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https://www.readbyqxmd.com/read/28340013/implications-of-thoracic-epidural-analgesia-on-hospital-charges-in-rib-fracture-patients
#1
Courtney D Jensen, Jamie T Stark, Lewis E Jacobson, Jan M Powers, Kathy L Leslie, Jeffrey M Kinsella-Shaw, Michael F Joseph, Craig R Denegar
Objective.:  Rib fractures are present in more than 150,000 patients admitted to US trauma centers each year. Those who fracture two or more ribs are typically treated with oral analgesic drugs and are discharged with few complications. The cost of this care generally reflects its brevity. When a patient fractures three or more ribs, there is an elevated risk of complication. In response, treatments are often broadened and their durations prolonged; this affects cost. While health, function, and survival have been widely explored, patient billing has not...
March 7, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28339965/opioid-prescriptions-by-specialty-in-ohio-2010-2014
#2
Scott G Weiner, Olesya Baker, Ann F Rodgers, Chad Garner, Lewis S Nelson, Peter W Kreiner, Jeremiah D Schuur
Background. : The current US opioid epidemic is attributed to the large volume of prescribed opioids. This study analyzed the contribution of different medical specialties to overall opioids by evaluating the pill counts and morphine milligram equivalents (MMEs) of opioid prescriptions, stratified by provider specialty, and determined temporal trends. Methods. : This was an analysis of the Ohio prescription drug monitoring program database, which captures scheduled medication prescriptions filled in the state as well as prescriber specialty...
March 6, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28337975/a-chemical-chaperone-improves-muscle-function-in-mice-with-a-ryr1-mutation
#3
Chang Seok Lee, Amy D Hanna, Hui Wang, Adan Dagnino-Acosta, Aditya D Joshi, Mark Knoblauch, Yan Xia, Dimitra K Georgiou, Jianjun Xu, Cheng Long, Hisayuki Amano, Corey Reynolds, Keke Dong, John C Martin, William R Lagor, George G Rodney, Ergun Sahin, Caroline Sewry, Susan L Hamilton
Mutations in the RYR1 gene cause severe myopathies. Mice with an I4895T mutation in the type 1 ryanodine receptor/Ca(2+) release channel (RyR1) display muscle weakness and atrophy, but the underlying mechanisms are unclear. Here we show that the I4895T mutation in RyR1 decreases the amplitude of the sarcoplasmic reticulum (SR) Ca(2+) transient, resting cytosolic Ca(2+) levels, muscle triadin content and calsequestrin (CSQ) localization to the junctional SR, and increases endoplasmic reticulum (ER) stress/unfolded protein response (UPR) and mitochondrial ROS production...
March 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28337452/teratogenic-effect-of-usnic-acid-from-cladonia-substellata-vainio-during-organogenesis
#4
C R Silva, K S N Marinho, T D S Silva, D K S Ferreira, G M Aguiar, M C B Martins, K R P Santos, F C A Aguiar Júnior, N P S Santos, E C Pereira, N H Silva
Studies about toxicological potential of usnic acid are limited. This way, the vast majority of data available in the literature are related only to biological activities. This is the first study that aimed to evaluate the oral toxicity of usnic acid during the period of organogenesis. Females rats were distributed in the control groups, treated I and II, at doses of 15 and 25 mg/kg, administered by gavage during the 6° to 15° days of pregnancy. After 20 days the fetuses were removed and analyzed. A reduction in weight gain during pregnancy, increased resorption, reduction in the number of viable fetuses, and their body weight were observed...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28337147/3d-proximal-tubule-tissues-recapitulate-key-aspects-of-renal-physiology-to-enable-nephrotoxicity-testing
#5
Shelby M King, J William Higgins, Celina R Nino, Timothy R Smith, Elizabeth H Paffenroth, Casey E Fairbairn, Abigail Docuyanan, Vishal D Shah, Alice E Chen, Sharon C Presnell, Deborah G Nguyen
Due to its exposure to high concentrations of xenobiotics, the kidney proximal tubule is a primary site of nephrotoxicity and resulting attrition in the drug development pipeline. Current pre-clinical methods using 2D cell cultures and animal models are unable to fully recapitulate clinical drug responses due to limited in vitro functional lifespan, or species-specific differences. Using Organovo's proprietary 3D bioprinting platform, we have developed a fully cellular human in vitro model of the proximal tubule interstitial interface comprising renal fibroblasts, endothelial cells, and primary human renal proximal tubule epithelial cells to enable more accurate prediction of tissue-level clinical outcomes...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28336552/prospective-comprehensive-molecular-characterization-of-lung-adenocarcinomas-for-efficient-patient-matching-to-approved-and-emerging-therapies
#6
Emmet J Jordan, Hyunjae R Kim, Maria E Arcila, David A Barron, Debyani Chakravarty, Jianjiong Gao, Matthew T Chang, Andy Ni, Ritika Kundra, Philip Jonsson, Gowtham Jayakumaran, Sizhi P Gao, Hannah C Johnsen, Aphrothiti J Hanrahan, Ahmet Zehir, Natasha Rekhtman, Michelle S Ginsberg, Bob T Li, Helena Yu, Paul K Paik, Alexander Drilon, Matthew D Hellmann, Dalicia N Reales, Ryma Benayed, Valerie W Rusch, Mark G Kris, Jamie E Chaft, José Baselga, Barry S Taylor, Nikolaus Schultz, Charles M Rudin, David M Hyman, Michael F Berger, David B Solit, Marc Ladanyi, Gregory J Riely
Tumor genetic testing is standard of care for patients with advanced lung adenocarcinoma but the fraction of patients who derive clinical benefit remains undefined. Here, we report the experience of 860 patients with metastatic lung adenocarcinoma analyzed prospectively for mutations in >300 cancer-associated genes. Potentially actionable genetic events were stratified into one of four levels based upon published clinical or laboratory evidence that the mutation in question confers increased sensitivity to standard or investigational therapies...
March 23, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28333232/prevalence-of-hiv-1-drug-resistance-in-treated-patients-with-viral-load-50%C3%A2-copies-ml-a-2014-french-nationwide-study
#7
L Assoumou, C Charpentier, P Recordon-Pinson, M Grudé, C Pallier, L Morand-Joubert, S Fafi-Kremer, A Krivine, B Montes, V Ferré, M Bouvier-Alias, J-C Plantier, J Izopet, M-A Trabaud, S Yerly, J Dufayard, C Alloui, L Courdavault, H Le Guillou-Guillemette, A Maillard, C Amiel, A Vabret, C Roussel, S Vallet, J Guinard, A Mirand, A Beby-Defaux, F Barin, A Allardet-Servent, R Ait-Namane, M Wirden, C Delaugerre, V Calvez, M-L Chaix, D Descamps, S Reigadas
Background: Surveillance of HIV-1 resistance in treated patients with a detectable viral load (VL) is important to monitor, in order to assess the risk of spread of resistant viruses and to determine the proportion of patients who need new antiretroviral drugs with minimal cross-resistance. Methods: The HIV-1 protease and reverse transcriptase (RT) and integrase genes were sequenced in plasma samples from 782 consecutive patients on failing antiretroviral regimens, seen in 37 specialized centres in 2014...
February 25, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28332439/use-of-biopartitioning-micellar-chromatography-and-rp-hplc-for-the-determination-of-blood-brain-barrier-penetration-of-%C3%AE-adrenergic-imidazoline-receptor-ligands-and-qspr-analysis
#8
J Vucicevic, M Popovic, K Nikolic, S Filipic, D Obradovic, D Agbaba
For this study, 31 compounds, including 16 imidazoline/α-adrenergic receptor (IRs/α-ARs) ligands and 15 central nervous system (CNS) drugs, were characterized in terms of the retention factors (k) obtained using biopartitioning micellar and classical reversed phase chromatography (log kBMC and log kwRP, respectively). Based on the retention factor (log kwRP) and slope of the linear curve (S) the isocratic parameter (φ0) was calculated. Obtained retention factors were correlated with experimental log BB values for the group of examined compounds...
March 2017: SAR and QSAR in Environmental Research
https://www.readbyqxmd.com/read/28331050/first-in-human-clinical-trial-of-oral-onc201-in-patients-with-refractory-solid-tumors
#9
Mark N Stein, Joseph R Bertino, Howard L Kaufman, Tina Mayer, Rebecca Moss, Ann Silk, Nancy Chan, Jyoti Malhotra, Lorna Rodriguez-Rodriguez, Joseph Aisner, Robert D Aiken, Bruce G Haffty, Robert S DiPaola, Tracie Saunders, Andrew Zloza, Sherri Damare, Yasmeen Beckett, Bangning Yu, Saltanat Najmi, Christian Gabel, Siobhan Dickerson, Ling Zheng, Wafik S El-Deiry, Joshua Allen, Martin Stogniew, Wolfgang Oster, Janice M Mehnert
Purpose ONC201 is a small molecule selective antagonist of the G protein-coupled receptor DRD2 that is the founding member of the imipridone class of compounds. A first-in-human phase I study of ONC201 was conducted to determine its recommended phase II dose (RP2D). Experimental Design This open-label study treated 10 patients during dose escalation with histologically-confirmed advanced solid tumors. Patients received ONC201 orally once every 3 weeks, defined as one cycle, at doses from 125 to 625 mg using an accelerated titration design...
March 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28330649/effect-of-sacubitril-valsartan-versus-enalapril-on-glycaemic-control-in-patients-with-heart-failure-and-diabetes-a-post-hoc-analysis-from-the-paradigm-hf-trial
#10
Jelena P Seferovic, Brian Claggett, Sara B Seidelmann, Ellen W Seely, Milton Packer, Michael R Zile, Jean L Rouleau, Karl Swedberg, Martin Lefkowitz, Victor C Shi, Akshay S Desai, John J V McMurray, Scott D Solomon
BACKGROUND: Diabetes is an independent risk factor for heart failure progression. Sacubitril/valsartan, a combination angiotensin receptor-neprilysin inhibitor, improves morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), compared with the angiotensin-converting enzyme inhibitor enalapril, and improves peripheral insulin sensitivity in obese hypertensive patients. We aimed to investigate the effect of sacubitril/valsartan versus enalapril on HbA1c and time to first-time initiation of insulin or oral antihyperglycaemic drugs in patients with diabetes and HFrEF...
March 17, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28329343/commonly-transmitted-hiv-1-drug-resistance-mutations-in-reverse-transcriptase-and-protease-in-antiretroviral-treatment-na%C3%A3-ve-patients-do-not-affect-response-to-tenofovir-disoproxil-fumarate-or-tenofovir-alafenamide-containing-regimens
#11
Nicolas A Margot, Pamela Wong, Rima Kulkarni, Kirsten White, Danielle Porter, Michael E Abram, Christian Callebaut, Michael D Miller
Background.: The presence of transmitted drug-resistance mutations (TDRM) in antiretroviral (ARV) treatment-naïve patients can adversely affect the outcome of ARV therapy. Methods.: Resistance testing was conducted in 6704 ARV-naïve subjects predominantly from the U.S. and Europe in 9 Gilead clinical studies from 2000 to 2013. Results.: The presence of TDRM increased during this period (5.2% to 11.4%), primarily driven by non-nucleoside RT inhibitor resistance mutations (NNRTI; 0...
January 30, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28328236/treated-prevalence-of-attention-deficit-hyperactivity-disorder-increased-from-2009-to-2015-among-school-aged-children-and-adolescents-in-the-united-states
#12
Kwame A Nyarko, Scott D Grosse, Melissa L Danielson, Joseph R Holbrook, Susanna N Visser, Stuart K Shapira
OBJECTIVES: The purpose of this brief is to describe changes in the treated prevalence of medically managed attention-deficit/hyperactivity disorder (ADHD) among insured school-aged children and adolescents in the United States from 2009 to 2015. We examine the differences between those with employer-sponsored insurance (ESI) and with Medicaid insurance. METHODS: We utilized two large longitudinal administrative datasets containing medical and drug claims data on individuals with ESI and Medicaid insurance from Truven Health MarketScan(®) Administrative Claims Databases...
March 22, 2017: Journal of Child and Adolescent Psychopharmacology
https://www.readbyqxmd.com/read/28327907/a-randomized-open-label-phase-2-study-of-everolimus-in-combination-with-pasireotide-lar-or-everolimus-alone-in-advanced-well-differentiated-progressive-pancreatic-neuroendocrine-tumors-cooperate-2-trial
#13
M H Kulke, P Ruszniewski, E Van Cutsem, C Lombard-Bohas, J W Valle, W W De Herder, M Pavel, E Degtyarev, J C Brase, L Bubuteishvili-Pacaud, M Voi, R Salazar, I Borbath, N Fazio, D Smith, J Capdevila, R P Riechelmann, J C Yao
Background: Several studies have demonstrated the antitumor activity of first-generation somatostatin analogs (SSAs), primarily targeting somatostatin receptor (sstr) subtypes 2 and 5, in neuroendocrine tumors (NET). Pasireotide, a second-generation SSA, targets multiple sstr subtypes. We compared the efficacy and safety of pasireotide plus everolimus to everolimus alone in patients with advanced, well-differentiated, progressive pancreatic NET (pNET). Patients and methods: Patients were randomized 1:1 to receive a combination of everolimus (10 mg/d, orally) and pasireotide long-acting release (LAR; 60 mg/28 d, intramuscularly) or everolimus alone (10 mg/d, orally); stratified by prior SSA use, and baseline serum chromogranin A and neuron-specific enolase...
March 6, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327896/a-randomised-phase-iii-study-of-72%C3%A2-hour-infusional-versus-bolus-bleomycin-in-bep-bleomycin-etoposide-and-cisplatin-chemotherapy-to-treat-igcccg-good-prognosis-metastatic-germ-cell-tumours-te-3
#14
J Shamash, S-J Sarker, R Huddart, S Harland, J K Joffe, D Mazhar, A Birtle, J White, K Chowdhury, P Wilson, M R Marshall, S Vinnicombe
Background: Bleomycin is an integral part of combination chemotherapy in germ cell tumours. Pulmonary toxicity often necessitates drug cessation and death occurs in 1-2% of patients. A continuous infusion of bleomycin might reduce lung toxicity when compared to the conventional weekly boluses given as part of standard BEP chemotherapy. Patients and Methods: A phase 3 trial was conducted based on 212 men with IGCCCG good prognosis metastatic germ cell tumours with 1:1 randomisation...
February 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327633/cardiac-drug-drug-interaction-between-hcv-ns5b-pronucleotide-inhibitors-and-amiodarone-is-determined-by-their-specific-diastereochemistry
#15
Armando Lagrutta, Christopher P Regan, Haoyu Zeng, John P Imredy, Kenneth Koeplinger, Pierre Morissette, Liping Liu, Gordon Wollenberg, Christopher Brynczka, José Lebrón, Joseph DeGeorge, Frederick Sannajust
Severe bradycardia/bradyarrhythmia following coadministration of the HCV-NS5B prodrug sofosbuvir with amiodarone was recently reported. Our previous preclinical in vivo experiments demonstrated that only certain HCV-NS5B prodrugs elicit bradycardia when combined with amiodarone. In this study, we evaluate the impact of HCV-NS5B prodrug phosphoramidate diastereochemistry (D-/L-alanine, R-/S-phosphoryl) in vitro and in vivo. Co-applied with amiodarone, L-ala,SP prodrugs increased beating rate and decreased beat amplitude in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), but D-ala,RP produgs, including MK-3682, did not...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28325368/chagas-disease-diagnostic-applications-present-knowledge-and-future-steps
#16
V Balouz, F Agüero, C A Buscaglia
Chagas disease, caused by the protozoan Trypanosoma cruzi, is a lifelong and debilitating illness of major significance throughout Latin America and an emergent threat to global public health. Being a neglected disease, the vast majority of Chagasic patients have limited access to proper diagnosis and treatment, and there is only a marginal investment into R&D for drug and vaccine development. In this context, identification of novel biomarkers able to transcend the current limits of diagnostic methods surfaces as a main priority in Chagas disease applied research...
2017: Advances in Parasitology
https://www.readbyqxmd.com/read/28325214/antibody-based-cancer-therapy-successful-agents-and-novel-approaches
#17
D Hendriks, G Choi, M de Bruyn, V R Wiersma, E Bremer
Since their discovery, antibodies have been viewed as ideal candidates or "magic bullets" for use in targeted therapy in the fields of cancer, autoimmunity, and chronic inflammatory disorders. A wave of antibody-dedicated research followed, which resulted in the clinical approval of a first generation of monoclonal antibodies for cancer therapy such as rituximab (1997) and cetuximab (2004), and infliximab (2002) for the treatment of autoimmune diseases. More recently, the development of antibodies that prevent checkpoint-mediated inhibition of T cell responses invigorated the field of cancer immunotherapy...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28325171/pregnancy-and-neonatal-outcomes-among-a-cohort-of-hiv-infected-women-in-a-large-italian-teaching-hospital-a-30-year-retrospective-study
#18
S Grignolo, R Agnello, D Gerbaldo, C Gotta, C Alicino, F Del Puente, L Taramasso, B Bruzzone, C Gustavino, S Trasino, A DE Maria, G Icardi, C Viscoli, A DI Biagio
The primary study objective was to investigate three decades from 1985 to 2014 of changes in pregnancies among HIV-infected women. The secondary objective was to assess risk factors associated with preterm delivery and severe small-for-gestational-age (SGA) infants in HIV-infected women. A retrospective review of deliveries among pregnant HIV-infected women at the University of Genoa and IRCCS San Martino-IST in Genoa between 1985 and 2014 was performed. Univariate and multivariable analyses were used to study the variables associated with neonatal outcomes...
March 22, 2017: Epidemiology and Infection
https://www.readbyqxmd.com/read/28320941/potent-neuroprotection-after-stroke-afforded-by-a-double-knot-spider-venom-peptide-that-inhibits-acid-sensing-ion-channel-1a
#19
Irène R Chassagnon, Claudia A McCarthy, Yanni K-Y Chin, Sandy S Pineda, Angelo Keramidas, Mehdi Mobli, Vi Pham, T Michael De Silva, Joseph W Lynch, Robert E Widdop, Lachlan D Rash, Glenn F King
Stroke is the second-leading cause of death worldwide, yet there are no drugs available to protect the brain from stroke-induced neuronal injury. Acid-sensing ion channel 1a (ASIC1a) is the primary acid sensor in mammalian brain and a key mediator of acidosis-induced neuronal damage following cerebral ischemia. Genetic ablation and selective pharmacologic inhibition of ASIC1a reduces neuronal death following ischemic stroke in rodents. Here, we demonstrate that Hi1a, a disulfide-rich spider venom peptide, is highly neuroprotective in a focal model of ischemic stroke...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28320722/in-vitro-and-in-vivo-antibacterial-activities-of-patchouli-alcohol-a-natural-occurring-tricyclic-sesquiterpene-against-helicobacter-pylori-infection
#20
Y F Xu, D W Lian, Y Q Chen, Y F Cai, Y F Zheng, P L Fan, W K Ren, L J Fu, Y C Li, J H Xie, H Y Cao, B Tan, Z R Su, P Huang
This study further evaluated the in vitro and in vivo anti-Helicobacter pylori activity and potential underlying mechanism of patchouli alcohol (PA), a tricyclic sesquiterpene. In in vitro assay, the capacities of PA to inhibit and kill H. pylori were tested on three standard strains at different pH values and 12 clinical isolates. The effects of PA on H. pylori adhesion (and its alpA, alpB and babA genes), motility (and its flaA and flaB genes), ultrastructure and flagellation were investigated. Moreover, the H...
March 20, 2017: Antimicrobial Agents and Chemotherapy
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