materials and methods: Participants completed an initial 6-month lifestyle intervention for weight loss, comprised of weekly group sessions, followed by 12 months of extended care with biweekly contacts. Weight and fasting blood samples were assessed at baseline, month 6, and month 18; data regarding adverse events were collected throughout the duration of the study. Results: Both middle-aged (n = 162) and older (n = 56) women achieved significant weight reductions from baseline to month 6 (10.1 +/- 0.68 kg and 9.3 +/- 0.76 kg, respectively) and maintained a large proportion of their losses at month 18 (7.6 +/- 0.87 kg and 7.6 +/- 1.3 kg, respectively); there were no significant differences between the two groups with respect to weight change. Older women further experienced significant reductions in systolic blood pressure, HbA(1c), and C-reactive protein from baseline to month 6 and maintained these improvements at month 18. Despite potential safety concerns, we found that older women were no more likely to experience musculoskeletal adverse events during the intervention as compared with their middle-aged counterparts. Conclusion: These results suggest that older, obese women can experience significant health benefits from lifestyle treatment for obesity, including weight loss and improvements in disease risk factors. Further investigation of the impact of weight loss on additional health-related parameters and risks (eg, body composition, muscular strength, physical functioning, and injuries) in older adults is needed.National Heart, Lung and Blood Institute R18HL73326University of FloridaDivision of Statistics and Scientific Computatio

A cross-sectional study on prevalence and predictors of burnout among a sample of pharmacists employed in pharmacies in Central Italy

Burnout is defined as an occupational phenomenon linked to chronic workplace stress that has not been successfully managed and included among the factors influencing health status or contact with health services. Although several studies were performed for assessing this phenomenon, there is a lack of data on the prevalence of burnout and associated predictors, due to different definitions of the syndrome and heterogeneity of assessment methods. One of the well-known evidences on burnout is related to the highest risk professions, which include policemen, firemen, teachers, psychologists, medical students, nurses, physicians, and other health professionals, such as pharmacists. Objective. The aims of the present study were to (1) assess the occurrence of burnout syndrome among a sample of pharmacists employed in public and private pharmacies located in Rome province (Latium Region; central Italy); (2) evaluate the role of some potential predictors for the development of the syndrome. Materials and Methods. A questionnaire elaborated ad hoc was administered online to 2,000 members of the Association of Professional Pharmacists of Rome and its province and employed in public or private pharmacies. The questionnaire included the 14-item Shirom-Melamed Burnout Measure (SMBM) tool and questions on demographic characteristics and working conditions. Results. Physical exhaustion was the burnout dimension with the highest score; besides, approximately 11% of the studied pharmacists were categorized as having clinically relevant burnout levels (≥4.40). Several of the investigated variables significantly influenced the single burnout dimensions at the univariate analyses; multivariate analyses demonstrated that alcohol consumption and workplace location have a significant independent role on the overall SMBM index, while working time significantly influences clinically relevant burnout level. Conclusions. The results revealed that pharmacists are at risk of burnout, and thus, it is necessary to perform specific preventive intervention for managing this occupational threat

The 26 year-long X-ray light curve and the X-ray spectrum of the BL Lac Object 1E 1207.9+3945 in its brightest state

We studied the temporal and spectral evolution of the synchrotron emission from the high energy peaked BL Lac object 1E 1207.9+3945. Two recent observations have been performed by the XMM-Newton and Swift satellites; we carried out X-ray spectral analysis for both of them, and photometry in optical-ultraviolet filters for the Swift one. Combining the results thus obtained with archival data we built the long-term X-ray light curve, spanning a time interval of 26 years, and the Spectral Energy Distribution (SED) of this source. The light curve shows a large flux increasing, about a factor of six, in a time interval of a few years. After reaching its maximum in coincidence with the XMM-Newton pointing in December 2000 the flux decreased in later years, as revealed by Swift. The very good statistics available in the 0.5-10 keV XMM-Newton X-ray spectrum points out a highly significant deviation from a single power law. A log-parabolic model with a best fit curvature parameter of 0.25 and a peak energy at ~1 keV describes well the spectral shape of the synchrotron emission. The simultaneous fit of Swift UVOT and XRT data provides a milder curvature (b~0.1) and a peak at higher energies (~15 keV), suggesting a different state of source activity. In both cases UVOT data support the scenario of a single synchrotron emission component extending from the optical/UV to the X-ray band. New X-ray observations are important to monitor the temporal and spectral evolution of the source; new generation gamma-ray telescopes like AGILE and GLAST could for the first time detect its inverse Compton emission.Comment: 7 pages, 6 figures, accepted for publication in A&

Log-parabolic spectra and particle acceleration in blazars - II: The BeppoSAX wide band X-ray spectra of Mkn 501

We present the results of a spectral and temporal study of the complete set of BeppoSAX NFI (11) and WFC (71) observations of the BL Lac object Mkn 501. The WFC 2-28 keV data, reported here for the first time, were collected over a period of about five years, from September 1996 to October 2001. These observations, although not evenly distributed, show that Mkn 501, after going through a very active phase from spring 1997 to early 1999, remained in a low brightness state until late 2001. The data from the LECS, MECS and PDS instruments, covering the wide energy interval 0.1-150 keV, have been used to study in detail the spectral variability of the source. We show that the X-ray energy distribution of Mkn 501 is well described by a log-parabolic law in all luminosity states. This model allowed us to obtain good estimates of the SED synchrotron peak energy and of its associated power. The strong spectral variability observed, consisting of strictly correlated changes between the synchrotron peak energy and bolometric flux, suggests that the main physical changes are not only due to variations of the maximum Lorentz factor of the emitting particles but that other quantities must be varying as well. During the 1997 flare the high energy part of the spectrum of Mkn 501 shows evidence of an excess above the best fit log-parabolic law suggesting the existence of a second emission component that may be responsible for most of the observed variability.Comment: Accepted for publication in Astronomy & Astrophysics (11 pages, 7 figures