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https://www.readbyqxmd.com/read/28109167/cell-cycle-tailored-targeting-of-metastatic-melanoma-challenges-opportunities
#1
Nikolas K Haass, Brian Gabrielli
The advent of targeted therapies of metastatic melanoma, such as MAPK pathway inhibitors and immune checkpoint antagonists, has turned dermato-oncology from the 'bad guy' to the 'poster child' in oncology. Current targeted therapies are effective; although here is a clear need to develop combination therapies to delay the onset of resistance. Many anti-melanoma drugs impact on the cell cycle but are also dependent on certain cell cycle phases resulting in cell cycle phase-specific drug insensitivity. Here, we raise the question: Have combination trials been abandoned prematurely as ineffective possibly only because drug scheduling was not optimized? Firstly, if both drugs of a combination hit targets in the same melanoma cell, cell cycle-mediated drug insensitivity should be taken into account when planning combination therapies, timing of dosing schedules and choice of drug therapies in solid tumors...
January 21, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28109128/population-pharmacokinetics-and-pharmacodynamics-of-benralizumab-in-healthy-volunteers-and-patients-with-asthma
#2
B Wang, L Yan, Z Yao, L K Roskos
Benralizumab is a humanized, afucosylated, anti-interleukin-5 receptor α, immunoglobulin G (IgG) 1 κ monoclonal antibody. We developed a population pharmacokinetic (PK)/pharmacodynamic (PD) model for benralizumab by analyzing PK and blood eosinophil count data from two healthy volunteer studies (N = 48) and four studies in patients with asthma (N = 152). Benralizumab PK was dose-proportional and adequately described by a two-compartment model with first-order elimination from the central compartment and first-order absorption from the subcutaneous dosing site...
January 21, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28109077/simultaneous-but-not-consecutive-combination-with-folinate-salts-potentiates-5-fluorouracil-antitumor-activity-in-vitro-and-in-vivo
#3
Antonello Di, Paola Orlandi, Teresa Di, Romano Danesi, Guido Bocci
The combination of folinate salts to 5-fluoruracil (5-FU)-based schedules is an established clinical routine in the landscape of the colorectal cancer treatment. The aim of this study was to investigate the pharmacological differences between the sequential administration of folinate salts (1 h before, as in clinical routine) followed by 5-FU and the simultaneous administration of both drugs. Proliferation and apoptotic assays were performed on human colon cancer cells exposed to 5-FU, calcium (CaLV) or disodium (NaLV) levofolinate or their simultaneous and sequential combination for 24 and 72h...
January 20, 2017: Oncology Research
https://www.readbyqxmd.com/read/28108765/score-study-quality-indicators-for-rheumatology-nursing-clinics
#4
Santiago Muñoz-Fernández, Ma Dolores Aguilar, Raquel Almodóvar, Laura Cano-García, Sandra Fortea, Cristina Patricia Alcañiz-Escandell, José R Rodríguez, Laura Cebrián, Pablo Lázaro
Nursing clinics in rheumatology (NCR) are organizational care models that provide care centred within the scope of nurses abilities. To analyse patients differences in the knowledge of the disease, adherence to the treatment, quality indicators of the Rheumatology Departments included quality perceived by the patients with and without NCR. National multicenter observational prospective cohort study 1 year follow-up, comparing patients attending rheumatology services with and without NCR. NCR was defined by the presence of: (1) office itself; (2) at least one dedicated nurse; (3) its own appointment schedule, and (4) phone...
January 20, 2017: Rheumatology International
https://www.readbyqxmd.com/read/28108642/the-potential-role-for-smartphones-among-older-adults-with-chronic-noncancer-pain-a-qualitative-study
#5
Joshua E Richardson, Jennifer I Lee, Anita Nirenberg, M Carrington Reid
: OBJECTIVE : To determine the role that smartphones may play in supporting older adults with chronic noncancer pain (CNCP) in order to improve pain management in this expanding population. DESIGN:  Qualitative study. SETTING:  One academically affiliated primary care practice serving older adults with CNCP in New York City. SUBJECTS : Thirteen older adults (age 65-85 years) with CNCP on chronic opioid therapy, that is, continuous use of opioids for at least six months...
January 20, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28108230/timeliness-and-risk-factors-associated-with-delay-for-pneumococcal-conjugate-10-valent-routine-immunization-in-brazilian-children
#6
Ana Lucia Sartori, Ruth Minamisava, Eliane Terezinha Afonso, Gabriela Moreira Policena, Grécia Carolina Pessoni, Ana Luiza Bierrenbach, Ana Lucia Andrade
BACKGROUND: Vaccination coverage is the usual metrics to evaluate the immunization programs performance. For the 10-valent pneumococcal conjugate (PCV10) vaccine, measuring the delay of vaccination is also important, particularly as younger children are at increased risk of disease. Routinely collected administrative data was used to assess the timeliness of PCV10 vaccination, and the factors associated with delay to receive the first and second doses, and the completion of the PCV10 3+1 schedule...
January 17, 2017: Vaccine
https://www.readbyqxmd.com/read/28107887/associations-between-positive-emotional-well-being-and-stress-induced-myocardial-ischemia-well-being-scores-predict-exercise-induced-ischemia
#7
Jacob P Feigal, Stephen H Boyle, Zainab Samad, Eric J Velazquez, Jennifer L Wilson, Richard C Becker, Redford B Williams, Cynthia M Kuhn, Thomas L Ortel, Joseph G Rogers, Christopher M O'Connor, Wei Jiang
OBJECTIVE: Depressive symptoms have been associated with myocardial ischemia induced by mental (MSIMI) and exercise (ESIMI) stress in clinically stable ischemic heart disease (IHD) patients, but the association between positive emotions and inducible ischemia is less well characterized. The objective of this study was to examine the associations between ratings of well-being and stress-induced ischemia. METHODS: Subjects were adult patients with documented IHD underwent mental and exercise stress testing for the Responses of Myocardial Ischemia to Escitalopram Treatment (REMIT) trial...
February 2017: Journal of Psychosomatic Research
https://www.readbyqxmd.com/read/28107869/measles-outbreaks-in-the-kyeongin-area-of-the-republic-of-korea-2013-2014-a-single-center-experience-in-a-country-of-measles-elimination
#8
Sun Hyoung Park, Dong Hun Lee, Jang Yong Jin, Young-Lim Shin, Meeyong Shin, Sung Shin Kim, Won Suk Suh, Jae Ock Park, Yong Hee Hong
OBJECTIVE: To identify the source of infection and determine the clinical features and laboratory finding of measles infection. METHODS: In 27 measles patients, except for 3 adult patients, the rest of 24 pediatric measles cases were analyzed with regard to age, sex, immunization status, transmission routes and molecular genotyping of measles virus. Eighteen measles patients who admitted in isolation ward were set apart to investigate clinical findings and its correlation with laboratory characteristics...
January 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28107772/a-preliminary-randomized-controlled-trial-of-contingency-management-for-alcohol-use-reduction-using-a-transdermal-alcohol-sensor
#9
Nancy P Barnett, Mark A Celio, Jennifer W Tidey, James G Murphy, Suzanne M Colby, Robert M Swift
AIMS: We tested the efficacy of daily contingent reinforcement for reducing alcohol use compared with (yoked) noncontingent reinforcement (NR) using a transdermal alcohol sensor to detect alcohol use. DESIGN: Pilot randomized controlled design with one baseline week, three intervention weeks, and one-month follow up. SETTING: New England, USA. PARTICIPANTS: Heavy drinking adults (47% female) not seeking treatment were randomized to 1) an escalating schedule of cash reinforcement (CR; n =15) for days on which alcohol was neither reported nor detected or 2) yoked NR (n =15)...
January 20, 2017: Addiction
https://www.readbyqxmd.com/read/28107765/lower-adenoma-miss-rate-with-fuse-vs-conventional-colonoscopy-with-proximal-retroflexion-a-randomized-back-to-back-trial
#10
Ioannis S Papanikolaou, Periklis Apostolopoulos, Georgios Tziatzios, Erasmia Vlachou, Athanasios D Sioulas, Dimitrios Polymeros, Andreas Karameris, Ioannis Panayiotides, Georgios Alexandrakis, George D Dimitriadis, Konstantinos Triantafyllou
Background and study aims Full-spectrum colonoscopy (FSC) promises to increase adenoma detection by providing a wider field of view. The aim of this study was to compare adenoma miss rates of FSC with those of conventional colonoscopy complemented by right-colon re-examination using scope retroflexion (CC/R). Patients and methods At two tertiary endoscopy facilities, patients who were scheduled for colonoscopy for the assessment of symptoms or for colorectal cancer screening/surveillance were randomized (1:1) to undergo same-day, back-to-back colonoscopies (FSC or CC/R first), performed by one of five endoscopists who had documented adenoma detection rates > 35 %...
January 20, 2017: Endoscopy
https://www.readbyqxmd.com/read/28107598/dropout-in-clinical-trials-of-pharmacologic-treatment-for-methamphetamine-dependence-the-role-of-initial-abstinence
#11
Ryan Cook, Brendan Quinn, Keith Heinzerling, Steve Shoptaw
BACKGROUND AND AIMS: High rates of loss to follow-up represent a significant challenge to clinical trials of pharmacologic treatments for methamphetamine (MA) use disorder. We aimed to estimate and test the relationship between achieving and maintaining abstinence in the initial weeks of study participation and subsequent retention in such trials, hypothesizing that participants able to achieve early abstinence would be less likely to drop out. DESIGN: Data from four randomized controlled trials (RCTs) of pharmacologic treatments for MA use disorder were pooled and analyzed using a random-effects approach...
January 20, 2017: Addiction
https://www.readbyqxmd.com/read/28107554/inclusion-of-a-variable-rbe-into-proton-and-photon-plan-comparison-for-various-fractionation-schedules-in-prostate-radiation-therapy
#12
Jakob Ödén, Kjell Eriksson, Iuliana Toma-Dasu
PURPOSE: A constant relative biological effectiveness (RBE) of 1.1 is currently used in proton radiation therapy to account for the increased biological effectiveness compared to photon therapy. However, there is increasing evidence that proton RBE vary with the linear energy transfer (LET), the dose per fraction and the type of the tissue. Therefore, this study aims to evaluate the impact of disregarding variations in RBE when comparing proton and photon dose plans for prostate treatments for various fractionation schedules using published RBE models and several α/β assumptions...
January 20, 2017: Medical Physics
https://www.readbyqxmd.com/read/28107451/effect-of-nocturnal-hemodialysis-versus-conventional-hemodialysis-on-end-stage-renal-disease-a-meta-analysis-and-systematic-review
#13
Fangjie Liu, Yiting Sun, Tianhua Xu, Li Sun, Linlin Liu, Wei Sun, Xin Feng, Jianfei Ma, Lining Wang, Li Yao
OBJECTIVES: The purpose of this study is to assess the efficacy and safety of nocturnal hemodialysis on end-stage renal disease (ESRD) patients. METHODS: We searched Medline, EmBase, and the Cochrance Central Register of Controlled Trials for studies up to January 2016. Analysis was done to compare variant outcomes of different hemodialysis schedules, including mortality, cardiovascular-associated variables, uremia-associated variables, quality of life (QOL), side-effects, and drug usage...
2017: PloS One
https://www.readbyqxmd.com/read/28107402/risk-factors-for-postoperative-pain-intensity-in-patients-undergoing-lumbar-disc-surgery-a-systematic-review
#14
Marie Dorow, Margrit Löbner, Janine Stein, Alexander Konnopka, Hans J Meisel, Lutz Günther, Jürgen Meixensberger, Katarina Stengler, Hans-Helmut König, Steffi G Riedel-Heller
OBJECTIVES: Pain relief has been shown to be the most frequently reported goal by patients undergoing lumbar disc surgery. There is a lack of systematic research investigating the course of postsurgical pain intensity and factors associated with postsurgical pain. This systematic review focuses on pain, the most prevalent symptom of a herniated disc as the primary outcome parameter. The aims of this review were (1) to examine how pain intensity changes over time in patients undergoing surgery for a lumbar herniated disc and (2) to identify socio-demographic, medical, occupational and psychological factors associated with pain intensity...
2017: PloS One
https://www.readbyqxmd.com/read/28106622/effect-of-combination-vaccines-on-hepatitis-b-vaccine-compliance-in-children-in-the-united-states
#15
Samantha K Kurosky, Keith L Davis, Claudia M Galindo
BACKGROUND: An increasingly crowded immunization schedule threatens the completion and compliance of hepatitis B vaccinations (HepB), the primary method of hepatitis B prevention. Combination vaccines have been proposed to alleviate this problem. METHODS: Data from the 2011 National Immunization Survey Public Use File were utilized (GSK study identifier: HO-11-770) to compare HepB completion and compliance rates between 3 groups of children: those who received HepB combination vaccine, those who received non-HepB combination vaccine, and those who received HepB single-antigen vaccine only...
January 17, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28106498/performing-concurrent-operations-in-academic-vascular-neurosurgery-does-not-affect-patient-outcomes
#16
Corinna C Zygourakis, Janelle Lee, Julio Barba, Errol Lobo, Michael T Lawton
OBJECTIVE Concurrent surgeries, also known as "running two rooms" or simultaneous/overlapping operations, have recently come under intense scrutiny. The goal of this study was to evaluate the operative time and outcomes of concurrent versus nonconcurrent vascular neurosurgical procedures. METHODS The authors retrospectively reviewed 1219 procedures performed by 1 vascular neurosurgeon from 2012 to 2015 at the University of California, San Francisco. Data were collected on patient age, sex, severity of illness, risk of mortality, American Society of Anesthesiologists (ASA) status, procedure type, admission type, insurance, transfer source, procedure time, presence of resident or fellow in operating room (OR), number of co-surgeons, estimated blood loss (EBL), concurrent vs nonconcurrent case, severe sepsis, acute respiratory failure, postoperative stroke causing neurological deficit, unplanned return to OR, 30-day mortality, and 30-day unplanned readmission...
January 20, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28106355/comparative-study-of-fiberoptic-guided-versus-intubating-laryngeal-mask-airway-assisted-awake-orotracheal-intubation-in-patients-with-unstable-cervical-spine-a-randomized-controlled-trial
#17
Tanmay Jadhav, Kamath Sriganesh, Madhusudan K Reddy, Dhritiman Chakrabarti
BACKGROUND: A safe airway technique minimizes intubation-associated cervical-spine movement and consequent neurological injury in patients with unstable cervical spine (UCS). Awake fiberoptic-guided intubation (FGI) is preferred in patients with UCS. Alternatively, intubating laryngeal mask airway assisted intubation (ILMA-AI) can be performed both during elective and emergency, requires less expertise and is cost-effective. This study evaluated cervical-spine movement during FGI and ILMA-AI in patients with UCS...
January 20, 2017: Minerva Anestesiologica
https://www.readbyqxmd.com/read/28106354/adding-dexmedetomidine-to-ropivacaine-for-femoral-nerve-block-inhibit-local-inflammatory-response
#18
Jing Li, Hanghui Wang, Buhuai Dong, Jianbing Ma, Xucai Wu
BACKGROUND: Peripheral nerve block has an anti-inflammatory effect that is confirmed in animal studies, while inconclusive in human studies. Dexmedetomidine (DEX), a highly selective α2-adenoceptor agonist, has a potent anti-inflammatory effect. The aim of this study was to evaluate the effect of DEX added to ropivacaine for femoral nerve block (FNB) on local inflammatory response after total knee arthroplasty (TKA). METHODS: Sixty patients scheduled for TKA were randomized into two equal groups in a prospective randomized study...
January 20, 2017: Minerva Anestesiologica
https://www.readbyqxmd.com/read/28106022/complicated-left-sided-infective-endocarditis-in-chronic-hemodialysis-patients-a-case-report
#19
Öykü Gülmez, Mehtap Aydın
Infective endocarditis (IE) is a serious infectious condition with high morbidity and mortality in patients with end-stage renal disease (ESRD). It has been particularly associated with recurrent bacteremia due to vascular access via lumen catheters. The most common pathogen is Staphylococcus (S.) aureus, and most affected valve is mitral valve, which frequently calcified. Two patients with ESRD who received hemodialysis treatment via tunneled catheters, aged 56 and 88 years, were admitted with fever and high troponin level...
January 2017: Türk Kardiyoloji Derneği Arşivi: Türk Kardiyoloji Derneğinin Yayın Organıdır
https://www.readbyqxmd.com/read/28105997/first-successful-transcatheter-double-valve-replacement-from-a-transapical-access-and-nine-month-follow-up
#20
Robert Bauernschmitt, Stefan Bauer, Christian Liewald, Ramiz Emini, Wolfgang Oechsner, Meinrad Beer, Ralf Sodian, Andreas Liebold
AIMS: While TAVI is the treatment of choice in patients with aortic stenosis considered inoperable or at high risk, interventional replacement of the mitral valve is still in the preclinical or early clinical phase. Our aim was to report on the first transcatheter double valve replacement into native valves from a transapical access. METHODS AND RESULTS: A 67-year-old, highly symptomatic female patient considered inoperable due to severe calcification of the mitral annulus and comorbidities was scheduled for transcatheter double valve replacement by the local Heart Team...
January 20, 2017: EuroIntervention
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