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https://www.readbyqxmd.com/read/28445097/phase-iib-randomized-double-blind-placebo-controlled-study-of-naldemedine-for-the-treatment-of-opioid-induced-constipation-in-patients-with-cancer
#1
Nobuyuki Katakami, Koji Oda, Katsunori Tauchi, Ken Nakata, Katsunori Shinozaki, Takaaki Yokota, Yura Suzuki, Masaru Narabayashi, Narikazu Boku
Purpose This randomized, double-blind, multicenter study aimed to determine the dose of naldemedine, a peripherally-acting μ-opioid receptor antagonist, for future trials by comparing the efficacy and safety of three doses of naldemedine versus placebo in patients with cancer and opioid-induced constipation. Methods Patients ≥ 18 years old with cancer, an Eastern Cooperative Oncology Group performance status ≤ 2, who had been receiving a stable regimen of opioid analgesics for ≥ 2 weeks, had at least one constipation symptom despite laxative use, and no more than five spontaneous bowel movements (SBMs) during the past 14 days, were randomly assigned (1:1:1:1) to oral, once-daily naldemedine 0...
April 26, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28445047/development-of-selective-orally-active-gpr4-antagonists-with-modulatory-effects-on-nociception-inflammation-and-angiogenesis
#2
Juraj Velcicky, Wolfgang Miltz, Berndt Oberhauser, David Orain, Andrea Vaupel, Klaus Weigand, Janet Dawson King, Amanda Littlewood-Evans, Mark Nash, Roland Feifel, Pius Loetscher
A novel, selective, and efficacious GPR4 antagonist 13 was developed starting from lead compound 1a. While compound 1a showed promising efficacy in several disease models, its binding to a H3 receptor as well as a hERG channel prevented it from further development. Therefore, a new round of optimization addressing the key liabilities was performed and led to discovery of compound 13 with an improved profile. Compound 13 showed significant efficacy in the rat antigen induced arthritis as well as in the hyperalgesia and angiogenesis model at a well-tolerated dose of 30 mg/kg...
April 26, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28444546/continuous-magnesium-infusions-in-the-management-of-systemic-anti-cancer-therapy-related-hypomagnesaemia
#3
Hector Mateo-Carrasco, Oluwakemi Kostrzynski, Onyinye Ndefo, Simon Stapley, Elaine Davies, Roshan Agarwal
Background Hypomagnesaemia is a relatively-common side effect of some systemic anti-cancer therapies (SACT). Oral and intravenous magnesium (given as injections or short infusions) have problems arising from their poor tolerability, and need for frequent administrations, respectively. Objective Assessing the effectiveness and safety of weekly continuous magnesium infusions (CMI) in the management of SACT-related hypomagnesaemia. Methods CMIs (initiated at 10 mmol/day and up-titrated subject to response) were prescribed to patients with ≥3 magnesium readings <0...
April 25, 2017: International Journal of Clinical Pharmacy
https://www.readbyqxmd.com/read/28443950/chronic-kidney-disease-determinants-of-progression-and-cardiovascular-risk-progredir-cohort-study-design-and-methods
#4
Maria Alice Muniz Domingos, Alessandra Carvalho Goulart, Paulo Andrade Lotufo, Isabela Judith Martins Benseñor, Silvia Maria de Oliveira Titan
CONTEXT AND OBJECTIVE: Chronic kidney disease (CKD) has become an important public health issue. The socioeconomic burden of renal replacement therapy (RRT) is very high, as is CKD-related cardiovascular mortality and morbidity. Preventive and therapeutic measures only have modest impact and more research is needed. Few cohort studies have been conducted on populations with CKD. Our aim was to establish a cohort that would include more advanced forms of CKD (stages 3 and 4). Data collection was focused on renal and cardiovascular parameters...
April 20, 2017: São Paulo Medical Journal, Revista Paulista de Medicina
https://www.readbyqxmd.com/read/28443029/superior-effects-of-eccentric-to-concentric-knee-extensor-resistance-training-on-physical-fitness-insulin-sensitivity-and-lipid-profiles-of-elderly-men
#5
Trevor Chung-Ching Chen, Wei-Chin Tseng, Guan-Ling Huang, Hsin-Lian Chen, Kuo-Wei Tseng, Kazunori Nosaka
It has been reported that eccentric training of knee extensors is effective for improving blood insulin sensitivity and lipid profiles to a greater extent than concentric training in young women. However, it is not known whether this is also the case for elderly individuals. Thus, the present study tested the hypothesis that eccentric training of the knee extensors would improve physical function and health parameters (e.g., blood lipid profiles) of older adults better than concentric training. Healthy elderly men (60-76 years) were assigned to either eccentric training or concentric training group (n = 13/group), and performed 30-60 eccentric or concentric contractions of knee extensors once a week...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28442822/effects-of-implementing-international-association-of-diabetes-and-pregnancy-study-groups-gestational-diabetes-screening-on-pregnancy-outcomes-at-a-small-community-teaching-hospital
#6
Jody M Gerome, Lucy K M Bucher, Godwin Dogbey
IN BRIEF Traditional methods of screening for and diagnosing gestational diabetes mellitus (GDM) have been challenged, leading to the development of new screening guidelines by the International Association of Diabetes and Pregnancy Study Groups (IADPSG). This study is a retrospective comparison of pregnancy outcomes based on the Carpenter and Coustan (CC) and IADPSG screening guidelines. It demonstrates that adoption of IADPSG guidelines increased the rate of GDM diagnosis and resulted in more women with diet-controlled GDM...
April 2017: Clinical Diabetes: a Publication of the American Diabetes Association
https://www.readbyqxmd.com/read/28442582/lx2761-a-sodium-glucose-cotransporter-1-inhibitor-restricted-to-the-intestine-improves-glycemic-control-in-mice
#7
David R Powell, Melinda G Smith, Deon D Doree, Angela L Harris, Jennifer Greer, Christopher M DaCosta, Andrea Thompson, Sabrina Jeter-Jones, Wendy Xiong, Kenneth G Carson, Nicole C Goodwin, Bryce A Harrison, David B Rawlins, Eric D Strobel, Suma Gopinathan, Alan Wilson, Faika Mseeh, Brian Zambrowicz, Zhi-Ming Ding
LX2761 is a potent sodium/glucose cotransporter 1 inhibitor restricted to the intestinal lumen after oral administration. Studies presented here evaluated the effect of orally administered LX2761 on glycemic control in preclinical models. In healthy mice and rats treated with LX2761, blood glucose excursions were lower and plasma total glucagon-like peptide-1 (GLP-1) levels higher after an oral glucose challenge; these decreased glucose excursions persisted even when the glucose challenge occurred 15 hours after LX2761 dosing in ad-lib-fed mice...
April 25, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28442580/ethanol-reversal-of-tolerance-to-the-antinociceptive-effects-of-oxycodone-and-hydrocodone
#8
Joanna C Jacob, Justin L Poklis, Hamid I Akbarali, Graeme Henderson, William L Dewey
This study compared the development of tolerance and its reversal by ethanol of two orally-bioavailable prescription opioids, oxycodone and hydrocodone, to that of morphine. Oxycodone (s.c) was significantly more potent in the mouse tail withdrawal assay than either morphine or hydrocodone. Oxycodone was also significantly more potent in this assay than hydrocodone when administered orally. Tolerance was seen following chronic subcutaneous administration of each of the three drugs and by the chronic administration of oral oxycodone, but not following the chronic oral administration of hydrocodone...
April 25, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28441966/maintenance-tegafur-uracil-versus-observation-following-an-adjuvant-oxaliplatin-based-regimen-in-patients-with-stage-iii-colon-cancer-after-radical-resection-study-protocol-for-a-randomized-controlled-trial
#9
Yung-Sung Yeh, Hsiang-Lin Tsai, Ching-Wen Huang, Po-Li Wei, Yung-Chuan Sung, Hsiu-Chih Tang, Jaw-Yuan Wang
BACKGROUND: We conducted a prospective randomized study of an adjuvant oxaliplatin-based regimen plus orally administered tegafur-uracil in patients with stage III colon cancer after radical resection to evaluate the feasibility of this drug combination in cancer clinical outcomes, acute toxicity, disease-free survival (DFS), and overall survival (OS) in Taiwan. METHODS/DESIGN: This is an open-label, randomized, comparative, double-arm, multicenter, phase III study to assess DFS, OS, and safety profiles of the aforementioned drug combination as maintenance therapy for 1 year in patients with stage III colon cancer after radical resection in Taiwan...
April 26, 2017: Trials
https://www.readbyqxmd.com/read/28440853/antibiotic-strategies-for-eradicating-pseudomonas-aeruginosa-in-people-with-cystic-fibrosis
#10
REVIEW
Simon C Langton Hewer, Alan R Smyth
BACKGROUND: Respiratory tract infection with Pseudomonas aeruginosa occurs in most people with cystic fibrosis. Once chronic infection is established, Pseudomonas aeruginosa is virtually impossible to eradicate and is associated with increased mortality and morbidity. Early infection may be easier to eradicate.This is an update of a Cochrane review first published in 2003, and previously updated in 2006, 2009 and 2014. OBJECTIVES: To determine whether antibiotic treatment of early Pseudomonas aeruginosa infection in children and adults with cystic fibrosis eradicates the organism, delays the onset of chronic infection, and results in clinical improvement...
April 25, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28440417/increased-cd19-cd24-cd27-b-regulatory-cells-are-associated-with-insulin-resistance-in-patients-with-type-i-hashimoto-s-thyroiditis
#11
Min Yang, Changji Du, Yinping Wang, Jun Liu
Hashimoto's thyroiditis (HT) is characterized by dysregulated immune responses and is commonly associated with insulin resistance. However, the mechanism of insulin resistance in HT remains to be fully elucidated. The aim of the present study was to investigate the correlation between the percentage of B regulatory lymphocytes (Bregs) and insulin resistance in patients with HT but with normal thyroid function (type I). A total of 59 patients with type I HT and 38 healthy volunteers were enrolled in the study...
April 25, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28439747/management-of-cirrhotic-patients-after-successful-hcv-eradication
#12
REVIEW
Ryan M Kwok, Tram T Tran
Chronic hepatitis C (HCV) is a hepatotropic virus which, when untreated, can lead to progressive inflammation and fibrosis resulting in cirrhosis, hepatocellular carcinoma (HCC), and decompensations related to end-stage liver disease. The relatively recent introduction of all oral, interferon-free, direct-acting antiviral medications against HCV has transformed the management of these patients. Previous treatment regimens were prolonged, poorly tolerated, and frequently did not result in cure. Current therapies achieve sustained viral response (SVR) in the vast majority of patients including those with decompensated liver disease; a previously challenging population to treat...
April 24, 2017: Current Treatment Options in Gastroenterology
https://www.readbyqxmd.com/read/28439738/prospective-open-uncontrolled-phase-i-study-to-define-a-well-tolerated-dose-of-oral-artesunate-as-add-on-therapy-in-patients-with-metastatic-breast-cancer-artic-m33-2
#13
Cornelia von Hagens, Ingeborg Walter-Sack, Maren Goeckenjan, Julia Osburg, Brigitte Storch-Hagenlocher, Serkan Sertel, Michael Elsässer, Bjoern Andrew Remppis, Lutz Edler, Judith Munzinger, Thomas Efferth, Andreas Schneeweiss, Thomas Strowitzki
PURPOSE: The antimalarial drug artesunate (ART) is a promising candidate for cancer treatment as it displays anticancer effects in various models. While in short-term treatment of malaria, an excellent safety profile has been found for ART, the potential long-term treatment of cancer patients demands a phase I dose-finding clinical trial determining the daily ART dose which would be well tolerated as add-on therapy. METHODS: Patients with metastatic breast cancer were to receive either 100 or 150 or 200 mg oral ART daily as add-on to their guideline-based oncological therapy for a study period of four weeks with frequent clinical and laboratory monitoring until 4-8 weeks thereafter...
April 24, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28439004/endocannabinoid-system-acts-as-a-regulator-of-immune-homeostasis-in-the-gut
#14
Nandini Acharya, Sasi Penukonda, Tatiana Shcheglova, Adam T Hagymasi, Sreyashi Basu, Pramod K Srivastava
Endogenous cannabinoids (endocannabinoids) are small molecules biosynthesized from membrane glycerophospholipid. Anandamide (AEA) is an endogenous intestinal cannabinoid that controls appetite and energy balance by engagement of the enteric nervous system through cannabinoid receptors. Here, we uncover a role for AEA and its receptor, cannabinoid receptor 2 (CB2), in the regulation of immune tolerance in the gut and the pancreas. This work demonstrates a major immunological role for an endocannabinoid. The pungent molecule capsaicin (CP) has a similar effect as AEA; however, CP acts by engagement of the vanilloid receptor TRPV1, causing local production of AEA, which acts through CB2...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438879/definitive-intensity-modulated-radiation-therapy-in-elderly-patients-with-locally-advanced-oropharyngeal-cancer
#15
Francesca DE Felice, Alessandro Galdieri, Gessica Abate, Nadia Bulzonetti, Daniela Musio, Vincenzo Tombolini
BACKGROUND: To evaluate the treatment tolerance and clinical outcomes in patients aged 70 years and older with locally advanced oropharyngeal cancer treated by definitive intensity-modulated radiation therapy (IMRT). PATIENTS AND METHODS: We retrospectively analyzed 15 consecutive elderly patients, with histologically-proven squamous cell carcinoma of the oropharynx, staged T3-4 with or without involved lymph nodes at diagnosis, who received definitive sequential IMRT (70 Gy; 2 Gy/fraction)...
May 2017: In Vivo
https://www.readbyqxmd.com/read/28438674/current-state-and-challenges-in-developing-oral-vaccines
#16
REVIEW
Julia E Vela Ramirez, Lindsey A Sharpe, Nicholas A Peppas
While vaccination remains the most cost effective strategy for disease prevention, communicable diseases persist as the second leading cause of death worldwide. There is a need to design safe, novel vaccine delivery methods to protect against unaddressed and emerging diseases. Development of vaccines administered orally is preferable to traditional injection-based formulations for numerous reasons including improved safety and compliance, and easier manufacturing and administration. Additionally, the oral route enables stimulation of humoral and cellular immune responses at both systemic and mucosal sites to establish broader and long-lasting protection...
April 21, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28438257/pharmacokinetics-and-relative-bioavailability-of-two-allopurinol-tablets-in-healthy-chinese-volunteers%C3%A2
#17
Zhen-Yan Hou, Hua-Lin Cai, Yang Deng, Zhi-Hua Li, Si-Si Cao, Ying Chen, Yao Li, Miao Yan, Bi-Kui Zhang
OBJECTIVE: To evaluate the pharmacokinetics and relative bioavailability of two allopurinol tablets in healthy Chinese volunteers. METHODS: A single-center, randomized, cross-over, two-period study design was conducted in healthy male subjects who were identified as not carrying the HLA-B*58:01 allele. Under fasting conditions, a single oral dose of 300 mg test or reference tablets was given with a 1-week washout period. The blood samples were collected for up to 12 hours after the administration and the plasma concentrations of allopurinol were determined by high performance liquid chromatography...
April 25, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28437585/chronic-intestinal-electrical-stimulation-improves-glucose-intolerance-and-insulin-resistance-in-diet-induced-obesity-rats
#18
Shiying Li, Weijian Zhu, Sujuan Zhang, Jiande Dz Chen
OBJECTIVE: Obesity is a contributing factor to insulin resistance and type 2 diabetes. The aim of this study was to study the therapeutic potential of intestinal electrical stimulation (IES) for obesity and associated glucose intolerance and insulin resistance in diet-induced obesity (DIO) rats. METHODS: DIO rats were divided into two groups to receive sham or IES for 8 weeks. Oral glucose tolerance and insulin tolerance tests were performed. Gastric emptying and small bowel transit tests were performed...
April 24, 2017: Obesity
https://www.readbyqxmd.com/read/28437538/effects-of-diagnosis-by-newborn-screening-for-cystic-fibrosis-on-weight-and-length-in-the-first-year-of-life
#19
Daniel H Leung, Sonya L Heltshe, Drucy Borowitz, Daniel Gelfond, Margaret Kloster, James E Heubi, Michael Stalvey, Bonnie W Ramsey
Importance: Since the implementation of universal newborn screening (NBS) for cystic fibrosis (CF), the timing and magnitude of growth deficiency or its association with correlates of disease among infants with CF who underwent NBS has not been well described. Objective: To examine incremental weight gain, linear growth, and clinical features in the first year of life among infants with CF who underwent NBS. Design, Setting, and Participants: The Baby Observational and Nutrition Study (BONUS), a multicenter, longitudinal, observational cohort study, was conducted during regular CF clinic visits in the first 12 months of life at 28 US Cystic Fibrosis Foundation-accredited Care Centers from January 7, 2012, through May 31, 2015...
April 24, 2017: JAMA Pediatrics
https://www.readbyqxmd.com/read/28437263/a-randomised-trial-to-evaluate-preoperative-oral-carbohydrate-administration-on-insulin-resistance-in-off-pump-coronary-artery-bypass-patients
#20
Bora Lee, Sarah Soh, Jae-Kwang Shim, Ha Y Kim, Hyelin Lee, Young-Lan Kwak
BACKGROUND: In fasting cardiac surgery patients, preoperative carbohydrate (CHO) drink intake attenuated insulin resistance and improved cardiac metabolism, although its beneficial effects were not evident after cardiac surgery possibly due to cardiopulmonary bypass-related extreme systemic inflammation. OBJECTIVE: We aimed to evaluate whether preoperative CHO intake affected insulin resistance and free-fatty acid (FFA) concentrations in off-pump coronary revascularisation...
April 21, 2017: European Journal of Anaesthesiology
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