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https://www.readbyqxmd.com/read/29157398/new-advances-in-disease-modifying-therapies-for-relapsing-and-progressive-forms-of-multiple-sclerosis
#1
REVIEW
Angela Vidal-Jordana
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system in which inflammation, demyelination, and axonal loss occurs from early stages of the disease. It mainly affects people between 20 and 40 years old, with a female predominance. Treatment options have been increasingly growing in the past years and newer drugs, some with novel mechanisms of action, are being developed for treating patients with MS. There is an increasing interest in developing new drugs that will promote neuroprotection and/or myelin repair through different mechanisms of action that may target the most degenerative component of the disease...
February 2018: Neurologic Clinics
https://www.readbyqxmd.com/read/29156677/overcoming-resistance-to-single-agent-therapy-for-oncogenic-braf-gene-fusions-via-combinatorial-targeting-of-mapk-and-pi3k-mtor-signaling-pathways
#2
Payal Jain, Amanda Silva, Harry J Han, Shih-Shan Lang, Yuankun Zhu, Katie Boucher, Tiffany E Smith, Aesha Vakil, Patrick Diviney, Namrata Choudhari, Pichai Raman, Christine M Busch, Tim Delaney, Xiaodong Yang, Aleksandra K Olow, Sabine Mueller, Daphne Haas-Kogan, Elizabeth Fox, Phillip B Storm, Adam C Resnick, Angela J Waanders
Pediatric low-grade gliomas (PLGGs) are frequently associated with activating BRAF gene fusions, such as KIAA1549-BRAF, that aberrantly drive the mitogen activated protein kinase (MAPK) pathway. Although RAF inhibitors (RAFi) have been proven effective in BRAF-V600E mutant tumors, we have previously shown how the KIAA1549-BRAF fusion can be paradoxically activated by RAFi. While newer classes of RAFi, such as PLX8394, have now been shown to inhibit MAPK activation by KIAA1549-BRAF, we sought to identify alternative MAPK pathway targeting strategies using clinically relevant MEK inhibitors (MEKi), along with potential escape mechanisms of acquired resistance to single-agent MAPK pathway therapies...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152232/recent-therapeutic-advances-in-chronic-lymphocytic-leukemia
#3
REVIEW
Prithviraj Bose, Varsha Gandhi
The last several years have witnessed a paradigm shift in the management of patients with chronic lymphocytic leukemia (CLL). The course of this very heterogeneous disease, traditionally treated with chemotherapeutic agents usually in combination with rituximab, typically has been characterized by remissions and relapses, and survival times vary greatly, depending on intrinsic biological attributes of the leukemia. The developments of the last few years have been transformative, ushering in an era of novel, molecularly targeted therapies, made possible by extensive efforts to elucidate the biology of the disease that predated the new targeted drugs...
2017: F1000Research
https://www.readbyqxmd.com/read/29151989/human-induced-pluripotent-stem-cells-and-the-modelling-of-alzheimer-s-disease-the-human-brain-outside-the-dish
#4
REVIEW
Godwin Tong, Pablo Izquierdo, Rana Arham Raashid
Background: Neurodegenerative diseases like Alzheimer's Disease (AD) are a global health issue primarily in the elderly. Although AD has been investigated using primary cultures, animal models and post-mortem human brain tissues, there are currently no effective treatments. Summary: With the advent of induced pluripotent stem cells (iPSCs) reprogrammed from fully differentiated adult cells such as skin fibroblasts, newer opportunities have arisen to study the pathophysiology of many diseases in more depth...
2017: Open Neurology Journal
https://www.readbyqxmd.com/read/29151439/clopidogrel-or-ticagrelor-in-acute-coronary-syndrome-patients-treated-with-newer-generation-drug-eluting-stents-change-dapt
#5
Paolo Zocca, Liefke C van der Heijden, Marlies M Kok, Marije M Löwik, Marc Hartmann, Martin G Stoel, J W Louwerenburg, Frits H A F de Man, Gerard C M Linssen, Iris L Knottnerus, Carine J M Doggen, K Gert van Houwelingen, Clemens von Birgelen
AIMS: Acute coronary syndrome (ACS) guidelines have been changed, favouring more potent antiplatelet drugs. We aimed to evaluate the safety and efficacy of a ticagrelor- instead of a clopidogrel-based primary dual antiplatelet (DAPT) regimen in ACS patients treated with newer-generation drug-eluting stents (DES). METHODS AND RESULTS: CHANGE DAPT (clinicaltrials.gov: NCT03197298) assessed 2,062 consecutive real-world ACS patients, treated by percutaneous coronary intervention (PCI), the primary composite endpoint being net adverse clinical and cerebral events (NACCE: all-cause death, any myocardial infarction, stroke or major bleeding)...
November 20, 2017: EuroIntervention
https://www.readbyqxmd.com/read/29145545/treatment-of-alcohol-induced-psychotic-disorder-alcoholic-hallucinosis-a-systematic-review
#6
Barkat Masood, Peter Lepping, Dmitry Romanov, Rob Poole
Aims: To evaluate the effectiveness of evidence based treatments for alcohol-induced psychotic disorder (AIPD) as described by ICD-10 and DSM-5, a condition that is distinct from schizophrenia and has a close relationship with alcohol withdrawal states. Method: Systematic review using PRISMA guidelines. Results: Of 6205 abstracts found, fifteen studies and ten case reports met criteria and were examined. Larger studies examined the use of first-generation antipsychotic drugs, reporting full or partial remission in most patients...
November 14, 2017: Alcohol and Alcoholism: International Journal of the Medical Council on Alcoholism
https://www.readbyqxmd.com/read/29140112/a-2017-review-of-pharmacotherapy-for-treating-focal-epilepsy-where-are-we-now-and-how-will-treatment-develop
#7
Andreas Schulze-Bonhage
Focal epilepsy is the most common type of epilepsy with approximately 30 million patients affected worldwide. There is a major challenge to develop new antiepileptic treatments as currently approximately one third of patients remain uncontrolled under our best standards of care. Areas covered: An overview is given on first- and second generation antiepileptic drugs and their mechanisms of action, and on recent new strategies for antiepileptic targets, including drugs aiming at disease modification. Expert opinion: Newer antiepileptic drugs have enabled a better tolerated and individualized treatment for many patients...
November 15, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29137347/antiandrogenic-and-antimineralocorticoid-health-benefits-of-coc-containing-newer-progestogens-dienogest-and-drospirenone
#8
REVIEW
Pedro-Antonio Regidor, Adolf E Schindler
Data have demonstrated that COCs, besides offering a satisfactory and safe contraception, offer a variety of non-contraceptive health benefits and therapeutic positive aspects. Many prescribes and users, however, do not realize these positive aspects especially the non-contraceptive health benefits. While the contraceptive use is the primary indication for COC use for most women, these users should be advised in regard of the non-contraceptive benefits when contraception is discussed and prescribed. Using COCs specifically for non-contraceptive indications is an off-label use in many clinical situations (only some exceptions as e...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29131238/the-role-of-prasugrel-in-the-management-of-acute-coronary-syndromes-a-systematic-review
#9
M Spartalis, E Tzatzaki, E Spartalis, C Damaskos, A Athanasiou, D Moris, M Politou
OBJECTIVE: Dual antiplatelet therapy (DAPT) is the treatment of choice in the medical management of patients with acute coronary syndrome (ACS). The combination of aspirin and a P2Y12 inhibitor in patients who receive a coronary stent reduces the rate of stent thrombosis and the rates of major adverse cardiovascular events. However, patients with acute coronary syndrome remain at risk of recurrent cardiovascular events despite the advance of medical therapy. The limitations of clopidogrel with variable antiplatelet effects and delayed onset of action are well established and lead to the development of newer P2Y12 inhibitors...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29129253/rationale-of-a-novel-study-design-for-the-bioflow-v-study-a-prospective-randomized-multicenter-study-to-assess-the-safety-and-efficacy-of-the-orsiro-sirolimus-eluting-coronary-stent-system-using-a-bayesian-approach
#10
Gheorghe Doros, Joseph M Massaro, David E Kandzari, Ron Waksman, Jacques J Koolen, Donald E Cutlip, Laura Mauri
BACKGROUND: Traditional study design submitted to the Food and Drug Administration to test newer drug-eluting stents (DES) for marketing approval is the prospective randomized controlled trial. However, several DES have extensive clinical data from trials conducted outside the United States that have led to utilization of a novel design using the Bayesian approach. This design was proposed for testing DES with bioresorbable polymer compared with DES most commonly in use today that use durable polymers for drug elution...
November 2017: American Heart Journal
https://www.readbyqxmd.com/read/29126866/advances-in-diagnosis-and-management-of-diffuse-large-b-cell-lymphoma
#11
REVIEW
Fernando Cabanillas, Bijal Shah
The management of diffuse large B-cell lymphoma (DLBCL) has been gradually evolving since the discovery of its 2 major forms, the germinal center B-like (GCB) and activated B-cell (ABC) types. Although the reference standard for the identification of these cell types is considered gene expression profiling (GEP), currently the only method commercially available is immunohistochemistry (IHC). The application of various IHC-based algorithms and their correlation with GEP and clinical outcome are discussed. Because of the adverse prognostic implications of the non-GCB type and its potential effects on treatment selection, the recently revised World Health Organization classification has included these biologic cell types...
November 7, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29125840/are-there-physicochemical-differences-between-allosteric-and-competitive-ligands
#12
Richard D Smith, Jing Lu, Heather A Carlson
Previous studies have compared the physicochemical properties of allosteric compounds to non-allosteric compounds. Those studies have found that allosteric compounds tend to be smaller, more rigid, more hydrophobic, and more drug-like than non-allosteric compounds. However, previous studies have not properly corrected for the fact that some protein targets have much more data than other systems. This generates concern regarding the possible skew that can be introduced by the inherent bias in the available data...
November 10, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29118712/comparative-long-term-effect-of-three-anti-p2y12-drugs-after-percutaneous-angioplasty-an-observational-study-based-on-electronic-drug-adherence-monitoring
#13
Valentina Forni Ogna, Isabelle Bassi, Isabelle Menetrey, Olivier Muller, Eric Tousset, Pierre Fontana, Eric Eeckhout, Chin B Eap, Bernard Vrijens, Michel Burnier, Grégoire Wuerzner
Aims: Dual platelet inhibition using anti-P2Y12 drugs and aspirin is the standard of care in patients after percutaneous coronary interventions (PCI). Prasugrel and ticagrelor have been shown to be more potent than clopidogrel with less high on-treatment platelet reactivity. Whether differences in long-term adherence to these drugs can partly explain different antiplatelet efficacy has not been studied so far. The objective was to compare the long-term P2Y12 receptor inhibition and drug adherence to different anti-P2Y12 drugs, and to assess the impact of adherence on the pharmacodynamic effect...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29111505/when-adverse-effects-are-seen-as-desirable-abuse-potential-of-the-newer-generation-antiepileptic-drugs
#14
REVIEW
Kelsey L Hawkins, Barry E Gidal
There has been growing recognition of the possible abuse potential of newer generation antiepileptic drugs, and several of these agents have been categorized as controlled substances in the United States. To properly schedule a new medication, the abuse potential, or the potential for a drug to be used for its nonmedical positive subjective effects, must be determined. Performing a human abuse potential study is one step in the overall abuse potential assessment. These studies analyze the abuse potential of a new drug in a very specific population of known recreational drug users...
October 27, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29109299/long-term-trends-in-antidiabetes-drug-usage-in-the-u-s-real-world-evidence-in-patients-newly-diagnosed-with-type-2-diabetes
#15
Olga Montvida, Jonathan Shaw, John J Atherton, Frances Stringer, Sanjoy K Paul
OJBECTIVE: To explore temporal trends in antidiabetes drug (ADD) prescribing and intensification patterns, along with glycemic levels and comorbidities, and possible benefits of novel ADDs in delaying the need for insulin initiation in patients diagnosed with type 2 diabetes. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes aged 18-80 years, who initiated any ADD, were selected (n = 1,023,340) from the U.S. Centricity Electronic Medical Records. Those who initiated second-line ADD after first-line metformin were identified (subcohort 1, n = 357,482); the third-line therapy choices were further explored...
November 6, 2017: Diabetes Care
https://www.readbyqxmd.com/read/29106654/the-population-level-costs-of-immunosuppression-medications-for-the-treatment-of-glomerulonephritis-are-increasing-over-time-due-to-changing-patterns-of-practice
#16
Sean Barbour, Clifford Lo, Gabriela Espino-Hernandez, Sharareh Sajjadi, John Feehally, Scott Klarenbach, Jagbir Gill
Background: Immunosuppression (IS) is the main treatment for most types of glomerulonephritis (GN). Quantifying the cost of IS is necessary to ensure equitable access to therapies and optimal health outcomes, but the real-world cost of IS treatment for GN is largely unknown. We examined temporal changes in the population-level IS medication costs for GN over a 14-year period in a large Canadian province. Methods: We linked a provincial pathology database (containing all GN cases from 2000 to 2012) with renal and medication administrative databases to capture clinical characteristics and IS medications, with follow-up until 2013...
July 2, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29105160/strength-in-amalgamation-newer-combination-agents-for-hiv-and-implications-for-practice
#17
Christopher McCoy, Melissa Badowski, Elizabeth Sherman, Rustin Crutchley, Ethan Smith, Daniel B Chastain
Antiretroviral (ART) therapy for treatment of human immunodeficiency virus (HIV) infection has undergone significant changes over the past 30 years. Many single tablet regimens (STR), including newer fixed dose combination (FDC) tablets, are available, offering patients several options for choosing a treatment regimen that works best for them. Given these changes, patients are more likely to adhere to treatment, achieve better clinical outcomes, and experience both fewer side effects and drug-drug interactions...
November 3, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/29098574/immune-contributions-to-osteoarthritis
#18
REVIEW
Erika Barboza Prado Lopes, Adrian Filiberti, Syed Ali Husain, Mary Beth Humphrey
PURPOSE OF THE REVIEW: Mounting evidence supports a role of low-grade inflammation in the pathophysiology of osteoarthritis (OA). We review and discuss the role of synovitis, complement activation, cytokines, and immune cell population in OA. RECENT FINDINGS: Using newer imaging modalities, synovitis is found in the majority of knees with OA. Complement activation and pro-inflammatory cytokines play a significant role in the development of cartilage destruction and synovitis...
November 2, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/29098140/mpgn-and-mixed-cryoglobulinemia-in-a-patient-with-hepatitis-c-new-treatment-implications-and-renal-outcomes
#19
Shannon B Palombo, Eric C Wendel, Laura R Kidd, Farshid Yazdi, Mihran V Naljayan
. INTRODUCTION: The association of hepatitis C virus (HCV), cryoglobulinemia, and membranoproliferative glomerulonephritis (MPGN) is well known. Treatment of underlying HCV infection has greatly improved in recent years with the introduction of direct-acting antivirals (DAA), which have demonstrated curative sustained viral response (SVR) rates for select viral genotypes with the added benefit of less drug side effects. However, a mainstay of newer DAAs is sofosbuvir, which is contraindicated in patients with severe renal impairment...
2017: Clin Nephrol Case Stud
https://www.readbyqxmd.com/read/29097018/antiepileptic-drugs-and-liver-disease
#20
REVIEW
Jorge Vidaurre, Satya Gedela, Shannon Yarosz
Acute, symptomatic seizures or epilepsy may complicate the course of hepatic disease. Choosing the most appropriate antiepileptic drug in this setting represents a difficult challenge, as most medications are metabolized by the liver. This article focuses on the acute and chronic treatment of seizures in patients with advanced liver disease and reviews the hepatotoxic potential of specific antiepileptic drugs. Newer antiepileptic drugs without, or with minimal, hepatic metabolism, such as levetiracetam, lacosamide, topiramate, gabapentin, and pregabalin should be used as first-line therapy...
September 22, 2017: Pediatric Neurology
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