Repeated intravitreal injections of antivascular endothelial growth factors and risk of intraocular pressure medication use

Graefe's Archive for Clinical and Experimental Ophthalmology - To determine the risk of initiating ocular hypertension and glaucoma treatment with repeated injections of antivascular...     

A Web-Based Intervention to Reduce Indoor Tanning Motivations in Adolescents: a Randomized Controlled Trial

Youthful indoor tanning as few as ten sessions can increase the risk of melanoma by two to four times with each additional session adding another 2 % to the risk. Recent research estimates that indoor tanning can be linked to approximately 450,000 cases of skin cancer annually in the USA, Europe, and Australia. Despite these risks, indoor tanning remains popular with adolescents. This study tested the efficacy of a web-based skin cancer prevention intervention designed to reduce indoor tanning motivations in adolescent females. A nationally representative sample of 443 female teens was enrolled from an online panel into a two-arm, parallel group design, randomized controlled trial. Treatment participants received an appearance-focused intervention grounded in established health behavior change models. Controls viewed a teen alcohol prevention website. Outcome variables included willingness and intentions to indoor tan, willingness to sunless tan, and measures of indoor tanning attitudes and beliefs. The intervention decreased willingness and intentions to indoor tan and increased sunless tanning willingness relative to controls. We also examined indirect mechanisms of change through intervening variables (e.g., indoor tanning attitudes, norms, positive and negative expectancies) using the product of coefficient approach. The web-based intervention demonstrated efficacy in changing adolescent indoor tanning motivations and improving their orientation toward healthier alternatives. Results from the intervening variable analyses give guidance to future adolescent skin cancer prevention interventions.     

Bioequivalence and Food Effect of Dapagliflozin/Saxagliptin/Metformin Extended-release Fixed-combination Drug Products Compared With Coadministration of the Individual Components in Healthy Subjects

PurposeFixed-combination drug products (FCDPs) for patients with type 2 diabetes mellitus (T2DM) may show efficacy comparable to their individual components (ICs) while improving adherence to treatment. This study evaluated the bioequivalence and safety of 2 dapagliflozin/saxagliptin/metformin extended-release (XR) FCDPs relative to their ICs: saxagliptin and dapagliflozin/metformin XR.MethodsThis randomized, open-label, single-dose, single-center crossover study was conducted in 84 healthy subjects aged 18–55 years. The primary objective was to evaluate the fed-state bioequivalence of a dapagliflozin 5-mg/saxagliptin 2.5-mg/metformin 1000-mg XR FCDP and a dapagliflozin 10-mg/saxagliptin 5-mg/metformin 1000-mg XR FCDP relative to the ICs. Secondary objectives included the evaluation of the effect of food on the pharmacokinetic (PK) parameters of saxagliptin, dapagliflozin, and metformin in both FCDPs and characterization of the PK parameters of the active metabolite of saxagliptin, 5-hydroxy saxagliptin, in healthy subjects. PK parameters (AUC_0–∞, AUC_0–t, and C_max) were used to assess the bioequivalence of the 2 FCDPs with their ICs. The C_max and AUC_0–t of the study drugs were compared between female and male subjects to assess sex differences in exposure. Safety and tolerability of both FCDPs and ICs were also assessed with adverse events, vital signs (systolic and diastolic blood pressures and pulse rate), 12-lead ECG, physical examinations, and laboratory assessments.FindingsBoth dapagliflozin/saxagliptin/metformin XR FCDPs were bioequivalent to their ICs. For the dapagliflozin 5-mg/saxagliptin 2.5-mg/metformin 1000-mg XR FCDP, the 90% CI for the geometric mean ratio of dapagliflozin C_max was slightly above the 80%–125% bioequivalence limit, which is unlikely to be clinically relevant. Food delayed the absorption of the study drugs in both FCDPs, which is unlikely to have a clinically relevant impact on efficacy. In both cohorts, exposure was higher in female subjects compared with male subjects, potentially due to the lower body weight of the female subjects. The safety profile and tolerability of the FCDPs were similar to those of their ICs, and no deaths or serious adverse events were reported.ImplicationsThese data support the use of the dapagliflozin/saxagliptin/metformin XR FCDP in patients with T2DM. ClinicalTrials.gov identifier: NCT03169959.     

Assessment of volume preservation performed before or after partial nephrectomy accurately predicts postoperative renal function: Results from a prospective multicenter study

Purpose

Partial nephrectomy (PN) is standard for small renal masses, improving renal function by preserving renal parenchyma compared with radical nephrectomy. Recent work demonstrated that postoperative surgeon assessment of volume preservation (SAVP) and 3D imaging measurements agree and correlate with postoperative function. We hypothesize preoperative assessment of volume preservation (PAVP) with PN based on preoperative imaging will reliably indicate postoperative renal function.

Etiology and Pathogenesis of Late-Onset Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative condition that occurs in two forms, an early-onset form that is genetically determined and a far more common late-onset form that is not. In both cases, the disease results in severe cognitive dysfunction, among other problems, and the late-onset form of the disease is now considered to be the most common cause of dementia among the elderly. While a good deal of research has been focused on elucidating the etiology of the late-onset form for more than two decades, results to date have been modest and have not yet engendered useful therapeutic strategies for cure of the disease. In this review, we discuss the prevalent ideas that have governed this research for several years, and we challenge these ideas with alternative findings suggesting a multifactorial etiology. We review promising newer ideas that may prove effective as therapeutic interventions for late-onset AD, as well as providing reliable means of earlier and more specific diagnosis of the disease process. In the discussions included here, we reference relevant clinical and basic science literature underlying research into disease etiology and pathogenesis, and we highlight current reviews on the various topics addressed.