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https://www.readbyqxmd.com/read/28328624/long-term-maintenance-of-clinical-endoscopic-and-radiographic-response-to-ustekinumab-in-moderate-to-severe-crohn-s-disease-real-world-experience-from-a-multicenter-cohort-study
#1
Christopher Ma, Richard N Fedorak, Gilaad G Kaplan, Levinus A Dieleman, Shane M Devlin, Nathan Stern, Karen I Kroeker, Cynthia H Seow, Yvette Leung, Kerri L Novak, Brendan P Halloran, Vivian W Huang, Karen Wong, Philip K Blustein, Subrata Ghosh, Remo Panaccione
BACKGROUND: Ustekinumab is a monoclonal antibody targeting interleukins 12 and 23. While effective in clinical trials for Crohn's disease (CD), long-term maintenance of response in the real-world setting is unclear. We aim to assess the efficacy of ustekinumab for maintaining clinical, endoscopic, and radiographic response in CD. METHODS: A retrospective multicenter cohort study was performed on patients with CD achieving steroid-free clinical response to ustekinumab induction, and advanced onto a regularly scheduled maintenance ustekinumab regimen between 2011 and 2016...
March 21, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28327089/uniform-fdg-pet-guided-gradient-dose-prescription-to-reduce-late-radiation-toxicity-upgrade-rt-study-protocol-for-a-randomized-clinical-trial-with-dose-reduction-to-the-elective-neck-in-head-and-neck-squamous-cell-carcinoma
#2
Sven van den Bosch, Tim Dijkema, Martina C Kunze-Busch, Chris H J Terhaard, Cornelis P J Raaijmakers, Patricia A H Doornaert, Frank J P Hoebers, Marije R Vergeer, Bas Kreike, Oda B Wijers, Wim J G Oyen, Johannes H A M Kaanders
BACKGROUND: In definitive radiation therapy for head and neck cancer, clinically uninvolved cervical lymph nodes are irradiated with a so-called 'elective dose' in order to achieve control of clinically occult metastases. As a consequence of high-resolution diagnostic imaging, occult tumor volume has significantly decreased in the last decades. Since the elective dose is dependent on occult tumor volume, the currently used elective dose may be higher than necessary. Because bilateral irradiation of the neck contributes to dysphagia, xerostomia and hypothyroidism in a dose dependent way, dose de-escalation to these regions can open a window of opportunity to reduce toxicity and improve quality of life after treatment...
March 21, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28326546/public-private-differences-in-short-term-neonatal-outcomes-following-birth-by-prelabour-caesarean-section-at-early-and-full-term
#3
Nicole Adams, Kristen S Gibbons, David Tudehope
BACKGROUND: Prelabour caesarean section (CS) at early term (37(0) -38(6)  weeks) is associated with higher rates of adverse short-term neonatal outcomes and higher costs than those performed at full term (39(0) -40(6)  weeks). Prelabour CS is more common in private than in public hospitals in Australia, particularly at early term. AIMS: To evaluate the impact of hospital sector (public or private) and timing of delivery on short-term neonatal outcomes following prelabour CS at term...
March 22, 2017: Australian & New Zealand Journal of Obstetrics & Gynaecology
https://www.readbyqxmd.com/read/28326356/effect-of-four-monthly-doses-of-a-human-monoclonal-anti-fgf23-antibody-krn23-on-quality-of-life-in-x-linked-hypophosphatemia
#4
Mary D Ruppe, Xiaoping Zhang, Erik A Imel, Thomas J Weber, Mark A Klausner, Takahiro Ito, Maria Vergeire, Jeffrey S Humphrey, Francis H Glorieux, Anthony A Portale, Karl Insogna, Munro Peacock, Thomas O Carpenter
X-linked hypophosphatemia (XLH) is characterized by lower extremity deformities that lead to bone and/or joint pain that result from decreased renal tubular reabsorption leading to hypophosphatemia caused by elevated levels of fibroblast growth factor 23 (FGF23). OBJECTIVE: Validate the use of SF-36v2 Health Survey (SF-36v2) and the Western Ontario and McMaster Osteoarthritis Index (WOMAC) to measure previously unstudied health-related quality of life (HRQoL) in XLH patients and determine the change in HRQoL before and after treatment with KRN23, a human monoclonal anti-FGF23 antibody...
December 2016: Bone Reports
https://www.readbyqxmd.com/read/28324749/a-phase-i-study-of-sar405838-a-novel-human-double-minute-2-hdm2-antagonist-in-patients-with-solid-tumours
#5
Maja de Jonge, Vincent A de Weger, Mark A Dickson, Marlies Langenberg, Axel Le Cesne, Andrew J Wagner, Karl Hsu, Wei Zheng, Sandrine Macé, Gilles Tuffal, Koruth Thomas, Jan H M Schellens
PURPOSE: In tumours with wild-type TP53, the tumour-suppressive function of p53 is frequently inhibited by HDM2. This phase I, dose-escalating study investigated the maximum tolerated dose (MTD), safety, pharmacokinetics and pharmacodynamics of SAR405838, an HDM2 inhibitor, in patients with advanced solid tumours (NCT01636479). METHODS: In dose escalation, patients with any locally advanced/metastatic solid tumour with TP53 mutation prevalence below 40%, or documented as TP53 wild-type, were eligible...
March 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28324671/dose-de-escalation-of-intrapleural-tissue-plasminogen-activator-therapy-for-pleural-infection-the-adapt-project
#6
Natalia Popowicz, Oliver Bintcliffe, Duneesha De Fonseka, Kevin G Blyth, Nicola A Smith, Francesco Piccolo, Geoffrey Martin, Donny Wong, Anthony Edey, Nick Maskell, Y C Gary Lee
RATIONALE: Intrapleural therapy with a combination of tissue plasminogen activator (tPA) 10mg and deoxyribonuclease (DNase) 5mg administered twice daily has been shown in randomized and open-label studies to enable adequate drainage of over 90% of infected pleural effusions without surgery. Potential bleeding risks associated with intrapleural tPA and the drug costs remain important concerns. The ongoing ADAPT (Alteplase Dose Assessment for Pleural infection Therapy) project aims to investigate the efficacy and safety of dose de-escalation for intrapleural tPA...
March 21, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28322866/decreased-anxiety-voluntary-ethanol-intake-and-ethanol-induced-cpp-acquisition-following-activation-of-the-metabotropic-glutamate-receptor-8-mglur8
#7
Amine Bahi
Metabotropic glutamate receptors (mGluRs) are important modulators of excitatory neurotransmission, and have been implicated in addiction to alcohol and anxiety-related behaviors. However, the behavioral consequence and contribution of individual subtypes are not known yet. This study determined the effects of mGluR8 activation on anxiety-like behavior, voluntary ethanol intake and ethanol-induced conditioned reward. To this aim, anxiety and spontaneous behavior were measured in C57BL/6J mice using the elevated plus maze (EPM), open field (OF) and light-dark box (LDB) tests after systemic injection of the selective mGluR8 agonist (S)-3,4-dicarboxyphenylglycine ((S)-3,4-DCPG)...
March 17, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28321512/four-year-maintenance-treatment-with-adalimumab-in-japanese-patients-with-moderately-to-severely-active-ulcerative-colitis
#8
Yasuo Suzuki, Satoshi Motoya, Hiroyuki Hanai, Toshifumi Hibi, Shiro Nakamura, Andreas Lazar, Anne Martin Robinson, Martha Skup, Nael Mohamed Mostafa, Bidan Huang, Roopal Thakkar, Mamoru Watanabe
BACKGROUND: The 52-week safety and efficacy of adalimumab in Japanese patients with moderately to severely active ulcerative colitis were demonstrated in a placebo-controlled phase 2/3 trial. Data from patients who enrolled in the open-label extension study are presented. METHODS: Remission and response per the full Mayo score (FMS) and the partial Mayo score (PMS), remission per the Inflammatory Bowel Disease Questionnaire (IBDQ) score, corticosteroid-free remission, and mucosal healing were assessed up to week 196 (week 208 for remission/response per PMS) of adalimumab treatment in patients who received one or more doses of adalimumab with use of a hybrid nonresponder imputation (hNRI) method...
March 20, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28320724/piperacillin-tazobactam-versus-other-antibacterial-agents-for-treatment-of-bloodstream-infections-due-to-ampc-beta-lactamase-producing-enterobacteriaceae
#9
Lucy Cheng, Brian C Nelson, Monica Mehta, Nikhil Seval, Sarah Park, Marla J Giddins, Qiuhu Shi, Susan Whittier, Angela Gomez-Simmonds, Anne-Catrin Uhlemann
In vivo induction of AmpC beta-lactamases produces high-level resistance to many beta-lactam antibiotics in Enterobacteriaceae, often resulting in the use of carbapenems or cefepime (FEP). The clinical effectiveness of piperacillin-tazobactam (TZP), a weak inducer of AmpC beta-lactamases, is poorly understood. Here we conducted a case-control study of adult inpatients with bloodstream infections (BSIs) due to Enterobacter, Serratia, or Citrobacter spp. from 2009 to 2015 to assess outcomes following treatment with TZP compared to FEP or meropenem (MEM)...
March 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28320635/safety-and-efficacy-of-multipotent-adult-progenitor-cells-in-acute-ischaemic-stroke-masters-a-randomised-double-blind-placebo-controlled-phase-2-trial
#10
David C Hess, Lawrence R Wechsler, Wayne M Clark, Sean I Savitz, Gary A Ford, David Chiu, Dileep R Yavagal, Ken Uchino, David S Liebeskind, Alexander P Auchus, Souvik Sen, Cathy A Sila, Jeffrey D Vest, Robert W Mays
BACKGROUND: Multipotent adult progenitor cells are a bone marrow-derived, allogeneic, cell therapy product that modulates the immune system, and represents a promising therapy for acute stroke. We aimed to identify the highest, well-tolerated, and safest single dose of multipotent adult progenitor cells, and if they were efficacious as a treatment for stroke recovery. METHODS: We did a phase 2, randomised, double-blind, placebo-controlled, dose-escalation trial of intravenous multipotent adult progenitor cells in 33 centres in the UK and the USA...
March 17, 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28315818/sclerosing-encapsulated-peritonitis-a-devastating-and-infrequent-disease-complicating-kidney-transplantation-case-report-and-literature-review
#11
Liliana Caicedo, Alejandro Delgado, Luis A Caicedo, Juan Carlos Bravo, Laura S Thomas, Martin Rengifo, Jorge I Villegas, Oscar Serrano, Gabriel J Echeverri
INTRODUCTION: Sclerosing Encapsulating Peritonitis (SEP) is a rare condition with an incidence of up to 3% and a mortality of up to 51% among peritoneal dialysis (PD) patients (Brown et al., Korte et al. and Kawanishi et al.). In the last ten years, the incidence of SEP in kidney transplant recipients has increased (Nakamoto, de Sousa et al. and Korte et al.). PRESENTATION OF CASE: A 31-year old male with a 15 years history of PD and later kidney retransplantation was admitted to the emergency service after experiencing several weeks of diffuse abdominal pain which had escalated to include vomiting and diarrhea during the 24h previous to admission...
March 1, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28314877/fully-automated-vmat-treatment-planning-for-advanced-stage-nsclc-patients
#12
Giuseppe Della Gala, Maarten L P Dirkx, Nienke Hoekstra, Dennie Fransen, Nico Lanconelli, Marjan van de Pol, Ben J M Heijmen, Steven F Petit
PURPOSE: To develop a fully automated procedure for multicriterial volumetric modulated arc therapy (VMAT) treatment planning (autoVMAT) for stage III/IV non-small cell lung cancer (NSCLC) patients treated with curative intent. MATERIALS AND METHODS: After configuring the developed autoVMAT system for NSCLC, autoVMAT plans were compared with manually generated clinically delivered intensity-modulated radiotherapy (IMRT) plans for 41 patients. AutoVMAT plans were also compared to manually generated VMAT plans in the absence of time pressure...
March 17, 2017: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/28314838/a-phase-i-study-of-abiraterone-acetate-combined-with-bez235-a-dual-pi3k-mtor-inhibitor-in-metastatic-castration-resistant-prostate-cancer
#13
Xiao X Wei, Andrew C Hsieh, Won Kim, Terence Friedlander, Amy M Lin, Mirela Louttit, Charles J Ryan
LESSONS LEARNED: The combination of standard dose abiraterone acetate and BEZ235, a pan-class I PI3K and mTORC1/2 inhibitor, was poorly tolerated in men with progressive mCRPC.Although the clinical development of BEZ235 has been discontinued in prostate cancer, agents that more selectively target PI3K-AKT-mTOR signaling may have a more favorable therapeutic index and should continue to be explored. BACKGROUND: Androgen receptor (AR) and phosphatidylinositol-3 kinase (PI3K) signaling are two commonly perturbed pathways in prostate cancer...
March 17, 2017: Oncologist
https://www.readbyqxmd.com/read/28314755/a-randomised-controlled-trial-of-the-efficacy-and-safety-of-allopurinol-dose-escalation-to-achieve-target-serum-urate-in-people-with-gout
#14
Lisa K Stamp, Peter T Chapman, Murray L Barclay, Anne Horne, Christopher Frampton, Paul Tan, Jill Drake, Nicola Dalbeth
OBJECTIVES: To determine the efficacy and safety of allopurinol dose escalation using a treat-to-target serum urate (SU) approach. METHODS: A randomised, controlled, parallel-group, comparative clinical trial was undertaken. People with gout receiving at least creatinine clearance (CrCL)-based allopurinol dose for ≥1 month and SU ≥6 mg/dL were recruited. Participants were randomised to continue current dose (control) or allopurinol dose escalation for 12 months...
March 17, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28306192/histone-deacetylase-activity-mediates-acquired-resistance-towards-structurally-diverse-hsp90-inhibitors
#15
Ryan C Chai, Jessica L Vieusseux, Benjamin J Lang, Chau H Nguyen, Michelle M Kouspou, Kara L Britt, John T Price
Heat Shock Protein 90 (HSP90) regulates multiple signaling pathways critical for tumor growth. As such, HSP90 inhibitors have been shown to act as effective anticancer agents in preclinical studies but, for a number of reasons, the same effect has not been observed in the clinical trials to date. One potential reason for this may the presence of de novo or acquired resistance within the tumors. To investigate mechanisms of resistance, we generated resistant cell lines through gradual dose escalation of the HSP90 inhibitor 17-AAG...
March 17, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28303006/short-course-high-dose-rifampicin-achieves-wolbachia-depletion-predictive-of-curative-outcomes-in-preclinical-models-of-lymphatic-filariasis-and-onchocerciasis
#16
Ghaith Aljayyoussi, Hayley E Tyrer, Louise Ford, Hanna Sjoberg, Nicolas Pionnier, David Waterhouse, Jill Davies, Joanne Gamble, Haelly Metugene, Darren A N Cook, Andrew Steven, Raman Sharma, Ana F Guimaraes, Rachel H Clare, Andrew Cassidy, Kelly L Johnston, Laura Myhill, Laura Hayward, Samuel Wanji, Joseph D Turner, Mark J Taylor, Stephen A Ward
Lymphatic filariasis (LF) and onchocerciasis are priority neglected tropical diseases targeted for elimination. The only safe drug treatment with substantial curative activity against the filarial nematodes responsible for LF (Brugia malayi, Wuchereria bancrofti) or onchocerciasis (Onchocerca volvulus) is doxycycline. The target of doxycycline is the essential endosymbiont, Wolbachia. Four to six weeks doxycycline therapy achieves >90% depletion of Wolbachia in worm tissues leading to blockade of embryogenesis, adult sterility and premature death 18-24 months post-treatment...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28302661/severe-co-trimoxazole-induced-hypoglycaemia-in-a-patient-with-microscopic-polyangiitis
#17
Thomas Edward Conley, Atif Mohiuddin, Noshaba Naz
A 69-year-old man presented to the emergency department with lower respiratory tract infection and febrile neutropaenia. He was recently discharged following a 50-day hospital stay with newly diagnosed microscopic polyangiitis, complicated by pulmonary haemorrhage and severe renal dysfunction requiring renal replacement therapy, plasma exchange and immunosuppression (cyclophosphamide and methylprednisolone). High risk of pneumocystis pneumonia (PCP) led to an escalation in treatment from prophylactic to therapeutic oral co-trimoxazole, alongside broad-spectrum antibiotics...
March 16, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28302576/adolescent-chronic-escalating-morphine-administration-induces-long-lasting-changes-in-tolerance-and-dependence-to-morphine-in-rats
#18
Hamed Salmanzadeh, Hossein Azizi, Saeed Semnanian
Adolescence is a gradual period of transition from childhood to adulthood. It is considered as a sensitive developmental time point that long lasting changes occur in the brain. The present study examined adolescent chronic escalating morphine administration on morphine tolerance and dependence in adulthood. Adolescent male Wistar rats (30days old) were administered increasing doses of morphine (2.5 to 25mg/kg, s.c.) every 12h, for 10days. Control rats received saline according to the same protocol. Thereafter, during adulthood (65-75days old), tolerance to antinociceptive effect of morphine was induced by subcutaneous injection of 3mg/kg morphine, once a day for 7days...
March 13, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28297326/quantification-of-the-margin-required-for-treating-intraprostatic-lesions
#19
Matthew T Studenski, Yanisley Valenciaga, Matthew C Abramowitz, Radka Stoyanova, Elizabeth Bossart, Nesrin Dogan, Alan Pollack
Advances in magnetic resonance imaging (MRI) sequences allow physicians to define the dominant intraprostatic lesion (IPL) in prostate radiation therapy treatments allowing for dose escalation and potentially increased tumor control. This work quantifies the margin required around the MRI-defined IPL accounting for both prostate motion and deformation. Ten patients treated with a simultaneous integrated intraprostatic boost (SIIB) were retrospectively selected and replanned with incremental 1 mm margins from 0-5 mm around the IPL to determine if there were any significant differences in dosimetric parameters...
May 2016: Journal of Applied Clinical Medical Physics
https://www.readbyqxmd.com/read/28296770/evaluation-of-intrathecal-drug-delivery-system-for-intractable-pain-in-advanced-malignancies-a-prospective-cohort-study
#20
Shuyue Zheng, Liangliang He, Xiaohui Yang, Xiuhua Li, Zhanmin Yang
Pain is prevalent in advanced malignancies; however, some patients cannot get adequate pain relief by conservative routes of analgesic administration or experience serious side effects related to high dose of opioids. For those who have exhausted multimodal conservative analgesic, intrathecal drug delivery is an alternative intervention for truly effective pain management. The objective of this study was to evaluate the clinical efficacy and safety of intrathecal drug delivery system (IDDS) for the treatment of intractable pain in advanced cancer patients...
March 2017: Medicine (Baltimore)
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