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Drug event

Fernando J Sialana, Peter Gulyassy, Peter Májek, Evelina Sjöstedt, Viktor Kis, André C Müller, Elena L Rudashevskaya, Jan Mulder, Keiryn L Bennett, Gert Lubec
The molecular composition of synaptic signal transduction machineries shapes synaptic neurotransmission. The repertoire of receptors, transporters and channels (RTCs) comprises major signaling events in the brain. RTCs are conventionally studied by candidate immunohistochemistry and biochemistry, which are low throughput with resolution greatly affected by available immunoreagents and membrane interference. Therefore, a comprehensive resource of synaptic brain RTCs is still lacking. In particular, studies on the detergent-soluble synaptosomal fraction, known to contain transporters and channels, are limited...
October 19, 2016: Proteomics
Roberto Hegg, André Mattar, João Nunes de Matos-Neto, José Luiz Pedrini, Sabina Bandeira Aleixo, Roberto Odebrecht Rocha, Renato Peixoto Cramer-Junior, Sylvie van-Eyll-Rocha
OBJECTIVES: To compare the efficacy and safety of two filgrastim formulations for controlling chemotherapy-induced neutropenia and to evaluate the non-inferiority of the test drug relative to the originator. METHODS: This phase III non-inferiority study had a randomized, multicenter, and open-label design. The patients were randomized at a ratio of 1:1 with a follow-up period of 6 weeks for each patient. In both study arms, filgrastim was administered subcutaneously at a daily dose of 5 mg/kg body weight...
October 1, 2016: Clinics
Ajit Dash, Robert A Figler, Arun J Sanyal, B R Wamhoff
Drug induced steatohepatitis (DISH), a form of drug induced liver injury (DILI) is characterized by intracellular accumulation of lipids in hepatocytes and subsequent inflammatory events, in some ways similar to the pathology seen with other metabolic, viral and genetic causes of non alcoholic fatty liver disease and steatohepatitis (NAFLD and NASH). Areas covered: This paper provides a comprehensive review of the main underlying mechanisms by which various drugs cause DISH, and outlines existing preclinical tools to predict it and study underlying pathways involved...
October 19, 2016: Expert Opinion on Drug Metabolism & Toxicology
Gino A Vena, Maria Concetta Fargnoli, Nicoletta Cassano, Giuseppe Argenziano
The sudden eruption of melanocytic nevi has been associated with a number of conditions, such as bullous skin diseases, immunodeficiency and immunosuppression. The exact mechanisms leading to the development of eruptive melanocytic nevi are unknown. Areas covered: The aim of this article is to review the literature concerning eruptive melanocytic nevi following the administration of immunosuppressive drugs and other medications. Expert opinion: The literature regarding the development of eruptive nevi in association with pharmacological therapies includes a relatively low number of reports...
October 19, 2016: Expert Opinion on Drug Metabolism & Toxicology
Samuel R Friedman, Enrique R Pouget, Milagros Sandoval, Diana Rossi, Pedro Mateu-Gelabert, Georgios K Nikolopoulos, John A Schneider, Pavlo Smyrnov, Ron D Stall
Attacks on peoples' dignity help to produce and maintain stigmatization and interpersonal hostility. As part of an effort to develop innovative measures of possible pathways between structural interventions or socially-disruptive Big Events and HIV outbreaks, we developed items to measure dignity denial. These measures were administered to 300 people who inject drugs (PWID), 260 high-risk heterosexuals who do not inject drugs, and 191 men who have sex with men who do not inject drugs (MSM). All of the PWID and many of the high risk heterosexuals and MSM were referred to our study in 2012-2015 by a large New York city study that used respondent-driven sampling; the others were recruited by chain-referral...
October 17, 2016: AIDS and Behavior
E Wardal, A Kuch, I Gawryszewska, D Żabicka, W Hryniewicz, E Sadowy
The objective of this study was to investigate the antimicrobial resistance, Tn1546 transposon variability and plasmid diversity among Polish vancomycin-resistant Enterococcus faecium (VREfm) isolates of VanA phenotype in the context of their clonal structure. Two hundred sixteen clinical VREfm isolates collected between 1997 and 2010 were studied by antimicrobial susceptibility testing, MLST, MLVA and detection of IS16, esp Efm, pilA, intA and plasmid-specific genes by PCR. Tn1546 structure was revealed by overlapping PCR and sequencing...
October 17, 2016: European Journal of Clinical Microbiology & Infectious Diseases
Kyung Sik Kang, Hyung Il Kim, Oh Hyun Kim, Kyoung Chul Cha, Hyun Kim, Kang Hyun Lee, Sung Oh Hwang, Yong Sung Cha
OBJECTIVE: Adverse cardiovascular events (ACVEs) account for a large proportion of the morbidities and mortalities associated with drug overdose emergencies. However, there are no published reports regarding outcomes of ACVEs associated with acute dapsone poisoning. Here, the authors retrospectively analyzed ACVEs reported within 48 hours of treatment in patients with acute dapsone poisoning and assessed the significance of ACVEs as early predictors of mortality. METHODS: Sixty-one consecutive cases of acute dapsone poisoning that were diagnosed and treated at a regional emergency center between 2006 and 2014 were included in the study...
March 2016: Clin Exp Emerg Med
Laura C Cappelli, Ami A Shah, Clifton O Bingham
Immune checkpoint inhibitors (ICIs) are newly approved treatments for advanced malignancies that are increasing survival. The mechanism of these drugs, non-specifically activating T cells, also leads to immune-mediated damage of tissue or immune-related adverse events (IRAE). IRAEs with rheumatic phenotypes are increasingly being recognised. Inflammatory arthritis, sicca syndrome, inflammatory myopathy, vasculitis and lupus nephritis have been described as a result of ICIs. Use of ICIs will be expanding in the coming years for several reasons...
2016: RMD Open
Hassan Fares, James J DiNicolantonio, James H O'Keefe, Carl J Lavie
OBJECTIVES: Hypertension is well established as a major risk factor for cardiovascular disease. Although there is undeniable evidence to support the beneficial effects of antihypertensive therapy on morbidity and mortality, adequate blood pressure management still remains suboptimal. Research into the treatment of hypertension has produced a multitude of drug classes with different efficacy profiles. These agents include β-blockers, diuretics, ACE inhibitors, angiotensin receptor blockers and calcium channel blockers...
2016: Open Heart
Jake Luo, Christina Eldredge, Chi C Cho, Ron A Cisler
BACKGROUND: Understanding adverse event patterns in clinical studies across populations is important for patient safety and protection in clinical trials as well as for developing appropriate drug therapies, procedures, and treatment plans. OBJECTIVES: The objective of our study was to conduct a data-driven population-based analysis to estimate the incidence, diversity, and association patterns of adverse events by age of the clinical trials patients and participants...
October 17, 2016: JMIR Medical Informatics
Zachary R Noel, Craig J Beavers
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors serve as a valuable addition to the armamentarium of lipid lowering agents and have promising potential. By inhibiting the PCSK9 enzyme, this novel molecule leads to increase low density lipoprotiein (LDL) receptor density and decreased circulation of LDL. The fact the agent is a monoclonal antibody has led to limited drug interactions and minimized adverse drug events. It is critical for all providers to have a basic understanding of these novel therapies with their introduction and use for treatment...
October 14, 2016: American Journal of Medicine
Janis C Weeks, William M Roberts, Kristin J Robinson, Melissa Keaney, Jon J Vermeire, Joseph F Urban, Shawn R Lockery, John M Hawdon
The screening of candidate compounds and natural products for anthelmintic activity is important for discovering new drugs against human and animal parasites. We previously validated in Caenorhabditis elegans a microfluidic device ('chip') that records non-invasively the tiny electrophysiological signals generated by rhythmic contraction (pumping) of the worm's pharynx. These electropharyngeograms (EPGs) are recorded simultaneously from multiple worms per chip, providing a medium-throughput readout of muscular and neural activity that is especially useful for compounds targeting neurotransmitter receptors and ion channels...
September 15, 2016: International Journal for Parasitology, Drugs and Drug Resistance
Christina Binder, Caroline Zotter-Tufaro, Diana Bonderman
The development of pulmonary hypertension (PH) has multifactorial underlying pathophysiological causes and can be classified into five groups. While three different classes of therapeutic drugs are licensed for the treatment of pulmonary arterial hypertension (PAH, WHO group 1), specific medical therapies are lacking for other forms of PH, such as PH due to left heart disease. In 2013 riociguat, a first-in class soluble guanylate cyclase stimulator, has also become available for the treatment of PAH. Riociguat was further introduced as the first approved pharmacotherapy for the treatment of patients with chronic thromboembolic PH (WHO group 4, CTEPH)...
October 18, 2016: Expert Opinion on Drug Safety
Hiroshi Yamazaki
Research over the past 30 years has elucidated the roles of polymorphic human liver cytochrome P450 (P450) enzymes associated with toxicological and/or pharmacological actions. Thalidomide exerts its various pharmacological and toxic actions in primates through multiple mechanisms, including nonspecific modification of many protein networks after bioactivation by autoinduced human P450 enzymes. To overcome species-differences between rodents, currently, nonhuman primates and/or mouse models with transplanted human hepatocytes are used...
October 17, 2016: Chemical Research in Toxicology
Jane Schröder, Lisa Goltz, Holger Knoth
The clinical relevance of the drug-drug interaction simvastatin and amlodipine is appraised controversially by german simvastatin Summary of Product Characteristics (SPCs) and different drug interaction databases. Results of clinical trials have shown that simultaneous administration of simvastatin and amlodipine can increase simvastatin bioavailability. However, it is unclear whether this increase is associated with a higher risk for adverse drug events. So far there is no evidence that the combination might increase cases of myopathy or rhabdomyolysis...
October 2016: Deutsche Medizinische Wochenschrift
Manuela Casula, Lorenza Scotti, Elena Tragni, Luca Merlino, Giovanni Corrao, Alberico L Catapano
BACKGROUND AND AIMS: We aimed at describing the therapeutic approach in young adult patients diagnosed with heterozygous familial hypercholesterolemia (HeFH) and their adherence and persistence to treatment. METHODS: From regional administrative databases, individuals aged ≤40 years, who received exemption for HeFH between January 1, 2003 and December 31, 2011, and concomitantly started statin treatment, were identified. Within the first year of treatment, we evaluated therapeutic changes, adherence as MPR (medication possession ratio), persistence as continuous drug coverage without gaps ≥60 days, and influencing factors using log binomial models...
October 12, 2016: Atherosclerosis
Dawood Yusef, Blanca E Gonzalez, Charles B Foster, Johanna Goldfarb, Carla Saracusa, Sarah Worley, Camille Sabella
We report a significantly higher occurrence of adverse events associated with prolonged courses of piperacillin-tazobactam compared with other antibacterial agents used for pediatric outpatient parenteral antimicrobial therapy. These adverse events were characterized by a constellation of clinical findings including fever, hematologic abnormalities, and transaminitis. Adverse events related to piperacillin-tazobactam should be considered in patients who develop a febrile illness associated with a prolonged course of therapy...
October 3, 2016: Pediatric Infectious Disease Journal
Josep M Llibre, Alessandro Cozzi-Lepri, Court Pedersen, Matti Ristola, Marcelo Losso, Amanda Mocroft, Viktar Mitsura, Karolin Falconer, Fernando Maltez, Marek Beniowski, Vincenzo Vullo, Gamal Hassoun, Elena Kuzovatova, János Szlavik, Anastasiia Kuznetsova, Hans-Jürgen Stellbrink, Claudine Duvivier, Simon Edwards, Kamilla Laut, Roger Paredes
Effectiveness data of an unboosted atazanavir (ATV) with abacavir/lamivudine (ABC/3TC) switch strategy in clinical routine are scant.We evaluated treatment outcomes of ATV + ABC/3TC in pretreated subjects in the EuroSIDA cohort when started with undetectable plasma HIV-1 viral load (pVL), performing a time to loss of virological response (TLOVR <50 copies/mL) and a snapshot analysis at 48, 96, and 144 weeks. Virological failure (VF) was defined as confirmed pVL >50 copies/mL.We included 285 subjects, 67% male, with median baseline CD4 530 cells, and 44 months with pVL ≤50 copies/mL...
October 2016: Medicine (Baltimore)
Santoshi Billakota, Saurabh R Sinha
INTRODUCTION: Continuous EEG (cEEG) monitoring is used in the intensive care unit (ICU) setting to detect seizures, especially nonconvulsive seizures and status epilepticus. The utility and impact of such monitoring in non-ICU patients are largely unknown. METHODS: Hospitalized patients who were not in an ICU and underwent cEEG monitoring in the first half of 2011 and 2014 were identified. Reason for admission, admitting service (neurologic and nonneurologic), indication for cEEG, comorbid conditions, duration of recording, EEG findings, whether an event/seizure was recorded, and impact of EEG findings on management were reviewed...
October 2016: Journal of Clinical Neurophysiology: Official Publication of the American Electroencephalographic Society
Andrea Matucci, Francesca Nencini, Sara Pratesi, Enrico Maggi, Alessandra Vultaggio
PURPOSE OF REVIEW: Biological agents have been a treatment option for many chronic immune-mediated diseases as well as oncological conditions. The issue of infusion reactions is of particular importance and at least in some cases related to the immunogenicity of these drugs with the production of antidrug antibodies. Infectious diseases are a well described side-effect of certain biological agents, even if, at least regarding the biological agents used for the treatment of allergic diseases and immune-mediated diseases, the risk has been reduced...
October 5, 2016: Current Opinion in Allergy and Clinical Immunology
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