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Clinical Pharmacology and Therapeutics

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https://www.readbyqxmd.com/read/30006942/enlisting-emergency-medicine-clinicians-to-help-reduce-strokes-in-high-risk-patients-with-atrial-fibrillation-and-flutter
#1
LETTER
David R Vinson, Bory Kea, Blanca Coll-Vinent, Tyler W Barrett, Clare L Atzema
No abstract text is available yet for this article.
July 14, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/30006932/response-to-enlisting-emergency-medicine-clinicians-to-help-reduce-strokes-in-high-risk-patients-with-atrial-fibrillation-and-flutter
#2
LETTER
Jonathan C Hsu, James V Freeman
No abstract text is available yet for this article.
July 14, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/30006934/the-jury-is-still-out-on-the-benefits-and-harms-of-methylphenidate-for-children-and-adolescents-with-attention-deficit-hyperactivity-disorder
#3
Ole Jakob Storebø, Erlend Faltinsen, Morris Zwi, Erik Simonsen, Christian Gluud
Much remains unclear about the benefits and harms of methylphenidate for children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Between 2012 and 2018, we conducted two Cochrane systematic reviews on methylphenidate for ADHD. This article explores the main findings in relation to evidence-based practice and our current understanding of ADHD.
July 13, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/30005135/response-to-discontinuation-of-angiotensin-converting-enzyme-inhibitors-due-to-dry-cough-incidence-and-clinical-determinants
#4
Davor Vukadinović, Michael Böhm
No abstract text is available yet for this article.
July 13, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/30005131/discontinuation-of-angiotensin-converting-enzyme-inhibitors-due-to-dry-cough-incidence-and-clinical-determinants
#5
Jasper J Brugts
No abstract text is available yet for this article.
July 13, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/30004115/ldl-cholesterol-is-not-the-only-clinically-relevant-biomarker-for-coronary-artery-disease-or-acute-coronary-syndrome
#6
Patrick A Field, Ramachandran S Vasan
Coronary artery disease (CAD) is a progressive disorder and its risk is best determined using multiple biomarkers and risk factors. Many novel biomarkers have been shown to improve cardiovascular disease risk beyond that of the traditional risk factors, including polygenic risk scores, small very low-density lipoprotein (VLDL), ApoB, triglycerides (TG), non-HDL-c, lipoprotein (a) (Lp(a)), coronary calcium scores, C-reactive protein (CRP), B-type natriuretic peptide (BNP), troponins, and many other novel biomarkers that have been measured using high throughput assays...
July 13, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/30004113/ldl-cholesterol-is-the-only-clinically-relevant-biomarker-for-atherosclerotic-cardiovascular-disease-ascvd-risk
#7
Richard Ofori-Asenso, Sophia Zoungas, Andrew Tonkin, Danny Liew
No abstract text is available yet for this article.
July 13, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29999516/pharmacogenomics-of-vincristine-induced-peripheral-neuropathy-implicates-pharmacokinetic-and-inherited-neuropathy-genes
#8
Galen E B Wright, Ursula Amstutz, Britt I Drögemöller, Joanne Shih, Shahrad R Rassekh, Michael R Hayden, Bruce C Carleton, Colin J D Ross
Vincristine is an effective chemotherapeutic drug for various cancers, including acute lymphoblastic leukemia (ALL). Unfortunately, clinical utility is restricted by dose-limiting vincristine-induced peripheral neuropathies (VIPN). We sought to determine the association of VIPN with a recently-identified risk variant, CEP72 rs924607 and drug absorption, distribution, metabolism, and excretion (ADME) gene variants in pediatric ALL. This was followed by a meta-analysis of pharmacogenomic data from over 500 patients...
July 12, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29998536/clinical-lipidology-and-the-prevention-of-vascular-disease-time-for-personalized-therapy
#9
William Virgil Brown
Genetic, metabolic, and lifestyle modifications can cause elevations of lipoproteins that contribute to atherosclerotic lesions over time. In the modern world with life extension from many improvements in medicine and public health, most humans live long enough to develop atherosclerosis with concentrations of blood plasma lipoproteins that are very common. Familial abnormalities are prevalent and provide additional challenges in identifying unhealthy but treatable values of low-density (LDL) and very low-density lipoproteins (VLDL)...
July 12, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29998574/cyp3a4-22-impairs-the-elimination-of-ticagrelor-but-has-no-significant-effect-on-the-bioactivation-of-clopidogrel-or-prasugrel
#10
Mikko T Holmberg, Aleksi Tornio, Maria Paile-Hyvärinen, E Katriina Tarkiainen, Mikko Neuvonen, Pertti J Neuvonen, Janne T Backman, Mikko Niemi
CYP3A enzymes participate in the elimination of ticagrelor and the bioactivation of clopidogrel and prasugrel. We studied the effects of functional CYP3A genetic variants (CYP3A4*22; rs35599367 and CYP3A5*3; rs776746) on the pharmacokinetics and pharmacodynamics of ticagrelor, clopidogrel, and prasugrel. Six healthy volunteers with the CYP3A4*1/*22 and CYP3A5*3/*3 genotype (CYP3A4*22 carriers), eight with the CYP3A4*1/*1 and CYP3A5*1/*3 genotype (CYP3A5 expressors), and 11 to 13 with the CYP3A4*1/*1 and CYP3A5*3/*3 genotypes (controls) ingested single doses of ticagrelor, clopidogrel, and prasugrel on separate occasions...
July 11, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29992538/use-of-lipid-lowering-drugs-and-the-risk-of-cataract-a-population-based-nested-case-control-study
#11
Julien Bezin, Yohann Mansiaux, Pernelle Noize, Francesco Salvo, Bernard Bégaud, Antoine Pariente
Eye lens membrane cells require high cholesterol concentrations that might be counteracted by lipid-lowering drugs. Using a nationwide database, we conducted a nested case-control study to evaluate the risk of cataract development associated with the use of lipid-lowering drugs. Patients aged 45 years and over with first cataract surgery in 2014 (cases) and up to four controls matched on age, gender, diabetes, hypothyroidism, glucocorticoid use, cardiovascular risk and area of residence were included in the study...
July 10, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29981151/molecular-modeling-of-drug-transporter-interactions-an-international-transporter-consortium-perspective
#12
Avner Schlessinger, Matthew A Welch, Herman van Vlijmen, Ken Korzekwa, Peter W Swaan, Pär Matsson
Membrane transporters play diverse roles in the pharmacokinetics and pharmacodynamics of small-molecule drugs. Understanding the mechanisms of drug-transporter interactions at the molecular level is therefore essential for the design of drugs with optimal therapeutic effects. This white paper examines recent progress, applications and challenges of molecular modeling of membrane transporters, including modeling techniques that are centered on the structures of transporter ligands, and those focusing on the structures of the transporters...
July 7, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29969839/post-authorisation-changes-to-specific-obligations-of-conditionally-authorised-medicines-in-the-eu-a-retrospective-cohort-study
#13
Lourens T Bloem, Aukje K Mantel-Teeuwisse, Hubert G M Leufkens, Marie L De Bruin, Olaf H Klungel, Jarno Hoekman
When medicines are granted a Conditional Marketing Authorisation (CMA) in Europe, specific obligations are requested to obtain comprehensive data on benefits and risks. We performed a retrospective cohort study to characterise obligations, examine changes to their description and due dates after initial authorisation, determine timing of data submission relative to due dates, and identify drug-, procedure- and obligation-related factors associated with change. We identified 69 obligations for 26 medicines conditionally authorised between 2006 and 2016...
July 3, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29953581/using-genetic-variants-in-the-targets-of-lipid-lowering-therapies-to-inform-drug-discovery-and-development-current-and-future-treatment-options
#14
Brian A Ference
Mendelian randomization studies and "human knock-out" studies of rare loss-of-function coding variants suggest that plasma levels of LDL-C, triglycerides and Lp(a) are causally associated with the risk of cardiovascular disease, and therefore therapies directed against these targets should reduce the risk of cardiovascular events. However, several therapies directed against these targets have failed to reduce the risk of cardiovascular events in large-scale randomized trials, thus suggesting that causality is not sufficient evidence to establish genetic target validation...
June 28, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29953578/assessment-of-consistency-of-drug-interaction-information-in-drug-labels-among-the-us-the-uk-china-japan-and-korea
#15
Sohyun Jeong, Gyungmin Kam, Junqing Li, Sejin Lee, Hyesung Lee, Yunha Noh, Ju-Young Shin
Information gap in drug labelingamong countries create challenges in therapeutic use of drugs.We aimed to evaluate the consistency ofdrug interaction information in drug labels among five countries. The studydrugs were chosen fromthe commonly approved drug list inthe United States, United Kingdom, China, Japan, and Korea. The degree of agreement of drug interaction data wasevaluated by kappa coefficient.Thirty-eight drugs wereevaluated, and moderate degree of agreement was observed among all countries' labeling (κ = 0...
June 28, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29952004/randomized-phase-1-healthy-volunteer-study-of-uttr1147a-il-22fc-a-potential-therapy-for-epithelial-injury
#16
Michael E Rothenberg, Yehong Wang, Annemarie Lekkerkerker, Dimitry M Danilenko, Romeo Maciuca, Rich Erickson, Ann Herman, Eric Stefanich, Timothy T Lu
Most treatments for epithelial injury target hematopoietic mechanisms, possibly causing immunosuppression. Interleukin (IL)-22 promotes tissue regeneration, acting directly on epithelial cells. UTTR1147A, a human IL-22Fc (IgG4) fusion protein, activates IL-22 signaling. This phase 1 placebo-controlled trial of single, ascending, intravenous (IV; 1-120 μg/kg) and subcutaneous (SC; 3-120 μg/kg) doses of UTTR1147A analyzed its effects on safety, tolerability, pharmacokinetics, and pharmacodynamic biomarkers in healthy volunteers...
June 28, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29951994/a-novel-method-to-estimate-long-term-chronological-changes-from-fragmented-observations-in-disease-progression
#17
Takaaki Ishida, Keita Tokuda, Akihiro Hisaka, Masashi Honma, Shinichi Kijima, Hiroyuki Takatoku, Takeshi Iwatsubo, Takashi Moritoyo, Hiroshi Suzuki
Clinical observations of patients with chronic diseases are often restricted in terms of duration. Therefore, obtaining a quantitative and comprehensive understanding of the chronology of chronic diseases is challenging, due to the inability to precisely estimate the patient's disease stage at the time-point of observation. We developed a novel method to reconstitute long-term disease progression from temporally fragmented data by extending the nonlinear mixed-effects model to incorporate the estimation of "disease time" of each subject...
June 28, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29947417/cinnamon-and-cassia-nomenclature-confusion-a-challenge-to-the-applicability-of-clinical-data
#18
Hellen A Oketch-Rabah, Robin J Marles, Josef A Brinckmann
Several Cinnamomum species' barks are generally labeled as cinnamon although only Cinnamomum verum carries the common name of true cinnamon. Cassia, a common name for a related species, is rarely used on labels; instead various cassia types may also be labeled cinnamon. Confusion of true cinnamon and cassia spices in foods generally does not present a risk to health, except possibly at the highest intake levels. However, clinical studies with Cinnamomum investigational products have been published that inadequately describe or lack botanical identification information...
June 27, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/30007034/response-to-the-role-of-quantitative-systems-pharmacology-in-the-design-of-first-in-human-trials
#19
LETTER
Kevin Blake, Milton Bonelli, Stefano Ponzano, Harald Enzmann
No abstract text is available yet for this article.
June 26, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29943816/the-role-of-quantitative-systems-pharmacology-in-the-design-of-first-in-human-trials
#20
LETTER
Piet H van der Graaf, Neil Benson
No abstract text is available yet for this article.
June 26, 2018: Clinical Pharmacology and Therapeutics
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