Effect of Hepatic Impairment on the Pharmacokinetics of Fenfluramine and Norfenfluramine.

Fenfluramine (Fintepla) is approved for the treatment of seizures associated with the rare epileptic encephalopathies Dravet syndrome and Lennox-Gastaut syndrome. Fenfluramine is extensively metabolized; thus, patients with hepatic impairment (HI) might experience changes in exposure to fenfluramine or its metabolites. In this phase 1 study, we investigated the pharmacokinetics (PK) and safety of a single oral dose of 0.

Translational Approach to Predicting the Efficacy of Maraviroc-Based Regimens as HIV Preexposure Prophylaxis.

Maraviroc-based regimens have been explored as preexposure prophylaxis (PrEP) against human immunodeficiency virus (HIV). In this study, we utilized mucosal tissue drug exposure data, combined with target concentrations generated , in a pharmacokinetic-pharmacodynamic analysis to predict the effects of drug combinations and adherence on PrEP efficacy. Mucosal tissue concentrations of maraviroc were measured in 24 healthy women.

Virological and immunological responses to raltegravir and dolutegravir in the gut-associated lymphoid tissue of HIV-infected men and women.

Background: Raltegravir (RTG) and dolutegravir (DTG) have different pharmacokinetic patterns in the gastrointestinal tract. To determine if this results in pharmacodynamic differences, we compared HIV RNA, HIV DNA and immunological markers in gut-associated lymphoid tissue (GALT) of HIV-infected participants receiving RTG or DTG with tenofovir+emtricitabine (TDF/FTC).

Methods: GALT specimens from the terminal ileum, splenic flexure and rectum were obtained by colonoscopy at a single time point in 20 adults treated with RTG (n=10) or DTG (n=10) with HIV RNA <50 copies/ml.

Medical Treatment of Gastroesophageal Reflux Disease.

Medical treatment is effective in the majority of patients with gastroesophageal reflux disease (GERD). Lifestyle modifications are often recommended for patients with GERD, although the data supporting lifestyle recommendations are limited. Antacids are often used to treat the symptoms of GERD, but their effect is short-lived.

Clinical Outcomes Following Recurrence of Intestinal Metaplasia After Successful Treatment of Barrett's Esophagus With Radiofrequency Ablation.

Objectives: Radiofrequency ablation (RFA) is an effective treatment for Barrett's esophagus (BE). However, recurrence of BE after initially successful RFA is common, and outcomes following recurrence not well described. We report the outcomes associated with recurrence following initially successful RFA.

Quantifying the Twitter Influence of Third Party Commercial Entities versus Healthcare Providers in Thirteen Medical Conferences from 2011 - 2013.

Introduction: Twitter channels are increasingly popular at medical conferences. Many groups, including healthcare providers and third party entities (e.g.

Cervicovaginal and Rectal Fluid as a Surrogate Marker of Antiretroviral Tissue Concentration: Implications for Clinical Trial Design.

Background: Quantifying tissue drug concentrations can yield important information during drug development, but complicates pharmacokinetic study design. Mucosal fluids collected by direct aspiration (cervicovaginal fluid; CVF) or swab (rectal fluid; RF) might be used as tissue concentration surrogates, but these relationships are not well characterized.

Methods: Forty-nine healthy women, given a single oral dose of tenofovir, maraviroc, emtricitabine, or raltegravir at 50%-200% of the treatment dose, provided 13 plasma, 12 CVF, 12 RF and one cervical, vaginal and rectal tissue biopsy over 48 hours.

A Translational Pharmacology Approach to Predicting Outcomes of Preexposure Prophylaxis Against HIV in Men and Women Using Tenofovir Disoproxil Fumarate With or Without Emtricitabine.

Background: A novel translational pharmacology investigation was conducted by combining an in vitro efficacy target with mucosal tissue pharmacokinetic (PK) data and mathematical modeling to determine the number of doses required for effective human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP).

Methods: A PK/pharmacodynamic (PD) model was developed by measuring mucosal tissue concentrations of tenofovir, emtricitabine, their active metabolites (tenofovir diphosphate [TFVdp] and emtricitabine triphosphate [FTCtp], respectively), and competing endogenous nucleotides (dATP and dCTP) in 47 healthy women. TZM-bl and CD4(+) T cells were used to identify 90% effective concentration (EC90) ratios of TFVdp to dATP and FTCtp to dCTP (alone and in combination) for protection against HIV.

Advanced Esophageal Squamous Cell Dysplasia and Early Carcinoma Detected After Remote Esophagectomy for Adenocarcinoma.

We present a case of squamous dysplasia and early squamous carcinoma of the esophagus after esophagectomy for esophageal adenocarcinoma. We briefly discuss mucosectomy and ablative therapy as potential treatment options.

Sex and race and/or ethnicity differences in patients undergoing radiofrequency ablation for Barrett's esophagus: results from the U.S. RFA Registry.

Background: Little is known about differences in Barrett's esophagus (BE) characteristics by sex and race and/or ethnicity or these differences in response to radiofrequency ablation (RFA).

Objective: We compared disease-specific characteristics, treatment efficacy, and safety outcomes by sex and race and/or ethnicity in patients treated with RFA for BE.

Design: The U.

Recurrent intestinal metaplasia after radiofrequency ablation for Barrett's esophagus: endoscopic findings and anatomic location.

Background: Radiofrequency ablation (RFA) is a safe and effective treatment for Barrett's esophagus (BE) that results in high rates of complete eradication of intestinal metaplasia (CEIM). However, recurrence is common after CEIM, and surveillance endoscopy is recommended. Neither the anatomic location nor the endoscopic appearance of these recurrences is well-described.

Extraesophageal presentations of GERD: where is the science?

This article reviews the evaluation and management of patients with suspected extraesophageal manifestations of gastroesophageal reflux disease, such as asthma, chronic cough, and laryngitis, which are commonly encountered in gastroenterology practices. Otolaryngologists and gastroenterologists commonly disagree upon the underlying cause for complaints in patients with one of the suspected extraesophageal reflux syndromes. The accuracy of diagnostic tests (laryngoscopy, endoscopy, and pH- or pH-impedance monitoring) for patients with suspected extraesophageal manifestations of gastroesophageal reflux disease is suboptimal.

Clinical and endoscopic characteristics do not reliably differentiate PPI-responsive esophageal eosinophilia and eosinophilic esophagitis in patients undergoing upper endoscopy: a prospective cohort study.

Objectives: Proton-pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is a newly recognized entity that must be differentiated from eosinophilic esophagitis (EoE). Little is known about this condition. We aimed to determine the prevalence of PPI-REE and EoE in patients undergoing upper endoscopy and determine features that distinguish the two groups.

Differential penetration of raltegravir throughout gastrointestinal tissue: implications for eradication and cure.

Objective: To investigate the concentration of the integrase strand inhibitor raltegravir (RAL) throughout gastrointestinal (GI) tissue, especially gut-associated lymphoid tissue (GALT), as an adjunct to current prevention and cure strategies.

Design: Open-label pharmacokinetic (PK) study.

Methods: HIV-negative men received RAL 400 mg twice daily for 7 days.

Dolutegravir pharmacokinetics in the genital tract and colorectum of HIV-negative men after single and multiple dosing.

Objectives: To describe first-dose and steady state pharmacokinetics (PKs) of dolutegravir (DTG) in blood plasma (BP), seminal fluid (SF), colorectal tissue (RT), and rectal mucosal fluid (RF) of healthy HIV-negative men.

Design: A phase 1, open-label, PK study that enrolled 12 healthy men taking 50 mg DTG daily for 8 days.

Methods: Eleven paired BP samples and 3 SF and RF samples were collected over 24 hours after first (PK1) and multiple (PK2) dosing.

Intestinal metaplasia recurs infrequently in patients successfully treated for Barrett's esophagus with radiofrequency ablation.

Objectives: Radiofrequency ablation (RFA) of Barrett's esophagus (BE) is safe and effective in eradicating dysplasia and intestinal metaplasia, and may reduce rates of esophageal adenocarcinoma (EAC). We assessed rates of and risk factors for disease recurrence after successful treatment of BE with RFA.

Methods: We performed a retrospective cohort study of patients who completed RFA for dysplastic BE or intramucosal carcinoma (IMC), achieved complete eradication of dysplasia (CE-D) or intestinal metaplasia (CE-IM), and underwent subsequent endoscopic surveillance at a single center.

Safety and efficacy of endoscopic mucosal therapy with radiofrequency ablation for patients with neoplastic Barrett's esophagus.

Background & Aims: The goal of radiofrequency ablation (RFA) for patients with Barrett's esophagus (BE) is to eliminate dysplasia and metaplasia. The efficacy and safety of RFA for patients with BE and neoplasia are characterized incompletely.

Methods: We performed a retrospective study of 244 patients treated with RFA for BE with dysplasia or intramucosal carcinoma.

Focal endoscopic mucosal resection before radiofrequency ablation is equally effective and safe compared with radiofrequency ablation alone for the eradication of Barrett's esophagus with advanced neoplasia.

Background: EMR is commonly performed before radiofrequency ablation (RFA) for nodular dysplastic Barrett's esophagus (BE).

Objective: To determine the efficacy and safety of EMR before RFA for nodular BE with advanced neoplasia (high-grade dysplasia [HGD] or intramucosal carcinoma [IMC]).

Design: Retrospective study.

Viscous topical is more effective than nebulized steroid therapy for patients with eosinophilic esophagitis.

We performed a randomized trial to compare nebulized and viscous topical corticosteroid treatments for eosinophilic esophagitis (EoE). Subjects with incident EoE (n = 25) received budesonide 1 mg twice daily, either nebulized and then swallowed (NEB) or as an oral viscous slurry (OVB), for 8 weeks. Baseline eosinophil counts for the NEB and OVB groups were 101 and 83 (P = .

Antireflux surgery in the proton pump inhibitor era.

Although proton pump inhibitors (PPIs) are now the first-line treatment for gastroesophageal reflux disease (GERD), surgery still has several specific indications. We review the current treatment of GERD and discuss how antireflux surgery fits into the overall scheme.