STARTVerso1: A Randomized Trial of Faldaprevir Plus Pegylated Interferon/Ribavirin for Chronic HCV Genotype-1 Infection

BACKGROUND & AIMS: The efficacy and tolerability of faldaprevir, a potent hepatitis C virus (HCV) NS3/4A protease inhibitor, plus peginterferon (PegIFN) and ribavirin (RBV) was assessed in a double-blind, placebo-controlled phase 3 study of treatment-naïve patients with HCV genotype-1 infection. METHODS: Patients were randomly assigned (1:2:2) to PegIFN/RBV plus: placebo (arm 1, n = 132) for 24 weeks; faldaprevir (120 mg, once daily) for 12 or 24 weeks (arm 2, n = 259); or faldaprevir (240 mg, once daily) for 12 weeks (arm 3, n = 261). In arms 2 and 3, patients with early treatment success (HCV-RNA <25 IU/ml at week 4 and undetectable at week 8) stopped all treatment at week 24. Other patients received PegIFN/RBV until week 48 unless they met futility criteria. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12). RESULTS: SVR12 was achieved by 52%, 79%, and 80% of patients in arms 1, 2, and 3, respectively (estimated difference for arms 2 and 3 vs. arm 1: 27%, 95% confidence interval 17%-36%; and 29%, 95% confidence interval, 19%-38%, respectively; p < 0.0001 for both). Early treatment success was achieved by 87% (arm 2) and 89% (arm 3) of patients, of whom 86% and 89% achieved SVR12. Adverse event rates were similar among groups; few adverse events led to discontinuation of all regimen components. CONCLUSIONS: Faldaprevir plus PegIFN/RBV significantly increased SVR12, compared with PegIFN/RBV, in treatment-naïve patients with HCV genotype-1 infection. No differences were seen in responses of patients given faldaprevir once daily at 120 or 240 mg.

Safety and Efficacy of Oral Fexofenadine in Children with Seasonal Allergic Rhinitis - a Pooled Analysis of Three Studies

Allergic rhinitis is one of the most common clinical conditions in children; however, data regarding the safety of antihistamines in children with seasonal allergic rhinitis are limiting. To evaluate the safety and efficacy of fexofenadine in children with seasonal allergic rhinitis, data were pooled from three, double-blind, randomized, placebo-controlled, parallel-group, 2-week trials in children (6-11 year) with seasonal allergic rhinitis. All studies assessed fexofenadine HCl 30 mg b.i.d.; two studies included fexofenadine HCl at 15 and 60 mg b.i.d. Patients (and investigators) reported any adverse events during the trial. Physical examinations, including measurements of vital signs and laboratory tests, were performed. Efficacy assessments (total symptom score and individual symptom scores) were evaluated. Exposure to fexofenadine HCl 30 mg b.i.d. and to any fexofenadine dose exceeded 10,000 and 17,000 patient days, respectively. Incidences of adverse events, and discontinuations because of adverse events, were low and similar across treatment groups. In the placebo group, 24.4% of subjects reported adverse events compared with 24.1% for fexofenadine HCl 30 mg b.i.d., and 28.4% for all fexofenadine-treated groups. The most common adverse event overall was headache (4.3% placebo; 5.8% fexofenadine HCl 30 mg b.i.d.; and 7.2% any fexofenadine doses). Treatment-related adverse events were similar across treatment groups with no sedative effects. Fexofenadine HCl 30 mg b.i.d. was significantly superior to placebo in reducing the total symptom score and all individual seasonal allergic rhinitis symptoms, including nasal congestion (p < 0.05). Fexofenadine, at doses of up to 60 mg b.i.d., is safe and non-sedating, and fexofenadine HCl 30 mg b.i.d. effectively reduces all seasonal allergic rhinitis symptoms in children aged 6-11 years.

The Effect of Carbohydrate Mouth Rinsing On Skill Specific Performance and Cognitive Function Following a Fatigue Inducing Bout of Fencing

The aim of this study was to investigate whether rinsing the mouth with a carbohydrate solution could improve skill-specific fencing performance and cognitive function following a fatigue inducing simulated bout of fencing in epee fencers. Eleven healthy, competitive epee fencers (three female; eight male; 33.9 ± 14.7 years; body mass 79 ± 16 kg; height 162 ± 54 cm) volunteered to participant in a single-blind crossover design study. During visit 1 participants completed a 1-minute lunge test and stroop test pre and post fatigue inducing fencing protocol. A 30 second electroencephalography (EEG) recording was taken pre-protocol participants were instructed stay in a seated stationary position with their eyes closed. Heart rate and ratings of perceived exertion were recorded following each fight during the fatiguing protocol. Participants mouth rinsed (10 seconds) either 25ml of a 6.7% maltodextrin solution (CHO) or 25ml of water (placebo) between fights and during the EEG recording. Blood lactate and glucose measurements were taken at baseline, pre and post protocol. All measurements and tests were repeated during a 2nd visit to the laboratory, except participants were given a different solution to mouth rinse, separated by a minimum of 5 days. The results showed an increase in heart rate (P < 0.05) and overall RPE (P < 0.001) over time in both trials. There were no recorded differences in blood glucose (F(1,8) = 0.634, P = 0.4, ηp 0.07) or blood lactate levels (F(1,8) = 0.123, P = 0.7, ηp 0.01) between trials. There was a significant improvement in lunge test accuracy in the CHO trial (F(1,8) = 5.214, P = 0.05, ηp 0.40). However, there was no recorded difference in response time to congruent (F(1,8) = 0.326, P = 0.58, ηp 0.04) or incongruent (F(1,8) = 0.189, P = 0.68, ηp 0.02) stimuli between trials. In conclusion mouth rinsing a CHO solution significantly improves accuracy of skill-specific fencing performance but does not affect cognitive function following a fatigue inducing fencing protocol in epee fencers.

The effect of metoclopramide in capsule enteroscopy

Clinical utility of prokinetics in capsule endoscopy (CE) is not clearly established. The objective of this prospective, randomized, single-blind, controlled trial was to determine if metoclopramide is useful in CE by increasing the rate of complete enteroscopy. Ninety-five patients referred for CE were randomized to no metoclopramide (group B, n = 48) or 10 mg metoclopramide (group A, n = 47). Complete enteroscopy was possible in 38 patients of group A (80.9%) and 37 of group B (77.1%) (P = 0.422) with two cases of gastric retention in group B (4.2%; P = 0.253). Median gastric transit time was 26 min (1-211) in group A and 28 min (4-200) in group B (P = 0.511). Mean small bowel transit time, calculated after excluding 20 patients with incomplete enteroscopy, was similar in both groups (221.2 +/- 89 min vs. 256 +/- 82.2 min; P = 0.083). There were also no differences in the total number of findings (group A 4.5 +/- 4.7; group B 4.7 +/- 3.7, P = 0.815). Administration of 10 mg metoclopramide orally 15 min before capsule ingestion did not significantly increase the rate of total enteroscopies and had no effect on transit times. It also did not modify CE diagnostic yield.

Interference lithography for optical devices and coatings

Interference lithography can create large-area, defect-free nanostructures with unique optical properties. In this thesis, interference lithography will be utilized to create photonic crystals for functional devices or coatings. For instance, typical lithographic processing techniques were used to create 1, 2 and 3 dimensional photonic crystals in SU8 photoresist. These structures were in-filled with birefringent liquid crystal to make active devices, and the orientation of the liquid crystal directors within the SU8 matrix was studied. Most of this thesis will be focused on utilizing polymerization induced phase separation as a single-step method for fabrication by interference lithography. For example, layered polymer/nanoparticle composites have been created through the one-step two-beam interference lithographic exposure of a dispersion of 25 and 50 nm silica particles within a photopolymerizable mixture at a wavelength of 532 nm. In the areas of constructive interference, the monomer begins to polymerize via a free-radical process and concurrently the nanoparticles move into the regions of destructive interference. The holographic exposure of the particles within the monomer resin offers a single-step method to anisotropically structure the nanoconstituents within a composite. A one-step holographic exposure was also used to fabricate self- healing coatings that use water from the environment to catalyze polymerization. Polymerization induced phase separation was used to sequester an isocyanate monomer within an acrylate matrix. Due to the periodic modulation of the index of refraction between the monomer and polymer, the coating can reflect a desired wavelength, allowing for tunable coloration. When the coating is scratched, polymerization of the liquid isocyanate is catalyzed by moisture in air; if the indices of the two polymers are matched, the coatings turn transparent after healing. Interference lithography offers a method of creating multifunctional self-healing coatings that readout when damage has occurred.

Despertar anestésico con remifentanilo versus sin remifentanilo en los pacientes del Hospital Vicente Corral Moscoso. Cuenca, 2013

OBJETIVO: Comparar el despertar anestésico con remifentanilo y sin remifentanilo en los pacientes sometidos a anestesia general. MATERIAL Y MÉTODOS: Se trata de un estudio clínico aleatorizado simple ciego de 140 pacientes sometidos a anestesia general balanceada. Se dividieron en dos grupos iguales, al grupo A (n=70) se le retiró el remifentanilo 10 minutos antes y el grupo B (n=70) recibió remifentanilo en infusión continua a dosis de 0.05 ug/kg/min hasta la extubación. RESULTADOS: Las variables edad, peso, talla, presión arterial media y frecuencia cardíaca basales entre ambos grupos no tuvieron diferencias estadísticamente significativas, con una p>0.05. En el grupo “A” durante el despertar anestésico, la presión arterial media en la extubación y 5 minutos después fueron mayores con respecto al grupo “B”, con una diferencia estadísticamente significativa (p=0.009 y p=0.01). La náusea fue el efecto adverso que presentó diferencia significativa en el grupo que recibió remifentanilo, con una p=0.023. El grupo que presentó con más frecuencia y más intensidad la tos fue el grupo “A”, con una p=0.047 y p=0.005 respectivamente. En cuanto a la frecuencia cardíaca y al tiempo del despertar no tuvieron diferencia en los grupos. CONCLUSIONES: El grupo que recibió remifentanilo tuvo una menor presión arterial media, frecuencia e intensidad de la tos, que el grupo que no recibió remifentanilo, con igual tiempo en el despertar y escasos efectos adversos

High-performance liquid chromatography (HPLC) and high-performance liquid chromatography mass spectrometry (HPLC/MS) for the analysis of date rape drugs

The drugs studied in this work have been reportedly used to commit drug-facilitated sexual assault (DFSA), commonly known as "date rape". Detection of the drugs was performed using high-performance liquid chromatography with ultraviolet detection (HPLC/UV) and identified with high performance-liquid chromatography mass spectrometry (HPLC/MS) using selected ion monitoring (SIM). The objective of this study was to develop a single HPLC method for the simultaneous detection, identification and quantitation of these drugs. The following drugs were simultaneously analyzed: Gamma-hydroxybutyrate (GHB), scopolamine, lysergic acid diethylamide, ketamine, flunitrazepam, and diphenhydramine. The results showed increased sensitivity with electrospray (ES) ionization versus atmospheric pressure chemical ionization (APCI) using HPLC/MS. HPLC/ES/MS was approximately six times more sensitive than HPLC/APCI/MS and about fifty times more sensitive than HPLC/UV. A limit of detection (LOD) of 100 ppb was achieved for drug analysis using this method. The average linear regression coefficient of correlation squared (r2) was 0.933 for HPLC/UV and 0.998 for HPLC/ES/MS. The detection limits achieved by this method allowed for the detection of drug dosages used in beverage tampering. This method can be used to screen beverages suspected of drug tampering. The results of this study demonstrated that solid phase microextraction (SPME) did not improve sensitivity as an extraction technique when compared to direct injections of the drug standards.

Postprandial serum endotoxin in healthy humans is modulated by dietary fat in a randomized, controlled, cross-over study

Background: High-fat diets may contribute to metabolic disease via postprandial changes in serum endotoxin and inflammation. It is unclear how dietary fat composition may alter these parameters. We hypothesized that a meal rich in n-3 (ω3) fatty acids would reduce endotoxemia and associated inflammation but a saturated or n-6 (ω6) fatty acid-rich meal would increase postprandial serum endotoxin concentrations and systemic inflammation in healthy adults. Methods: Healthy adults (n = 20; mean age 25 ± 3.2 S.D. years) were enrolled in this single-blind, randomized, cross-over study. Participants were randomized to treatment and reported to the laboratory, after an overnight fast, on four occasions separated by at least one week. Participants were blinded to treatment meal and consumed one of four isoenergetic meals that provided: 1) 20 % fat (control; olive oil) or 35 % fat provided from 2) n-3 (ω3) (DHA = 500 mg; fish oil); 3) n-6 (ω6) (7.4 g; grapeseed oil) or 4) saturated fat (16 g; coconut oil). Baseline and postprandial blood samples were collected. Primary outcome was defined as the effect of treatment meal on postprandial endotoxemia. Serum was analyzed for metabolites, inflammatory markers, and endotoxin. Data from all 20 participants were analyzed using repeated-measures ANCOVA. Results: Participant serum endotoxin concentration was increased during the postprandial period after the consumption of the saturated fat meal but decreased after the n-3 meal (p < 0.05). The n-6 meal did not effect a different outcome in participant postprandial serum endotoxin concentration from that of the control meal (p > 0.05). There was no treatment meal effect on participant postprandial serum biomarkers of inflammation. Postprandial serum triacylglycerols were significantly elevated following the n-6 meal compared to the n-3 meal. Non-esterified fatty acids were significantly increased after consumption of the saturated fat meal compared to other treatment meals. Conclusions: Meal fatty acid composition modulates postprandial serum endotoxin concentration in healthy adults. However, postprandial endotoxin was not associated with systemic inflammation in vivo. Trial registration: This study was retrospectively registered at clinicaltrials.gov as NCT02521779 on July 28, 2015.

Oral Administration of Lactobacillus reuteri during the First Year of Life Reduces Caries Prevalence in the Primary Dentition at 9 Years of Age

The aim of this study was to evaluate the effect on oral health, at age 9 years, of daily oral supplementation with the probiotic Lactobacillus reuteri, strain ATCC 55730, to mothers during the last month of gestation and to children through the first year of life. The study was a single-blind, placebo-controlled, multicenter trial involving 113 children: 60 in the probiotic and 53 in the placebo group. The subjects underwent clinical and radiographic examination of the primary dentition and carious lesions, plaque and gingivitis were recorded. Saliva and plaque were sampled for determination of mutans streptococci (MS) and lactobacilli (LB) in saliva and plaque as well as salivary secretory IgA (SIgA). Forty-nine (82%) children in the probiotic group and 31 (58%) in the placebo group were caries-free (p < 0.01). The prevalence of approximal caries lesions was lower in the probiotic group (0.67 ± 1.61 vs. 1.53 ± 2.64; p < 0.05) and there were fewer sites with gingivitis compared to the placebo group (p < 0.05). There were no significant differences between the groups with respect to frequency of toothbrushing, plaque and dietary habits, but to intake of fluoride supplements (p < 0.05). There were no intergroup differences with respect to L. reuteri, MS, LB or SIgA in saliva. Within the limitation of this study it seems that daily supplementation with L. reuteri from birth and during the first year of life is associated with reduced caries prevalence and gingivitis score in the primary dentition at 9 years of age.

Tiempo promedio del efecto máximo de la insulina análoga en la glucemia postprandial y factores relacionados

Introducción: El tiempo promedio del efecto máximo de la insulina regular rápida en la glucemia postprandial ha sido considerado durante años de 120 minutos. En pacientes con Diabetes Mellitus (DM) que usan insulinas análogas este tiempo y los factores asociados no se encuentran reportados para ser aplicados en el automonitoreo. El objetivo de este estudio fue calcular el tiempo y factores relacionados al efecto máximo de la insulina en la glucemia postprandial. Metodología: Se desarrolló un estudio longitudinal retrospectivo a partir de una fuente secundaria donde se realizó un análisis descriptivo y bivariado con las variables demográficas y clínicas presentes en la población. Resultados: El tiempo promedio del pico máximo de insulina en pacientes con DM1 fue de 78.4 (DE± 16.512) y DM2 75.01(DE± 12.02) minutos. El 75% de la población con DM1 y el 54.2% en DM2 era de sexo femenino, la edad promedio en DM1 era 42.38 años y en DM2 68 años, en cuanto a la categorización del IMC el 50% de la población en DM1 y el 37.5% en DM2 estaban dentro del rango de obesidad y se encontró una relación con respecto al tipo de comida “desayuno-cena” vs el tiempo promedio del efecto máximo de la insulina calculado para ambos grupos (p:0.010). Conclusiones: El tiempo promedio del efecto máximo de la insulina calculado fue menor al tiempo reportado en la literatura clínica de 120 minutos. El tipo de comida principal mostró una relación con el tiempo promedio del efecto máximo en ambos grupos.