Longitudinal Results With Intratympanic Dexamethasone in the Treatment of Ménière’s Disease

To assess patient satisfaction with vertigo control using intratympanic (IT) dexamethasone (12 mg/mL) for medically refractory unilateral Meniere's disease. STUDY DESIGN: Retrospective study. SETTING: Tertiary referral neurotology clinic. PATIENTS: One hundred twenty-nine subjects diagnosed with unilateral Meniere's disease still having vertigo despite medical therapy. INTERVENTION: IT dexamethasone injections as needed to control vertigo attacks. MAIN OUTCOME MEASURE: A Kaplan-Meier time-to-event method was used to determine the rate of "survival," meaning sufficient satisfaction with vertigo control that the subject did not wish to have subsequent ablative treatment. "Failure" was defined as poor control and the choice to proceed to ablative treatment. RESULTS: Acceptable vertigo control ("survival") was achieved in 117 (91%) of 129 subjects. Vertigo control required only one dexamethasone injection in 48 (37%), 2 injections in 26 (20%), 3 injections in 18 (14%), and 4 injections in 10 (8%). More than 4 injections were needed in 15 subjects (21%). Of 12 failures (9%), 9 occurred within 6 months of the first IT dexamethasone injection. Follow-up data for 2 years were available for 96 subjects. Of these, 87 (91%) had vertigo control with IT dexamethasone, of whom 61 (70)% required no further injections after 2 years, 23 (26%) continued to receive IT dexamethasone injections, and 3 (3%) chose IT gentamicin treatment. CONCLUSION: IT dexamethasone injection therapy on an as-needed outpatient basis can provide vertigo control that is satisfactory in patients with Meniere's disease. The Kaplan-Meier method addresses the need for an outcome measure suited to repeated treatments and variable lengths of follow-up. However, due to the retrospective nature of this study, the presence of bias caused by loss of subjects from follow-up cannot be ruled out

Hearing loss and satisfaction with healthcare: An unexplored relationship

Patient healthcare satisfaction has become increasingly important since Medicare’s introduction of the Hospital Care Quality Information from the Consumer Perspective (HCAHPS) survey. Greater satisfaction is associated with important healthcare outcomes including lower risk of 30-day readmission

Production of topological defects at the end of inflation

Hybrid inflation within supersymmetric grand unified theories, as well as inflation through brane collisions within braneworld cosmological models, lead to the formation of one-dimensional defects. Observational data, mainly from the cosmic microwave background temperature anisotropies but also from the gravitational wave background, impose constraints on the free parameters of the models. I review these inflationary models and discuss the constraints from the currently available data.Comment: 9 pages, Invited talk in the Conference "Challenges in Particle Astrophysics" -- 6th Rencontres du Vietnam, Hanoi (Vietnam) 6-12 Aug. 200

Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group

Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P<5 × 10−8), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis

Functional diversity of chemokines and chemokine receptors in response to viral infection of the central nervous system.

Encounters with neurotropic viruses result in varied outcomes ranging from encephalitis, paralytic poliomyelitis or other serious consequences to relatively benign infection. One of the principal factors that control the outcome of infection is the localized tissue response and subsequent immune response directed against the invading toxic agent. It is the role of the immune system to contain and control the spread of virus infection in the central nervous system (CNS), and paradoxically, this response may also be pathologic. Chemokines are potent proinflammatory molecules whose expression within virally infected tissues is often associated with protection and/or pathology which correlates with migration and accumulation of immune cells. Indeed, studies with a neurotropic murine coronavirus, mouse hepatitis virus (MHV), have provided important insight into the functional roles of chemokines and chemokine receptors in participating in various aspects of host defense as well as disease development within the CNS. This chapter will highlight recent discoveries that have provided insight into the diverse biologic roles of chemokines and their receptors in coordinating immune responses following viral infection of the CNS

Estimated pulse wave velocity (ePWV) as a potential gatekeeper for MRI-assessed PWV: a linear and deep neural network based approach in 2254 participants of the Netherlands Epidemiology of Obesity study

Pulse wave velocity (PWV) assessed by magnetic resonance imaging (MRI) is a prognostic marker for cardiovascular events. Prediction modelling could enable indirect PWV assessment based on clinical and anthropometric data. The aim was to calculate estimated-PWV (ePWV) based on clinical and anthropometric measures using linear ridge regression as well as a Deep Neural Network (DNN) and to determine the cut-off which provides optimal discriminative performance between lower and higher PWV values. In total 2254 participants from the Netherlands Epidemiology of Obesity study were included (age 45-65 years, 51% male). Both a basic and expanded prediction model were developed. PWV was estimated using linear ridge regression and DNN. External validation was performed in 114 participants (age 30-70 years, 54% female). Performance was compared between models and estimation accuracy was evaluated by ROC-curves. A cut-off for optimal discriminative performance was determined using Youden's index. The basic ridge regression model provided an adjusted R-2 of 0.33 and bias of < 0.001, the expanded model did not add predictive performance. Basic and expanded DNN models showed similar model performance. Optimal discriminative performance was found for PWV < 6.7 m/s. In external validation expanded ridge regression provided the best performance of the four models (adjusted R-2: 0.29). All models showed good discriminative performance for PWV < 6.7 m/s (AUC range 0.81-0.89). ePWV showed good discriminative performance with regard to differentiating individuals with lower PWV values (< 6.7 m/s) from those with higher values, and could function as gatekeeper in selecting patients who benefit from further MRI-based PWV assessment.Clinical epidemiolog

Potentiation of 5-fluorouracil encapsulated in zeolites as drug delivery systems for in vitro models of colorectal carcinoma

The studies of potentiation of 5-fluorouracil (5-FU), a traditional drug used in the treatment of several cancers, including colorectal (CRC), were carried out with zeolites Faujasite in the sodium form, with different particle sizes (NaY, 700nm and nanoNaY, 150nm) and Linde type L in the potassium form (LTL) with a particle size of 80nm. 5-FU was loaded into zeolites by liquid-phase adsorption. Characterization by spectroscopic techniques (FTIR, 1H NMR and 13C and 27Al solid-state MAS NMR), chemical analysis, thermal analysis (TGA), nitrogen adsorption isotherms and scanning electron microscopy (SEM), demonstrated the successful loading of 5-FU into the zeolite hosts. In vitro drug release studies (PBS buffer pH 7.4, 37°C) revealed the release of 80-90% of 5-FU in the first 10min. To ascertain the drug release kinetics, the release profiles were fitted to zero-order, first-order, Higuchi, Hixson-Crowell, Korsmeyer-Peppas and Weibull kinetic models. The in vitro dissolution from the drug delivery systems (DDS) was explained by the Weibull model. The DDS efficacy was evaluated using two human colorectal carcinoma cell lines, HCT-15 and RKO. Unloaded zeolites presented no toxicity to both cancer cells, while all DDS allowed an important potentiation of the 5-FU effect on the cell viability. Immunofluorescence studies provided evidence for zeolite-cell internalization.RA is recipient of fellowship SFRH/BI/51118/2010 from Fundacao para a Ciencia e a Tecnologia (FCT, Portugal). This work was supported by the FCT projects refs. PEst-C/QUI/UI0686/2011 and PEst-C/CTM/LA0011/2011 and the Centre of Chemistry and Life and Health Sciences Research Institute (University of Minho, Portugal). The NMR spectrometer is part of the National NMR Network (RNRMN), supported with funds from FCT/QREN (Quadro de Referencia Estrategico Nacional)