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https://www.readbyqxmd.com/read/29350327/hypermutated-tumors-and-immune-checkpoint-inhibition
#1
Kristen K Ciombor, Richard M Goldberg
Microsatellite instability-high/DNA mismatch repair deficient tumors are found across the cancer spectrum and often harbor markedly increased numbers of mutations when compared to microsatellite stable/DNA mismatch repair proficient tumors. As a result of this high mutational load, tumor-infiltrating lymphocyte density is increased and more immunogenic neoepitopes are expressed, leading to upregulation of immune checkpoints in these tumors. Checkpoint inhibitors such as pembrolizumab and nivolumab, both immunoglobulin G4 (IgG4) monoclonal antibodies that block interactions between the programmed cell death receptor-1 and its ligands, have significant activity in this tumor class...
January 19, 2018: Drugs
https://www.readbyqxmd.com/read/29305768/pharmacological-prevention-of-cardiovascular-outcomes-in-diabetes-mellitus-established-and-emerging-agents
#2
REVIEW
David R Saxon, Neda Rasouli, Robert H Eckel
Cardiovascular disease is a major cause of morbidity and mortality in patients with type 2 diabetes. For this reason, there is a great deal of interest in determining how therapies commonly used to treat patients with diabetes impact cardiovascular outcomes. Results from recently completed cardiovascular outcomes trials of diabetes agents from several medication classes are leading to a sea change in how we think about diabetes treatment. The primary focus of this paper is to review recently completed and ongoing diabetes medication cardiovascular outcomes trials...
January 5, 2018: Drugs
https://www.readbyqxmd.com/read/29299849/lipid-management-in-chronic-kidney-disease-systematic-review-of-pcsk9-targeting
#3
REVIEW
BinBin Zheng-Lin, Alberto Ortiz
Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD) and CKD is considered a coronary artery disease risk equivalent. So far, statins have been the mainstay of primary and secondary prevention of cardiovascular disease in the general population. However, their benefit on outcomes is limited and controversial in CKD patients and new therapeutic approaches to reduce cardiovascular risk are needed. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin 9 (PCSK9) reduce low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) in high-risk populations and cardiovascular events in secondary prevention...
January 3, 2018: Drugs
https://www.readbyqxmd.com/read/29264783/drug-induced-kidney-stones-and-crystalline-nephropathy-pathophysiology-prevention-and-treatment
#4
REVIEW
Michel Daudon, Vincent Frochot, Dominique Bazin, Paul Jungers
Drug-induced calculi represent 1-2% of all renal calculi. The drugs reported to produce calculi may be divided into two groups. The first one includes poorly soluble drugs with high urine excretion that favour crystallisation in the urine. Among them, drugs used for the treatment of patients with human immunodeficiency, namely atazanavir and other protease inhibitors, and sulphadiazine used for the treatment of cerebral toxoplasmosis, are the most frequent causes. Besides these drugs, about 20 other molecules may induce nephrolithiasis, such as ceftriaxone or ephedrine-containing preparations in subjects receiving high doses or long-term treatment...
December 20, 2017: Drugs
https://www.readbyqxmd.com/read/29260457/correction-to-tocilizumab-a-review-in-rheumatoid-arthritis
#5
Lesley J Scott
The article Tocilizumab: A Review in Rheumatoid Arthritis, written by Lesley J. Scott, was originally published Online First without open access. After publication in volume 77, issue 17, pages 1865-1879 F. Hoffmann-La Roche Ltd requested that the article be Open Choice to make the article an open access publication. Post-publication open access was funded by F. Hoffmann-La Roche Ltd. Further details may be found at http://www.medengine.com/Redeem/68FBF06068F81EA7 . The article is forthwith distributed under the terms of the Creative Commons Attribution-NonCommercial 4...
December 19, 2017: Drugs
https://www.readbyqxmd.com/read/29236231/dimethyl-fumarate-a-review-in-moderate-to-severe-plaque-psoriasis
#6
Hannah A Blair
Fumaric acid esters (FAEs) have been used in the treatment of psoriasis in some European countries for over 20 years, and are recommended in the European guidelines for the management of moderate to severe plaque psoriasis. Dimethyl fumarate (Skilarence®; hereafter referred to as DMF) is an orally administered FAE indicated for the treatment of moderate to severe plaque psoriasis in adults in need of systemic medicinal therapy; unlike other available FAEs, it is not formulated in combination with monoethyl fumarate salts...
December 13, 2017: Drugs
https://www.readbyqxmd.com/read/29230684/imipenem-relebactam-and-meropenem-vaborbactam-two-novel-carbapenem-%C3%AE-lactamase-inhibitor-combinations
#7
REVIEW
George G Zhanel, Courtney K Lawrence, Heather Adam, Frank Schweizer, Sheryl Zelenitsky, Michael Zhanel, Philippe R S Lagacé-Wiens, Andrew Walkty, Andrew Denisuik, Alyssa Golden, Alfred S Gin, Daryl J Hoban, Joseph P Lynch, James A Karlowsky
Relebactam (formerly known as MK-7655) is a non-β-lactam, bicyclic diazabicyclooctane, β-lactamase inhibitor that is structurally related to avibactam, differing by the addition of a piperidine ring to the 2-position carbonyl group. Vaborbactam (formerly known as RPX7009) is a non-β-lactam, cyclic, boronic acid-based, β-lactamase inhibitor. The structure of vaborbactam is unlike any other currently marketed β-lactamase inhibitor. Both inhibitors display activity against Ambler class A [including extended-spectrum β-lactamases (ESBLs), Klebsiella pneumoniae carbapenemases (KPCs)] and class C β-lactamases (AmpC)...
December 12, 2017: Drugs
https://www.readbyqxmd.com/read/29218501/evaluating-safety-reporting-in-paediatric-antibiotic-trials-2000-2016-a-systematic-review-and-meta-analysis
#8
REVIEW
Paola Pansa, Yingfen Hsia, Julia Bielicki, Irja Lutsar, A Sarah Walker, Mike Sharland, Laura Folgori
BACKGROUND: There are very few options to treat multidrug-resistant bacterial infections in children. A major barrier is the duration and complexity of regulatory trials of new antibiotics. Extrapolation of safety data from adult trials could facilitate drug development for children. OBJECTIVE: We performed a systematic review on the safety of antibiotic clinical trials (CTs) in children (0-18 years) to evaluate the overall quality of safety trials conducted in children and to determine if age-specific adverse events (AEs) could be identified for specific antibiotic classes...
December 7, 2017: Drugs
https://www.readbyqxmd.com/read/29188449/current-and-new-therapeutic-strategies-for-relapsed-and-refractory-multiple-myeloma-an-update
#9
REVIEW
Inger S Nijhof, Niels W C J van de Donk, Sonja Zweegman, Henk M Lokhorst
Although survival of multiple myeloma patients has at least doubled during recent years, most patients eventually relapse, and treatment at this stage may be particularly complex. At the time of relapse, the use of alternative drugs to those given upfront is current practice. However, many new options are currently available for the treatment of relapsed multiple myeloma, including recently approved drugs, such as the second- and third-generation proteasome inhibitors carfilzomib and ixazomib, the immunomodulatory agent pomalidomide, the monoclonal antibodies daratumumab and elotuzumab and the histone deacetylase inhibitor panobinostat, but also new targeted agents are under active investigation (e...
November 29, 2017: Drugs
https://www.readbyqxmd.com/read/29177572/aripiprazole-lauroxil-a-review-in-schizophrenia
#10
James E Frampton
Aripiprazole lauroxil long-acting injectable (LAI) [Aristada®] is an intramuscularly administered, extended-release prodrug of aripiprazole, an established atypical antipsychotic agent that, in terms of its relative position within the class, is at the low end of the risk spectrum for metabolic side effects. In the USA, aripiprazole lauroxil LAI is indicated for the treatment of schizophrenia; approved doses of the drug can be injected once-monthly (q4w), every 6 weeks (q6w) or every 2 months (q8w). The efficacy of the 441 and 882 mg q4w dosages in the treatment of acute exacerbations of schizophrenia and as long-term maintenance therapy in stable schizophrenia has been directly demonstrated in a phase III clinical trial and extension, while the efficacy of the 662 mg q4w, 882 mg q6w and 1064 mg q8w dosing regimens has been established on the basis of pharmacokinetic bridging studies...
November 25, 2017: Drugs
https://www.readbyqxmd.com/read/29164496/correction-to-opicapone-a-review-in-parkinson-s-disease
#11
Lesley J Scott
Parkinson's disease (PD) is the most common chronic, progressive, neurodegenerative disease, with a mean age of onset of 57 years [1, 2].
November 21, 2017: Drugs
https://www.readbyqxmd.com/read/29159797/correlation-of-opioid-mortality-with-prescriptions-and-social-determinants-a-cross-sectional-study-of-medicare-enrollees
#12
Christos A Grigoras, Styliani Karanika, Elpida Velmahos, Michail Alevizakos, Myrto-Eleni Flokas, Christos Kaspiris-Rousellis, Ioannis-Nektarios Evaggelidis, Panagiotis Artelaris, Constantinos I Siettos, Eleftherios Mylonakis
BACKGROUND: The opioid epidemic is an escalating health crisis. We evaluated the impact of opioid prescription rates and socioeconomic determinants on opioid mortality rates, and identified potential differences in prescription patterns by categories of practitioners. METHODS: We combined the 2013 and 2014 Medicare Part D data and quantified the opioid prescription rate in a county level cross-sectional study with data from 2710 counties, 468,614 unique prescribers and 46,665,037 beneficiaries...
November 20, 2017: Drugs
https://www.readbyqxmd.com/read/29139092/effects-of-allopurinol-on-endothelial-function-a-systematic-review-and-meta-analysis-of-randomized-placebo-controlled-trials
#13
REVIEW
Arrigo F G Cicero, Matteo Pirro, Gerald F Watts, Dimitri P Mikhailidis, Maciej Banach, Amirhossein Sahebkar
INTRODUCTION: Uric acid (UA), the final product of purine catabolism, may be associated with an increased risk of cardiovascular disease. AIM: The aim of this meta-analysis of randomized placebo-controlled trials was to evaluate whether lowering serum UA (SUA) levels with allopurinol is associated with improved flow-mediated dilation (FMD), a validated marker of early vascular damage. METHODS: A literature search was carried out from inception until 20 June 2017...
November 14, 2017: Drugs
https://www.readbyqxmd.com/read/29139091/pharmacological-approach-to-the-management-of-crohn-s-disease-patients-with-perianal-disease
#14
REVIEW
Fernando Bermejo, Iván Guerra, Alicia Algaba, Antonio López-Sanromán
Perianal localization of Crohn's disease involves significant morbidity, affects quality of life and results in an increased use of healthcare resources. Medical and surgical therapies contribute to its management. The objective of this review is to address the current understanding in the management of perianal Crohn's disease, with the main focus in reviewing pharmacological therapies, including stem cells. In complex fistulas, once local sepsis has been controlled by surgical drainage and/or antibiotics, anti-TNF drugs (infliximab, adalimumab) are the first-line therapy, with or without associated immunomodulators...
January 2018: Drugs
https://www.readbyqxmd.com/read/29124682/nonacog-beta-pegol-a-review-in-haemophilia-b
#15
Yahiya Y Syed
Nonacog beta pegol [Refixia(®) (EU)] is an intravenously-administered, glycoPEGylated recombinant factor IX (FIX), with an extended terminal half-life. It is approved in the EU for the treatment and prophylaxis of bleeding in patients aged ≥ 12 years with haemophilia B. The therapeutic efficacy and safety of nonacog beta pegol was demonstrated in the phase 3 Paradigm trials in previously treated adolescents and adults with haemophilia B. In Paradigm 2, nonacog beta pegol showed good haemostatic effects when treating bleeds on-demand, and reduced annualized bleeding rates when used as a once-weekly prophylaxis...
November 9, 2017: Drugs
https://www.readbyqxmd.com/read/29094313/progress-in-elucidating-biomarkers-of-antidepressant-pharmacological-treatment-response-a-systematic-review-and-meta-analysis-of-the-last-15-years
#16
REVIEW
G Voegeli, M L Cléry-Melin, N Ramoz, P Gorwood
BACKGROUND: Antidepressant drugs are widely prescribed, but response rates after 3 months are only around one-third, explaining the importance of the search of objectively measurable markers predicting positive treatment response. These markers are being developed in different fields, with different techniques, sample sizes, costs, and efficiency. It is therefore difficult to know which ones are the most promising. OBJECTIVE: Our purpose was to compute comparable (i...
November 2, 2017: Drugs
https://www.readbyqxmd.com/read/29288370/letermovir-first-global-approval
#17
Esther S Kim
Letermovir (Prevymis™) is an orally or intravenously administered cytomegalovirus (CMV) DNA terminase complex inhibitor being developed by Merck & Co., Inc., under a global license from AiCuris Anti-infective Cures GmbH. Letermovir has been approved in Canada and the USA for the prophylaxis of CMV infection and disease in adult CMV-seropositive recipients of an allogeneic haematopoietic stem cell transplant (HSCT). In addition, letermovir has received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use, and is under review in several countries, including Japan...
January 2018: Drugs
https://www.readbyqxmd.com/read/29270913/fulvestrant-a-review-in-advanced-breast-cancer-not-previously-treated-with-endocrine-therapy
#18
Emma D Deeks
Fulvestrant (Faslodex®), a selective estrogen receptor (ER) degrader, is now indicated for the treatment of ER+ or hormone-receptor positive (HR+)/HER2- advanced breast cancer in postmenopausal women previously untreated with endocrine therapy. In the phase 3 FALCON trial conducted in this setting, intramuscular fulvestrant 500 mg/month (plus an additional dose at 2 weeks) was significantly more effective in prolonging progression-free survival (PFS) than oral anastrozole 1 mg/day (particularly in patients with non-visceral disease), with this benefit seemingly driven by fulvestrant recipients responding significantly longer to treatment...
January 2018: Drugs
https://www.readbyqxmd.com/read/29209955/acalabrutinib-first-global-approval
#19
Anthony Markham, Sohita Dhillon
Acerta Pharma is developing the Bruton's tyrosine kinase inhibitor acalabrutinib (Calquence®) for the treatment of various haematological and solid malignancies. The drug has received accelerated approval from the US FDA for the treatment of mantle cell lymphoma based on the results of a phase II study, and phase III trials in mantle cell lymphoma and chronic lymphocytic leukaemia are currently underway. This article summarizes the milestones in the development of acalabrutinib leading to this first approval for mantle cell lymphoma...
January 2018: Drugs
https://www.readbyqxmd.com/read/29196953/preservative-free-prostaglandin-analogs-and-prostaglandin-timolol-fixed-combinations-in-the-treatment-of-glaucoma-efficacy-safety-and-potential-advantages
#20
REVIEW
Gábor Holló, Andreas Katsanos, Kostas G Boboridis, Murat Irkec, Anastasios G P Konstas
Glaucoma therapy-related ocular surface disease (OSD) is a serious pathology with a broad spectrum of insidious clinical presentations and complex pathogenesis that undermines long-term glaucoma care. Preservatives, especially benzalkonium chloride (BAK), contained in topical intraocular pressure-lowering medications frequently cause or aggravate OSD in glaucoma. Management of these patients is challenging, and to date often empirical due to the scarcity of controlled long-term clinical trials. Most of the available data are extracted from case series and retrospective analysis...
January 2018: Drugs
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