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https://www.readbyqxmd.com/read/29691919/impact-of-different-assumptions-on-estimates-of-childhood-diseases-obtained-from-health-care-data-a-retrospective-cohort-study
#1
Osemeke U Osokogu, Alexandra Pacurariu, Mees Mosseveld, Peter Rijnbeek, Daniel Weibel, Katia Verhamme, Miriam C J M Sturkenboom
PURPOSE: Accurate estimates of disease incidence in children are required to support pediatric drug development. Analysis of electronic health care records (EHR) may yield such estimates but pediatric-specific methods are lacking. We aimed to understand the impact of assumptions regarding duration of disease episode and length of run-in period on incidence estimates from EHRs. METHODS: Children aged 0 to 17 years (5-17 years for asthma) registered in the Integrated Primary Care Information database between 2002 and 2014 were studied...
April 24, 2018: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/29691835/rufinamide-add-on-therapy-for-refractory-epilepsy
#2
REVIEW
Mariangela Panebianco, Hemanshu Prabhakar, Anthony G Marson
BACKGROUND: Epilepsy is a central nervous system disorder (neurological disorder). Epileptic seizures are the result of excessive and abnormal cortical nerve cell electrical activity in the brain. Despite the development of more than 10 new antiepileptic drugs (AEDs) since the early 2000s, approximately a third of people with epilepsy remain resistant to pharmacotherapy, often requiring treatment with a combination of AEDs. In this review, we summarised the current evidence regarding rufinamide, a novel anticonvulsant medication, which, as a triazole derivative, is structurally unrelated to any other currently used anticonvulsant medication, when used as an add-on treatment for refractory epilepsy...
April 25, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29691712/gc-formula-see-text-nmf-a-novel-matrix-factorization-framework-for-gene-phenotype-association-prediction
#3
Yaogong Zhang, Jiahui Liu, Xiaohu Liu, Yuxiang Hong, Xin Fan, Yalou Huang, Yuan Wang, Maoqiang Xie
Gene-phenotype association prediction can be applied to reveal the inherited basis of human diseases and facilitate drug development. Gene-phenotype associations are related to complex biological processes and influenced by various factors, such as relationship between phenotypes and that among genes. While due to sparseness of curated gene-phenotype associations and lack of integrated analysis of the joint effect of multiple factors, existing applications are limited to prediction accuracy and potential gene-phenotype association detection...
April 24, 2018: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/29691694/-which-medications-are-safe-while-breastfeeding-a-synopsis-for-the-anesthetist-obstetrician-and-pediatrician
#4
REVIEW
Arabella Fischer, Clemens Ortner, Thomas Hartmann, Stefan Jochberger, Klaus Ulrich Klein
Pharmacokinetic data on drug administration during lactation are often inconsistent or missing. For legal reasons medicinal drug product information generally advises to interrupt breastfeeding for 24 h after medication intake. However this is not standard of care in clinical practice as the mother should be instructed to initiate breastfeeding as soon as possible after giving birth. At the same time the medication exposure over the breast milk for the newborn should be minimized. Aim of this article is to summarize pharmacokinetic data and to give important clinical information on medications frequently administered during the lactation period...
April 24, 2018: Wiener Medizinische Wochenschrift
https://www.readbyqxmd.com/read/29691287/systematic-modelling-and-design-evaluation-of-unperturbed-tumour-dynamics-in-xenografts
#5
Zinnia P Patricia Parra Guillen, Victor Mangas Sanjuan, Maria Garcia-Cremades, Inaki F Troconiz, Gary Mo, Celine Pitou, Philip W Iversen, Johan E Wallin
Xenograft mice are largely used to evaluate the efficacy of oncological drugs during preclinical phases of drug discovery and development. Mathematical models provide a useful tool to quantitatively characterise tumour growth dynamics and also optimise upcoming experiments. To the best of our knowledge, this is the first report where unperturbed growth of a large set of tumour cell lines (n=28) has been systematically analysed using the model proposed by Simeoni in the context of non-linear mixed effect (NLME)...
April 24, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29690793/clinical-implementation-of-pharmacogenetic-decision-support-tools-for-antidepressant-drug-prescribing
#6
Zane Zeier, Linda L Carpenter, Ned H Kalin, Carolyn I Rodriguez, William M McDonald, Alik S Widge, Charles B Nemeroff
The accrual and analysis of genomic sequencing data have identified specific genetic variants that are associated with major depressive disorder. Moreover, substantial investigations have been devoted to identifying gene-drug interactions that affect the response to antidepressant medications by modulating their pharmacokinetic or pharmacodynamic properties. Despite these advances, individual responses to antidepressants, as well as the unpredictability of adverse side effects, leave clinicians with an imprecise prescribing strategy that often relies on trial and error...
April 25, 2018: American Journal of Psychiatry
https://www.readbyqxmd.com/read/29689486/concurrent-use-of-alcohol-with-other-drugs-and-dsm-5-alcohol-use-disorder-comorbid-with-other-drug-use-disorders-sociodemographic-characteristics-severity-and-psychopathology
#7
Tulshi D Saha, Bridget F Grant, S Patricia Chou, Bradley T Kerridge, Roger P Pickering, W June Ruan
BACKGROUND: Little is known about the sociodemographic profiles, the intensity of drinking, the severity of alcohol use disorder (AUD), and psychopathology among individuals with specific patterns of concurrent alcohol and drug use and AUD and other drug use disorders (DUDs) comorbidity. METHODS: Data were from the National Epidemiologic Survey on Alcohol and Related Conditions-III. We examined sociodemographic correlates and psychopathology among individuals with specific patterns of concurrent use of alcohol and drug and AUD-DUD comorbidity relative to alcohol use or AUD only, respectively, using multinomial logistic regression...
April 10, 2018: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/29689360/a-systematic-toxicity-evaluation-of-cephalosporins-via-transcriptomics-in-zebrafish-and-in-silico-admet-studies
#8
Ying Han, Jingpu Zhang, Changqin Hu
Cephalosporins are beta-lactam antibiotics that are widely used in clinics in China. However, information on their toxicity to zebrafish is limited. This study reports that the toxicity effects of cephalosporins containing an N-methyltetrazolthio ring at the C-3 position (CNMTs) exposure on zebrafish were comparable to those predicted by in silico analysis. The effects of CNMTs on the mortality and malformation rate of zebrafish were concentration-dependent. The transcriptional levels of the has1 and cnnm2a genes, which are related to embryo development and absorption of Mg2+ in vivo, significantly changed...
April 21, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29689319/experiences-of-young-adults-with-type-1-diabetes-while-using-alcohol-and-recreational-drugs-an-interpretative-phenomenological-analysis-ipa-of-semi-structured-interviews
#9
Adam Pastor, Casey L O'Brien, Jessie Teng, Jennifer Conn, Margaret Loh, Lisa Collins, Richard MacIsaac, Yvonne Bonomo
AIMS: Alcohol and recreational drug use is common in young adults with type 1 diabetes (T1DM) and may account for increased morbidity and mortality. This study explores the motivations and experiences unique to this population while using alcohol and recreational drugs. METHODS: Semi-structured interviews focusing on substance use were performed with 16 young adults aged 18-35 with T1DM who drink alcohol (at least 50 grams, 5 Australian standard drinks, in a single session) and/or used recreational drugs...
April 21, 2018: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29689305/quality-and-cost-assessment-of-a-recombinant-antibody-fragment-produced-from-mammalian-yeast-and-prokaryotic-host-cells-a-case-study-prior-to-pharmaceutical-development
#10
Kristell Lebozec, Martine Jandrot-Perrus, Gilles Avenard, Olivier Favre-Bulle, Philippe Billiald
Monoclonal antibody fragments (Fab) are a promising class of therapeutic agents. Fabs are aglycosylated proteins and so many expression platforms have been developed including prokaryotic, yeast and mammalian cells. However, these platforms are not equivalent in terms of cell line development and culture time, product quality and possibly cost of production that greatly influence the success of a drug candidate's pharmaceutical development. This study is an assessment of the humanized Fab fragment ACT017 produced from two microorganisms (Escherichia coli and Pichia pastoris) and one mammalian cell host (CHO)...
April 21, 2018: New Biotechnology
https://www.readbyqxmd.com/read/29689086/phase-i-ii-evaluation-of-rv1001-a-novel-pi3k%C3%AE-inhibitor-in-spontaneous-canine-lymphoma
#11
Heather L Gardner, Sarah B Rippy, Misty D Bear, Kim L Cronin, Heather Heeb, Holly Burr, Claire M Cannon, Kumar V Penmetsa, Srikant Viswanadha, Swaroop Vakkalanka, Cheryl A London
BACKGROUND: RV1001 is a novel, potent, and selective PI3Kδ inhibitor. The purpose of this study was to evaluate the safety and efficacy of RV1001 in canine Non-Hodgkin lymphoma (NHL). METHODS AND RESULTS: Inhibition of endogenous pAKT by RV1001 in primary canine NHL cells was determined by Western blotting. A phase I study of RV1001 was performed in 21 dogs with naïve and drug resistant T and B-cell NHL to assess safety, pharmacokinetic profile, and response to therapy...
2018: PloS One
https://www.readbyqxmd.com/read/29689040/-potentially-inappropriate-prescriptions-in-elderly-outpatiens-results-of-implicit-criteria-applied-by-clinical-pharmacists
#12
Concetta Di Giorgio, Alessio Provenzani, Piera Polidori
BACKGROUND: Management of therapy in elderly patients is a critical issue in primary care. The physiopathological status is usually complex, and the prescription of multiple drugs is typically required, with a consequent higher risk of adverse effects. Many tools have been developed to cope with this problem, and identify drugs that are inappropriate in the elderly. The objective of the study was to evaluate the appropriateness of therapies in the elderly according to implicit criteria...
April 2018: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/29688914/antipsychotic-drug-exposure-and-risk-of-fracture-a-systematic-review-and-meta-analysis-of-observational-studies
#13
Davide Papola, Giovanni Ostuzzi, Lehana Thabane, Gordon Guyatt, Corrado Barbui
To investigate the extent to which exposure to first-generation and second-generation antipsychotics (APs) is associated with an increased risk of fractures, with a particular focus on hip fractures, and to ascertain the risk associated with exposure to individual drugs. We included observational studies that reported data on fractures in individuals exposed to APs compared with unexposed individuals or individuals with previous exposure. We extracted information on study design, source of data, population characteristics, outcomes of interest, matching and confounding factors, and used a modified version of the Newcastle-Ottawa Scale to judge study risk of bias...
April 23, 2018: International Clinical Psychopharmacology
https://www.readbyqxmd.com/read/29688583/safe-use-of-proton-pump-inhibitors-in-patients-with-cirrhosis
#14
Rianne A Weersink, Margriet Bouma, David M Burger, Joost P H Drenth, S Froukje Harkes-Idzinga, Nicole G M Hunfeld, Herold J Metselaar, Margje H Monster-Simons, Sandra A W van Putten, Katja Taxis, Sander D Borgsteede
AIMS: Proton pump inhibitors (PPIs) belong to the most frequently used drugs, also in patients with cirrhosis. PPIs are extensively metabolized by the liver, but practice guidance on prescribing in cirrhosis is lacking. We aim to develop practical guidance on the safe use of PPIs in cirrhosis. METHODS: A systematic literature search identified studies about the safety (i.e. adverse events) and pharmacokinetics of PPIs in cirrhotic patients. This evidence and data from the product information was reviewed by an expert panel who classified drugs as safe; no additional risks known; additional risks known; unsafe; or unknown...
April 24, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29688578/cumulative-exposure-to-phthalates-from-phthalate-containing-drug-products-a-danish-population-wide-study
#15
Zandra Nymand Ennis, Anne Broe, Anton Pottegård, Thomas P Ahern, Jesper Hallas, Per Damkier
AIMS: Up to 50-fold higher levels of urinary phthalate metabolites have been observed in users of phthalate-containing drug products compared with non-users. This is of concern, as phthalates are suspected endocrine disrupters and have been associated with cancer development. This study aims to quantify annual cumulated phthalate exposure from drug products among users of phthalate-containing oral medications in Denmark throughout the period of 2004-2016. METHODS: We conducted a Danish nationwide cohort study using The Danish National Prescription Registry and an internal database held by The Danish Medicines Agency...
April 24, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29688573/antidepressants-for-the-treatment-of-people-with-co-occurring-depression-and-alcohol-dependence
#16
REVIEW
Roberta Agabio, Emanuela Trogu, Pier Paolo Pani
BACKGROUND: Alcohol dependence is a major public health problem characterized by recidivism, and medical and psychosocial complications. The co-occurrence of major depression in people entering treatment for alcohol dependence is common, and represents a risk factor for morbidity and mortality, which negatively influences treatment outcomes. OBJECTIVES: To assess the benefits and risks of antidepressants for the treatment of people with co-occurring depression and alcohol dependence...
April 24, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29688481/neutral-theory-and-rapidly-evolving-viral-pathogens
#17
Simon D W Frost, Brittany Rife Magalis, Sergei L Kosakovsky Pond
The evolution of viral pathogens is shaped by strong selective forces that are exerted during jumps to new hosts, confrontations with host immune responses and antiviral drugs, and numerous other processes. However, while undeniably strong and frequent, adaptive evolution is largely confined to small parts of information-packed viral genomes, and the majority of observed variation is effectively neutral. The predictions and implications of the neutral theory have proven immensely useful in this context, with applications spanning understanding within-host population structure, tracing the origins and spread of viral pathogens, predicting evolutionary dynamics, and modeling the emergence of drug resistance...
April 24, 2018: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/29688317/hiv-and-viral-hepatitis-among-imprisoned-key-populations
#18
Andrea L Wirtz, Ping T Yeh, Natalie L Flath, Chris Beyrer, Kate Dolan
Prisons and other closed facilities create opportunities for transmission of human immunodeficiency virus (HIV) and viral hepatitis during detention and after release. We conducted a systematic review and meta-analysis of peer-reviewed publications (2005-2015) to describe the prevalence of HIV, hepatitis C virus, and hepatitis B virus among key populations in prisons worldwide and to compare estimates of infection with those of other prison populations. Most data were reported for people who inject drugs (PWID; n = 72) and for men who have sex with men (MSM; n = 21); few data were reported on sex workers (SW; n = 6), or transgender women (n = 2)...
April 21, 2018: Epidemiologic Reviews
https://www.readbyqxmd.com/read/29688307/rwen-response-weighted-elastic-net-for-prediction-of-chemosensitivity-of-cancer-cell-lines
#19
Amrita Basu, Ritwik Mitra, Han Liu, Stuart L Schreiber, Paul A Clemons
Motivation: In recent years there have been several efforts to generate sensitivity profiles of collections of genomically characterized cell lines to panels of candidate therapeutic compounds. These data provide the basis for the development of in silico models of sensitivity based on cellular, genetic, or expression biomarkers of cancer cells. However, a remaining challenge is an efficient way to identify accurate sets of biomarkers to validate. To address this challenge, we developed methodology using gene-expression profiles of human cancer cell lines to predict the responses of these cell lines to a panel of compounds...
April 24, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29688279/benchmarking-inpatient-antimicrobial-use-a-comparison-of-risk-adjusted-observed-to-expected-ratios
#20
Kalvin Yu, Elizabeth Moisan, Sara Tartof, Hien M Nguyen, Gunter Rieg, Charulata Ramaprasad, Jason Jones
Background: Increasing antibiotic resistance has made benchmarking appropriate inpatient antibiotic use a worldwide priority supported by expert societies and regulatory bodies, however standard risk-adjustment for fair inter-facility comparison has been elusive. We describe a risk-adjusted antibiotic exposure ratio that may help facilitate assessment of antimicrobial use. Methods: Retrospective cohort study of 2.7 million admissions evaluating a wide array of potential explanatory variables for correlation with expected antibiotic consumption in a two-step approach using recursive partitioning and Poisson regression...
April 24, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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