Aspirin and its Metabolites Enhance the Expression of Vascular Endothelial Growth Factor in Retinal Pigment Epithelial Cell Cultures – Implications in the Pathophysiology of Age-Related Macular Degeneration

Purpose: An estimated 19.3% of adults, especially the elderly in the United States regularly use Aspirin for cardioprotection. Recently, multiple cohort studies have concluded that regular aspirin use for 10-15 years was associated with a statistically significant increase in the risk of incident age-related and neovascular acute macular degeneration. It has been hypothesized that aspirin or its metabolites induce the expression of vascular endothelial growth factor (VEGF). Materials & Methods: Retinal pigment epithelial cells, ARPE-19 (ATCC®CRL-2302™) were cultured. The cells were grown to achieve 95% confluence and then the media was changed. Cells cultured under blue light, red light, or darkness were subjected to a challenge with high dose aspirin (0.925 mg/dL), low dose aspirin (0.325 mg/dL), or hippuric acid (0.325 mg/dL). Light was generated using 2 red or blue LEDs powered by 3v CR2032 batteries. The 24-well plate was incubated with or without drugs in blue light, red light or darkness at 37C for 16 hours. The supernatants were harvested, and VEGF was quantified. One-way ANOVA using Dunnett’s multiple comparison test was performed to analyze statistical significance. Results: Cells exposed to blue light or darkness and hippuric acid showed a statistically significant increase in VEGF secretion (P=0.0012). However, cells exposed to red light with hippuric acid challenge showed no significant difference from the mean of cells exposed to darkness and sham control. Conclusions: Retinal pigment epithelial cells challenged with oxidative stress provided by blue light or darkness in the presence of hippuric acid increased VEGF secretion, suggesting a possible cause for neovascularization in age-related macular degeneration. RPE cells exposed to red light, known to abrogate oxidative stress, had decreased levels of VEGF induction by hippuric acid

Investigating differences in treatment effect estimates between propensity score matching and weighting: A demonstration using STAR*D trial data

The choice of propensity score (PS) implementation influences treatment effect estimates not only because different methods estimate different quantities, but also because different estimators respond in different ways to phenomena such as treatment effect heterogeneity and limited availability of potential matches. Using effectiveness data, we describe lessons learned from sensitivity analyses with matched and weighted estimates

Prescription refill records as a screening tool to identify antidepressant non-adherence

Non-adherence is a significant problem with antidepressants. Identifying patients at highest risk for discontinuing antidepressant treatment can be used to target clinical management. Accordingly, our purpose was to determine the shortest gap in medication supply that is predictive of discontinuation, while minimizing false positive results

The application of precision dosing in the use of sertraline throughout pregnancy for poor and ultra-rapid metaboliser CYP 2C19 subjects: a virtual clinical trial pharmacokinetics study:A virtual clinical trial pharmacokinetics study

Sertraline is known to undergo changes in pharmacokinetics during pregnancy. CYP 2C19 has been implicated in the interindividual variation in clinical effect associated with sertraline activity. However, knowledge of suitable dose titrations during pregnancy and within CYP 2C19 phenotypes is lacking. A pharmacokinetic modeling virtual clinical trials approach was implemented to: (i) assess gestational changes in sertraline trough plasma concentrations for CYP 2C19 phenotypes, and (ii) identify appropriate dose titration strategies to stabilize sertraline levels within a defined therapeutic range throughout gestation. Sertraline trough plasma concentrations decreased throughout gestation, with maternal volume expansion and reduction in plasma albumin being identified as possible causative reasons. All CYP 2C19 phenotypes required a dose increase throughout gestation. For extensive metabolizer (EM) and ultrarapid metabolizer (UM) phenotypes, doses of 100–150 mg daily are required throughout gestation. For poor metabolizers (PM), 50 mg daily during trimester 1 followed by a dose of 100 mg daily in trimesters 2 and 3 are required

Performance of a Culturally Tailored Cognitive-Behavioral Intervention Integrated in a Public Health Setting to Reduce Risk of Antepartum Depression: A Randomized Controlled Trial

Cognitive behavioral group interventions have been shown to improve depressive symptoms in adult populations. This article details the feasibility and efficacy of a 6-week culturally tailored cognitive behavioral intervention offered to rural, minority, low-income women at risk for antepartum depression

Predictors of Recovery from Prenatal Depressive Symptoms from Pregnancy Through Postpartum

Abstract Background: Identifying predictors of the course of depressive symptoms from pregnancy through postpartum is important to inform clinical interventions. Methods: This longitudinal study investigated predictors of recovery from prenatal elevated depressive symptoms in the postpartum period. Forty-one pregnant women completed demographic, interpersonal, and psychosocial self-report assessment measures at 32 weeks of gestation and again 12 weeks postpartum. Results: Of those with elevated depressive symptoms, defined as a Beck Depression Inventory-II (BDI-II) score ≥10, at the prenatal baseline, 39% (n=16) recovered to nonelevated symptom levels postpartum, whereas 61% (n=25) experienced sustained elevated symptoms. Women who recovered evidenced significantly lower baseline depression severity and more frequent engagement in physical activity and cohabitated with a romantic partner. In multiparous women (n=25), history of past postpartum depression (PPD) differentiated between those with transient and those with persisting symptoms, although history of lifetime depression did not. None of the additional demographic, interpersonal, or psychosocial variables investigated differentiated between groups. Logistic regression analysis showed prenatal depression severity and exercise frequency as predictors of recovery postpartum. Conclusions: Results suggest most women will not experience spontaneous recovery. Women with prenatal heightened symptom severity and previous experiences with PPD are acutely vulnerable to experience sustained symptoms. In contrast, having a cohabitating partner and engagement in prenatal exercise predicted symptom improvement. Physical exercise may be an important clinical recommendation, as it may improve mood. Given the small sample size, these results are preliminary. Implications and future research recommendations are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98461/1/jwh%2E2010%2E2266.pd

Treatment Use and Costs among Privately-Insured Youth with Bipolar Diagnoses

Recent evidence suggests that children are increasingly diagnosed with bipolar disorder, yet no studies have quantified treatment costs for pediatric patients. The objectives are to identify one-year health services utilization and treatment costs among youth with new bipolar diagnoses

Controlling for Drug Dose in Systematic Review and Meta-Analysis: A Case Study of the Effect of Antidepressant Dose

To describe a method for quantitatively dealing with drug dose in comparative effectiveness reviews. Second-generation antidepressants are used as an example to illustrate this method, and to determine whether dose influences conclusions on comparative effectiveness

Confounding control in a nonexperimental study of STAR*D data: logistic regression balanced covariates better than boosted CART

Propensity scores, a powerful bias-reduction tool, can balance treatment groups on measured covariates in non-experimental studies. We demonstrate the use of multiple propensity score estimation methods to optimize covariate balance