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https://www.readbyqxmd.com/read/28088251/lucerastat-an-iminosugar-with-potential-as-substrate-reduction-therapy-for-glycolipid-storage-disorders-safety-tolerability-and-pharmacokinetics-in-healthy-subjects
#1
N Guérard, O Morand, J Dingemanse
BACKGROUND: Lucerastat, an inhibitor of glucosylceramide synthase, has the potential to restore the balance between synthesis and degradation of glycosphingolipids in glycolipid storage disorders such as Gaucher disease and Fabry disease. The safety, tolerability, and pharmacokinetics of oral lucerastat were evaluated in two separate randomized, double-blind, placebo-controlled, single- and multiple-ascending dose studies (SAD and MAD, respectively) in healthy male subjects. METHODS: In the SAD study, 31 subjects received placebo or a single oral dose of 100, 300, 500, or 1000 mg lucerastat...
January 14, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28088030/efficacy-and-safety-of-linagliptin-metformin-single-pill-combination-as-initial-therapy-in-drug-na%C3%A3-ve-asian-patients-with-type-2-diabetes
#2
Yiming Mu, Changyu Pan, Bei Fan, Uwe Hehnke, Xiuzhen Zhang, Xuejun Zhang, Xiaoyue Wang, Jingdong Liu, Ying Zhang, Jianling Du, Jianhua Ma, Yan Gong
AIM: To assess efficacy/safety of initial linagliptin/metformin single-pill combination (SPC) therapies versus individual drug components over 24weeks in treatment-naïve Asian patients with type 2 diabetes mellitus and insufficient glycemic control. METHODS: Patients (initial glycated hemoglobin [HbA1c] ⩾7.5% to <11.0% [58-97mmol/mol]; main group) were randomized to: linagliptin 5mg once daily (qd); metformin 500mg twice daily (bid); metformin 1000mg bid; linagliptin 2...
December 5, 2016: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28087597/membrane-depolarizing-channel-blockers-induce-selective-glioma-cell-death-by-impairing-nutrient-transport-and-unfolded-protein-amino-acid-responses
#3
Mia Niklasson, Gianluca Maddalo, Zuzana Sramkova, Ercan Mutlu, Shimei Wee, Petra Sekyrova, Linnéa Schmidt, Nicolas Fritz, Ivar Dehnisch, Gregorios Kyriatzis, Michaela Krafcikova, Brittany B Carson, Jennifer Feenstra, Voichita D Marinescu, Anna Segerman, Martin Haraldsson, Anna-Lena Gustavsson, Lars Gj Hammarström, Annika Jenmalm-Jensen, Lene Uhrbom, A F Maarten Altelaar, Sten Linnarsson, Per Uhlén, Lukas Trantirek, C Theresa Vincent, Sven Nelander, Per Øyvind Enger, Michael Andäng
Glioma-initiating cells (GIC) are considered the underlying cause of recurrences of aggressive glioblastomas, replenishing the tumor population and undermining the efficacy of conventional chemotherapy. Here we report the discovery that inhibiting T-type voltage-gated Ca2+ and KCa channels can effectively induce selective cell death of GIC and increase host survival in an orthotopic mouse model of human glioma. At present, the precise cellular pathways affected by the drugs affecting these channels are unknown...
January 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28087585/standard-based-comprehensive-detection-of-adverse-drug-reaction-signals-from-nursing-statements-and-laboratory-results-in-electronic-health-records
#4
Suehyun Lee, Jiyeob Choi, Hun-Sung Kim, Grace Juyun Kim, Kye Hwa Lee, Chan Hee Park, Jongsoo Han, Dukyong Yoon, Man Young Park, Rae Woong Park, Hye-Ryun Kang, Ju Han Kim
OBJECTIVE: We propose 2 Medical Dictionary for Regulatory Activities-enabled pharmacovigilance algorithms, MetaLAB and MetaNurse, powered by a per-year meta-analysis technique and improved subject sampling strategy. MATRIALS AND METHODS: This study developed 2 novel algorithms, MetaLAB for laboratory abnormalities and MetaNurse for standard nursing statements, as significantly improved versions of our previous electronic health record (EHR)-based pharmacovigilance method, called CLEAR...
January 13, 2017: Journal of the American Medical Informatics Association: JAMIA
https://www.readbyqxmd.com/read/28087362/clinical-phenotypes-and-outcomes-of-heritable-and-sporadic-pulmonary-veno-occlusive-disease-a-population-based-study
#5
David Montani, Barbara Girerd, Xavier Jaïs, Marilyne Levy, David Amar, Laurent Savale, Peter Dorfmüller, Andrei Seferian, Edmund M Lau, Mélanie Eyries, Jérôme Le Pavec, Florence Parent, Damien Bonnet, Florent Soubrier, Elie Fadel, Olivier Sitbon, Gérald Simonneau, Marc Humbert
BACKGROUND: Bi-allelic mutations of the EIF2AK4 gene cause heritable pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis (PVOD/PCH). We aimed to assess the effect of EIF2AK4 mutations on the clinical phenotypes and outcomes of PVOD/PCH. METHODS: We did a population-based study using clinical, functional, and haemodynamic data from the registry of the French Pulmonary Hypertension Network. We reviewed the clinical data and outcomes from all patients referred to the French Referral Centre (Pulmonary Department, Hospital Kremlin-Bicêtre, University Paris-Sud) with either confirmed or highly probable PVOD/PCH with DNA available for mutation screening (excluding patients with other risk factors of pulmonary hypertension, such as chronic respiratory diseases)...
January 10, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28086976/impact-of-a-tailored-program-on-the-implementation-of-evidence-based-recommendations-for-multimorbid-patients-with-polypharmacy-in-primary-care-practices-results-of-a-cluster-randomized-controlled-trial
#6
Cornelia Jäger, Tobias Freund, Jost Steinhäuser, Christian Stock, Johannes Krisam, Petra Kaufmann-Kolle, Michel Wensing, Joachim Szecsenyi
BACKGROUND: Multimorbid patients receiving polypharmacy represent a growing population at high risk for negative health outcomes. Tailoring is an approach of systematic intervention development taking account of previously identified determinants of practice. The aim of this study was to assess the effect of a tailored program to improve the implementation of three important processes of care for this patient group: (a) structured medication counseling including brown bag reviews, (b) the use of medication lists, and (c) structured medication reviews to reduce potentially inappropriate medication...
January 13, 2017: Implementation Science: IS
https://www.readbyqxmd.com/read/28086885/harnessing-the-early-post-injury-inflammatory-responses-for-cardiac-regeneration
#7
REVIEW
Bill Cheng, H C Chen, I W Chou, Tony W H Tang, Patrick C H Hsieh
Cardiac inflammation is considered by many as the main driving force in prolonging the pathological condition in the heart after myocardial infarction. Immediately after cardiac ischemic injury, neutrophils are the first innate immune cells recruited to the ischemic myocardium within the first 24 h. Once they have infiltrated the injured myocardium, neutrophils would then secret proteases that promote cardiac remodeling and chemokines that enhance the recruitment of monocytes from the spleen, in which the recruitment peaks at 72 h after myocardial infarction...
January 13, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28081585/drug-eluting-stent-placement-versus-coronary-artery-bypass-surgery-for-unprotected-left-main-coronary-artery-disease-a-meta-analysis-of-randomized-controlled-trials
#8
Sunil Upadhaya, Ramkaji Baniya, Seetharamprasad Madala, Suresh Kumar Subedi, Jahangir Khan, Ravi Kanth Velagapudi, Ghassan Bachuwa
BACKGROUND: Coronary artery bypass grafting (CABG) is the standard of care for treating left main coronary lesions. However, recently published randomized controlled trials (RCT) have shown conflicting results. We sought to compare clinical outcomes of percutaneous coronary intervention (PCI) with drug-eluting stent placement to CABG using a meta-analysis of randomized controlled trials. METHODS: A systemic search of Pubmed, Scopus, Cochrane library, and Clinicaltrials...
January 12, 2017: Journal of Cardiac Surgery
https://www.readbyqxmd.com/read/28081545/mathematical-optimisation-of-the-cisplatin-plus-etoposide-combination-for-managing-extensive-stage-small-cell-lung-cancer-patients
#9
C Faivre, R El Cheikh, D Barbolosi, F Barlesi
BACKGROUND: Small-cell lung cancer (SCLC) represents one of the most aggressive forms of lung cancer. Despite the fair sensitivity of SCLC to chemotherapy and radiotherapy, the current standard treatment regimens have modest survival rates and are associated with potential life-threatening adverse events. Therefore, research into new optimised regimens that increase drug efficacy while respecting toxicity constraints is of primary importance. METHODS: A PK/PD model for the combination of cisplatin and etoposide to treat extensive-stage SCLC patients was generated...
January 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28080917/results-of-the-megaverebrate-analgesia-survey-giraffe-and-hippopotamus
#10
Matthew Boothe, Jack Kottwitz, Roy Harmon, Scott B Citino, Jeffery R Zuba, Dawn M Boothe
Results of an online survey posted on the American Association of Zoo Veterinarians listserv examined the patterns of analgesic medication and pain management modalities used for captive giraffe and hippopotami. Compiled data included signalment, drugs administered, dosing regimens, subjective efficacy scores, ease of administration, and adverse events. Nineteen institutions exhibiting hippopotami ( Hippopotamus amphibious ) and pygmy hippopotami (Choeropsis liberiensis) and 45 exhibiting giraffe ( Giraffa camelopardalis spp...
December 2016: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
https://www.readbyqxmd.com/read/28079659/suspected-malignant-hyperthermia-in-the-setting-of-hypothermic-circulatory-arrest-for-type-a-aortic-dissection-repair-a-case-report
#11
Bryant Bunting, Joshua Knight, Stephen M McHugh
Malignant Hyperthermia (MH) is a life-threatening biochemical process of hypermetabolism brought about in susceptible individuals by a triggering drug or event. Type A aortic dissections are surgical emergencies requiring cardiopulmonary bypass and frequently deep hypothermic circulatory arrest. We present a case of suspected MH in a patient undergoing emergent repair of a type A aortic dissection. Upon arrival at our institution, the patient had multiple signs of MH. However, no known triggering agent had been administered...
January 11, 2017: A & A Case Reports
https://www.readbyqxmd.com/read/28079518/angiotensin-receptor-blockers-and-the-risk-of-cancer-data-mining-of-a-spontaneous-reporting-database-and-a-claims-database%C3%A2
#12
Mai Fujimoto, Migiwa Kanou, Kouichi Hosomi, Mitsutaka Takada
OBJECTIVE: The aim of this study was to examine the associations between angiotensin receptor blockers (ARBs) and the risk of 10 major cancers by employing different pharmacoepidemiological assessments. MATERIALS AND METHODS: Data from the first quarter of 2004 through 2012 were downloaded from the US Food and Drug Administration Adverse Event Reporting System (FAERS). The reporting odds ratio (ROR) and information component (IC) were used to detect the signals...
January 12, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28079510/a-comparison-of-discontinuation-rates-of-tofacitinib-and-biologic-disease-modifying-antirheumatic-drugs-in-rheumatoid-arthritis-a-systematic-review-and-bayesian-network-meta-analysis
#13
Sun-Kyeong Park, Min-Young Lee, Eun-Jin Jang, Hye-Lin Kim, Dong-Mun Ha, Eui-Kyung Lee
OBJECTIVES: The purpose of this study was to compare the discontinuation rates of tofacitinib and biologics (tumour necrosis factor inhibitors (TNFi), abatacept, rituximab, and tocilizumab) in rheumatoid arthritis (RA) patients considering inadequate responses (IRs) to previous treatment(s). METHODS: Randomised controlled trials of tofacitinib and biologics - reporting at least one total discontinuation, discontinuation due to lack of efficacy (LOE), and discontinuation due to adverse events (AEs) - were identified through systematic review...
January 5, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28079270/treatment-of-adults-with-idiopathic-recurrent-pericarditis-novel-use-of-immunotherapy
#14
Nicholas C Schwier, Genevieve Hale, Marie L Davies
Idiopathic recurrent pericarditis (IRP) can be challenging to treat. Even after guideline-directed, first-line treatment consisting of aspirin (ASA) or a nonsteroidal antiinflammatory drug (NSAID) in combination with colchicine therapy, recurrences still occur in greater than 20% of patients. Many patients then require treatment with long-term corticosteroids, which is not a favorable option due to their short- and long-term adverse effects. Since it is theorized that the pathophysiology of IRP may possess autoimmune sequelae, the use of immunotherapy for the treatment of IRP has emerged...
January 12, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28079254/pharmacological-treatment-of-vascular-risk-factors-for-reducing-mortality-and-cardiovascular-events-in-patients-with-abdominal-aortic-aneurysm
#15
REVIEW
Lindsay Robertson, Edmond Atallah, Gerard Stansby
BACKGROUND: Pharmacological prophylaxis has been proven to reduce the risk of cardiovascular events in individuals with atherosclerotic occlusive arterial disease. However, the role of prophylaxis in individuals with abdominal aortic aneurysm (AAA) remains unclear. Several studies have shown that despite successful repair, those people with AAA have a poorer rate of survival than healthy controls. People with AAA have an increased prevalence of coronary heart disease and risk of cardiovascular events...
January 12, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28078989/a-comprehensive-review-of-mtor-inhibiting-pharmacotherapy-for-the-treatment-of-non-infectious-uveitis
#16
Joshua Blair, Robert Barry, David J Moore, Alastair K Denniston
BACKGROUND: Non-infectious uveitis is a sight-threatening inflammatory disease that often necessitates prolonged use of high-dose corticosteroids, resulting in significant systemic side effects. There is a need for efficacious steroid-sparing immunomodulatory therapy for these patients, and the mTOR inhibitors (sirolimus and everolimus) may be contenders for this role. METHODS: A comprehensive review of preclinical and clinical research on mTOR inhibitors for non-infectious uveitis was performed...
January 11, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28078868/minoxidil-dose-response-study-in-female-pattern-hair-loss-patients-determined-to-be-non-responders-to-5-topical-minoxidil
#17
J McCoy, A Goren, M Kovacevic, J Shapiro
Topical minoxidil is the only US FDA approved drug for the treatment of female pattern hair loss (FPHL). 5% minoxidil foam is only effective at re-growing hair in a minority of women (approximately 40%). Thus, the majority of FPHL patients remain untreated. Previously, we demonstrated that nonresponders to 5% minoxidil have low metabolism of minoxidil in hair follicles. As such, we hypothesized that increasing the dosage of topical minoxidil to low metabolizers would increase the number of responders without increasing the incidence of adverse events...
October 2016: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28078798/systematic-review-with-meta-analysis-rifaximin-is-effective-and-safe-for-the-treatment-of-small-intestine-bacterial-overgrowth
#18
REVIEW
L Gatta, C Scarpignato
BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is a heterogeneous syndrome, characterised by an increased number and/or abnormal type of bacteria in the small bowel. Over the past decades, rifaximin has gained popularity for this indication despite its use is not evidence based. AIM: To perform a systematic review and meta-analysis to summarise evidence about the efficacy and safety of rifaximin to eradicate SIBO in adult patients. METHODS: MEDLINE, EMBASE, CCRCT, Scopus and Web of Science were searched from inception to March 16, 2015 for RCTs and observational studies...
January 12, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28078723/real-world-use-effectiveness-and-safety-of-anti-viral-treatment-in-chronic-hepatitis-c-genotype-3-infection
#19
M Cornberg, J Petersen, A Schober, S Mauss, K H W Böker, R Link, R Günther, Y Serfert, H Pfeiffer-Vornkahl, M P Manns, C Sarrazin, D Hüppe, T Berg, C Niederau
BACKGROUND: Treatment of chronic hepatitis C genotype 3 (GT3) is more challenging compared with other genotypes. Since 2014, several new treatment regimens have been approved but sometimes based on limited data. AIM: To validate the use, effectiveness and safety of anti-viral treatment in chronic hepatitis C genotype 3 infection under real-word conditions. METHODS: The German Hepatitis C-Registry is a large national non-interventional real-world study for patients with chronic hepatitis C...
January 12, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28078647/sitagliptin-a-review-in-type-2-diabetes
#20
Lesley J Scott
The dipeptidyl peptidase-4 inhibitor sitagliptin (Januvia(®); Glactiv(®); Tesavel(®); Xelevia™) is approved in more than 130 countries worldwide as monotherapy and in combination with other antihyperglycaemic drugs for the treatment of adult patients with type 2 diabetes (T2D). Extensive clinical experience has firmly established the glycaemic efficacy of oral sitagliptin (±other antihyperglycaemic drugs) in a broad spectrum of patients with T2D, including obese, elderly and renally impaired patients and those with established cardiovascular (CV) disease (CVD)...
January 11, 2017: Drugs
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