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https://www.readbyqxmd.com/read/27919901/safety-and-pharmacokinetics-of-cd101-iv-a-novel-echinocandin-in-healthy-adults
#1
Taylor Sandison, Voon Ong, Jonathan Lee, Dirk Thye
CD101 IV is a novel echinocandin with distinctive pharmacokinetic properties that is being developed as a once-weekly treatment for candidemia and invasive candidiasis. CD101 has potent in vitro activity and in vivo efficacy against a broad range of Candida and Aspergillus species. The primary objective of two randomized, double-blind, placebo-controlled, dose-escalation studies in healthy adults was to determine the safety and tolerability of CD101 IV. Sequential cohorts of 8 subjects (n=6, active; n=2, placebo) were administered single (50, 100, 200, 400 mg) or multiple once-weekly (100 mg ×2, 200 mg ×2, 400 mg ×3) doses of CD101 IV infused over 1 hour...
December 5, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27919760/proton-therapy-present-and-future
#2
REVIEW
Radhe Mohan, David Grosshans
In principle, proton therapy offers a substantial clinical advantage over the conventional photon therapy. This is because of the unique depth-dose characteristics of protons, which can be exploited to achieve significant reductions in normal tissue doses proximal and distal to the target volume. These may, in turn, allow escalation of tumor doses, greater sparing of normal tissues, thus potentially improving local control and survival while at the same time reducing toxicity and improving quality of life. Protons, accelerated to therapeutic energies ranging from 70 to 250MeV, typically with a cyclotron or a synchrotron, are transported to the treatment room where they enter the treatment head mounted on a rotating gantry...
December 2, 2016: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/27918781/the-role-of-adjuvant-chemotherapy-in-surgically-managed-p16-positive-oropharyngeal-squamous-cell-carcinoma
#3
S Andrew Skillington, Dorina Kallogjeri, James S Lewis, Jay F Piccirillo
Importance: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) has a favorable prognosis, and p16 immunohistochemistry is a surrogate marker of high-risk HPV infection and strong prognosticator. Given this favorable prognosis, treatment de-escalation for p16-positive OPSCC is now being considered with the goal of decreasing treatment-associated morbidity without compromising tumor control. The role of adjuvant chemotherapy in this setting is becoming increasingly unclear...
December 1, 2016: JAMA Otolaryngology—Head & Neck Surgery
https://www.readbyqxmd.com/read/27917870/high-frequency-stimulation-of-the-subthalamic-nucleus-blocks-compulsive-like-re-escalation-of-heroin-taking-in-rats
#4
Carrie L Wade, Marsida Kallupi, Daniel O Hernandez, Emmanuel Breysse, Giordano de Guglielmo, Elena Crawford, George F Koob, Paul Schweitzer, Christelle Baunez, Olivier George
Opioid addiction, including addiction to heroin, has dramatically increased in the last decade. The cost and pervasiveness of heroin addiction, including resistance to recovery from addiction, provide a compelling basis for developing novel therapeutic strategies. Deep brain stimulation may represent a viable alternative strategy for the treatment of intractable heroin addiction particularly in individuals who are resistant to traditional therapies. Here, we provide preclinical evidence of the therapeutic potential of high-frequency stimulation of the subthalamic nucleus (STN HFS) for heroin addiction...
December 5, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27917735/top-1-of-inpatients-administered-antimicrobial-agents-comprising-50-of-expenditures-a-descriptive-study-and-opportunities-for-stewardship-intervention
#5
Jennifer Dela-Pena, Luiza Kerstenetzky, Lucas Schulz, Ron Kendall, Alexander Lepak, Barry Fox
OBJECTIVE To characterize the top 1% of inpatients who contributed to the 6-month antimicrobial budget in a tertiary, academic medical center and identify cost-effective intervention opportunities targeting high-cost antimicrobial utilization. DESIGN Retrospective cohort study. PATIENTS Top 1% of the antimicrobial budget from July 1 through December 31, 2014. METHODS Patients were identified through a pharmacy billing database. Baseline characteristics were collected through a retrospective medical chart review...
December 5, 2016: Infection Control and Hospital Epidemiology
https://www.readbyqxmd.com/read/27917453/phase-i-study-of-mrx34-a-liposomal-mir-34a-mimic-administered-twice-weekly-in-patients-with-advanced-solid-tumors
#6
Muhammad S Beg, Andrew J Brenner, Jasgit Sachdev, Mitesh Borad, Yoon-Koo Kang, Jay Stoudemire, Susan Smith, Andreas G Bader, Sinil Kim, David S Hong
Purpose Naturally occurring tumor suppressor microRNA-34a (miR-34a) downregulates the expression of >30 oncogenes across multiple oncogenic pathways, as well as genes involved in tumor immune evasion, but is lost or under-expressed in many malignancies. This first-in-human, phase I study assessed the maximum tolerated dose (MTD), safety, pharmacokinetics, and clinical activity of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumors. Patients and Methods Adult patients with solid tumors refractory to standard treatment were enrolled in a standard 3 + 3 dose escalation trial...
December 5, 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/27916416/dosimetric-feasibility-of-ablative-dose-escalated-focal-monotherapy-with-mri-guided-high-dose-rate-hdr-brachytherapy-for-prostate-cancer
#7
Ali Hosni, Marco Carlone, Alexandra Rink, Cynthia Ménard, Peter Chung, Alejandro Berlin
PURPOSE: To determine the dosimetric feasibility of dose-escalated MRI-guided high-dose-rate brachytherapy (HDR-BT) focal monotherapy for prostate cancer (PCa). METHODS: In all patients, GTV was defined with mpMRI, and deformably registered onto post-catheter insertion planning MRI. PTV included the GTV plus 9mm craniocaudal and 5mm in every other direction. In discovery-cohort, plans were obtained for each PTV independently aiming to deliver ⩾16.5Gy/fraction (two fraction schedule) while respecting predefined organs-at-risk (OAR) constraints or halted when achieved equivalent single-dose plan (24Gy)...
December 1, 2016: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/27913497/response-adapted-frontline-therapy-for-hodgkin-lymphoma-are-we-there-yet
#8
Peter W M Johnson
Treating Hodgkin lymphoma by using chemotherapy with or without radiotherapy is highly successful, with substantially fewer deaths from lymphoma than from other causes in recent studies of both early-stage and advanced-stage disease. Long-term toxicity is a major consideration in this context, and recent trials have used functional imaging with [(18)F]fluorodeoxyglucose (FDG) positron emission tomography early in the course of treatment (interim PET) to assess response and modulate subsequent therapy. In early-stage disease, this has allowed omission of consolidation radiotherapy after a good response to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy, and trials have shown that this can be done without detriment to overall survival, despite a small increase in rates of recurrence of ∼5%...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27912833/treatment-of-locally-advanced-non-small-cell-lung-cancer
#9
REVIEW
Kit Tam, Megan Daly, Karen Kelly
Locally advanced non-small cell lung cancer is a heterogeneous disease with typically poor outcomes. Select patients may benefit from the integration of surgery, whereas patients with bulky, multistation, or contralateral (N3) mediastinal involvement are managed with definitive chemoradiation. Attempts to improve outcomes through induction, consolidation, or maintenance chemotherapy or radiation dose escalation have not demonstrated a survival benefit. Current research efforts focus on the integration of novel systemic agents that exploit tumor-specific driver mutations, augment antitumor immune response, or enhance radiation sensitivity...
February 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/27911138/phase-1-dose-escalation-study-of-oral-abexinostat-for-the-treatment-of-patients-with-relapsed-refractory-higher-risk-myelodysplastic-syndromes-acute-myeloid-leukemia-or-acute-lymphoblastic-leukemia
#10
Norbert Vey, Thomas Prebet, Claire Thalamas, Aude Charbonnier, Jerome Rey, Ioana Kloos, Emily Liu, Ying Luan, Remus Vezan, Thorsten Graef, Christian Recher
Histone deacetylase (HDAC) inhibitor abexinostat is under investigation for the treatment of various cancers. Epigenetic changes including aberrant HDAC activity are associated with cancers, including myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL). In this phase 1 dose-escalation study, 17 patients with relapsed/refractory higher-risk MDS, AML, or ALL received oral abexinostat (60, 80 [starting dose], 100, or 120 mg) twice daily (bid) on Days 1-14 of 21-day cycles...
December 2, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27911128/s-1-in-combination-with-docetaxel-and-oxaliplatin-in-patients-with-advanced-gastro-esophageal-adenocarcinoma-two-parallel-phase-1-2a-studies
#11
Per Pfeiffer, Camilla Qvortrup, Merete Krogh, Katrine Schoennemann, Lene W Vestermark, Helle A Jensen, Jon K Bjerregaard
BACKGROUND: Docetaxel in combination with cisplatin and 5-fluorouracil (5-FU) is one of several standard chemotherapy regimens for patients with advanced gastro-esophageal adenocarcinoma (aGEA) in Europe. To enable outpatient treatment, we evaluated the maximum tolerated dose (MTD), recommended dose (RD), dose limiting toxicity (DLT) and safety of docetaxel in combination with oxaliplatin (O) and S-1 (DOS) in Caucasian patients with aGEA. METHODS: We present final results of two parallel phase 1/2a studies (3 + 3 design)...
December 2, 2016: Acta Oncologica
https://www.readbyqxmd.com/read/27910037/effect-of-activated-charcoal-on-rivaroxaban-complex-absorption
#12
Edouard Ollier, Sophie Hodin, Julien Lanoiselée, Jean Escal, Sandrine Accassat, Elodie De Magalhaes, Thierry Basset, Laurent Bertoletti, Patrick Mismetti, Xavier Delavenne
OBJECTIVE: To quantify the impact of activated charcoal (AC) on rivaroxaban exposure in healthy volunteers. METHODS: This was an open-label study with an incomplete cross-over design of single-dose rivaroxaban (40 mg) administered alone or with AC in 12 healthy volunteers. The study comprised three treatment periods in randomised sequence, one with rivaroxaban administered alone and two with AC given at 2, 5 or 8 h post-dose. Rivaroxaban plasma concentration was measured in blood samples drawn at 16 time points...
December 2, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27907959/status-epilepticus-in-the-intensive-care-unit
#13
Adriana Bermeo-Ovalle, Thomas Bleck
Status epilepticus (SE) is a common neurologic emergency and a frequent reason for admission to the intensive care unit. During the last decade, the advent and availability of diagnostic tools for the recognition of nonconvulsive SE has highlighted an even higher incidence of this condition among the critically ill. New alternatives in treatment have also become available within recent years. The recommendation of early escalation toward the use of general anesthetics in the treatment of convulsive SE follows the theory that the duration of the event defines the aggressiveness of the condition and the potential for long-term neuronal injury...
December 2016: Seminars in Neurology
https://www.readbyqxmd.com/read/27905916/study-protocol-a-dose-escalating-phase-2-study-of-oral-lisdexamfetamine-in-adults-with-methamphetamine-dependence
#14
Nadine Ezard, Adrian Dunlop, Brendan Clifford, Raimondo Bruno, Andrew Carr, Alexandra Bissaker, Nicholas Lintzeris
BACKGROUND: The treatment of methamphetamine dependence is a continuing global health problem. Agonist type pharmacotherapies have been used successfully to treat opioid and nicotine dependence and are being studied for the treatment of methamphetamine dependence. One potential candidate is lisdexamfetamine, a pro-drug for dexamphetamine, which has a longer lasting therapeutic action with a lowered abuse potential. The purpose of this study is to determine the safety of lisdexamfetamine in this population at doses higher than those currently approved for attention deficit hyperactivity disorder or binge eating disorder...
December 1, 2016: BMC Psychiatry
https://www.readbyqxmd.com/read/27899808/autoimmunity-to-hsp60-during-diet-induced-obesity-in-mice
#15
M E Şelli, G Wick, D C Wraith, A C Newby
Adaptive immunity has been implicated in adipose tissue inflammation, obesity and its adverse metabolic consequences. No obesity-related autoantigen has yet been identified, although heat shock protein 60 (HSP60) has been implicated in other autoimmune diseases. We investigated whether feeding a high fat diet to C57BL/6J mice would cause autoimmunity to HSP60 and whether immunomodulation with peptides from HSP60 would reverse the resulting obesity or metabolic dysfunction. Obese mice had higher circulating levels of HSP60 associated with increased T-lymphocyte proliferation responses and the emergence of circulating IgG1 and IgG2c antibody levels against HSP60...
November 30, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/27898208/-design-and-implementation-of-an-outpatient-parenteral-antimicrobial-therapy-program-in-primary-care-the-experience-at-a-second-level-hospital
#16
M Ruiz-Campuzano, E García-Vázquez, J J Hernández-Roca, J Gómez-Gómez, M Canteras-Jordana, E Mené-Fenor, A Hernández-Torres, A Peláez-Ballesta
OBJECTIVE: Outpatient parenteral antimicrobial therapy (OPAT) programs are a good assistance option in a wide variety of infectious diseases. Our aim was to design and implement an OPAT program in the area of influence of a second-level hospital, with no Home Hospitalization Service available, being necessary close collaboration between hospitalization and Primary Care teams, describe our cohort, analyse the antimicrobial treatment indicated and evaluate the prognostic and risk factors associated with readmission and mortality...
November 28, 2016: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
https://www.readbyqxmd.com/read/27897060/potential-for-adaptive-dose-escalation-in-radiotherapy-for-patients-with-locally-advanced-non-small-cell-lung-cancer-in-a-low-mid-income-setting
#17
Sushma Agrawal, Sunil Kumar, Anil Kumar Maurya
OBJECTIVE: To evaluate the effect of tumour volume regression on adaptive treatment planning, reduction in doses to organs at risk (OAR) and dose escalation. METHODS: 20 patients undergoing radical chemoradiotherapy were imaged in fifth week of radiotherapy (CT_45) to evaluate differences in tumour volume regression between concurrent (CONC) and sequential chemoradiotherapy (SEQ). Replanning was done on CT_45 in those with >20% regression (n=10) and evaluated for change in target coverage indices (coverage index [CI], external volume index [EI]) and doses to OAR [mean lung dose, V20 and V5 of whole and ipsilateral lung (MLDWL, V20WL, V5WL, MLDIL, V20IL, V5IL), mean esophagus dose, V50 esophagus and maximum spinal cord doses]...
November 29, 2016: British Journal of Radiology
https://www.readbyqxmd.com/read/27896689/pharmacokinetics-of-daratumumab-following-intravenous-infusion-in-relapsed-or-refractory-multiple-myeloma-after-prior-proteasome-inhibitor-and-immunomodulatory-drug-treatment
#18
Pamela L Clemens, Xiaoyu Yan, Henk M Lokhorst, Sagar Lonial, Nedjad Losic, Imran Khan, Richard Jansson, Tahamtan Ahmadi, Kristen Lantz, Honghui Zhou, Thomas Puchalski, Xu Steven Xu
Daratumumab is a CD38 monoclonal antibody recently approved for the treatment of multiple myeloma (MM). We report daratumumab pharmacokinetic data from GEN501, a phase I/II dose-escalation (0.005-24 mg/kg) and dose-expansion (8 or 16 mg/kg) study, and SIRIUS, a phase II study (8 or 16 mg/kg), in relapsed or refractory MM. Noncompartmental analysis was conducted to characterize daratumumab pharmacokinetics, and, in both studies, daratumumab exhibited nonlinear pharmacokinetic characteristics. Decreasing daratumumab clearance with increasing dose suggests saturation of target-mediated clearance at higher dose levels, whereas decreasing clearance over time with repeated dosing may be due to tumor burden reductions as CD38-positive cells are eliminated...
November 29, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27896522/tapering-biologics-in-rheumatoid-arthritis-a-pragmatic-approach-for-clinical-practice
#19
Aleksander Lenert, Petar Lenert
Optimal rheumatoid arthritis (RA) therapy in daily clinical practice is based on the treat-to-target strategy. Quicker escalation of therapy and earlier introduction of biological disease-modifying anti-rheumatic drugs have led to improved outcomes in RA. However, chronic immunosuppressive therapy is associated with adverse events and higher costs. In addition, our patients frequently express a desire for lower dosing and drug holidays. Current clinical practice guidelines from the American College of Rheumatology and European League Against Rheumatism suggest that rheumatologists consider tapering treatment after achieving remission...
November 28, 2016: Clinical Rheumatology
https://www.readbyqxmd.com/read/27895479/cationic-pegylated-liposomes-incorporating-an-antimicrobial-peptide-tilapia-hepcidin-2-3-an-adjuvant-of-epirubicin-to-overcome-multidrug-resistance-in-cervical-cancer-cells
#20
Vivian Juang, Hsin-Pin Lee, Anya Maan-Yuh Lin, Yu-Li Lo
Antimicrobial peptides (AMPs) have been recently evaluated as a new generation of adjuvants in cancer chemotherapy. In this study, we designed PEGylated liposomes encapsulating epirubicin as an antineoplastic agent and tilapia hepcidin 2-3, an AMP, as a multidrug resistance (MDR) transporter suppressor and an apoptosis/autophagy modulator in human cervical cancer HeLa cells. Cotreatment of HeLa cells with PEGylated liposomal formulation of epirubicin and hepcidin 2-3 significantly increased the cytotoxicity of epirubicin...
2016: International Journal of Nanomedicine
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