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https://www.readbyqxmd.com/read/29905658/a-preliminary-examination-of-the-effects-of-transdiagnostic-versus-single-diagnosis-protocols-on-anger-during-the-treatment-of-anxiety-disorders
#1
Clair Cassiello-Robbins, Shannon Sauer-Zavala, Julianne G Wilner, Kate H Bentley, Laren R Conklin, Todd J Farchione, David H Barlow
Dysregulated anger is often present in the emotional (i.e., anxiety, mood, and related) disorders; however, it is rarely targeted in treatment. Transdiagnostic treatments, which focus on processes that contribute to dysregulated emotions across the range of psychopathology, might represent an efficient way to treat this anger. Using a subset of data from a recently completed equivalency trial comparing the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) to single diagnosis protocols (SDPs) for specific disorders, this study began exploring whether the UP led to great reductions in anger compared with the SDPs...
June 14, 2018: Journal of Nervous and Mental Disease
https://www.readbyqxmd.com/read/29881820/clinical-application-of-the-globe-and-united-kingdom-primary-biliary-cholangitis-risk-scores-in-a-trial-cohort-of-patients-with-primary-biliary-cholangitis
#2
Marco Carbone, Maren H Harms, Willem J Lammers, Tonya Marmon, Richard Pencek, Leigh MacConell, David Shapiro, David E Jones, George F Mells, Bettina E Hansen
The GLOBAL Primary Biliary Cholangitis (PBC) Study Group and United Kingdom-PBC (UK-PBC) Consortium have demonstrated that dichotomous response criteria are not as accurate as continuous equations at predicting mortality or liver transplantation in PBC. The aim of this analysis was to assess the clinical utility of the GLOBE and UK-PBC risk scores using data from POISE, a phase 3 trial investigating obeticholic acid (OCA) in patients with PBC. Data (N = 216) at baseline and month 12 were used to calculate the GLOBE and UK-PBC risk scores to assess the projected change in risk with OCA versus placebo...
June 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29848610/are-peptide-conjugates-the-golden-pill-against-obesity
#3
Sara J Brandt, Maximilian Kleinert, Matthias Tschöp, Timo Müller
Obesity is a world-wide pandemic which can be fatal for the most extremely affected individuals. Lifestyle interventions such as diet and exercise are largely ineffective, and current anti-obesity medications offer little in the way of significant or sustained weight loss. Bariatric surgery is effective, but largely restricted to only a small subset of extremely obese patients. While the hormonal factors mediating sustained weight loss and remission of diabetes by bariatric surgery remain elusive, a new class of polypharmacological drugs shows potential to shrink the gap in efficacy between a surgery and pharmacology...
May 30, 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/29802965/habit-formation-intervention-to-prevent-obesity-in-low-income-preschoolers-and-their-mothers-a-randomized-controlled-trial-protocol
#4
Sarah-Jeanne Salvy, Gareth R Dutton, Alena Borgatti, Young-Il Kim
BACKGROUND: Low-income and racial/ethnic minority mothers and their young children are at increased risk for obesity. Lack of access to evidence-based obesity prevention and treatment services further contributes to these disparities. METHODS: This two-arm, parallel, randomized controlled trial (RCT) tests the effectiveness of a simple obesity intervention (HABITS) delivered as part of ongoing home visitation services, compared to the existing home visitation services without obesity-related content on mothers' and children's obesity risks...
May 24, 2018: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/29794536/moonshot-objectives-catalyze-new-scientific-breakthroughs-proteogenomics
#5
Karin D Rodland, Paul Piehowski, Richard D Smith
Breaking down the silos between disciplines to accelerate the pace of cancer research is a key paradigm for the Cancer Moonshot. Molecular analyses of cancer biology have tended to segregate between a focus on nucleic acids-DNA, RNA, and their modifications-and a focus on proteins and protein function. Proteogenomics represents a fusion of those two approaches, leveraging the strengths of each to provide a more integrated vision of the flow of information from DNA to RNA to protein and eventually function at the molecular level...
May 2018: Cancer Journal
https://www.readbyqxmd.com/read/29792526/phages-antibiotic-resistance-are-the-most-abundant-entities-on-earth-ready-for-a-comeback
#6
Colin Hill, Susan Mills, Reynolds P Ross
Bacteriophages, which lost out to antibiotic therapy in the past, may be poised to make a comeback. Once discarded because of their narrow activity spectrum, it can now be viewed as a major advantage that these intracellular, self-replicating entities can exert their killing effect with minimal damage to the commensal microbiome. In eastern Europe, phages continue to be used both prophylactically and therapeutically to treat infections. More recently, much needed regulated clinical trials are underway with a view to restoring phage therapy as a tool for mainstream medicine, although current regulations may impede their full potential...
May 24, 2018: Future Microbiology
https://www.readbyqxmd.com/read/29753563/critical-appraisal-of-the-2018-acc-scientific-sessions-late-breaking-trials-from-a-statistician-s-perspective
#7
REVIEW
Stuart J Pocock, Tim J Collier
The late-breaking clinical trials presentations at the American College of Cardiology Scientific Sessions in March 2018 are an important contribution to the field of cardiology. This paper presents a constructive critical appraisal of 7 key studies: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), VEST (Vest Prevention of Early Sudden Death Trial), SECURE-PCI (Statins Evaluation in Coronary Procedures and Revascularization), TREAT (Ticagrelor in Patients with ST-Elevation Myocardial Infarction treated with Pharmacological Thrombolysis), POISE (PeriOperative ISchemic Evaluation), SMART-DATE (Safety of 6-Month Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome), and CVD-REAL 2 (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors)...
May 7, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29584915/interleukin-1-blockade-in-cardiovascular-diseases-a-clinical-update
#8
Leo F Buckley, Antonio Abbate
Interleukin-1 (IL-1) is the prototypical pro-inflammatory cytokine. IL-1 was implicated as a cardiodepressant factor in septic shock, and subsequent pre-clinical and clinical research has defined important roles for IL-1 in atherosclerosis, acute myocardial infarction (AMI), and heart failure (HF). IL-1 promotes the formation of the atherosclerotic plaque and facilitates its progression and complication. In a large phase III clinical trial of stable patients with prior AMI, blocking IL-1 activity using a monoclonal antibody prevented recurrent atherothrombotic cardiovascular events...
June 7, 2018: European Heart Journal
https://www.readbyqxmd.com/read/29563078/evaluating-a-web-based-social-anxiety-intervention-among-university-students-randomized-controlled-trial
#9
Hugh Cameron McCall, Chris G Richardson, Fjola Dogg Helgadottir, Frances S Chen
BACKGROUND: Treatment rates for social anxiety, a prevalent and potentially debilitating condition, remain among the lowest of all major mental disorders today. Although computer-delivered interventions are well poised to surmount key barriers to the treatment of social anxiety, most are only marginally effective when delivered as stand-alone treatments. A new, Web-based cognitive behavioral therapy (CBT) intervention called Overcome Social Anxiety was recently created to address the limitations of prior computer-delivered interventions...
March 21, 2018: Journal of Medical Internet Research
https://www.readbyqxmd.com/read/29518918/protein-biomarkers-for-early-detection-of-pancreatic-ductal-adenocarcinoma-progress-and-challenges
#10
Alex Root, Peter Allen, Paul Tempst, Kenneth Yu
Approximately 75% of patients with pancreatic ductal adenocarcinoma are diagnosed with advanced cancer, which cannot be safely resected. The most commonly used biomarker CA19-9 has inadequate sensitivity and specificity for early detection, which we define as Stage I/II cancers. Therefore, progress in next-generation biomarkers is greatly needed. Recent reports have validated a number of biomarkers, including combination assays of proteins and DNA mutations; however, the history of translating promising biomarkers to clinical utility suggests that several major hurdles require careful consideration by the medical community...
March 7, 2018: Cancers
https://www.readbyqxmd.com/read/29517535/the-institutional-development-award-states-pediatric-clinical-trials-network-building-research-capacity-among-the-rural-and-medically-underserved
#11
Jessica Snowden, Paul Darden, Paul Palumbo, Phil Saul, Jeannette Lee
PURPOSE OF REVIEW: The institutional development award (IDeA) program was created to increase the competitiveness of investigators in states with historically low success rates for National Institutes of Health (NIH) research funding applications. IDeA states have high numbers of rural and medically underserved residents with disproportionately high rates of infant mortality, obesity, and poverty. This program supports the development and expansion of research infrastructure and research activities in these states...
April 2018: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/29398575/rigor-and-reproducibility-in-research-with-transcranial-electrical-stimulation-an-nimh-sponsored-workshop
#12
REVIEW
Marom Bikson, Andre R Brunoni, Leigh E Charvet, Vincent P Clark, Leonardo G Cohen, Zhi-De Deng, Jacek Dmochowski, Dylan J Edwards, Flavio Frohlich, Emily S Kappenman, Kelvin O Lim, Colleen Loo, Antonio Mantovani, David P McMullen, Lucas C Parra, Michele Pearson, Jessica D Richardson, Judith M Rumsey, Pejman Sehatpour, David Sommers, Gozde Unal, Eric M Wassermann, Adam J Woods, Sarah H Lisanby
BACKGROUND: Neuropsychiatric disorders are a leading source of disability and require novel treatments that target mechanisms of disease. As such disorders are thought to result from aberrant neuronal circuit activity, neuromodulation approaches are of increasing interest given their potential for manipulating circuits directly. Low intensity transcranial electrical stimulation (tES) with direct currents (transcranial direct current stimulation, tDCS) or alternating currents (transcranial alternating current stimulation, tACS) represent novel, safe, well-tolerated, and relatively inexpensive putative treatment modalities...
May 2018: Brain Stimulation
https://www.readbyqxmd.com/read/29348854/acid-ceramidase-and-its-inhibitors-a-de-novo-drug-target-and-a-new-class-of-drugs-for-killing-glioblastoma-cancer-stem-cells-with-high-efficiency
#13
Ninh B Doan, Hisham Alhajala, Mona M Al-Gizawiy, Wade M Mueller, Scott D Rand, Jennifer M Connelly, Elizabeth J Cochran, Christopher R Chitambar, Paul Clark, John Kuo, Kathleen M Schmainda, Shama P Mirza
Glioblastoma remains the most common, malignant primary cancer of the central nervous system with a low life expectancy and an overall survival of less than 1.5 years. The treatment options are limited and there is no cure. Moreover, almost all patients develop recurrent tumors, which typically are more aggressive. Therapeutically resistant glioblastoma or glioblastoma stem-like cells (GSCs) are hypothesized to cause this inevitable recurrence. Identifying prognostic biomarkers of glioblastoma will potentially advance knowledge about glioblastoma tumorigenesis and enable discovery of more effective therapies...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29347996/the-apathy-in-dementia-methylphenidate-trial-2-admet-2-study-protocol-for-a-randomized-controlled-trial
#14
Roberta W Scherer, Lea Drye, Jacobo Mintzer, Krista Lanctôt, Paul Rosenberg, Nathan Herrmann, Prasad Padala, Olga Brawman-Mintzer, William Burke, Suzanne Craft, Alan J Lerner, Allan Levey, Anton Porsteinsson, Christopher H van Dyck
BACKGROUND: Alzheimer's disease (AD) is characterized not only by cognitive and functional decline, but also often by the presence of neuropsychiatric symptoms. Apathy, which can be defined as a lack of motivation, is one of the most prevalent neuropsychiatric symptoms in AD and typically leads to a worse quality of life and greater burden for caregivers. Treatment options for apathy in AD are limited, but studies have examined the use of the amphetamine, methylphenidate. The Apathy in Dementia Methylphenidate Trial (ADMET) found that treatment of apathy in AD with methylphenidate was associated with significant improvement in apathy in two of three outcome measures, some evidence of improvement in global cognition, and minimal adverse events...
January 18, 2018: Trials
https://www.readbyqxmd.com/read/29313063/using-gene-expression-data-to-direct-breast-cancer-therapy-evidence-from-a-preclinical-trial
#15
REVIEW
Shams Reaz, Deimante Tamkus, Eran R Andrechek
The heterogeneity both within and between breast cancers presents a significant clinical challenge for both diagnosis and therapy. This heterogeneity is present at all levels of analysis in breast cancer, ranging from genomic to metabolomic. A function of this heterogeneity is that numerous signaling networks are activated, and while treatment of one arm may be initially effective, this allows the tumor to be poised to evolve a resistance mechanism. Here we review the classification of breast cancers and discuss therapy of hormone positive, HER2 positive, and triple negative breast cancers...
February 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29275007/fexinidazole-a-new-drug-for-african-sleeping-sickness-on-the-horizon
#16
Michael P Pollastri
Decades after the last new chemical entity was added to the pharmacopeia for human African trypanosomiasis (or sleeping sickness), orally dosed fexinidazole stands poised to replace the current treatment regimen for Trypanosoma brucei gambiense infections, following a positive Phase 2/3 clinical trial.
March 2018: Trends in Parasitology
https://www.readbyqxmd.com/read/29207939/tocilizumab-for-the-management-of-immune-mediated-adverse-events-secondary-to-pd-1-blockade
#17
Chipman Rg Stroud, Aparna Hegde, Cynthia Cherry, Abdul R Naqash, Nitika Sharma, Srikala Addepalli, Sulochana Cherukuri, Teresa Parent, Jessica Hardin, Paul Walker
Background Immune checkpoint inhibitors are poised to revolutionize the management of a growing number of malignancies. Unfortunately, the management of steroid-refractory immune mediated adverse events is based on a paucity of randomized data and limited to single center experiences. Our initial experience with the IL-6 receptor antagonist tocilizumab showed clinical improvement in a wide variety of irAEs. As a result, we adopted the use of tocilizumab for the management of steroid refractory irAEs. Methods The character and clinical course of irAEs were abstracted from the medical record and analyzed...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29189290/period-dependent-associations-between-hypotension-during-and-for-four-days-after-noncardiac-surgery-and-a-composite-of-myocardial-infarction-and-death-a-substudy-of-the-poise-2-trial
#18
Daniel I Sessler, Christian S Meyhoff, Nicole M Zimmerman, Guangmei Mao, Kate Leslie, Skarlet M Vásquez, Packianathaswamy Balaji, Jesús Alvarez-Garcia, Alexandre B Cavalcanti, Joel L Parlow, Prashant V Rahate, Manfred D Seeberger, Bruno Gossetti, S A Walker, Rajendra K Premchand, Rikke M Dahl, Emmanuelle Duceppe, Reitze Rodseth, Fernando Botto, P J Devereaux
BACKGROUND: The relative contributions of intraoperative and postoperative hypotension to perioperative morbidity remain unclear. We determined the association between hypotension and a composite of 30-day myocardial infarction and death over three periods: (1) intraoperative, (2) remaining day of surgery, and (3) during the initial four postoperative days. METHODS: This was a substudy of POISE-2, a 10,010-patient factorial-randomized trial of aspirin and clonidine for prevention of myocardial infarction...
February 2018: Anesthesiology
https://www.readbyqxmd.com/read/29136283/population-pk-analyses-of-ubrogepant-mk-1602-a-cgrp-receptor-antagonist-enriching-in-clinic-plasma-pk-sampling-with-outpatient-dried-blood-spot-sampling
#19
Chi-Chung Li, Marissa Dockendorf, Ken Kowalski, Bei Yang, Yang Xu, Iris Xie, Huub Jan Kleijn, Rolien Bosch, Christopher Jones, Bob Thornton, Eugene E Marcantonio, Tiffini Voss, Kevin P Bateman, Prajakti A Kothare
Merck & Co., Inc. (Kenilworth, New Jersey) has recently published an integrated strategy for implementation of dried blood spots (DBS) in late-stage trials for population pharmacokinetic (PK) modeling. We applied this strategy for another late-stage clinical program: ubrogepant (MK-1602), a novel oral calcitonin gene-related peptide receptor antagonist for acute treatment of migraine. At the time of implementation, ubrogepant was entering phase 2 development. DBS was implemented to acquire PK information proximal to an acute migraine event to enable exposure-response modeling...
November 14, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29133290/cd137-4-1bb-costimulation-modifies-dna-methylation-in-cd8-t-cell-relevant-genes
#20
M Angela Aznar, Sara Labiano, Angel Diaz-Lagares, Carmen Molina, Saray Garasa, Arantza Azpilikueta, Iñaki Etxeberria, Alfonso R Sanchez-Paulete, Alan J Korman, Manel Esteller, Juan Sandoval, Ignacio Melero
CD137 (4-1BB) costimulation imprints long-term changes that instruct the ultimate behavior of T cells that have previously experienced CD137 ligation. Epigenetic changes could provide a suitable mechanism for these long-term consequences. Genome-wide DNA methylation arrays were carried out on human peripheral blood CD8+ T lymphocytes stimulated with agonist monoclonal antibody to CD137, including urelumab, which is in phase I/II clinical trials for cancer immunotherapy. Several genes showed consistent methylation patterns in response to CD137 costimulation, which were confirmed by pyrosequencing in a series of healthy donors...
January 2018: Cancer Immunology Research
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