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https://www.readbyqxmd.com/read/29045952/-progress-in-diagnosis-and-management-of-syncope-in-children
#1
W R Xu, Y Liao, H F Jin, Q Y Zhang, C S Tang, J B DU
Syncope is a common emergency of children and adolescents, which has serious influence on the quality of life. Neurally-mediated syncope, including postural tachycardia syndrome, vasovagal syncope, orthostatic hypotension and orthostatic hypertension, is the main cause of syncope in children and adolescents. The main manifestations of neurally-mediated syncope are diverse, such as dizziness, headache, chest tightness, chest pain, pale complexion, fatigue, pre-syncope and syncope. Although the clinical manifestations are similar, each subtype of syncope has its hemodynamic feature and optimal treatment option...
October 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/29045883/in-vitro-in-vivo-correlations-of-carbamazepine-nano-dispersions-for-application-in-formulation-development
#2
Zachary Warnken, Michael Puppolo, Justin Hughey, Iris Duarte, Susan Jansen-Varnum
During formulation development, efficiently integrating in vitro dissolution testing can significantly improve one's ability to estimate in vivo performance and aide in the selection of premier drug candidates. The concept of in vitro - in vivo relationship/correlation (IVIVR/IVIVC) has garnered significant attention from pharmaceutical scientists to predict expected bioavailability characteristics for drug substances and products. The current work illustrates a comparative evaluation of in vitro tests to access crystalline carbamazepine and various types of amorphous and crystalline dispersions of carbamazepine and Eudragit L100 produced by spray-drying, including a membrane-permeation dissolution methodology and non-sink dissolution...
October 15, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29045769/placebo-effects-in-the-treatment-of-noncognitive-symptoms-of-alzheimer-s-disease-analysis-of-the-catie-ad-data
#3
Chisa Ozawa, Rachel Roberts, Kazunari Yoshida, Takefumi Suzuki, Barry Lebowitz, Suzanne Reeves, Robert Howard, Takayuki Abe, Masaru Mimura, Hiroyuki Uchida
OBJECTIVE: To compare symptom trajectories between placebo and active drug responders and to examine whether early placebo improvement would be associated with subsequent placebo response in the treatment of patients with behavioral and psychological symptoms of dementia. METHODS: A post hoc analysis of data from 371 patients with DSM-IV Alzheimer's disease in Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness for Alzheimer's disease (CATIE-AD) (April 2001 to November 2004) was conducted...
October 17, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/29045749/immune-checkpoint-inhibitor-related-myocarditis
#4
Kazuko Tajiri, Kazutaka Aonuma, Ikuo Sekine
Immune checkpoint inhibitors have demonstrated significant clinical benefit in many cancers. The clinical benefit afforded by these treatments can be accompanied by a unique and distinct spectrum of adverse events. Recently, several fatal cases of immune checkpoint inhibitor-related myocarditis were reported. Although its frequency is comparatively lower than that of other immune-related adverse events, myocarditis can lead to circulatory collapse and lethal ventricular arrhythmia. Immune checkpoints, cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1), play important roles in establishing peripheral tolerance to the heart...
October 17, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29045642/patient-and-tumor-characteristics-and-their-influence-on-early-therapy-persistence-with-letrozole-in-postmenopausal-patients-with-early-breast-cancer
#5
N Nabieva, S Kellner, T Fehm, L Häberle, J de Waal, M Rezai, B Baier, G Baake, H-C Kolberg, M Guggenberger, M Warm, N Harbeck, R Wuerstlein, J-U Deuker, P Dall, B Richter, G Wachsmann, C Brucker, J W Siebers, N Fersis, T Kuhn, C Wolf, H-W Vollert, G-P Breitbach, W Janni, R Landthaler, A Kohls, D Rezek, T Noesselt, G Fischer, S Henschen, T Praetz, V Heyl, T Kühn, T Krauss, C Thomssen, A Hohn, H Tesch, C Mundhenke, A Hein, C Rauh, C M Bayer, A Jacob, K Schmidt, E Belleville, S Y Brucker, S Kümmel, M W Beckmann, D Wallwiener, P Hadji, P A Fasching
Background: Patients' compliance and persistence with endocrine treatment has a significant effect on the prognosis in early breast cancer (EBC). The purpose of this analysis was to identify possible reasons for non-persistence, defined as premature cessation of therapy, on the basis of patient and tumor characteristics in individuals receiving adjuvant treatment with letrozole. Patients and methods: The EvAluate-TM Study is a prospective, multicenter, noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive EBC in the early therapy phase...
October 10, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045529/impact-of-genetic-variations-in-the-mapk-signaling-pathway-on-outcome-in-metastatic-colorectal-cancer-patients-treated-with-first-line-folfiri-and-bevacizumab-data-from-fire-3-and-tribe-trials
#6
M D Berger, S Stintzing, V Heinemann, D Yang, S Cao, Y Sunakawa, Y Ning, S Matsusaka, S Okazaki, Y Miyamoto, M Suenaga, M Schirripa, S Soni, W Zhang, A Falcone, F Loupakis, H-J Lenz
Background: The MAPK-interacting kinase 1 (MKNK1) is localized downstream of the RAS/RAF/ERK and the MAP3K1/MKK/p38 signaling pathway. Through phosphorylation MKNK1 regulates the function of eukaryotic translation initiation factor 4E, a key player in translational control, whose expression is often upregulated in metastatic colorectal cancer patients (mCRC). Preclinical data suggest that MKNK1 increases angiogenesis by upregulating angiogenic factors. We therefore hypothesize that variations in the MKNK1 gene predict outcome in mCRC patients treated with first-line FOLFIRI and bevacizumab (bev)...
August 2, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045509/the-antibody-drug-conjugate-target-landscape-across-a-broad-range-of-tumour-types
#7
K L Moek, D J A de Groot, E G E de Vries, R S N Fehrmann
Background: Antibody-drug conjugates (ADCs), consisting of an antibody designed against a specific target at the cell membrane linked with a cytotoxic agent, are an emerging class of therapeutics. Since ADC tumour cell targets do not have to be drivers of tumour growth, ADCs are potentially relevant for a wide range of tumours currently lacking clear oncogenic drivers. Therefore, we aimed to define the landscape of ADC targets in a broad range of tumours. Materials and methods: PubMed and ClinicalTrials...
September 25, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045339/blood-pressure-response-to-renal-denervation-is-correlated-with-baseline-blood-pressure-variability-a-patient-level-meta-analysis
#8
Alexandre Persu, Daniel Gordin, Lotte Jacobs, Lutgarde Thijs, Michiel L Bots, Wilko Spiering, Atena Miroslawska, Jonas Spaak, Ján Rosa, Mark R de Jong, Elena Berra, Fadl Elmula M Fadl Elmula, Grégoire Wuerzner, Alison H M Taylor, Agnieszka Olszanecka, Danuta Czarnecka, Patrick B Mark, Michel Burnier, Jean Renkin, Sverre E Kjeldsen, Jiří Widimský, Arif Elvan, Thomas Kahan, Terje K Steigen, Peter J Blankestijn, Ilkka Tikkanen, Jan A Staessen
BACKGROUND: Sympathetic tone is one of the main determinants of blood pressure (BP) variability and treatment-resistant hypertension. The aim of our study was to assess changes in BP variability after renal denervation (RDN). In addition, on an exploratory basis, we investigated whether baseline BP variability predicted the BP changes after RDN. METHODS: We analyzed 24-h BP recordings obtained at baseline and 6 months after RDN in 167 treatment-resistant hypertension patients (40% women; age, 56...
October 16, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/29045077/subjective-complaints-as-main-reason-for-biosimilar-discontinuation-after-open-label-transitioning-from-originator-to-biosimilar-infliximab
#9
Lieke Tweehuysen, Bart J F van den Bemt, Iris L van Ingen, Alphons J L de Jong, Willemijn H van der Laan, Frank H J van den Hoogen, Alfons A den Broeder
OBJECTIVE: To evaluate drug survival, effectiveness, pharmacokinetics, immunogenicity and safety after transitioning treatment from originator infliximab (Remicade(®) , REM) to biosimilar infliximab (CT-P13) in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis in daily practice. METHODS: 192 of 222 REM-treated patients agreed to transition to CT-P13 and were included in this multicenter prospective cohort study. Change in DAS28-CRP, BASDAI, CRP and (anti-) infliximab levels were assessed after six months and adverse events (AEs) were documented...
October 18, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29045053/ensamble-based-adme-tox-profiling-and-virtual-screening-for-the-discovery-of-new-inhibitors-of-the-leishmania-mexicana-cysteine-protease-cpb2-8%C3%AE-cte
#10
Angela Scala, Antonio Rescifina, Nicola Micale, Anna Piperno, Tanja Schirmeister, Louis Maes, Giovanni Grassi
In an effort to identify novel molecular warheads able to inhibit Leishmania mexicana cysteine protease CPB2.8ΔCTE, fused benzo[b]thiophenes and β,β'-triketones emerged as covalent inhibitors binding the active site cysteine residue. Enzymatic screening showed a moderate to excellent activity (12-90% inhibition of the target enzyme at 20 μM). The most promising compounds were selected for further profiling including in vitro cell-based assays and docking studies. Computational data suggest that benzo[b]thiophenes act immediately as non-covalent inhibitors and then as irreversible covalent inhibitors, whereas a reversible covalent mechanism emerged for the 1,3,3'-triketones with a Y-topology...
October 17, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29044435/impact-of-clinical-parameters-in-the-intrahost-evolution-of-hiv-1-subtype-b-in-pediatric-patients-a-machine-learning-approach
#11
Patricia Rojas Sánchez, Alberto Cobos, Marisa Navaro, José Tomas Ramos, Israel Pagán, África Holguín
Determining the factors modulating the genetic diversity of HIV-1 populations is essential to understand viral evolution. This study analyzes the relative importance of clinical factors in the intrahost HIV-1 subtype B (HIV-1B) evolution and in the fixation of drug resistance mutations (DRM) during longitudinal pediatric HIV-1 infection. We recovered 162 partial HIV-1B pol sequences (from 3 to 24 per patient) from 24 perinatally infected patients from the Madrid Cohort of HIV-1 infected children and adolescents in a time interval ranging from 2...
October 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/29044374/human-and-livestock-trematode-infections-in-a-mobile-pastoralist-setting-at-lake-chad-added-value-of-a-one-health-approach-beyond-zoonotic-diseases-research
#12
Helena Greter, Annour A Batil, Bongo N Ngandolo, Idriss O Alfaroukh, Doumagoum D Moto, Jan Hattendorf, Jürg Utzinger, Jakob Zinsstag
Background: At Lake Chad in Central Africa, mobile pastoralists face economic losses due to livestock trematodiases. Fasciola gigantica and Schistosoma bovis-trematodes that affect livestock-share transmission ecology traits with Schistosoma haematobium and S. mansoni that cause human schistosomiasis. This project aimed at assessing treatment strategies and elucidating the predictive potential of human and livestock trematode infections. Methods: Schistosomiasis and fascioliasis were investigated concurrently in humans and cattle by repeated cross-sectional surveys...
June 1, 2017: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29043886/assessing-the-risk-of-alcohol-induced-dose-dumping-from-sustained-release-oral-dosage-forms-in-vitro-in-silico-approach
#13
Sandra Cvijić, Ivana Aleksić, Svetlana Ibrić, Jelena Parojčić
Consumption of alcoholic beverages with sustained-release oral dosage forms may pose a risk to patients due to potential alcohol-induced dose dumping (ADD). Regulatory guidances recommend in vitro dissolution testing to identify the risk of ADD, but the question remains whether currently proposed test conditions can be considered biopredictive. The purpose of this study was to evaluate different dissolution setups to assess ADD, and the potential of combined in vitro-in silico approach to predict drug absorption after concomitant alcohol intake for hydrophilic and lipophilic sustained-release tablets containing ibuprofen or diclofenac sodium...
October 18, 2017: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/29043496/erlotinib-plus-bevacizumab-phase-ll-study-in-patients-with-advanced-non-small-cell-lung-cancer-jo25567-updated-safety-results
#14
Terufumi Kato, Takashi Seto, Makoto Nishio, Koichi Goto, Noboru Yamamoto, Isamu Okamoto, Liang Tao, Wei Yu, Tarik Khaznadar, Kosei Tajima, Masahiko Shibata, Akihiro Seki, Nobuyuki Yamamoto
INTRODUCTION: The phase II JO25567 study compared the efficacy and safety of erlotinib plus bevacizumab vs. erlotinib alone as first-line therapy for advanced epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). OBJECTIVE: Our objective is to provide updated analyses of safety and the assessment of manageability of specific adverse events. METHODS: Patients with stage IIIB/IV or recurrent, non-squamous, EGFR mutation-positive NSCLC were randomized to receive erlotinib plus bevacizumab or erlotinib...
October 17, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/29043071/recent-advances-in-the-management-of-peptic-ulcer-bleeding
#15
REVIEW
Ian Beales
Acute upper gastrointestinal haemorrhage due to peptic ulcer bleeding remains an important cause of emergency presentation and hospital admission. Despite advances in many aspects of management, peptic ulcer bleeding is still associated with significant morbidity, mortality, and healthcare costs. Comprehensive international guidelines have been published, but advances as well as controversies continue to evolve. Important recent advances include the evidence supporting a more restrictive transfusion strategy aiming for a target haemoglobin of 70-90 g/l...
2017: F1000Research
https://www.readbyqxmd.com/read/29042898/prediction-of-treatment-response-to-donepezil-using-automated-hippocampal-subfields-volumes-segmentation-in-patients-with-mild-alzheimer-s-disease
#16
Yoo Hyun Um, Tae-Won Kim, Jong-Hyun Jeong, Ho-Jun Seo, Jin-Hee Han, Seung-Chul Hong, Chang-Uk Lee, Hyun Kook Lim
Previous studies reported some relationships between donepezil treatment and hippocampus in Alzheimer's disease (AD). However, due to methodological limitations, their close relationships remain unclear. The aim of this study is to predict treatment response to donepezil by utilizing the automated segmentation of hippocampal subfields volumes (ASHS) in AD. Sixty four AD patients were prescribed with donepezil and were followed up for 24 weeks. Cognitive function was measured to assess whether there was a response from the donepezil treatment...
September 2017: Psychiatry Investigation
https://www.readbyqxmd.com/read/29042700/preoperative-risk-factors-for-conversion-of-laparoscopic-cholecystectomy-to-open-cholecystectomy-and-the-usefulness-of-the-2013-tokyo-guidelines
#17
Masashi Utsumi, Hideki Aoki, Tomoyoshi Kunitomo, Yutaka Mushiake, Isao Yasuhara, Fumitaka Taniguchi, Takashi Arata, Koh Katsuda, Kohji Tanakaya, Hitoshi Takeuchi
To identify predictive factors for conversion from laparoscopic cholecystectomy (LC) to open cholecystectomy performed for mixed indications as an acute or elective procedure. We retrospectively analyzed the data of 236 consecutive cases of LC performed in our department between January 2012 and January 2015, and evaluated preoperative risk factors for conversion and the usefulness of the 2013 Tokyo guidelines (TG2013) for diagnosing acute cholecystitis. The conversion rate in our series was 8% (19/236 cases)...
October 2017: Acta Medica Okayama
https://www.readbyqxmd.com/read/29042646/effects-of-long-term-aspirin-use-on-molecular-alterations-in-precancerous-gastric-mucosa-in-patients-with-and-without-gastric-cancer
#18
Yuki Michigami, Jiro Watari, Chiyomi Ito, Ken Hara, Takahisa Yamasaki, Takashi Kondo, Tomoaki Kono, Katsuyuki Tozawa, Toshihiko Tomita, Tadayuki Oshima, Hirokazu Fukui, Takeshi Morimoto, Kiron M Das, Hiroto Miwa
The risk of gastric cancer (GC) remains even after H. pylori eradication; thus, other combination treatments, such as chemopreventive drugs, are needed. We evaluated the effects of aspirin on genetic/epigenetic alterations in precancerous conditions, i.e., atrophic mucosa (AM) and intestinal metaplasia (IM), in patients with chronic gastritis who had taken aspirin for more than 3 years. A total of 221 biopsy specimens from 74 patients, including atrophic gastritis (AG) cases without aspirin use (control), AG cases with aspirin use (AG group), and GC cases with aspirin use (GC group), were analyzed...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29042527/-biomarkers-for-mood-disorders-and-a-novel-antidepressant-r-ketamine
#19
Kenji Hashimoto
Depression is often misdiagnosed as major depressive disorder in patients with bipolar disorder. Therapeutic drugs for these two disorders are quite different, but the anesthetic ketamine shows fast-acting antidepressant effects in treatment-resistant patients with these disorders. Here, we discuss biomarkers for both disorders, recent findings regarding ketamine, and predictable biomarkers for ketamine's antidepressant actions.
October 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/29042293/development-of-novel-prediction-model-for-drug-induced-mitochondrial-toxicity-by-using-na%C3%A3-ve-bayes-classifier-method
#20
Hui Zhang, Peng Yu, Ji-Xia Ren, Xi-Bo Li, He-Li Wang, Lan Ding, Wei-Bao Kong
Mitochondrial dysfunction has been considered as an important contributing factor in the etiology of drug-induced organ toxicity, and even plays an important role in the pathogenesis of some diseases. The objective of this investigation was to develop a novel prediction model of drug-induced mitochondrial toxicity by using a naïve Bayes classifier. For comparison, the recursive partitioning classifier prediction model was also constructed. Among these methods, the prediction performance of naïve Bayes classifier established here showed best, which yielded average overall prediction accuracies for the internal 5-fold cross validation of the training set and external test set were 95 ± 0...
October 14, 2017: Food and Chemical Toxicology
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