Predictors of coronary artery disease in patients with left bundle branch block who undergo myocardial perfusion imaging

Background: Due to difficulties in diagnosing coronary ischemia in patients with left bundle branch block (LBBB), identifying clinical characteristics that might help to predict coronary artery disease (CAD) is important. Our study aimed to identify clinical predictors of CAD among patients with and without LBBB who undergo myocardial perfusion imaging (MPI). Methods: All patients with LBBB who underwent MPI (LBBB group) from June 2005 to February 2007 were compared with patients with normal baseline electrocardiography who underwent treadmill MPI (non-LBBB group) during the same period. Results: LBBB patients with CAD were younger and had lower ejection fraction (EF) compared to LBBB patients without CAD. Similarly non-LBBB patients with CAD had lower EF, but did not differ significantly in age compared to non-LBBB patients without CAD. Regression analysis among patients with LBBB showed that EF < 55% was the most significant predictor of CAD, after controlling for other factors. A regression analysis in non-LBBB patients showed that male gender and EF &#163; 55% were significant predictors of CAD. A regression analysis conducted in the combined data of both LBBB and non-LBBB groups showed male gender, EF &#163; 55% and LBBB to be the most significant predictors of CAD. Conclusions: Patients with LBBB have a high probability of CAD based on MPI findings. Patients with LBBB and reduced EF have a much higher likelihood of CAD compared to patients without LBBB and normal EF. Further studies on early invasive approach in patients with LBBB and reduced EF seem warranted

Differential Effects of Emotional Information on Interference Task Performance Across the Life Span

While functioning in multiple domains declines with age, emotional regulation appears to remain preserved in older adults. The Emotion Inhibition (Emotional Stroop) Test requires participants to name the ink color in which neutrally and emotionally valenced words are printed. It was employed in the current investigation as a measure of affective regulation in the context of an interference task in relation to age. Results demonstrated that while participants ranging from 20 to 50 years of age performed significantly worse on the emotion Stroop Inhibition relative to the neutral Stroop Inhibition condition, subjects over 60 years of age displayed the converse of this pattern, performing better on the emotion than the neutral condition, suggesting that they are less affected by the emotional impact of the positive and negative words used in the former condition. This pattern of age-related change in the ability to manage emotion may be related to blunting of affective signaling in limbic structures or, at the psychological level, focusing on emotional regulation

Efficacy, Safety, and Timing of Anticoagulant Thromboprophylaxis for the Prevention of Venous Thromboembolism in Patients With Acute Spinal Cord Injury: A Systematic Review

Study Design: Systematic review. Objectives: The objective of this study was to answer 5 key questions: What is the comparative effectiveness and safety of (1a) anticoagulant thromboprophylaxis compared to no prophylaxis, placebo, or another anticoagulant strategy for preventing deep vein thrombosis (DVT) and pulmonary embolism (PE) after acute spinal cord injury (SCI)? (1b) Mechanical prophylaxis strategies alone or in combination with other strategies for preventing DVT and PE after acute SCI? (1c) Prophylactic inferior vena cava filter insertion alone or in combination with other strategies for preventing DVT and PE after acute SCI? (2) What is the optimal timing to initiate and/or discontinue anticoagulant, mechanical, and/or prophylactic inferior vena cava filter following acute SCI? (3) What is the cost-effectiveness of these treatment options? Methods: A systematic literature search was conducted to identify studies published through February 28, 2015. We sought randomized controlled trials evaluating efficacy and safety of antithrombotic strategies. Strength of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Results: Nine studies satisfied inclusion criteria. We found a trend toward lower risk of DVT in patients treated with enoxaparin. There were no significant differences in rates of DVT, PE, bleeding, and mortality between patients treated with different types of low-molecular-weight heparin or between low-molecular-weight heparin and unfractionated heparin. Combined anticoagulant and mechanical prophylaxis initiated within 72 hours of SCI resulted in lower risk of DVT than treatment commenced after 72 hours of injury. Conclusion: Prophylactic treatments can be used to lower the risk of venous thromboembolic events in patients with acute SCI, without significant increase in risk of bleeding and mortality and should be initiated within 72 hours. © 2017, © The Author(s) 2017

Venue-based recruitment of women at elevated risk for HIV: An HIV prevention trials network study

Background: The challenge of identifying and recruiting U.S. women at elevated risk for HIV acquisition impedes prevention studies and services. HIV Prevention Trials Network (HPTN) 064 was a U.S. multisite, longitudinal cohort study designed to estimate HIV incidence among women living in communities with prevalent HIV and poverty. Venue-based sampling (VBS) methodologies and participant and venue characteristics are described. Methods: Eligible women were recruited from 10 U.S. communities with prevalent HIV and poverty using VBS. Participant eligibility criteria included age 18–44 years, residing in a designated census tract/zip code, and self-report of at least one high-risk personal and/or male sexual partner characteristic associated with HIV acquisition (e.g., incarceration history). Ethnography was conducted to finalize recruitment areas and venues. Results: Eight thousand twenty-nine women were screened and 2,099 women were enrolled (88% black, median age 29 years) over 14 months. The majority of participants were recruited from outdoor venues (58%), retail spaces (18%), and social service organizations (13%). The proportion of women recruited per venue category varied by site. Most participants (73%) had both individual and partner characteristics that qualified them for the study; 14% were eligible based on partner risk only. Conclusion: VBS is a feasible and effective approach to rapidly recruit a population of women at enhanced risk for HIV in the United States. Such a recruitment approach is needed in order to engage women most at risk and requires strong community engagement

Functional characterization of a panel of high-grade serous ovarian cancer cell lines as representative experimental models of the disease.

Genomic analysis of ovarian cancer cell lines has revealed a panel that best represents the most common ovarian cancer subtype, high-grade serous ovarian cancer (HGSOC). However, these HGSOC-like cell lines have not been extensively applied by ovarian cancer researchers to date, and the most commonly used cell lines in the ovarian cancer field do not genetically resemble the major clinical type of the disease. For the HGSOC-like lines to serve as suitable models, they need to be characterized for common functional assays. To achieve that objective, we systematically studied a panel of HGSOC cells CAOV3, COV362, Kuramochi, OVCAR4, OVCAR5, OVCAR8, OVSAHO and SNU119 for migration, invasion, proliferation, clonogenicity, EMT phenotype and cisplatin resistance. They exhibited a range of efficacies and OVCAR5, OVCAR8 and Kuramochi were the most aggressive. SNU119 and OVSAHO cells demonstrated the lowest functional activities. Wide differences in expression of EMT markers were observed between cell lines. SNU119 were the most epithelial and OVCAR8 had the most mesenchymal phenotype. COV362 was the most resistant to cisplatin while CAOV3 was the most sensitive. Taken together, our systematic characterization represents a valuable resource to help guide the application of HGSOC cells by the cancer research community

A systems view of epithelial–mesenchymal transition signaling states

Epithelial–mesenchymal transition (EMT) is an important contributor to the invasion and metastasis of epithelial-derived cancers. While considerable effort has focused in the regulators involved in the transition process, we have focused on consequences of EMT to prosurvival signaling. Changes in distinct metastable and ‘epigentically-fixed’ EMT states were measured by correlation of protein, phosphoprotein, phosphopeptide and RNA transcript abundance. The assembly of 1167 modulated components into functional systems or machines simplified biological understanding and increased prediction confidence highlighting four functional groups: cell adhesion and migration, metabolism, transcription nodes and proliferation/survival networks. A coordinate metabolic reduction in a cluster of 17 free-radical stress pathway components was observed and correlated with reduced glycolytic and increased oxidative phosphorylation enzyme capacity, consistent with reduced cell cycling and reduced need for macromolecular biosynthesis in the mesenchymal state. An attenuation of EGFR autophosphorylation and a switch from autocrine to paracrine-competent EGFR signaling was implicated in the enablement of tumor cell chemotaxis. A similar attenuation of IGF1R, MET and RON signaling with EMT was observed. In contrast, EMT increased prosurvival autocrine IL11/IL6-JAK2-STAT signaling, autocrine fibronectin-integrin α5β1 activation, autocrine Axl/Tyro3/PDGFR/FGFR RTK signaling and autocrine TGFβR signaling. A relatively uniform loss of polarity and cell–cell junction linkages to actin cytoskeleton and intermediate filaments was measured at a systems level. A more heterogeneous gain of ECM remodeling and associated with invasion and migration was observed. Correlation to stem cell, EMT, invasion and metastasis datasets revealed the greatest similarity with normal and cancerous breast stem cell populations, CD49f(hi)/EpCAM(-/lo) and CD44(hi)/CD24(lo), respectively. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10585-010-9367-3) contains supplementary material, which is available to authorized users

Aripiprazole lauroxil, a novel injectable long-acting antipsychotic treatment for adults with schizophrenia: A comprehensive review

Purpose of Review. This is a comprehensive review of the literature regarding the use of Aripiprazole lauroxil for schizophrenia. This review presents the background, evidence, and indications for using aripiprazole lauroxil to treat schizophrenia in the context of current theories on the development of schizophrenia. Recent Findings. Schizophrenia is a chronic mental health disorder that currently affects approximately 3.3 million people in the United States. Its symptoms, which must be present for more than six months, are comprised of disorganized behavior and speech, a diminished capacity to comprehend reality, hearing voices unheard by others, seeing things unseen by others, delusions, decreased social commitment, and decreased motivation. The majority of these symptoms can be managed with antipsychotic medication. Aripiprazole lauroxil is a long-acting intramuscular injection that works as a combination of partial agonist activity at D2 and 5-HT1A receptors combined with antagonist activity at 5-HT2A receptors. It can be dosed as a 4-, 6-, or 8-week injection, depending on oral dosage. Aripiprazole lauroxil was FDA approved in October of 2015. Summary. Schizophrenia is a severe psychiatric disorder if left untreated. There are multiple medications to help treat schizophrenia. One antipsychotic agent, aripiprazole lauroxil, offers long duration injections that optimize and improve compliance. Known side effects include weight gain, akathisia, neuroleptic malignant syndrome, tardive dyskinesia, and orthostatic hypotension. Aripiprazole lauroxil is an FDA-approved drug that can be administered monthly, every six weeks, or every two months and has been shown to be both safe and effective

Aripiprazole lauroxil, a novel injectable long-acting antipsychotic treatment for adults with schizophrenia: A comprehensive review

Purpose of Review. This is a comprehensive review of the literature regarding the use of Aripiprazole lauroxil for schizophrenia. This review presents the background, evidence, and indications for using aripiprazole lauroxil to treat schizophrenia in the context of current theories on the development of schizophrenia. Recent Findings. Schizophrenia is a chronic mental health disorder that currently affects approximately 3.3 million people in the United States. Its symptoms, which must be present for more than six months, are comprised of disorganized behavior and speech, a diminished capacity to comprehend reality, hearing voices unheard by others, seeing things unseen by others, delusions, decreased social commitment, and decreased motivation. The majority of these symptoms can be managed with antipsychotic medication. Aripiprazole lauroxil is a long-acting intramuscular injection that works as a combination of partial agonist activity at D2 and 5-HT1A receptors combined with antagonist activity at 5-HT2A receptors. It can be dosed as a 4-, 6-, or 8-week injection, depending on oral dosage. Aripiprazole lauroxil was FDA approved in October of 2015. Summary. Schizophrenia is a severe psychiatric disorder if left untreated. There are multiple medications to help treat schizophrenia. One antipsychotic agent, aripiprazole lauroxil, offers long duration injections that optimize and improve compliance. Known side effects include weight gain, akathisia, neuroleptic malignant syndrome, tardive dyskinesia, and orthostatic hypotension. Aripiprazole lauroxil is an FDA-approved drug that can be administered monthly, every six weeks, or every two months and has been shown to be both safe and effective

Physician decision making in selection of second-line treatments in immune thrombocytopenia in children.

Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder which presents with isolated thrombocytopenia and risk of hemorrhage. While most children with ITP promptly recover with or without drug therapy, ITP is persistent or chronic in others. When needed, how to select second-line therapies is not clear. ICON1, conducted within the Pediatric ITP Consortium of North America (ICON), is a prospective, observational, longitudinal cohort study of 120 children from 21 centers starting second-line treatments for ITP which examined treatment decisions. Treating physicians reported reasons for selecting therapies, ranking the top three. In a propensity weighted model, the most important factors were patient/parental preference (53%) and treatment-related factors: side effect profile (58%), long-term toxicity (54%), ease of administration (46%), possibility of remission (45%), and perceived efficacy (30%). Physician, health system, and clinical factors rarely influenced decision-making. Patient/parent preferences were selected as reasons more often in chronic ITP (85.7%) than in newly diagnosed (0%) or persistent ITP (14.3%, P = .003). Splenectomy and rituximab were chosen for the possibility of inducing long-term remission (P < .001). Oral agents, such as eltrombopag and immunosuppressants, were chosen for ease of administration and expected adherence (P < .001). Physicians chose rituximab in patients with lower expected adherence (P = .017). Treatment choice showed some physician and treatment center bias. This study illustrates the complexity and many factors involved in decision-making in selecting second-line ITP treatments, given the absence of comparative trials. It highlights shared decision-making and the need for well-conducted, comparative effectiveness studies to allow for informed discussion between patients and clinicians